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Sample records for address specific clinical

  1. Public Address Systems. Specifications - Installation - Operation.

    ERIC Educational Resources Information Center

    Palmer, Fred M.

    Provisions for public address in new construction of campus buildings (specifications, installations, and operation of public address systems), are discussed in non-technical terms. Consideration is given to microphones, amplifiers, loudspeakers and the placement and operation of various different combinations. (FS)

  2. Addressing the Mathematics-Specific Needs of Beginning Mathematics Teachers

    ERIC Educational Resources Information Center

    Britton, Edward

    2012-01-01

    Beginning mathematics teachers at the secondary level (middle and high school grades) have mathematics-specific needs that induction programs should address more substantially. However, a number of issues in how programs can accomplish this are more complex than often framed in discussions occurring in the induction programs and the field of…

  3. Addressing the Mathematics-Specific Needs of Beginning Mathematics Teachers

    ERIC Educational Resources Information Center

    Britton, Edward

    2012-01-01

    Beginning mathematics teachers at the secondary level (middle and high school grades) have mathematics-specific needs that induction programs should address more substantially. However, a number of issues in how programs can accomplish this are more complex than often framed in discussions occurring in the induction programs and the field of…

  4. Addressing cultural diversity: the hepatitis B clinical specialist perspective.

    PubMed

    Wallace, Jack; Smith, Elizabeth; Hajarizadeh, Behzad; Richmond, Jacqueline; Lucke, Jayne

    2017-08-31

    Hepatitis B is a viral infection primarily affecting people from culturally diverse communities in Australia. While vaccination prevents infection, there is increasing mortality resulting from liver damage associated with chronic infection. Deficits in the national policy and clinical response to hepatitis B result in a low diagnosis rate, inadequate testing and diagnosis processes, and poor access to hepatitis B treatment services. While research identifies inadequate hepatitis B knowledge among people with the virus and primary health care workers, this project sought to identify how specialist clinicians in Australia negotiate cultural diversity, and provide often complex clinical information to people with hepatitis B. A vignette was developed and presented to thirteen viral hepatitis specialist clinicians prior to an electronically recorded interview. Recruitment continued until saturation of themes was reached. Data were thematically coded into themes outlined in the interview schedule. Ethical approval for the research was provided by the La Trobe University Human Research Ethics Committee. Key messages provided to patients with hepatitis B by clinical specialists were identified. These messages were not consistently provided to all patients with hepatitis B, but were determined on perceptions of patient knowledge, age and highest educational level. While the vignette stated that English was not an issue for the patient, most specialists identified the need for an interpreter. Combating stigma related to hepatitis B was seen as important by the specialists and this was done through normalising the virus. Having an awareness of different cultural understandings about hepatitis B specifically, and health and well-being generally, was noted as a communication strategy. Key core competencies need to be developed to deliver educational messages to people with hepatitis B within clinical encounters. The provision of adequate resources to specialist clinics will

  5. Addressing the needs of traumatic brain injury with clinical proteomics

    PubMed Central

    2014-01-01

    Background Neurotrauma or injuries to the central nervous system (CNS) are a serious public health problem worldwide. Approximately 75% of all traumatic brain injuries (TBIs) are concussions or other mild TBI (mTBI) forms. Evaluation of concussion injury today is limited to an assessment of behavioral symptoms, often with delay and subject to motivation. Hence, there is an urgent need for an accurate chemical measure in biofluids to serve as a diagnostic tool for invisible brain wounds, to monitor severe patient trajectories, and to predict survival chances. Although a number of neurotrauma marker candidates have been reported, the broad spectrum of TBI limits the significance of small cohort studies. Specificity and sensitivity issues compound the development of a conclusive diagnostic assay, especially for concussion patients. Thus, the neurotrauma field currently has no diagnostic biofluid test in clinical use. Content We discuss the challenges of discovering new and validating identified neurotrauma marker candidates using proteomics-based strategies, including targeting, selection strategies and the application of mass spectrometry (MS) technologies and their potential impact to the neurotrauma field. Summary Many studies use TBI marker candidates based on literature reports, yet progress in genomics and proteomics have started to provide neurotrauma protein profiles. Choosing meaningful marker candidates from such ‘long lists’ is still pending, as only few can be taken through the process of preclinical verification and large scale translational validation. Quantitative mass spectrometry targeting specific molecules rather than random sampling of the whole proteome, e.g., multiple reaction monitoring (MRM), offers an efficient and effective means to multiplex the measurement of several candidates in patient samples, thereby omitting the need for antibodies prior to clinical assay design. Sample preparation challenges specific to TBI are addressed. A

  6. Addressing dual agency: getting specific about the expectations of professionalism.

    PubMed

    Tilburt, Jon C

    2014-01-01

    Professionalism requires that physicians uphold the best interests of patients while simultaneously insuring just use of health care resources. Current articulations of these obligations like the American Board of Internal Medicine (ABIM) Foundation's Physician Charter do not reconcile how these obligations fit together when they conflict. This is the problem of dual agency. The most common ways of dealing with dual agency: "bunkering"--physicians act as though societal cost issues are not their problem; "bailing"--physicians assume that they are merely agents of society and deliver care typically based on a strongly consequentialist public health ethic; or "balancing"--a vaguely specified attempt to uphold both patient welfare and societal need for judicious resource use simultaneously--all fail. Here I propose how the problem of dual agency might begin to be addressed with rigor and consistency. Without dealing with the dual agency problem and getting more specific about how to reconcile its norms when they conflict, the expectations of professionalism risk being written off as cute, nonbinding aphorisms from the medical profession.

  7. Republished: Respiratory microbiota: addressing clinical questions, informing clinical practice

    PubMed Central

    Rogers, Geraint B; Shaw, Dominick; Marsh, Robyn L; Carroll, Mary P; Serisier, David J; Bruce, Kenneth D

    2015-01-01

    Over the last decade, technological advances have revolutionised efforts to understand the role played by microbes in airways disease. With the application of ever more sophisticated techniques, the literature has become increasingly inaccessible to the non-specialist reader, potentially hampering the translation of these gains into improvements in patient care. In this article, we set out the key principles underpinning microbiota research in respiratory contexts and provide practical guidance on how best such studies can be designed, executed and interpreted. We examine how an understanding of the respiratory microbiota both challenges fundamental assumptions and provides novel clinical insights into lung disease, and we set out a number of important targets for ongoing research. PMID:26304986

  8. Utilizing Motivational Interviewing to Address Resistant Behaviors in Clinical Supervision

    ERIC Educational Resources Information Center

    Wahesh, Edward

    2016-01-01

    Motivational interviewing is presented as an approach to address resistant behaviors in clinical supervision. A case example is used to illustrate the process in which the relational and technical elements of motivational interviewing can be applied to supervisee resistance. Implications for supervisors and researchers are discussed.

  9. Utilizing Motivational Interviewing to Address Resistant Behaviors in Clinical Supervision

    ERIC Educational Resources Information Center

    Wahesh, Edward

    2016-01-01

    Motivational interviewing is presented as an approach to address resistant behaviors in clinical supervision. A case example is used to illustrate the process in which the relational and technical elements of motivational interviewing can be applied to supervisee resistance. Implications for supervisors and researchers are discussed.

  10. Beyond Values Clarification: Addressing Client Values in Clinical Behavior Analysis

    PubMed Central

    Bonow, Jordan T; Follette, William C

    2009-01-01

    Ethical principles of psychology, as exemplified in the American Psychological Association (APA) Code of Ethics (2002), provide impractical advice for addressing client values during psychotherapy. These principles seem to argue that each client's values should be respected and protected at all times, except in cases in which this would result in harm to the client or the general public. Although the code is appropriately designed as a defense against potential and actual abuses of professional power, this general proscription against directly targeting client values for change is based on an understanding of values that grants them special ontological status and has resulted in limited clinical interventions focusing solely on “values clarification.” With its strong foundation in a unified philosophical system, clinical behavior analysis offers a sophisticated alternative approach to values that both defines what they are and identifies when they can be ethically targeted to improve the lives of clients. PMID:22478514

  11. Clinical strategies for addressing muscle weakness following knee injury.

    PubMed

    Pietrosimone, Brian; Blackburn, J Troy; Harkey, Matthew S; Luc, Brittney A; Pamukoff, Derek N; Hart, Joe M

    2015-04-01

    Muscle strength is a determinate of physical function and increasing muscle strength is an important clinical goal for patients with knee injury. This article discusses the emerging evidence regarding a novel rehabilitation strategy that uses disinhibitory modalities to increase neuromuscular activation in conjunction with traditional muscle strengthening for the purpose of maximizing strength gains following acute knee injury or surgery and in patients with knee osteoarthritis. The use of disinhibitory modalities and specific types of neuromuscular training for clinically maximizing strength are discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Identifying and addressing specific student difficulties in advanced thermal physics

    NASA Astrophysics Data System (ADS)

    Smith, Trevor I.

    As part of an ongoing multi-university research study on student understanding of concepts in thermal physics at the upper division, I identified several student difficulties with topics related to heat engines (especially the Carnot cycle), as well as difficulties related to the Boltzmann factor. In an effort to address these difficulties, I developed two guided-inquiry worksheet activities (a.k.a. tutorials) for use in advanced undergraduate thermal physics courses. Both tutorials seek to improve student understanding of the utility and physical background of a particular mathematical expression. One tutorial focuses on a derivation of Carnot's theorem regarding the limit on thermodynamic efficiency, starting from the Second Law of Thermodynamics. The other tutorial helps students gain an appreciation for the origin of the Boltzmann factor and when it is applicable; focusing on the physical justification of its mathematical derivation, with emphasis on the connections between probability, multiplicity, entropy, and energy. Student understanding of the use and physical implications of Carnot's theorem and the Boltzmann factor was assessed using written surveys both before and after tutorial instruction within the advanced thermal physics courses at the University of Maine and at other institutions. Classroom tutorial sessions at the University of Maine were videotaped to allow in-depth scrutiny of student successes and failures following tutorial prompts. I also interviewed students on various topics related to the Boltzmann factor to gain a more complete picture of their understanding and inform tutorial revisions. Results from several implementations of my tutorials at the University of Maine indicate that students did not have a robust understanding of these physical principles after lectures alone, and that they gain a better understanding of relevant topics after tutorial instruction; Fisher's exact tests yield statistically significant improvement at the

  13. The AMA clinical quality improvement forum on addressing patient safety.

    PubMed

    Berman, S

    2000-07-01

    More than 200 health care policy makers and researchers, clinicians, quality professionals, and other representatives of health care organizations, government, and academia attended the Division of American Medical Association Clinical Quality Improvement's conference, "Addressing Patient Safety," April 28, 2000, in Chicago--the first national conference to respond to the recent Institute of Medicine (IOM) report, To Err Is Human: Building a Safer Health System. ADDRESSING PATIENT SAFETY--PUBLIC AND PRIVATE PERSPECTIVES: John M. Eisenberg, MD, stated that research on errors is needed to describe the scope and nature of the problem, understand the barriers to and benefits of improvement, and develop and test strategies for improvement. Kenneth W. Kizer, MD, MPH, stated that the National Quality Forum will develop a compendium of best practices and will develop core measures for serious adverse events, and health care organizations and government health programs should act now to make a clear organizational commitment to patient safety, create a nonpunitive health care culture of safety, and implement known safe medication practices. Alan R. Nelson, MD, stated that the IOM report places its emphasis on continuous quality improvement and technology that can be used to mitigate the risks in a complex health system. Donald M. Nielsen, MD, discussed the American Hospital Association's (AHA's) Medication Safety Initiative, which promised to provide its members with successful practices, tools, and resources and to track progress of implementation of the recommended successful practices. Dennis S. O'Leary, MD, stated that when a hospital reports a sentinel event, the hospital is expected to implement improvements to reduce risk and monitor their effectiveness. The National Committee for Quality Assurance is considering changes to its accreditation standards to further address patient safety.

  14. Addressing electronic clinical information in the construction of quality measures.

    PubMed

    Bailey, L Charles; Mistry, Kamila B; Tinoco, Aldo; Earls, Marian; Rallins, Marjorie C; Hanley, Kendra; Christensen, Keri; Jones, Meredith; Woods, Donna

    2014-01-01

    Electronic health records (EHR) and registries play a central role in health care and provide access to detailed clinical information at the individual, institutional, and population level. Use of these data for clinical quality/performance improvement and cost management has been a focus of policy initiatives over the past decade. The Children's Health Insurance Program Reauthorization Act of 2009 (CHIPRA)-mandated Pediatric Quality Measurement Program supports development and testing of quality measures for children on the basis of electronic clinical information, including de novo measures and respecification of existing measures designed for other data sources. Drawing on the experience of Centers of Excellence, we review both structural and pragmatic considerations in e-measurement. The presence of primary observations in EHR-derived data make it possible to measure outcomes in ways that are difficult with administrative data alone. However, relevant information may be located in narrative text, making it difficult to interpret. EHR systems are collecting more discrete data, but the structure, semantics, and adoption of data elements vary across vendors and sites. EHR systems also differ in ability to incorporate pediatric concepts such as variable dosing and growth percentiles. This variability complicates quality measurement, as do limitations in established measure formats, such as the Quality Data Model, to e-measurement. Addressing these challenges will require investment by vendors, researchers, and clinicians alike in developing better pediatric content for standard terminologies and data models, encouraging wider adoption of technical standards that support reliable quality measurement, better harmonizing data collection with clinical work flow in EHRs, and better understanding the behavior and potential of e-measures.

  15. Addressing the clinical needs of problem drug user patients

    PubMed Central

    Krupski, Antoinette; West, Imara I.; Graves, Meredith C.; Atkins, David C.; Maynard, Charles; Bumgardner, Kristin; Donovan, Dennis; Ries, Richard; Roy-Byrne, Peter

    2016-01-01

    Introduction Illicit drug use is a serious public health problem associated with significant co-occurring medical disorders, mental disorders, and social problems. Yet most individuals with drug use disorders have never been treated, though they often seek medical treatment in primary care. The purpose of the present study was to examine baseline characteristics of persons presenting in primary care across a range of problem drug use severity to identify their clinical needs. Methods We examined socio-demographic characteristics, medical and psychiatric comorbidities, drug use severity, social and legal problems, and service utilization for 868 patients with drug problems recruited from primary care clinics in a safety-net medical setting. Based on Drug Abuse Screening Test (DAST-10) results, individuals were categorized as having low, intermediate, or substantial/severe drug use severity. Results Patients with substantial/severe drug use severity had serious drug use (opiates, stimulants, sedatives, intravenous drug use), high levels of homelessness (50%), psychiatric comorbidity (69%), arrests for serious crimes (24%), and frequent use of expensive emergency department and inpatient hospitals. Patients with low drug use severity were primarily users of marijuana with little reported use of other drugs, less psychiatric co-morbidity, and more stable lifestyles. Patients with intermediate drug use severity fell in-between the substantial/severe and low drug use severity subgroups on most variables. Conclusions Patients with highest drug use severity are likely to require specialized psychiatric and substance abuse care in addition to ongoing medical care that is equipped to address the consequences of severe/substantial drug use including intravenous drug use. Because of their milder symptoms, patients with low drug use severity may benefit from a collaborative care model that integrates psychiatric and substance abuse care in the primary care setting. Patients

  16. Beyond Values Clarification: Addressing Client Values in Clinical Behavior Analysis

    ERIC Educational Resources Information Center

    Bonow, Jordan T.; Follette, William C.

    2009-01-01

    Ethical principles of psychology, as exemplified in the American Psychological Association (APA) Code of Ethics (2002), provide impractical advice for addressing client values during psychotherapy. These principles seem to argue that each client's values should be respected and protected at all times, except in cases in which this would result in…

  17. 46 CFR 107.317 - Addresses for submittal of plans, specifications, and calculations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 4 2013-10-01 2013-10-01 false Addresses for submittal of plans, specifications, and calculations. 107.317 Section 107.317 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) A-MOBILE OFFSHORE DRILLING UNITS INSPECTION AND CERTIFICATION Plan Approval § 107.317 Addresses for...

  18. 46 CFR 107.317 - Addresses for submittal of plans, specifications, and calculations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 4 2014-10-01 2014-10-01 false Addresses for submittal of plans, specifications, and calculations. 107.317 Section 107.317 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) A-MOBILE OFFSHORE DRILLING UNITS INSPECTION AND CERTIFICATION Plan Approval § 107.317 Addresses for...

  19. Addressing canine and feline aggression in the veterinary clinic.

    PubMed

    Moffat, Kelly

    2008-09-01

    Handling aggressive dogs and cats in the veterinary clinic can be frustrating, time consuming, and injurious for both employee and animal. This article discusses the etiology of the aggressive dog and cat patient and how best to approach these cases. A variety of handling techniques, safety products, and drug therapy are reviewed.

  20. Addressing Low Literacy and Health Literacy in Clinical Oncology Practice

    PubMed Central

    Garcia, Sofia F.; Hahn, Elizabeth A.; Jacobs, Elizabeth A.

    2011-01-01

    Low functional literacy and low health literacy continue to be under-recognized and are associated with poorer patient health outcomes. Health literacy is a dynamic state influenced by how well a healthcare system delivers information and services that match patients’ abilities, needs and preferences. Oncology care poses considerable health literacy demands on patients who are expected to process high stakes information about complex multidisciplinary treatment over lengths of time. Much of the information provided to patients in clinical care and research is beyond their literacy levels. In this paper, we provide an overview of currently available guidelines and resources to improve how the needs of patients with diverse literacy skills are met by cancer care providers and clinics. We present recommendations for health literacy assessment in clinical practice and ways to enhance the usability of health information and services by improving written materials and verbal communication, incorporating multimedia and culturally appropriate approaches, and promoting health literacy in cancer care settings. The paper also includes a list of additional resources that can be used to develop and implement health literacy initiatives in cancer care clinics. PMID:20464884

  1. Current Issues Concerning Clinical Optometric Education. Keynote Address.

    ERIC Educational Resources Information Center

    Imperato, Pascal James

    1996-01-01

    Clinical optometric education is in flux. It must meet the challenges of advances in bioscience, newer diagnostic and therapeutic modalities, a changing health care environment, and interdisciplinary learning for problem solving; engender social responsibility; promote good provider-patient relations; stress primary care; and emphasize prevention.…

  2. Addressing missing participant outcome data in dental clinical trials.

    PubMed

    Spineli, Loukia M; Fleming, Padhraig S; Pandis, Nikolaos

    2015-06-01

    Missing outcome data are common in clinical trials and despite a well-designed study protocol, some of the randomized participants may leave the trial early without providing any or all of the data, or may be excluded after randomization. Premature discontinuation causes loss of information, potentially resulting in attrition bias leading to problems during interpretation of trial findings. The causes of information loss in a trial, known as mechanisms of missingness, may influence the credibility of the trial results. Analysis of trials with missing outcome data should ideally be handled with intention to treat (ITT) rather than per protocol (PP) analysis. However, true ITT analysis requires appropriate assumptions and imputation of missing data. Using a worked example from a published dental study, we highlight the key issues associated with missing outcome data in clinical trials, describe the most recognized approaches to handling missing outcome data, and explain the principles of ITT and PP analysis.

  3. Next-generation clinical trials: Novel strategies to address the challenge of tumor molecular heterogeneity

    PubMed Central

    Catenacci, Daniel V.T.

    2014-01-01

    The promise of ‘personalized cancer care’ with therapies toward specific molecular aberrations has potential to improve outcomes. However, there is recognized heterogeneity within any given tumor-type from patient to patient (inter-patient heterogeneity), and within an individual (intra-patient heterogeneity) as demonstrated by molecular evolution through space (primary tumor to metastasis) and time (after therapy). These issues have become hurdles to advancing cancer treatment outcomes with novel molecularly targeted agents. Classic trial design paradigms are challenged by heterogeneity, as they are unable to test targeted therapeutics against low frequency genomic ‘oncogenic driver’ aberrations with adequate power. Usual accrual difficulties to clinical trials are exacerbated by low frequencies of any given molecular driver. To address these challenges, there is need for innovative clinical trial designs and strategies implementing novel diagnostic biomarker technologies to account for inter-patient molecular diversity and scarce tissue for analysis. Importantly, there is also need for pre-defined treatment priority algorithms given numerous aberrations commonly observed within any one individual sample. Access to multiple available therapeutic agents simultaneously is crucial. Finally intra-patient heterogeneity through time may be addressed by serial biomarker assessment at the time of tumor progression. This report discusses various ‘next-generation’ biomarker-driven trial designs and their potentials and limitations to tackle these recognized molecular heterogeneity challenges. Regulatory hurdles, with respect to drug and companion diagnostic development and approval, are considered. Focus is on the ‘Expansion Platform Design Types I and II’, the latter demonstrated with a first example, ‘PANGEA: Personalized Anti-Neoplastics for Gastro-Esophageal Adenocarcinoma’. Applying integral medium-throughput genomic and proteomic assays along with

  4. Event-Specific Prevention: Addressing College Student Drinking During Known Windows of Risk

    PubMed Central

    Neighbors, Clayton; Walters, Scott T.; Lee, Christine M.; Vader, Amanda M.; Vehige, Tamara; Szigethy, Thomas; DeJong, William

    2007-01-01

    The unique drinking patterns of college students call for Event-Specific Prevention (ESP) strategies that address college student drinking associated with peak times and events. Despite limited research evaluating ESP, many college campuses are currently implementing programming for specific events. The present paper provides a review of existing literature related to ESP and offers practical guidance for research and practice. The prevention typology proposed by DeJong and Langford (2002) provides a framework for strategic planning, suggesting that programs and policies should address problems at the individual, group, institution, community, state, and society level, and that these interventions should focus on knowledge change, environmental change, health protection, and intervention and treatment services. From this typology, specific examples are provided for comprehensive program planning related to orientation/beginning of school year, homecoming, 21st birthday celebrations, spring break, and graduation. In addition, the University of Connecticut’s efforts to address problems resulting from its annual Spring Weekend are described as an illustration of how advance planning by campus and community partners can produce a successful ESP effort. PMID:17616260

  5. Structural Vulnerability: Operationalizing the Concept to Address Health Disparities in Clinical Care.

    PubMed

    Bourgois, Philippe; Holmes, Seth M; Sue, Kim; Quesada, James

    2017-03-01

    The authors propose reinvigorating and extending the traditional social history beyond its narrow range of risk behaviors to enable clinicians to address negative health outcomes imposed by social determinants of health. In this Perspective, they outline a novel, practical medical vulnerability assessment questionnaire that operationalizes for clinical practice the social science concept of "structural vulnerability." A structural vulnerability assessment tool designed to highlight the pathways through which specific local hierarchies and broader sets of power relationships exacerbate individual patients' health problems is presented to help clinicians identify patients likely to benefit from additional multidisciplinary health and social services. To illustrate how the tool could be implemented in time- and resource-limited settings (e.g., emergency department), the authors contrast two cases of structurally vulnerable patients with differing outcomes. Operationalizing structural vulnerability in clinical practice and introducing it in medical education can help health care practitioners think more clearly, critically, and practically about the ways social structures make people sick. Use of the assessment tool could promote "structural competency," a potential new medical education priority, to improve understanding of how social conditions and practical logistics undermine the capacities of patients to access health care, adhere to treatment, and modify lifestyles successfully. Adoption of a structural vulnerability framework in health care could also justify the mobilization of resources inside and outside clinical settings to improve a patient's immediate access to care and long-term health outcomes. Ultimately, the concept may orient health care providers toward policy leadership to reduce health disparities and foster health equity.

  6. Shifting the clinical teaching paradigm in undergraduate nursing education to address the nursing faculty shortage.

    PubMed

    Richardson, Hila; Gilmartin, Mattia J; Fulmer, Terry

    2012-04-01

    To address the faculty shortage problem, schools of nursing are reexamining how they provide clinical education to undergraduate students to find ways to use faculty resources more efficiently and to maintain student enrollment. We describe a unique clinical teaching model implemented at the New York University College of Nursing. The new model currently being evaluated shifts from the traditional clinical education model, in which all clinical education is in a hospital or agency setting, to a model that substitutes high-fidelity human patient simulation for up to half of the clinical education experience. This article describes the clinical teaching model and its effects on nurse faculty capacity.

  7. Vocal imitation in parrots allows addressing of specific individuals in a dynamic communication network.

    PubMed

    Balsby, Thorsten J S; Momberg, Jane Vestergaard; Dabelsteen, Torben

    2012-01-01

    Parrots in captivity are known for their ability to vocally imitate humans and recently it has been shown that wild-living orange-fronted conures are able to immediately imitate other individuals' contact calls. The function of this exceptional ability to imitate remains unclear. However, orange-fronted conures live in fission-fusion flocks where they encounter many different individuals every day, and it is possible that their vocal imitation ability is a flexible means to address a specific individual within a flock. We tested this via playback to short-term captive wild conures. Test birds were placed together in pairs in outdoor aviaries to form simple flocks. To simulate imitation of a specific individual these pairs received playback of contact calls that primarily imitate one of the two birds. Overall, individuals that received simulated vocal imitations of its calls responded more frequently and faster than the other individual. This suggests that orange-fronted conures can use imitations of contact calls to address specific individuals of a flock. In the discussion we argue that the fission-fusion flock dynamics of many parrot species has been an important factor in evolving conures' and other parrots' exceptional ability to imitate.

  8. Strategies addressing barriers to clinical trial enrollment of underrepresented populations: a systematic review.

    PubMed

    Heller, Caren; Balls-Berry, Joyce E; Nery, Jill Dumbauld; Erwin, Patricia J; Littleton, Dawn; Kim, Mimi; Kuo, Winston P

    2014-11-01

    Underrepresentation of racial and ethnic minorities in clinical trials remains a reality while they have disproportionately higher rates of health disparities. The purpose of this study was to identify successful community-engaged interventions that included health care providers as a key strategy in addressing barriers to clinical trial enrollment of underrepresented patients. A systematic review of the literature on interventions addressing enrollment barriers to clinical trials for racial and ethnic minorities was performed in Ovid MEDLINE, EBSCO Megafile, and EBSCO CINAHL. The systematic review identified 360 studies, and 20 were selected using the inclusion criteria. An iterative process extracted information from the eligible studies. The 20 selected studies were analyzed and then grouped by first author, nature of the clinical research initiative, priority populations, key strategies, and study outcomes. Nine of the studies addressed cancer clinical trials and 11 related to chronic medical conditions, including diabetes, hypertension management, and chronic kidney disease. The key strategies employed were categorized according to their presumed impact on barriers incurred at distinct steps in study recruitment: clinical trial awareness, opportunity to participate, and acceptance of enrollment. The strategies were further categorized by whether they would address barriers associated with minority perceptions of the research process and barriers related to how studies were designed and implemented. Multiple and flexible strategies targeting providers and participants at provider sites and within communities might be needed to enroll underrepresented populations into clinical trials. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Community-Clinic-Based Parent Intervention Addressing Noncompliance in Children with Attention-Deficit/Hyperactivity Disorder

    ERIC Educational Resources Information Center

    Canu, Will H.; Bearman, Sarah Kate

    2011-01-01

    The current study tested whether an abbreviated version of "Defiant Children" (Barkley, 1987), an efficacious parent training program to address the behavioral noncompliance often associated with disruptive behavior disorders, could be implemented successfully within a community mental health clinic setting by master's-level therapists. Ethnically…

  10. Clinical Behaviors for Addressing Religious/Spiritual Issues: Do We Practice What We Preach?

    ERIC Educational Resources Information Center

    Cashwell, Craig S.; Young, J. Scott; Fulton, Cheryl L.; Willis, Ben T.; Giordano, Amanda; Daniel, Laura Wyatt; Crockett, Jamie; Tate, B. Nicole; Welch, Metoka L.

    2013-01-01

    To determine if counselors integrate clinical behaviors for addressing religious/spiritual issues in counseling consistent with their ratings of the importance of such behaviors, the authors conducted a national survey of American Counseling Association (ACA) members. Seventy-eight ACA members rated the importance of and frequency with which they…

  11. Using Systems Approaches to Address Challenges for Clinical Implementation of Pharmacogenomics

    PubMed Central

    Karnes, Jason H; Van Driest, Sara; Bowton, Erica A; Weeke, Peter E; Mosley, Jonathan D; Peterson, Josh F; Denny, Joshua C

    2014-01-01

    Many genetic variants have been shown to affect drug response through changes in drug efficacy and likelihood of adverse effects. Much of pharmacogenomic science has focused on discovering and clinically implementing single gene variants with large effect sizes. Given the increasing complexities of drug responses and their variability, a systems approach may be enabling for discovery of new biology in this area. Further, systems approaches may be useful in addressing challenges in moving these data to clinical implementation, including creation of predictive models of drug response phenotypes, improved clinical decision-making through complex biological models, improving strategies for integrating genomics into clinical practice, and evaluating the impact of implementation programs on public health. PMID:24319008

  12. Randomized Trial of a Web-Based Intervention to Address Barriers to Clinical Trials.

    PubMed

    Meropol, Neal J; Wong, Yu-Ning; Albrecht, Terrance; Manne, Sharon; Miller, Suzanne M; Flamm, Anne Lederman; Benson, Al Bowen; Buzaglo, Joanne; Collins, Michael; Egleston, Brian; Fleisher, Linda; Katz, Michael; Kinzy, Tyler G; Liu, Tasnuva M; Margevicius, Seunghee; Miller, Dawn M; Poole, David; Roach, Nancy; Ross, Eric; Schluchter, Mark D

    2016-02-10

    Lack of knowledge and negative attitudes have been identified as barriers to participation in clinical trials by patients with cancer. We developed Preparatory Education About Clinical Trials (PRE-ACT), a theory-guided, Web-based, interactive computer program, to deliver tailored video educational content to patients in an effort to overcome barriers to considering clinical trials as a treatment option. A prospective, randomized clinical trial compared PRE-ACT with a control condition that provided general clinical trials information produced by the National Cancer Institute (NCI) in text format. One thousand two hundred fifty-five patients with cancer were randomly allocated before their initial visit with an oncologist to PRE-ACT (n = 623) or control (n = 632). PRE-ACT had three main components: assessment of clinical trials knowledge and attitudinal barriers, values assessment with clarification back to patients, and provision of a video library tailored to address each patient's barriers. Outcomes included knowledge and attitudes and preparation for decision making about clinical trials. Both PRE-ACT and control interventions improved knowledge and attitudes (all P < .001) compared with baseline. Patients randomly allocated to PRE-ACT showed a significantly greater increase in knowledge (P < .001) and a significantly greater decrease in attitudinal barriers (P < .001) than did their control (text-only) counterparts. Participants in both arms significantly increased their preparedness to consider clinical trials (P < .001), and there was a trend favoring the PRE-ACT group (P < .09). PRE-ACT was also associated with greater patient satisfaction than was NCI text alone. These data show that patient education before the first oncologist visit improves knowledge, attitudes, and preparation for decision making about clinical trials. Both text and tailored video were effective. The PRE-ACT interactive video program was more effective than NCI text in improving

  13. SHAPING A NEW GENERATION OF HISPANIC CLINICAL AND TRANSLATIONAL RESEARCHERS ADDRESSING MINORITY HEALTH AND HEALTH DISPARITIES

    PubMed Central

    Estape, Estela S.; Segarra, Barbara; Baez, Adriana; Huertas, Aracelis; Diaz, Clemente; Frontera, Walter

    2012-01-01

    In 2011, research educators face significant challenges. Training programs in Clinical and Translational Research need to develop or enhance their curriculum to comply with new scientific trends and government policies. Curricula must impart the skills and competencies needed to help facilitate the dissemination and transfer of scientific advances at a faster pace than current health policy and practice. Clinical and translational researchers are facing also the need of new paradigms for effective collaboration, and resource sharing while using the best educational models. Both government and public policy makers emphasize addressing the goals of improving health quality and elimination of health disparities. To help achieve this goal, our academic institution is taking an active role and striving to develop an environment that fosters the career development of clinical and translational researchers. Consonant with this vision, in 2002 the University of Puerto Rico, Medical Sciences Campus School of Health Professions and School of Medicine initiated a multidisciplinary post-doctoral Master of Science in Clinical Research focused in training Hispanics who will address minority health and health disparities research. Recently, we proposed a curriculum revision to enhance this commitment in promoting competency-based curricula for clinician-scientists in clinical and translational sciences. The revised program will be a post-doctoral Master of Science in Clinical and Translational Research (MCTR), expanding its outreach by actively engaging in establishing new collaborations and partnerships that will increase our capability to diversify our educational efforts and make significant contributions to help reduce and eliminate the gap in health disparities. PMID:22263296

  14. Randomized Trial of a Web-Based Intervention to Address Barriers to Clinical Trials

    PubMed Central

    Wong, Yu-Ning; Albrecht, Terrance; Manne, Sharon; Miller, Suzanne M.; Flamm, Anne Lederman; Benson, Al Bowen; Buzaglo, Joanne; Collins, Michael; Egleston, Brian; Fleisher, Linda; Katz, Michael; Kinzy, Tyler G.; Liu, Tasnuva M.; Margevicius, Seunghee; Miller, Dawn M.; Poole, David; Roach, Nancy; Ross, Eric; Schluchter, Mark D.

    2016-01-01

    Purpose Lack of knowledge and negative attitudes have been identified as barriers to participation in clinical trials by patients with cancer. We developed Preparatory Education About Clinical Trials (PRE-ACT), a theory-guided, Web-based, interactive computer program, to deliver tailored video educational content to patients in an effort to overcome barriers to considering clinical trials as a treatment option. Patients and Methods A prospective, randomized clinical trial compared PRE-ACT with a control condition that provided general clinical trials information produced by the National Cancer Institute (NCI) in text format. One thousand two hundred fifty-five patients with cancer were randomly allocated before their initial visit with an oncologist to PRE-ACT (n = 623) or control (n = 632). PRE-ACT had three main components: assessment of clinical trials knowledge and attitudinal barriers, values assessment with clarification back to patients, and provision of a video library tailored to address each patient’s barriers. Outcomes included knowledge and attitudes and preparation for decision making about clinical trials. Results Both PRE-ACT and control interventions improved knowledge and attitudes (all P < .001) compared with baseline. Patients randomly allocated to PRE-ACT showed a significantly greater increase in knowledge (P < .001) and a significantly greater decrease in attitudinal barriers (P < .001) than did their control (text-only) counterparts. Participants in both arms significantly increased their preparedness to consider clinical trials (P < .001), and there was a trend favoring the PRE-ACT group (P < .09). PRE-ACT was also associated with greater patient satisfaction than was NCI text alone. Conclusion These data show that patient education before the first oncologist visit improves knowledge, attitudes, and preparation for decision making about clinical trials. Both text and tailored video were effective. The PRE-ACT interactive video program was

  15. A New Method to Address Verification Bias in Studies of Clinical Screening Tests: Cervical Cancer Screening Assays as an Example

    PubMed Central

    Xue, Xiaonan; Kim, Mimi Y; Castle, Philip E; Strickler, Howard D

    2013-01-01

    Objective Studies to evaluate clinical screening tests often face the problem that the “gold standard” diagnostic approach is costly and/or invasive. It is therefore common to verify only a subset of negative screening tests using the gold standard method. However, under-sampling the screen-negatives can lead to substantial overestimation of the sensitivity and underestimation of the specificity of the diagnostic test. Our objective was to develop a simple and accurate statistical method to address this “verification bias”. Study Design and Setting We developed a weighted generalized estimating equation approach to estimate, in a single model, the accuracy (e.g., sensitivity/specificity) of multiple assays as well as simultaneously compare results between assays while addressing verification bias. This approach can be implemented using standard statistical software. Simulations were conducted to assess the proposed method. An example is provided using a cervical cancer screening trial that compared the accuracy of human papillomavirus and Pap tests, with histological data as the gold standard. Results The proposed approach performed well in estimating and comparing the accuracy of multiple assays in the presence of verification bias. Conclusion The proposed approach is an easy to apply and accurate method for addressing verification bias in studies of multiple screening methods. PMID:24332397

  16. To What Extent Is Criminal Justice Content Specifically Addressed in MSW Programs?

    ERIC Educational Resources Information Center

    Epperson, Matthew W.; Roberts, Leslie E.; Ivanoff, Andre; Tripodi, Stephen J.; Gilmer, Christy N.

    2013-01-01

    This study examined the extent to which criminal justice content is addressed in all CSWE-accredited MSW programs in the United States ("N"?=?192). Criminal justice content was measured in three areas: (1) dual or joint degree programs, (2) concentrations or specializations, and (3) coursework. Excluding social work and law classes, 22%…

  17. To What Extent Is Criminal Justice Content Specifically Addressed in MSW Programs?

    ERIC Educational Resources Information Center

    Epperson, Matthew W.; Roberts, Leslie E.; Ivanoff, Andre; Tripodi, Stephen J.; Gilmer, Christy N.

    2013-01-01

    This study examined the extent to which criminal justice content is addressed in all CSWE-accredited MSW programs in the United States ("N"?=?192). Criminal justice content was measured in three areas: (1) dual or joint degree programs, (2) concentrations or specializations, and (3) coursework. Excluding social work and law classes, 22%…

  18. [Continuous challenges in Japanese forensic toxicology practice: strategy to address specific goals].

    PubMed

    Kageura, Mitsuyoshi

    2002-09-01

    In this paper, the status quo of forensic toxicology in Japan and the West is surveyed and a strategy to address future goals of Japanese forensic toxicology is proposed. Forensic toxicology in the West consists of three main areas--post-mortem forensic toxicology, human-performance forensic toxicology and forensic urine drug testing. In Japan, post-mortem forensic toxicology is practiced in university forensic medicine departments while most of the human-performance forensic toxicology is carried out in police laboratories. However, at least at present, strictly controlled workplace urine drug testing is not being performed, despite the abuse of drugs even by uniformed members of the National Defence Forces and police. For several years, the author has been introducing Western forensic toxicology guidelines and recommendations, translated into Japanese with the help of Western forensic toxicologists, to Japanese forensic toxicologists. Western forensic toxicology practice is at an advanced stage, whereas Japanese practice is in a critical condition and holds many problems awaiting solution, as exemplified by the urine drug testing in police laboratories. There is never any sample left for re-examination by the defence in all cases, though the initial volume of the urine sample available for examination is 30-50 ml. Only one organisation carries out everything from sampling to reporting and, in addition, the parent drug and its metabolites are not quantified. It is clear that the police laboratories do not work within good laboratory practice guidelines, nor do they have quality manuals or standard operating procedures manuals. A basic change in Japanese forensic toxicology practice is now essential. The author strongly recommends that, first of all, Japanese toxicologists should prepare forensic toxicology guidelines based on the Western models. The guidelines would progress the following objectives for forensic toxicology laboratories: 1) to have documented good

  19. [Application of tipping-point analysis to address missing data in clinical studies].

    PubMed

    Zhang, S J; Wang, Y; Li, W

    2017-05-10

    To use a visualized method, tipping-point analysis to address missing data in clinical study and discuss related problems. All the possible outcomes caused by missing data were listed and the tipping points where P-values of hypothesis test changed at 0.05 significant level were found out, then the ratio of P<0.05 was calculated, reflecting the reliability of the study's result. Tipping-point analysis can be applied to both continuous and binary data to help find points where p-values are changed. The area of P<0.05 of continuous data is 93.6%, indicating that the reliability of success of the study is large; and the area of P<0.05 of binary data is 29.7%, reflecting that the reliability of success of the study is small. Tipping-point analysis, which provides a visualized evidence for decision making, is suitable for analyzing clinical studies with missing data.

  20. A systematic review of strategies to address the clinical nursing faculty shortage.

    PubMed

    Wyte-Lake, Tamar; Tran, Kim; Bowman, Candice C; Needleman, Jack; Dobalian, Aram

    2013-05-01

    This systematic review provides a comprehensive assessment of models used to expand the ranks of clinical nursing faculty. Nursing faculty shortages constrict the pipeline for educating nurses and make addressing the projected nursing shortage more difficult. Schools of nursing have denied admission to qualified applicants, citing insufficient numbers of nursing faculty as one major reason. Using key search terms in PubMed(®) and CINAHL(®), we identified 14 peer-reviewed articles published between 1980 and 2010 about models for expanding clinical faculty. Partnership models (n = 11) and expanded use of faculty resources (n = 9) were the most common strategies. Few (n = 8) studies assessed program efficacy. A need was identified for studies to assess the effect of alternative models on educational capacity and student performance and to examine the subcomponents of academic-practice partnerships and other innovative approaches to understand the essential factors necessary to implement successful programs.

  1. Translating Life Course Theory to clinical practice to address health disparities.

    PubMed

    Cheng, Tina L; Solomon, Barry S

    2014-02-01

    Life Course Theory (LCT) is a framework that explains health and disease across populations and over time and in a powerful way, conceptualizes health and health disparities to guide improvements. It suggests a need to change priorities and paradigms in our healthcare delivery system. In "Rethinking Maternal and Child Health: The Life Course Model as an Organizing Framework," Fine and Kotelchuck identify three areas of rethinking that have relevance to clinical care: (1) recognition of context and the "whole-person, whole-family, whole-community systems approach;" (2) longitudinal approach with "greater emphasis on early ("upstream") determinants of health"; and (3) need for integration and "developing integrated, multi-sector service systems that become lifelong "pipelines" for healthy development". This paper discusses promising clinical practice innovations in these three areas: addressing social influences on health in clinical practice, longitudinal and vertical integration of clinical services and horizontal integration with community services and resources. In addition, barriers and facilitators to implementation are reviewed.

  2. Presidential address. American College of Clinical Pharmacology has provided a variety of educational opportunities.

    PubMed

    Lathers, C M

    1995-04-01

    At the current time, the College is in an excellent position to support the educational needs of its growing membership. The fund balance has increased over the past few years and is continuing to increase during the current year. The unprecedented speed of changes in the health care environment in which all clinical pharmacologists are now working necessitates that the American College of Clinical Pharmacology continually examine and update its Strategic Plan and Long Range Goals to allow all of its members to keep abreast of these changes. As hospitals, medical schools, and other allied health colleges address the need for economic accountability, as educators in medical and pharmacy and other schools encounter state and federal reductions in financial assistance to students, and as new roles are developed for the clinical pharmacologists working within the professions of medicine, pharmacy and allied health specialties, the College must maintain its role as a leader for all clinical pharmacologists. The success of the College will be directly related to the effort invested by all of the committee members and chairpersons, the Board of Regents, the Officers of the College, and most of all, the membership. During the next two years, I look forward to working with the entire membership to encourage growth of the College.

  3. Operational and Clinical Strategies to Address Drug Cost Containment in the Acute Care Setting.

    PubMed

    McConnell, Karen J; Guzman, Oscar E; Pherwani, Nisha; Spencer, Dustin D; Van Cura, Jennifer D; Shea, Katherine M

    2017-01-01

    To provide clinical and operational strategies to generate drug cost savings in the hospital setting. A search of the PubMed database was performed with no time limit through July 2016. All original prospective and retrospective studies, peer-reviewed guidelines, consensus statements, review articles, and accompanying references were evaluated for inclusion. Only articles published in the English language were included. Investigators reviewed 937 abstracts. The review of the literature showed that acute care hospitals are under increasing financial pressures, and the pharmacy is often responsible for opportunities to manage drug costs. The literature also indicated that cost-containment strategies in the acute care setting range from pharmacy-directed activities to initiatives requiring interdisciplinary collaboration and strategic planning. Hospital pharmacies should consider establishing an interdisciplinary team that is responsible for systematically reviewing drug cost implications and leading any initiatives that are deemed necessary. Acute care settings can use various operational and clinical strategies to lower their expenditures on high-cost drugs. Operational strategies include various activities that pharmacy staff implement related to contracting, purchasing, and inventory management. Clinical strategies utilize clinical pharmacists working with interdisciplinary teams to develop and maintain a formulary, implement established-use criteria for select drugs, use dose optimization, and implement other clinical tactics aimed at cost containment. After initiatives are implemented, assessing the outcomes of the initiatives is important to determine how successful they were at lowering costs safely and effectively. Acute care hospitals can use various operational and clinical strategies to lower overall drug costs. A systematic stepwise approach is recommended to ensure relevant drugs are regularly reviewed and addressed as needed. © 2016 Pharmacotherapy

  4. Using imprecise probabilities to address the questions of inference and decision in randomized clinical trials.

    PubMed

    Gurrin, Lyle C; Sly, Peter D; Burton, Paul R

    2002-05-01

    Randomized controlled clinical trials play an important role in the development of new medical therapies. There is, however, an ethical issue surrounding the use of randomized treatment allocation when the patient is suffering from a life threatening condition and requires immediate treatment. Such patients can only benefit from the treatment they actually receive and not from the alternative therapy, even if it ultimately proves to be superior. We discuss a novel new way to analyse data from such clinical trials based on the use of the recently developed theory of imprecise probabilities. This work draws an explicit distinction between the related but nevertheless distinct questions of inference and decision in clinical trials. The traditional question of scientific interest asks 'Which treatment offers the greater chance of success?' and is the primary reason for conducting the clinical trial. The question of decision concerns the welfare of the patients in the clinical trial, asking whether the accumulated evidence favours one treatment over the other to such an extent that the next patient should decline randomization and instead express a preference for one treatment. Consideration of the decision question within the framework of imprecise probabilities leads to a mathematical definition of equipoise and a method for governing the randomization protocol of a clinical trial. This paper describes in detail the protocol for the conduct of clinical trials based on this new method of analysis, which is illustrated in a retrospective analysis of data from a clinical trial comparing the anti-emetic drugs ondansetron and droperidol in the treatment of postoperative nausea and vomiting. The proposed methodology is compared quantitatively using computer simulation studies with conventional clinical trial designs and is shown to maintain high statistical power with reduced sample sizes, at the expense of a high type I error rate that we argue is irrelevant in some

  5. Engaging Stakeholders to Inform Clinical Practice Guidelines That Address Multiple Chronic Conditions.

    PubMed

    Bennett, Wendy L; Robbins, Craig W; Bayliss, Elizabeth A; Wilson, Renee; Tabano, Heather; Mularski, Richard A; Chan, Wiley V; Puhan, Milo; Yu, Tsung; Leff, Bruce; Li, Tianjing; Dickersin, Kay; Glover, Carol; Maslow, Katie; Armacost, Karen; Mintz, Suzanne; Boyd, Cynthia M

    2017-08-01

    Having more than one chronic condition is common and is associated with greater health care utilization, higher medication burden and complexity of treatment. However, clinical practice guidelines (CPGs) do not routinely address the balance between harms and benefits of treatments for people with multiple chronic conditions (MCCs). To partner with the Kaiser Permanente Integrated Cardiovascular Health (ICVH) program to engage multiple stakeholders in a mixed-methods approach in order to: 1) identify two high-priority clinical questions related to MCCs, and 2) understand patients' and family caregivers' perceptions of meaningful outcomes to inform benefit/harm assessments for these two high-priority questions. These clinical questions and outcomes will be used to inform CPG recommendations for people with MCCs. DESIGN AND PARTICIPANTS: The ICVH program provided 130 topics rank-ordered by the potential for finding evidence that would change clinical recommendations regarding the topic. We used a modified Delphi method to identify and reword topics into questions relevant to people with MCCs. We used two sets of focus groups (n = 27) to elicit patient and caregiver perspectives on two important research questions and relevant patient-important outcomes on benefit/harm balance for people with MCCs. Co-investigators, patients and caregivers identified "optimal blood pressure goals" and "diabetes medication management" as important clinical topics for CPGs related to people with MCCs. Stakeholders identified a list of relevant outcomes to be addressed in future CPG development including 1) physical function and energy, 2) emotional health and well-being, 3) avoidance of treatment burden, side effects and risks, 4) interaction with providers and health care system, and 5) prevention of adverse long-term health outcomes. Through the application of a mixed-methods process, we identified the questions regarding optimal blood pressure goals and diabetes medication management

  6. Addressing the key communication barriers between microbiology laboratories and clinical units: a qualitative study.

    PubMed

    Skodvin, Brita; Aase, Karina; Brekken, Anita Løvås; Charani, Esmita; Lindemann, Paul Christoffer; Smith, Ingrid

    2017-09-01

    Many countries are on the brink of establishing antibiotic stewardship programmes in hospitals nationwide. In a previous study we found that communication between microbiology laboratories and clinical units is a barrier to implementing efficient antibiotic stewardship programmes in Norway. We have now addressed the key communication barriers between microbiology laboratories and clinical units from a laboratory point of view. Qualitative semi-structured interviews were conducted with 18 employees (managers, doctors and technicians) from six diverse Norwegian microbiological laboratories, representing all four regional health authorities. Interviews were recorded and transcribed verbatim. Thematic analysis was applied, identifying emergent themes, subthemes and corresponding descriptions. The main barrier to communication is disruption involving specimen logistics, information on request forms, verbal reporting of test results and information transfer between poorly integrated IT systems. Furthermore, communication is challenged by lack of insight into each other's area of expertise and limited provision of laboratory services, leading to prolonged turnaround time, limited advisory services and restricted opening hours. Communication between microbiology laboratories and clinical units can be improved by a review of testing processes, educational programmes to increase insights into the other's area of expertise, an evaluation of work tasks and expansion of rapid and point-of-care test services. Antibiotic stewardship programmes may serve as a valuable framework to establish these measures.

  7. Issue-Specific Barriers to Addressing Environmental Issues in the Classroom: An Exploratory Study

    ERIC Educational Resources Information Center

    Kim, Chankook; Fortner, Rosanne W.

    2006-01-01

    To explore issue-specific barriers to teaching environmental issues, the authors investigated secondary science teachers' perceived current and preferred teaching levels for 23 environmental issues and perceived barriers to teaching the selected issues. Subjects in this graduate project were 41 secondary science teachers self-selected to answer a…

  8. Issue-Specific Barriers to Addressing Environmental Issues in the Classroom: An Exploratory Study

    ERIC Educational Resources Information Center

    Kim, Chankook; Fortner, Rosanne W.

    2006-01-01

    To explore issue-specific barriers to teaching environmental issues, the authors investigated secondary science teachers' perceived current and preferred teaching levels for 23 environmental issues and perceived barriers to teaching the selected issues. Subjects in this graduate project were 41 secondary science teachers self-selected to answer a…

  9. [Clinical and biological specificities of female alcoholism].

    PubMed

    Limosin, F

    2002-01-01

    Even though the number of alcohol-dependent women is only about 1/3 of the number of alcoholic men, the alcoholism in women, by its clinical features and its course, is the source of therapeutic and economic stakes, particularly in young women among whom an increase of alcohol consumption related problems is reported. Another specificity of the female alcoholism is the lack of care seeking, whereas women have tendency globally to solicit more often care structures than men. Women represent only 1/4 of the overall treated alcoholic patients. The main explanation for this phenomenon is the pejorative social and moral connotation of the female alcoholism, with frequent feelings of shame and deep guilt, that also account for the frequency of hidden and lonely alcohol intakes. The female alcoholism is essentially characterized by an increased vulnerability to the toxic effects of the alcohol, whereas the pathological consumption starts later and with smaller daily amounts. Most studies have revealed a higher vulnerability in women to somatic complications directly attributable to the alcohol organs toxicity, such as hepatic cirrhosis and cardiovascular complications (high blood pressure, non obstructive cardiomyopathy). The reported brain morphological abnormalities could also occur more precociously in alcoholic women than in men. A decreased corpus callosum size among alcoholic women, but not in alcoholic men, was thus found in a recent study, compared with healthy controls. Among the different hypothesis proposed to explain this increased alcohol toxicity, the most incriminated is higher alcohol blood rates for the same ingested amount, mainly of the fact of a lower size with a weaker proportion of the bodily total water, but also of weaker concentrations of gastro-intestinal tract ADH, or of a longer metabolism during some menstrual phases. Indeed, some experimental studies on animal showed that the alcohol toxic effects may occur only from a threshold of alcohol

  10. AAPS workshop report: strategies to address therapeutic protein-drug interactions during clinical development.

    PubMed

    Girish, Sandhya; Martin, Steven W; Peterson, Mark C; Zhang, Lei K; Zhao, Hong; Balthasar, Joseph; Evers, Raymond; Zhou, Honghui; Zhu, Min; Klunk, Lewis; Han, Chao; Berglund, Eva Gil; Huang, Shiew-Mei; Joshi, Amita

    2011-09-01

    Therapeutic proteins (TPs) are increasingly combined with small molecules and/or with other TPs. However preclinical tools and in vitro test systems for assessing drug interaction potential of TPs such as monoclonal antibodies, cytokines and cytokine modulators are limited. Published data suggests that clinically relevant TP-drug interactions (TP-DI) are likely from overlap in mechanisms of action, alteration in target and/or drug-disease interaction. Clinical drug interaction studies are not routinely conducted for TPs because of the logistical constraints in study design to address pharmacokinetic (PK)- and pharmacodynamic (PD)-based interactions. Different pharmaceutical companies have developed their respective question- and/or risk-based approaches for TP-DI based on the TP mechanism of action as well as patient population. During the workshop both company strategies and regulatory perspectives were discussed in depth using case studies; knowledge gaps and best practices were subsequently identified and discussed. Understanding the functional role of target, target expression and their downstream consequences were identified as important for assessing the potential for a TP-DI. Therefore, a question-and/or risk-based approach based upon the mechanism of action and patient population was proposed as a reasonable TP-DI strategy. This field continues to evolve as companies generate additional preclinical and clinical data to improve their understanding of possible mechanisms for drug interactions. Regulatory agencies are in the process of updating their recommendations to sponsors regarding the conduct of in vitro and in vivo interaction studies for new drug applications (NDAs) and biologics license applications (BLAs).

  11. Discovery and Subtyping of Neo-Epitope Specific T-Cell Responses for Cancer Immunotherapy: Addressing the Mutanome.

    PubMed

    Diken, Mustafa; Vormehr, Mathias; Grunwitz, Christian; Kreiter, Sebastian; Türeci, Özlem; Sahin, Ugur

    2017-01-01

    Cancer accumulates 10s to 1000s of genomic mutations of which a fraction is immunogenic and may serve as an Achilles' heel of tumor cells. Mutation-specific T cells can recognize these antigens and destroy malignant cells. Strategies to immunotherapeutically address individual tumor mutations employing peptide or mRNA based vaccines are now actively investigated in mice and humans. An important step of determining the therapeutic potential of a mutanome vaccine is the detection of mutation reactive T-cell responses. In this chapter we provide protocols to identify and subtype mutation specific T cells in mice based on IFN-γ ELISpot and flow cytometry.

  12. Management of type 2 diabetes: more evidence is required to address the clinical and contextual facets.

    PubMed

    Hernandez-Jimenez, Sergio; Aguilar-Salinas, Carlos A; Mehta, Roopa; Rull, Juan A; Gómez-Pérez, Francisco J

    2011-03-01

    Evidence based medicine has changed the manner in which medicine is practiced and learned. Epidemiological studies, meta-analyses and systematic reviews have been used to create algorithms for the treatment of hyperglycemia in patients with type 2 diabetes. Recently, several randomized controlled trials (i.e. ACCORD, ADVANCE, VADT) have generated new and valuable information regarding the benefits and risks of achieving optimal glucose control. As a result, guidelines and algorithms have been updated. However, many aspects remain controversial. In this article, the clinical implications of the existing guidelines are critically analyzed. The limitations of the current guidelines include the lack of applicability to relevant diabetic subgroups, the exclusion of important factors that modify the therapeutic response to glucose-lowering agents and the limited recognition of the importance of the socioeconomic situation on treatment efficacy. Many subgroups of patients have not been included in the studies used to generate recommendations. There is insufficient evidence to support the use of current treatment recommendations in patients with early onset type 2 diabetes, patients with advanced microvascular complications, and the elderly with or without chronic complications. The characteristics of the candidates for conservative or intensive treatment are poorly defined. Interventions are recommended without considering clinical variables (i.e. obesity, time since diagnosis or prolonged exposure to hyperglycemia) that may modify treatment efficacy and the occurrence of side effects. Finally, no consideration is given to the socioeconomic context of the population in which the guidelines are to be applied. In summary, this manuscript highlights the key areas which require further work. If these issues are adequately addressed, the guidelines for the management of type 2 diabetes will be relevant and applicable to all diabetic groups.

  13. Clinical Evaluation of a Multi-Modal Facial Serum That Addresses Hyaluronic Acid Levels in Skin.

    PubMed

    Raab, Susana; Yatskayer, Margarita; Lynch, Stephen; Manco, Megan; Oresajo, Christian

    2017-09-01

    Hyaluronic acid (HA), the major glycosaminoglycan present in the human skin, is a key contributor to water retention and mechanical support in skin. The level, size, and functionality of cutaneous HA are known to diminish with age. Topical treatments designed to increase the HA content of skin have been met with limited success. The purpose of this study was to evaluate the tolerance and efficacy of a multi-modal facial serum containing HA, Proxylane (C-Xyloside), purple rice extract, and dipotassium glycyrrhizate in addressing HA levels in skin. A 12-week, single center, clinical study was conducted on 59 women with mild to moderate photodamage. Clinical grading to assess the efficacy and tolerability was conducted on the face at baseline and at weeks 4, 8, and 12. Bioinstrumentation measurements were taken, including corneometer, tewameter, ultrasound, and standardized digital imaging. A randomized subset of 20 subjects from the study population had 3 mm punch biopsies collected for quantitative RT-PCR analysis from 2 sites on the face at baseline and week 12. Additionally, a 4-week, single center, clinical study was conducted on the photodamaged forearms of 12 subjects. At both baseline and week 4, a 4 mm punch biopsy was obtained from the subjects' randomized forearms. Biopsy samples were subjected to immunohistochemical staining and analysis of HA content. Statistically-significant improvements in all facial skin attributes (weeks 4, 8, and 12), stratum corneum hydration (week 12), and transepidermal water loss (week 12) were observed. Tolerability was excellent, with no increases in irritation parameters noted. A significant increase of HA content in skin after 4 weeks of treatment was observed. By PCR analysis, there was a significant increase in hyaluronan synthase 2, as well as a significant increase in collagen type 1a1 after 12 weeks of application. The findings suggest that this novel topical facial serum is capable of stimulating HA and skin

  14. The SSC cycle: a PDCA approach to address site-specific characteristics in a continuous shallow water quality monitoring project.

    PubMed

    Miles, Eduardo J

    2008-05-01

    In any water quality-monitoring project there are several critical success factors that must be adequately addressed in order to ensure the implementation and realization of the monitoring objectives. Site selection is one of these critical success factors. The monitoring sites must be selected to comply with the monitoring and data quality objectives. In the real world, ideal monitoring setting conditions are difficult to achieve, and compromises must be made in order to locate the monitoring stations that best represent the environment to be monitored. Site-specific characteristics are all the environmental, logistical and management factors particular to the monitoring site, that could influence the fulfilment of the monitoring and data quality objectives. Therefore, during the site selection process, it is essential to properly consider and evaluate these site-specific characteristics. The SSC cycle was developed with this goal in mind, to assist the monitoring team to systematically address site-specific characteristics. The cycle is a methodology to organize the site-specific characteristics in different categories, and to ensure a comprehensive overview of these characteristics throughout the project life cycle.

  15. Insular primary glioblastomas with IDH mutations: Clinical and biological specificities.

    PubMed

    Hata, Nobuhiro; Hatae, Ryusuke; Yoshimoto, Koji; Murata, Hideki; Kuga, Daisuke; Akagi, Yojiro; Sangatsuda, Yuhei; Suzuki, Satoshi O; Iwaki, Toru; Mizoguchi, Masahiro; Iihara, Koji

    2017-01-24

    Isocitrate dehydrogenase (IDH) mutation is a good prognostic marker for glioblastoma (GBM). Although it is infrequent in primary tumors, it is found in most lower-grade gliomas. Thus, it is unclear whether IDH mutation is a marker for a specific phenotype of apparently primary de novo GBMs (pGBMs), or a marker for secondary tumors (sGBMs). We addressed this issue by analyzing clinical, radiographic and molecular findings in our institutional case series. Our cases included 92 pGBMs, with five cases of IDH1 mutations at R132 and no IDH2 mutations. The median overall survival of these five patients was 29 months (range: 4 to >40 months), which is considered good prognoses. Clinical and radiographic characteristics were distinct from IDH-wildtype (IDH-wt) pGBMs. IDH-mutant (IDH-mut) tumors consistently involved insular lesions and were subdivided into: (i) the two cases of elderly patients with long clinical histories and features implying multistep tumor development; and (ii) the three cases of younger patients with diffusely swelling insular tumors, slight contrast enhancement and no necrosis. Genetic and expression analyses of IDH-mut pGBMs were similar to those of sGBMs, suggesting that they are indeed distinct from their IDH-wt counterparts. TERT promoter mutation, a genetic marker of oligodendroglial derivation, was detected in one long-surviving case, but genetic alterations in the astrocyte-sGBM pathway were generally prevalent in IDH-mut pGBMs. Our results present a unique phenotype of IDH-mut pGBMs arising from insular cortex region, the molecular backgrounds of which are similar to sGBMs.

  16. Addressing culture shock in first year midwifery students: Maximising the initial clinical experience.

    PubMed

    Cummins, Allison M; Catling, Christine; Hogan, Rosemarie; Homer, Caroline S E

    2014-12-01

    Many Bachelor of Midwifery students have not had any exposure to the hospital setting prior to their clinical placement. Students have reported their placements are foreign to them, with a specialised confusing 'language'. It is important to provide support to students to prevent culture shock that may lead to them leaving the course. To assist first year midwifery students with the transition into clinical practice by providing a preparatory workshop. An action research project developed resources for a workshop held prior to students' first clinical placement. Four phases were held: Phase one involved holding discussion groups with students returning from clinical practice; Phase two was the creation of vodcasts; Phase three was integration of resources into the clinical subject and phase four was the evaluation and reflection on the action research project. Evaluations of the workshops were undertaken through surveying the students after they returned from their clinical placement. A descriptive analysis of the evaluations was performed. Students rated the workshop, vodcasts and the simulated handover positively. Further recommendations were that complications of labour and birth be included in their first semester as students were unexpectedly exposed to this in their first clinical placement. The students evaluated the workshop positively in reducing the amount of culture shock experienced on the first clinical placement. In addition the students provided further recommendations of strategies that would assist with clinical placement. Copyright © 2014 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

  17. Hispanic Women's Expectations of Campus-Based Health Clinics Addressing Sexual Health Concerns

    ERIC Educational Resources Information Center

    Stephens, Dionne P.; Thomas, Tami L.

    2011-01-01

    Although the number of Hispanic women attending postsecondary institutions has significantly increased in the past decade, knowledge about their use of campus health services to address sexuality-related issues remains low. Increased information about this population is crucial given that sexual health indicators have shown Hispanic women in…

  18. Hispanic Women's Expectations of Campus-Based Health Clinics Addressing Sexual Health Concerns

    ERIC Educational Resources Information Center

    Stephens, Dionne P.; Thomas, Tami L.

    2011-01-01

    Although the number of Hispanic women attending postsecondary institutions has significantly increased in the past decade, knowledge about their use of campus health services to address sexuality-related issues remains low. Increased information about this population is crucial given that sexual health indicators have shown Hispanic women in…

  19. Addressing anxiety in vivo in physiotherapy treatment of women with severe vaginismus: a clinical approach.

    PubMed

    Rosenbaum, Talli

    2011-01-01

    Physiotherapy for the treatment of vaginismus is perceived as an intervention aimed to normalize muscle tone of the pelvic floor in order to allow vaginal penetration in accordance with the traditional view of vaginal spasm as its defining feature. Newer definitions recognize the experience of anxiety as well as pain, and effective treatment approaches should address these components as well. Physiotherapists often encounter women who, as a result of severe anxiety, are unable to undergo examination and treatment, despite their expressed desire to do so. This article describes a therapeutic intervention designed to help women with vaginismus prepare for examination and treatment by addressing the component of anxiety in real-life situations. This approach is also appropriate for nurse practitioners and physicians who work with this patient population and may be adapted for sex therapists to teach as a home exercise.

  20. Healthy me: A gender-specific program to address body image concerns and risk factors among preadolescents.

    PubMed

    McCabe, Marita P; Connaughton, Catherine; Tatangelo, Gemma; Mellor, David; Busija, Lucy

    2017-03-01

    This study evaluated a gender-specific, school-based program to promote positive body image and address risk factors for body dissatisfaction. In total, 652 children aged 8-10 years participated (335 intervention, 317 wait-list control). Children participated in four 60min sessions and a recap session at three months post-intervention. The broad content areas were body image, peer relationships, media awareness, healthy diet, and exercise. The activities and examples for each session were gender specific. The recap session was an overview of the four sessions. Assessment measures were completed at pre-intervention, post-intervention, and after the recap. Boys and girls in the intervention demonstrated higher muscle esteem and vegetable intake at post-intervention, compared to children in the control condition. Boys and girls demonstrated higher body esteem, muscle esteem and fruit and vegetable intake at the recap. Boys in the intervention demonstrated less investment in masculine gender norms at post-intervention and at recap. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Implementing Peer Learning in Clinical Education: A Framework to Address Challenges In the "Real World".

    PubMed

    Tai, Joanna Hong Meng; Canny, Benedict J; Haines, Terry P; Molloy, Elizabeth K

    2017-01-01

    Phenomenon: Peer learning has many benefits and can assist students in gaining the educational skills required in future years when they become teachers themselves. Peer learning may be particularly useful in clinical learning environments, where students report feeling marginalized, overwhelmed, and unsupported. Educational interventions often fail in the workplace environment, as they are often conceived in the "ideal" rather than the complex, messy real world. This work sought to explore barriers and facilitators to implementing peer learning activities in a clinical curriculum.

  2. Linking HIV-positive adolescents to care in 15 different clinics across the United States: creating solutions to address structural barriers for linkage to care.

    PubMed

    Philbin, Morgan M; Tanner, Amanda E; Duval, Anna; Ellen, Jonathan; Kapogiannis, Bill; Fortenberry, J Dennis

    2014-01-01

    Linkage to care is a critical corollary to expanded HIV testing, but many adolescents are not successfully linked to care, in part due to fragmented care systems. Through a collaboration of the National Institutes of Health (NIH), Centers for Disease Control and Prevention (CDC) and the Adolescent Trials Network (ATN), a linkage to care outreach worker was provided to ATN clinics. Factors related to linkage were explored to better understand how to improve retention rates and health outcomes for HIV-positive adolescents. We conducted 124 interviews with staff at 15 Adolescent Trials Network clinics to better understand linkage to care processes, barriers, and facilitators. Content analysis was conducted focusing on structural barriers to care and potential solutions, specifically at the macro-, meso-, and micro-levels. Macro-level barriers included navigating health insurance policies, transportation to appointments, and ease of collecting and sharing client-level contact information between testing agencies, local health departments and clinics; meso-level barriers included lack of youth friendliness within clinic space and staff, and duplication of linkage services; micro-level barriers included adolescents' readiness for care and adolescent developmental capacity. Staff initiated solutions included providing transportation for appointments and funding clinic visits and tests with a range of grants and clinic funds while waiting for insurance approval. However, such solutions were often ad hoc and partial, using micro-level solutions to address macro-level barriers. Comprehensive initiatives to improve linkage to care are needed to address barriers to HIV-care for adolescents, whose unique developmental needs make accessing care particularly challenging. Matching the level of structural solution to the level of structural barriers (i.e., macro-level with macro-level), such as creating policy to address needed youth healthcare entitlements versus covering

  3. Time to do more: addressing clinical inertia in the management of type 2 diabetes mellitus.

    PubMed

    Strain, W D; Cos, X; Hirst, M; Vencio, S; Mohan, V; Vokó, Z; Yabe, D; Blüher, M; Paldánius, P M

    2014-09-01

    Clinical inertia, the tendency to maintain current treatment strategies despite results demanding escalation, is thought to substantially contribute to the disconnect between clinical aspirations for patients with diabetes and targets achieved. We wished to explore potential causes of clinical inertia among physicians and people with diabetes. A 20-min online survey of 652 adults with diabetes and 337 treating physicians in six countries explored opinions relating to clinical inertia from both perspectives, in order to correlate perceptions and expectations relating to diagnosis, treatment, diabetes complications and therapeutic escalation. Physicians had low expectations for their patients, despite the belief that the importance of good glycaemic control through lifestyle and pharmacological interventions had been adequately conveyed. Conversely, people with diabetes had, at best, a rudimentary understanding of the risks of complications and the importance of good control; indeed, only a small proportion believed lifestyle changes were important and the majority did not intend to comply. The principal findings of this survey suggest that impairments in communication are at the heart of clinical inertia. This manuscript lays out four key principles that we believe are achievable in all environments and can improve the lives of people with diabetes. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  4. Bioethics in practice: Addressing ethically sensitive requests in a Dutch fertility clinic.

    PubMed

    Gerrits, Trudie; Reis, Ria; Braat, Didi D M; Kremer, Jan A M; Hardon, Anita P

    2013-12-01

    This article provides insight into how ethically sensitive requests for the use of assisted reproductive technologies (ARTs) are dealt within the daily practice of a Dutch fertility clinic. The findings presented are part of an ethnographic study conducted in this clinic from September 2003 until April 2005. Information for this article was gathered by attending the multidisciplinary ethics meetings and conversations with clinic staff. By looking at 'bioethics in practice', this article provides insight into the complex and dynamic interplay between particular couples' situations, contextual features, bioethical principles, doctors' subjective feelings and views, and the employment of medical practices. Our study suggests that personal views to a certain extent inform the agenda of the ethics meetings, but in the end neither these views nor bioethical principles fully determine the decisions made. Clinic staff members employ routine medical practices with the intention to carefully resolve ethically sensitive cases. These practices include: collegial consultation, searching for scientific evidence in the literature, obtaining more medical information, offering medical tests, referring couples to other clinics and ensuring informed consent. Rather than examining hypothetical cases, which evoke principles, observations of practices regarding real life cases of which many details are known, allowed us to identify the influence of routine medical practice on ethical decisions. Despite initial concerns from the side of the medical professionals (some of which might be regarded as paternalistic), at the end the reproductive autonomy of most couples seeking ARTs was not jeopardized. The format of the multidisciplinary ethics meetings seems to be promising as it provides a space for clinic staff members to express and reflect on their subjective views and feelings of unease regarding certain requests for ARTs, while at the same time it diminishes the risk that decision

  5. Addressing Heavy Drinking in Smoking Cessation Treatment: A Randomized Clinical Trial

    ERIC Educational Resources Information Center

    Kahler, Christopher W.; Metrik, Jane; LaChance, Heather R.; Ramsey, Susan E.; Abrams, David B.; Monti, Peter M.; Brown, Richard A.

    2008-01-01

    Heavy alcohol use frequently co-occurs with cigarette smoking and may impede smoking cessation. This clinical trial examined whether smoking cessation treatment that incorporates brief alcohol intervention can improve smoking cessation outcomes (7-day verified point prevalence abstinence) and reduce drinks consumed per week. Heavy drinkers seeking…

  6. Addressing Heavy Drinking in Smoking Cessation Treatment: A Randomized Clinical Trial

    ERIC Educational Resources Information Center

    Kahler, Christopher W.; Metrik, Jane; LaChance, Heather R.; Ramsey, Susan E.; Abrams, David B.; Monti, Peter M.; Brown, Richard A.

    2008-01-01

    Heavy alcohol use frequently co-occurs with cigarette smoking and may impede smoking cessation. This clinical trial examined whether smoking cessation treatment that incorporates brief alcohol intervention can improve smoking cessation outcomes (7-day verified point prevalence abstinence) and reduce drinks consumed per week. Heavy drinkers seeking…

  7. Direct Versus Remote Clinical Observation: Assessing Learners' Milestones While Addressing Adolescent Patients' Needs

    PubMed Central

    Pitts, Sarah; Borus, Joshua; Goncalves, Adrianne; Gooding, Holly

    2015-01-01

    Background Direct clinical observation is an essential component of medical trainee assessment, particularly in the era of milestone-based competencies. However, the adolescent patient's perspective on this practice is missing from the literature. Quality health care is patient centered, yet we did not know if our educational practices align with this clinical goal. Objective We sought to better understand our adolescent/young adult patients' perspectives of the direct observation of our medical trainees in the outpatient clinical setting. Methods As a quality improvement initiative, we surveyed adolescent/young adult patients, medical trainees, and physician observers in our outpatient clinical practice regarding their experience following a direct observation encounter. We performed descriptive analyses of the data. Results During a 1-year period, responses were received from 23 adolescent/young adult patients, 8 family members, 14 trainees, and 6 faculty observers. Nearly all adolescent/young adult patients (n = 22) and all surveyed family members (n = 8) expressed comfort with direct observation, and all respondents felt the care they received was the same or better. All patient/family respondents preferred direct observation to the idea of remote observation, and most, but not all, trainees and faculty observers expressed similar opinions. Conclusions Adolescent/young adult patients and their family members found direct observation of their trainee providers to be comfortable and beneficial. Despite adolescent and young adults' facility and comfort with modern technologies, there was an expressed preference for direct versus remote observation. PMID:26221445

  8. Direct Versus Remote Clinical Observation: Assessing Learners' Milestones While Addressing Adolescent Patients' Needs.

    PubMed

    Pitts, Sarah; Borus, Joshua; Goncalves, Adrianne; Gooding, Holly

    2015-06-01

    Direct clinical observation is an essential component of medical trainee assessment, particularly in the era of milestone-based competencies. However, the adolescent patient's perspective on this practice is missing from the literature. Quality health care is patient centered, yet we did not know if our educational practices align with this clinical goal. We sought to better understand our adolescent/young adult patients' perspectives of the direct observation of our medical trainees in the outpatient clinical setting. As a quality improvement initiative, we surveyed adolescent/young adult patients, medical trainees, and physician observers in our outpatient clinical practice regarding their experience following a direct observation encounter. We performed descriptive analyses of the data. During a 1-year period, responses were received from 23 adolescent/young adult patients, 8 family members, 14 trainees, and 6 faculty observers. Nearly all adolescent/young adult patients (n=22) and all surveyed family members (n=8) expressed comfort with direct observation, and all respondents felt the care they received was the same or better. All patient/family respondents preferred direct observation to the idea of remote observation, and most, but not all, trainees and faculty observers expressed similar opinions. Adolescent/young adult patients and their family members found direct observation of their trainee providers to be comfortable and beneficial. Despite adolescent and young adults' facility and comfort with modern technologies, there was an expressed preference for direct versus remote observation.

  9. 'Nursing research culture' in the context of clinical nursing practice: addressing a conceptual problem.

    PubMed

    Berthelsen, Connie Bøttcher; Hølge-Hazelton, Bibi

    2017-05-01

    To report an analysis of the concept of nursing research culture in the context of clinical nursing practice. Nursing research culture should be valued for its contribution to improving patient care and should be considered as a routine hospital activity. However, the demand for efficiency, nurses' barriers to research use and the lack of definition of the concept of nursing research culture make it difficult to establish. Concept analysis. Data were collected through a literature review in PubMed, CINAHL and PsycINFO during March 2016. Walker and Avant's eight-step framework for concept analysis. Five defining attributes of nursing research culture in the context of clinical nursing practice were identified: strong monodisciplinary nursing professionalism, academic thinking and socialization, research use as a part of daily nursing practice, acceptance by colleagues and management and facilitation of resources from management and organization. Although the method of concept analysis has been criticized and heavily debated, the development of nursing research cultures based on the defining attributes and antecedents of the concept will be important to emphasize evidence-based clinical nursing care. Further research should support the development and the implementation of nursing research culture in clinical nursing practice. © 2016 John Wiley & Sons Ltd.

  10. Teaching to Transform? Addressing Race and Racism in the Teaching of Clinical Social Work Practice

    ERIC Educational Resources Information Center

    Varghese, Rani

    2016-01-01

    Faculty members are key stakeholders to support social work students' learning about race and racism in practice and to promote the professional standards established by the field. This qualitative study examines how 15 clinical social work faculty members teaching advanced practice in the Northeast conceptualize and incorporate their…

  11. Teaching to Transform? Addressing Race and Racism in the Teaching of Clinical Social Work Practice

    ERIC Educational Resources Information Center

    Varghese, Rani

    2016-01-01

    Faculty members are key stakeholders to support social work students' learning about race and racism in practice and to promote the professional standards established by the field. This qualitative study examines how 15 clinical social work faculty members teaching advanced practice in the Northeast conceptualize and incorporate their…

  12. CPTAC Collaborates with Molecular & Cellular Proteomics to Address Reproducibility in Targeted Assay Development | Office of Cancer Clinical Proteomics Research

    Cancer.gov

    The journal Molecular & Cellular Proteomics (MCP), in collaboration with the Clinical Proteomic Tumor Analysis Consortium (CPTAC) of the National Cancer Institute (NCI), part of the National Institutes of Health, announce new guidelines and requirements for papers describing the development and application of targeted mass spectrometry measurements of peptides, modified peptides and proteins (Mol Cell Proteomics 2017; PMID: 28183812).  NCI’s participation is part of NIH’s overall effort to address the r

  13. Practical guidelines addressing ethical issues pertaining to the curation of human locus-specific variation databases (LSDBs)

    PubMed Central

    Povey, Sue; Al Aqeel, Aida I; Cambon-Thomsen, Anne; Dalgleish, Raymond; den Dunnen, Johan T; Firth, Helen V; Greenblatt, Marc S; Barash, Carol Isaacson; Parker, Michael; Patrinos, George P; Savige, Judith; Sobrido, Maria-Jesus; Winship, Ingrid; Cotton, Richard GH

    2010-01-01

    More than 1,000 Web-based locus-specific variation databases (LSDBs) are listed on the Website of the Human Genetic Variation Society (HGVS). These individual efforts, which often relate phenotype to genotype, are a valuable source of information for clinicians, patients, and their families, as well as for basic research. The initiators of the Human Variome Project recently recognized that having access to some of the immense resources of unpublished information already present in diagnostic laboratories would provide critical data to help manage genetic disorders. However, there are significant ethical issues involved in sharing these data worldwide. An international working group presents second-generation guidelines addressing ethical issues relating to the curation of human LSDBs that provide information via a Web-based interface. It is intended that these should help current and future curators and may also inform the future decisions of ethics committees and legislators. These guidelines have been reviewed by the Ethics Committee of the Human Genome Organization (HUGO). Hum Mutat 31:–6, 2010. © 2010 Wiley-Liss, Inc. PMID:20683926

  14. Mobile farm clinic outreach to address health conditions among Latino migrant farmworkers in Georgia.

    PubMed

    Luque, John S; Reyes-Ortiz, Carlos; Marella, Prasen; Bowers, Angelica; Panchal, Viral; Anderson, Lisa; Charles, Simone

    2012-01-01

    Agricultural labor involves exposure to many occupational hazards, some of which can lead to chronic health conditions. The purpose of this study was to conduct an occupational health needs assessment of illnesses and work-related injuries among a Latino migrant farmworker population (recruited to harvest Vidalia onions) in South Georgia. Study data included survey responses from 100 farmworkers attending mobile farm clinics in 2010 at their worker housing residences, supplemented by medical diagnoses data from the same clinics collected over 3 years (2009-2011) for 1161 farmworkers at six different farms. From the survey, the main health problems reported were hypertension (25%), eye problems (12%), musculoskeletal problems (11%), diabetes (10%), and depression (7%). In multivariate analyses, depression scores were associated with having a history of musculoskeletal problems (p = .002). According to the mobile farm clinic data, the most common medical diagnoses included back pain (11.8%), hypertension (11.4%), musculoskeletal problems (11.3%), gastrointestinal disorders (8.6%), eye problems (7.2%), dermatitis or rash (7.0%), and tinea or fungal skin infections (5.6%). The study identified eye and musculoskeletal problems as the major occupational health conditions for this population of farmworkers.

  15. Pedagogical Tools to Address Clinical Anatomy and Athletic Training Student Learning Styles

    ERIC Educational Resources Information Center

    Mazerolle, Stephanie; Yeargin, Susan

    2010-01-01

    Context: A thorough knowledge of anatomy is needed in four of the six domains of athletic training: prevention, injury/condition recognition, immediate care, and treatment/rehabilitation. Students with a solid foundation can achieve competency in these specific domains. Objective: To provide educators with pedagogical tools to promote a deeper…

  16. Pedagogical Tools to Address Clinical Anatomy and Athletic Training Student Learning Styles

    ERIC Educational Resources Information Center

    Mazerolle, Stephanie; Yeargin, Susan

    2010-01-01

    Context: A thorough knowledge of anatomy is needed in four of the six domains of athletic training: prevention, injury/condition recognition, immediate care, and treatment/rehabilitation. Students with a solid foundation can achieve competency in these specific domains. Objective: To provide educators with pedagogical tools to promote a deeper…

  17. Trial Design and Endpoint Evaluation in Clinical Studies Addressing Chronic Back Pain.

    PubMed

    Staats, Peter S

    2017-07-15

    A review of the literature evaluating clinical trials of chronic back pain. To assist physicians in assessing the quality of clinical trial data to make the most informed treatment decisions. Chronic pain is a tremendous public health issue, affecting close to 100 million adults in the United States, and costs the American people billions of dollars. One traditional treatment approach, the long-term use of opiate medications, has recently come under intense scrutiny for problems with complications, diversion, abuse, addiction, and lack of efficacy. In addition, the Centers for Disease Control and Prevention has recognized that overprescribing opiates has enabled an overdose crisis, and written guidelines that are intended to limit their use. It is for this reason that physicians must have a comprehensive understanding of the range of drug-free alternative therapies available and have the tools needed to rigorously evaluate the chronic pain literature so they can make appropriate treatment decisions. An evaluation of how clinical trials are designed and ranked, outcome measures, and costs for a variety of therapies is necessary to determine which treatment option is the most efficacious for an individual patient. Clinical trial data demonstrate that spinal cord stimulation (SCS) is a safe and effective treatment option for many types of chronic pain, including back pain. The last 10 years has brought tremendous advances in the field of neuromodulation. Today, several treatment modalities exist for SCS requiring the physician to be able to critically evaluate and interpret the literature and determine which modality has the strongest evidence. When evaluating clinical trial data of patients with chronic back pain, emphasis must be placed on well designed, randomized controlled trials with long-term follow-up producing level I evidence. These data are obtained in a rigorous manner and are likely to have less bias when compared with lower level studies. The level I

  18. Potential Strategies to Address the Major Clinical Hurdles Facing Stem Cell Regenerative Therapy for Cardiovascular Disease: A Review

    PubMed Central

    Nguyen, Patricia K.; Neofytou, Evgenios; Rhee, June-Wha; Wu, Joseph C.

    2017-01-01

    Importance While progress continues to be made in the field of stem cell regenerative medicine for the treatment of cardiovascular disease, significant barriers to clinical translation still exist that have thwarted the delivery of cell therapy to the bedside. Objective The purpose of this review is to summarize the major current hurdles for the clinical implementation of stem cell therapy and discuss potential strategies to overcome them. Evidence Review Information for this review was obtained through a search of PubMed and the Cochrane database for English language studies published between January 1, 2000 and June 15, 2016. Ten randomized clinical trials and eight systematic reviews were included in this review. Findings One of the major clinical hurdles facing the routine implementation of stem cell therapy is the limited and inconsistent benefit observed thus far. Reasons for this are unclear but may be due to poor cell retention and survival, as suggested by numerous preclinical studies and a handful of human studies incorporating cell fate imaging. Additional cell fate imaging studies in humans are needed to determine how these factors contribute to limited efficacy. Treatment strategies to address poor cell retention and survival are under investigation and include the following: 1) co-administering of immunosuppressive and pro-survival agents, 2) delivering cardioprotective factors packaged in exosomes rather than the cells themselves, and 3) using tissue engineering strategies to provide structural support for cells. If larger grafts are achieved using the aforementioned strategies, it will be imperative to carefully monitor the potential risks of tumorigenicity, immunogenicity, and arrhythmogenicity. Conclusions and Relevance Despite important achievements to date, stem cell therapy is not yet ready for routine clinical implementation. Significant research is still needed to address the clinical hurdles outlined herein before the next wave of large

  19. Tailoring clinical services to address the unique needs of adolescents from the pregnancy test to parenthood.

    PubMed

    Moriarty Daley, Alison; Sadler, Lois S; Dawn Reynolds, Heather

    2013-04-01

    Clinicians across disciplines and practice settings are likely to encounter adolescents who are at risk for a pregnancy. In 2010, 34.2/1000 15-19-year-old teens had a live birth in the United States, many more will seek care for a pregnancy scare or options counseling. Teen mothers are also at risk for a second or higher-order pregnancy during adolescence. This paper provides clinicians with adolescent-friendly clinical and counseling strategies for pregnancy prevention, pre- and post-pregnancy test counseling, pregnancy-related care, and a review of the developmental challenges encountered by teens in the transition to parenthood. Clinicians are in a better position to approach the developmental, health and mental health needs of adolescents related to pregnancy if they understand and appreciate the obstacles adolescents may face negotiating the healthcare system. In addition, when clinical services are specially tailored to the needs of the adolescent, fewer opportunities will be lost to prevent unintended pregnancies, assist teens into timely prenatal services, and improve outcomes for their pregnancies and the transition to parenthood.

  20. Tailoring Clinical Services to Address the Unique Needs of Adolescents from the Pregnancy Test to Parenthood

    PubMed Central

    Daley, Alison Moriarty; Sadler, Lois S.; Reynolds, Heather Dawn

    2013-01-01

    Clinicians across disciplines and practice settings are likely to encounter adolescents who are at risk for a pregnancy. In 2010, 34.2/1000 15–19 year old teens had a live birth in the United States, many more will seek care for a pregnancy scare or options counseling. Teen mothers are also at risk for a second or higher order pregnancy during adolescence. This paper provides clinicians with adolescent-friendly clinical and counseling strategies for pregnancy prevention, pre- and post-pregnancy test counseling, pregnancy-related care, and a review of the developmental challenges encountered by teens in the transition to parenthood. Clinicians are in a better position to approach the developmental, health and mental health needs of adolescents related to pregnancy if they understand and appreciate the obstacles adolescents may face negotiating the health care system. In addition, when clinical services are specially tailored to the needs of the adolescent, fewer opportunities will be lost to prevent unintended pregnancies, assist teens into timely prenatal services, and improve outcomes for their pregnancies and the transition to parenthood. PMID:23522339

  1. Are current standards of reporting quality for clinical trials sufficient in addressing important sources of bias?

    PubMed

    Mills, Edward J; Ayers, Dieter; Chou, Roger; Thorlund, Kristian

    2015-11-01

    Determining the quality of a randomized clinical trial (RCT) is necessary for decision-makers to determine the believability and applicability of the trial findings. Issues that are likely to affect the utility of RCT evidence include issues of bias, random error and applicability. In this article we focus primarily on issues of bias and examine the evidence for whether reporting methodological items, including allocation concealment, sequence generation, and blinding of participants can be relied upon as evidence of bias. We present the findings of a systematic review of meta-epidemiological studies and a simulation study demonstrating that commonly examined sources of bias likely play little role in treatment exaggeration. We discuss other issues that may additionally influence trial outcomes including sample size, publication bias, and expertise of trialists. We conclude by discussing strategies to moderate the effect of known biases in assessing overall estimates of treatment effects.

  2. Developing a contextual consciousness: learning to address gender, societal power, and culture in clinical practice.

    PubMed

    Esmiol, Elisabeth E; Knudson-Martin, Carmen; Delgado, Sarah

    2012-10-01

    Despite the growing number of culturally sensitive training models and considerable literature on the importance of training clinicians in larger contextual issues, research examining how students learn to apply these issues is limited. In this participatory action research project, we systematically studied our own process as marriage and family therapy (MFT) practicum students developing a contextual consciousness. Using grounded theory, we identified a three-stage process: (a) raised awareness through clinical experimentation and developing a theoretical rationale, (b) reflective questioning involving challenging old perspectives and experiencing positive client-therapist interactions, and (c) an intentional new lens based on personal responsibility and commitment. Creating and maintaining a contextual lens required a safe, empowering group dynamic and accessing other forms of support and accountability after the practicum.

  3. HPV 9G DNA chip: 100% clinical sensitivity and specificity.

    PubMed

    An, Heejung; Song, Keum-Soo; Nimse, Satish Balasaheb; Kim, Junghoon; Nguyen, Van-Thuan; Ta, Van-Thao; Sayyed, Danishmalik Rafiq; Kim, Taisun

    2012-03-01

    We describe a novel HPV 9G DNA chip test for the accurate and reliable genotyping of human papillomavirus (HPV). The HPV 9G DNA chip test established its efficiency in terms of a signal-to-background ratio (SBR) of 200, which is 50 times superior to commercial HPV DNA chips, and 100% target-specific hybridization at 25°C. We compared the genotyping results for the 439 clinical samples by the HPV 9G DNA chip test with the sequencing results for the MY11/GP6+ (M2) primer set-mediated PCR products. The discrimination of HPV genotypes in the 151 HPV-positive clinical samples by the HPV 9G DNA chip test were 100% identical with the sequencing analysis. The clinical sensitivities of HPV genotyping by the HPV 9G DNA chip test and a commercial HPV DNA chip test were 100% and 88%, respectively. However, the clinical specificities of HPV genotyping by the HPV 9G DNA chip test and the commercial HPV DNA chip test were 100% and 94%, respectively. The 100% clinical sensitivity and specificity of the HPV 9G DNA chip test make it a promising diagnostic tool for HPV genotyping.

  4. HPV 9G DNA Chip: 100% Clinical Sensitivity and Specificity

    PubMed Central

    An, Heejung; Song, Keum-Soo; Nimse, Satish Balasaheb; Kim, Junghoon; Nguyen, Van-Thuan; Ta, Van-Thao; Sayyed, Danishmalik Rafiq

    2012-01-01

    We describe a novel HPV 9G DNA chip test for the accurate and reliable genotyping of human papillomavirus (HPV). The HPV 9G DNA chip test established its efficiency in terms of a signal-to-background ratio (SBR) of 200, which is 50 times superior to commercial HPV DNA chips, and 100% target-specific hybridization at 25°C. We compared the genotyping results for the 439 clinical samples by the HPV 9G DNA chip test with the sequencing results for the MY11/GP6+ (M2) primer set-mediated PCR products. The discrimination of HPV genotypes in the 151 HPV-positive clinical samples by the HPV 9G DNA chip test were 100% identical with the sequencing analysis. The clinical sensitivities of HPV genotyping by the HPV 9G DNA chip test and a commercial HPV DNA chip test were 100% and 88%, respectively. However, the clinical specificities of HPV genotyping by the HPV 9G DNA chip test and the commercial HPV DNA chip test were 100% and 94%, respectively. The 100% clinical sensitivity and specificity of the HPV 9G DNA chip test make it a promising diagnostic tool for HPV genotyping. PMID:22170909

  5. Specific Gene Loci of Clinical Pseudomonas putida Isolates

    PubMed Central

    Molina, Lázaro; Udaondo, Zulema; Duque, Estrella; Fernández, Matilde; Bernal, Patricia; Roca, Amalia; de la Torre, Jesús; Ramos, Juan Luis

    2016-01-01

    Pseudomonas putida are ubiquitous inhabitants of soils and clinical isolates of this species have been seldom described. Clinical isolates show significant variability in their ability to cause damage to hosts because some of them are able to modulate the host’s immune response. In the current study, comparisons between the genomes of different clinical and environmental strains of P. putida were done to identify genetic clusters shared by clinical isolates that are not present in environmental isolates. We show that in clinical strains specific genes are mostly present on transposons, and that this set of genes exhibit high identity with genes found in pathogens and opportunistic pathogens. The set of genes prevalent in P. putida clinical isolates, and absent in environmental isolates, are related with survival under oxidative stress conditions, resistance against biocides, amino acid metabolism and toxin/antitoxin (TA) systems. This set of functions have influence in colonization and survival within human tissues, since they avoid host immune response or enhance stress resistance. An in depth bioinformatic analysis was also carried out to identify genetic clusters that are exclusive to each of the clinical isolates and that correlate with phenotypical differences between them, a secretion system type III-like was found in one of these clinical strains, a determinant of pathogenicity in Gram-negative bacteria. PMID:26820467

  6. A model for integrating clinical care and basic science research, and pitfalls of performing complex research projects for addressing a clinical challenge.

    PubMed

    Steck, R; Epari, D R; Schuetz, M A

    2010-07-01

    The collaboration of clinicians with basic science researchers is crucial for addressing clinically relevant research questions. In order to initiate such mutually beneficial relationships, we propose a model where early career clinicians spend a designated time embedded in established basic science research groups, in order to pursue a postgraduate qualification. During this time, clinicians become integral members of the research team, fostering long term relationships and opening up opportunities for continuing collaboration. However, for these collaborations to be successful there are pitfalls to be avoided. Limited time and funding can lead to attempts to answer clinical challenges with highly complex research projects characterised by a large number of "clinical" factors being introduced in the hope that the research outcomes will be more clinically relevant. As a result, the complexity of such studies and variability of its outcomes may lead to difficulties in drawing scientifically justified and clinically useful conclusions. Consequently, we stress that it is the basic science researcher and the clinician's obligation to be mindful of the limitations and challenges of such multi-factorial research projects. A systematic step-by-step approach to address clinical research questions with limited, but highly targeted and well defined research projects provides the solid foundation which may lead to the development of a longer term research program for addressing more challenging clinical problems. Ultimately, we believe that it is such models, encouraging the vital collaboration between clinicians and researchers for the work on targeted, well defined research projects, which will result in answers to the important clinical challenges of today. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  7. Collaborative community-based teaching clinics at the Canadian Memorial Chiropractic College: addressing the needs of local poor communities.

    PubMed

    Kopansky-Giles, Deborah; Vernon, Howard; Steiman, Igor; Tibbles, Anthony; Decina, Philip; Goldin, Jarrod; Kelly, Maureen

    2007-10-01

    Inequities in access to health services, resulting from cuts in public sector budgets and inflation, greatly affect Canada's poorest and most vulnerable people. The purpose of this article is to describe the experiences of the community-based teaching clinics of the Canadian Memorial Chiropractic College (CMCC), located in the poor, inner city region of Toronto, where access to chiropractic care for this population has been enabled. Three chiropractic teaching clinics have been established in host facilities in the inner city community of Toronto. For over a decade, CMCC has had collaborative chiropractic clinics in the Sherbourne Health Centre (a southeast Toronto primary care facility), and Anishnawbe Health Toronto (an aboriginal health facility addressing the needs of urban First Nations people). For 3 years, we have been providing chiropractic services in the Department of Family and Community Medicine at St Michael's Hospital. The priority for these programs was the minimization of economic barriers to accessing care for poor and marginalized people. Outcomes have demonstrated high use when there is no economic barrier, excellent clinical outcomes and patient satisfaction, and a high level of collaboration with other health practitioners. The CMCC's external clinics program has enabled access to chiropractic services to thousands of people living in the inner city and urban aboriginal communities of Toronto. This has resulted in the minimization of barriers to accessing care, the provision of appropriate and effective care, and collaboration. These clinics also greatly increase students' awareness of, sensitivity to, and commitment to being part of the solution to these problems.

  8. Efficacy of a Transdiagnostic internet-based treatment for emotional disorders with a specific component to address positive affect: Study protocol for a randomized controlled trial.

    PubMed

    Díaz-García, Amanda; González-Robles, Alberto; Fernández-Álvarez, Javier; García-Palacios, Azucena; Baños, Rosa María; Botella, Cristina

    2017-04-20

    Emotional disorders (ED) are among the most prevalent mental disorders. However, less than 50% of people suffering from ED receive the appropriate treatment. This situation has led to the development of new intervention proposals based on the transdiagnostic perspective, which tries to address the underlying processes common to ED. Most of these programs focus primarily on down-regulating negative affectivity, rather than increasing strengths and up-regulating positive affectivity. The data suggest the existence of disturbances in positive affectivity in these disorders, and so new interventions focusing on these problems are greatly needed. It is also essential to provide assistance to all the people in need. Information and Communication Technologies can be very useful. This study aims to evaluate the efficacy of a transdiagnostic Internet-based treatment for ED in a community sample. The protocol includes traditional CBT components, as well as a specific component to address positive affect. We intend to test this protocol, including this specific component or not, versus a waiting list control group. Moreover, we aim to test the differential effect of this specific component, and study the effectiveness (in terms of patients' acceptance) of using a self-applied Internet-based program. This paper presents the study protocol. The study is a randomized controlled trial. 207 participants will be randomly assigned to: a)Transdiagnostic Internet-based protocol (TIBP), b)Transdiagnostic Internet-based protocol + positive affect component (TIBP + PA), or c)a Waiting List control group (WL). Primary outcomes measures will be the BDI-II, the BAI, and the PANAS. Secondary outcomes will include diagnosis-specific measures of the principal disorder. Participants' treatment acceptance will also be measured. Participants will be assessed at pre-, post-treatment, and 3- and 12- month follow-ups. The data will be analyzed based on the Intention-to-treat principle. Per

  9. The Infectious Diseases Clinical Research Program: addressing the challenge of infections related to war injuries and skin and soft tissues.

    PubMed

    Martin, Gregory J; Tribble, David R

    2010-07-01

    The Infectious Diseases Clinical Research Program (IDCRP) at the Uniformed Services University of the Health Sciences (USU) is a National Institute of Allergy and Infectious Diseases (NIAID)-funded network of military treatment and research facilities coordinated through USU and the Henry M. Jackson Foundation for the Advancement of Military Medicine (HJF). IDCRP functions in collaboration with the NIAID, universities, and industry to address infectious diseases threats to the U.S. military and to the nation. Although IDCRP has projects in diseases from HIV to tuberculosis, a major focus has been on skin, soft-tissue, and war-related infections.

  10. The 2011 Leona Tyler Award Address: The Relationship--And Its Relationship to the Common and Specific Factors of Psychotherapy

    ERIC Educational Resources Information Center

    Wampold, Bruce E.; Budge, Stephanie L.

    2012-01-01

    A debate exists about whether the common factors or specific ingredients are critical to producing the benefits of psychotherapy. A model of the relationship, based on evolved human characteristics related to healing, is presented that integrates common factors and specific ingredients. After the initial bond is formed, the relationship involves…

  11. The 2011 Leona Tyler Award Address: The Relationship--And Its Relationship to the Common and Specific Factors of Psychotherapy

    ERIC Educational Resources Information Center

    Wampold, Bruce E.; Budge, Stephanie L.

    2012-01-01

    A debate exists about whether the common factors or specific ingredients are critical to producing the benefits of psychotherapy. A model of the relationship, based on evolved human characteristics related to healing, is presented that integrates common factors and specific ingredients. After the initial bond is formed, the relationship involves…

  12. The Buffalo Model: Shifting the Focus of Clinical Licensure Exams in Dentistry to Address Ethical Concerns Regarding Patient Care.

    PubMed

    Gambacorta, Joseph E; Glick, Michael; Anker, Ashley E; Shampaine, Guy S

    2016-06-01

    Most jurisdictions grant dental licensure to graduating students following successful completion of a clinical exam. Testing agencies, which are independent of dental schools, nevertheless conduct their exams at school facilities. Patient participation in these exams raises ethical concerns regarding such issues as unlicensed providers' performing irreversible procedures with minimal supervision and graduates' limited accessibility to provide follow-up treatment. To address these concerns, a collaborative effort between University at Buffalo School of Dental Medicine faculty and testing agency personnel was launched. The aims of this article are to describe the development and implementation of the resulting Buffalo Model, to highlight ethical advantages in its application, and to identify areas of improvement to be addressed in future iterations. With the Buffalo Model, modifications were made to the traditional exam format in order to integrate the exam into the school curriculum, enabling candidates to take it at various points during their fourth year. In addition, after calibration of school faculty members, 98.5% of cases verified by faculty were accepted by the Commission on Dental Competency Assessments for use in the exam. In two cases, restorative treatment completed during the exam did not meet the school's competency standard. This new approach ameliorates ethical concerns associated with clinical licensure exams because treatment is provided only to patients of record within a sequenced treatment plan and timely and appropriate treatment is provided to all patients. The results of this first year of implementation also suggest that calibrated faculty members will not show bias in the selection of lesions or competency evaluations of candidates.

  13. Patient and healthcare perspectives on the importance and efficacy of addressing spiritual issues within an interdisciplinary bone marrow transplant clinic: a qualitative study

    PubMed Central

    Sinclair, Shane; McConnell, Shelagh; Raffin Bouchal, Shelley; Ager, Naree; Booker, Reanne; Enns, Bert; Fung, Tak

    2015-01-01

    Objectives The purpose of this study was to use a qualitative approach to better understand the importance and efficacy of addressing spiritual issues within an interdisciplinary bone marrow transplant clinic from the perspectives of patients and healthcare providers. Setting Participants were recruited from the bone marrow transplant clinic of a large urban outpatient cancer care centre in western Canada. Participants: Focus groups were conducted with patients (n=7) and healthcare providers (n=9) to explore the importance of addressing spiritual issues across the treatment trajectory and to identify factors associated with effectively addressing these needs. Results Data were analysed using the qualitative approach of latent content analysis. Addressing spiritual issues was understood by patients and healthcare providers, as a core, yet under addressed, component of comprehensive care. Both sets of participants felt that addressing basic spiritual issues was the responsibility of all members of the interdisciplinary team, while recognising the need for specialised and embedded support from a spiritual care professional. While healthcare providers felt that the impact of the illness and treatment had a negative effect on patients’ spiritual well-being, patients felt the opposite. Skills, challenges, key time points and clinical indicators associated with addressing spiritual issues were identified. Conclusions Despite a number of conceptual and clinical challenges associated with addressing spiritual issues patients and their healthcare providers emphasised the importance of an integrated approach whereby basic spiritual issues are addressed by members of the interdisciplinary team and by an embedded spiritual care professional, who in addition also provides specialised support. The identification of clinical issues associated with addressing spiritual needs provides healthcare providers with clinical guidance on how to better integrate this aspect of care into

  14. Patient and healthcare perspectives on the importance and efficacy of addressing spiritual issues within an interdisciplinary bone marrow transplant clinic: a qualitative study.

    PubMed

    Sinclair, Shane; McConnell, Shelagh; Raffin Bouchal, Shelley; Ager, Naree; Booker, Reanne; Enns, Bert; Fung, Tak

    2015-11-27

    The purpose of this study was to use a qualitative approach to better understand the importance and efficacy of addressing spiritual issues within an interdisciplinary bone marrow transplant clinic from the perspectives of patients and healthcare providers. Participants were recruited from the bone marrow transplant clinic of a large urban outpatient cancer care centre in western Canada. Focus groups were conducted with patients (n=7) and healthcare providers (n=9) to explore the importance of addressing spiritual issues across the treatment trajectory and to identify factors associated with effectively addressing these needs. Data were analysed using the qualitative approach of latent content analysis. Addressing spiritual issues was understood by patients and healthcare providers, as a core, yet under addressed, component of comprehensive care. Both sets of participants felt that addressing basic spiritual issues was the responsibility of all members of the interdisciplinary team, while recognising the need for specialised and embedded support from a spiritual care professional. While healthcare providers felt that the impact of the illness and treatment had a negative effect on patients' spiritual well-being, patients felt the opposite. Skills, challenges, key time points and clinical indicators associated with addressing spiritual issues were identified. Despite a number of conceptual and clinical challenges associated with addressing spiritual issues patients and their healthcare providers emphasised the importance of an integrated approach whereby basic spiritual issues are addressed by members of the interdisciplinary team and by an embedded spiritual care professional, who in addition also provides specialised support. The identification of clinical issues associated with addressing spiritual needs provides healthcare providers with clinical guidance on how to better integrate this aspect of care into their clinical practice, while also identifying acute

  15. Institution-Specific Victimization Surveys: Addressing Legal and Practical Disincentives to Gender-Based Violence Reporting on College Campuses.

    PubMed

    Cantalupo, Nancy Chi

    2014-07-01

    This review brings together both the legal literature and original empirical research regarding the advisability of amending the Jeanne Clery Disclosure of Campus Security Policy and Campus Crime Statistics Act or creating new Department of Education regulations to mandate that all higher education institutions survey their students approximately every 5 years about students' experiences with sexual violence. Legal research conducted regarding the three relevant federal legal regimes show inconsistent incentives for schools to encourage victim reporting and proactively address sexual violence on campus. Moreover, the original research carried out for this article shows that the experience of institutions that have voluntarily conducted such surveys suggests many benefits not only for students, prospective students, parents, and the general public but also for schools themselves. These experiences confirm the practical viability of a mandated survey by the Department of Education.

  16. Administering and Assessing Culture-Specific Interventions to Address Culture-Bound Issues among Asian American College Students

    ERIC Educational Resources Information Center

    Kim, Josephine M.

    2009-01-01

    This article describes how researchers can design and use a culture-sensitive intervention model to inform and influence attitudes of various cultural groups toward seeking professional counseling services. Special emphasis is given to the implications of culture specificity in the processes of designing and conducting intervention studies with…

  17. Clinical decision-making to address poor outcomes in persistent horizontal semicircular canal benign paroxysmal positional vertigo: A case study.

    PubMed

    Moore, Brian M

    2017-05-01

    Horizontal semicircular canal BPPV (HSC-BPPV) can occur in 10-30% of BPPV cases. Lower success rates are reported for HSC-BPPV. The apogeotropic form of HSC-BPPV is more difficult to treat, as 5-40% of cases are described to be refractory to repositioning maneuvers. To describe the assessment and treatment of a patient presenting with HSC-BPPV and to demonstrate the potential use of Forced-Prolonged Positioning (FPP) as a home exercise program (HEP) for persistent HSC-BPPV in an elderly patient. An 89-year-old female referred to physical therapy with a diagnosis of BPPV. She experienced dizziness with positional changes and was found to have apogeotropic form of HSC-BPPV. To supplement maneuvers performed in the clinic, the patient was provided instructions for the FPP as her HEP. With continued symptoms and positive positional tests by week four of treatment, the patient was instructed to switch the FPP with the opposing ear directed toward the floor. Following 2 weeks of performing FPP on the opposite side, the patient reported symptoms had resolved and positional testing confirmed resolution of HSC-BPPV. There is a potential benefit of using FPP as a HEP to supplement maneuvers used in the clinic to improve outcomes in patients with HSC-BPPV that are refractory to traditional repositioning maneuvers. Prescribing the FPP maneuver as a HEP is feasible, and clinicians should consider the FPP technique as a HEP to adjunct repositioning maneuvers performed in the clinic to address persistent HSC-BPPV.

  18. Hybrid specification, storage, retrieval and runtime application of clinical guidelines.

    PubMed

    Shahar, Y

    2006-06-01

    Clinical guidelines are a major tool in improving the quality of medical care. However, most guidelines are in free text, are not machine-comprehensible and are not easily accessible to clinicians at the point of care. We have designed and implemented a web-based, modular, distributed architecture, the Digital Electronic Guideline Library (DeGeL), which facilitates gradual conversion of clinical guidelines from text to a formal representation in the chosen target guideline ontology. The architecture supports guideline classification, semantic markup, context-sensitive search, browsing, run-time application and retrospective quality assessment. The DeGeL hybrid meta-ontology includes elements common to all guideline ontologies, such as semantic classification and domain knowledge; it also includes four content-representation formats: free text, semi-structured text, semi-formal representation and a formal representation. These formats support increasingly sophisticated computational tasks. Guidelines can thus be in a hybrid representation in which guidelines, and even parts of the same guideline, might exist at different formalisation levels. We have also developed and rigorously evaluated a methodology and an associated web-based tool, Uruz, for gradually structuring and semi-formalising free-text clinical guidelines. Finally, we have designed, implemented and evaluated a new approach, the hybrid runtime application model, for supporting runtime application of clinical guidelines that are not necessarily in a machine-comprehensible format; in particular, when the guideline is in a semi-formal representation and the patient's data are either in an electronic medical record or in a paper format. The tool implementing this new approach, the Spock module, is customised at this point to the Asbru guideline specification language and exploits the hybrid structure of guidelines in DeGeL. The Spock module also exploits our temporal-abstraction mediator to the patient

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

    PubMed

    Cohen, Benita E; Gregory, David

    2009-01-01

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

  20. Drug-specific clinical pattern in fixed drug eruptions.

    PubMed

    Thankappan, T P; Zachariah, J

    1991-12-01

    One hundred thirteen patients with fixed drug eruption (FDE) were studied for any drug-specific clinical pattern. The causative drugs were identified and confirmed by provocation tests. A trimethoprim-sulfamethoxazole combination caused maximum incidence (36.3%), followed by tetracycline (15.9%), pyrazolones (14.2%), sulfadiazine (12.4%), dipyrine (9.3%), acetaminophen (7.9%), aspirin (1.7%), thiacetazone (0.88%), and levamizole (0.88%). Sulfas, including trimethoprim-sulfamethoxazole, induced lesions on the lips (91%) and trunk and limbs (89%), with only minimal involvement of mucosae. Tetracycline caused lesions only on the glans penis, sparing other sites. Pyrazolones affected mainly the lips and mucosae, with a few lesions of the trunk and limbs. Dipyrine, aspirin, and acetaminophen caused lesions of the trunk and limbs, sparing the lips, genitalia, and mucosae. Levamizole caused associated constitutional disturbances with extensive skin lesions, as did thiacetazone. The current study indicates that the clinical pattern and distribution of lesions in FDE are influenced by the drug in question, and the study of the pattern may provide useful information in selecting the most likely causative drug, especially when the details of the drugs are unknown.

  1. No clinical benefit of gender-specific total knee arthroplasty

    PubMed Central

    Zhu, Chen; Wang, Jiaxing; Cheng, Mengqi; Peng, Xiaochun; Wang, Qi; Zhang, Xianlong

    2014-01-01

    Background and purpose There is no consensus regarding the clinical relevance of gender-specific prostheses in total knee arthroplasty (TKA). We summarize the current best evidence in a comparison of clinical and radiographic outcomes between gender-specific prostheses and standard unisex prostheses in female patients. Methods We used the PubMed, Embase, Cochrane, Science Citation Index, and Scopus databases. We included randomized controlled trials published up to January 2013 that compared gender-specific prostheses with standard unisex prostheses in female patients who underwent primary TKAs. Results 6 trials involving 423 patients with 846 knee joints met the inclusion criteria. No statistically significant differences were observed between the 2 designs regarding pain, range of motion (ROM), knee scores, satisfaction, preference, complications, and radiographic results. The gender-specific design (Gender Solutions; Zimmer Inc, Warsaw, Indiana) reduced the prevalence of overhang. However, it had less overall coverage of the femoral condyles compared to the unisex group. In fact, the femoral prosthesis in the standard unisex group matched better than that in the gender-specific group. Interpretation Gender-specific prostheses do not appear to confer any benefit in terms of clinician- and patient-reported outcomes for the female knee. PMID:24954488

  2. Cardioembolic Stroke: Clinical Features, Specific Cardiac Disorders and Prognosis

    PubMed Central

    Arboix, Adrià; Alió, Josefina

    2010-01-01

    This article provides the reader with an overview and up-date of clinical features, specific cardiac disorders and prognosis of cardioembolic stroke. Cardioembolic stroke accounts for 14-30% of ischemic strokes and, in general, is a severe condition; patients with cardioembolic infarction are prone to early and long-term stroke recurrence, although recurrences may be preventable by appropriate treatment during the acute phase and strict control at follow-up. Certain clinical features are suggestive of cardioembolic infarction, including sudden onset to maximal deficit, decreased level of consciousness at onset, Wernicke’s aphasia or global aphasia without hemiparesis, a Valsalva manoeuvre at the time of stroke onset, and co-occurrence of cerebral and systemic emboli. Lacunar clinical presentations, a lacunar infarct and especially multiple lacunar infarcts, make cardioembolic origin unlikely. The more common high risk cardioembolic conditions are atrial fibrillation, recent myocardial infarction, mechanical prosthetic valve, dilated myocardiopathy, and mitral rheumatic stenosis. Transthoracic and transesophageal echocardiogram can disclose structural heart diseases. Paroxysmal atrial dysrhyhtmia can be detected by Holter monitoring. In-hospital mortality in cardioembolic stroke (27.3%, in our series) is the highest as compared with other subtypes of cerebral infarction. In our experience, in-hospital mortality in patients with early embolic recurrence (within the first 7 days) was 77%. Patients with alcohol abuse, hypertension, valvular heart disease, nausea and vomiting, and previous cerebral infarction are at increased risk of early recurrent systemic embolization. Secondary prevention with anticoagulants should be started immediately if possible in patients at high risk for recurrent cardioembolic stroke in which contraindications, such as falls, poor compliance, uncontrolled epilepsy or gastrointestinal bleeding are absent. PMID:21804774

  3. Clinical Genetic Testing for the Cardiomyopathies and Arrhythmias: A Systematic Framework for Establishing Clinical Validity and Addressing Genotypic and Phenotypic Heterogeneity

    PubMed Central

    Garcia, John; Tahiliani, Jackie; Johnson, Nicole Marie; Aguilar, Sienna; Beltran, Daniel; Daly, Amy; Decker, Emily; Haverfield, Eden; Herrera, Blanca; Murillo, Laura; Nykamp, Keith; Topper, Scott

    2016-01-01

    Advances in DNA sequencing have made large, diagnostic gene panels affordable and efficient. Broad adoption of such panels has begun to deliver on the promises of personalized medicine, but has also brought new challenges such as the presence of unexpected results, or results of uncertain clinical significance. Genetic analysis of inherited cardiac conditions is particularly challenging due to the extensive genetic heterogeneity underlying cardiac phenotypes, and the overlapping, variable, and incompletely penetrant nature of their clinical presentations. The design of effective diagnostic tests and the effective use of the results depend on a clear understanding of the relationship between each gene and each considered condition. To address these issues, we developed simple, systematic approaches to three fundamental challenges: (1) evaluating the strength of the evidence suggesting that a particular condition is caused by pathogenic variants in a particular gene, (2) evaluating whether unusual genotype/phenotype observations represent a plausible expansion of clinical phenotype associated with a gene, and (3) establishing a molecular diagnostic strategy to capture overlapping clinical presentations. These approaches focus on the systematic evaluation of the pathogenicity of variants identified in clinically affected individuals, and the natural history of disease in those individuals. Here, we applied these approaches to the evaluation of more than 100 genes reported to be associated with inherited cardiomyopathies and arrhythmias including hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic right ventricular dysplasia or cardiomyopathy, long QT syndrome, short QT syndrome, Brugada, and catecholaminergic polymorphic ventricular tachycardia, and to a set of related syndromes such as Noonan Syndrome and Fabry disease. These approaches provide a framework for delivering meaningful and accurate genetic test results to individuals with hereditary

  4. Addressing Adherence Using Genotype-Specific PBPK Modeling—Impact of Drug Holidays on Tamoxifen and Endoxifen Plasma Levels

    PubMed Central

    Dickschen, Kristin J. R.; Willmann, Stefan; Hempel, Georg; Block, Michael

    2017-01-01

    Introduction: Tamoxifen is one of the most common treatment opportunities for hormonal positive breast cancer. Despite its good tolerability, patients demonstrate decreasing adherence over years impacting on therapeutic success. PBPK modeling was applied to demonstrate the impact of drug holidays on plasma levels of tamoxifen and its active metabolite endoxifen for different CYP2D6 genotypes. Materials and Methods: A virtual study with 24,000 patients was conducted in order to investigate the development of tamoxifen steady-state kinetics in patient groups of different CYP2D6 genotypes. The impact of drug holidays on steady-state kinetics was investigated assuming changing drug holiday scenarios. Results: Drug holidays in CYP2D6 extensive and intermediate metabolizers (EMs, IMs) exceeding 1 month lead to a decrease of endoxifen steady-state trough levels below the 5th percentile of the control group. Assuming drug holidays of 1, 2, or 3 months and administering a fixed-dose combination of 20 mg tamoxifen and 3 mg endoxifen EMs demonstrated re-established endoxifen steady-state trough levels after 5, 8, and 9 days. IMs receiving the same fixed-dose combination demonstrated re-established endoxifen steady-state trough levels after 7, 10, and 11 days. Discussion: The PBPK model impressively demonstrates the impact of drug holidays in different CYP2D6 genotypes on PK. Population simulation results indicate that drug holidays of more than 2 weeks cause a tremendous decrease of plasma levels despite the long half-life of tamoxifen. To improve therapeutic success, PBPK modeling allows identifying genotype-specific differences in PK following drug holidays and adequate treatment with loading doses. PMID:28382001

  5. Screening for prostate cancer with prostate-specific antigen testing: American Society of Clinical Oncology Provisional Clinical Opinion.

    PubMed

    Basch, Ethan; Oliver, Thomas K; Vickers, Andrew; Thompson, Ian; Kantoff, Philip; Parnes, Howard; Loblaw, D Andrew; Roth, Bruce; Williams, James; Nam, Robert K

    2012-08-20

    An American Society of Clinical Oncology (ASCO) provisional clinical opinion (PCO) offers timely clinical direction to the ASCO membership after publication or presentation of potentially practice-changing data from major studies. This PCO addresses the role of prostate-specific antigen (PSA) testing in the screening of men for prostate cancer. Prostate cancer is the second leading cause of cancer deaths among men in the United States. The rationale for screening men for prostate cancer is the potential to reduce the risk of death through early detection. Evidence from a 2011 Agency for Healthcare Research and Quality systematic review primarily informs this PCO on the benefits and harms of PSA-based screening. An update search was conducted to March 16, 2012, for additional evidence related to the topic. In one randomized trial, PSA testing in men who would not otherwise have been screened resulted in reduced death rates from prostate cancer, but it is uncertain whether the size of the effect was worth the harms associated with screening and subsequent unnecessary treatment. Although there are limitations to the existing data, there is evidence to suggest that men with longer life expectancy may benefit from PSA testing. Adverse events associated with prostate biopsy are low for the majority of men; however, several population-based studies have shown increasing rates of infectious complications after prostate biopsy, which is a concern.

  6. Technical challenges in designing post-marketing eCRFs to address clinical safety and pharmacovigilance needs.

    PubMed

    Lu, Zhengwu

    2010-01-01

    To identify key challenges and propose technical considerations in designing electronic case report form (eCRF) for post-marketing studies, the author undertakes a comprehensive literature review of peer reviewed and grey literature to assess the key aspects, processes, standards, recommendations, and best practices in designing eCRFs based on industry experience in designing and supporting electronic data capture (EDC) studies. Literature search using strings on MEDLINE and PUBMED returned few papers directly related to CRF design. Health informatics and general practice journals were searched and results reviewed. Many conference, government commission, health professional and special interests group websites provide relevant information from practical experience - summarization of this information is presented. Further, we presented a list of concrete technical considerations in dealing with EDC technology/system limitations based on literature assessment and industry implementation experience. It is recognized that cross-functional teams be involved in eCRF design process and decision making. To summarize the keys in designing eCRFs to address post-market study safety and pharmacovigilance needs, the first is to identify required data elements from the study protocol supporting data analyses and reporting requirements. Secondly, accepted best practices, CDASH & CDISC guidelines, and company internal or therapeutic unit standard should be considered and applied. Coding (MedDRA & WHODD) mapping should be managed and implemented as well when possible. Finally, we need to be on top of the EDC technologies, challenge the technologies, drive EDC improvement via working with vendors, and utilize the technologies to drive clinical effectiveness. Copyright (c) 2009 Elsevier Inc. All rights reserved.

  7. Non specific aorto-arteritis. Clinical picture, diagnosis and therapy.

    PubMed

    Miani, S; De Monti, M; Keller, G; Bordoni, M G; Bianchi, E; Giordanengo, F

    1999-06-01

    This study is aimed at analyzing clinical features, angiographic findings and evolution of Takayasu's arteritis and the criteria adopted to establish the indication for non-surgical versus operative treatment. Eighteen patients affected by non specific aortarteritis were observed and treated at our Department between 1973 and 1996. All patients met the American College of Rheumatology 1990 criteria of classification of Takayasu's arteritis. Sixteen patients were young females. Two patients were males. Nine patients underwent surgical procedures. One young female underwent a PTA. All eight asymptomatic patients were only medically treated. One patient died some days after an aorto-bicarotid bypass graft due to acute myocardial infarction. Two other patients died two and four years after intervention for renal and cardiac failure respectively. One patient after an aorto bicarotid bypass underwent a left hemiplegia due to thrombosis of the right graft branch. All the other 14 patients either surgically or medically treated are well and are under strict surveillance through rigorous follow-up. The 10 patients who underwent surgical or interventional radiological treatment were certainly the most seriously affected patients and were symptomatic (presented neurological disturbances or a severe hypertensive state). This fact explains, to some extent, the mortality and morbidity rate observed in this group. The seven medically treated patients were completely asymptomatic in spite of a major involvement of various vascular districts.

  8. Clinical and no-clinical setting specificities in first session short-term psychotherapy psychodrama group.

    PubMed

    Drakulić, Aleksandra Mindoljević

    2011-03-01

    Modern history of short-term group psychotherapy dates back to the late 1950-ies. From then to present day, this psychotherapeutic method has been used in various forms, from dynamic-oriented to cognitive behavioural psychotherapies. Although it has always been considered rather controversial, due its cost-effectiveness, it has been capturing more and more popularity. This paper presents the specificities of first session short-term psychotherapy psychodrama group through session work with two examined groups: a group of 20 adult women who suffer from mild or moderate forms of unipolar depression and a group of 20 students of the School of Medicine in Zagreb without any psychiatric symptomatology. The results indicate the high importance of having structure in first psychodrama session, of relating it with the previously thoroughly conducted, initial, clinical, interviews, and of the clarity and focus in terms of determining the goals of therapy, especially in a clinical context. This study also confirmed assumptions regarding the need for different approaches of warming-up in psychodrama, both in the clinical and in non-clinical samples. A psychodrama psychotherapist should have good time managing skills and capability to convert the time available into an opportunity for directly boosting the group energy and work on therapeutic alliance.

  9. Revised Hammersmith Scale for spinal muscular atrophy: A SMA specific clinical outcome assessment tool.

    PubMed

    Ramsey, Danielle; Scoto, Mariacristina; Mayhew, Anna; Main, Marion; Mazzone, Elena S; Montes, Jacqueline; de Sanctis, Roberto; Dunaway Young, Sally; Salazar, Rachel; Glanzman, Allan M; Pasternak, Amy; Quigley, Janet; Mirek, Elizabeth; Duong, Tina; Gee, Richard; Civitello, Matthew; Tennekoon, Gihan; Pane, Marika; Pera, Maria Carmela; Bushby, Kate; Day, John; Darras, Basil T; De Vivo, Darryl; Finkel, Richard; Mercuri, Eugenio; Muntoni, Francesco

    2017-01-01

    Recent translational research developments in Spinal Muscular Atrophy (SMA), outcome measure design and demands from regulatory authorities require that clinical outcome assessments are 'fit for purpose'. An international collaboration (SMA REACH UK, Italian SMA Network and PNCRN USA) undertook an iterative process to address discontinuity in the recorded performance of the Hammersmith Functional Motor Scale Expanded and developed a revised functional scale using Rasch analysis, traditional psychometric techniques and the application of clinical sensibility via expert panels. Specifically, we intended to develop a psychometrically and clinically robust functional clinician rated outcome measure to assess physical abilities in weak SMA type 2 through to strong ambulant SMA type 3 patients. The final scale, the Revised Hammersmith Scale (RHS) for SMA, consisting of 36 items and two timed tests, was piloted in 138 patients with type 2 and 3 SMA in an observational cross-sectional multi-centre study across the three national networks. Rasch analysis demonstrated very good fit of all 36 items to the construct of motor performance, good reliability with a high Person Separation Index PSI 0.98, logical and hierarchical scoring in 27/36 items and excellent targeting with minimal ceiling. The RHS differentiated between clinically different groups: SMA type, World Health Organisation (WHO) categories, ambulatory status, and SMA type combined with ambulatory status (all p < 0.001). Construct and concurrent validity was also confirmed with a strong significant positive correlation with the WHO motor milestones rs = 0.860, p < 0.001. We conclude that the RHS is a psychometrically sound and versatile clinical outcome assessment to test the broad range of physical abilities of patients with type 2 and 3 SMA. Further longitudinal testing of the scale with regards change in scores over 6 and 12 months are required prior to its adoption in clinical trials.

  10. Revised Hammersmith Scale for spinal muscular atrophy: A SMA specific clinical outcome assessment tool

    PubMed Central

    Scoto, Mariacristina; Mayhew, Anna; Main, Marion; Mazzone, Elena S.; Montes, Jacqueline; de Sanctis, Roberto; Dunaway Young, Sally; Salazar, Rachel; Glanzman, Allan M.; Pasternak, Amy; Quigley, Janet; Mirek, Elizabeth; Duong, Tina; Gee, Richard; Civitello, Matthew; Tennekoon, Gihan; Pane, Marika; Pera, Maria Carmela; Bushby, Kate; Day, John; Darras, Basil T.; De Vivo, Darryl; Finkel, Richard; Mercuri, Eugenio; Muntoni, Francesco

    2017-01-01

    Recent translational research developments in Spinal Muscular Atrophy (SMA), outcome measure design and demands from regulatory authorities require that clinical outcome assessments are ‘fit for purpose’. An international collaboration (SMA REACH UK, Italian SMA Network and PNCRN USA) undertook an iterative process to address discontinuity in the recorded performance of the Hammersmith Functional Motor Scale Expanded and developed a revised functional scale using Rasch analysis, traditional psychometric techniques and the application of clinical sensibility via expert panels. Specifically, we intended to develop a psychometrically and clinically robust functional clinician rated outcome measure to assess physical abilities in weak SMA type 2 through to strong ambulant SMA type 3 patients. The final scale, the Revised Hammersmith Scale (RHS) for SMA, consisting of 36 items and two timed tests, was piloted in 138 patients with type 2 and 3 SMA in an observational cross-sectional multi-centre study across the three national networks. Rasch analysis demonstrated very good fit of all 36 items to the construct of motor performance, good reliability with a high Person Separation Index PSI 0.98, logical and hierarchical scoring in 27/36 items and excellent targeting with minimal ceiling. The RHS differentiated between clinically different groups: SMA type, World Health Organisation (WHO) categories, ambulatory status, and SMA type combined with ambulatory status (all p < 0.001). Construct and concurrent validity was also confirmed with a strong significant positive correlation with the WHO motor milestones rs = 0.860, p < 0.001. We conclude that the RHS is a psychometrically sound and versatile clinical outcome assessment to test the broad range of physical abilities of patients with type 2 and 3 SMA. Further longitudinal testing of the scale with regards change in scores over 6 and 12 months are required prior to its adoption in clinical trials. PMID:28222119

  11. Clinical Competence: General Ability or Case-Specific?

    ERIC Educational Resources Information Center

    Wimmers, Paul F.; Splinter, Ted A. W.; Hancock, Gregory R.; Schmidt, Henk G.

    2007-01-01

    Background: Before the 1970s, research into the development of clinical competence was mainly focused on general problem-solving abilities. The scope of research changed when Elstein and colleagues discovered that individual ability to solve clinical problems varies considerably across cases. It was concluded that problem solving abilities are…

  12. A Manual-Based Intervention to Address Clinical Crises and Retain Patients in the Treatment of Adolescents with Depression Study (TADS)

    ERIC Educational Resources Information Center

    May, Diane E.; Kratochvil, Christopher J.; Puumala, Susan E.; Silva, Susan G.; Rezac, Amy J.; Hallin, Mary J.; Reinecke, Mark A.; Vitiello, Benedetto; Weller, Elizabeth B.; Pathak, Sanjeev; Simons, Anne D.; March, John S.

    2007-01-01

    Objective: To describe a manual-based intervention to address clinical crises and retain participants in the Treatment for Adolescents with Depression Study (TADS). Method: The use of adjunct services for attrition prevention (ASAP) is described for adolescents (ages 12-17 years) during the 12-week acute treatment in TADS, from 2000 to 2003.…

  13. A Manual-Based Intervention to Address Clinical Crises and Retain Patients in the Treatment of Adolescents with Depression Study (TADS)

    ERIC Educational Resources Information Center

    May, Diane E.; Kratochvil, Christopher J.; Puumala, Susan E.; Silva, Susan G.; Rezac, Amy J.; Hallin, Mary J.; Reinecke, Mark A.; Vitiello, Benedetto; Weller, Elizabeth B.; Pathak, Sanjeev; Simons, Anne D.; March, John S.

    2007-01-01

    Objective: To describe a manual-based intervention to address clinical crises and retain participants in the Treatment for Adolescents with Depression Study (TADS). Method: The use of adjunct services for attrition prevention (ASAP) is described for adolescents (ages 12-17 years) during the 12-week acute treatment in TADS, from 2000 to 2003.…

  14. A Domain Analysis Model for eIRB Systems: Addressing the Weak Link in Clinical Research Informatics

    PubMed Central

    He, Shan; Narus, Scott P.; Facelli, Julio C.; Lau, Lee Min; Botkin, Jefferey R.; Hurdle, John F.

    2014-01-01

    Institutional Review Boards (IRBs) are a critical component of clinical research and can become a significant bottleneck due to the dramatic increase, in both volume and complexity of clinical research. Despite the interest in developing clinical research informatics (CRI) systems and supporting data standards to increase clinical research efficiency and interoperability, informatics research in the IRB domain has not attracted much attention in the scientific community. The lack of standardized and structured application forms across different IRBs causes inefficient and inconsistent proposal reviews and cumbersome workflows. These issues are even more prominent in multi-institutional clinical research that is rapidly becoming the norm. This paper proposes and evaluates a domain analysis model for electronic IRB (eIRB) systems, paving the way for streamlined clinical research workflow via integration with other CRI systems and improved IRB application throughput via computer-assisted decision support. PMID:24929181

  15. A domain analysis model for eIRB systems: addressing the weak link in clinical research informatics.

    PubMed

    He, Shan; Narus, Scott P; Facelli, Julio C; Lau, Lee Min; Botkin, Jefferey R; Hurdle, John F

    2014-12-01

    Institutional Review Boards (IRBs) are a critical component of clinical research and can become a significant bottleneck due to the dramatic increase, in both volume and complexity of clinical research. Despite the interest in developing clinical research informatics (CRI) systems and supporting data standards to increase clinical research efficiency and interoperability, informatics research in the IRB domain has not attracted much attention in the scientific community. The lack of standardized and structured application forms across different IRBs causes inefficient and inconsistent proposal reviews and cumbersome workflows. These issues are even more prominent in multi-institutional clinical research that is rapidly becoming the norm. This paper proposes and evaluates a domain analysis model for electronic IRB (eIRB) systems, paving the way for streamlined clinical research workflow via integration with other CRI systems and improved IRB application throughput via computer-assisted decision support. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Suicide Risk Protocols: Addressing the Needs of High Risk Youths Identified through Suicide Prevention Efforts and in Clinical Settings

    ERIC Educational Resources Information Center

    Heilbron, Nicole; Goldston, David; Walrath, Christine; Rodi, Michael; McKeon, Richard

    2013-01-01

    Several agencies have emphasized the importance of establishing clear protocols or procedures to address the needs of youths who are identified as suicidal through suicide prevention programs or in emergency department settings. What constitutes optimal guidelines for developing and implementing such protocols, however, is unclear. At the request…

  17. An Official American Thoracic Society Workshop Report. A Framework for Addressing Multimorbidity in Clinical Practice Guidelines for Pulmonary Disease, Critical Illness, and Sleep Disorders.

    PubMed

    Wilson, Kevin C; Gould, Michael K; Krishnan, Jerry A; Boyd, Cynthia M; Brozek, Jan L; Cooke, Colin R; Douglas, Ivor S; Goodman, Richard A; Joo, Min J; Lareau, Suzanne; Mularski, Richard A; Patel, Minal R; Rosenfeld, Richard M; Shanawani, Hasan; Slatore, Christopher; Sockrider, Marianna; Sufian, Beth; Thomson, Carey C; Wiener, Renda Soylemez

    2016-03-01

    Coexistence of multiple chronic conditions (i.e., multimorbidity) is the most common chronic health problem in adults. However, clinical practice guidelines have primarily focused on patients with a single disease, resulting in uncertainty about the care of patients with multimorbidity. The American Thoracic Society convened a workshop with the goal of establishing a strategy to address multimorbidity within clinical practice guidelines. In this Workshop Report, we describe a framework that addresses multimorbidity in each of the key steps of guideline development: topic selection, panel composition, identifying clinical questions, searching for and synthesizing evidence, rating the quality of that evidence, summarizing benefits and harms, formulating recommendations, and rating the strength of the recommendations. For the consideration of multimorbidity in guidelines to be successful and sustainable, the process must be both feasible and pragmatic. It is likely that this will be achieved best by the step-wise addition and refinement of the various components of the framework.

  18. PET scans relate clinical picture to more specific nerve function

    SciTech Connect

    Ziporyn, T.

    1985-02-15

    This article describes the historical development of the use of positron emission tomography in studies of brain chemistry and the specific pathways associated with specific disease states. Fluorine-18 is used to label dopa since dopa can cross the blood-brain barrier. This radiopharmaceutical has been used to study the role of dopamine in Parkinson's disease and other motor disorders. The new PET technologies may also allow insight into the cause of variable responses to levo-dopa therapy.

  19. A methodology for evaluation of a markup-based specification of clinical guidelines.

    PubMed

    Shalom, Erez; Shahar, Yuval; Taieb-Maimon, Meirav; Lunenfeld, Eitan

    2008-11-06

    We introduce a three-phase, nine-step methodology for specification of clinical guidelines (GLs) by expert physicians, clinical editors, and knowledge engineers, and for quantitative evaluation of the specification's quality. We applied this methodology to a particular framework for incremental GL structuring (mark-up) and to GLs in three clinical domains with encouraging results.

  20. Specific Genetic Disorders and Autism: Clinical Contribution towards Their Identification

    ERIC Educational Resources Information Center

    Cohen, David; Pichard, Nadege; Tordjman, Sylvie; Baumann, Clarisse; Burglen, Lydie; Excoffier, Elsa; Lazar, Gabriela; Mazet, Philippe; Pinquier, Clement; Verloes, Alian; Heron, Delphine

    2005-01-01

    Autism is a heterogeneous disorder that can reveal a specific genetic disease. This paper describes several genetic diseases consistently associated with autism (fragile X, tuberous sclerosis, Angelman syndrome, duplication of 15q11-q13, Down syndrome, San Filippo syndrome, MECP2 related disorders, phenylketonuria, Smith-Magenis syndrome, 22q13…

  1. Specific Genetic Disorders and Autism: Clinical Contribution towards Their Identification

    ERIC Educational Resources Information Center

    Cohen, David; Pichard, Nadege; Tordjman, Sylvie; Baumann, Clarisse; Burglen, Lydie; Excoffier, Elsa; Lazar, Gabriela; Mazet, Philippe; Pinquier, Clement; Verloes, Alian; Heron, Delphine

    2005-01-01

    Autism is a heterogeneous disorder that can reveal a specific genetic disease. This paper describes several genetic diseases consistently associated with autism (fragile X, tuberous sclerosis, Angelman syndrome, duplication of 15q11-q13, Down syndrome, San Filippo syndrome, MECP2 related disorders, phenylketonuria, Smith-Magenis syndrome, 22q13…

  2. Clinical Trials Using Adenovirus/Cytomegalovirus/Epstein-Barr Virus-specific Allogeneic Cytotoxic T Lymphocytes

    Cancer.gov

    NCI supports clinical trials that test new and more effective ways to treat cancer. Find clinical trials studying adenovirus/cytomegalovirus/epstein-barr virus-specific allogeneic cytotoxic t lymphocytes.

  3. Addressing challenges in nursing education through a clinical instruction model based on a hybrid, inquiry-based learning framework.

    PubMed

    Holaday, Stephanie D; Buckley, Kathleen M

    2008-01-01

    This article describes an innovative hybrid, inquiry-based learning clinical instruction model used in accelerated baccalaureate nursing programs at three university nursing schools in the Washington DC metropolitan area. The authors describe student and faculty roles and offer examples of grading criteria. Nurse faculty and students from the three schools of nursing regard the clinical instruction model as a valuable teaching-learning approach that strengthens the relationship between theory and practice, prepares students to think critically and act effectively, and grooms students and faculty for a lifetime of learning in a changing world.

  4. Addressing healthcare.

    PubMed

    Daly, Rich

    2013-02-11

    Though President Barack Obama has rarely made healthcare references in his State of the Union addresses, health policy experts are hoping he changes that strategy this year. "The question is: Will he say anything? You would hope that he would, given that that was the major issue he started his presidency with," says Dr. James Weinstein, left, of the Dartmouth-Hitchcock health system.

  5. Addressing narcissistic personality features in the context of medical care: integrating diverse perspectives to inform clinical practice.

    PubMed

    Magidson, J F; Collado-Rodriguez, A; Madan, A; Perez-Camoirano, N A; Galloway, S K; Borckardt, J J; Campbell, W K; Miller, J D

    2012-04-01

    Narcissistic personality disorder (NPD) is characterized by an unrealistic need for admiration, lack of empathy toward others, and feelings of superiority. NPD presents a unique and significant challenge in clinical practice, particularly in medical settings with limited provider contact time, as health professionals treat individuals who often require excessive admiration and have competing treatment needs. This practice review highlights real case examples across three distinct medically oriented clinical settings (inpatient and outpatient behavioral medicine and a Level I trauma center) to demonstrate the difficult and compromising situations that providers face when treating patients with general medical conditions and comorbid narcissistic personality features. The main goal of this article is to discuss the various challenges and obstacles associated with these cases in medical settings and discuss some strategies that may prove successful. A second goal is to bridge diverse conceptualizations of narcissism/NPD through the discussion of theoretical and empirical perspectives that can inform understanding of the clinical examples. Despite differing perspectives regarding the underlying motivation of narcissistic behavior, this practice review highlights that these paradigms can be integrated when sharing the same ultimate goal: to improve delivery of care across medically oriented clinical settings for patients with narcissistic features.

  6. Addressing prior-data conflict with empirical meta-analytic-predictive priors in clinical studies with historical information.

    PubMed

    Li, Judy X; Chen, Wei-Chen; Scott, John A

    2016-01-01

    A common question in clinical studies is how to use historical data from earlier studies, leveraging relevant information into the design and analysis of a new study. Bayesian approaches are particularly well-suited to this task, with their natural ability to borrow strength across data sources. In this paper, we propose an eMAP approach for incorporating historical data into the analysis of clinical studies, and we discuss an application of this method to the analysis of observational safety studies for a class of products for patients with hemophilia A. The eMAP prior approach is flexible and robust to prior-data conflict. We conducted simulations to compare the frequentist operating characteristics of three approaches under different prior-data conflict assumptions and sample size scenarios.

  7. [Pathological nighttime fears in children: Clinical specificities and effective therapeutics].

    PubMed

    Ducasse, D; Denis, H

    2015-09-01

    Pathological nighttime fears in children have been little studied. However, this disorder is commonly encountered in medical consultations and is discomforting and dysfunctional for both the child and the family. Most nighttime fears are part and parcel of normal development, and emanate from increasingly sophisticated cognitive development in the growing child. Thus, most children report a variety of coping strategies generally helpful in reducing their anxiety, which resolves spontaneously in the growing child. Nevertheless, in about 10% of children, nighttime fears are related to one or more anxiety disorders according to Diagnostic and Statistical Manual of Mental Disorders criteria. Then, it is estimated that severe nighttime fears and sleep problems occur in 20-30% of children. This problem is not transient and has to be treated. This study aims to review clinical features of nighttime fears and possible treatments for these patients and their families. This systematic review follows the preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement guidelines. Two databases (Medline and Web of Science) were searched combining the search terms: nighttime fears AND children. English and French languages were imposed. There were no publication date or publication status limitations. Pathological nighttime fears are responsible for emotional (crying, panic, tantrums at bedtime, loss of confidence, self-disparaging negative statements, and feeling of social embarrassment) and behavioral (wandering alone in the house at night, calls for parental or sibling comfort, bed sharing with parents or siblings, light source at night, refusal to go to the toilet alone at night) disturbances. This leads to a poor quality of sleep interfering with school learning, and also affects social development and family functioning. A full assessment has to be made to eliminate organic causes, have a baseline functioning, and search for comorbid anxiety diseases

  8. Disease-specific clinical problems associated with the subchondral bone.

    PubMed

    Pape, Dietrich; Filardo, Giuseppe; Kon, Elisaveta; van Dijk, C Niek; Madry, Henning

    2010-04-01

    The subchondral bone is involved in a variety of diseases affecting both the articular cartilage and bone. Osteochondral defects in distinct locations and of variable sizes are the final results of different etiologies. These include traumatic osteochondral defects, osteochondritis dissecans, osteonecrosis, and osteoarthritis. Traumatic osteochondral defects are caused by osteochondral fractures, separating an osteochondral fragment that includes articular cartilage and both subchondral and trabecular bone from the joint surface. In osteochondritis dissecans, the disease originates in the subchondral bone and secondarily affects the articular cartilage. Location, stage, size, and depth of osteochondral lesions play a role in the treatment of traumatic osteochondral defects and osteochondritis dissecans. Surgical options include fragment refixation, transplantation of osteochondral autografts, or bone restoration by impacted cancellous bone grafts combined with autologous chondrocyte transplantation. An insufficiency fracture of the subchondral bone may be the initiating factor of what was formerly believed to be a spontaneous osteonecrosis of the knee (SPONK). Recent histopathological studies suggest that each stage of SPONK reflects different types of bone repair reactions following a fracture of the subchondral bone plate. Osteoarthritis is a disease that does affect not only the articular cartilage, but also the subchondral bone. Reconstructive surgical techniques aim at preserving joint function, inducing fibrocartilaginous repair, and at correcting malalignment. This review summarizes the current status of the clinical treatment of traumatic osteochondral defects, osteochondritis dissecans, osteonecrosis, and osteoarthritis as they affect the subchondral bone region and its adjacent structures.

  9. Serotype-specific differences in clinical manifestations of dengue.

    PubMed

    Balmaseda, Angel; Hammond, Samantha N; Pérez, Leonel; Tellez, Yolanda; Saborío, Saira Indira; Mercado, Juan Carlos; Cuadra, Ricardo; Rocha, Julio; Pérez, Maria Angeles; Silva, Sheyla; Rocha, Crisanta; Harris, Eva

    2006-03-01

    Dengue, the most prevalent arthropod-borne viral disease of humans, is caused by four serotypes of dengue virus (DENV 1-4). Although all four DENV serotypes cause a range of illness, defining precisely which clinical characteristics are associated with the distinct serotypes has been elusive. A cross-sectional study was conducted on 984 and 313 hospitalized children with confirmed DENV infections during two time periods, respectively, in the same hospitals in Nicaragua: a 3-year period (1999-2001) when DENV-2 accounted for 96% of the viruses identified, and the 2003 dengue season when DENV-1 predominated (87% of identified serotypes). When the two periods were compared, more shock (OR 1.91, 95% CI 1.35-2.71) and internal hemorrhage (OR 2.05, CI 1.16-3.78) were observed in the period when DENV-2 predominated, whereas increased vascular permeability was associated to a greater degree with the DENV-1 period (OR 2.36, CI 1.80-3.09). Compared with the DENV-2 period, the DENV-1 season was associated with more hospitalized primary dengue cases (OR 3.86, CI 2.72-5.48) and more primary DENV infections with severe manifestations (OR 2.93, CI 2.00-4.28). These findings provide new data to characterize the pathogenic potential of distinct DENV serotypes in human populations.

  10. Nonnutritive, Low Caloric Substitutes for Food Sugars: Clinical Implications for Addressing the Incidence of Dental Caries and Overweight/Obesity

    PubMed Central

    Roberts, Michael W.; Wright, J. Timothy

    2012-01-01

    Caries and obesity are two common conditions affecting children in the United States and other developed countries. Caries in the teeth of susceptible children have often been associated with frequent ingestion of fermentable sugars such as sucrose, fructose, glucose, and maltose. Increased calorie intake associated with sugars and carbohydrates, especially when associated with physical inactivity, has been implicated in childhood obesity. Fortunately, nonnutritive artificial alternatives and non-/low-caloric natural sugars have been developed as alternatives to fermentable sugars and have shown promise in partially addressing these health issues. Diet counseling is an important adjunct to oral health instruction. Although there are only five artificial sweeteners that have been approved as food additives by the Food and Drug Administration (FDA), there are additional five non-/low caloric sweeteners that have FDA GRAS (Generally Recognized as Safe) designation. Given the health impact of sugars and other carbohydrates, dental professionals should be aware of the nonnutritive non-/low caloric sweeteners available on the market and both their benefits and potential risks. Dental health professionals should also be proactive in helping identify patients at risk for obesity and provide counseling and referral when appropriate. PMID:22505906

  11. Nonnutritive, low caloric substitutes for food sugars: clinical implications for addressing the incidence of dental caries and overweight/obesity.

    PubMed

    Roberts, Michael W; Wright, J Timothy

    2012-01-01

    Caries and obesity are two common conditions affecting children in the United States and other developed countries. Caries in the teeth of susceptible children have often been associated with frequent ingestion of fermentable sugars such as sucrose, fructose, glucose, and maltose. Increased calorie intake associated with sugars and carbohydrates, especially when associated with physical inactivity, has been implicated in childhood obesity. Fortunately, nonnutritive artificial alternatives and non-/low-caloric natural sugars have been developed as alternatives to fermentable sugars and have shown promise in partially addressing these health issues. Diet counseling is an important adjunct to oral health instruction. Although there are only five artificial sweeteners that have been approved as food additives by the Food and Drug Administration (FDA), there are additional five non-/low caloric sweeteners that have FDA GRAS (Generally Recognized as Safe) designation. Given the health impact of sugars and other carbohydrates, dental professionals should be aware of the nonnutritive non-/low caloric sweeteners available on the market and both their benefits and potential risks. Dental health professionals should also be proactive in helping identify patients at risk for obesity and provide counseling and referral when appropriate.

  12. How do clinical genetics consent forms address the familial approach to confidentiality and incidental findings? A mixed-methods study.

    PubMed

    Dheensa, Sandi; Crawford, Gillian; Salter, Claire; Parker, Michael; Fenwick, Angela; Lucassen, Anneke

    2017-04-12

    Genetic test results can be relevant to patients and their relatives. Questions thus arise around whether clinicians regard genetic information as confidential to individuals or to families, and about how they broach this and other issues, including the potential for incidental findings, in consent (forms) for genetic testing. We conducted a content analysis of UK-wide genetic testing consent forms and interviewed 128 clinicians/laboratory scientists. We found that almost all genetic services offered patients multiple, sometimes unworkable, choices on forms, including an option to veto the use of familial genetic information to benefit relatives. Participants worried that documented choices were overriding professional judgement and cautioned against any future forms dictating practice around incidental findings. We conclude that 'tick-box' forms, which do little to enhance autonomy, are masking valid consent processes in clinical practice. As genome-wide testing becomes commonplace, we must re-consider consent processes, so that they protects patients'-and relatives'-interests.

  13. Addressing Missing Data Mechanism Uncertainty using Multiple-Model Multiple Imputation: Application to a Longitudinal Clinical Trial

    PubMed Central

    Siddique, Juned; Harel, Ofer; Crespi, Catherine M.

    2012-01-01

    We present a framework for generating multiple imputations for continuous data when the missing data mechanism is unknown. Imputations are generated from more than one imputation model in order to incorporate uncertainty regarding the missing data mechanism. Parameter estimates based on the different imputation models are combined using rules for nested multiple imputation. Through the use of simulation, we investigate the impact of missing data mechanism uncertainty on post-imputation inferences and show that incorporating this uncertainty can increase the coverage of parameter estimates. We apply our method to a longitudinal clinical trial of low-income women with depression where nonignorably missing data were a concern. We show that different assumptions regarding the missing data mechanism can have a substantial impact on inferences. Our method provides a simple approach for formalizing subjective notions regarding nonresponse so that they can be easily stated, communicated, and compared. PMID:23503984

  14. Addressing Missing Data Mechanism Uncertainty using Multiple-Model Multiple Imputation: Application to a Longitudinal Clinical Trial.

    PubMed

    Siddique, Juned; Harel, Ofer; Crespi, Catherine M

    2012-12-01

    We present a framework for generating multiple imputations for continuous data when the missing data mechanism is unknown. Imputations are generated from more than one imputation model in order to incorporate uncertainty regarding the missing data mechanism. Parameter estimates based on the different imputation models are combined using rules for nested multiple imputation. Through the use of simulation, we investigate the impact of missing data mechanism uncertainty on post-imputation inferences and show that incorporating this uncertainty can increase the coverage of parameter estimates. We apply our method to a longitudinal clinical trial of low-income women with depression where nonignorably missing data were a concern. We show that different assumptions regarding the missing data mechanism can have a substantial impact on inferences. Our method provides a simple approach for formalizing subjective notions regarding nonresponse so that they can be easily stated, communicated, and compared.

  15. Specific and Non-specific Clinical Presentations in the Year Before the Diagnosis of Childhood Leukaemia.

    PubMed

    Yang, TienYu Owen; Liu, Yen-Lin; Huang, Wan-Ting; Chen, Mei-Huei; Chen, Pau-Chung

    2016-08-01

    Clinical presentations of childhood leukaemia have been reported in case-only studies. The timing when these presentations start to occur prior to diagnosis is less clear. In this nested case-control study, 1,025 and 334 children with lymphoid and myeloid leukaemia, respectively, were matched (1:30) to population-based controls by sex, region and year of birth. An index date was assigned for each control when the matched case was diagnosed. Healthcare access records of cases and controls in the year before the index date were extracted. Children with lymphoid leukaemia started to visit doctors more often at least 2 months before leukaemia diagnosis (P < 0.05). Various presentations were recorded in these visits: rates of haematological presentations, musculoskeletal presentations, and injuries started to increase significantly at least 3 months before diagnosis; rates of respiratory, gastrointestinal and urinary tract presentations did not increase significantly until the last month. The findings for myeloid lymphoma were less clear, but children appeared to visit doctors more often at least 4 months before diagnosis, and the rate of haematological presentations also started to increase at least 4 months before leukaemia diagnosis. Although haematological presentations were most strongly associated with undiagnosed leukaemia (odds ratio > 290 in the last month), the majority (>96%) of children with haematological presentations did not have leukaemia if they had not been diagnosed in their first visit. We described a clinical picture in the year before leukaemia diagnosis. These findings revealed ongoing difficulties in early diagnosis of childhood leukaemia in healthcare settings. © 2016 Wiley Periodicals, Inc.

  16. Ethics Standards (HRPP) and Public Partnership (PARTAKE) to Address Clinical Research Concerns in India: Moving Toward Ethical, Responsible, Culturally Sensitive, and Community-Engaging Clinical Research

    PubMed Central

    Burt, Tal; Gupta, Yogendra K; Mehta, Nalin; Swamy, Nagendra; Sovani, Vishwas; Speers, Marjorie A

    2014-01-01

    Like other emerging economies, India’s quest for independent, evidence-based, and affordable healthcare has led to robust and promising growth in the clinical research sector, with a compound annual growth rate (CAGR) of 20.4% between 2005 and 2010. However, while the fundamental drivers and strengths are still strong, the past few years witnessed a declining trend (CAGR −16.7%) amid regulatory concerns, activist protests, and sponsor departure. And although India accounts for 17.5% of the world’s population, it currently conducts only 1% of clinical trials. Indian and international experts and public stakeholders gathered for a 2-day conference in June 2013 in New Delhi to discuss the challenges facing clinical research in India and to explore solutions. The main themes discussed were ethical standards, regulatory oversight, and partnerships with public stakeholders. The meeting was a collaboration of AAHRPP (Association for the Accreditation of Human Research Protection Programs)—aimed at establishing responsible and ethical clinical research standards—and PARTAKE (Public Awareness of Research for Therapeutic Advancements through Knowledge and Empowerment)—aimed at informing and engaging the public in clinical research. The present article covers recent clinical research developments in India as well as associated expectations, challenges, and suggestions for future directions. AAHRPP and PARTAKE provide etiologically based solutions to protect, inform, and engage the public and medical research sponsors. PMID:25558428

  17. Trends in Research with U.S. Military Service Member Participants: A Population-Specific ClinicalTrials.gov Review.

    PubMed

    Cook, Wendy A; Doorenbos, Ardith Z; Bridges, Elizabeth J

    2016-08-15

    ClinicalTrials.gov reviews have evaluated research trends for specific conditions and age groups but not for specific populations of research participants. No ClinicalTrials.gov reviews have evaluated research with military service member participants. Study objectives were (a) to use ClinicalTrials.gov to identify trends in biomedical research from 2005 to 2014 in which U.S. military service members actively participated as research participants and (b) to describe a search strategy for adaptation in future ClinicalTrials.gov reviews of specific participant populations. A systematic review of ClinicalTrials.gov was performed to identify studies that included U.S. service members as participants, either exclusively or with other groups of participants. U.S. service members were identified as participants in 512 studies. Service members participated together with other groups in 392 studies, while 120 studies included only service members. The top five conditions of interest were post-traumatic stress disorder, traumatic brain injury, amputations, burns, and ocular injuries/disorders. The number of studies started each year peaked in 2011 and declined from 2012 to 2014. Twenty-five percent of studies exclusive to service members aimed to enroll 500 or more participants. Research exclusive to Guard and Reserve service members during this period was limited. U.S. military service members participate in biomedical research. To address the health needs of U.S. service members, it is important to ensure there is not a prolonged decline in research among this population. The search strategy may be adapted to ClinicalTrials.gov reviews of specific participant populations for which straightforward searches are not possible.

  18. Chimeric Antigen Receptor (CAR)-Specific Monoclonal Antibody to Detect CD19-Specific T Cells in Clinical Trials

    PubMed Central

    Jena, Bipulendu; Maiti, Sourindra; Huls, Helen; Singh, Harjeet; Lee, Dean A.; Champlin, Richard E.; Cooper, Laurence J. N.

    2013-01-01

    Clinical trials targeting CD19 on B-cell malignancies are underway with encouraging anti-tumor responses. Most infuse T cells genetically modified to express a chimeric antigen receptor (CAR) with specificity derived from the scFv region of a CD19-specific mouse monoclonal antibody (mAb, clone FMC63). We describe a novel anti-idiotype monoclonal antibody (mAb) to detect CD19-specific CAR+ T cells before and after their adoptive transfer. This mouse mAb was generated by immunizing with a cellular vaccine expressing the antigen-recognition domain of FMC63. The specificity of the mAb (clone no. 136.20.1) was confined to the scFv region of the CAR as validated by inhibiting CAR-dependent lysis of CD19+ tumor targets. This clone can be used to detect CD19-specific CAR+ T cells in peripheral blood mononuclear cells at a sensitivity of 1∶1,000. In clinical settings the mAb is used to inform on the immunophenotype and persistence of administered CD19-specific T cells. Thus, our CD19-specific CAR mAb (clone no. 136.20.1) will be useful to investigators implementing CD19-specific CAR+ T cells to treat B-lineage malignancies. The methodology described to develop a CAR-specific anti-idiotypic mAb could be extended to other gene therapy trials targeting different tumor associated antigens in the context of CAR-based adoptive T-cell therapy. PMID:23469246

  19. Chimeric antigen receptor (CAR)-specific monoclonal antibody to detect CD19-specific T cells in clinical trials.

    PubMed

    Jena, Bipulendu; Maiti, Sourindra; Huls, Helen; Singh, Harjeet; Lee, Dean A; Champlin, Richard E; Cooper, Laurence J N

    2013-01-01

    Clinical trials targeting CD19 on B-cell malignancies are underway with encouraging anti-tumor responses. Most infuse T cells genetically modified to express a chimeric antigen receptor (CAR) with specificity derived from the scFv region of a CD19-specific mouse monoclonal antibody (mAb, clone FMC63). We describe a novel anti-idiotype monoclonal antibody (mAb) to detect CD19-specific CAR(+) T cells before and after their adoptive transfer. This mouse mAb was generated by immunizing with a cellular vaccine expressing the antigen-recognition domain of FMC63. The specificity of the mAb (clone no. 136.20.1) was confined to the scFv region of the CAR as validated by inhibiting CAR-dependent lysis of CD19(+) tumor targets. This clone can be used to detect CD19-specific CAR(+) T cells in peripheral blood mononuclear cells at a sensitivity of 1∶1,000. In clinical settings the mAb is used to inform on the immunophenotype and persistence of administered CD19-specific T cells. Thus, our CD19-specific CAR mAb (clone no. 136.20.1) will be useful to investigators implementing CD19-specific CAR(+) T cells to treat B-lineage malignancies. The methodology described to develop a CAR-specific anti-idiotypic mAb could be extended to other gene therapy trials targeting different tumor associated antigens in the context of CAR-based adoptive T-cell therapy.

  20. Inaugural address

    NASA Astrophysics Data System (ADS)

    Joshi, P. S.

    2014-03-01

    From jets to cosmos to cosmic censorship P S Joshi Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai 400005, India E-mail: psj@tifr.res.in 1. Introduction At the outset, I should like to acknowledge that part of the title above, which tries to capture the main flavour of this meeting, and has been borrowed from one of the plenary talks at the conference. When we set out to make the programme for the conference, we thought of beginning with observations on the Universe, but then we certainly wanted to go further and address deeper questions, which were at the very foundations of our inquiry, and understanding on the nature and structure of the Universe. I believe, we succeeded to a good extent, and it is all here for you in the form of these Conference Proceedings, which have been aptly titled as 'Vishwa Mimansa', which could be possibly translated as 'Analysis of the Universe'! It is my great pleasure and privilege to welcome you all to the ICGC-2011 meeting at Goa. The International Conference on Gravitation and Cosmology (ICGC) series of meetings are being organized by the Indian Association for General Relativity and Gravitation (IAGRG), and the first such meeting was planned and conducted in Goa in 1987, with subsequent meetings taking place at a duration of about four years at various locations in India. So, it was thought appropriate to return to Goa to celebrate the 25 years of the ICGC meetings. The recollections from that first meeting have been recorded elsewhere here in these Proceedings. The research and teaching on gravitation and cosmology was initiated quite early in India, by V V Narlikar at the Banares Hindu University, and by N R Sen in Kolkata in the 1930s. In course of time, this activity grew and gained momentum, and in early 1969, at the felicitation held for the 60 years of V V Narlikar at a conference in Ahmedabad, P C Vaidya proposed the formation of the IAGRG society, with V V Narlikar being the first President. This

  1. Core outcome domains for clinical trials in non-specific low back pain.

    PubMed

    Chiarotto, Alessandro; Deyo, Richard A; Terwee, Caroline B; Boers, Maarten; Buchbinder, Rachelle; Corbin, Terry P; Costa, Leonardo O P; Foster, Nadine E; Grotle, Margreth; Koes, Bart W; Kovacs, Francisco M; Lin, Chung-Wei Christine; Maher, Chris G; Pearson, Adam M; Peul, Wilco C; Schoene, Mark L; Turk, Dennis C; van Tulder, Maurits W; Ostelo, Raymond W

    2015-06-01

    Inconsistent reporting of outcomes in clinical trials of patients with non-specific low back pain (NSLBP) hinders comparison of findings and the reliability of systematic reviews. A core outcome set (COS) can address this issue as it defines a minimum set of outcomes that should be reported in all clinical trials. In 1998, Deyo et al. recommended a standardized set of outcomes for LBP clinical research. The aim of this study was to update these recommendations by determining which outcome domains should be included in a COS for clinical trials in NSLBP. An International Steering Committee established the methodology to develop this COS. The OMERACT Filter 2.0 framework was used to draw a list of potential core domains that were presented in a Delphi study. Researchers, care providers and patients were invited to participate in three Delphi rounds and were asked to judge which domains were core. A priori criteria for consensus were established before each round and were analysed together with arguments provided by panellists on importance, overlap, aggregation and/or addition of potential core domains. The Steering Committee discussed the final results and made final decisions. A set of 280 experts was invited to participate in the Delphi; response rates in the three rounds were 52, 50 and 45%. Of 41 potential core domains presented in the first round, 13 had sufficient support to be presented for rating in the third round. Overall consensus was reached for the inclusion of three domains in this COS: 'physical functioning', 'pain intensity' and 'health-related quality of life'. Consensus on 'physical functioning' and 'pain intensity' was consistent across all stakeholders, 'health-related quality of life' was not supported by the patients, and all the other domains were not supported by two or more groups of stakeholders. Weighting all possible argumentations, the Steering Committee decided to include in the COS the three domains that reached overall consensus and

  2. Salud Para Su Corazon (health for your heart) community health worker model: community and clinical approaches for addressing cardiovascular disease risk reduction in Hispanics/Latinos.

    PubMed

    Balcazar, H; Alvarado, M; Ortiz, G

    2011-01-01

    This article describes 6 Salud Para Su Corazon (SPSC) family of programs that have addressed cardiovascular disease risk reduction in Hispanic communities facilitated by community health workers (CHWs) or Promotores de Salud (PS). A synopsis of the programs illustrates the designs and methodological approaches that combine community-based participatory research for 2 types of settings: community and clinical. Examples are provided as to how CHWs can serve as agents of change in these settings. A description is presented of a sustainability framework for the SPSC family of programs. Finally, implications are summarized for utilizing the SPSC CHW/PS model to inform ambulatory care management and policy.

  3. Convocation address.

    PubMed

    Kakodkar, A

    1999-07-01

    This convocation addressed by Dr. Anil Kakodkar focuses on the challenges faced by graduating students. In his speech, he emphasized the high level of excellence achieved by the industrial sector; however, he noted that there has been a loss of initiative in maximizing value addition, which was worsened by an increasing population pressure. In facing a stiff competition in the external and domestic markets, it is imperative to maximize value addition within the country in a competitive manner and capture the highest possible market share. To achieve this, high-quality human resources are central. Likewise, family planning programs should become more effective and direct available resources toward national advantage. To boost the domestic market, he suggests the need to search for strengths to achieve leadership position in those areas. First, an insight into the relationship between the lifestyles and the needs of our people and the natural resource endowment must be gained. Second, remodeling of the education system must be undertaken to prepare the people for adding the necessary innovative content in our value addition activities. Lastly, Dr. Kakodkar emphasizes the significance of developing a strong bond between parents and children to provide a sound foundation and allow the education system to grow upon it.

  4. Evaluation of nursing-specific drug information PDA databases used as clinical decision support tools.

    PubMed

    Polen, Hyla H; Clauson, Kevin A; Thomson, Wendy; Zapantis, Antonia; Lou, Jennie Q

    2009-10-01

    Nursing is arguably the most organizationally diverse healthcare profession. Educational backgrounds may vary, even among similarly credentialed nurses. Drug information databases used as clinical decision support tools can improve access to pharmacologic information at point-of-care when housed on personal digital assistants. They may also help address the disparity in drug information and pharmacology education between nurses. To evaluate nursing-specific drug information database content on personal digital assistants (PDAs). Seven nursing-specific PDA databases were evaluated for scope (absence or presence of an answer) and completeness (three-point scale) via the use of 80 general category and 80 subspecialty drug information questions. Erroneous information was also tracked. Individual scope and completeness scores were delineated by rank order and chi square was performed to determine differences in scope and completeness scores between the databases. Davis's Drug Guide for Nurses (DDGN) and Nursing Lexi-Drugs (NLD) tied for the highest scores for scope, including each answering 72.5% of the 160 evaluation questions. No significant differences existed between their scores and those earned by Nursing2008 Drug Handbook (p<0.05). The highest scores for completeness were earned by NLD with 58.1% and DDGN at 57.1%. Saunders Nursing Drug Handbook was the only database that showed a significantly lower score in completeness as compared to the other six databases (p<0.05). A 4.2% overall error rate was found among database answers. Significant differences were found among the performances in the databases evaluated in this study for their ability to answer commonly encountered drug information issues in nursing practice. All databases contained some erroneous information and even the top performers failed to provide answers to more than one-fourth of the questions posed. The availability of accurate and timely drug information at point-of-care can play a vital role

  5. Opening Address

    NASA Astrophysics Data System (ADS)

    Yamada, T.

    2014-12-01

    Ladies and Gentlemen, it is my great honor and pleasure to present an opening address of the 3rd International Workshop on "State of the Art in Nuclear Cluster Physics"(SOTANCP3). On the behalf of the organizing committee, I certainly welcome all your visits to KGU Kannai Media Center belonging to Kanto Gakuin University, and stay in Yokohama. In particular, to whom come from abroad more than 17 countries, I would appreciate your participations after long long trips from your homeland to Yokohama. The first international workshop on "State of the Art in Nuclear Cluster Physics", called SOTANCP, was held in Strasbourg, France, in 2008, and the second one was held in Brussels, Belgium, in 2010. Then the third workshop is now held in Yokohama. In this period, we had the traditional 10th cluster conference in Debrecen, Hungary, in 2012. Thus we have the traditional cluster conference and SOTANCP, one after another, every two years. This obviously shows our field of nuclear cluster physics is very active and flourishing. It is for the first time in about 10 years to hold the international workshop on nuclear cluster physics in Japan, because the last cluster conference held in Japan was in Nara in 2003, about 10 years ago. The president in Nara conference was Prof. K. Ikeda, and the chairpersons were Prof. H. Horiuchi and Prof. I. Tanihata. I think, quite a lot of persons in this room had participated at the Nara conference. Since then, about ten years passed. So, this workshop has profound significance for our Japanese colleagues. The subjects of this workshop are to discuss "the state of the art in nuclear cluster physics" and also discuss the prospect of this field. In a couple of years, we saw significant progresses of this field both in theory and in experiment, which have brought better and new understandings on the clustering aspects in stable and unstable nuclei. I think, the concept of clustering has been more important than ever. This is true also in the

  6. Convocation address.

    PubMed

    Ghatowar, P S

    1993-07-01

    The Union Deputy Minister of Health and Family Welfare in India addressed the 35th convocation of the International Institute for Population Sciences in Bombay in 1993. Officials in developing countries have been concerned about population growth for more than 30 years and have instituted policies to reduce population growth. In the 1960s, population growth in developing countries was around 2.5%, but today it is about 2%. Despite this decline, the world will have 1 billion more individuals by the year 2001. 95% of these new people will be born in developing countries. India's population size is so great that India does not have the time to wait for development to reduce population growth. Population needs to be viewed as an integrated part of overall development, since it is linked to poverty, illiteracy, environmental damage, gender issues, and reproductive health. Despite a large population size, India has made some important advancements in health and family planning. For example, India has reduced population growth (to 2.14% annually between 1981-1991), infant mortality, and its birth rate. It has increased the contraceptive use rate and life expectancy. Its southern states have been more successful at achieving demographic goals than have the northern states. India needs to implement efforts to improve living conditions, to change attitudes and perceptions about small families and contraception, and to promote family planning acceptance earlier among young couples. Improvement of living conditions is especially important in India, since almost 33% of the people live in poverty. India needs to invest in nutrition, health, and education. The mass media and nongovernmental organizations need to create population awareness and demand for family planning services. Improvement in women's status accelerates fertility decline, as has happened in Kerala State. The government needs to facilitate generation of jobs. Community participation is needed for India to achieve

  7. Presidential address.

    PubMed

    Vohra, U

    1993-07-01

    The Secretary of India's Ministry of Health and Family Welfare serves as Chair of the Executive Council of the International Institute for Population Sciences in Bombay. She addressed its 35th convocation in 1993. Global population stands at 5.43 billion and increases by about 90 million people each year. 84 million of these new people are born in developing countries. India contributes 17 million new people annually. The annual population growth rate in India is about 2%. Its population size will probably surpass 1 billion by the 2000. High population growth rates are a leading obstacle to socioeconomic development in developing countries. Governments of many developing countries recognize this problem and have expanded their family planning programs to stabilize population growth. Asian countries that have done so and have completed the fertility transition include China, Japan, Singapore, South Korea, and Thailand. Burma, Malaysia, North Korea, Sri Lanka, and Vietnam have not yet completed the transition. Afghanistan, Bangladesh, Iran, Nepal, and Pakistan are half-way through the transition. High population growth rates put pressure on land by fragmenting finite land resources, increasing the number of landless laborers and unemployment, and by causing considerable rural-urban migration. All these factors bring about social stress and burden civic services. India has reduced its total fertility rate from 5.2 to 3.9 between 1971 and 1991. Some Indian states have already achieved replacement fertility. Considerable disparity in socioeconomic development exists among states and districts. For example, the states of Bihar, Madhya Pradesh, Rajasthan, and Uttar Pradesh have female literacy rates lower than 27%, while that for Kerala is 87%. Overall, infant mortality has fallen from 110 to 80 between 1981 and 1990. In Uttar Pradesh, it has fallen from 150 to 98, while it is at 17 in Kerala. India needs innovative approaches to increase contraceptive prevalence rates

  8. Welcome Address

    NASA Astrophysics Data System (ADS)

    Kiku, H.

    2014-12-01

    Ladies and Gentlemen, It is an honor for me to present my welcome address in the 3rd International Workshop on "State of the Art in Nuclear Cluster Physics"(SOTANCP3), as the president of Kanto Gakuin University. Particularly to those from abroad more than 17 countries, I am very grateful for your participation after long long trips from your home to Yokohama. On the behalf of the Kanto Gakuin University, we certainly welcome your visit to our university and stay in Yokohama. First I would like to introduce Kanto Gakuin University briefly. Kanto Gakuin University, which is called KGU, traces its roots back to the Yokohama Baptist Seminary founded in 1884 in Yamate, Yokohama. The seminary's founder was Albert Arnold Bennett, alumnus of Brown University, who came to Japan from the United States to establish a theological seminary for cultivating and training Japanese missionaries. Now KGU is a major member of the Kanto Gakuin School Corporation, which is composed of two kindergartens, two primary schools, two junior high schools, two senior high schools as well as KGU. In this university, we have eight faculties with graduate school including Humanities, Economics, Law, Sciences and Engineering, Architecture and Environmental Design, Human and Environmental Studies, Nursing, and Law School. Over eleven thousands students are currently learning in our university. By the way, my major is the geotechnical engineering, and I belong to the faculty of Sciences and Engineering in my university. Prof. T. Yamada, here, is my colleague in the same faculty. I know that the nuclear physics is one of the most active academic fields in the world. In fact, about half of the participants, namely, more than 50 scientists, come from abroad in this conference. Moreover, I know that the nuclear physics is related to not only the other fundamental physics such as the elementary particle physics and astrophysics but also chemistry, medical sciences, medical cares, and radiation metrology

  9. President's Address

    PubMed Central

    Craig, Maurice

    1928-01-01

    Conditions which experience has proved conducive to mental disturbance considered.—Suggestions as to their treatment.—A weakened inhibition, rather than any positive condition, is probably the most important factor in the production of the exhaustion psycho-neuroses or psychoses. This view is supported by the prophylactic value of giving for prolonged periods small doses of bromide to hypersensitive children or to highly-strung persons exposed to stress or tropical climate, etc.—Pavlov's work on the conditioned reflexes in dogs quoted in support of the author's clinical experience: Pavlov states that bromides should not be regarded as sedatives, diminishing the excitability of the central nervous system, but as simply regulating the nervous system by strengthening the intensity of internal inhibition. This agrees with the author's clinical experience, as small doses of bromide taken regularly over a period of many years do not diminish the mental powers but in fact increase them. Question of sleeplessness considered with regard to the way in which sedatives act. Most of these do not act as so-called “sleeping draughts”; research may ultimately show that their action is to strengthen a weakened inhibition and that sleep is only a secondary benefit.—Value of sedatives before and after surgical operation. Importance of toxæmia in the production of mental disorder; insomnia often precedes a toxic process and permits it to become active. The theory of weakened inhibition explains many problems; e.g., why certain brilliant children or adults break down and why at first there is no interference with their normal mental activity which only becomes involved as sleep and other bodily functions become affected; why a toxæmia may affect the nervous system of certain people; why a breakdown may follow over-stimulation or occur with advancing years; why some persons relapse when certain treatment is discontinued; why treatment should at times be continuous, and why

  10. Clinical task-specific query expansion for the retrieval of scientifically rigorous research documents.

    PubMed

    Yoo, Sooyoung; Choi, Jinwook; Choi, Sungbin

    2010-01-01

    To support the practice of evidence-based medicine (EBM), clinically relevant and scientifically sound articles should be easily accessible. Due to the huge volume of medical literature and the low performance of present retrieval models, clinicians could only get relevant documents in the order of publication time. This study propose a new clinical task-specific retrieval technique that improves retrieval accuracy by exploiting clinical task-specific EBM terms to query expansion using co-occurrence analysis technique. The idea is aimed at selecting query expansion terms that are relevant to a specific clinical-task using task-specific EBM terms. Focusing on treatment and diagnosis tasks, the new method which was performed on the OHSUMED collection showed a further improved result than the existing method.

  11. Addressing Mental Health Disparities through Clinical Competence Not Just Cultural Competence: The Need for Assessment of Sociocultural Issues in the Delivery of Evidence-Based Psychosocial Rehabilitation Services

    PubMed Central

    Yamada, Ann-Marie; Brekke, John S

    2008-01-01

    Recognition of ethnic/racial disparities in mental health services has not directly resulted in the development of culturally responsive psychosocial interventions. There remains a fundamental need for assessment of sociocultural issues that have been linked with the expectations, needs, and goals of culturally diverse consumers with severe and persistent mental illness. The authors posit that embedding the assessment of sociocultural issues into psychosocial rehabilitation practice is one step in designing culturally relevant empirically supported practices. It becomes a foundation on which practitioners can examine the relevance of their interventions to the diversity encountered in everyday practice. This paper provides an overview of the need for culturally and clinically relevant assessment practices and asserts that by improving the assessment of sociocultural issues the clinical competence of service providers is enhanced. The authors offer a conceptual framework for linking clinical assessment of sociocultural issues to consumer outcomes and introduce an assessment tool adapted to facilitate the process in psychosocial rehabilitation settings. Emphasizing competent clinical assessment skills will ultimately offer a strategy to address disparities in treatment outcomes for understudied populations of culturally diverse consumers with severe and persistent mental illness. PMID:18778881

  12. President's Address

    PubMed Central

    Moore, John

    1928-01-01

    The paper recalls how matters veterinary were regarded forty-six years ago, what has been achieved since, and future progress is reflected. The paper is divided into parts relating respectively to: (a) medicine; (b) surgery (c) teaching and research; (d) administration. Formerly, glanders and farcy, and rabies, though acknowledged as contagious and specific, were also believed to be of spontaneous origin. Experiences with regard to these two diseases, and the mallein test for glanders, are related. The discovery of the Bacillus anthracis led to the development of veterinary research, but for some time confusion existed. Tuberculosis was believed to be endogenous and the result of the absorption of caseous products of a previous inflammation. Treatment of “milk fever” in cows by udder inflation and biochemistry in relation to that disease are considered. The advance in veterinary surgery stands out most prominently; in canine practice, operations are now attempted which were never thought possible in the early days. Allusion is made to the recent formidable operations for the cure of “windsucking” in horses, and for traumatic pericarditis in bovines. The powers of observance of the old practitioners in diagnosing lameness, and some of the old methods of treatment for lameness, are supported. The great progress in veterinary research is referred to, also its advantages from an imperial point of view. The causative agents of those diseases which are at present ultravisible, particularly foot-and-mouth disease, will probably be found, and better methods of prevention result. In training, thorough instruction in animal physiology, animal nutrition and biochemistry is advocated, also affiliation of veterinary colleges to universities, the individuality of such colleges, and the one-portal system of qualification being maintained. PMID:19986709

  13. Clinical Outcomes of Specific Immunotherapy in Advanced Pancreatic Cancer: A Systematic Review and Meta-Analysis.

    PubMed

    Chen, Jiang; Xiao-Zhong, Guo; Qi, Xing-Shun

    2017-01-01

    Specific immunotherapies, including vaccines with autologous tumor cells and tumor antigen-specific monoclonal antibodies, are important treatments for PC patients. To evaluate the clinical outcomes of PC-specific immunotherapy, we performed a systematic review and meta-analysis of the relevant published clinical trials. The effects of specific immunotherapy were compared with those of nonspecific immunotherapy and the meta-analysis was executed with results regarding the overall survival (OS), immune responses data, and serum cancer markers data. The pooled analysis was performed by using the random-effects model. We found that significantly improved OS was noted for PC patients utilizing specific immunotherapy and an improved immune response was also observed. In conclusion, specific immunotherapy was superior in prolonging the survival time and enhancing immunological responses in PC patients.

  14. Clinical Outcomes of Specific Immunotherapy in Advanced Pancreatic Cancer: A Systematic Review and Meta-Analysis

    PubMed Central

    Qi, Xing-Shun

    2017-01-01

    Specific immunotherapies, including vaccines with autologous tumor cells and tumor antigen-specific monoclonal antibodies, are important treatments for PC patients. To evaluate the clinical outcomes of PC-specific immunotherapy, we performed a systematic review and meta-analysis of the relevant published clinical trials. The effects of specific immunotherapy were compared with those of nonspecific immunotherapy and the meta-analysis was executed with results regarding the overall survival (OS), immune responses data, and serum cancer markers data. The pooled analysis was performed by using the random-effects model. We found that significantly improved OS was noted for PC patients utilizing specific immunotherapy and an improved immune response was also observed. In conclusion, specific immunotherapy was superior in prolonging the survival time and enhancing immunological responses in PC patients. PMID:28265583

  15. Molecular forms of serum prostate-specific antigen. The clinical value of percent free prostate-specific antigen.

    PubMed

    Abrahamsson, P A; Lilja, H; Oesterling, J E

    1997-05-01

    The concept of measuring the proportions of various forms of PSA in serum, particularly the proportion of free to total PSA, represents a new and exciting method of detecting early curable prostate cancers and avoiding unnecessary prostate biopsies in men who have BPH only. Compared with other methods of improving diagnostic specificity, it does not require transrectal ultrasound for determination of prostate volume, as does the use of PSA density, and it does not require multiple blood sampling over a sufficiently long period, as does PSA velocity. Recent findings suggest determination of the proportion of free to total PSA, rather than that of complexed to total PSA, to be the optimal discriminator between patients with prostate cancer and those with BPH in the PSA reflex range of 2.5 or 3 ng/mL to 10 ng/mL, and to improve the clinical accuracy of the PSA test substantially. If the total PSA value is normal, percent free PSA improves the sensitivity (increases cancer detection) of the PSA test; if the total PSA value is slightly elevated, percent free PSA enhances the specificity (eliminates unnecessary negative prostate biopsies) of the PSA test. Both of these outcomes are clinically desirable in attempting to diagnose early, curable prostate cancers in a cost-effective manner among men who also have varying degrees of BPH. Figure 5 contains a diagnostic algorithm for the detection of clinically significant prostate cancers at a curable stage, employing the concept of percent free PSA. As more is learned about percent free PSA, however, it may be necessary to make modifications in how this concept is used clinically.

  16. Implementation pearls from a new guidebook on improving medication use and outcomes with clinical decision support. Effective CDS is essential for addressing healthcare performance improvement imperatives.

    PubMed

    Sirajuddin, Anwar M; Osheroff, Jerome A; Sittig, Dean F; Chuo, John; Velasco, Ferdinand; Collins, David A

    2009-01-01

    Effective clinical decision support (CDS) is essential for addressing healthcare performance improvement imperatives, but care delivery organizations (CDO) typically struggle with CDS deployment. Ensuring safe and effective medication delivery to patients is a central focus of CDO performance improvement efforts, and this article provides an overview of best-practice strategies for applying CDS to these goals. The strategies discussed are drawn from a new guidebook, co-published and co-sponsored by more than a dozen leading organizations. Developed by scores of CDS implementers and experts, the guidebook outlines key steps and success factors for applying CDS to medication management. A central thesis is that improving outcomes with CDS interventions requires that the CDS five rights be addressed successfully. That is, the interventions must deliver the right information, to the right person, in the right format, through the right channel, at the right point in workflow. This paper provides further details about these CDS five rights, and highlights other important strategies for successful CDS programs.

  17. Relationship-Specific Condom Attitudes Predict Condom Use among STD Clinic Patients with both Primary and Non-Primary Partners

    PubMed Central

    Senn, Theresa E.; Scott-Sheldon, Lori A. J.; Carey, Michael P.

    2014-01-01

    Although condom use differs by partner type (i.e., primary vs. non-primary partner), attitudes towards condom use are typically measured without consideration of partner type. This study investigated the predictive utility of condom attitudes measured separately by partner type. Participants were 270 patients (37% women, 72% Black) recruited from a publicly-funded STD clinic who reported having both primary and non-primary partners. They completed a computerized survey assessing relationship-specific condom attitudes by partner type, condom attitudes related to pleasure and respect, and condom use with primary and non-primary partners. Participants reported more positive relationship-specific condom attitudes with a non-primary vs. primary partner. When considering pleasure-related, respect-related, and relationship-specific condom attitudes simultaneously, only relationship-specific condom attitudes predicted unprotected sex, with both primary and non-primary partners. In general, pleasure and respect-related condom attitudes did not predict unprotected sex; however, pleasure-related attitudes predicted unprotected sex with a non-primary partner for men. Future research should assess relationship-specific condom attitudes. Sexual risk reduction interventions that address interpersonal consequences of condom use in both primary and non-primary relationships should be a priority. PMID:24567031

  18. A software system to collect expert relevance ratings of medical record items for specific clinical tasks.

    PubMed

    Harvey, H Benjamin; Krishnaraj, Arun; Alkasab, Tarik K

    2014-02-28

    Development of task-specific electronic medical record (EMR) searches and user interfaces has the potential to improve the efficiency and safety of health care while curbing rising costs. The development of such tools must be data-driven and guided by a strong understanding of practitioner information requirements with respect to specific clinical tasks or scenarios. To acquire this important data, this paper describes a model by which expert practitioners are leveraged to identify which components of the medical record are most relevant to a specific clinical task. We also describe the computer system that was created to efficiently implement this model of data gathering. The system extracts medical record data from the EMR of patients matching a given clinical scenario, de-identifies the data, breaks the data up into separate medical record items (eg, radiology reports, operative notes, laboratory results, etc), presents each individual medical record item to experts under the hypothetical of the given clinical scenario, and records the experts' ratings regarding the relevance of each medical record item to that specific clinical scenario or task. After an iterative process of data collection, these expert relevance ratings can then be pooled and used to design point-of-care EMR searches and user interfaces tailored to the task-specific needs of practitioners.

  19. States Address Achievement Gaps.

    ERIC Educational Resources Information Center

    Christie, Kathy

    2002-01-01

    Summarizes 2 state initiatives to address the achievement gap: North Carolina's report by the Advisory Commission on Raising Achievement and Closing Gaps, containing an 11-point strategy, and Kentucky's legislation putting in place 10 specific processes. The North Carolina report is available at www.dpi.state.nc.us.closingthegap; Kentucky's…

  20. Analyzing multiple endpoints in a confirmatory randomized clinical trial-an approach that addresses stratification, missing values, baseline imbalance and multiplicity for strictly ordinal outcomes.

    PubMed

    Sun, Hengrui; Kawaguchi, Atsushi; Koch, Gary

    2017-03-01

    Confirmatory randomized clinical trials with a stratified design may have ordinal response outcomes, ie, either ordered categories or continuous determinations that are not compatible with an interval scale. Also, multiple endpoints are often collected when 1 single endpoint does not represent the overall efficacy of the treatment. In addition, random baseline imbalances and missing values can add another layer of difficulty in the analysis plan. Therefore, the development of an approach that provides a consolidated strategy to all issues collectively is essential. For a real case example that is from a clinical trial comparing a test treatment and a control for the pain management for patients with osteoarthritis, which has all aforementioned issues, multivariate Mann-Whitney estimators with stratification adjustment are applicable to the strictly ordinal responses with stratified design. Randomization based nonparametric analysis of covariance is applied to account for the possible baseline imbalances. Several approaches that handle missing values are provided. A global test followed by a closed testing procedure controls the family wise error rate in the strong sense for the analysis of multiple endpoints. Four outcomes indicating joint pain, stiffness, and functional status were analyzed collectively and also individually through the procedures. Treatment efficacy was observed in the combined endpoint as well as in the individual endpoints. The proposed approach is effective in addressing the aforementioned problems simultaneously and straightforward to implement.

  1. Clinical and Preclinical Use of LOX-1-Specific Antibodies in Diagnostics and Therapeutics.

    PubMed

    De Siqueira, Jonathan; Abdul Zani, Izma; Russell, David A; Wheatcroft, Stephen B; Ponnambalam, Sreenivasan; Homer-Vanniasinkam, Shervanthi

    2015-11-01

    Lectin-like oxidized low-density lipoprotein receptor-1 (SR-E1, LOX-1, OLR1) was first discovered as a vascular receptor for modified lipoprotein particles nearly 20 years ago. Since then, in vitro and in vivo studies have demonstrated an association between LOX-1, a soluble form (sLOX-1) and a number of diseases including atherosclerosis, arthritis, hypertension and pre-eclampsia. However, converting such discoveries into tools and drugs for routine clinical use is dependent on translational preclinical and clinical studies but such studies have only begun to emerge in the past decade. In this review, we identify the key clinical applications and corresponding criteria that need to be addressed for the effective use of LOX-1-related probes and molecules for patient benefit in different disease states.

  2. Urine specific gravity values in clinically healthy young pet ferrets (Mustela furo).

    PubMed

    Eshar, D; Wyre, N R; Brown, D C

    2012-02-01

    To determine urine specific gravity values in clinically healthy pet ferrets and explore possible associations with sex, sampling techniques, hydration status and urine analytes. Sixty-nine entire ferrets of both sexes, under one year of age, were included in this study. Physical examination, complete blood count, blood biochemistry, urine microscopy, urine dipstick and urine specific gravity were performed on all ferrets. Urine specific gravity was determined using a handheld urine refractometer. Statistical analysis was performed to determine urine specific gravity value intervals and to test for associations with sex, sample collection method, packed cell volume, plasma total protein concentrations and urine analytes. Urine specific gravity differed by sex in ferrets as females exhibited a lower urine specific gravity (P<0·001). There was no significant correlation between urine specific gravity, sampling method, packed cell volume/total protein and urine dipstick analytes. Mean urine specific gravity reported in this study was 1·051 for entire males (sd ±9; range 1·034 to 1·070) and 1·042 for entire females (sd ±8; range 1·026 to 1·060). Results of this study may allow clinicians to have a more accurate evaluation of the ability of those animals to concentrate urine by comparing their urine specific gravity results to those obtained from this cohort of clinically healthy animals. © 2012 British Small Animal Veterinary Association.

  3. Commercial insurance vs community-based health plans: time for a policy option with clinical emphasis to address the cost spiral.

    PubMed

    Amundson, Bruce

    2005-01-01

    The nation continues its ceaseless struggle with the spiraling cost of health care. Previous efforts (regulation, competition, voluntary action) have included almost every strategy except clinical. Insurers have largely failed in their cost-containment efforts. There is a strong emerging body of literature that demonstrates the relationship between various clinical strategies and reductions in utilization and costs. This article describes the organization of health services, including integration of delivery and financing systems, at the community level as a model that effectively addresses the critical structural flaws that have frustrated control of costs. Community-based health plans (CHPs) have been developed and have demonstrated viability. The key elements of CHPs are a legal organizational structure, a full provider network, advanced care-management systems, and the ability to assume financial risk. Common misconceptions regarding obstacles to CHP development are the complexity of the undertaking, difficulty assuming the insurance function, and insured pools that are too small to be viable. The characteristics of successful CHPs and 2 case studies are described, including the types of advanced care-management systems that have resulted in strong financial performance. The demonstrated ability of CHPs to establish financial viability with small numbers of enrollees challenges the common assumption that there is a fixed relationship between health plan enrollment size and financial performance. Organizing the health system at the community/regional level provides an attractive alternative model in the health-reform debate. There is an opportunity for clinical systems and state and federal leaders to support the development of community-based integrated delivery and financing system models that, among other advantages, have significant potential to modulate the pernicious cost spiral.

  4. Sensitivity and specificity should never be interpreted in isolation without consideration of other clinical utility metrics.

    PubMed

    Lange, Rael T; Lippa, Sara M

    The purpose of this paper is to highlight the risks and pitfalls of interpreting sensitivity and specificity in isolation when evaluating the clinical utility of a new test/measure to predict a target behavior, disease, or condition. This paper (a) provides a primer for a set of metrics that can be used to appropriately examine the clinical utility of a test/measure (i.e. test operating characteristics - TOC), and (b) provides a discussion regarding various interpretative considerations when using TOCs that supports the tenet of this paper. There are two primary conclusions. First, sensitivity and specificity should never be interpreted in isolation as a means for evaluating the clinical utility of a test/measure. When sensitivity and specificity are used in this manner, more often than not, this will result in erroneous and/or incomplete conclusions regarding the clinical utility of a new test/measure. Second, sensitivity and specificity values are important, but they must be interpreted in conjunction with other more relevant clinical utility metrics (e.g. positive predictive power and negative predictive power).

  5. PR1 peptide vaccine induces specific immunity with clinical responses in myeloid malignancies.

    PubMed

    Qazilbash, M H; Wieder, E; Thall, P F; Wang, X; Rios, R; Lu, S; Kanodia, S; Ruisaard, K E; Giralt, S A; Estey, E H; Cortes, J; Komanduri, K V; Clise-Dwyer, K; Alatrash, G; Ma, Q; Champlin, R E; Molldrem, J J

    2017-03-01

    PR1, an HLA-A2-restricted peptide derived from both proteinase 3 and neutrophil elastase, is recognized on myeloid leukemia cells by cytotoxic T lymphocytes (CTLs) that preferentially kill leukemia and contribute to cytogenetic remission. To evaluate safety, immunogenicity and clinical activity of PR1 vaccination, a phase I/II trial was conducted. Sixty-six HLA-A2+ patients with acute myeloid leukemia (AML: 42), chronic myeloid leukemia (CML: 13) or myelodysplastic syndrome (MDS: 11) received three to six PR1 peptide vaccinations, administered subcutaneously every 3 weeks at dose levels of 0.25, 0.5 or 1.0 mg. Patients were randomized to the three dose levels after establishing the safety of the highest dose level. Primary end points were safety and immune response, assessed by doubling of PR1/HLA-A2 tetramer-specific CTL, and the secondary end point was clinical response. Immune responses were noted in 35 of 66 (53%) patients. Of the 53 evaluable patients with active disease, 12 (24%) had objective clinical responses (complete: 8; partial: 1 and hematological improvement: 3). PR1-specific immune response was seen in 9 of 25 clinical responders versus 3 of 28 clinical non-responders (P=0.03). In conclusion, PR1 peptide vaccine induces specific immunity that correlates with clinical responses, including molecular remission, in AML, CML and MDS patients.

  6. Retinal Diseases Caused by Mutations in Genes Not Specifically Associated with the Clinical Diagnosis.

    PubMed

    Wang, Xia; Feng, Yanming; Li, Jianli; Zhang, Wei; Wang, Jing; Lewis, Richard A; Wong, Lee-Jun

    2016-01-01

    When seeking a confirmed molecular diagnosis in the research setting, patients with one descriptive diagnosis of retinal disease could carry pathogenic variants in genes not specifically associated with that description. However, this event has not been evaluated systematically in clinical diagnostic laboratories that validate fully all target genes to minimize false negatives/positives. We performed targeted next-generation sequencing analysis on 207 ocular disease-related genes for 42 patients whose DNA had been tested negative for disease-specific panels of genes known to be associated with retinitis pigmentosa, Leber congenital amaurosis, or exudative vitreoretinopathy. Pathogenic variants, including single nucleotide variations and copy number variations, were identified in 9 patients, including 6 with variants in syndromic retinal disease genes and 3 whose molecular diagnosis could not be distinguished easily from their submitted clinical diagnosis, accounting for 21% (9/42) of the unsolved cases. Our study underscores the clinical and genetic heterogeneity of retinal disorders and provides valuable reference to estimate the fraction of clinical samples whose retinal disorders could be explained by genes not specifically associated with the corresponding clinical diagnosis. Our data suggest that sequencing a larger set of retinal disorder related genes can increase the molecular diagnostic yield, especially for clinically hard-to-distinguish cases.

  7. PR1 Peptide Vaccine Induces Specific Immunity With Clinical Responses In Myeloid Malignancies

    PubMed Central

    Qazilbash, Muzaffar H.; Wieder, Eric; Thall, Peter F.; Wang, Xuemei; Rios, Rosa; Lu, Sijie; Kanodia, Shreya; Ruisaard, Kathryn E.; Giralt, Sergio A.; Estey, Elihu H.; Cortes, Jorge; Komanduri, Krishna V.; Clise-Dwyer, Karen; Alatrash, Gheath; Ma, Qing; Champlin, Richard E.; Molldrem, Jeffrey J.

    2016-01-01

    PR1, an HLA-A2-restricted peptide derived from both proteinase 3 and neutrophil elastase, is recognized on myeloid leukemia cells by cytotoxic T lymphocytes (CTL) that preferentially kill leukemia and contribute to cytogenetic remission. To evaluate safety, immunogenicity and clinical activity of PR1 vaccination, a phase I/II trial was conducted. Sixty-six HLA-A2+ patients with acute myeloid leukemia (AML: 42), chronic myeloid leukemia (CML: 13) or myelodysplastic syndrome (MDS: 11) received three to six PR1 peptide vaccinations, administered subcutaneously every 3 weeks at dose levels of 0.25, 0.5 or 1.0 mg. Patients were randomized to the 3 dose levels after establishing the safety of the highest dose level. Primary endpoints were safety and immune response, assessed by doubling of PR1/HLA-A2 tetramer-specific CTL, and the secondary endpoint was clinical response. Immune responses were noted in 35 of 66 (53%) patients. Of the 53 evaluable patients with active disease, 12 (24%) had objective clinical responses (complete: 8, partial: 1 and hematological improvement: 3). PR1-specific immune response was seen in 9 of 25 clinical responders vs. 3 of 28 clinical non-responders (p=0.03). In conclusion, PR1 peptide vaccine induces specific immunity that correlates with clinical responses, including molecular remission, in AML, CML and MDS patients. PMID:27654852

  8. Retinal Diseases Caused by Mutations in Genes Not Specifically Associated with the Clinical Diagnosis

    PubMed Central

    Feng, Yanming; Li, Jianli; Zhang, Wei; Wang, Jing; Lewis, Richard A.; Wong, Lee-Jun

    2016-01-01

    Purpose When seeking a confirmed molecular diagnosis in the research setting, patients with one descriptive diagnosis of retinal disease could carry pathogenic variants in genes not specifically associated with that description. However, this event has not been evaluated systematically in clinical diagnostic laboratories that validate fully all target genes to minimize false negatives/positives. Methods We performed targeted next-generation sequencing analysis on 207 ocular disease-related genes for 42 patients whose DNA had been tested negative for disease-specific panels of genes known to be associated with retinitis pigmentosa, Leber congenital amaurosis, or exudative vitreoretinopathy. Results Pathogenic variants, including single nucleotide variations and copy number variations, were identified in 9 patients, including 6 with variants in syndromic retinal disease genes and 3 whose molecular diagnosis could not be distinguished easily from their submitted clinical diagnosis, accounting for 21% (9/42) of the unsolved cases. Conclusion Our study underscores the clinical and genetic heterogeneity of retinal disorders and provides valuable reference to estimate the fraction of clinical samples whose retinal disorders could be explained by genes not specifically associated with the corresponding clinical diagnosis. Our data suggest that sequencing a larger set of retinal disorder related genes can increase the molecular diagnostic yield, especially for clinically hard-to-distinguish cases. PMID:27788217

  9. Patient-specific bone modeling and analysis: the role of integration and automation in clinical adoption.

    PubMed

    Zadpoor, Amir A; Weinans, Harrie

    2015-03-18

    Patient-specific analysis of bones is considered an important tool for diagnosis and treatment of skeletal diseases and for clinical research aimed at understanding the etiology of skeletal diseases and the effects of different types of treatment on their progress. In this article, we discuss how integration of several important components enables accurate and cost-effective patient-specific bone analysis, focusing primarily on patient-specific finite element (FE) modeling of bones. First, the different components are briefly reviewed. Then, two important aspects of patient-specific FE modeling, namely integration of modeling components and automation of modeling approaches, are discussed. We conclude with a section on validation of patient-specific modeling results, possible applications of patient-specific modeling procedures, current limitations of the modeling approaches, and possible areas for future research. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Integration of Disease Specific Clinical and Genomics Datasets using I2B2 Framework.

    PubMed

    2015-01-01

    The availability of a patient's genomic profile along with the clinical profile for providing individualized care and treatment is paving the road for a new era of personalized medicine, and is an important area of focus in current biomedical research. One of the prominent and globally implemented solutions for clinical and genomics data integration in biomedical research is an NIH funded NCBC initiative--Informatics for Integrating Biology and the Beside (I2B2). This paper presents the development of a pilot prototype for integrating patient's clinical and genomics datasets using open source and scalable I2B2 Framework. It focuses on disease specific clinical data and genomic variants, when combined together can be used for informed decision making in clinical practices by healthcare professionals and for further investigations by biomedical researchers. The research was carried out using a case study of King Abdullah International Medical Research Center (KAIMRC) in collaboration with King Fahad National Guard Hospital (KFNGH).

  11. Precision autophagy: Will the next wave of selective autophagy markers and specific autophagy inhibitors feed clinical pipelines?

    PubMed

    Lebovitz, Chandra B; DeVorkin, Lindsay; Bosc, Damien; Rothe, Katharina; Singh, Jagbir; Bally, Marcel; Jiang, Xiaoyan; Young, Robert N; Lum, Julian J; Gorski, Sharon M

    2015-01-01

    Research presented at the Vancouver Autophagy Symposium (VAS) 2014 suggests that autophagy's influence on health and disease depends on tight regulation and precision targeting of substrates. Discussions recognized a pressing need for robust biomarkers that accurately assess the clinical utility of modulating autophagy in disease contexts. Biomarker discovery could flow from investigations of context-dependent triggers, sensors, and adaptors that tailor the autophagy machinery to achieve target specificity. In his keynote address, Dr. Vojo Deretic (University of New Mexico) described the discovery of a cargo receptor family that utilizes peptide motif-based cargo recognition, a mechanism that may be more precise than generic substrate tagging. The keynote by Dr. Alec Kimmelman (Harvard Medical School) emphasized that unbiased screens for novel selective autophagy factors may accelerate the development of autophagy-based therapies. Using a quantitative proteomics screen for de novo identification of autophagosome substrates in pancreatic cancer, Kimmelman's group discovered a new type of selective autophagy that regulates bioavailable iron. Additional presentations revealed novel autophagy regulators and receptors in metabolic diseases, proteinopathies, and cancer, and outlined the development of specific autophagy inhibitors and treatment regimens that combine autophagy modulation with anticancer therapies. VAS 2014 stimulated interdisciplinary discussions focused on the development of biomarkers, drugs, and preclinical models to facilitate clinical translation of key autophagy discoveries.

  12. Early-Onset Obsessive-Compulsive Disorder: A Subgroup with a Specific Clinical and Familial Pattern?

    ERIC Educational Resources Information Center

    Chabane, Nadia; Delorme, Richard; Millet, Bruno; Mouren, Marie-Christine; Leboyer, Marion; Pauls, David

    2005-01-01

    Background: The familial nature of obsessive-compulsive disorder (OCD) has been previously demonstrated. The identification of candidate symptoms such as age at onset may help to disentangle the clinical and genetic heterogeneity of the disorder. In this study, the specificity of early-onset OCD was investigated, focusing on the effect of gender,…

  13. Clinical Markers for Identification of Children with Specific Language Impairment (SLI)

    ERIC Educational Resources Information Center

    Rao, Prema K. S.; Prasitha, P.; Savitha, S.; Purushothaman, P.; Chitra, R.; Balaji, R.

    2010-01-01

    The condition of Specific Language Impairment (SLI) has aroused immense interest among researchers and practitioners owing to its unique characteristics and clinical manifestations. Children with SLI have offered rich data for understanding of language processing with reference to cognitive functions as well as structural aspects of a given…

  14. Early-Onset Obsessive-Compulsive Disorder: A Subgroup with a Specific Clinical and Familial Pattern?

    ERIC Educational Resources Information Center

    Chabane, Nadia; Delorme, Richard; Millet, Bruno; Mouren, Marie-Christine; Leboyer, Marion; Pauls, David

    2005-01-01

    Background: The familial nature of obsessive-compulsive disorder (OCD) has been previously demonstrated. The identification of candidate symptoms such as age at onset may help to disentangle the clinical and genetic heterogeneity of the disorder. In this study, the specificity of early-onset OCD was investigated, focusing on the effect of gender,…

  15. Precision Oncology Medicine: The Clinical Relevance of Patient-Specific Biomarkers Used to Optimize Cancer Treatment.

    PubMed

    Schmidt, Keith T; Chau, Cindy H; Price, Douglas K; Figg, William D

    2016-12-01

    Precision medicine in oncology is the result of an increasing awareness of patient-specific clinical features coupled with the development of genomic-based diagnostics and targeted therapeutics. Companion diagnostics designed for specific drug-target pairs were the first to widely utilize clinically applicable tumor biomarkers (eg, HER2, EGFR), directing treatment for patients whose tumors exhibit a mutation susceptible to an FDA-approved targeted therapy (eg, trastuzumab, erlotinib). Clinically relevant germline mutations in drug-metabolizing enzymes and transporters (eg, TPMT, DPYD) have been shown to impact drug response, providing a rationale for individualized dosing to optimize treatment. The use of multigene expression-based assays to analyze an array of prognostic biomarkers has been shown to help direct treatment decisions, especially in breast cancer (eg, Oncotype DX). More recently, the use of next-generation sequencing to detect many potential "actionable" cancer molecular alterations is further shifting the 1 gene-1 drug paradigm toward a more comprehensive, multigene approach. Currently, many clinical trials (eg, NCI-MATCH, NCI-MPACT) are assessing novel diagnostic tools with a combination of different targeted therapeutics while also examining tumor biomarkers that were previously unexplored in a variety of cancer histologies. Results from ongoing trials such as the NCI-MATCH will help determine the clinical utility and future development of the precision-medicine approach. © 2016, The American College of Clinical Pharmacology.

  16. What specifications for a centre or network of excellence in clinical research?

    PubMed

    Diebolt, Vincent; Lang, Marie; Thoby, Frédérique

    2016-02-01

    The Giens 2015 Workshop Round Table entitled "What specifications for a centre or network of excellence in clinical research?" took a viewpoint distinct from earlier work and studies on changes in clinical research activities in France. The purpose of the present work was to identify, starting from concrete examples, the main strengths and advantages of clinical research activity in France related, in part, to the background environment and also to the specific characteristics of the investigation centres considered to be among the most high-performance units in activity. The criteria retained were grouped into a set of specifications that could be used to establish a "label of excellence" upon which the different teams and clinical research centres could model themselves. It was thus considered that belonging to a centre or structured network with at least a national configuration, when this is possible for the medial topic in question, constitutes a real advantage. Four benchmarks were identified: the scientific and clinical expertise of the head investigator, as well as the qualification and operational capacity of the centre's team; definition and measurement of performance using clearly displayed indicators and evaluation procedures; the quality of the overall trial "process" and of each of its component steps; communication, because know-how and promotion go hand in hand, with the main objective of informing the professional and general public about the value of the research centre meeting the above-mentioned criteria, about its networks of competencies, and more generally, about the important assets of the background of clinical research in France. This sector of research is funded by the public authorities via calls for public grants, financial aids for structures supporting clinical research in the University Hospital Centres and other healthcare institutions allowing for a professionalization of the research occupations, and the national public health

  17. Untying the gordian knot: what we do and don't know about gender-specific medicine-keynote address for the 2014 Academic Emergency Medicine Consensus Conference.

    PubMed

    Legato, Marianne

    2014-12-01

    Over the past two decades, a burgeoning interest in women's health, the direct consequence of the feminist movement, has inspired a worldwide interest in the differences between the normal function of men and women and their unique experiences of the same illnesses. The scope and significance of what we have discovered and continue to find has fundamentally changed the way we prevent, diagnose, and treat diseases. Important questions remain, however, and deserve specific investigation and analysis.

  18. Constructing Patient Specific Clinical Trajectories from Electronic Healthcare Reimbursement Claims using Sequential Pattern Mining

    SciTech Connect

    Pullum, Laura L; Hobson, Tanner C

    2015-01-01

    We examine the use of electronic healthcare reimbursement claims (EHRC) for analyzing healthcare delivery and practice patterns across the United States (US). By analyzing over 1 billion EHRCs, we track patterns of clinical procedures administered to patients with heart disease (HD) using sequential pattern mining algorithms. Our analyses reveal that the clinical procedures performed on HD patients are highly varied leading up to and after the primary diagnosis. The discovered clinical procedure sequences reveal significant differences in the overall costs incurred across different parts of the US, indicating significant heterogeneity in treating HD patients. We show that a data-driven approach to understand patient specific clinical trajectories constructed from EHRC can provide quantitative insights into how to better manage and treat patients.

  19. Treatment selection in a randomized clinical trial via covariate-specific treatment effect curves.

    PubMed

    Ma, Yunbei; Zhou, Xiao-Hua

    2017-02-01

    For time-to-event data in a randomized clinical trial, we proposed two new methods for selecting an optimal treatment for a patient based on the covariate-specific treatment effect curve, which is used to represent the clinical utility of a predictive biomarker. To select an optimal treatment for a patient with a specific biomarker value, we proposed pointwise confidence intervals for each covariate-specific treatment effect curve and the difference between covariate-specific treatment effect curves of two treatments. Furthermore, to select an optimal treatment for a future biomarker-defined subpopulation of patients, we proposed confidence bands for each covariate-specific treatment effect curve and the difference between each pair of covariate-specific treatment effect curve over a fixed interval of biomarker values. We constructed the confidence bands based on a resampling technique. We also conducted simulation studies to evaluate finite-sample properties of the proposed estimation methods. Finally, we illustrated the application of the proposed method in a real-world data set.

  20. Non-specific (anaerobic) vaginitis: relevance of clinical and laboratory studies in a practice population

    PubMed Central

    Kelsey, M.C.; Mann, G.K.; Bangham, A.M.; Milnthorpe, J.

    1987-01-01

    Non-specific vaginitis is a commonly diagnosed condition defined in a similar manner by most authors. Although assumed to be of infective aetiology, no single organism has yet been accepted as the primary agent. This syndrome was studied in two groups of women presenting to general practitioners or attending a family planning clinic. The two groups were of similar ages and had similar markers of sexual activity. Of the 173 women studied, 90 had symptoms. Of the symptomatic women 9.5% could be categorized as having non-specific vaginitis and 36.7% as having an alternative cause for their discharge. Gardnerella vaginalis were found to be associated with anaerobes, clue cells and staphylococci more frequently than by chance. The isolation of G. vaginalis or anaerobes was assessed for their ability to help confirm the diagnosis of non-specific vaginitis and to distinguish this from other possible pathology. In patients with clinical non-specific vaginitis, the isolation of G. vaginalis proved the most sensitive (100%) though not a very specific (77.4%) indicator, whereas anaerobes were more specific (93.2%). The presence of anaerobes was a better predictor of non-specific vaginitis (30.8%) than G. vaginalis (18.9%). It was concluded that providing laboratory facilities specifically for the isolation of G. vaginalis would be of little benefit to the general practitioner in diagnosing non-specific vaginitis since it would add to the cost of processing specimens, whereas reporting the presence of heavy growths of anaerobes provides some confirmation and adds little to the cost. PMID:3499507

  1. Addressing the Question of Disorder-Specific Risk Factors of Internet Addiction: A Comparison of Personality Traits in Patients with Addictive Behaviors and Comorbid Internet Addiction

    PubMed Central

    Müller, K. W.; Koch, A.; Dickenhorst, U.; Beutel, M. E.; Duven, E.; Wölfling, K.

    2013-01-01

    Uncontrolled use of the internet has been reported to affect the lives of some users in a negative way. According to epidemiological studies, about 1% of the general population is showing signs of internet addiction. Since internet addiction is becoming a growing health concern, research on potential risk factors is becoming more important in order to develop strategies for prevention and to adopt therapeutic treatment. Although there are some studies investigating personality traits in internet addiction, most of these studies are based on samples of healthy subjects. In this research project, we compared personality profiles of a sample of patients in different rehabilitation centers. 70 patients with an addiction disorder that additionally met the criteria for internet addiction were compared to 48 patients suffering from alcohol dependence. Besides Big Five personality traits, we also assessed depressive symptoms. It was shown that patients with comorbid internet addiction can be discriminated from other patients by higher neuroticism and lower extraversion as well as lower conscientiousness. After controlling for depressive symptoms, lower conscientiousness especially turned out to be a disorder-specific risk factor. As internet addiction is related to unique patterns of personality traits and can be discriminated from alcohol dependence, treatment approaches are needed that meet the specific requirements of patients with internet addiction. PMID:23865056

  2. Addressing the question of disorder-specific risk factors of internet addiction: a comparison of personality traits in patients with addictive behaviors and comorbid internet addiction.

    PubMed

    Müller, K W; Koch, A; Dickenhorst, U; Beutel, M E; Duven, E; Wölfling, K

    2013-01-01

    Uncontrolled use of the internet has been reported to affect the lives of some users in a negative way. According to epidemiological studies, about 1% of the general population is showing signs of internet addiction. Since internet addiction is becoming a growing health concern, research on potential risk factors is becoming more important in order to develop strategies for prevention and to adopt therapeutic treatment. Although there are some studies investigating personality traits in internet addiction, most of these studies are based on samples of healthy subjects. In this research project, we compared personality profiles of a sample of patients in different rehabilitation centers. 70 patients with an addiction disorder that additionally met the criteria for internet addiction were compared to 48 patients suffering from alcohol dependence. Besides Big Five personality traits, we also assessed depressive symptoms. It was shown that patients with comorbid internet addiction can be discriminated from other patients by higher neuroticism and lower extraversion as well as lower conscientiousness. After controlling for depressive symptoms, lower conscientiousness especially turned out to be a disorder-specific risk factor. As internet addiction is related to unique patterns of personality traits and can be discriminated from alcohol dependence, treatment approaches are needed that meet the specific requirements of patients with internet addiction.

  3. Association of immunological cell profiles with specific clinical phenotypes of scleroderma disease.

    PubMed

    López-Cacho, José Manuel; Gallardo, Soledad; Posada, Manuel; Aguerri, Miriam; Calzada, David; Mayayo, Teodoro; González-Rodríguez, María Luisa; Rabasco, Antonio María; Lahoz, Carlos; Cárdaba, Blanca

    2014-01-01

    This study aimed to search the correlation among immunological profiles and clinical phenotypes of scleroderma in well-characterized groups of scleroderma patients, comparing forty-nine scleroderma patients stratified according to specific clinical phenotypes with forty-nine healthy controls. Five immunological cell subpopulations (B, CD4(+) and CD8(+) T-cells, NK, and monocytes) and their respective stages of apoptosis and activation were analyzed by flow cytometry, in samples of peripheral blood mononuclear cells (PBMCs). Analyses of results were stratified according to disease stage, time since the diagnosis, and visceral damage (pulmonary fibrosis, pulmonary hypertension, and cardiac affliction) and by time of treatment with corticosteroids. An increase in the percentages of monocytes and a decrease in the B cells were mainly related to the disease progression. A general apoptosis decrease was found in all phenotypes studied, except in localized scleroderma. An increase of B and NK cells activation was found in patients diagnosed more than 10 years ago. Specific cell populations like monocytes, NK, and B cells were associated with the type of affected organ. This study shows how, in a heterogeneous disease, proper patient's stratification according to clinical phenotypes allows finding specific cellular profiles. Our data may lead to improvements in the knowledge of prognosis factors and to aid in the analysis of future specific therapies.

  4. Association of Immunological Cell Profiles with Specific Clinical Phenotypes of Scleroderma Disease

    PubMed Central

    Calzada, David; Mayayo, Teodoro; González-Rodríguez, María Luisa; Rabasco, Antonio María; Lahoz, Carlos

    2014-01-01

    This study aimed to search the correlation among immunological profiles and clinical phenotypes of scleroderma in well-characterized groups of scleroderma patients, comparing forty-nine scleroderma patients stratified according to specific clinical phenotypes with forty-nine healthy controls. Five immunological cell subpopulations (B, CD4+ and CD8+ T-cells, NK, and monocytes) and their respective stages of apoptosis and activation were analyzed by flow cytometry, in samples of peripheral blood mononuclear cells (PBMCs). Analyses of results were stratified according to disease stage, time since the diagnosis, and visceral damage (pulmonary fibrosis, pulmonary hypertension, and cardiac affliction) and by time of treatment with corticosteroids. An increase in the percentages of monocytes and a decrease in the B cells were mainly related to the disease progression. A general apoptosis decrease was found in all phenotypes studied, except in localized scleroderma. An increase of B and NK cells activation was found in patients diagnosed more than 10 years ago. Specific cell populations like monocytes, NK, and B cells were associated with the type of affected organ. This study shows how, in a heterogeneous disease, proper patient's stratification according to clinical phenotypes allows finding specific cellular profiles. Our data may lead to improvements in the knowledge of prognosis factors and to aid in the analysis of future specific therapies. PMID:24818126

  5. Prolonged elevation of serum neuron-specific enolase in children after clinical diagnosis of brain death.

    PubMed

    Suzuki, Yasuhiro; Mogami, Yukiko; Toribe, Yausihisa; Yamada, Keitaro; Yanagihara, Keiko; Hirata, Ikuko; Mano, Toshiyuki

    2012-01-01

    To elucidate the time course of neuronal cell death after the clinical criteria for brain death are met, the authors reviewed serial changes of serum neuron-specific enolase levels in 3 children (age range, 3-15 years) clinically diagnosed as brain dead due to cardiopulmonary arrest. All patients survived for more than 2 months after brain death. Children with brain death had higher peak neuron-specific enolase values (1069-2849 ng/mL) than did 3 control children (256-1800 ng/mL) who did not become brain dead but had poor neurological outcome (1 death, 2 vegetative state) after cardiopulmonary arrest. A major finding is that children with brain death showed persistent elevation of neuron-specific enolase at 4 weeks (>400 ng/mL) and 8 weeks (>50 ng/mL) after cardiopulmonary arrest, in comparison with 2 surviving patients without brain death (<50 ng/mL at 4 weeks). This prolonged elevation of neuron-specific enolase suggests that total brain necrosis might not be present at the time of clinical diagnosis of brain death.

  6. Clinic diagnosis of anaerobic vaginosis (non-specific vaginitis). A practical guide.

    PubMed Central

    Blackwell, A; Barlow, D

    1982-01-01

    Anaerobic vaginosis (non-specific vaginitis) can be readily diagnosed at the time of first attendance without recourse to expensive and time-consuming laboratory investigations. Diagnosis is based on careful history-taking, clinical examination, and simple investigations in the clinic. Although the presence of a malodorous vaginal discharge and the finding of clue cells on microscopy (in the absence of Trichomonas vaginalis) are sufficient for the diagnosis, a positive amine test and a vaginal pH of more than 5.0 are useful confirmatory tests. Images PMID:7171981

  7. Surgical Risk Preoperative Assessment System (SURPAS): II. Parsimonious Risk Models for Postoperative Adverse Outcomes Addressing Need for Laboratory Variables and Surgeon Specialty-specific Models.

    PubMed

    Meguid, Robert A; Bronsert, Michael R; Juarez-Colunga, Elizabeth; Hammermeister, Karl E; Henderson, William G

    2016-07-01

    To develop parsimonious prediction models for postoperative mortality, overall morbidity, and 6 complication clusters applicable to a broad range of surgical operations in adult patients. Quantitative risk assessment tools are not routinely used for preoperative patient assessment, shared decision making, informed consent, and preoperative patient optimization, likely due in part to the burden of data collection and the complexity of incorporation into routine surgical practice. Multivariable forward selection stepwise logistic regression analyses were used to develop predictive models for 30-day mortality, overall morbidity, and 6 postoperative complication clusters, using 40 preoperative variables from 2,275,240 surgical cases in the American College of Surgeons National Surgical Quality Improvement Program data set, 2005 to 2012. For the mortality and overall morbidity outcomes, prediction models were compared with and without preoperative laboratory variables, and generic models (based on all of the data from 9 surgical specialties) were compared with specialty-specific models. In each model, the cumulative c-index was used to examine the contribution of each added predictor variable. C-indexes, Hosmer-Lemeshow analyses, and Brier scores were used to compare discrimination and calibration between models. For the mortality and overall morbidity outcomes, the prediction models without the preoperative laboratory variables performed as well as the models with the laboratory variables, and the generic models performed as well as the specialty-specific models. The c-indexes were 0.938 for mortality, 0.810 for overall morbidity, and for the 6 complication clusters ranged from 0.757 for infectious to 0.897 for pulmonary complications. Across the 8 prediction models, the first 7 to 11 variables entered accounted for at least 99% of the c-index of the full model (using up to 28 nonlaboratory predictor variables). Our results suggest that it will be possible to develop

  8. Significance of frailty for predicting adverse clinical outcomes in different patient groups with specific medical conditions.

    PubMed

    Ritt, Martin; Gaßmann, Karl-Günter; Sieber, Cornel Christian

    2016-10-01

    Frailty is a major health burden in an aging society. It constitutes a clinical state of reduced physiological reserves that is associated with a diminished ability to withstand internal and external stressors. Frail patients have an increased risk for adverse clinical outcomes, such as mortality, readmission to hospital, institutionalization and falls. Of further clinical interest, frailty might be at least in part reversible in some patients and subject to preventive strategies. In daily clinical practice older patients with a complex health status, who are mostly frail or at least at risk of developing frailty, are frequently cared for by geriatricians. Recently, clinicians and scientists from other medical disciplines, such as cardiology, pulmonology, gastroenterology, nephrology, endocrinology, rheumatology, surgery and critical care medicine also discovered frailty to be an interesting instrument for risk stratification of patients, including younger patients. In this review we highlight the results of recent studies that demonstrated the significance of frailty to predict adverse clinical outcomes in patients with specific medical conditions, such as cardiac, lung, liver and kidney diseases as well as diabetes mellitus, osteoarthritis, trauma patients, patients undergoing surgery and critically ill patients. Multiple studies in patients with the aforementioned specific medical conditions could be identified demonstrating a predictive role of frailty for several adverse clinical outcomes. The association between frailty and adverse clinical outcomes reported in these studies was in part independent of several major potential confounder factors, such as age, sex, race, comorbidities and disabilities and were also detected in younger patients.

  9. Anomalies and specific functions in the clinical identification of defense mechanisms.

    PubMed

    Perry, J Christopher

    2014-05-01

    Standard teaching about defense mechanisms generally focuses on definitions, which do not readily aid the clinician in identifying defenses whenever individuals use them. This report demonstrates a process by which the clinician can identify when a defense is used, which ones are likely being used, and with what aim. Clinicians first notice that a defense may be operating whenever the other individual presents with anomalies in the expression of affect, behavior, speech, or its content. Some of these anomalies are described. Next, to identify the specific defense or general level of defensive functioning used, the clinician must identify the specific function of the defense in context using a process of guided clinical inference. This report examines 2 verbatim examples from recorded interviews of one case to demonstrate this process. The examples present a microcosm of clinical concerns that have a surprising relationship to the individual's course and prognosis.

  10. Correlation of Serotype-Specific Dengue Virus Infection with Clinical Manifestations

    PubMed Central

    Halsey, Eric S.; Marks, Morgan A.; Gotuzzo, Eduardo; Fiestas, Victor; Suarez, Luis; Vargas, Jorge; Aguayo, Nicolas; Madrid, Cesar; Vimos, Carlos; Kochel, Tadeusz J.; Laguna-Torres, V. Alberto

    2012-01-01

    Background Disease caused by the dengue virus (DENV) is a significant cause of morbidity throughout the world. Although prior research has focused on the association of specific DENV serotypes (DENV-1, DENV-2, DENV-3, and DENV-4) with the development of severe outcomes such as dengue hemorrhagic fever and dengue shock syndrome, relatively little work has correlated other clinical manifestations with a particular DENV serotype. The goal of this study was to estimate and compare the prevalence of non-hemorrhagic clinical manifestations of DENV infection by serotype. Methodology and Principal Findings Between the years 2005–2010, individuals with febrile disease from Peru, Bolivia, Ecuador, and Paraguay were enrolled in an outpatient passive surveillance study. Detailed information regarding clinical signs and symptoms, as well as demographic information, was collected. DENV infection was confirmed in patient sera with polyclonal antibodies in a culture-based immunofluorescence assay, and the infecting serotype was determined by serotype-specific monoclonal antibodies. Differences in the prevalence of individual and organ-system manifestations were compared across DENV serotypes. One thousand seven hundred and sixteen individuals were identified as being infected with DENV-1 (39.8%), DENV-2 (4.3%), DENV-3 (41.5%), or DENV-4 (14.4%). When all four DENV serotypes were compared with each other, individuals infected with DENV-3 had a higher prevalence of musculoskeletal and gastrointestinal manifestations, and individuals infected with DENV-4 had a higher prevalence of respiratory and cutaneous manifestations. Conclusions/Significance Specific clinical manifestations, as well as groups of clinical manifestations, are often overrepresented by an individual DENV serotype. PMID:22563516

  11. The sensitivity and specificity of clinical measures of sport concussion: three tests are better than one

    PubMed Central

    Resch, Jacob E; Brown, Cathleen N; Schmidt, Julianne; Macciocchi, Stephen N; Blueitt, Damond; Cullum, C Munro; Ferrara, Michael S

    2016-01-01

    Context A battery of clinical measures of neurocognition, balance and symptoms has been recommended for the management of sport concussion (SC) but is based on variable evidence. Objective To examine the sensitivity and specificity of a battery of tests to assess SC in college athletes. Design Cross-sectional. Setting Research laboratory. Patients or other participants Division 1 athletes diagnosed with a SC (n=40) who were 20.2±1.60 years of age and 180.5±11.12 cm tall and healthy athletes (n=40) who were 19.0±0.93 years of age and 179.1±11.39 cm tall were enrolled. Intervention(s) Participants were administered Immediate Postconcussion Assessment and Cognitive Test (ImPACT), the Sensory Organization Test (SOT) and the Revised Head Injury Scale (HIS-r) prior to and up to 24 h following injury between the 2004 and 2014 sport seasons. Sensitivity and specificity were calculated using predictive discriminant analyses (PDA) and clinical interpretation guidelines. Main outcome measures Outcome measures included baseline and postinjury ImPACT, SOT and HIS-r composite scores. Results Using PDA, each clinical measure's sensitivity ranged from 55.0% to 77.5% and specificity ranged from 52.5% to 100%. The test battery possessed a sensitivity and specificity of 80.0% and 100%, respectively. Using clinical interpretation guidelines, sensitivity ranged from 55% to 97.5% individually, and 100% when combined. Conclusions Our results support a multidimensional approach to assess SC in college athletes which correctly identified 80–100% of concussed participants as injured. When each test was evaluated separately, up to 47.5% of our sample was misclassified. Caution is warranted when using singular measures to manage SC. PMID:27900145

  12. Assessing clinical communication skills in physicians: are the skills context specific or generalizable

    PubMed Central

    Baig, Lubna A; Violato, Claudio; Crutcher, Rodney A

    2009-01-01

    Background Communication skills are essential for physicians to practice Medicine. Evidence for the validity and domain specificity of communication skills in physicians is equivocal and requires further research. This research was conducted to adduce evidence for content and context specificity of communication skills and to assess the usefulness of a generic instrument for assessing communication skills in International Medical Graduates (IMGs). Methods A psychometric design was used for identifying the reliability and validity of the communication skills instruments used for high-stakes exams for IMG's. Data were collected from 39 IMGs (19 men – 48.7%; 20 women – 51.3%; Mean age = 41 years) assessed at 14 station OSCE and subsequently in supervised clinical practice with several instruments (patient surveys; ITERs; Mini-CEX). Results All the instruments had adequate reliability (Cronbach's alpha: .54 – .96). There were significant correlations (r range: 0.37 – 0.70, p < .05) of communication skills assessed by examiner with standardized patients, and of mini-CEX with patient surveys, and ITERs. The intra-item reliability across all cases for the 13 items was low (Cronbach's alpha: .20 – .56). The correlations of communication skills within method (e.g., OSCE or clinical practice) were significant but were non-significant between methods (e.g., OSCE and clinical practice). Conclusion The results provide evidence of context specificity of communication skills, as well as convergent and criterion-related validity of communication skills. Both in OSCEs and clinical practice, communication checklists need to be case specific, designed for content validity. PMID:19445685

  13. Quantitative assessment of the benefits of specific information technologies applied to clinical studies in developing countries.

    PubMed

    Avilés, William; Ortega, Oscar; Kuan, Guillermina; Coloma, Josefina; Harris, Eva

    2008-02-01

    Clinical studies and trials require accessibility of large amounts of high-quality information in a timely manner, often daily. The integrated application of information technologies can greatly improve quality control as well as facilitate compliance with established standards such as Good Clinical Practice (GCP) and Good Laboratory Practice (GLP). We have customized and implemented a number of information technologies, such as personal data assistants (PDAs), geographic information system (GIS), and barcode and fingerprint scanning, to streamline a pediatric dengue cohort study in Managua, Nicaragua. Quantitative data was obtained to assess the actual contribution of each technology in relation to processing time, accuracy, real-time access to data, savings in consumable materials, and time to proficiency in training sessions. In addition to specific advantages, these information technologies benefited not only the study itself but numerous routine clinical and laboratory processes in the health center and laboratories of the Nicaraguan Ministry of Health.

  14. Current strategies and findings in clinically relevant post-translational modification-specific proteomics

    PubMed Central

    Pagel, Oliver; Loroch, Stefan; Sickmann, Albert; Zahedi, René P

    2015-01-01

    Mass spectrometry-based proteomics has considerably extended our knowledge about the occurrence and dynamics of protein post-translational modifications (PTMs). So far, quantitative proteomics has been mainly used to study PTM regulation in cell culture models, providing new insights into the role of aberrant PTM patterns in human disease. However, continuous technological and methodical developments have paved the way for an increasing number of PTM-specific proteomic studies using clinical samples, often limited in sample amount. Thus, quantitative proteomics holds a great potential to discover, validate and accurately quantify biomarkers in body fluids and primary tissues. A major effort will be to improve the complete integration of robust but sensitive proteomics technology to clinical environments. Here, we discuss PTMs that are relevant for clinical research, with a focus on phosphorylation, glycosylation and proteolytic cleavage; furthermore, we give an overview on the current developments and novel findings in mass spectrometry-based PTM research. PMID:25955281

  15. Approaches for Establishing Clinically Relevant Dissolution Specifications for Immediate Release Solid Oral Dosage Forms.

    PubMed

    Hermans, Andre; Abend, Andreas M; Kesisoglou, Filippos; Flanagan, Talia; Cohen, Michael J; Diaz, Dorys A; Mao, Y; Zhang, Limin; Webster, Gregory K; Lin, Yiqing; Hahn, David A; Coutant, Carrie A; Grady, Haiyan

    2017-08-22

    This manuscript represents the perspective of the Dissolution Analytical Working Group of the IQ Consortium. The intent of this manuscript is to highlight the challenges of, and to provide a recommendation on, the development of clinically relevant dissolution specifications (CRS) for immediate release (IR) solid oral dosage forms. A roadmap toward the development of CRS for IR products containing active ingredients with a non-narrow therapeutic window is discussed, within the context of mechanistic dissolution understanding, supported by in-human pharmacokinetic (PK) data. Two case studies present potential outcomes of following the CRS roadmap and setting dissolution specifications. These cases reveal some benefits and challenges of pursuing CRS with additional PK data, in light of current regulatory positions, including that of the US Food and Drug Administration (FDA), who generally favor this approach, but with the understanding that both industry and regulatory agency perspectives are still evolving in this relatively new field. The CRS roadmap discussed in this manuscript also describes a way to develop clinically relevant dissolution specifications based primarily on dissolution data for batches used in pivotal clinical studies, acknowledging that not all IR product development efforts need to be supported by additional PK studies, albeit with the associated risk of potentially unnecessarily tight manufacturing controls. Recommendations are provided on what stages during the life cycle investment into in vivo studies may be valuable. Finally, the opportunities for CRS within the context of post-approval changes, Modeling and Simulation (M&S), and the application of biowaivers, are briefly discussed.

  16. Three Decades of Comprehensive Geriatric Assessment: Evidence Coming From Different Healthcare Settings and Specific Clinical Conditions.

    PubMed

    Pilotto, Alberto; Cella, Alberto; Pilotto, Andrea; Daragjati, Julia; Veronese, Nicola; Musacchio, Clarissa; Mello, Anna Maria; Logroscino, Giancarlo; Padovani, Alessandro; Prete, Camilla; Panza, Francesco

    2017-02-01

    Comprehensive geriatric assessment (CGA) is a multidisciplinary diagnostic and treatment process that identifies medical, psychosocial, and functional capabilities of older adults to develop a coordinated plan to maximize overall health with aging. Specific criteria used by CGA programs to evaluate patients include age, medical comorbidities, psychosocial problems, previous or predicted high healthcare utilization, change in living situation, and specific geriatric conditions. However, no universal criteria have been agreed upon to readily identify patients who are likely to benefit from CGA. Evidence from randomized controlled trials and large systematic reviews and meta-analyses suggested that the healthcare setting may modify the effectiveness of CGA programs. Home CGA programs and CGA performed in the hospital were shown to be consistently beneficial for several health outcomes. In contrast, the data are conflicting for posthospital discharge CGA programs, outpatient CGA consultation, and CGA-based inpatient geriatric consultation services. The effectiveness of CGA programs may be modified also by particular settings or specific clinical conditions, with tailored CGA programs in older frail patients evaluated for preoperative assessment, admitted or discharged from emergency departments and orthogeriatric units or with cancer and cognitive impairment. CGA is capable of effectively exploring multiple domains in older age, being the multidimensional and multidisciplinary tool of choice to determine the clinical profile, the pathologic risk and the residual skills as well as the short- and long-term prognosis to facilitate the clinical decision making on the personalized care plan of older persons.

  17. Further Validation of the Female Sexual Function Index: Specificity and Associations With Clinical Interview Data.

    PubMed

    Stephenson, Kyle R; Toorabally, Nasreen; Lyons, Leah; M Meston, Cindy

    2016-07-03

    Female sexual function is a multi-faceted psychophysiological construct. The Female Sexual Function Index (FSFI) is considered a "gold standard" self-report instrument that assesses the various aspects of sexual function. However, researchers have recently proposed potential limitations of the FSFI, highlighting the need for continued validation research. The aims of the current analyses were (a) to assess the correlations between FSFI scores and information regarding specific rates of functional impairment gained via clinical interview; and (b) to assess the specificity of FSFI subscale scores in reflecting corresponding aspects of sexual function (e.g., whether the Sexual Desire subscale reflects sexual desire specifically rather than sexual arousal, orgasm, etc.). The participants were 97 sexually active women who reported impairments in sexual function. Clinical interview data exhibited moderate-to-strong correlations with FSFI scores. Additionally, FSFI subscales generally exhibited adequate specificity in terms of reflecting their corresponding aspects of sexual function more strongly than other aspects. The results generally supported the validity of the FSFI. Implications for the measurement and conceptualization of female sexual function are discussed.

  18. A Rapid In-Clinic Test Detects Acute Leptospirosis in Dogs with High Sensitivity and Specificity

    PubMed Central

    Kodjo, Angeli; Calleja, Christophe; Loenser, Michael; Lin, Dan; Lizer, Joshua

    2016-01-01

    A rapid IgM-detection immunochromatographic test (WITNESS® Lepto, Zoetis) has recently become available to identify acute canine leptospirosis at the point of care. Diagnostic sensitivity and specificity of the test were evaluated by comparison with the microscopic agglutination assay (MAT), using a positive cut-off titer of ≥800. Banked serum samples from dogs exhibiting clinical signs and suspected leptospirosis were selected to form three groups based on MAT titer: (1) positive (n = 50); (2) borderline (n = 35); and (3) negative (n = 50). Using an analysis to weight group sizes to reflect French prevalence, the sensitivity and specificity were 98% and 93.5% (88.2% unweighted), respectively. This test rapidly identifies cases of acute canine leptospirosis with high levels of sensitivity and specificity with no interference from previous vaccination. PMID:27110562

  19. A Rapid In-Clinic Test Detects Acute Leptospirosis in Dogs with High Sensitivity and Specificity.

    PubMed

    Kodjo, Angeli; Calleja, Christophe; Loenser, Michael; Lin, Dan; Lizer, Joshua

    2016-01-01

    A rapid IgM-detection immunochromatographic test (WITNESS® Lepto, Zoetis) has recently become available to identify acute canine leptospirosis at the point of care. Diagnostic sensitivity and specificity of the test were evaluated by comparison with the microscopic agglutination assay (MAT), using a positive cut-off titer of ≥800. Banked serum samples from dogs exhibiting clinical signs and suspected leptospirosis were selected to form three groups based on MAT titer: (1) positive (n = 50); (2) borderline (n = 35); and (3) negative (n = 50). Using an analysis to weight group sizes to reflect French prevalence, the sensitivity and specificity were 98% and 93.5% (88.2% unweighted), respectively. This test rapidly identifies cases of acute canine leptospirosis with high levels of sensitivity and specificity with no interference from previous vaccination.

  20. Complement is a central mediator of radiotherapy-induced tumor-specific immunity and clinical response.

    PubMed

    Surace, Laura; Lysenko, Veronika; Fontana, Andrea Orlando; Cecconi, Virginia; Janssen, Hans; Bicvic, Antonela; Okoniewski, Michal; Pruschy, Martin; Dummer, Reinhard; Neefjes, Jacques; Knuth, Alexander; Gupta, Anurag; van den Broek, Maries

    2015-04-21

    Radiotherapy induces DNA damage and cell death, but recent data suggest that concomitant immune stimulation is an integral part of the therapeutic action of ionizing radiation. It is poorly understood how radiotherapy supports tumor-specific immunity. Here we report that radiotherapy induced tumor cell death and transiently activated complement both in murine and human tumors. The local production of pro-inflammatory anaphylatoxins C3a and C5a was crucial to the tumor response to radiotherapy and concomitant stimulation of tumor-specific immunity. Dexamethasone, a drug frequently given during radiotherapy, limited complement activation and the anti-tumor effects of the immune system. Overall, our findings indicate that anaphylatoxins are key players in radiotherapy-induced tumor-specific immunity and the ensuing clinical responses.

  1. Lack of specific association between gastric autoimmunity hallmarks and clinical presentations of atrophic body gastritis

    PubMed Central

    Annibale, Bruno; Lahner, Edith; Negrini, Riccardo; Baccini, Flavia; Bordi, Cesare; Monarca, Bruno; Fave, Gianfranco Delle

    2005-01-01

    AIM: To investigate the possible relationships between gastric autoimmune phenomena and clinical presentations of this disorder, in consecutive atrophic body gastritis patients. METHODS: A total of 140 atrophic body gastritis patients, diagnosed as consecutive outpatients presenting with macrocytic or iron deficiency anemia, or longstanding dyspepsia underwent gastroscopy with antral and body biopsies, assay of intrinsic factor, parietal cells and Helicobacter pylori (H pylori) antibodies. Gastritis was assessed according to Sydney System. RESULTS: Parietal cell antibodies were equally distributed in all clinical presentations, whereas the positivity of intrinsic factor antibodies (49/140, 35%) was significantly higher in pernicious anemia patients (49.2%) than in iron deficiency (21.1%) and dyspeptic patients (27.8%). No specific pattern of autoantibodies was related to the clinical presentations of atrophic body gastritis. A positive correlation was obtained between the body atrophy score and the intrinsic factor antibody levels (r = 0.2216, P = 0.0085). Associated autoimmune diseases were present in 25/140 (17.9%) patients, but the prevalence of autoimmune diseases was comparable, irrespective of the clinical presentations. CONCLUSION: The so-called hallmarks of gastric autoimmunity, particularly in intrinsic factor antibody cannot be usefully employed in defining an autoimmune pattern in the clinical presentations of ABG. PMID:16149145

  2. [Clinical profiles and transitions in the spectrum of specific language impairment in childhood].

    PubMed

    Crespo-Eguílaz, N; Narbona, J

    2003-02-01

    To test the clinical nature and diversity of specific language impairment (SLI) in Spanish individuals, in the framework of the neuropsycholinguistic model of Chevrie-Muller and the classification of Rapin and Allen. Forty two language impaired children with normal intelligence and audition have been followed during a mean period of 3 years 7 months in preschool and school ages; all of them have participated in an intervention program for language abilities. The evolutive neuropsychological evaluation at our hospital has comprised measurement of general cognitive abilities, formal (phonology, vocabulary, syntax) and pragmatic aspects of language. Phonological and syntactic abilities are the better evolutive predictors. The group clinical profiles, in general, fill into the clustering system proposed by Rapin and Allen, but mixed transitional forms are observed in individuals. Also in six patients a transition from one to another clinical form have been observed; in these subjects, mixed phonological syntactical syndrome is an obligate step during their evolutive changes; these changes can be attributed to natural evolutive processes and/or to effects of intervention. Our results permit hypothesize that the spectrum of SLI is an unique basic disorder whose clinical manifestations (interindividual and intraindividual during evolution) can be diverse in form and severity. This clinical interpretation is reinforced by the results of recent publications showing that members of the same familial group with identical genetic mutation had different forms of SLI.

  3. CSF Proteomics Identifies Specific and Shared Pathways for Multiple Sclerosis Clinical Subtypes

    PubMed Central

    Avsar, Timucin; Durası, İlknur Melis; Uygunoğlu, Uğur; Tütüncü, Melih; Demirci, Nuri Onat; Saip, Sabahattin; Sezerman, O. Uğur; Siva, Aksel; Tahir Turanlı, Eda

    2015-01-01

    Multiple sclerosis (MS) is an immune-mediated, neuro-inflammatory, demyelinating and neurodegenerative disease of the central nervous system (CNS) with a heterogeneous clinical presentation and course. There is a remarkable phenotypic heterogeneity in MS, and the molecular mechanisms underlying it remain unknown. We aimed to investigate further the etiopathogenesis related molecular pathways in subclinical types of MS using proteomic and bioinformatics approaches in cerebrospinal fluids of patients with clinically isolated syndrome, relapsing remitting MS and progressive MS (n=179). Comparison of disease groups with controls revealed a total of 151 proteins that are differentially expressed in clinically different MS subtypes. KEGG analysis using PANOGA tool revealed the disease related pathways including aldosterone-regulated sodium reabsorption (p=8.02x10-5) which is important in the immune cell migration, renin-angiotensin (p=6.88x10-5) system that induces Th17 dependent immunity, notch signaling (p=1.83x10-10) pathway indicating the activated remyelination and vitamin digestion and absorption pathways (p=1.73x10-5). An emerging theme from our studies is that whilst all MS clinical forms share common biological pathways, there are also clinical subtypes specific and pathophysiology related pathways which may have further therapeutic implications. PMID:25942430

  4. Comparison of Patient-Specific Computational Modeling Predictions and Clinical Outcomes of LASIK for Myopia

    PubMed Central

    Seven, Ibrahim; Vahdati, Ali; De Stefano, Vinicius Silbiger; Krueger, Ronald R.; Dupps, William J.

    2016-01-01

    Purpose To assess the predictive accuracy of simulation-based LASIK outcomes. Methods Preoperative and 3-month post-LASIK tomographic data from 20 eyes of 12 patients who underwent wavefront-optimized LASIK for myopia were obtained retrospectively. Patient-specific finite element models were created and case-specific treatment settings were simulated. Simulated keratometry (SimK) values and the mean tangential curvature of the central 3 mm (Kmean) were obtained from the anterior surfaces of the clinical tomographies, and computational models were compared. Correlations between Kmean prediction error and patient age, preoperative corneal hysteresis (CH), and corneal resistance factor (CRF) were assessed. Results The mean difference for Kmean between simulated and actual post-LASIK cases was not statistically significant (−0.13 ± 0.36 diopters [D], P = 0.1). The mean difference between the surgically induced clinical change in Kmean and the model-predicted change was −0.11 ± 0.34 D (P = 0.2). Kmean prediction error was correlated to CH, CRF, and patient age (r = 0.63, 0.53, and 0.5, respectively, P < 0.02), and incorporation of CH values into predictions as a linear offset increased their accuracy. Simulated changes in Kmean accounted for 97% of the variance in actual spherical equivalent refractive change. Conclusions Clinically feasible computational simulations predicted corneal curvature and manifest refraction outcomes with a level of accuracy in myopic LASIK cases that approached the limits of measurement error. Readily available preoperative biomechanical measures enhanced simulation accuracy. Patient-specific simulation may be a useful tool for clinical guidance in de novo LASIK cases. PMID:27893094

  5. Improving Treatment Trial Outcomes for Rett Syndrome: The Development of Rett-specific Anchors for the Clinical Global Impression Scale.

    PubMed

    Neul, Jeffrey L; Glaze, Daniel G; Percy, Alan K; Feyma, Tim; Beisang, Arthur; Dinh, Thuy; Suter, Bernhard; Anagnostou, Evdokia; Snape, Mike; Horrigan, Joseph; Jones, Nancy E

    2015-11-01

    Rett syndrome is a genetically based neurodevelopmental disorder. Although the clinical consequences of Rett syndrome are profound and lifelong, currently no approved drug treatments are available specifically targeted to Rett symptoms. High quality outcome measures, specific to the core symptoms of a disorder are a critical component of well-designed clinical trials for individuals with neurodevelopmental disorders. The Clinical Global Impression Scale is a measure of global clinical change with strong face validity that has been widely used as an outcome measure in clinical trials of central nervous system disorders. Despite its favorable assay sensitivity in clinical trials, as a global measure, the Clinical Global Impression Scale is not specific to the signs and symptoms of the disorder under study. Development of key anchors for the scale, specific to the disorder being assessed, holds promise for enhancing the validity and reliability of the measure for disorders such as Rett syndrome. © The Author(s) 2015.

  6. The use of simulation to address the acute care skills deficit in pre-registration nursing students: a clinical skill perspective.

    PubMed

    Nickless, Lesley J

    2011-05-01

    The increase in patient acuity in primary and secondary settings is continuing, with a corresponding increase in the need for technological competence in these areas. Evidence, however, both nationally and internationally, suggests that these expectations are not being met. This paper offers a review of the literature on acute care, with a specific focus on pre-registration nursing students and the development of acute care skills. Three themes are discussed: factors contributing to the acute care skills deficit, the knowledge and skills required to work in acute care and strategies used to support the acquisition of acute care skills. In response to the review, and based upon the evidence-based solutions identified, the clinical skills team at Bournemouth University designed and developed two teaching sessions, using simulation and role play to support the acquisition of acute care skills in pre-registration students. Student evaluations identify that their knowledge, competence and confidence in this area have increased following the teaching sessions, although caution remains regarding transferability of these skills into the practice environment.

  7. Sex-Specific Clinical Correlates of Hoarding in Obsessive-Compulsive Disorder

    PubMed Central

    Samuels, Jack F.; Bienvenu, O. Joseph; Pinto, Anthony; Murphy, Dennis L.; Piacentini, John; Rauch, Scott L.; Fyer, Abby J.; Grados, Marco A.; Greenberg, Benjamin D.; Knowles, James A.; McCracken, James T.; Cullen, Bernadette; Riddle, Mark A.; Rasmussen, Steven A.; Pauls, David L.; Liang, Kung-Yee; Hoehn-Saric, Rudolf; Pulver, Ann E.; Nestadt, Gerald

    2008-01-01

    Little is known about whether the clinical correlates of hoarding behavior are different in men and women with obsessive-compulsive disorder (OCD). In the current study, we evaluated the association of hoarding with categories of obsessions and compulsions, psychiatric disorders, personality dimensions, and other clinical characteristics separately in 151 men and 358 women with OCD who were examined during the OCD Collaborative Genetics Study. We found that, among men but not women, hoarding was associated with aggressive, sexual, and religious obsessions and checking compulsions. In men, hoarding was associated with generalized anxiety disorder and tics whereas, among women, hoarding was associated with social phobia, post-traumatic stress disorder, body dysmorphic disorder, nail biting, and skin picking. In women but not men, hoarding was associated with schizotypal and dependent personality disorder dimensions, and with low conscientiousness. These findings indicate that specific clinical correlates of hoarding in OCD are different in men and women and may reflect sex-specific differences in the course, expression, and/or etiology of hoarding behavior in OCD. PMID:18692168

  8. A Pedagogy to Address Plagiarism.

    ERIC Educational Resources Information Center

    Whitaker, Elaine E.

    1993-01-01

    Presents strategies and methods by which writing teachers can openly address the potential problem of plagiarism. Details specific methods used by one teacher to train students how to quote and cite materials without plagiarizing. (HB)

  9. Clinical assessment of the specificity of an adipsin rapid test for the diagnosis of preeclampsia.

    PubMed

    Wang, Tao; Zhou, Rong; Gao, Linbo; Wang, Yanyun; Liu, Xinghui; Zhang, Lin

    2016-08-01

    To evaluate the specificity of the adipsin rapid test in clinical practice for the diagnosis of preeclampsia (PE). A total of 1144 pregnant women were recruited in this study: 44 pregnant women with PE and 1100 healthy pregnancies as controls. Urine samples were collected and used, respectively, for the adipsin rapid test and the urinary dipstick test for protein detection. Sensitivity and specificity were calculated on the basis of the detection results. In the 1144 women examined with the adipsin rapid test for PE diagnosis, the sensitivity and specificity were 93.2% and 98.8%, respectively; the total accuracy was 98.6%. For the 1144 women tested with urinary dipstick, the sensitivity and specificity were 93.2% and 40.5%, respectively; and the total accuracy was 42.5%. Both the adipsin rapid test and the urinary dipstick test are noninvasive and inexpensive rapid tests for the diagnosis of PE. However, the adipsin rapid test was proven more reliable since it had a higher sensitivity, specificity, and accuracy.

  10. Autobiographical memory specificity in response to verbal and pictorial cues in clinical depression.

    PubMed

    Ridout, Nathan; Dritschel, Barbara; Matthews, Keith; O'Carroll, Ronan

    2016-06-01

    Depressed individuals have been consistently shown to exhibit problems in accessing specific memories of events from their past and instead tend to retrieve categorical summaries of events. The majority of studies examining autobiographical memory changes associated with psychopathology have tended to use word cues, but only one study to date has used images (with PTSD patients). to determine if using images to cue autobiographical memories would reduce the memory specificity deficit exhibited by patients with depression in comparison to healthy controls. Twenty-five clinically depressed patients and twenty-five healthy controls were assessed on two versions of the autobiographical memory test; cued with emotional words and images. Depressed patients retrieved significantly fewer specific memories, and a greater number of categorical, than did the controls. Controls retrieved a greater proportion of specific memories to images compared to words, whereas depressed patients retrieved a similar proportion of specific memories to both images and words. no information about the presence and severity of past trauma was collected. results suggest that the overgeneral memory style in depression generalises from verbal to pictorial cues. This is important because retrieval to images may provide a more ecologically valid test of everyday memory experiences than word-cued retrieval.. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Personality and Defense Styles: Clinical Specificities and Predictive Factors of Alcohol Use Disorder in Women.

    PubMed

    Ribadier, Aurélien; Dorard, Géraldine; Varescon, Isabelle

    2016-01-01

    This study investigated personality traits and defense styles in order to determine clinical specificities and predictive factors of alcohol use disorders (AUDs) in women. A female sample, composed of AUD outpatients (n = 48) and a control group (n = 50), completed a sociodemographic self-report and questionnaires assessing personality traits (BFI), defense mechanisms and defense styles (DSQ-40). Comparative and correlational analyses, as well as univariate and multivariate logistic regressions, were performed. AUD women presented with higher neuroticism and lower extraversion and conscientiousness. They used less mature and more neurotic and immature defense styles than the control group. Concerning personality traits, high neuroticism and lower conscientiousness were predictive of AUD, as well as low mature, high neurotic, and immature defense styles. Including personality traits and defense styles in a logistic model, high neuroticism was the only AUD predictive factor. AUD women presented clinical specificities and predictive factors in personality traits and defense styles that must be taken into account in AUD studies. Implications for specific treatment for women are discussed.

  12. Conducting community-based, culturally specific, eye disease screening clinics for urban African Americans with diabetes.

    PubMed

    Anderson, Robert M; Wolf, Fredric M; Musch, David C; Fitzgerald, James T; Johnson, Mark W; Nwankwo, Robin B; Robins, Lynne S; Oh, Mary S; Gillard, Mary Lou

    2002-01-01

    The purpose of this study was to evaluate the need for, and efficacy of, community-based culturally specific eye disease screening clinics for urban African Americans with diabetes. The study employed a variety of culturally specific methods in the design and performance of 43 community-based eye disease screening clinics in southeastern Michigan. One thousand, thirty-seven subjects were recruited for the study. Of that number, 817 identified themselves as African Americans and are the focus of this report. Of the 817 African-American patients screened, 84 (10%) needed to be examined by an ophthalmologist immediately (< 30 days), and 180 (22%) needed to be examined soon (within 1 to 3 months), while 544 (67%) were advised to return for another exam a year later. The project demonstrated that it was possible to use culturally specific techniques to identify a significant number of urban African Americans with diabetes in need of eye screening and treatment. However, lack of health insurance proved to be the primary barrier to receiving needed treatment. Although the project was successful, it is not a solution to what is essentially a health systems problem, ie, inadequate access to appropriate diabetes care for a significant number of our population.

  13. A Causal Model for Joint Evaluation of Placebo and Treatment-Specific Effects in Clinical Trials

    PubMed Central

    Zhang, Zhiwei; Kotz, Richard M.; Wang, Chenguang; Ruan, Shiling; Ho, Martin

    2014-01-01

    Summary Evaluation of medical treatments is frequently complicated by the presence of substantial placebo effects, especially on relatively subjective endpoints, and the standard solution to this problem is a randomized, double-blinded, placebo-controlled clinical trial. However, effective blinding does not guarantee that all patients have the same belief or mentality about which treatment they have received (or treatmentality, for brevity), making it difficult to interpret the usual intent-to-treat effect as a causal effect. We discuss the causal relationships among treatment, treatmentality and the clinical outcome of interest, and propose a causal model for joint evaluation of placebo and treatment-specific effects. The model highlights the importance of measuring and incorporating patient treatmentality and suggests that each treatment group should be considered a separate observational study with a patient's treatmentality playing the role of an uncontrolled exposure. This perspective allows us to adapt existing methods for dealing with confounding to joint estimation of placebo and treatment-specific effects using measured treatmentality data, commonly known as blinding assessment data. We first apply this approach to the most common type of blinding assessment data, which is categorical, and illustrate the methods using an example from asthma. We then propose that blinding assessment data can be collected as a continuous variable, specifically when a patient's treatmentality is measured as a subjective probability, and describe analytic methods for that case. PMID:23432119

  14. Cancer registries in Japan: National Clinical Database and site-specific cancer registries.

    PubMed

    Anazawa, Takayuki; Miyata, Hiroaki; Gotoh, Mitsukazu

    2015-02-01

    The cancer registry is an essential part of any rational program of evidence-based cancer control. The cancer control program is required to strategize in a systematic and impartial manner and efficiently utilize limited resources. In Japan, the National Clinical Database (NCD) was launched in 2010. It is a nationwide prospective registry linked to various types of board certification systems regarding surgery. The NCD is a nationally validated database using web-based data collection software; it is risk adjusted and outcome based to improve the quality of surgical care. The NCD generalizes site-specific cancer registries by taking advantage of their excellent organizing ability. Some site-specific cancer registries, including pancreatic, breast, and liver cancer registries have already been combined with the NCD. Cooperation between the NCD and site-specific cancer registries can establish a valuable platform to develop a cancer care plan in Japan. Furthermore, the prognosis information of cancer patients arranged using population-based and hospital-based cancer registries can help in efficient data accumulation on the NCD. International collaboration between Japan and the USA has recently started and is expected to provide global benchmarking and to allow a valuable comparison of cancer treatment practices between countries using nationwide cancer registries in the future. Clinical research and evidence-based policy recommendation based on accurate data from the nationwide database may positively impact the public.

  15. Towards tract-specific fractional anisotropy (TSFA) at crossing-fiber regions with clinical diffusion MRI

    PubMed Central

    Mishra, Virendra; Guo, Xiaohu; Delgado, Mauricio R.; Huang, Hao

    2014-01-01

    Purpose White matter fractional anisotropy (FA), a measure implying microstructure, is significantly underestimated with single diffusion tensor model at crossing-fiber regions (CFR). We propose a tract-specific FA (TSFA), corrected for the effects of crossing-fiber geometry and free water at CFR, and adapted for tract analysis with diffusion MRI (dMRI) in clinical research. Methods At CFR voxels, the proposed technique estimates free water fraction (fiso) as a linear function of mean apparent diffusion coefficient (mADC), fits the dual tensors and estimates TSFA. Digital phantoms were designed for testing the accuracy of fiso and fitted dual-anisotropies at CFR. The technique was applied to clinical dMRI of normal subjects and hereditary spastic paraplegia (HSP) patients to test the effectiveness of TSFA. Results Phantom simulation showed unbiased estimates of dual-tensor anisotropies at CFR and high accuracy of fiso as a linear function of mADC. TSFA at CFR was highly consistent to the single tensor FA at non-CFR within the same tract with normal human dMRI. Additional HSP imaging biomarkers with significant correlation to clinical motor function scores could be identified with TSFA. Conclusion Results suggest the potential of the proposed technique in estimating unbiased TSFA at CFR and conducting tract analysis in clinical research. PMID:25447208

  16. Use of Specific IgE and Skin Prick Test to Determine Clinical Reaction Severity.

    PubMed

    Ta, Von; Weldon, Brittany; Yu, Grace; Humblet, Olivier; Neale-May, Susan; Nadeau, Kari

    2011-01-01

    AIMS: To determine whether specific IgE and skin prick test correlate better in predicting reaction severity during a double-blinded placebo controlled food challenge (DBPCFC) for egg, milk, and multiple tree nut allergens. STUDY DESIGN: Prospective study. PLACE AND DURATION OF STUDY: Department of Pediatrics, Stanford University School of Medicine, August 2009 and ongoing. METHODOLOGY: We examined the reaction severity of twenty-four subjects to nine possible food allergens: milk, egg, almond, cashew, hazelnut, peanut, sesame, pecan and walnut. Specific IgE and SPT were performed before each DBPCFC. DBPCFC results were classified into mild (1), moderate (2), or severe (3) reactions using a modified Bock's criteria. RESULTS: Twenty four subjects underwent a total of 80 DBPCFC. Eighty percent of all DBPCFCs resulted in a positive reaction. A majority, 71%, were classified as mild. No reactions occurred with a SPT of zero mm while three reactions occurred with a negative specific IgE. All reactions were reversible with medication. CONCLUSION: These data suggest that SPT and specific IgE levels are not associated with reaction severity (p<0.64 and 0.27, respectively). We also found that combining specific IgE and SPT improved specificity but did not help to achieve clinically useful sensitivity. For instance, an SPT > 5mm had a sensitivity of 91% and specificity of 50%. Combining SPT > 5mm and IgE > 7 resulted in a reduced sensitivity of 64%. Unexpectedly, a history of anaphylaxis 70% (n=17) was not predictive of anaphylaxis on challenge 4% (n=2).

  17. USING FORMATIVE RESEARCH TO DEVELOP A CONTEXT-SPECIFIC APPROACH TO INFORMED CONSENT FOR CLINICAL TRIALS

    PubMed Central

    Corneli, Amy L.; Bentley, Margaret E.; Sorenson, James R.; Henderson, Gail E.; van der Horst, Charles; Moses, Agnes; Nkhoma, Jacqueline; Tenthani, Lyson; Ahmed, Yusuf; Heilig, Charles M.; Jamieson, Denise J.

    2009-01-01

    Participant understanding is of particular concern when obtaining informed consent. Recommendations for improving understanding include disclosing information using culturally appropriate and innovative approaches. To increase the effectiveness of the consent process for a clinical trial in Malawi on interventions to prevent mother-to-child transmission of HIV during breastfeeding, formative research was conducted to explore the community’s understanding of medical research as well as how to explain research through local terms and meanings. Contextual analogies and other approaches were identified to explain consent information. Guided by theory, strategies for developing culturally appropriate interventions, and recommendations from the literature, we demonstrate how the formative data were used to develop culturally appropriate counseling cards specifically for the trial in Malawi. With appropriate contextual modifications, the steps outlined here could be applied in other clinical trials conducted elsewhere, as well as in other types of research. PMID:19385837

  18. Using formative research to develop a context-specific approach to informed consent for clinical trials.

    PubMed

    Corneli, Amy L; Bentley, Margaret E; Sorenson, James R; Henderson, Gail E; van der Horst, Charles; Moses, Agnes; Nkhoma, Jacqueline; Tenthani, Lyson; Ahmed, Yusuf; Heilig, Charles M; Jamieson, Denise J

    2006-12-01

    PARTICIPANT UNDERSTANDING is of particular concern when obtaining informed consent. Recommendations for improving understanding include disclosing information using culturallyappropriate and innovative approaches. To increase the effectiveness of the consent process for a clinical trial in Malawi on interventions to prevent mother-tochild transmission of HIV during breastfeeding, formative research was conducted to explore the community's understanding of medical research as well as how to explain research through local terms and meanings. Contextual analogies and other approaches were identified to explain consent information. Guided by theory, strategies for developing culturally appropriate interventions, and recommendations from the literature, we demonstrate how the formative data were used to develop culturally appropriate counseling cards specifically for the trial in Malawi. With appropriate contextual modifications, the steps outlined here could be applied in other clinical trials conducted elsewhere, as well as in other types of research.

  19. Cow-specific risk factors for clinical mastitis in Brazilian dairy cattle.

    PubMed

    Oliveira, C S F; Hogeveen, H; Botelho, A M; Maia, P V; Coelho, S G; Haddad, J P A

    2015-10-01

    Information related to mastitis risk factors is useful for the design and implementation of clinical mastitis (CM) control programs. The first objective of our study was to model the risk of CM under Brazilian conditions, using cow-specific risk factors. Our second objective was to explore which risk factors were associated with the occurrence of the most common pathogens involved in Brazilian CM infections. The analyses were based on 65 months of data from 9,789 dairy cows and 12,464 CM cases. Cow-specific risk factors that could easily be measured in standard Brazilian dairy farms were used in the statistical analyses, which included logistic regression and multinomial logistic regression. The first month of lactation, high somatic cell count, rainy season and history of clinical mastitis cases were factors associated with CM for both primiparous and multiparous cows. In addition, parity and breed were also associated risk factors for multiparous cows. Of all CM cases, 54% showed positive bacteriological culturing results from which 57% were classified as environmental pathogens, with a large percentage of coliforms (35%). Coagulase-negative Staphylococcus (16%), Streptococcus uberis (9%), Streptococcus agalactiae (7%) and other Streptococci (9%) were also common pathogens. Among the pathogens analyzed, the association of cow-specific risk factors, such as Zebu breed (OR=5.84, 95%CI 3.77-10.77) and accumulated history of SCC (1.76, 95%CI 1.37-2.27), was different for CM caused by Coagulase-negative Staphylococcus and S. agalactiae in comparison to CM caused by coliforms. Our results suggest that CM control programs in Brazil should specially consider the recent history of clinical mastitis cases and the beginning of the lactations, mainly during the rainy season as important risk factor for mastitis.

  20. Clinical Experience with (18)F-Labeled Small Molecule Inhibitors of Prostate-Specific Membrane Antigen.

    PubMed

    Rowe, Steven P; Gorin, Michael A; Salas Fragomeni, Roberto A; Drzezga, Alexander; Pomper, Martin G

    2017-04-01

    Prostate cancer (PCa) is the most common noncutaneous malignancy diagnosed in men. Despite the large number of men who will suffer from PCa at some point during their lives, conventional imaging modalities for this important disease (contrast-enhanced computed tomography, bone scan, and MR imaging) have provided only marginal to moderate success in appropriately guiding patient management in certain clinical contexts. In this review, the authors discuss radiofluorinated small molecule radiotracers that have been developed to bind to the transmembrane glycoprotein prostate-specific membrane antigen, a target that is nearly universally overexpressed on PCa epithelial cells.

  1. Derivation of Patient Specific Pluripotent Stem Cells Using Clinically Discarded Cumulus Cells

    PubMed Central

    Xu, Jie; Lin, Chen-Ju; Wang, Sheng-Wen; Cheng, An-Sheng; Lu, Jean; Lu, Chung-Hao; Sung, Li-Ying

    2016-01-01

    Induced pluripotent stem cells (iPSCs) are powerful tools for basic and translational research, as well as regenerative medicine. In routine human in vitro fertilization (IVF) practices, cumulus cells (CCs) are discarded, representing a potential source of biological materials for regenerative medicine. In this study, we derived patient-specific iPSCs using CCs from human infertility clinics for the first time. The human cumulus cell derived iPSCs (hc-iPSCs) were characterized for growth, karyotype, expression of pluripotency genes, and were subjected to embryoid bodies (EBs) and teratoma assays to evaluate their differentiation capacity. Hc-iPSCs display typical iPSC characteristics, and are capable of differentiating into all germ layers in vitro and in vivo. We further show that putative primordial germ cell like cells (PGCLCs) can be derived using hc-iPSCs. Our data demonstrate the feasibility of deriving patient-specific pluripotent stem cells using CCs. PMID:27802323

  2. Specific autoantibodies in dermatomyositis: a helpful tool to classify different clinical subsets.

    PubMed

    Merlo, Giulia; Clapasson, Andrea; Cozzani, Emanuele; Sanna, Luigi; Pesce, Giampaola; Bagnasco, Marcello; Burlando, Martina; Parodi, Aurora

    2017-03-01

    Autoantibodies are important in the diagnosis of dermatomyositis. They can be divided in two different groups: myositis-associated autoantibodies (MAA) prevailing in overlap syndromes, and myositis-specific autoantibodies (MSA), with diagnostic specificity exceeding 90%. Our purpose was to detect retrospectively the prevalence of the most common MSAs in a group of 19 adult DM patients (13 women, 6 men). A severe DM (SDM), with extensive cutaneous and muscular manifestations, dysphagia, and sometimes pneumopathy, was detected in ten cases. Three patients had a mild DM (MDM), with little muscle and skin impairment, and a short course. Four patients suffered from amyopathic DM (ADM), two from paraneoplastic DM (PDM). Each serum was tested for ANA, ENA, MAAs, MSAs. Myositis-specific autoantibodies were detected in 15 cases. The most frequent was anti-TIF1γ, associated with SDM or PDM in four out of seven cases. Anti-MDA5 antibodies were recorded in a SDM and in a ADM with lung fibrosis. Anti-Mi2 and anti-SRP antibodies were both detected in a MDM and in a SDM, whereas anti-SAE1 in a amyopathic form. Other antibodies (anti-NXP2, -Jo1, -PL7, -PL12, -OJ) were found in single patients with SDM. Our series confirmed that specific autoantibodies could be helpful to classify different clinical subsets, particularly in the case of paraneoplastic forms or association with pneumopathy. Moreover, they can help in predicting the disease evolution and influence therapeutic strategies. A greater number of cases should be useful to highlight the clinical and pathogenic role of these antibodies, and develop a homogeneous protocol for diagnosis and treatment.

  3. Clinical implications for biochemical diagnostic thresholds of adrenal sufficiency using a highly specific cortisol immunoassay.

    PubMed

    Kline, G A; Buse, J; Krause, R D

    2017-06-01

    Recent guidelines recommend a diagnosis of adrenal insufficiency when a stimulated peak cortisol level falls below 500nmol/L. This may not be valid using a highly specific cortisol immunoassay or liquid chromatography-mass spectroscopy (LCMS/MS). We sought to determine the diagnostic threshold for adrenal insufficiency using a new and widely available, highly specific cortisol immunoassay. All patients having a dynamic test of adrenal reserve had results measured using the historical cortisol assay (Roche Cortisol) and the newer assay (Roche Cortisol II). Subjects were categorized according to the traditional assay (normal>500nmol/L) with clinical case adjudication where necessary. Results from Cortisol II assay were concomitantly measured along with cortisol levels measured by LCMS/MS. ROC curve analysis was performed to generate new diagnostic thresholds. The Roche Cortisol II compared favourably with measures by LCMS/MS, generating cortisol levels approximately 30% lower than the older immunoassay. Many normal subjects had peak cortisols as low as 300nmol/L with Cortisol II. The optimized diagnostic threshold for adrenal insufficiency was 350nmol/L with a sensitivity of 91% and specificity 97%. Use of the old diagnostic threshold with the Cortisol II assay would have inappropriately doubled the rate of patient-classification as adrenal insufficient. Transition to a more specific cortisol assay requires revision of diagnostic thresholds for dynamic tests of adrenal insufficiency. With the Roche Cortisol II assay, a cut-off of 350nmol/L should replace the traditional 500nmol/L although some healthy subjects may be very close to this level. Copyright © 2017 The Canadian Society of Clinical Chemists. All rights reserved.

  4. Task-specific writing tremor: clinical phenotypes, progression, treatment outcomes, and proposed nomenclature.

    PubMed

    Ondo, William G; Satija, Pankaj

    2012-02-01

    Task-specific tremor diagnoses remain controversial. We evaluated 56 subjects seen with writing tremor. The diagnosis was made if there was a clear history of exclusive tremor while writing for at least 3 years before noticing tremor in any other scenario and the continued presence of writing tremor as the most prominent aspect of their tremor disorder on examination. The age of tremor onset was 47.2 ± 18.0 years (73.2% male). Ethnic backgrounds were Caucasian (68.4%), African (23.2%), Hispanic (5.2%), and Asian/Indian (3.3%), and 44% reported any tremor in a first degree relative. Writing tremor often progressed to other task-specific tremors or rest tremor but not to immediate postural tremor, as usually seen in essential tremor. The other tremor provoking scenarios were eating/drinking (14), brushing teeth/shaving/make-up (5), typing (2), suture removal (1), and drafting (1) and occurred a mean of 7.5 years after the onset of writing tremor. Fourteen developed a "rest" (true rest or crescendo) tremor but only 2 of these met clinical criteria for Parkinson's disease. Pharmacologic treatments of writing tremor, including with ethanol, were generally poor, whereas deep brain stimulation of the ventral intermediate (VIM) thalamus was successful. Compared with patients with "classic" essential tremor in our clinic, writing tremor patients were more likely African, more likely male, had an older age of onset, a lower likelihood of familial tremor, and were more refractory to tremor medications and ethanol. This supports segregation between task-specific tremor and essential tremor but does not support the specific diagnosis of "writing tremor" because many patients progress to tremor with other tasks.

  5. Elbow-specific clinical rating systems: extent of established validity, reliability, and responsiveness.

    PubMed

    The, Bertram; Reininga, Inge H F; El Moumni, Mostafa; Eygendaal, Denise

    2013-10-01

    The modern standard of evaluating treatment results includes the use of rating systems. Elbow-specific rating systems are frequently used in studies aiming at elbow-specific pathology. However, proper validation studies seem to be relatively sparse. In addition, these scoring systems might not always be used for appropriate populations of interest. Both of these issues might give rise to invalid conclusions being reported in the literature. Our aim was to investigate the extent to which the available elbow-specific outcome measurement tools have been validated and the quality of the validation itself. We also aimed to provide characteristics of the populations used for validation of these scales to enable clinicians to use them appropriately. A literature search identified 17 studies of 12 different elbow-specific scoring systems. These were assessed for validity, reliability, and responsiveness characteristics. The quality of these assessments was rated according to the Consensus Based Standards for the Selection of Health Measurement Instruments (COSMIN) checklist criteria, a standardized and validated tool developed specifically for this purpose. Currently, the only elbow-specific rating system that is validated using high-quality methodology is the Oxford Elbow Score, a patient-administered outcome measure tool that has been validated on heterogeneous study populations. Other rating systems still have to be proven in the future to be as good as the Oxford Elbow Score for clinical or research purposes. Additional validation studies are needed. Copyright © 2013 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.

  6. Implementing specific oral tolerance induction to milk into routine clinical practice: experience from first 50 patients

    PubMed Central

    Luyt, David; Bravin, Kristian; Luyt, Jessica

    2014-01-01

    Background Although the natural history of cow’s milk allergy is to resolve during childhood or adolescence, a small but significant proportion of children will remain allergic. Specific oral tolerance induction to cow’s milk (CM-SOTI) provides a treatment option in these children with continuing allergy with high success rates. However current sentiment limits widespread availability as existing reports advise that it is too soon to translate CM-SOTI into routine clinical practice. Methods In January 2007 we implemented a slow up-dosing CM-SOTI program. Eligible subjects were identified at routine visits to our children’s allergy clinic. Persisting cow’s milk allergy was confirmed from recent contact symptoms or a positive baked milk challenge. As allergic symptoms are common during CM-SOTI, families were provided with ready dietetic access for advice on dosing and symptom treatment. Subjects were continuously monitored at subsequent clinic visits or telephonically, where no longer followed, for a median of 49 months. Results The first 50 subjects (35 males) treated ranged in age from 5.1 to 15.8 years (median 10.3 years). Full tolerance (250 mL) was achieved in 23 subjects, 9 without any symptoms, and a further 9 achieved partial tolerance with continued ingestion. Eighteen children failed to achieve any regular milk ingestion; 11 because of persistent or significant symptoms whilst 8 withdrew against medical advice. Allergic symptoms were predominantly mild to moderate in severity, although 2 cases needed treatment with inhaled salbutamol and a further 2 required intramuscular adrenaline. Clinical tolerance, both full and partial, persists beyond 5 years. Conclusion We have demonstrated that a CM-SOTI program can be successfully and safely implemented as routine clinical practice with acceptable compliance during prolonged home up-dosing, despite frequent allergic symptoms, and for up to 4 years after starting treatment. CM-SOTI can thus be put into

  7. The clinical utility of pain classification in non-specific arm pain.

    PubMed

    Moloney, Niamh A; Hall, Toby M; Leaver, Andrew M; Doody, Catherine M

    2015-02-01

    Mechanisms-based pain classification has received considerable attention recently for its potential use in clinical decision making. A number of algorithms for pain classification have been proposed. Non-specific arm pain (NSAP) is a poorly defined condition, which could benefit from classification according to pain mechanisms to improve treatment selection. This study used three published classification algorithms (hereafter called NeuPSIG, Smart, Schafer) to investigate the frequency of different pain classifications in NSAP and the clinical utility of these systems in assessing NSAP. Forty people with NSAP underwent a clinical examination and quantitative sensory testing. Findings were used to classify participants according to three classification algorithms. Frequency of pain classification including number unclassified was analysed using descriptive statistics. Inter-rater agreement was analysed using kappa coefficients. NSAP was primarily classified as 'unlikely neuropathic pain' using NeuPSIG criteria, 'peripheral neuropathic pain' using the Smart classification and 'peripheral nerve sensitisation' using the Schafer algorithm. Two of the three algorithms allowed classification of all but one participant; up to 45% of participants (n = 18) were categorised as mixed by the Smart classification. Inter-rater agreement was good for the Schafer algorithm (к = 0.78) and moderate for the Smart classification (к = 0.40). A kappa value was unattainable for the NeuPSIG algorithm but agreement was high. Pain classification was achievable with high inter-rater agreement for two of the three algorithms assessed. The Smart classification may be useful but requires further direction regarding the use of clinical criteria included. The impact of adding a pain classification to clinical assessment on patient outcomes needs to be evaluated.

  8. Anatomic and clinical pathology boot camps: filling pathology-specific gaps in undergraduate medical education.

    PubMed

    Naritoku, Wesley Y; Vasovic, Ljiljana; Steinberg, Jacob J; Prystowsky, Michael B; Powell, Suzanne Z

    2014-03-01

    The Liaison Committee on Medical Education began an initiative to change medical education across the United States in the early 2000s. With the explosion in medical science knowledge, the need arose to teach selected fundamental information both in a contextual and in an active learning manner. To identify ways to address gaps in training and knowledge that became apparent following implementation of learner-centered teaching methods, with devotion of more time to Internet-based learning and less emphasis on face-to-face lecture time. There was a dramatic departure from or de-emphasis of many traditional courses, such as embryology, gross anatomy, microscopic anatomy, and pathology, to the integration of these sciences into system-based active learning courses. This change in medical school curricula produces a medical graduate who hopefully thinks differently but certainly lacks subject-specific knowledge for a variety of medical specialties. Pathology residency programs have developed "boot camps" for the initial months of residency training both to provide the necessary foundation of pathology-specific medical science and to introduce basic skills and processes required for practice of anatomic pathology and laboratory medicine. The College of American Pathologists Graduate Medical Education Committee sent a questionnaire out on the Program Directors Section Listserv; the results are discussed and 3 boot camp programs are described. Boot camps have 2 purposes: (1) to teach or strengthen knowledge required to practice pathology and (2) to introduce basic skills and processes that will be used during the practitioner's career.

  9. Clinical anxiety, cortisol and interleukin-6: evidence for specificity in emotion-biology relationships.

    PubMed

    O'Donovan, Aoife; Hughes, Brian M; Slavich, George M; Lynch, Lydia; Cronin, Marie-Therese; O'Farrelly, Cliona; Malone, Kevin M

    2010-10-01

    Anxiety confers increased risk for inflammatory diseases, and elevated inflammatory activity in anxious individuals may contribute to this increased risk. One complication, however, is that anxiety could be associated with inflammatory activity either through a specific anxiety pathway or through a more general negative emotionality pathway. To investigate, we measured levels of the stress hormone cortisol, the pro-inflammatory cytokine interleukin-6 (IL-6), and the systemic inflammatory marker C-reactive protein (CRP), as well as depression and neuroticism, in clinically anxious and non-anxious adults. Compared with non-anxious participants, clinically anxious participants exhibited significantly lower levels of morning cortisol and significantly higher levels of IL-6, independent of age, sex, and depressive symptoms. These group differences were robust when controlling for neuroticism. Conversely, the groups had equivalent levels of CRP in all analyses. Results are indicative of anxiety-specific effects on inflammatory activity, and highlight a pathway by which anxiety may increase risk for inflammatory diseases. Copyright © 2010 Elsevier Inc. All rights reserved.

  10. Sensitivity and specificity of the World Health Organization pertussis clinical case definition.

    PubMed

    Ghanaie, Roxana Mansour; Karimi, Abdollah; Sadeghi, Hossein; Esteghamti, Abdolreza; Falah, Fateme; Armin, Shahnaz; Fahimzad, Alireza; Shamshiri, Ahmadreza; Kahbazi, Manige; Shiva, Faride

    2010-12-01

    Bordetella pertussis continues to circulate even in countries with good childhood vaccination coverage. This study was undertaken to define the relationship between documented disease and the clinical criteria proposed by the World Health Organization (WHO). Nasopharyngeal swab samples were collected from previously healthy 6-14-year-old school children in Tehran, presenting with persistent cough of at least 2- week duration. Specimens were examined for Bordetella pertussis and Bordetella parapertussis by culture and polymerase chain reaction (PCR). Out of 6601 students, 328 (5.0%) had been coughing for at least 2 weeks. Of these children with cough, 182 (55.5%) experienced whooping, 194 (59.1%) suffered a paroxysmal cough, and 73 (22.3%) had post-tussive vomiting. Twenty-one (6.4%) samples tested positive for B. pertussis and six (1.8%) for B. parapertussis by PCR. Culture of four (1.2%) specimens was positive for B. pertussis. In comparison to PCR, the sensitivity and the specificity of the WHO clinical criteria (year 2000) were 95.2% and 15.0%, respectively. Pertussis remains one of the etiologies of prolonged cough, even in communities with high immunization in children. The specificity of the WHO criteria is low in diagnosing pertussis compared with PCR. Copyright © 2010 International Society for Infectious Diseases. All rights reserved.

  11. Clinical anxiety, cortisol and interleukin-6: Evidence for specificity in emotion–biology relationships

    PubMed Central

    O'Donovan, Aoife; Hughes, Brian M.; Slavich, George M.; Lynch, Lydia; Cronin, Marie-Therese; O'Farrelly, Cliona; Malone, Kevin M.

    2015-01-01

    Anxiety confers increased risk for inflammatory diseases, and elevated inflammatory activity in anxious individuals may contribute to this increased risk. One complication, however, is that anxiety could be associated with inflammatory activity either through a specific anxiety pathway or through a more general negative emotionality pathway. To investigate, we measured levels of the stress hormone cortisol, the pro-inflammatory cytokine interleukin-6 (IL-6), and the systemic inflammatory marker C-reactive protein (CRP), as well as depression and neuroticism, in clinically anxious and non-anxious adults. Compared with non-anxious participants, clinically anxious participants exhibited significantly lower levels of morning cortisol and significantly higher levels of IL-6, independent of age, sex, and depressive symptoms. These group differences were robust when controlling for neuroticism. Conversely, the groups had equivalent levels of CRP in all analyses. Results are indicative of anxiety-specific effects on inflammatory activity, and highlight a pathway by which anxiety may increase risk for inflammatory diseases. PMID:20227485

  12. Characteristics of specific reading disability in children from a neuropsychological clinic in Mexico City.

    PubMed

    Poblano, Adrián; Borja, Sonia; Elías, Yolanda; García-Pedroza, Felipe; Arias, Ma de Lourdes

    2002-01-01

    This report describes the main clinical features associated with specific reading disability (RD) in a group of 778 school-age children studied in a Neuropsychological Clinic in Mexico City. The study was performed retrospectively, using data abstracted from clinical records of subjects seen in 1995-1996. Children were mainly from low and middle economic strata and aged between 6 to 12 years. The following data were collected: age, gender, diagnosis, school grade, food intake, maternal complications during pregnancy, perinatal and postnatal neurological risk factors, and neurological signs and handedness. Subjects with RD had a mean age of 102.9 months, were predominantly male (male female ratio, 2:1). Among the study group, 49.1% of the children were diagnosed with RD of a visuo-sensory-motor type, and 75.1% were from early school years (1st to 3rd grades); 27.6% showed evidence of malnutrition. A previous history of language disorders (49.2%), and a high frequency of perinatal risk factors and neurological soft signs were also found. This study shows that variables such as gender, food intake, and genetic and neurological risk factors, were associated with reading disabilities in school children. The English version of this paper is available too at: http://www.insp.mx/salud/index.html.

  13. Chromatin immunoprecipitation from fixed clinical tissues reveals tumor-specific enhancer profiles.

    PubMed

    Cejas, Paloma; Li, Lewyn; O'Neill, Nicholas K; Duarte, Melissa; Rao, Prakash; Bowden, Michaela; Zhou, Chensheng W; Mendiola, Marta; Burgos, Emilio; Feliu, Jaime; Moreno-Rubio, Juan; Guadalajara, Héctor; Moreno, Víctor; García-Olmo, Damián; Bellmunt, Joaquim; Mullane, Stephanie; Hirsch, Michelle; Sweeney, Christopher J; Richardson, Andrea; Liu, X Shirley; Brown, Myles; Shivdasani, Ramesh A; Long, Henry W

    2016-06-01

    Extensive cross-linking introduced during routine tissue fixation of clinical pathology specimens severely hampers chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq) analysis from archived tissue samples. This limits the ability to study the epigenomes of valuable, clinically annotated tissue resources. Here we describe fixed-tissue chromatin immunoprecipitation sequencing (FiT-seq), a method that enables reliable extraction of soluble chromatin from formalin-fixed paraffin-embedded (FFPE) tissue samples for accurate detection of histone marks. We demonstrate that FiT-seq data from FFPE specimens are concordant with ChIP-seq data from fresh-frozen samples of the same tumors. By using multiple histone marks, we generate chromatin-state maps and identify cis-regulatory elements in clinical samples from various tumor types that can readily allow us to distinguish between cancers by the tissue of origin. Tumor-specific enhancers and superenhancers that are elucidated by FiT-seq analysis correlate with known oncogenic drivers in different tissues and can assist in the understanding of how chromatin states affect gene regulation.

  14. The clinical course and prognostic factors of non-specific neck pain: a systematic review.

    PubMed

    Borghouts, J A; Koes, B W; Bouter, L M

    1998-07-01

    Neck pain occurs frequently in western societies. In the majority of cases, no specific cause can be identified. In order to gain insight into the clinical course and prognostic factors of non-specific neck pain, a systematic review was conducted. A computerized literature search was carried out to identify observational studies on non-specific neck pain and randomized clinical trials (RCTs) on conservative treatment of non-specific neck pain. Two reviewers scored independently, the methodological quality of all identified publications, using a standardized set of 13 criteria which were divided into five categories according to: study population, study design, follow-up, outcome measures and analysis/data presentation. To determine prognosis per study, an overall percentage of recovery for the most important outcome measures (pain, general improvement, functional status, health care utilization and lost days of work) was calculated. In total 23 eligible publications were identified (six observational studies and 17 RCTs). Only seven of 23 studies scored 50% or more of the 13 items, indicating a generally poor quality of methods. The most prevalent methodological shortcomings appeared to be selection of the study population, the sample size and analysis techniques. Most information regarding the clinical course is available for the group of patients with complaints for more than 6 months, who are treated in a secondary care or an occupational setting. In this group of patients, 46% (median) had less pain, with a range of 22-79% and a general improvement that ranged between 37 and 95% (47% median). The reduction in the use of analgesics ranged between 32 and 80% (37% median). Six studies reported on prognostic factors. Bearing in mind the limited number of studies and the low methodological quality, there are some indications that the localization (radiation to the arms/neurologic signs) and radiologic findings (degenerative changes in the discs and joints) are not

  15. Clinical practice recommendations for allergen-specific immunotherapy in children: the Italian consensus report.

    PubMed

    Pajno, Giovanni Battista; Bernardini, Roberto; Peroni, Diego; Arasi, Stefania; Martelli, Alberto; Landi, Massimo; Passalacqua, Giovanni; Muraro, Antonella; La Grutta, Stefania; Fiocchi, Alessandro; Indinnimeo, Luciana; Caffarelli, Carlo; Calamelli, Elisabetta; Comberiati, Pasquale; Duse, Marzia

    2017-01-23

    Allergen-specific immunotherapy (AIT) is currently recognized as a clinically effective treatment for allergic diseases, with a unique disease-modifying effect. AIT was introduced in clinical practice one century ago, and performed in the early years with allergenic extracts of poor quality and definition. After the mechanism of allergic reaction were recognized, the practice of AIT was refined, leading to remarkable improvement in the efficacy and safety profile of the treatment. Currently AIT is accepted and routinely prescribed worldwide for respiratory allergies and hymenoptera venom allergy. Both the subcutaneous (SCIT) and sublingual (SLIT) routes of administration are used in the pediatric population.AIT is recommended in allergic rhinitis/conjunctivitis with/without allergic asthma, with an evidence of specific IgE-sensitization towards clinically relevant inhalant allergens. Long-term studies provided evidence that AIT can also prevent the onset of asthma and of new sensitizations. The favorable response to AIT is strictly linked to adherence to treatment, that lasts 3-5 years. Therefore, several factors should be carefully evaluated before starting this intervention, including the severity of symptoms, pharmacotherapy requirements and children and caregivers' preference and compliance.In recent years, there have been increasing interest in the role of AIT for the treatment of IgE-associated food allergy and extrinsic atopic dermatitis. A growing body of evidence shows that oral immunotherapy represents a promising treatment option for IgE-associated food allergy. On the contrary, there are still controversies on the effectiveness of AIT for patients with atopic dermatitis.This consensus document was promoted by the Italian Society of Pediatric Allergy and Immunology (SIAIP) to provide evidence-based recommendations on AIT in order to implement and optimize current prescription practices of this treatment for allergic children.

  16. Patient-specific instrumentation does not improve radiographic alignment or clinical outcomes after total knee arthroplasty

    PubMed Central

    Huijbregts, Henricus J T A M; Khan, Riaz J K; Sorensen, Emma; Fick, Daniel P; Haebich, Samantha

    2016-01-01

    Background and purpose Patient-specific instrumentation (PSI) for total knee arthroplasty (TKA) has been introduced to improve alignment and reduce outliers, increase efficiency, and reduce operation time. In order to improve our understanding of the outcomes of patient-specific instrumentation, we conducted a meta-analysis. Patients and methods We identified randomized and quasi-randomized controlled trials (RCTs) comparing patient-specific and conventional instrumentation in TKA. Weighted mean differences and risk ratios were determined for radiographic accuracy, operation time, hospital stay, blood loss, number of surgical trays required, and patient-reported outcome measures. Results 21 RCTs involving 1,587 TKAs were included. Patient-specific instrumentation resulted in slightly more accurate hip-knee-ankle axis (0.3°), coronal femoral alignment (0.3°, femoral flexion (0.9°), tibial slope (0.7°), and femoral component rotation (0.5°). The risk ratio of a coronal plane outlier (> 3° deviation of chosen target) for the tibial component was statistically significantly increased in the PSI group (RR =1.64). No significance was found for other radiographic measures. Operation time, blood loss, and transfusion rate were similar. Hospital stay was significantly shortened, by approximately 8 h, and the number of surgical trays used decreased by 4 in the PSI group. Knee Society scores and Oxford knee scores were similar. Interpretation Patient-specific instrumentation does not result in clinically meaningful improvement in alignment, fewer outliers, or better early patient-reported outcome measures. Efficiency is improved by reducing the number of trays used, but PSI does not reduce operation time. PMID:27249110

  17. Incidence rate of pathogen-specific clinical mastitis on conventional and organic Canadian dairy farms.

    PubMed

    Levison, L J; Miller-Cushon, E K; Tucker, A L; Bergeron, R; Leslie, K E; Barkema, H W; DeVries, T J

    2016-02-01

    Mastitis is a common and costly production disease on dairy farms. In Canada, the incidence rate of clinical mastitis (IRCM) has been determined for conventionally managed dairy farms; however, no studies to date have assessed rates in organically managed systems. The objectives of this observational study were (1) to determine the producer-reported IRCM and predominant pathogen types on conventional and organic dairy farms in Southern Ontario, Canada, and (2) to evaluate the association of both mean overall IRCM and pathogen-specific IRCM with management system, housing type, and pasture access. Data from 59 dairy farms in Southern Ontario, Canada, distributed across conventional (n=41) and organic management (n=18) systems, were collected from April 2011 to May 2012. In addition to management system, farms were categorized by housing method (loose or tie-stall) and pasture access for lactating cows. Participating producers identified and collected samples from 936 cases of clinical mastitis. The most frequently isolated mastitis pathogens were coagulase-negative staphylococci, Bacillus spp., Streptococcus spp., Staphylococcus aureus, and Escherichia coli. The IRCM was higher on conventional farms than organic (23.7 vs. 13.2 cases per 100 cow-years) and was not associated with housing type (loose or tie-stall), pasture access, or herd-average milk yield. Bulk tank somatic cell count tended to be lower on conventional farms than organic (222,000 vs. 272,000 cells/mL). Pathogen-specific IRCM attributed to Staph. aureus, Bacillus spp., and E. coli was greater on conventional than organic farms, but was not associated with housing or any other factors. In conclusion, organic management was associated with reduced overall and pathogen-specific IRCM.

  18. Antiretroviral Medication Adherence and Class-Specific Resistance in a Large Prospective Clinical Trial

    PubMed Central

    GARDNER, Edward M.; HULLSIEK, Katherine H.; TELZAK, Edward E.; SHARMA, Shweta; PENG, Grace; BURMAN, William J.; MACARTHUR, Rodger D.; CHESNEY, Margaret; FRIEDLAND, Gerald; MANNHEIMER, Sharon B.

    2010-01-01

    Objective To assess the association between adherence to antiretroviral therapy and the presence of class-specific antiretroviral medication resistance. Design Secondary analysis of prospective clinical trial data Methods Participants randomized to the protease inhibitor (PI) or non-nucleoside reverse transcriptase inhibitor (NNRTI) strategies of the Community Programs for Clinical Research on AIDS (CPCRA) Flexible Initial Retrovirus Suppressive Therapies (FIRST) Study were included. Adherence was measured by 7-day self-report. Virological failure was defined as an HIV-RNA > 1000 at or after 4 months. The association between cumulative adherence and the development of class-specific genotypic resistance was assessed by Cox regression analysis. Results Included were 457 and 446 antiretroviral naïve participants on the PI and NNRTI strategies respectively. The median time to initial virological failure in the PI strategy was 1.2 years; 135 (30%) individuals failed with resistance. The median time to initial virological failure in the NNRTI strategy was 3.0 years; 127 (28%) failed with resistance. No association was found between cumulative adherence and PI resistance (HR 1.1, 95% CI 0.9 – 1.4 per 10% lower adherence). However, lower cumulative adherence was associated with an increased risk of NNRTI resistance at initial virological failure (HR 1.2, 95% CI 1.1 – 1.3 per 10% lower adherence). In both strategies lower cumulative adherence was associated with an increased risk of nucleoside reverse transcriptase inhibitor (NRTI) resistance at initial virological failure. Conclusions Adherence-resistance relationships are class-specific. For NRTIs and NNRTIs, initial virological failure with resistance is more likely at lower levels of cumulative adherence. PMID:20099399

  19. Impact of donor-specific antibodies on the outcomes of kidney graft: Pathophysiology, clinical, therapy

    PubMed Central

    Salvadori, Maurizio; Bertoni, Elisabetta

    2014-01-01

    Allo-antibodies, particularly when donor specific, are one of the most important factors that cause both early and late graft dysfunction. The authors review the current state of the art concerning this important issue in renal transplantation. Many antibodies have been recognized as mediators of renal injury. In particular donor-specific-Human Leukocyte Antigens antibodies appear to play a major role. New techniques, such as solid phase techniques and Luminex, have revealed these antibodies from patient sera. Other new techniques have uncovered alloantibodies and signs of complement activation in renal biopsy specimens. It has been acknowledged that the old concept of chronic renal injury caused by calcineurine inhibitors toxicity should be replaced in many cases by alloantibodies acting against the graft. In addition, the number of patients on waiting lists with preformed anti-human leukocyte antigens (HLA) antibodies is increasing, primarily from patients with a history of renal transplant failure already been sensitized. We should distinguish early and late acute antibody-mediated rejection from chronic antibody-mediated rejection. The latter often manifets late during the course of the post-transplant period and may be difficult to recognize if specific techniques are not applied. Different therapeutic strategies are used to control antibody-induced damage. These strategies may be applied prior to transplantation or, in the case of acute antibody-mediated rejection, after transplantation. Many new drugs are appearing at the horizon; however, these drugs are far from the clinic because they are in phase I-II of clinical trials. Thus the pipeline for the near future appears almost empty. PMID:24669363

  20. Formative evaluation of a patient-specific clinical knowledge summarization tool

    PubMed Central

    Del Fiol, Guilherme; Mostafa, Javed; Pu, Dongqiuye; Medlin, Richard; Slager, Stacey; Jonnalagadda, Siddhartha R.; Weir, Charlene R.

    2015-01-01

    Objective To iteratively design a prototype of a computerized clinical knowledge summarization (CKS) tool aimed at helping clinicians finding answers to their clinical questions; and to conduct a formative assessment of the usability, usefulness, efficiency, and impact of the CKS prototype on physicians’ perceived decision quality compared with standard search of UpToDate and PubMed. Materials and methods Mixed-methods observations of the interactions of 10 physicians with the CKS prototype vs. standard search in an effort to solve clinical problems posed as case vignettes. Results The CKS tool automatically summarizes patient-specific and actionable clinical recommendations from PubMed (high quality randomized controlled trials and systematic reviews) and UpToDate. Two thirds of the study participants completed 15 out of 17 usability tasks. The median time to task completion was less than 10 s for 12 of the 17 tasks. The difference in search time between the CKS and standard search was not significant (median = 4.9 vs. 4.5 min). Physician’s perceived decision quality was significantly higher with the CKS than with manual search (mean = 16.6 vs. 14.4; p = 0.036). Conclusions The CKS prototype was well-accepted by physicians both in terms of usability and usefulness. Physicians perceived better decision quality with the CKS prototype compared to standard search of PubMed and UpToDate within a similar search time. Due to the formative nature of this study and a small sample size, conclusions regarding efficiency and efficacy are exploratory. PMID:26612774

  1. Specific antibodies in oral immunotherapy for cow's milk allergy: kinetics and prediction of clinical outcome.

    PubMed

    Savilahti, Emma M; Kuitunen, Mikael; Savilahti, Erkki; Mäkelä, Mika J

    2014-01-01

    METHODS for predicting the clinical outcome of specific oral immunotherapy (OIT) would improve the safety of the therapy. We investigated 40 children aged 6-17 years with IgE-mediated cow's milk allergy (CMA) who either successfully completed OIT (n = 32) or discontinued the therapy due to adverse reactions (n = 8). From sera drawn before and after OIT, we analyzed specific IgA, IgG, IgG1 and IgG4 to cow's milk (CM), casein, β-lactoglobulin and ovalbumin (with enzyme-linked immunosorbent assay) and IgE to CM and hen's egg white [with enzymatic fluoroimmunoassay (Phadia ThermoFisher Scientific CAP system)]. As a reference, we also analyzed serum samples from 8- to 9-year-old children who either had no history of CMA (n = 76) or who had spontaneously recovered from IgE-mediated CMA (n = 56). Levels of specific IgA, IgG, IgG1 and IgG4 to CM and casein, and CM-specific IgE prior to OIT were higher in children who discontinued the therapy than in those who achieved desensitization (p < 0.05). Adverse reactions in the entire population were associated with low IgG and IgG4, but high IgG1 levels to ovalbumin (p < 0.05). Specific IgA, IgG, IgG1 and IgG4 to CM proteins significantly increased and IgE to CM decreased during OIT in children who achieved desensitization (p < 0.01). In those who discontinued OIT, only IgG, IgG1 and IgG4 to CM increased significantly (p < 0.03) and CM IgE remained unchanged. High specific IgE, IgA and IgG-class antibodies to CM proteins appear to predict failure to achieve desensitization in CM OIT. Specific IgA and IgG-class antibodies to CM increase and CM IgE decreases during desensitization. © 2014 S. Karger AG, Basel.

  2. The sensitivity and specificity of the neurological examination in polyneuropathy patients with clinical and electrophysiological correlations

    PubMed Central

    Alabdali, Majed; Alsulaiman, Abdulla; Albulaihe, Hana; Breiner, Ari; Katzberg, Hans D.; Aljaafari, Danah; Lovblom, Leif E.; Bril, Vera

    2017-01-01

    Introduction Polyneuropathy is one of the most prevalent neurologic disorders. Although several studies explored the role of the neurological examination in polyneuropathy, they were mostly restricted to specific subgroups of patients and have not correlated examination findings with symptoms and electrophysiological results. Objectives To explore the sensitivity and specificity of different neurological examination components in patients with diverse etiologies for polyneuropathy, find the most sensitive combination of examination components for polyneuropathy detection, and correlate examination findings with symptoms and electrophysiological results. Methods Patients with polyneuropathy attending the neuromuscular clinic from 01/2013 to 09/2015 were evaluated. Inclusion criteria included symptomatic polyneuropathy, which was confirmed by electrophysiological studies. 47 subjects with no symptoms or electrophysiological findings suggestive for polyneuropathy, served as controls. Results The total cohort included 312 polyneuropathy patients, with a mean age of 60±14 years. Abnormal examination was found in 95%, most commonly sensory findings (86%). The most common abnormal examination components were impaired ankle reflexes (74%), vibration (73%), and pinprick (72%) sensation. Combining ankle reflex examination with vibration or pinprick perception had the highest sensitivity, of 88%. The specificities of individual examination component were generally high, excluding ankle reflexes (62%), and vibration perception (77%). Abnormal examination findings were correlated with symptomatic weakness and worse electrophysiological parameters. Conclusion The neurological examination is a valid, sensitive and specific tool for diagnosing polyneuropathy, and findings correlate with polyneuropathy severity. Ankle reflex examination combined with either vibration or pinprick sensory testing is the most sensitive combination for diagnosing polyneuropathy, and should be

  3. Content addressable memory project

    NASA Technical Reports Server (NTRS)

    Hall, Josh; Levy, Saul; Smith, D.; Wei, S.; Miyake, K.; Murdocca, M.

    1991-01-01

    The progress on the Rutgers CAM (Content Addressable Memory) Project is described. The overall design of the system is completed at the architectural level and described. The machine is composed of two kinds of cells: (1) the CAM cells which include both memory and processor, and support local processing within each cell; and (2) the tree cells, which have smaller instruction set, and provide global processing over the CAM cells. A parameterized design of the basic CAM cell is completed. Progress was made on the final specification of the CPS. The machine architecture was driven by the design of algorithms whose requirements are reflected in the resulted instruction set(s). A few of these algorithms are described.

  4. Intuitive presentation of clinical forensic data using anonymous and person-specific 3D reference manikins.

    PubMed

    Urschler, Martin; Höller, Johannes; Bornik, Alexander; Paul, Tobias; Giretzlehner, Michael; Bischof, Horst; Yen, Kathrin; Scheurer, Eva

    2014-08-01

    The increasing use of CT/MR devices in forensic analysis motivates the need to present forensic findings from different sources in an intuitive reference visualization, with the aim of combining 3D volumetric images along with digital photographs of external findings into a 3D computer graphics model. This model allows a comprehensive presentation of forensic findings in court and enables comparative evaluation studies correlating data sources. The goal of this work was to investigate different methods to generate anonymous and patient-specific 3D models which may be used as reference visualizations. The issue of registering 3D volumetric as well as 2D photographic data to such 3D models is addressed to provide an intuitive context for injury documentation from arbitrary modalities. We present an image processing and visualization work-flow, discuss the major parts of this work-flow, compare the different investigated reference models, and show a number of cases studies that underline the suitability of the proposed work-flow for presenting forensically relevant information in 3D visualizations.

  5. Autologous anticancer antigen preparation for specific immunotherapy in advanced cancer patients. A phase I clinical trial.

    PubMed

    Slanetz, C A; McCollester, D L; Kanor, S

    1982-01-01

    A phase I clinical trial was performed to detect adverse reactions in far advanced cancer patients treated with a unique specific cancer immunotherapy. The vaccines consisted of autologous tumor cell membranes and manganese phosphate gel. From 133 patients admitted into the trial, 95 vaccine batches were made. No batch was toxic in animals. One batch was bacteriologically contaminated. Sufficient patients survived or complied to receive 32 complete and 23 partial courses for a total of 707 SC and ID injections. Minor swelling and occasional minimal pain occurred at injection sites. There were two possible vaccine-related systemic reactions but no evidence of tumor transplantation, tumor acceleration, sepsis or autoimmune disease. Subjective and objective improvement occurred in a number of patients. The vaccines are safe. Their efficacy must be determined. The value of ID vaccine skin testing and the unexpectedly little bacteriological contamination require further study.

  6. Cancer-Specific Telomerase Reverse Transcriptase (TERT) Promoter Mutations: Biological and Clinical Implications

    PubMed Central

    Liu, Tiantian; Yuan, Xiaotian; Xu, Dawei

    2016-01-01

    The accumulated evidence has pointed to a key role of telomerase in carcinogenesis. As a RNA-dependent DNA polymerase, telomerase synthesizes telomeric DNA at the end of linear chromosomes, and attenuates or prevents telomere erosion associated with cell divisions. By lengthening telomeres, telomerase extends cellular life-span or even induces immortalization. Consistent with its functional activity, telomerase is silent in most human normal somatic cells while active only in germ-line, stem and other highly proliferative cells. In contrast, telomerase activation widely occurs in human cancer and the enzymatic activity is detectable in up to 90% of malignancies. Recently, hotspot point mutations in the regulatory region of the telomerase reverse transcriptase (TERT) gene, encoding the core catalytic component of telomerase, was identified as a novel mechanism to activate telomerase in cancer. This review discusses the cancer-specific TERT promoter mutations and potential biological and clinical significances. PMID:27438857

  7. Specific CD4+ T-Cell Reactivity and Cytokine Release in Different Clinical Presentations of Leptospirosis.

    PubMed

    Volz, Magdalena Sarah; Moos, Verena; Allers, Kristina; Luge, Enno; Mayer-Scholl, Anne; Nöckler, Karsten; Loddenkemper, Christoph; Jansen, Andreas; Schneider, Thomas

    2015-12-01

    Clinical manifestations of leptospirosis are highly variable: from asymptomatic to severe and potentially fatal. The outcome of the disease is usually determined in the immunological phase, beginning in the second week of symptoms. The underlying mechanisms, predictive factors, and individual immune responses that contribute to clinical variations are not well understood. The aim of this study was to determine the specifics of CD4(+) T-cell reactivity and cytokine release after stimulation with leptospiral antigens in patients with leptospirosis of different disease severities (patients with mild and severe symptoms) and in control subjects (with and without proven exposure to Leptospira). Whole-blood specimens were stimulated with Leptospira antigens in vitro. Subsequently, intracellular staining of cytokines was performed, and flow cytometry was used to assess the expression of CD40 ligand (CD40L) and the production of gamma interferon (IFN-γ), interleukin-10 (IL-10), IL-2, and tumor necrosis factor alpha (TNF-α) by CD4(+) T cells. The production of inflammatory cytokines such as TNF-α by CD4(+) T cells after stimulation with leptospiral antigens was highest in patients with severe disease. In contrast, the ratio of IL-10 production to TNF-α production was higher in exposed subjects than in patients with mild and severe disease. Levels of proinflammatory cytokines such as TNF-α may be useful markers of the severity of the immunological phase of leptospirosis. IL-10 production by T cells after antigen-specific stimulation may indicate a more successful downregulation of the inflammatory response and may contribute to an asymptomatic course of the disease.

  8. Genetic analysis of pathogen-specific clinical mastitis in Norwegian Red cows.

    PubMed

    Haugaard, K; Heringstad, B; Whist, A C

    2012-03-01

    The objective of this study was to estimate heritabilities and genetic correlations for pathogen-specific clinical mastitis (CM) in Norwegian Red cows. In Norway, breeding values for mastitis are predicted based on records of veterinary treatments of clinical mastitis. Bacteriological milk sample results from the mastitis laboratories have been recorded routinely into the Norwegian Dairy Herd Recording System since 2000, but have so far not been used in genetic analyses. This additional source of data may provide valuable information on pathogen-specific CM. Records from 234,088 first-lactation Norwegian Red cows, daughters of 1,656 sires, were used for genetic analyses of unspecific, Staphylococcus aureus, Streptococcus dysgalactiae, and Escherichia coli CM. The 4 CM traits were defined as binary and scored as 1 if the cow had at least 1 case of the CM in question and 0 otherwise. A Bayesian approach using Gibbs sampling was applied, and a multivariate threshold liability model was used for the analyses. The posterior mean (SD ≤ 0.01) of the heritabilities were 0.06 for liability of unspecific CM, 0.04 for Staph. aureus CM, 0.02 for Strep. dysgalactiae CM, and 0.03 for E. coli CM. The posterior mean (SD) of the genetic correlations were all high, ranging from 0.75 (0.14) to 0.87 (0.07). The highest genetic correlation was found between unspecific CM and Strep. dysgalactiae CM, whereas the lowest was found for E. coli CM and Staph. aureus CM. Genetic correlations lower than 1 indicate that mastitis caused by different pathogens can be considered as partly different traits. In spite of high rank correlations (0.95-0.98), some re-ranking of sires was observed. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  9. Validity, specificity, feasibility and acceptability of a brief pediatric distress thermometer in outpatient clinics.

    PubMed

    Wiener, Lori; Battles, Haven; Zadeh, Sima; Widemann, Brigitte C; Pao, Maryland

    2017-04-01

    Psychosocial distress is under-recognized in children with cancer and other serious medical illnesses because of a focus on pressing medical concerns. This study assessed the validity, inter-rater reliability, sensitivity/specificity, acceptability, and feasibility of administration of a pediatric distress thermometer (DT) designed to screen for the presence of psychosocial distress in youth with serious medical illnesses. Two hundred eighty-one patient-caregiver-provider triads were enrolled from two hospital outpatient clinics. Patients diagnosed with cancer and other life-threatening diseases, caregivers, and providers completed the DT and a DT acceptability rating. Patients and caregivers completed standardized measures of anxiety, depression, pain, and fatigue. Providers completed a measure of disease severity. Data collectors completed a feasibility rating. The DT was significantly correlated with both caregiver and patient reports of depression, anxiety, pain, and fatigue, exhibiting concurrent validity. Parent, child, and caregiver report demonstrated significant, moderate inter-rater reliability, with lower concordance between raters in the youngest age group. The DT is a sensitive instrument for screening of psychosocial distress when compared with the selected gold standard (Brief Symptom Inventory 18 depression subscale and the Children's Depression Inventory). The DT is not highly specific but quickly identifies those in need of further psychosocial assessment. Screening, using an adapted pediatric DT, is valid, feasible, and acceptable to patients, caregivers, and medical providers across chronic medical illnesses. As patient and caregiver reports are not always concordant, both patient and caregiver report of distress are important for the provider to obtain clinically meaningful information to guide interventions. Published 2015. This article is a U.S. Government work and is in the public domain in the USA. Published 2015. This article is a U

  10. Sensitivity and specificity of univariate MRI analysis of experimentally degraded cartilage under clinical imaging conditions.

    PubMed

    Lukas, Vanessa A; Fishbein, Kenneth W; Reiter, David A; Lin, Ping-Chang; Schneider, Erika; Spencer, Richard G

    2015-07-01

    To evaluate the sensitivity and specificity of classification of pathomimetically degraded bovine nasal cartilage at 3 Tesla and 37°C using univariate MRI measurements of both pure parameter values and intensities of parameter-weighted images. Pre- and posttrypsin degradation values of T1 , T2 , T2 *, magnetization transfer ratio (MTR), and apparent diffusion coefficient (ADC), and corresponding weighted images, were analyzed. Classification based on the Euclidean distance was performed and the quality of classification was assessed through sensitivity, specificity and accuracy (ACC). The classifiers with the highest accuracy values were ADC (ACC = 0.82 ± 0.06), MTR (ACC = 0.78 ± 0.06), T1 (ACC = 0.99 ± 0.01), T2 derived from a three-dimensional (3D) spin-echo sequence (ACC = 0.74 ± 0.05), and T2 derived from a 2D spin-echo sequence (ACC = 0.77 ± 0.06), along with two of the diffusion-weighted signal intensities (b = 333 s/mm(2) : ACC = 0.80 ± 0.05; b = 666 s/mm(2) : ACC = 0.85 ± 0.04). In particular, T1 values differed substantially between the groups, resulting in atypically high classification accuracy. The second-best classifier, diffusion weighting with b = 666 s/mm(2) , as well as all other parameters evaluated, exhibited substantial overlap between pre- and postdegradation groups, resulting in decreased accuracies. Classification according to T1 values showed excellent test characteristics (ACC = 0.99), with several other parameters also showing reasonable performance (ACC > 0.70). Of these, diffusion weighting is particularly promising as a potentially practical clinical modality. As in previous work, we again find that highly statistically significant group mean differences do not necessarily translate into accurate clinical classification rules. © 2014 Wiley Periodicals, Inc.

  11. Specific CD4+ T-Cell Reactivity and Cytokine Release in Different Clinical Presentations of Leptospirosis

    PubMed Central

    Moos, Verena; Allers, Kristina; Luge, Enno; Mayer-Scholl, Anne; Nöckler, Karsten; Loddenkemper, Christoph; Jansen, Andreas; Schneider, Thomas

    2015-01-01

    Clinical manifestations of leptospirosis are highly variable: from asymptomatic to severe and potentially fatal. The outcome of the disease is usually determined in the immunological phase, beginning in the second week of symptoms. The underlying mechanisms, predictive factors, and individual immune responses that contribute to clinical variations are not well understood. The aim of this study was to determine the specifics of CD4+ T-cell reactivity and cytokine release after stimulation with leptospiral antigens in patients with leptospirosis of different disease severities (patients with mild and severe symptoms) and in control subjects (with and without proven exposure to Leptospira). Whole-blood specimens were stimulated with Leptospira antigens in vitro. Subsequently, intracellular staining of cytokines was performed, and flow cytometry was used to assess the expression of CD40 ligand (CD40L) and the production of gamma interferon (IFN-γ), interleukin-10 (IL-10), IL-2, and tumor necrosis factor alpha (TNF-α) by CD4+ T cells. The production of inflammatory cytokines such as TNF-α by CD4+ T cells after stimulation with leptospiral antigens was highest in patients with severe disease. In contrast, the ratio of IL-10 production to TNF-α production was higher in exposed subjects than in patients with mild and severe disease. Levels of proinflammatory cytokines such as TNF-α may be useful markers of the severity of the immunological phase of leptospirosis. IL-10 production by T cells after antigen-specific stimulation may indicate a more successful downregulation of the inflammatory response and may contribute to an asymptomatic course of the disease. PMID:26491036

  12. Trade-offs in producing patient-specific recommendations from a computer-based clinical guideline: a case study.

    PubMed Central

    Miller, P L; Frawley, S J

    1995-01-01

    This case study explored 1) how much online clinical data is required to obtain patient-specific recommendations from a computer-based clinical practice guideline, 2) whether the availability of increasing amounts of online clinical data might allow a higher specificity of those recommendations, and 3) whether that increased specificity is necessarily desirable. The "quick reference guide" version of the guideline for acute postoperative pain management in adults, developed by the Agency for Health Care Policy and Research, was analyzed. Patient-specific data items that might be used to tailor the computer's output for a particular case were grouped into rough categories depending on how likely they were to be available online and how readily they might be determined from online clinical data. The patient-specific recommendations were analyzed to determine to what degree the amount of text produced depended on the online availability of different categories of data. An examination of example recommendations, however, illustrated that high specificity may not always be desirable. The study provides a concrete illustration of how the richness of online clinical data can affect patient-specific recommendations, and describes a number of related design trade-offs in converting a clinical guideline into an interactive, computer-based form. PMID:7583647

  13. Long-term Clinical Relevance of De Novo Donor-Specific Antibodies After Pediatric Liver Transplantation.

    PubMed

    Grabhorn, Enke; Binder, Thomas M C; Obrecht, Denise; Brinkert, Florian; Lehnhardt, Anja; Herden, Uta; Peine, Sven; Nashan, Björn; Ganschow, Rainer; Briem-Richter, Andrea

    2015-09-01

    Anti-HLA antibodies and especially donor-specific antibodies (DSA) play a significant role in graft survival after solid organ transplantation. Their impact on long-term survival in adult liver transplantation (LT) is controversial, but they may be a risk factor. The effects of DSA after pediatric LT are still unclear. We performed a retrospective evaluation of DSA in sera from 43 children who had received transplants at our tertiary center. Twenty-four patients had good long-term clinical and laboratory graft function (group 1), whereas 19 LT recipients suffered from histologically confirmed and clinically relevant chronic allograft rejection (group 2); 16 of these have already undergone retransplantation due to graft dysfunction. Inclusion criteria were availability of sera before the first LT to identify preformed antibodies in case of DSA positivity after LT and long-term follow-up at our institution. Sera were analyzed for anti-HLA antibodies using Luminex single antigen beads, where a mean fluorescence intensity value of more than 1500 was considered positive. The prevalence of DSA was 33% for group 1 and 68% for group 2. Antibodies were predominantly HLA class II. Values of mean fluorescence intensity were comparable in both groups. Only one of the DSA+ ve patients from group 1 exhibited preformed antibodies. In conclusion, pediatric patients with chronic rejection revealed a higher rate of de novo DSA, especially of HLA-class II DSA. Further studies are necessary to confirm these data with a larger pediatric cohort.

  14. 47,XXY Klinefelter syndrome: clinical characteristics and age-specific recommendations for medical management.

    PubMed

    Aksglaede, Lise; Link, Katarina; Giwercman, Aleksander; Jørgensen, Niels; Skakkebaek, Niels E; Juul, Anders

    2013-02-15

    47,XXY (Klinefelter syndrome) is the most frequent sex chromosomal disorder and affects approximately one in 660 newborn boys. The syndrome is characterized by varying degrees of cognitive, social, behavioral, and learning difficulties and in adulthood additionally primary testicular failure with small testes, hypergonadotropic hypogonadism, tall stature, and eunuchoid body proportions. The phenotype is variable ranging from "near-normal" to a significantly affected individual. In addition, newborns with Klinefelter syndrome generally present with a normal male phenotype and the only consistent clinical finding in KS is small testes, that are most often not identified until after puberty. Decreased awareness of this syndrome among health professionals and a general perception that all patients with 47,XXY exhibit the classic textbook phenotype results in a highly under-diagnosed condition with up to 75% of the patients left undetected. Typically, diagnosis is delayed with the majority of patients identified during fertility workup in adulthood, and only 10% of patients diagnosed prior to puberty. Early detection of this syndrome is recommended in order to offer treatment and intervention at the appropriate ages and stages of development for the purpose of preventing osteopenia/osteoporosis, metabolic syndrome, and other medical conditions related to hypogonadism and to the XXY as well as minimizing potential learning and psychosocial problems. The aim of this review is to present the clinical aspects of XXY and the age-specific recommendations for medical management. © 2013 Wiley Periodicals, Inc.

  15. The Development of English as a Second Language With and Without Specific Language Impairment: Clinical Implications.

    PubMed

    Paradis, Johanne

    2016-02-01

    The purpose of this research forum article is to provide an overview of typical and atypical development of English as a second language (L2) and to present strategies for clinical assessment with English language learners (ELLs). A review of studies examining the lexical, morphological, narrative, and verbal memory abilities of ELLs is organized around 3 topics: timeframe and characteristics of typical English L2 development, comparison of the English L2 development of children with and without specific language impairment (SLI), and strategies for more effective assessment with ELLs. ELLs take longer than 3 years to converge on monolingual norms and approach monolingual norms asynchronously across linguistic subdomains. Individual variation is predicted by age, first language, language learning aptitude, length of exposure to English in school, maternal education, and richness of the English environment outside school. ELLs with SLI acquire English more slowly than ELLs with typical development; their morphological and nonword repetition abilities differentiate them the most. Use of strategies such as parent questionnaires on first language development and ELL norm referencing can result in accurate discrimination of ELLs with SLI. Variability in the language abilities of ELLs presents challenges for clinical practice. Increased knowledge of English language learning development with and without SLI together with evidence-based alternative assessment strategies can assist in overcoming these challenges.

  16. The Specificity of Emotional Switching in Borderline Personality Disorder in Comparison to Other Clinical Groups

    PubMed Central

    Houben, Marlies; Bohus, Martin; Santangelo, Philip; Ebner-Priemer, Ulrich; Trull, Timothy; Kuppens, Peter

    2016-01-01

    In an attempt to better understand the nature of emotion dysregulation in the daily lives of persons with a borderline personality disorder (BPD), Houben, Vansteelandt et al. (2015) recently identified emotional switching, which refers to the tendency to make large changes between positive and negative emotional states over time, as a possible defining characteristic of the emotion dynamics observed in BPD. The goal of this study was to examine the specificity of these previous findings in two samples, by comparing BPD patients (N = 43 in sample 1; N = 81 in sample 2) to patients with bulimia nervosa (N = 20) or posttraumatic stress disorder (N = 28) or healthy controls (N = 28) in sample 1, and to patients with depressive disorder (N = 50) in sample 2, with respect to measures of emotional switching. Analyses of these two experience sampling datasets revealed that contrary to expectations, BPD patients did not differ from the clinical groups regarding their mere tendency to switch between positive and negative emotional states on consecutive moments over time, and regarding the magnitude of such changes between positive and negative emotional states over time. However, all clinical groups did differ from healthy controls regarding all switch measures in dataset 1. These results indicate that emotional switching, similar to other more traditional indicators of overall changes in emotional intensity in daily life, might reflect a feature of emotional responding characterising a range of disorders with mood disturbances. PMID:26882282

  17. The effects of specific educational preparation on emergency nurses' clinical decisions regarding supplemental oxygen administration.

    PubMed

    Considine, Julie; Botti, Mari; Thomas, Shane

    2006-06-01

    The use of supplemental oxygen by emergency nurses has important implications for patient outcomes, yet there is significant variability in oxygen administration practises. Specific education related to oxygen administration increases factual knowledge in this domain; however, the impact of knowledge acquisition on nurses' clinical decisions is poorly understood. This study aimed to examine the effect of educational preparation on 20 emergency nurses' decisions regarding the assessment of oxygenation and the use of supplemental oxygen. A pre-test/post-test, quasi-experimental design was used. The intervention was a written, self-directed learning package. The major effects of the completion of the learning package included no change in the number or types of parameters used by nurses to assess oxygenation, a significant decrease in the selection of simple masks, a significant increase in the selection of air entrainment masks, fewer hypothetical outcomes of unresolved respiratory distress and more hypothetical outcomes of decreased respiratory distress. As many nursing education programs are aimed at increasing factual knowledge, while experience remains relatively constant, a greater understanding of the relationship between factual knowledge and clinical decisions is needed if educational interventions are to improve patient outcomes.

  18. Clinical impact of preformed donor-specific denatured class I HLA antibodies after kidney transplantation.

    PubMed

    Visentin, Jonathan; Marroc, Mélanie; Guidicelli, Gwendaline; Bachelet, Thomas; Nong, Thoa; Moreau, Jean-François; Lee, Jar-How; Merville, Pierre; Couzi, Lionel; Taupin, Jean-Luc

    2015-05-01

    Class I single-antigen flow beads (SAFB) carry native and denatured human leukocyte antigen (HLA) molecules. Using a cohort of 179 class I HLA-sensitized kidney recipients, we described incidence and clinical relevance of preformed denatured HLA donor-specific antibodies (DSA) using two different assays: an acid-treated SAFB assay (anti-dHLA DSA) and the iBeads assays (SAFB+/iBeads- DSA). Eighty-five class I DSA were found in 67 patients (median mean fluorescence intensity [MFI] of 1729 [range 520-13 882]). Anti-dHLA and SAFB+/iBeads- DSA represented 11% and 18% of class I DSA and were mainly low MFI DSA (500-1000 MFI). Concordance between these two assays was good (90%). None of the patients with only class I anti-dHLA DSA or only SAFB+/iBeads- DSA developed acute clinical antibody-mediated rejection in the first-year post-transplantation, and their five-yr death-censored graft survival was similar to that of patients without DSA. Moreover, all these patients displayed a negative current T-cell flow cytometry cross-match. Therefore, both anti-dHLA DSA and SAFB+/iBeads- DSA appear irrelevant, which could explain the good outcome observed in some patients with preformed class I DSA. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Classification, Identification, and Clinical Significance of Haemophilus and Aggregatibacter Species with Host Specificity for Humans

    PubMed Central

    2014-01-01

    SUMMARY The aim of this review is to provide a comprehensive update on the current classification and identification of Haemophilus and Aggregatibacter species with exclusive or predominant host specificity for humans. Haemophilus influenzae and some of the other Haemophilus species are commonly encountered in the clinical microbiology laboratory and demonstrate a wide range of pathogenicity, from life-threatening invasive disease to respiratory infections to a nonpathogenic, commensal lifestyle. New species of Haemophilus have been described (Haemophilus pittmaniae and Haemophilus sputorum), and the new genus Aggregatibacter was created to accommodate some former Haemophilus and Actinobacillus species (Aggregatibacter aphrophilus, Aggregatibacter segnis, and Aggregatibacter actinomycetemcomitans). Aggregatibacter species are now a dominant etiology of infective endocarditis caused by fastidious organisms (HACEK endocarditis), and A. aphrophilus has emerged as an important cause of brain abscesses. Correct identification of Haemophilus and Aggregatibacter species based on phenotypic characterization can be challenging. It has become clear that 15 to 20% of presumptive H. influenzae isolates from the respiratory tracts of healthy individuals do not belong to this species but represent nonhemolytic variants of Haemophilus haemolyticus. Due to the limited pathogenicity of H. haemolyticus, the proportion of misidentified strains may be lower in clinical samples, but even among invasive strains, a misidentification rate of 0.5 to 2% can be found. Several methods have been investigated for differentiation of H. influenzae from its less pathogenic relatives, but a simple method for reliable discrimination is not available. With the implementation of identification by matrix-assisted laser desorption ionization–time of flight mass spectrometry, the more rarely encountered species of Haemophilus and Aggregatibacter will increasingly be identified in clinical microbiology

  20. The Differences in Clinical Aspect Between Specific Language Impairment and Global Developmental Delay

    PubMed Central

    Kim, Seong Woo; Jeon, Ha Ra; Chung, Hee Jung; Song, Jung Eun

    2014-01-01

    Objective To compare and analyze the clinical characteristics of children with delayed language acquisition due to two different diagnoses, which were specific language impairment (SLI, a primarily delayed language development) and global developmental delay (GDD, a language delay related to cognitive impairment). Methods Among 1,598 children who had visited the developmental delay clinic from March 2005 to February 2011, 467 children who were diagnosed with GDD and 183 children who were diagnosed with SLI were included in this study. All children were questioned about past, family, and developmental history, and their language competences and cognitive function were assessed. Some children got electroencephalography (EEG), in case of need. Results The presence of the perinatal risk factors showed no difference in two groups. In the children with GDD, they had more delayed acquisition of independent walking and more frequent EEG abnormalities compared with the children with SLI (p<0.01). The positive family history of delayed language development was more prevalent in children with SLI (p<0.01). In areas of language ability, the quotient of receptive language and expressive language did not show any meaningful statistical differences between the two groups. Analyzing in each group, the receptive language quotient was higher than expressive language quotient in both group (p<0.01). In the GDD group, the Bayley Scales of Infant Development II (BSID-II) showed a marked low mental and motor quotient while the Wechsler Intelligence Scale showed low verbal and nonverbal IQ. In the SLI group, the BSID-II and Wechsler Intelligence Scale showed low scores in mental area and verbal IQ but sparing motor area and nonverbal IQ. Conclusion The linguistic profiles of children with language delay could not differentiate between SLI and GDD. The clinicians needed to be aware of these developmental issues, and history taking and clinical evaluation, including cognitive assessment

  1. The future of cardiovascular clinical research in North America and beyond-addressing challenges and leveraging opportunities through unique academic and grassroots collaborations.

    PubMed

    Roe, Matthew T; Mahaffey, Kenneth W; Ezekowitz, Justin A; Alexander, John H; Goodman, Shaun G; Hernandez, Adrian; Temple, Tracy; Berdan, Lisa; Califf, Robert M; Harrington, Robert A; Peterson, Eric D; Armstrong, Paul W

    2015-06-01

    Recent developments have highlighted the challenges facing cardiovascular clinical research in global contemporary practice, particularly in North America, including shifting priorities for drug development targets, increasing regulatory requirements, and expensive operational approaches for conducting randomized clinical trials. Nonetheless, emerging trends such as the consolidation of practices and hospitals into integrated health systems, the integration of electronic health records from thousands of practices into large data repositories to support prospective research studies, and streamlined operational approaches such as registry-based trials and risk-based monitoring have created numerous opportunities to disrupt the clinical research paradigm. Within this context, academic research organizations around the globe, particularly a strengthened collaboration of 3 established academic research organizations in North America, are uniquely positioned to promote and develop grassroots collaborations across all types of clinical practices, to delineate successful solutions to obstacles that limit clinical research initiatives, and to guide the future of cardiovascular research in the global research environment. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Clinical trials and systematic reviews addressing similar interventions for the same condition do not consider similar outcomes to be important: a case study in HIV/AIDS.

    PubMed

    Saldanha, Ian J; Li, Tianjing; Yang, Cui; Owczarzak, Jill; Williamson, Paula R; Dickersin, Kay

    2017-04-01

    The usefulness of clinical trials and systematic reviews is compromised when they report different outcomes. We compared outcomes in reviews of HIV/AIDS and the trials included in the reviews. We examined all Cochrane reviews of HIV/AIDS (as of June 2013) that included ≥1 trial and the trials that the reviews included. We compared outcomes within subgroups defined by type of intervention: clinical management, biomedical prevention, behavioral prevention, and health services. We included 84 reviews that encompassed 524 trials. Although the median number of outcomes per trial (8) and per review (7.5) was similar, the trials reported a considerably greater number of unique outcomes than the reviews (779 vs. 218), ranging from 2.3 times greater (clinical management) to 5.4 times greater (behavioral prevention). High proportions of trial outcomes were not in any review: 68% (clinical management) to 83% (behavioral prevention). Lower proportions of review outcomes were not in any trial: 11% (clinical management) to 39% (health services). Outcomes in trials and reviews are not well aligned for appropriate inclusion of trial results in reviews and meta-analyses. Differences in perspectives, goals, and constraints between trialists and reviewers may explain differences in outcomes they consider important. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Address tracing for parallel machines

    NASA Technical Reports Server (NTRS)

    Stunkel, Craig B.; Janssens, Bob; Fuchs, W. Kent

    1991-01-01

    Recently implemented parallel system address-tracing methods based on several metrics are surveyed. The issues specific to collection of traces for both shared and distributed memory parallel computers are highlighted. Five general categories of address-trace collection methods are examined: hardware-captured, interrupt-based, simulation-based, altered microcode-based, and instrumented program-based traces. The problems unique to shared memory and distributed memory multiprocessors are examined separately.

  4. Holoprosencephaly and ZIC2 microdeletions: novel clinical and epidemiological specificities delineated.

    PubMed

    Chabchoub, E; Willekens, D; Vermeesch, J R; Fryns, J-P

    2012-06-01

    Holoprosencephaly (HPE), the most common malformation of the human brain results from abnormal cleavage of the forebrain during the early embryonic developmental stages. The spectrum of malformations in HPE is wide, ranging from the classical cyclopia/proboscis to fairly asymptomatic forms [i.e. a single maxillary central incisor (SMCI)]. HPE may be caused by environmental or genetic factors. ZIC2 (13q32) was the second gene identified in which mutations cause HPE and recently a specific phenotype was ascribed to ZIC2-mutation HPE. Earlier, we reported a boy presenting HPE and deafness. Cytogenetic analyses were normal. Using array-comparative genomic hybridization (aCGH), we found a de novo 129 kb del(13)(q32) encompassing ZIC2 and ZIC5. There is no evidence for the involvement of ZIC5 in human diseases. We reviewed the literature for ZIC2-ZIC5 deletions and their involvement in neural tube defects (NTDs). Interestingly, we found evidence for a specific facial phenotype for ZIC2 gene deletion patients distinct from those with point mutations. In addition, based on the clinical data together with pathology, imaging and functional studies, we suggest an outline for a model explaining the genetic heterogeneity of ZIC2-ZIC5-associated NTDs and propose further studies for validation.

  5. The National Neurosurgery Quality and Outcomes Database Qualified Clinical Data Registry: 2015 measure specifications and rationale.

    PubMed

    Parker, Scott L; McGirt, Matthew J; Bekelis, Kimon; Holland, Christopher M; Davies, Jason; Devin, Clinton J; Atkins, Tyler; Knightly, Jack; Groman, Rachel; Zyung, Irene; Asher, Anthony L

    2015-12-01

    Meaningful quality measurement and public reporting have the potential to facilitate targeted outcome improvement, practice-based learning, shared decision making, and effective resource utilization. Recent developments in national quality reporting programs, such as the Centers for Medicare & Medicaid Services Qualified Clinical Data Registry (QCDR) reporting option, have enhanced the ability of specialty groups to develop relevant quality measures of the care they deliver. QCDRs will complete the collection and submission of Physician Quality Reporting System (PQRS) quality measures data on behalf of individual eligible professionals. The National Neurosurgery Quality and Outcomes Database (N(2)QOD) offers 21 non-PQRS measures, initially focused on spine procedures, which are the first specialty-specific measures for neurosurgery. Securing QCDR status for N(2)QOD is a tremendously important accomplishment for our specialty. This program will ensure that data collected through our registries and used for PQRS is meaningful for neurosurgeons, related spine care practitioners, their patients, and other stakeholders. The 2015 N(2)QOD QCDR is further evidence of neurosurgery's commitment to substantively advancing the health care quality paradigm. The following manuscript outlines the measures now approved for use in the 2015 N(2)QOD QCDR. Measure specifications (measure type and descriptions, related measures, if any, as well as relevant National Quality Strategy domain[s]) along with rationale are provided for each measure.

  6. Detection and specific targeting of hypoxic regions within solid tumors: current preclinical and clinical strategies.

    PubMed

    Bache, M; Kappler, M; Said, H M; Staab, A; Vordermark, D

    2008-01-01

    Poor oxygenation of solid tumors is a major indicator of adverse prognosis after standard treatment, e.g. radiotherapy. This observation founded on intratumoral pO(2) electrode measurements has been supported more recently by studies of injected hypoxia markers (pimonidazole, EF5) or hypoxia-related proteins (hypoxia-inducible factor-1alpha, carbonic anhydrase IX) detected immunohistochemically. Alternative approaches include imaging of tumor hypoxia by nuclear medicine studies and the measurement of hypoxia-related proteins (osteopontin) in patient plasma. Low oxygen levels as found in tumors are rarely observed in normal tissues. The presence of hypoxic tumor cells is therefore regarded not only as an adverse prognostic factor but as an opportunity for tumor-specific treatment. Classic approaches to normalize tumor oxygenation involve the breathing of modified gas mixtures and pharmacologic modification of blood flow as in the "accelerated radiotherapy, carbogen, nicotinamide" (ARCON) scheme. Specific killing of hypoxic tumor cells can potentially be achieved by hypoxia-selective cytotoxins (model substance tirapazamine), which has shown promise in head and neck cancer. Direct targeting of hypoxia-related molecules such as hypoxia-inducible factor-1alpha, the central regulator of the hypoxic response in tumor cells, is an attractive approach currently tested in preclinical models. For clinical applications, the appropriate combination of hypoxia detection for patient selection with a hypoxia-specific treatment is essential. A therapeutic benefit has been suggested for the selection of patients by plasma osteopontin level and treatment with the hypoxic radiosensitizer nimorazole in addition to radiotherapy, for selection by F-misonidazole positron-emission tomography (PET) and treatment with tirapazamine in addition to chemoradiation and for selection by pimonidazole immunohistochemistry and ARCON treatment, all in head and neck cancer.

  7. Addressing the challenges of cross-jurisdictional data linkage between a national clinical quality registry and government-held health data.

    PubMed

    Andrew, Nadine E; Sundararajan, Vijaya; Thrift, Amanda G; Kilkenny, Monique F; Katzenellenbogen, Judith; Flack, Felicity; Gattellari, Melina; Boyd, James H; Anderson, Phil; Grabsch, Brenda; Lannin, Natasha A; Johnston, Trisha; Chen, Ying; Cadilhac, Dominique A

    2016-10-01

    To describe the challenges of obtaining state and nationally held data for linkage to a non-government national clinical registry. We reviewed processes negotiated to achieve linkage between the Australian Stroke Clinical Registry (AuSCR), the National Death Index, and state held hospital data. Minutes from working group meetings, national workshop meetings, and documented communications with health department staff were reviewed and summarised. Time from first application to receipt of data was more than two years for most state data-sets. Several challenges were unique to linkages involving identifiable data from a non-government clinical registry. Concerns about consent, the re-identification of data, duality of data custodian roles and data ownership were raised. Requirements involved the development of data flow methods, separating roles and multiple governance and ethics approvals. Approval to link death data presented the fewest barriers. To our knowledge, this is the first time in Australia that person-level data from a clinical quality registry has been linked to hospital and mortality data across multiple Australian jurisdictions. Implications for Public Health: The administrative load of obtaining linked data makes projects such as this burdensome but not impossible. An improved national centralised strategy for data linkage in Australia is urgently needed. © 2016 Public Health Association of Australia.

  8. Commercial Insurance vs Community-Based Health Plans: Time for a Policy Option With Clinical Emphasis to Address the Cost Spiral

    ERIC Educational Resources Information Center

    Amundson, Bruce

    2005-01-01

    The nation continues its ceaseless struggle with the spiraling cost of health care. Previous efforts (regulation, competition, voluntary action) have included almost every strategy except clinical. Insurers have largely failed in their cost-containment efforts. There is a strong emerging body of literature that demonstrates the relationship…

  9. Commercial Insurance vs Community-Based Health Plans: Time for a Policy Option With Clinical Emphasis to Address the Cost Spiral

    ERIC Educational Resources Information Center

    Amundson, Bruce

    2005-01-01

    The nation continues its ceaseless struggle with the spiraling cost of health care. Previous efforts (regulation, competition, voluntary action) have included almost every strategy except clinical. Insurers have largely failed in their cost-containment efforts. There is a strong emerging body of literature that demonstrates the relationship…

  10. Addressing the expected survival benefit for clinical trial design in metastatic castration-resistant prostate cancer: Sensitivity analysis of randomized trials.

    PubMed

    Massari, Francesco; Modena, Alessandra; Ciccarese, Chiara; Pilotto, Sara; Maines, Francesca; Bracarda, Sergio; Sperduti, Isabella; Giannarelli, Diana; Carlini, Paolo; Santini, Daniele; Tortora, Giampaolo; Porta, Camillo; Bria, Emilio

    2016-02-01

    We performed a sensitivity analysis, cumulating all randomized clinical trials (RCTs) in which patients with metastatic castration-resistant prostate cancer (mCRPC) received systemic therapy, to evaluate if the comparison of RCTs may drive to biased survival estimations. An overall survival (OS) significant difference according to therapeutic strategy was more likely be determined in RCTs evaluating hormonal drugs versus those studies testing immunotherapy, chemotherapy or other strategies. With regard to control arm, an OS significant effect was found for placebo-controlled trials versus studies comparing experimental treatment with active therapies. Finally, regarding to docetaxel (DOC) timing, the OS benefit was more likely to be proved in Post-DOC setting in comparison with DOC and Pre-DOC. These data suggest that clinical trial design should take into account new benchmarks such as the type of treatment strategy, the choice of the comparator and the phase of the disease in relation to the administration of standard chemotherapy.

  11. The sensitivity and specificity of F-DOPA PET in a movement disorder clinic

    PubMed Central

    Ibrahim, Nevein; Kusmirek, Joanna; Struck, Aaron F; Floberg, John M; Perlman, Scott B; Gallagher, Catherine; Hall, Lance T

    2016-01-01

    Idiopathic Parkinson’s disease (PD) is the second most common neurodegenerative disorder. Early PD may present a diagnostic challenge with broad differential diagnoses that are not associated with nigral degeneration or striatal dopamine deficiency. Therefore, the early clinical diagnosis alone may not be accurate and this reinforces the importance of functional imaging targeting the pathophysiology of the disease process. 18F-DOPA L-6-[18F] fluoro-3,4-dihydroxyphenylalnine (18F-DOPA) is a positron emission tomography (PET) agent that measures the uptake of dopamine precursors for assessment of presynaptic dopaminergic integrity and has been shown to accurately reflect the monoaminergic disturbances in PD. In this study, we aim to illustrate our local experience to determine the accuracy of 18F-DOPA PET for diagnosis of PD. We studied a total of 27 patients. A retrospective analysis was carried out for all patients that underwent 18F-DOPA PET brain scan for motor symptoms suspicious for PD between 2001-2008. Both qualitative and semi-quantitative analyses of the scans were performed. The patient’s medical records were then assessed for length of follow-up, response to levodopa, clinical course of illness, and laterality of symptoms at time of 18F-DOPA PET. The eventual diagnosis by the referring neurologist, movement disorder specialist, was used as the reference standard for further analysis. Of the 28 scans, we found that one was a false negative, 20 were true positives, and 7 were true negatives. The resultant values are Sensitivity 95.4% (95% CI: 100%-75.3%), Specificity 100% (95% CI: 100%-59.0%), PPV 100% (95% CI 100%-80.7%), and NPV 87.5% (95% CI: 99.5%-50.5%). PMID:27069770

  12. Role of specific IgE in predicting the clinical course of lentil allergy in children.

    PubMed

    Yavuz, Suleyman T; Sahiner, Umit M; Buyuktiryaki, Betul; Tuncer, Ayfer; Yilmaz, Ebru A; Cavkaytar, Ozlem; Karabulut, Erdem; Sackesen, Cansin

    2013-06-01

    Legumes, and particularly lentils, are frequently consumed in Mediterranean, Middle Eastern, and some Asian countries. The aim of this study was to document the demographic features of children with lentil allergy and to determine the role of specific IgE (sIgE) in predicting the risk of clinical reactivity and disease persistence. Thirty children were enrolled. The diagnosis of lentil allergy was based on convincing history of symptoms or anaphylaxis after the ingestion of lentils, with positive skin tests and/or sIgE to lentils. To determine the diagnosis and prognosis of lentil allergy, 24 children were evaluated with food challenges. The median age at the onset of symptoms was 1.5 yr (0.9-2.3) (inter-quartile range). The most frequent symptoms were immediate cutaneous (97%) and respiratory (30%) reactions, whereas eight patients (27%) reported anaphylactic reactions. The median level of lentil sIgE at the time of diagnosis was 3 kU/l (1.2-9.6). Of the 24 challenges, 12 were positive. Fifteen patients (50%) outgrew the lentil allergy by the age of 3.5 (2.5-11) years. Children with an initial lentil sIgE < 4.9 kU/l had a significantly higher likelihood (68.4% vs. 18.2%) of outgrowing the lentil allergy than children with an initial lentil sIgE ≥ 4.9 k/l (p = 0.008). Our results suggest that sIgE levels may be important for predicting clinical reactivity and persistence of lentil allergy. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Specific medical conditions associated with clinically significant depressive symptoms in men.

    PubMed

    Atlantis, Evan; Lange, Kylie; Goldney, Robert D; Martin, Sean; Haren, Matthew T; Taylor, Anne; O'Loughlin, Peter D; Marshall, Villis; Tilley, Wayne; Wittert, Gary A

    2011-12-01

    To define specific medical conditions associated with clinically significant depressive symptoms in men. A cross-sectional study was conducted in a community-based sample of Australian men (N = 1,195, aged 35-80 years; for 2002-2005). Depression was defined by: (1) symptomatic depression (current symptoms) or (2) current prescription for antidepressant(s) or (3) previously diagnosed depression. Logistic regression was used to determine prevalence odds ratios (OR) for depression independently associated with an extensive range of demographic, lifestyle, and clinical factors. Adjusted population attributable risk (PAR%) estimates were also computed. Depression was significantly (ORs at P < 0.05) associated with previously diagnosed anxiety (12.0) and insomnia (4.4), not married (1.7), current smoker (1.7), low muscle strength tertile (1.7, P = 0.059), high triglycerides (1.6), high storage lower urinary tract symptoms (LUTS) tertile (1.8), past year general practitioner visits 5-9 (1.9), middle energy density tertile (0.4), and high systolic blood pressure (0.5). Significant PAR% estimates (at P < 0.05) were for previous anxiety (27.0%) and insomnia (16.1%), middle energy density tertile (-17.2%), high SBP (-23.5%), high triglycerides (15.2%), and high storage LUTS tertile (12.6%). Results strengthened when depression-related factors (previous anxiety and insomnia, psycholeptics, and cognition) were omitted, and became significant for CVD (OR 1.6; PAR 13.9%). Medical conditions associated with depression in men include high triglycerides, low muscle strength, CVD, and LUTS. Depressed men are likely to use health services frequently, be current smokers, not be married, eat unhealthily, and report previous diagnosis of anxiety and insomnia; which has important implications for clinicians managing male patients.

  14. Subgroup analyses in confirmatory clinical trials: time to be specific about their purposes.

    PubMed

    Tanniou, Julien; van der Tweel, Ingeborg; Teerenstra, Steven; Roes, Kit C B

    2016-02-18

    It is well recognized that treatment effects may not be homogeneous across the study population. Subgroup analyses constitute a fundamental step in the assessment of evidence from confirmatory (Phase III) clinical trials, where conclusions for the overall study population might not hold. Subgroup analyses can have different and distinct purposes, requiring specific design and analysis solutions. It is relevant to evaluate methodological developments in subgroup analyses against these purposes to guide health care professionals and regulators as well as to identify gaps in current methodology. We defined four purposes for subgroup analyses: (1) Investigate the consistency of treatment effects across subgroups of clinical importance, (2) Explore the treatment effect across different subgroups within an overall non-significant trial, (3) Evaluate safety profiles limited to one or a few subgroup(s), (4) Establish efficacy in the targeted subgroup when included in a confirmatory testing strategy of a single trial. We reviewed the methodology in line with this "purpose-based" framework. The review covered papers published between January 2005 and April 2015 and aimed to classify them in none, one or more of the aforementioned purposes. In total 1857 potentially eligible papers were identified. Forty-eight papers were selected and 20 additional relevant papers were identified from their references, leading to 68 papers in total. Nineteen were dedicated to purpose 1, 16 to purpose 4, one to purpose 2 and none to purpose 3. Seven papers were dedicated to more than one purpose, the 25 remaining could not be classified unambiguously. Purposes of the methods were often not specifically indicated, methods for subgroup analysis for safety purposes were almost absent and a multitude of diverse methods were developed for purpose (1). It is important that researchers developing methodology for subgroup analysis explicitly clarify the objectives of their methods in terms that can be

  15. A scalable architecture for incremental specification and maintenance of procedural and declarative clinical decision-support knowledge.

    PubMed

    Hatsek, Avner; Shahar, Yuval; Taieb-Maimon, Meirav; Shalom, Erez; Klimov, Denis; Lunenfeld, Eitan

    2010-01-01

    Clinical guidelines have been shown to improve the quality of medical care and to reduce its costs. However, most guidelines exist in a free-text representation and, without automation, are not sufficiently accessible to clinicians at the point of care. A prerequisite for automated guideline application is a machine-comprehensible representation of the guidelines. In this study, we designed and implemented a scalable architecture to support medical experts and knowledge engineers in specifying and maintaining the procedural and declarative aspects of clinical guideline knowledge, resulting in a machine comprehensible representation. The new framework significantly extends our previous work on the Digital electronic Guidelines Library (DeGeL) The current study designed and implemented a graphical framework for specification of declarative and procedural clinical knowledge, Gesher. We performed three different experiments to evaluate the functionality and usability of the major aspects of the new framework: Specification of procedural clinical knowledge, specification of declarative clinical knowledge, and exploration of a given clinical guideline. The subjects included clinicians and knowledge engineers (overall, 27 participants). The evaluations indicated high levels of completeness and correctness of the guideline specification process by both the clinicians and the knowledge engineers, although the best results, in the case of declarative-knowledge specification, were achieved by teams including a clinician and a knowledge engineer. The usability scores were high as well, although the clinicians' assessment was significantly lower than the assessment of the knowledge engineers.

  16. A Scalable Architecture for Incremental Specification and Maintenance of Procedural and Declarative Clinical Decision-Support Knowledge

    PubMed Central

    Hatsek, Avner; Shahar, Yuval; Taieb-Maimon, Meirav; Shalom, Erez; Klimov, Denis; Lunenfeld, Eitan

    2010-01-01

    Clinical guidelines have been shown to improve the quality of medical care and to reduce its costs. However, most guidelines exist in a free-text representation and, without automation, are not sufficiently accessible to clinicians at the point of care. A prerequisite for automated guideline application is a machine-comprehensible representation of the guidelines. In this study, we designed and implemented a scalable architecture to support medical experts and knowledge engineers in specifying and maintaining the procedural and declarative aspects of clinical guideline knowledge, resulting in a machine comprehensible representation. The new framework significantly extends our previous work on the Digital electronic Guidelines Library (DeGeL) The current study designed and implemented a graphical framework for specification of declarative and procedural clinical knowledge, Gesher. We performed three different experiments to evaluate the functionality and usability of the major aspects of the new framework: Specification of procedural clinical knowledge, specification of declarative clinical knowledge, and exploration of a given clinical guideline. The subjects included clinicians and knowledge engineers (overall, 27 participants). The evaluations indicated high levels of completeness and correctness of the guideline specification process by both the clinicians and the knowledge engineers, although the best results, in the case of declarative-knowledge specification, were achieved by teams including a clinician and a knowledge engineer. The usability scores were high as well, although the clinicians’ assessment was significantly lower than the assessment of the knowledge engineers. PMID:21611137

  17. Organ specific autoantibodies in preclinical and early clinical type 1 diabetes in Turkey.

    PubMed

    Erten, G; Gurol, A O; Deniz, G; Satman, I; Yilmaz, M T

    2007-01-01

    Type 1 diabetes mellitus (T1D) patients (G1; n=73) and first degree relatives with islet cell antibody (ICA) values of >or=10 JDF u twice or >or=20 JDF u one and loss of FPIR (G2; n=18) were screened for two other autoantibodies, anti-glutamic acid decarboxylase (GADA) and insulin autoantibodies (IAA), and for other organ-specific autoantibodies, anti-gastric parietal cell (anti-PCA) and anti-thyroid peroxidase (anti-TPO) as well. The two control groups consisted of healthy subjects (G3; n:55 and G4; n:13). In G1, positivity of ICA, GADA, IAA, anti-TPO and anti-PCA were 63%, 75.1%, 27.4%, 17.8% and 8.2%, respectively. In G2, positivity for GADA, IAA, anti-TPO and anti-PCA were 55.6%, 11.1%, 16.7% and 11.1%, respectively. None of the anti-TPO or anti-PCA positive cases had clinical or laboratory thyroid disease or pernicious anemia. Other organ specific antibodies, in case they accompany GADAand/or IAA in high risk individuals, result in higher risk for T1D. Moreover, this condition may indicate future potential for developing thyrogastric autoimmune diseases. In conclusion; autoantibodies are markers for autoimmune destruction in T1D, and for identification of subjects at risk for disease. Even at the time of diagnosis of T1D, screening for thyrogastric autoimmunity might be recommended for early detection of the relevant diseases.

  18. Clinical optimization of antigen specific modulation of type 1 diabetes with the plasmid DNA platform.

    PubMed

    Gottlieb, Peter; Utz, Paul J; Robinson, William; Steinman, Lawrence

    2013-12-01

    Some clinical trials in humans have aimed at modulation of type 1 diabetes (T1D) via alteration of the immune response to putative islet cell antigens, particularly proinsulin and insulin, glutamic acid decarboxylase and the peptide, DiaPep 277, derived from heat shock protein 60. The focus here is on development of a specially engineered DNA plasmid encoding proinsulin to treat T1D. The plasmid is engineered to turn off adaptive immunity to proinsulin. This approach yielded exciting results in a randomized placebo controlled trial in 80 adult patients with T1D. The implications of this trial are explored in regards to the potential for sparing inflammation in islets and thus allowing the functioning beta cells to recover and produce more insulin. Strategies to further strengthen the effects seen thus far with the tolerizing DNA plasmid to proinsulin will be elucidated. The DNA platform affords an opportunity for easy modifications. In addition standard exploration of dose levels, route of administration and frequency of dose are practical. Optimization of the effects seen to date on C-peptide and on depletion of proinsulin specific CD8 T cells are feasible, with expected concomitant improvement in other parameters like hemoglobin A1c and reduction in insulin usage. T1D is one of the few autoimmune conditions where antigen specific therapy can be achieved, provided the approach is tested intelligently. Tolerizing DNA vaccines to proinsulin and other islet cell autoantigens is a worthy pursuit to potentially treat, prevent and to perhaps even 'cure' or 'prevent' type 1 diabetes.

  19. Specificity of Incident Diagnostic Outcomes in Patients at Clinical High Risk for Psychosis

    PubMed Central

    Webb, Jadon R.; Addington, Jean; Perkins, Diana O.; Bearden, Carrie E.; Cadenhead, Kristin S.; Cannon, Tyrone D.; Cornblatt, Barbara A.; Heinssen, Robert K.; Seidman, Larry J.; Tarbox, Sarah I.; Tsuang, Ming T.; Walker, Elaine F.; McGlashan, Thomas H.; Woods, Scott W.

    2015-01-01

    It is not well established whether the incident outcomes of the clinical high-risk (CHR) syndrome for psychosis are diagnostically specific for psychosis or whether CHR patients also are at elevated risk for a variety of nonpsychotic disorders. We collected 2 samples (NAPLS-1, PREDICT) that contained CHR patients and a control group who responded to CHR recruitment efforts but did not meet CHR criteria on interview (help-seeking comparison patients [HSC]). Incident diagnostic outcomes were defined as the occurrence of a SIPS-defined psychosis or a structured interview diagnosis from 1 of 3 nonpsychotic Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) groups (anxiety, bipolar, or nonbipolar mood disorder), when no diagnosis in that group was present at baseline. Logistic regression revealed that the CHR vs HSC effect did not vary significantly across study for any emergent diagnostic outcome; data from the 2 studies were therefore combined. CHR (n = 271) vs HSC (n = 171) emergent outcomes were: psychosis 19.6% vs 1.8%, bipolar disorders 1.1% vs 1.2%, nonbipolar mood disorders 4.4% vs 5.3%, and anxiety disorders 5.2% vs 5.3%. The main effect of CHR vs HSC was statistically significant (OR = 13.8, 95% CI 4.2–45.0, df = 1, P < .001) for emergent psychosis but not for any emergent nonpsychotic disorder. Sensitivity analyses confirmed these findings. Within the CHR group emergent psychosis was significantly more likely than each nonpsychotic DSM-IV emergent disorder, and within the HSC group emergent psychosis was significantly less likely than most emergent nonpsychotic disorders. The CHR syndrome is specific as a marker for research on predictors and mechanisms of developing psychosis. PMID:26272875

  20. [Gender medicine. Sex- and gender-specific aspects of clinical medicine].

    PubMed

    Kautzky-Willer, A

    2014-09-01

    Gender medicine studies sex- and gender-based differences in the development and prevention of diseases, the awareness and presentation of symptoms, and the effectiveness of therapy. Gender medicine is part of personalized medicine, considering differences in biological and psychosocial factors individually. There are differences in genes, chromosomes, hormones, and metabolism as well as differences in culture, environment, and society. Lifelong interactions between physical and psychosocial factors will influence the health and ill-health of men and women in different ways. Epigenetic modifications provide evidence of the impact of environment and lifestyle during vulnerable phases on biological processes, effecting future generations. Maternal lifestyle and environmental factors during pregnancy can impact the health of offspring in later life already in utero in a sex-specific way. Pain, stress, and coping styles differ between men and women. Women experience more dramatic physical changes during their lifetime, which are associated with specific burdens and psychosocial alterations. Women with multiple roles and responsibilities suffering from stress develop depression more frequently. However, men are often not diagnosed and treated appropriately in cases of depression or osteoporosis, diseases that are typically considered "female." There are prominent differences between men and women in medicine regarding the immune system, inflammation, and noncommunicable diseases such as obesity, type 2 diabetes, hypertension, and cardiovascular disease. Women experience more often autoimmune diseases and suffer more frequently from (chronic) pain, neurodegenerative changes, and functional disabilities. Men have shorter life expectancy but relatively more healthy years of life, which is in greater part ascribed to psychosocial determinants. State-of-the-art clinical medicine comprises individual risk factors based on sex- and gender-sensitive health programs in order to

  1. Clinical relevance of HLA donor-specific antibodies detected by single antigen assay in kidney transplantation.

    PubMed

    Caro-Oleas, José Luis; González-Escribano, María Francisca; González-Roncero, Francisco Manuel; Acevedo-Calado, María José; Cabello-Chaves, Virginia; Gentil-Govantes, Miguel Ángel; Núñez-Roldán, Antonio

    2012-03-01

    Clinical relevance of donor-specific antibodies (DSAs) detected by a single antigen Luminex virtual crossmatch in pre-transplant serum samples from patients with a negative cytotoxicity-dependent complement crossmatch is controversial. The aim of this study was to analyse the influence of a pre-transplant positive virtual crossmatch in the outcome of kidney transplantation. A total of 892 patients who received a graft from deceased donors after a negative cytotoxicity crossmatch were included. Presence of anti-human leucocyte antigen (HLA) antibodies was investigated using a Luminex screening assay and anti-HLA specificities were assigned performing a Luminex single antigen assay. Graft survival was significantly worse among patients with anti-HLA DSA compared to both patients with anti-HLA with no DSA (P = 0.001) and patients without HLA antibodies (P < 0.001) using a log-rank test. No graft survival differences between anti-HLA with no DSA and no HLA antibodies patient groups were observed (P = 0.595). Influence of both anti-Class I and anti-Class II DSA was detected (P < 0.0001 in both cases). When the fluorescence values were stratified in four groups, no significant differences in graft survival were observed among the groups with fluorescence levels >1500 (global P > 0.05). The presence of preformed HLA DSA in transplanted patients with a negative cytotoxicity crossmatch is associated with a lower allograft survival. The detection of anti-HLA with no DSA has no influence in the graft outcome. Finally, there were no demonstrable effects of mean fluorescence intensity (MFI) values >1500 on graft survival.

  2. Impact on the dermatology educational experience of medical students with the introduction of online teaching support modules to help address the reduction in clinical teaching.

    PubMed

    Singh, Daram G; Boudville, Neil; Corderoy, Robert; Ralston, Sue; Tait, Clare P

    2011-11-01

    With increasing medical student numbers and decreasing clinical teaching opportunities, there has been a need to develop alternative learning resources. The aim of this study was to examine the effectiveness of a new dermatology online teaching resource, from a student perspective. The Australasian College of Dermatologists developed an undergraduate dermatology curriculum and subsequently created online teaching modules in partnership with the University of Sydney. These modules were introduced to final year medical students at the University of Western Australia in 2010. The dermatology learning experiences of these 142 students were compared with the 2009 medical student cohort who did not have access to this resource. A self-administered questionnaire, with a 5-point rating scale, was used. The 2010 cohort described an improved educational experience using the online modules. Despite a reduction in the number of clinics attended, knowledge and skills gained were scored higher among the 2010 cohort. The student's confidence in their ability to manage common dermatological conditions was also statistically higher in the cohort with the online teaching resource. The learning experience for dermatology compared to other subspecialty teaching in medical school was ranked as a significantly more positive experience in the 2010 cohort. Our results suggest that the introduction of the online modules described in this paper to support learning have improved the perceived educational experience of medical students and should be incorporated as a way to improve student teaching in the face of reduced clinic teaching. © 2011 The Authors. Australasian Journal of Dermatology © 2011 The Australasian College of Dermatologists.

  3. Implementation of an intern boot camp curriculum to address clinical competencies under the new Accreditation Council for Graduate Medical Education supervision requirements and duty hour restrictions.

    PubMed

    Krajewski, Aleksandra; Filippa, Dawn; Staff, Ilene; Singh, Rekha; Kirton, Orlando C

    2013-08-01

    Today's general surgery interns are faced with increased duty hour restrictions and stringent competency-based supervision milestone requirements (ie, from direct to indirect supervision). Working within these constraints, we instituted a unique 2-month intern curriculum (boot camp) incorporating knowledge-based, experiential, and practical components. To describe our curriculum and the effect on resident performance and teaching faculty and nursing staff perceptions. All interns underwent a 2-month (July and August 2011) boot camp curriculum consisting of two 2½-hour knowledge-based and procedural skills (SimMan) didactic sessions per week and completion of 25 core intensive introductory American College of Surgeons Fundamentals of Surgery web-based self-study modules, followed by a standardized patient clinical skills assessment. Integrated general surgery residency program at the University of Connecticut School of Medicine, Farmington. Postgraduate year 1 general surgery categorical and preliminary residents. We used several assessment tools, including an intern boot camp survey, clinical skills assessment scores, intern American Board of Surgeons In-Training Examination scores, and nursing staff and teaching faculty surveys of intern performance and aptitudes compared with the previous year's interns. Data were analyzed by independent group t test, χ2 tests of proportions, and Fisher exact test for small sample cross tables. In total, 84% (91 of 108) of intern respondents agreed or strongly agreed with the usefulness, relevance, and execution of the boot camp. Compared with the previous year's interns, the nursing staff agreed or strongly agreed that the cohort interns were better at patient assessment, collaboration, and effective communication and provided compassionate and respectful patient care. More than 40% (7 of 17) of surveyed teaching faculty agreed or strongly agreed that the cohort interns demonstrated better patient care and procedural skills

  4. [Clinical evaluation of calcium-polycarbophil in the treatment of non-specific diarrhea].

    PubMed

    Gizzi, G; Villani, V; Rubinetto, M P; Cianci, M; La Froscia, A; Barbara, L

    1993-09-01

    We performed a study on 10 patients aged between 26 and 54 males and females, affected by non-specific diarrhea. A single-blind clinical trial has been developed where Calcium-Polycarbophil was administered (2 cps t.i.d.) for a period of 8 weeks, half with placebo and half with drug in cross-over. No drop-out occurred. Number of evaluations, cramps and consistency of stools, have been evaluated before and after treatment. A definite decrease of evacuations per day and of cramps, when present, together with a higher consistency of stools, are reported when Calcium-Polycarbophil is administered, according to the favourable medical judgement. Haematochemical parameters, evaluated before, during and after the treatment didn't show any relevant variation, apart from slight increase (not statistically significant) of calcium both in blood and in urine). No other unwanted event has been detected. Hence, the high therapeutic index of Calcium-Polycarbophil makes it highly desirable in the treatment of diarrhea.

  5. Tolerance limits for short-term analytical bias and analytical imprecision derived from clinical assay specificity.

    PubMed

    Klee, G G

    1993-07-01

    I propose a method for defining tolerance limits for assay bias and assay imprecision, based on the effects of these tolerance limits on the clinical specificity of the assay. An analytical "error budget" is defined as the squared sums of the imprecision and bias errors. The maximum limit for this error budget is set at a value corresponding to a 50% increase in the false-positive rate for classifying healthy subjects. For gaussian distributions with +/- 2 SD used as decision limits, this error budget equates to 0.45 SD of combined within-person and between-person biological variation (SDBiol). To provide reasonable power for bias detection in an assay, I recommend that the SD of the assay be kept at less than half the bias limit. Then, for the gaussian distribution, the maximum bias limit should be < 0.36 SDBiol and the SD of the assay should be < 0.18 SDBiol. Procedures are provided for using the same principles to define tolerance limits for decision limits other than +/- 2 SD and for nongaussian distributions.

  6. The angiosome concept in clinical practice: implications for patient-specific recanalization procedures.

    PubMed

    Brodmann, M

    2013-10-01

    Below-the-knee (BTK) disease with the clinical presentation of critical limb ischemia is associated with a high rate of limb loss due to minor and major amputations. The main problem is to find a way to optimize blood flow to the critical limb area. BTK joint the down-stream diverges into 3 arms which supply different areas. Different concepts exist how optimal blood flow to the critical ischemic areas BTK can be achieved, either by treating as many vessels as can be reopened by an endovascular procedure, or by going for the two main BTK vessels, or in an outstanding situation also to treat the inflow of collaterals to achieve as much blood flow down the foot as possible. Derived from plastic surgery for the purpose of healing of flaps, the angiosome concept has been developed. An angiosome is an anatomic unit of tissue (consisting of skin, subcutaneous tissue, fascia, muscle and bone) fed by a source artery and drained by specific veins. From that point of view it can be presumed that revascularization of the source artery to the angiosome might result in better wound healing and limb salvage rates. The angiosome treatment concept of BTK disease refers to the concept in cardiology, where discrimination of reversible ischemia areas is made and respective vessels leading to these areas are treated in a distinctive way.

  7. Specific clinical manifestations of Nocardia: A case report and literature review

    PubMed Central

    Yu, Songsong; Wang, Jing; Fang, Qiuhong; Zhang, Jixin; Yan, Fengcai

    2016-01-01

    Nocardiosis is a rare bacterial infection of either the lungs (pulmonary) or body (systemic) that usually affects immunocompromised individuals. It is caused by Gram-positive, aerobic actinomycetes of the Nocardia genus. Multiple high-density sheet shadows in both lungs along with nodules or cavities are the most common presentations of nocardiosis, whereas a large pulmonary mass is considered to be rare. However, there is no specificity in the clinical manifestation of the disease. Therefore, isolation and identification of Nocardia strains is the only reliable diagnostic method. The present study describes the cases of two male patients of Asian descent with nocardiosis. Chest computed tomography scans showed a suspected tumor mass in both patients. Microscopic analysis and culturing of tissue samples obtained using a bronchoscope detected the presence of Nocardia wallacei. Neither patient showed signs of immunosuppression. The present study aimed to improve the understanding of lung nocardiosis and demonstrated that pulmonary nocardiosis should be suspected in the case of non-immunocompromised patients with a large mass in the lung. Furthermore, a review of the literature on infection with Nocardia was conducted. PMID:27698688

  8. Expression and clinical significance of placenta-specific 1 in pancreatic ductal adenocarcinoma.

    PubMed

    Yin, Yin; Zhu, Xu; Huang, Shanshan; Zheng, Jiawei; Zhang, Mengyun; Kong, Wencui; Chen, Qun; Zhang, Yan; Chen, Xiong; Lin, Kerong; Ouyang, Xuenong

    2017-06-01

    The limited efficacy of conventional therapies for pancreatic ductal adenocarcinoma has led to the growing interest for identifying potential antigenic targets for immunotherapy. Placenta-specific 1 (PLAC1) is a new member of cancer-testis antigens with restricted expression in normal tissues. Ectopic activation of PLAC1 has been found in different types of cancers, but its role in pancreatic ductal adenocarcinoma remains unknown. This study evaluated the protein expression of PLAC1 and its clinical significance in pancreatic ductal adenocarcinoma. We examined PLAC1 expression in 93 pancreatic ductal adenocarcinoma samples by immunohistochemistry. The expression of PLAC1 was detected in 41 (44.1%) patients. Among patients' clinicopathological characteristics, PLAC1 expression was only significantly correlated with tumor differentiation (p = 0.028). Univariate analysis revealed that PLAC1 expression (p = 0.016) and tumor differentiation (p = 0.003) were significantly correlated with poor survival in the whole cohort. Subgroup analysis showed that PLAC1 expression was an independent prognostic biomarker in the perineural invasion positive subgroup (p < 0.05). This study demonstrated that the protein expression of PLAC1 was significantly associated with decreased overall survival in patients with pancreatic ductal adenocarcinoma, indicating that it was a valuable prognostic marker for pancreatic ductal adenocarcinoma and might be a potential target for immunotherapy.

  9. Type-specific human papillomavirus infections among young heterosexual male and female STI clinic attendees.

    PubMed

    Vriend, Henrike J; Boot, Hein J; van der Sande, Marianne A B

    2012-01-01

    Baseline genotype-specific human papillomavirus (HPV) prevalence rates and associated risk factors per gender enable future assessment of the impact of vaccination on HPV dynamics. Before the start of national HPV vaccination for girls, data were collected cross-sectionally in nationwide Dutch sexually transmitted infections (STI) clinics among heterosexual males (n = 430) and females (n = 1136) aged 16 to 24 years. Self-collected vaginal or penile swabs were analyzed by a sensitive polymerase chain reaction (SPF10) and genotyped with line probe assay. Logistic regression was applied to estimate determinants of HPV prevalent infections. HPV prevalence was 54% among males and 72% among females. High-risk (HR) HPV was present in males and females, 40% and 58%, respectively. Independent risk factors for HR-HPV infection were female gender, number of lifetime sex partners and a history of chlamydia or gonorrhea. In addition, not having a casual partner and consistent condom use were protective factors in women, but not in men. For low-risk (LR) HPV, the odds were smaller. Multiple HR-HPV and sexual risk behavior showed a stronger association compared with a single HR-HPV infection. Prevalence of HR-HPV is high in both genders. Infection with multiple HR-HPV types was more associated with high-risk sexual behavior than infection with LR-HPV types or a single HR-HPV type.

  10. Further evidence on the validity of the MMPI-2 Restructured Clinical (RC) Scales: addressing questions raised by Rogers, Sewell, Harrison, and Jordan and Nichols.

    PubMed

    Tellegen, Auke; Ben-Porath, Yossef S; Sellbom, Martin; Arbisi, Paul A; McNulty, John L; Graham, John R

    2006-10-01

    The reviews by Rogers, Sewell, Harrison, and Jordan (2006/this issue), and by Nichols (2006/this issue) offer markedly contrasting appraisals of the MMPI-2 Restructured Clinical (RC) Scales introduced by Tellegen et al. (2003). The one common feature is that both reviews draw on the same atypical MMPI-2 (Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989) data set for their empirical analyses, with results warranting critical scrutiny. Rogers et al.'s critique provides an evaluation of the RC Scales from the perspective of Jackson's (1970) method of test development. One significant issue in Rogers et al.'s review concerns social desirability, prompting us to clarify our own views on this topic. We also highlight and discuss problems associated with Rogers et al.'s use of the unrepresentative data set. Nichols's polemical critique neglects empirical and theoretical support for demoralization as a central construct and misconstrues as "construct drift" the purposeful process of developing the RC scales. Nichols's criticisms and proposals overlook requirements for assessing syndromes and for construct validation and even rudiments of scale development. Our reply incorporates evidence, including new findings, refuting his criticisms and confirming that demoralization is a pervasive MMPI dimension, that the RC Scales capture the major distinctive features of the original Clinical Scales, and that they generate correspondingly meaningful validity patterns.

  11. Knowledge creation through total clinical outcomes management: a practice-based evidence solution to address some of the challenges of knowledge translation.

    PubMed

    Lyons, John S

    2009-02-01

    The challenges of knowledge translation in behavioural health care are unique to this field for a variety of reasons including the fact that effective treatment is invariably embedded in a strong relationship between practitioners and the people they serve. Practitioners' knowledge gained from experience and intuition become an even more important consideration in the knowledge translation process since clinicians are, in fact, a component of most treatments. Communication of findings from science must be conceptualized with sensitivity to this reality. Considering knowledge translation as a communication process suggests the application of contemporary theories of communication which emphasize the creation of shared meaning over the transmission of knowledge from one person to the next. In this context outcomes management approaches to create a learning environment within clinical practices that facilitate the goals of knowledge transfer while respecting that the scientific enterprise is neither the sole nor primary repository of knowledge.

  12. Knowledge Creation through Total Clinical Outcomes Management: A Practice-Based Evidence Solution to Address Some of the Challenges of Knowledge Translation

    PubMed Central

    Lyons, John S.

    2009-01-01

    Introduction The challenges of knowledge translation in behavioural health care are unique to this field for a variety of reasons including the fact that effective treatment is invariably embedded in a strong relationship between practitioners and the people they serve. Methods Practitioners’ knowledge gained from experience and intuition become an even more important consideration in the knowledge translation process since clinicians are, in fact, a component of most treatments. Communication of findings from science must be conceptualized with sensitivity to this reality. Results Considering knowledge translation as a communication process suggests the application of contemporary theories of communication which emphasize the creation of shared meaning over the transmission of knowledge from one person to the next. Conclusion In this context outcomes management approaches to create a learning environment within clinical practices that facilitate the goals of knowledge transfer while respecting that the scientific enterprise is neither the sole nor primary repository of knowledge. PMID:19270847

  13. Addressing the shortage of health professionals in South Africa through the development of a new cadre of health worker: the creation of Clinical Associates.

    PubMed

    Couper, Ian D; Hugo, Jannie F M

    2014-01-01

    South Africa made a decision in 2002 to develop so-called mid-level medical workers, now known as clinical associates. This article describes the background to this decision, and the national process of developing the profession and its scope of practice, which was aligned with the needs of the health service, particularly those of rural district hospitals. A common national curriculum was then developed, with implementation in three faculties. The first graduates have entered the profession, starting in 2011, and are in the process of establishing themselves across the country. They are already making an important contribution to rural health care, and are seeking ways in which the profession can be enhanced to ensure sustainability. The profession needs to adapt itself to the changing realities of the South African context.

  14. Addressing Health Disparities among Men: Demographic, Behavioral and Clinical Characteristics of Men who have Sex with Men Living in Puerto Rico

    PubMed Central

    Colón-López, Vivian; Soto-Salgado, Marievelisse; Rodríguez-Díaz, Carlos; Suárez, Erick L.; Pérez, Cynthia M.

    2013-01-01

    The objective of this study was to compare sociodemographic, behavioral and clinical characteristics associated with HIV among Men who have sex with Men (MSM) and men who have sex with women (MSW) in Puerto Rico. Data from a population-based cross-sectional study in PR (2005–2008) was analyzed. Descriptive statistics were used to describe the study sample and bivariate analyses were performed to identify differences of sociodemographic, behavioral and clinical characteristics between MSM and MSW. Exact logistic regression models adjusting for age were constructed for each risk behavior associated to MSM in bivariate analysis. Of the 674 men interviewed, 6.1% (n=41) reported ever having sex with men. Age-adjusted logistic regression models indicated that MSM were significantly more likely than MSW to have first sexual intercourse before the age of 15 (POR=2.6; 95%CI= 1.3, 5.3) and have at least 10 lifetime sex partners (POR=2.8; 95%CI= 1.4,5.9). Also, MSM were significantly more likely to report lifetime use of marihuana (POR=2.7; 95%CI= 1.3,5.8), cocaine (POR=2.5; 95%CI= 1.2,5.0), amphetamines (POR=3.8; 95%CI= 1.4,9.2) and sedatives or tranquilizers (POR=3.3; 95%CI= 1.4,7.2). Also, MSM were 13 times more likely to be HIV seropositive as compared to MSW (POR=13.3; 95%CI=1.7,102.0). In this population-based sample of men living in Puerto Rico, self-reported same-sex behavior is strongly associated with HIV, and other behavioral factors associated with HIV. Future targeted research is still necessary for the development of intervention programs among MSM in Puerto Rico. PMID:24288521

  15. The clinical and cost burden of coronary calcification in a Medicare cohort: An economic model to address under-reporting and misclassification.

    PubMed

    Garrison, Louis P; Lewin, Jack; Young, Christopher H; Généreux, Philippe; Crittendon, Janna; Mann, Marita R; Brindis, Ralph G

    2015-01-01

    Coronary artery calcification (CAC) is a well-established risk factor for the occurrence of adverse ischemic events. However, the economic impact of the presence of CAC is unknown. Through an economic model analysis, we sought to estimate the incremental impact of CAC on medical care costs and patient mortality for de novo percutaneous coronary intervention (PCI) patients in the 2012 cohort of the Medicare elderly (≥65) population. This aggregate burden-of-illness study is incidence-based, focusing on cost and survival outcomes for an annual Medicare cohort based on the recently introduced ICD9 code for CAC. The cost analysis uses a one-year horizon, and the survival analysis considers lost life years and their economic value. For calendar year 2012, an estimated 200,945 index (de novo) PCI procedures were performed in this cohort. An estimated 16,000 Medicare beneficiaries (7.9%) were projected to have had severe CAC, generating an additional cost in the first year following their PCI of $3500, on average, or $56 million in total. In terms of mortality, the model projects that an additional 397 deaths would be attributable to severe CAC in 2012, resulting in 3770 lost life years, representing an estimated loss of about $377 million, when valuing lost life years at $100,000 each. These model-based CAC estimates, considering both moderate and severe CAC patients, suggest an annual burden of illness approaching $1.3 billion in this PCI cohort. The potential clinical and cost consequences of CAC warrant additional clinical and economic attention not only on PCI strategies for particular patients but also on reporting and coding to achieve better evidence-based decision-making. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Clinical research: up from 'clinical epidemiology'.

    PubMed

    Miettinen, Olli S; Bachmann, Lucas M; Steurer, Johann

    2009-12-01

    Clinical research must be understood to be the foundation of scientific medicine of the clinical type. But the essence of scientific clinical medicine remains a matter of profound confusion, even in clinical academia, and so does the essence of clinical research. The confusion now revolves, principally, around 'clinical epidemiology'. We address clinical research in the meaning of quintessentially 'applied' clinical research, which we take to be the foundation of the scientific knowledge base of clinical medicine, of gnosis (dia-, etio-, pro-) in it. More specifically, we address the essence, priorities, and status quo of this research - and argue that the requisite theory of this is not a matter of 'clinical epidemiology' but of theory of clinical research endogenous to clinical (rather than epidemiological) academia.

  17. Factors associated with specific uropathogens in catheter-associated urinary tract infection: developing a clinical prediction model.

    PubMed

    Oh, Won Sup; Hur, Ji-An; Kim, Eu Suk; Park, Kyung-Hwa; Choi, Hee Kyoung; Moon, Chisook; Kim, Baek-Nam

    2014-12-01

    To identify characteristics associated with particular groups of uropathogens in catheter-associated urinary tract infection (CA-UTI) and to develop clinical prediction rules for identifying these groups. Demographic, clinical and microbiological data were analysed from patients with CA-UTI. Infections were categorized into enteric Gram-negative rods, nonfermenters, Gram-positive cocci and fungal. Variables were analysed using univariate and multiple logistic regression analyses, and were used to develop clinical prediction rules. A total of 492 patients were included in the study. Candida species were the most common uropathogens (30.7%), followed by enterococci (17.3%), Escherichia coli (12.0%), Pseudomonas spp. (10.8%), Klebsiella spp. (7.9%) and staphylococci (6.5%). Clinical prediction rules for the bacterial uropathogenic groups showed poor-to-fair discriminatory power, with sensitivities of <40% and specificities of >90%. However, clinical prediction rules showed good discriminatory power for fungal infections, with a sensitivity of 67.3% and a specificity of 78.1%. Clinical prediction rules developed for identifying specific groups of bacterial uropathogens in patients with CA-UTI had a low sensitivity, whereas those for fungal infections showed good discriminatory power. Further studies to develop more refined and sensitive tools for predicting specific bacterial uropathogens in CA-UTI are warranted. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  18. Clinical evaluation of an anatomy-based patient specific quality assurance system.

    PubMed

    Hauri, Pascal; Verlaan, Sarah; Graydon, Shaun; Ahnen, Linda; Klöck, Stephan; Lang, Stephanie

    2014-03-06

    The Delta(4DVH) Anatomy 3D quality assurance (QA) system (ScandiDos), which converts the measured detector dose into the dose distribution in the patient geometry was evaluated. It allows a direct comparison of the calculated 3D dose with the measured back-projected dose. In total, 16 static and 16 volumetric-modulated arc therapy (VMAT) fields were planned using four different energies. Isocenter dose was measured with a pinpoint chamber in homogeneous phantoms to investigate the dose prediction by the Delta(4DVH) Anatomy algorithm for static fields. Dose distributions of VMAT fields were measured using GAFCHROMIC film. Gravitational gantry errors up to 10° were introduced into all VMAT plans to study the potential of detecting errors. Additionally, 20 clinical treatment plans were verified. For static fields, the Delta(4DVH) Anatomy predicted the isocenter dose accurately, with a deviation to the measured phantom dose of 1.1% ± 0.6%. For VMAT fields the predicted Delta(4DVH) Anatomy dose in the isocenter plane corresponded to the measured dose in the phantom, with an average gamma agreement index (GAI) (3 mm/3%) of 96.9± 0.4%. The Delta(4DVH) Anatomy detected the induced systematic gantry error of 10° with a relative GAI (3 mm/3%) change of 5.8% ± 1.6%. The conventional Delta(4PT) QA system detected a GAI change of 4.2%± 2.0%. The conventional Delta(4PT) GAI (3 mm/3%) was 99.8% ± 0.4% for the clinical treatment plans. The mean body and PTV-GAI (3 mm/5%) for the Delta(4DVH) Anatomy were 96.4% ± 2.0% and 97.7%± 1.8%; however, this dropped to 90.8%± 3.4% and 87.1% ± 4.1% for passing criteria of 3 mm/3%. The anatomy-based patient specific quality assurance system predicts the dose distribution correctly for a homogeneous case. The limiting factor for the error detection is the large variability in the error-free plans. The dose calculation algorithm is inferior to that used in the TPS (Eclipse).

  19. Effects of pathogen-specific clinical mastitis on probability of conception in Holstein dairy cows.

    PubMed

    Hertl, J A; Schukken, Y H; Welcome, F L; Tauer, L W; Gröhn, Y T

    2014-11-01

    The objective of this study was to estimate the effects of pathogen-specific clinical mastitis (CM), occurring in different weekly intervals before or after artificial insemination (AI), on the probability of conception in Holstein cows. Clinical mastitis occurring in weekly intervals from 6 wk before until 6 wk after AI was modeled. The first 4 AI in a cow's lactation were included. The following categories of pathogens were studied: Streptococcus spp. (comprising Streptococcus dysgalactiae, Streptococcus uberis, and other Streptococcus spp.); Staphylococcus aureus; coagulase-negative staphylococci (CNS); Escherichia coli; Klebsiella spp.; cases with CM signs but no bacterial growth (above the level that can be detected from our microbiological procedures) observed in the culture sample and cases with contamination (≥ 3 pathogens in the sample); and other pathogens [including Citrobacter, yeasts, Trueperella pyogenes, gram-negative bacilli (i.e., gram-negative organisms other than E. coli, Klebsiella spp., Enterobacter, and Citrobacter), Corynebacterium bovis, Corynebacterium spp., Pasteurella, Enterococcus, Pseudomonas, Mycoplasma, Prototheca, and others]. Other factors included in the model were parity (1, 2, 3, 4 and higher), season of AI (winter, spring, summer, autumn), day in lactation of first AI, farm, and other non-CM diseases (retained placenta, metritis, ketosis, displaced abomasum). Data from 90,271 AI in 39,361 lactations in 20,328 cows collected from 2003/2004 to 2011 from 5 New York State dairy farms were analyzed in a generalized linear mixed model with a Poisson distribution. The largest reductions in probability of conception were associated with CM occurring in the week before AI or in the 2 wk following AI. Escherichia coli and Klebsiella spp. had the greatest adverse effects on probability of conception. The probability of conception for a cow with any combination of characteristics may be calculated based on the parameter estimates. These

  20. Pathogen-specific effects on milk yield in repeated clinical mastitis episodes in Holstein dairy cows.

    PubMed

    Hertl, J A; Schukken, Y H; Welcome, F L; Tauer, L W; Gröhn, Y T

    2014-03-01

    The objective of this study was to estimate the effects of clinical mastitis (CM) cases due to different pathogens on milk yield in Holstein cows. The first 3 CM cases in a cow's lactation were modeled. Eight categories of pathogens were included: Streptococcus spp.; Staphylococcus aureus; coagulase-negative staphylococci (CNS); Escherichia coli; Klebsiella spp.; cases with CM signs but no bacterial growth (above the level detectable by our microbiological procedures) observed in the culture sample, and cases with contamination (≥ 3 pathogens in the sample); other pathogens that may be treated with antibiotics (included Citrobacter, Corynebacterium bovis, Enterobacter, Enterococcus, Pasteurella, Pseudomonas; "other treatable"); and other pathogens not successfully treated with antibiotics (Trueperella pyogenes, Mycoplasma, Prototheca, yeasts; "other not treatable"). Data from 38,276 lactations in cows from 5 New York State dairy herds, collected from 2003-2004 until 2011, were analyzed. Mixed models with an autoregressive correlation structure (to account for correlation among the repeated measures of milk yield within a lactation) were estimated. Primiparous (lactation 1) and multiparous (lactations 2 and 3) cows were analyzed separately, as the shapes of their lactation curves differed. Primiparas were followed for up to 48 wk of lactation and multiparas for up to 44 wk. Fixed effects included parity, calving season, week of lactation, CM (type, case number, and timing of CM in relation to milk production cycle), and other diseases (milk fever, retained placenta, metritis, ketosis, displaced abomasum). Herd was modeled as a random effect. Clinical mastitis was more common in multiparas than in primiparas. In primiparas, Streptococcus spp. occurred most frequently as the first case. In multiparas, E. coli was most common as the first case. In subsequent cases, CM cases with no specific growth or contamination were most common in both parity groups. The hazard of

  1. A Simple Dietary Questionnaire Correlates With Formal Dietitian Evaluation and Frequently Identifies Specific Clinical Interventions in an Outpatient Gastroenterology Clinic.

    PubMed

    Dubin, Sterling M; Vadivelu, Jaya; Copur-Dahi, Nedret; Miranda, Leslie; Palermo, Dana; Pandey, Braj; Groessl, Erik J; Ho, Samuel B

    2016-09-01

    The spectrum of gastroenterology-related diseases related to obesity is growing. Few clinical tools exist to aid in clinician-guided dietary counseling. (1) Develop and validate a 1-page diet history form that would provide information on dietary factors that can contribute to gastrointestinal (GI) illness and to assess adherence to the Mediterranean diet; and (2) evaluate the form in a general GI clinic to determine its potential utility as a clinical tool. A 1-page diet history form was developed and underwent qualitative and quantitative validation in comparison to a formal diet evaluation by a registered dietitian. The form was then evaluated in consecutive patients attending a general GI clinic, and analyzed for overall diet content, compliance with a Mediterranean diet, and presence of high-risk (red flag) dietary behaviors. The form was evaluated in 134 patients. In a validation cohort (n=30) the qualitative dietary components measured were highly concordant with a formal dietary interview. Total daily calorie intake correlated with formal dietary review (R=0.61), but tended to underestimate total calories due to less precision in portion size. The prospective cohort (n=104) patients had a mean body mass index of 29.8. Overall, 52.9% were obese, 50% had metabolic syndrome, and 51% had a primary GI illness directly impacted by dietary factors (gastroesophageal reflux, irritable bowel, fatty liver). Overall, 85.6% of patients documented red flag behaviors. Patients with obesity trended for more red flags than overweight or normal body mass index groups. A 1-page diet questionnaire correlated well with formal dietary assessment and identified clinically relevant dietary interventions in a high percentage of GI patients.

  2. Critical differences in HIV-1 and HIV-2 protease specificity for clinical inhibitors

    SciTech Connect

    Tie, Yunfeng; Wang, Yuan-Fang; Boross, Peter I.; Chiu, Ting-Yi; Ghosh, Arun K.; Tozser, Jozsef; Louis, John M.; Harrison, Robert W.; Weber, Irene T.

    2012-03-15

    Clinical inhibitor amprenavir (APV) is less effective on HIV-2 protease (PR{sub 2}) than on HIV-1 protease (PR{sub 1}). We solved the crystal structure of PR{sub 2} with APV at 1.5 {angstrom} resolution to identify structural changes associated with the lowered inhibition. Furthermore, we analyzed the PR{sub 1} mutant (PR{sub 1M}) with substitutions V32I, I47V, and V82I that mimic the inhibitor binding site of PR{sub 2}. PR{sub 1M} more closely resembled PR{sub 2} than PR{sub 1} in catalytic efficiency on four substrate peptides and inhibition by APV, whereas few differences were seen for two other substrates and inhibition by saquinavir (SQV) and darunavir (DRV). High resolution crystal structures of PR{sub 1M} with APV, DRV, and SQV were compared with available PR{sub 1} and PR{sub 2} complexes. Val/Ile32 and Ile/Val47 showed compensating interactions with SQV in PR{sub 1M} and PR{sub 1}, however, Ile82 interacted with a second SQV bound in an extension of the active site cavity of PR{sub 1M}. Residues 32 and 82 maintained similar interactions with DRV and APV in all the enzymes, whereas Val47 and Ile47 had opposing effects in the two subunits. Significantly diminished interactions were seen for the aniline of APV bound in PR{sub 1M} and PR{sub 2} relative to the strong hydrogen bonds observed in PR{sub 1}, consistent with 15- and 19-fold weaker inhibition, respectively. Overall, PR{sub 1M} partially replicates the specificity of PR{sub 2} and gives insight into drug resistant mutations at residues 32, 47, and 82. Moreover, this analysis provides a structural explanation for the weaker antiviral effects of APV on HIV-2.

  3. Critical differences in HIV-1 and HIV-2 protease specificity for clinical inhibitors.

    PubMed

    Tie, Yunfeng; Wang, Yuan-Fang; Boross, Peter I; Chiu, Ting-Yi; Ghosh, Arun K; Tozser, Jozsef; Louis, John M; Harrison, Robert W; Weber, Irene T

    2012-03-01

    Clinical inhibitor amprenavir (APV) is less effective on HIV-2 protease (PR₂) than on HIV-1 protease (PR₁). We solved the crystal structure of PR₂ with APV at 1.5 Å resolution to identify structural changes associated with the lowered inhibition. Furthermore, we analyzed the PR₁ mutant (PR(1M) ) with substitutions V32I, I47V, and V82I that mimic the inhibitor binding site of PR₂. PR(1M) more closely resembled PR₂ than PR₁ in catalytic efficiency on four substrate peptides and inhibition by APV, whereas few differences were seen for two other substrates and inhibition by saquinavir (SQV) and darunavir (DRV). High resolution crystal structures of PR(1M) with APV, DRV, and SQV were compared with available PR₁ and PR₂ complexes. Val/Ile32 and Ile/Val47 showed compensating interactions with SQV in PR(1M) and PR₁, however, Ile82 interacted with a second SQV bound in an extension of the active site cavity of PR(1M). Residues 32 and 82 maintained similar interactions with DRV and APV in all the enzymes, whereas Val47 and Ile47 had opposing effects in the two subunits. Significantly diminished interactions were seen for the aniline of APV bound in PR₁ (M) and PR₂ relative to the strong hydrogen bonds observed in PR₁, consistent with 15- and 19-fold weaker inhibition, respectively. Overall, PR(1M) partially replicates the specificity of PR₂ and gives insight into drug resistant mutations at residues 32, 47, and 82. Moreover, this analysis provides a structural explanation for the weaker antiviral effects of APV on HIV-2. Copyright © 2012 The Protein Society.

  4. Adaptation of the application of good clinical practice depending on the features of specific research projects.

    PubMed

    Bertoye, Pierre-Henri; Courcier-Duplantier, Soizic; Best, Nicolas

    2006-01-01

    The conduct of clinical trials falls within a strict regulatory framework. The objective of the round table was to develop reasonable recommendations for the implementation of GCP according to the type of research and taking in account the risks and challenges related to this research. Two types of risks have been identified: those related to the characteristics of the research and those related to the impact of the study results. The group designed an evaluation table of these risks. The round table focused its investigations on 3 main themes: monitoring, the investigational medicinal product and undesirable effects. Three methods of monitoring adaptation were analysed in terms of advantages and disadvantages: the gradual approach, the central monitoring, monitoring on the basis of sampling. Examination of the investigational medicinal product focused on the medicinal product circuit. The group recommends using the following 'basic' decision-making tree, which takes three elements into account: 1) is it an investigational medicinal product?, 2) do the trial objectives and design require packaging specific to the research?, 3) is the risk of use higher than that in standard practice? Finally, adaptation of the implementation of GCP in terms of pharmacovigilance appeared very limited and could possibly be considered for the medicinal product, the subject of the research, which already holds a marketing authorisation, and for which the safety profile is well known; in this case, only simplified collection of non-serious adverse events may be envisaged, which may be implemented by designing and using a standard collection listing. The adaptation of the implementation of GCP is possible. This firstly takes into account the characteristics of the research: which objectives/which risks/which challenges. The options in terms of adaptation must be pre-defined, documented and justified; if necessary, they will also be re-assessed in the course of analysis.

  5. Addressing the theoretical and clinical advantages of combination therapy with inhibitors of the renin-angiotensin-aldosterone system: antihypertensive effects and benefits beyond BP control

    PubMed Central

    Ferrario, Carlos M.

    2010-01-01

    Aims This article reviews the importance of the renin-angiotensin-aldosterone system (RAAS) in the cardiometabolic continuum; presents the pros and cons of dual RAAS blockade with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs); and examines the theoretical and practical benefits supporting the use of direct renin inhibitors (DRIs) in combination with ACEIs or ARBs. Main methods The author reviewed the literature for key publications related to the biochemical physiology of the RAAS and the pharmacodynamic effects of ACEIs, ARBs, and DRIs, with a particular focus on dual RAAS blockade with these drug classes. Key findings Although ACEI/ARB combination therapy produces modest improvement in BP, it has not resulted in the major improvements predicted given the importance of the RAAS across the cardiorenal disease continuum. This may reflect the fact that RAAS blockade with ACEIs and/or ARBs leads to exacerbated renin release through loss of negative-feedback inhibition, as well as ACE/aldosterone escape through RAAS and non–RAAS-mediated mechanisms. Plasma renin activity (PRA) is an independent predictor of morbidity and mortality, even for patients receiving ACEIs and ARBs. When used alone or in combination with ACEIs and ARBs, the DRI aliskiren effectively reduces PRA. Reductions in BP are greater with these combinations, relative to the individual components alone. Significance It is possible that aliskiren plus either an ACEI or ARB may provide greater RAAS blockade than monotherapy with ACEIs or ARBs, and lead to additive improvement in BP and clinically important outcomes. PMID:19958778

  6. Addressing the theoretical and clinical advantages of combination therapy with inhibitors of the renin-angiotensin-aldosterone system: antihypertensive effects and benefits beyond BP control.

    PubMed

    Ferrario, Carlos M

    2010-02-27

    This article reviews the importance of the renin-angiotensin-aldosterone system (RAAS) in the cardiometabolic continuum; presents the pros and cons of dual RAAS blockade with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs); and examines the theoretical and practical benefits supporting the use of direct renin inhibitors (DRIs) in combination with ACEIs or ARBs. The author reviewed the literature for key publications related to the biochemical physiology of the RAAS and the pharmacodynamic effects of ACEIs, ARBs, and DRIs, with a particular focus on dual RAAS blockade with these drug classes. Although ACEI/ARB combination therapy produces modest improvement in BP, it has not resulted in the major improvements predicted given the importance of the RAAS across the cardiorenal disease continuum. This may reflect the fact that RAAS blockade with ACEIs and/or ARBs leads to exacerbated renin release through loss of negative-feedback inhibition, as well as ACE/aldosterone escape through RAAS and non-RAAS-mediated mechanisms. Plasma renin activity (PRA) is an independent predictor of morbidity and mortality, even for patients receiving ACEIs and ARBs. When used alone or in combination with ACEIs and ARBs, the DRI aliskiren effectively reduces PRA. Reductions in BP are greater with these combinations, relative to the individual components alone. It is possible that aliskiren plus either an ACEI or ARB may provide greater RAAS blockade than monotherapy with ACEIs or ARBs, and lead to additive improvement in BP and clinically important outcomes. Copyright 2009 Elsevier Inc. All rights reserved.

  7. The effects of post-exposure smallpox vaccination on clinical disease presentation: addressing the data gaps between historical epidemiology and modern surrogate model data.

    PubMed

    Keckler, M Shannon; Reynolds, Mary G; Damon, Inger K; Karem, Kevin L

    2013-10-25

    Decades after public health interventions - including pre- and post-exposure vaccination - were used to eradicate smallpox, zoonotic orthopoxvirus outbreaks and the potential threat of a release of variola virus remain public health concerns. Routine prophylactic smallpox vaccination of the public ceased worldwide in 1980, and the adverse event rate associated with the currently licensed live vaccinia virus vaccine makes reinstatement of policies recommending routine pre-exposure vaccination unlikely in the absence of an orthopoxvirus outbreak. Consequently, licensing of safer vaccines and therapeutics that can be used post-orthopoxvirus exposure is necessary to protect the global population from these threats. Variola virus is a solely human pathogen that does not naturally infect any other known animal species. Therefore, the use of surrogate viruses in animal models of orthopoxvirus infection is important for the development of novel vaccines and therapeutics. Major complications involved with the use of surrogate models include both the absence of a model that accurately mimics all aspects of human smallpox disease and a lack of reproducibility across model species. These complications limit our ability to model post-exposure vaccination with newer vaccines for application to human orthopoxvirus outbreaks. This review seeks to (1) summarize conclusions about the efficacy of post-exposure smallpox vaccination from historic epidemiological reports and modern animal studies; (2) identify data gaps in these studies; and (3) summarize the clinical features of orthopoxvirus-associated infections in various animal models to identify those models that are most useful for post-exposure vaccination studies. The ultimate purpose of this review is to provide observations and comments regarding available model systems and data gaps for use in improving post-exposure medical countermeasures against orthopoxviruses. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. The effects of post-exposure smallpox vaccination on clinical disease presentation: Addressing the data gaps between historical epidemiology and modern surrogate model data

    PubMed Central

    Keckler, M. Shannon; Reynolds, Mary G.; Damon, Inger K.; Karem, Kevin L.

    2015-01-01

    Decades after public health interventions – including pre- and post-exposure vaccination – were used to eradicate smallpox, zoonotic orthopoxvirus outbreaks and the potential threat of a release of variola virus remain public health concerns. Routine prophylactic smallpox vaccination of the public ceased worldwide in 1980, and the adverse event rate associated with the currently licensed live vaccinia virus vaccine makes reinstatement of policies recommending routine pre-exposure vaccination unlikely in the absence of an orthopoxvirus outbreak. Consequently, licensing of safer vaccines and therapeutics that can be used post-orthopoxvirus exposure is necessary to protect the global population from these threats. Variola virus is a solely human pathogen that does not naturally infect any other known animal species. Therefore, the use of surrogate viruses in animal models of orthopoxvirus infection is important for the development of novel vaccines and therapeutics. Major complications involved with the use of surrogate models include both the absence of a model that accurately mimics all aspects of human smallpox disease and a lack of reproducibility across model species. These complications limit our ability to model post-exposure vaccination with newer vaccines for application to human orthopoxvirus outbreaks. This review seeks to (1) summarize conclusions about the efficacy of post-exposure smallpox vaccination from historic epidemiological reports and modern animal studies; (2) identify data gaps in these studies; and (3) summarize the clinical features of orthopoxvirus-associated infections in various animal models to identify those models that are most useful for post-exposure vaccination studies. The ultimate purpose of this review is to provide observations and comments regarding available model systems and data gaps for use in improving post-exposure medical countermeasures against orthopoxviruses. PMID:23994378

  9. Reach Address Database (RAD)

    EPA Pesticide Factsheets

    The Reach Address Database (RAD) stores the reach address of each Water Program feature that has been linked to the underlying surface water features (streams, lakes, etc) in the National Hydrology Database (NHD). (A reach is the portion of a stream between two points of confluence. A confluence is the location where two or more streams flow together.)

  10. Quality of life in infants and children with atopic dermatitis: Addressing issues of differential item functioning across countries in multinational clinical trials

    PubMed Central

    McKenna, Stephen P; Doward, Lynda C; Meads, David M; Tennant, Alan; Lawton, Gemma; Grueger, Jens

    2007-01-01

    Background A previous study had identified 45 items assessing the impact of atopic dermatitis (AD) on the whole family. From these it was intended to develop two separate scales, one assessing impact on carers and the other determining the effect on the child. Methods The 45 items were included in three clinical trials designed to test the efficacy of a new topical treatment (pimecrolimus, Elidel cream 1%) in the treatment of AD in infants and children and in validation studies in the UK, US, Germany, France and the Netherlands. Rasch analyses were undertaken to determine whether an internationally valid, unidimensional scale could be developed that would inform on the direct impact of AD on the child. Results Rasch analyses applied to the data from the trials indicated that the draft measure consisted of two scales, one assessing the QoL of the carer and the other (consisting of 12 items) measuring the impact of AD on the child. Three of the 12 potential items failed to fit the measurement model in Europe and five in the US. In addition, four items exhibiting differential item functioning (DIF) by country were identified. After removing the misfitting items and controlling for DIF it was possible to derive a scale; The Childhood Impact of Atopic Dermatitis (CIAD) with good item fit for each trial analysis. Analysis of the validation data from each of the different countries confirmed that the CIAD had adequate internal consistency, reproducibility and construct validity. The CIAD demonstrated the benefits of treatment with Elidel over placebo in the European trial. A similar (non-significant) trend was found for the US trials. Conclusion The study represents a novel method of dealing with the problem of DIF associated with different cultures. Such problems are likely to arise in any multinational study involving patient-reported outcome measures, as items in the scales are likely to be valued differently in different cultures. However, where all items in a scale

  11. Genus Level Identification of Mycobacteria from Clinical Specimens by Using an Easy-To-Handle Mycobacterium-Specific PCR Assay

    PubMed Central

    Stauffer, Fritz; Haber, Heinrich; Rieger, Armin; Mutschlechner, Robert; Hasenberger, Petra; Tevere, Vincent J.; Young, Karen K. Y.

    1998-01-01

    An easy-to-handle Mycobacterium-specific PCR assay for detection of the presence of a wide range of mycobacterial species in clinical samples was evaluated. The performance of the genus probe was compared with the performance of probes specific for Mycobacterium tuberculosis and Mycobacterium avium and with that of standard culture. In addition, the utility of an internal control in monitoring amplification inhibitors was studied. Of 545 respiratory and 325 nonrespiratory specimens (a total of 870 specimens), 58 (6.7%) showed the presence of amplification inhibitors, as determined by a negative result for the internal control. Of these 58 specimens, 31 (53%) were stool specimens; other material, even citrate blood after lysis of erythrocytes, did not pose a problem with regard to inhibition of PCR amplification. Eighty-one of the remaining 812 specimens had a positive Mycobacterium culture result. Of these culture-positive specimens, 58 (71.6%) showed a positive result with the Mycobacterium genus-specific probe. Seventy-two samples had a positive result with the Mycobacterium-specific probe but a negative culture result. Of these 72 samples, 26 samples were regarded as true positive, either because the M. tuberculosis- or M. avium-specific probe was also positive at the same time or because other specimens from the same patient taken at the same time were culture positive. The sensitivity of the Mycobacterium-specific probe was 78.5% and the specificity was 93.5%. This study showed that pretesting of clinical specimens for mycobacteria to the genus level with a Mycobacterium-specific probe offers the routine clinical laboratory the possibility of detecting tuberculous and nontuberculous mycobacteria with one test. Furthermore, specimens testing positive with the genus-specific probe can be immediately identified with species-specific probes. PMID:9508282

  12. A collaborative clinical and population-based curriculum for medical students to address primary care needs of the homeless in New York City shelters : Teaching homeless healthcare to medical students.

    PubMed

    Asgary, Ramin; Naderi, Ramesh; Gaughran, Margaret; Sckell, Blanca

    2016-06-01

    Background Millions of Americans experience homelessness annually. Medical providers do not receive adequate training in primary care of the homeless.Methods Starting in 2012, a comprehensive curriculum was offered to medical students during their family medicine or ambulatory clerkship, covering clinical, social and advocacy, population-based, and policy aspects. Students were taught to: elicit specific social history, explore health expectations, and assess barriers to healthcare; evaluate clinical conditions specific to the homeless and develop plans for care tailored toward patients' medical and social needs; collaborate with shelter staff and community organizations to improve disease management and engage in advocacy efforts. A mixed methods design was used to evaluate students' knowledge, attitudes, and skills including pre- and post-curriculum surveys, debriefing sessions, and observed clinical skills.Results The mean age of the students (n = 30) was 26.5 years; 55 % were female. The overall scores improved significantly in knowledge, attitude, and self-efficacy domains using paired t‑test (p < 0.01). Specific skills in evaluating mental health, substance abuse, and risky behaviours improved significantly (p < 0.05). In evaluation of communication skills, the majority were rated as having 'outstanding rapport with patients.'Conclusions Comprehensive and ongoing clinical component in shelter clinics, complementary teaching, experienced faculty, and working relationship and collaboration with community organizations were key elements.

  13. Investigating the clinical usefulness of the Social Responsiveness Scale (SRS) in a tertiary level, autism spectrum disorder specific assessment clinic.

    PubMed

    Aldridge, Fiona J; Gibbs, Vicki M; Schmidhofer, Katherine; Williams, Megan

    2012-02-01

    The Social Responsiveness Scale (SRS; Constantino and Gruber in Social Responsiveness Scale (SRS). Western Psychological Services, Los Angeles, 2005) is a commonly used screening tool for identifying children with possible autism spectrum disorder (ASD). This study investigated the relationship between SRS scores and eventual diagnostic outcome for children referred to a tertiary level, autism specific assessment service. Forty eight children (mean age = 8.10; 92% male) underwent a comprehensive ASD assessment. Parent and teacher SRS scores were subsequently compared with diagnostic outcome. Sensitivity was high (91% for parent report; 84% for teacher report), however specificity was much lower (8% for parent report; 41% for teacher report). Results demonstrate a need for caution when interpreting SRS results based on current cut-off scores, particularly in children with previously identified social developmental problems.

  14. Saturation monitoring of VX15/2503, a novel semaphorin 4D‐specific antibody, in clinical trials

    PubMed Central

    Seils, Jennifer; Reilly, Christine; Litwin, Virginia; Green, Lisa; Salkowitz‐Bokal, Janelle; Walsh, Robin; Harville, Sarah; Leonard, John E.; Smith, Ernest; Zauderer, Maurice

    2015-01-01

    Background Receptor occupancy, or saturation, assays are often utilized in preclinical and clinical development programs to evaluate the binding of a biologic to a cellular target. These assays provide critical information regarding the dose of drug required to “saturate” the target as well as important pharmacodymamic (PD) data. A flow cytometric method was developed to measure the degree of Semaphorin 4D (SEMA4D; CD100) saturation by VX15/2303, an investigational monoclonal antibody specific for SEMA4D. Methods The assay detects VX15/2503, a human IgG4 specific for SEMA4D, with an IgG4‐specific monoclonal antibody. Results Data generated allowed assessment of two related SEMA4D‐specific pharmacodynamic (PD) markers: (1) The measurement of cellular SEMA4D (cSEMA4D) saturation by VX15/2503, and (2) the cell membrane expression levels of cSEMA4D. Conclusions This assay specifically and reproducibly measured cSEMA4D saturation and expression levels. Evaluation of the SEMA4D‐specific PD markers were critical in determining the clinical saturation threshold of cSEMA4D by VX15/2503. © 2015 he Authors Cytometry Part B: Clinical Cytometry Published by Wiley Periodicals, Inc. PMID:26566052

  15. Saturation monitoring of VX15/2503, a novel semaphorin 4D-specific antibody, in clinical trials.

    PubMed

    Fisher, Terrence L; Seils, Jennifer; Reilly, Christine; Litwin, Virginia; Green, Lisa; Salkowitz-Bokal, Janelle; Walsh, Robin; Harville, Sarah; Leonard, John E; Smith, Ernest; Zauderer, Maurice

    2016-03-01

    Receptor occupancy, or saturation, assays are often utilized in preclinical and clinical development programs to evaluate the binding of a biologic to a cellular target. These assays provide critical information regarding the dose of drug required to "saturate" the target as well as important pharmacodymamic (PD) data. A flow cytometric method was developed to measure the degree of Semaphorin 4D (SEMA4D; CD100) saturation by VX15/2303, an investigational monoclonal antibody specific for SEMA4D. The assay detects VX15/2503, a human IgG4 specific for SEMA4D, with an IgG4 -specific monoclonal antibody. Data generated allowed assessment of two related SEMA4D-specific pharmacodynamic (PD) markers: (1) The measurement of cellular SEMA4D (cSEMA4D) saturation by VX15/2503, and (2) the cell membrane expression levels of cSEMA4D. This assay specifically and reproducibly measured cSEMA4D saturation and expression levels. Evaluation of the SEMA4D-specific PD markers were critical in determining the clinical saturation threshold of cSEMA4D by VX15/2503. © 2015 he Authors Cytometry Part B: Clinical Cytometry Published by Wiley Periodicals, Inc.

  16. Clinically-relevant threshold of preformed donor-specific anti-HLA antibodies in kidney transplantation.

    PubMed

    Salvadé, Igor; Aubert, Vincent; Venetz, Jean-Pierre; Golshayan, Dela; Saouli, Anne-Catherine; Matter, Maurice; Rotman, Samuel; Pantaleo, Giuseppe; Pascual, Manuel

    2016-06-01

    Pretransplant anti-HLA donor-specific antibodies (DSA) are recognized as a risk factor for acute antibody-mediated rejection (AMR) in kidney transplantation. The predictive value of C4d-fixing capability by DSA or of IgG DSA subclasses for acute AMR in the pretransplant setting has been recently studied. In addition DSA strength assessed by mean fluorescence intensity (MFI) may improve risk stratification. We aimed to analyze the relevance of preformed DSA and of DSA MFI values. 280 consecutive patients with negative complement-dependent cytotoxicity crossmatches received a kidney transplant between 01/2008 and 03/2014. Sera were screened for the presence of DSA with a solid-phase assays on a Luminex flow analyzer, and the results were correlated with biopsy-proven acute AMR in the first year and survival. Pretransplant anti-HLA antibodies were present in 72 patients (25.7%) and 24 (8.6%) had DSA. There were 46 (16.4%) acute rejection episodes, 32 (11.4%) being cellular and 14 (5.0%) AMR. The incidence of acute AMR was higher in patients with pretransplant DSA (41.7%) than in those without (1.6%) (p<0.001). The median cumulative MFI (cMFI) of the group DSA+/AMR+ was 5680 vs 2208 in DSA+/AMR- (p=0.058). With univariate logistic regression a threshold value of 5280 cMFI was predictive for acute AMR. DSA cMFI's ability to predict AMR was also explored by ROC analysis. AUC was 0.728 and the best threshold was a cMFI of 4340. Importantly pretransplant DSA>5280 cMFI had a detrimental effect on 5-year graft survival. Preformed DSA cMFI values were clinically-relevant for the prediction of acute AMR and graft survival in kidney transplantation. A threshold of 4300-5300 cMFI was a significant outcome predictor. Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  17. Effect of Disorder-Specific vs Nonspecific Psychotherapy for Chronic Depression: A Randomized Clinical Trial.

    PubMed

    Schramm, Elisabeth; Kriston, Levente; Zobel, Ingo; Bailer, Josef; Wambach, Katrin; Backenstrass, Matthias; Klein, Jan Philipp; Schoepf, Dieter; Schnell, Knut; Gumz, Antje; Bausch, Paul; Fangmeier, Thomas; Meister, Ramona; Berger, Mathias; Hautzinger, Martin; Härter, Martin

    2017-03-01

    Chronic depression is a highly prevalent and disabling disorder. There is a recognized need to assess the value of long-term disorder-specific psychotherapy. To evaluate the efficacy of the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) compared with that of nonspecific supportive psychotherapy (SP). A prospective, multicenter, evaluator-blinded, randomized clinical trial was conducted among adult outpatients with early-onset chronic depression who were not taking antidepressant medication. Patients were recruited between March 5, 2010, and October 16, 2012; the last patient finished treatment on October 14, 2013. Data analysis was conducted from March 5, 2014, to October 27, 2016. The treatment included 24 sessions of CBASP or SP for 20 weeks in the acute phase, followed by 8 continuation sessions during the next 28 weeks. The primary outcome was symptom severity after 20 weeks (blinded observer ratings) as assessed by the 24-item Hamilton Rating Scale for Depression (HRSD-24). Secondary outcomes were rates of response (reduction in HRSD-24 score of ≥50% from baseline) and remission (HRSD-24 score ≤8), as well as self-assessed ratings of depression, global functioning, and quality of life. Among 622 patients assessed for eligibility, 268 were randomized: 137 to CBASP (96 women [70.1%] and 41 men [29.9%]; mean [SD] age, 44.7 [12.1] years) and 131 to SP (81 women [61.8%] and 50 men [38.2%]; mean [SD] age, 45.2 [11.6] years). The mean (SD) baseline HRSD-24 scores of 27.15 (5.49) in the CBASP group and 27.05 (5.74) in the SP group improved to 17.19 (10.01) and 20.39 (9.65), respectively, after 20 weeks, with a significant adjusted mean difference of -2.51 (95% CI, -4.16 to -0.86; P = .003) and a Cohen d of 0.31 in favor of CBASP. After 48 weeks, the HRSD-24 mean (SD) scores were 14.00 (9.72) for CBASP and 16.49 (9.96) for SP, with an adjusted difference of -3.13 (95% CI, -5.01 to -1.25; P = .001) and a Cohen d of 0.39. Patients undergoing

  18. Clinical-scale isolation of 'minimally manipulated' cytomegalovirus-specific donor lymphocytes for the treatment of refractory cytomegalovirus disease.

    PubMed

    Odendahl, Marcus; Grigoleit, G Ulrich; Bönig, Halvard; Neuenhahn, Michael; Albrecht, Julia; Anderl, Florian; Germeroth, Lothar; Schmitz, Marc; Bornhäuser, Martin; Einsele, Hermann; Seifried, Erhard; Busch, Dirk H; Tonn, Torsten

    2014-09-01

    Reactivation of cytomegalovirus (CMV) after hematopoietic stem cell transplantation remains a major cause of morbidity despite improved antiviral drug therapies. Selective restoration of CMV immunity by adoptive transfer of CMV-specific T cells is the only alternative approach that has been shown to be effective and non-toxic. We describe the results of clinical-scale isolations of CMV-specific donor lymphocytes with the use of a major histocompatibility (MHC) class I peptide streptamer-based isolation method that yields minimally manipulated cytotoxic T cells of high purity. Enrichment of CMV-specific cytotoxic T lymphocytes (CTLs) was performed by labeling 1 × 10(10) leukocytes from a non-mobilized mononuclear cell (MNC) apheresis with MHC class I streptamers and magnetic beads. Thereafter, positively labeled CMV-specific CTLs were isolated through the use of CliniMACS (magnetic-activated cell sorting), and MHC streptamers were released through the use of d-biotin. The purity of enriched CMV-specific CTLs was determined on the basis of MHC streptamer staining and fluorescence-activated cell sorting. A total of 22 processes were performed with the use of five different MHC class I streptamers. The median frequency of CMV-specific CTLs in the starting apheresis product was 0.41% among CD3+ T cells. The isolation process yielded a total of 7.77 × 10(6) CMV-specific CTLs, with a median purity of 90.2%. Selection reagents were effectively removed from the final cell product; the CMV-specific CTLs displayed excellent viability and cytotoxicity and were stable for at least 72 h at 4°C after MNC collection. Clinical-scale isolation of "minimally manipulated" CMV-specific donor CTLs through the use of MHC class I streptamers is feasible and yields functional CTLs at clinically relevant dosages. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  19. Specific clinical and brain MRI features in mentally retarded patients with mutations in the Oligophrenin-1 gene.

    PubMed

    des Portes, Vincent; Boddaert, Nathalie; Sacco, Silvia; Briault, Sylvain; Maincent, Kim; Bahi, Nadia; Gomot, Marie; Ronce, Nathalie; Bursztyn, Joseph; Adamsbaum, Catherine; Zilbovicius, Monica; Chelly, Jamel; Moraine, Claude

    2004-02-01

    Oligophrenin-1 (OPHN-1) gene disruption is known as responsible for so called "non-specific" X-linked mental retardation (MR) Billuart et al. [1998: Nature 392:923-926]. In order to search for a possible specific clinical and radiological profile for mutation in the OPHN-1 gene, clinical and 3D brain MRI studies were performed in the two families with a known mutation in OPHN-1 reported so far: a 19-year-old female with an X;12 balanced translocation encompassing OPHN-1, and four affected males of family MRX60 sharing a frameshift mutation in OPHN-1. Clinical data shared by affected individuals were neonatal hypotonia with motor delay but no obvious ataxia, marked strabismus, early onset complex partial seizures, and moderate to severe MR. Brain MRIs performed in three individuals exhibited a specific vermian dysgenesis including an incomplete sulcation of anterior and posterior vermis with the most prominent defect in lobules VI and VII. In addition, a non-specific cerebral cortico-subcortical atrophy was also observed. These clinical and radiological features suggest a distinct clinico-radiological syndrome. These preliminary data need to be confirmed in other families and will be helpful for further targeted mutation screening of the OPHN-1 gene in male patients with similar clinico-radiological features. In addition, OPHN-1 inactivation should be considered as a relevant model of developmental vermis disorganization, leading to a better understanding of the possible role of the cerebellum in MR. Copyright 2003 Wiley-Liss, Inc.

  20. [Development, problems and results of specialty-specific genetic counseling at the Neurology Clinic of the Karl Marx University].

    PubMed

    Bachmann, H

    1987-11-01

    Genetic counselling for inherited neurological diseases has been established at the Clinic for Neurology of Karl Marx University. Comprehensive experiences have been got with the specific and sometimes markedly different problems and aims of counselling in Wilsons disease, X-linked recessive muscular dystrophies, myotonic dystrophy and other neuromuscular disorders, Huntingtons chorea and hereditary ataxias.

  1. Addressing Ozone Layer Depletion

    EPA Pesticide Factsheets

    Access information on EPA's efforts to address ozone layer depletion through regulations, collaborations with stakeholders, international treaties, partnerships with the private sector, and enforcement actions under Title VI of the Clean Air Act.

  2. [Subtype-specific clinically important effects of alpha 2-adrenergic receptors].

    PubMed

    Shishkina, G T; Dygalo, N N

    2002-01-01

    A- B- and C-subtypes of alpha 2-adrenoreceptors present in all mammals are involved in responses to currently existing subtype-nonselective ligands of these receptors widely used in medicine. Each of the subtypes has its own specific distribution in tissue and cells, onthogenetic pattern, specific regulation of activity and expression, and, as result, specific physiological functions. The latter suggests opportunities of using the subtype-specific for correction of the functions depending on this receptor. The article reviews the role of individual subtypes of alpha 2-adrenoreceptors in regulation of neurochemical transmission of cardiovascular system, psychoemotional state and development of psychic disorders, and also male sexual behaviour.

  3. Prevalence of Legionella-specific IgG and IgM antibody in a dental clinic population.

    PubMed

    Fotos, P G; Westfall, H N; Snyder, I S; Miller, R W; Mutchler, B M

    1985-12-01

    This study was undertaken to determine the frequency of Legionella infection in a dental clinic setting. Serum samples from 270 dental clinic personnel were evaluated using an enzyme-linked immunosorbent assay to detect Legionella-specific IgM and IgG antibodies. The pooled-species whole-cell-antigen preparation used in these assays was derived from six Legionella pneumophila strains and one strain each from Legionella bozemanii and Legionella micdadei. Significant levels of IgG and IgM antibodies were found in 20% and 16%, respectively, of the samples. This compares with 8% and 10%, respectively, for a randomly selected non-clinical group from the region (P less than 0.005). Samples from clinic personnel with significant IgG titers (greater than 1:128) were also evaluated for activity to each of the eight single-species antigens, with the following results: L. pneumophila, 45% (combined six strains); L. micdadei, 37%; and L. bozemanii, 18%. Comparing individuals' "years spent in the clinic environment" with the incidence of significant antibody levels strongly suggests that the risk of Legionella infection increases proportionately with increased clinic exposure time (P less than 0.05). Analysis of these data implies that Legionella may be present in the dental clinic environment, thus creating an increased risk for clinical personnel or patients.

  4. The Asgaard project: a task-specific framework for the application and critiquing of time-oriented clinical guidelines.

    PubMed

    Shahar, Y; Miksch, S; Johnson, P

    1998-01-01

    Clinical guidelines can be viewed as generic skeletal-plan schemata that represent clinical procedural knowledge and that are instantiated and refined dynamically by care providers over significant time periods. In the Asgaard project, we are investigating a set of tasks that support the application of clinical guidelines by a care provider other than the guideline's designer. We are focusing on the application of the guideline, recognition of care providers' intentions from their actions, and critique of care providers' actions given the guideline and the patient's medical record. We are developing methods that perform these tasks in multiple clinical domains, given an instance of a properly represented clinical guideline and an electronic medical patient record. In this paper, we point out the precise domain-specific knowledge required by each method, such as the explicit intentions of the guideline designer (represented as temporal patterns to be achieved or avoided). We present a machine-readable language, called Asbru, to represent and to annotate guidelines based on the task-specific ontology. We also introduce an automated tool for the acquisition of clinical guidelines based on the same ontology, developed using the PROTEGE-II framework.

  5. Novel Junction-specific and Quantifiable In Situ Detection of AR-V7 and its Clinical Correlates in Metastatic Castration-resistant Prostate Cancer.

    PubMed

    Zhu, Yezi; Sharp, Adam; Anderson, Courtney M; Silberstein, John L; Taylor, Maritza; Lu, Changxue; Zhao, Pei; De Marzo, Angelo M; Antonarakis, Emmanuel S; Wang, Mindy; Wu, Xingyong; Luo, Yuling; Su, Nan; Nava Rodrigues, Daniel; Figueiredo, Ines; Welti, Jonathan; Park, Emily; Ma, Xiao-Jun; Coleman, Ilsa; Morrissey, Colm; Plymate, Stephen R; Nelson, Peter S; de Bono, Johann S; Luo, Jun

    2017-08-30

    Androgen receptor splice variant 7 (AR-V7) has been implicated in resistance to abiraterone and enzalutamide treatment in men with metastatic castration-resistant prostate cancer (mCRPC). Tissue- or cell-based in situ detection of AR-V7, however, has been limited by lack of specificity. To address current limitations in precision measurement of AR-V7 by developing a novel junction-specific AR-V7 RNA in situ hybridization (RISH) assay compatible with automated quantification. We designed a RISH method to visualize single splice junctions in cells and tissue. Using the validated assay for junction-specific detection of the full-length AR (AR-FL) and AR-V7, we generated quantitative data, blinded to clinical data, for 63 prostate tumor biopsies. We evaluated clinical correlates of AR-FL/AR-V7 measurements, including association with prostate-specific antigen progression-free survival (PSA-PFS) and clinical and radiographic progression-free survival (PFS), in a subset of patients starting treatment with abiraterone or enzalutamide following biopsy. Quantitative AR-FL/AR-V7 data were generated from 56 of the 63 (88.9%) biopsy specimens examined, of which 44 were mCRPC biopsies. Positive AR-V7 signals were detected in 34.1% (15/44) mCRPC specimens, all of which also co-expressed AR-FL. The median AR-V7/AR-FL ratio was 11.9% (range 2.7-30.3%). Positive detection of AR-V7 was correlated with indicators of high disease burden at baseline. Among the 25 CRPC biopsies collected before treatment with abiraterone or enzalutamide, positive AR-V7 detection, but not higher AR-FL, was significantly associated with shorter PSA-PFS (hazard ratio 2.789, 95% confidence interval 1.12-6.95; p=0.0081). We report for the first time a RISH method for highly specific and quantifiable detection of splice junctions, allowing further characterization of AR-V7 and its clinical significance. Higher AR-V7 levels detected and quantified using a novel method were associated with poorer response to

  6. Evaluation of Luminex xTAG fungal analyte-specific reagents for rapid identification of clinically relevant fungi.

    PubMed

    Babady, N Esther; Miranda, Edwin; Gilhuley, Kathleen A

    2011-11-01

    Invasive fungal infections (IFI) remain a serious threat to immunocompromised hosts. Current diagnostic methods, including fungal culture and antigen detection, are slow and often lack specificity. Rapid diagnostic tools with increased sensitivity and specificity could improve the care of patients with IFI. Recently, Luminex Molecular Diagnostics (Toronto, Canada) developed 23 analyte-specific reagents (ASRs) for the detection of the most common clinically relevant fungi. This study's objective was to evaluate the sensitivity and specificity of a subset of these ASRs for fungal isolates and clinical specimens. Previously characterized fungal and bacterial isolates (n = 110), blood culture specimens (n = 34), and respiratory specimens (n = 44) were tested using either a Candida 7-plex panel (Candida albicans, Candida glabrata, Candida tropicalis, Candida parapsilosis, Candida lusitaniae, Candida guilliermondii, and Candida krusei) or a mold 11-plex panel (Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, Aspergillus terreus, Scedosporium prolificans, Scedosporium apiospermum, Fusarium oxysporum/Fusarium solani, Rhizopus arrhizus, Rhizopus microsporus, Mucor indicus, and Cunninghamella bertholletiae). The Candida 7-plex panel correctly identified all Candida isolates as confirmed by fungal culture and biochemical tests, for a sensitivity and specificity of 100%. The mold 11-plex panel correctly identified all mold isolates tested except for A. niger. Fungal isolates of Rhizopus and Mucor species were not detected, either, although they could represent species other than those targeted by the ASRs. Further evaluation will be necessary to confirm the sensitivities of some of the mold ASRs. Implementation of these ASRs will allow same-day detection of fungal DNA in clinical specimens.

  7. The correlation between anti phospholipase A2 specific IgE and clinical symptoms after a bee sting in beekeepers

    PubMed Central

    Matysiak, Joanna; Bręborowicz, Anna; Dereziński, Paweł; Kokot, Zenon J.

    2016-01-01

    Introduction Beekeepers are a group of people with high exposure to honeybee stings and with a very high risk of allergy to bee venom. Therefore, they are a proper population to study the correlations between clinical symptoms and results of diagnostic tests. Aim The primary aim of our study was to assess the correlations between total IgE, venom- and phospholipase A2-specific IgE and clinical symptoms after a bee sting in beekeepers. The secondary aim was to compare the results of diagnostic tests in beekeepers and in individuals with standard exposure to bees. Material and methods Fifty-four individuals were divided into two groups: beekeepers and control group. The levels of total IgE (tIgE), venom-specific IgE (venom sIgE), and phospholipase A2-specific IgE (phospholipase A2 sIgE) were analyzed. Results Our study showed no statistically significant correlation between the clinical symptoms after a sting and tIgE in the entire analyzed group. There was also no correlation between venom sIgE level and clinical symptoms either in beekeepers or in the group with standard exposure to bees. We observed a statistically significant correlation between phospholipase A2 sIgE level and clinical signs after a sting in the group of beekeepers, whereas no such correlation was detected in the control group. Significantly higher venom-specific IgE levels in the beekeepers, as compared to control individuals were shown. Conclusions In beekeepers, the severity of clinical symptoms after a bee sting correlated better with phospholipase A2 sIgE than with venom sIgE levels. PMID:27512356

  8. Reproducibility of BMD measurements in the prosthetic knee comparing knee-specific software to traditional DXA software: a clinical validation.

    PubMed

    Tjørnild, Michael; Søballe, Kjeld; Bender, Thomas; Stilling, Maiken

    2011-01-01

    The aim of this study was to validate new knee-specific dual X-ray absorptiometry (DXA) software for cemented total knee arthroplasty (TKA) before initiation of a randomized controlled trial. Firstly, in a phantom study, we evaluated if cementation influenced the measured BMD (g/cm²), the scan reproducibility with the new knee-specific software, and the consequences of leg rotation around a vertical axis. Secondly, in a clinical study, we assessed the clinical reproducibility in repetitive scans performed with the new knee-specific software and with traditional spine-mode DXA software, and further compared the 2 softwares' ability to point type implant and bone edges correctly. Cementation increased the measured bone mineral density (BMD) (p < 0.01). For reproducibility, the coefficient of variation (CV) was 0.52-0.70% in vitro. Leg rotation around a vertical axis significantly changed the measured BMD in most scans. Automatic point typing of implant and bone edge was of varying quality with frequent need of manual correction for both softwares. CVs of clinical reproducibility ranged from 2.78% to 6.19% for knee-specific software and from 1.45% to 6.06% for spine-mode software. We found the new knee-specific software valid for BMD measurement of the bone in proximity of cemented TKA and with clinical reproducibility and corrections of point typing similar to traditional spine-mode software. Copyright © 2011 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

  9. Dye dilution proliferation assay: application of the DDPA to identify tumor-specific T cell precursor frequencies in clinical trials.

    PubMed

    Schwaab, Thomas; Fisher, Jan L; Meehan, Kenneth R; Fadul, Camilo E; Givan, Alice L; Ernstoff, Marc S

    2007-01-01

    A better understanding of immune effector and regulatory pathways has led to innovative, and complex, immunotherapy strategies. CD8(+) cytolytic T lymphocytes (CTL) provide one common pathway of tumor cell destruction. The peripheral blood CTL compartment typically comprises a minority of anti-tumor CD8(+) lymphocytes and the determination of their number during clinical trials is the focus of various laboratory methods. We have monitored tumor specific CD8(+) as well as CD4(+) lymphocyte precursor frequencies in the peripheral blood using a Dye Dilution Proliferation Assay (DDPA). We summarize our experience applying DDPA in a multi-parameter, antigen-specific assay, detailing some of its complexities and advantages. We provide examples of our clinical trial results showing tumor-specific CD8(+) and CD4(+) precursor frequency (PF) data in patients being treated on novel immunotherapy trials.

  10. Correction factors for ionization chamber dosimetry in CyberKnife: Machine-specific, plan-class, and clinical fields

    SciTech Connect

    Gago-Arias, Araceli; Antolin, Elena; Fayos-Ferrer, Francisco; Simon, Rocio; Gonzalez-Castano, Diego M.; Palmans, Hugo; Sharpe, Peter; Gomez, Faustino; Pardo-Montero, Juan

    2013-01-15

    Purpose: The aim of this work is the application of the formalism for ionization chamber reference dosimetry of small and nonstandard fields [R. Alfonso, P. Andreo, R. Capote, M. S. Huq, W. Kilby, P. Kjaell, T. R. Mackie, H. Palmans, K. Rosser, J. Seuntjens, W. Ullrich, and S. Vatnitsky, 'A new formalism for reference dosimetry of small and nonstandard fields,' Med. Phys. 35, 5179-5186 (2008)] to the CyberKnife robotic radiosurgery system. Correction factors for intermediate calibration fields, a machine-specific reference field (msr) and two plan-class specific reference fields (pcsr), have been studied. Furthermore, the applicability of the new formalism to clinical dosimetry has been analyzed through the investigation of two clinical treatments. Methods: PTW31014 and Scanditronix-Wellhofer CC13 ionization chamber measurements were performed for the fields under investigation. Absorbed dose to water was determined using alanine reference dosimetry, and experimental correction factors were calculated from alanine to ionization chamber readings ratios. In addition, correction factors were calculated for the intermediate calibration fields and one of the clinical treatment fields using the Monte Carlo method and these were compared with the experimental values. Results: Overall correction factors deviating from unity by approximately 2% were obtained from both measurements and simulations, with values below and above unity for the studied intermediate calibration fields and clinical fields for the ionization chambers under consideration. Monte Carlo simulations yielded correction factors comparable with those obtained from measurements for the machine-specific reference field, although differences from 1% to 3.3% were observed between measured and calculated correction factors for the composite intermediate calibration fields. Dose distribution inhomogeneities are thought to be responsible for such discrepancies. Conclusions: The differences found between overall

  11. GliomaPredict: a clinically useful tool for assigning glioma patients to specific molecular subtypes.

    PubMed

    Li, Aiguo; Bozdag, Serdar; Kotliarov, Yuri; Fine, Howard A

    2010-07-15

    Advances in generating genome-wide gene expression data have accelerated the development of molecular-based tumor classification systems. Tools that allow the translation of such molecular classification schemas from research into clinical applications are still missing in the emerging era of personalized medicine. We developed GliomaPredict as a computational tool that allows the fast and reliable classification of glioma patients into one of six previously published stratified subtypes based on sets of extensively validated classifiers derived from hundreds of glioma transcriptomic profiles. Our tool utilizes a principle component analysis (PCA)-based approach to generate a visual representation of the analyses, quantifies the confidence of the underlying subtype assessment and presents results as a printable PDF file. GliomaPredict tool is implemented as a plugin application for the widely-used GenePattern framework. GliomaPredict provides a user-friendly, clinically applicable novel platform for instantly assigning gene expression-based subtype in patients with gliomas thereby aiding in clinical trial design and therapeutic decision-making. Implemented as a user-friendly diagnostic tool, we expect that in time GliomaPredict, and tools like it, will become routinely used in translational/clinical research and in the clinical care of patients with gliomas.

  12. [Selected clinical and laboratory tests during specific immunotherapy of patients hypersensitive to insect bites].

    PubMed

    Szymański, W; Kazberuk, M; Michalska, I; Chyrek-Borowska, S

    The study aimed at determining selected immunologic parameters of the cellular histamine secretion and skin reactivity in the group of 9 patients hypersensitive to insect poison with effective immunotherapy following 2 years of maintenance treatment. It has been shown that the continuation of the specific immunotherapy for 2 years maintains and even increases favourable changes in humoral and cellular immunity induced already in the early phase of desensitization. An assay of the specific IgE and IgG4, cellular histamine secretion, and skin reactivity is of value in monitoring specific allergy to insect poison immunotherapy.

  13. Scleroderma: the role of serum autoantibodies in defining specific clinical phenotypes and organ system involvement

    PubMed Central

    Domsic, Robyn T.

    2014-01-01

    Purpose of review To discuss recent advances in serologic testing for SSc-associated antibodies with respect to the diagnosis and prognosis of the disease. Recent findings The importance of SSc antibodies for diagnosis has become increasingly recognized, as evidence by incorporation into the 2013 ACR/EULAR clinical classification criteria for SSc. Two new SSc-associated antibodies and their clinical associations have been described. Multiple cohort studies have reported variable antibody frequency distribution based on geography, but the clinical associations remain much the same. New associations include anti-RNA polymerase III antibodies with gastric antral vascular ectasia, and a temporal association between SSc onset and RNA polymerase III antibodies. Summary The role and associations of SSc-associated antibodies for diagnosis and internal organ involvement is becoming increasingly accepted. PMID:25203118

  14. Multisite artery disease: a common and challenging clinical condition calling for specific management.

    PubMed

    Di Noi, Paola; Brancati, Marta Francesca; Burzotta, Francesco; Trani, Carlo

    2014-05-01

    'Multisite' artery disease is defined as the simultaneous presence of clinically significant atherosclerotic lesions in at least two major vascular territories. The management of patients with multisite artery disease represents a common challenge in clinical practice, since they are at increased risk for both vascular and coronary surgery. Preliminary experiences suggest that percutaneous treatment may represent a promising strategy for patients with multisite artery disease. In this review, the prevalence and management of multisite artery disease are discussed with particular attention to coronary and peripheral revascularization related issues.

  15. A single institution's effort to translate codeine knowledge into specific clinical practice.

    PubMed

    Jerome, Joel; Solodiuk, Jean C; Sethna, Navil; McHale, Josh; Berde, Charles

    2014-07-01

    Codeine is an unpredictable analgesic because of its variable pharmacokinetic, pharmacodynamic, and pharmacogenetic properties. This variability may lead to ineffective analgesia in some and respiratory depression in others. Despite this, codeine is still widely used. At a pediatric tertiary medical institution, codeine was prescribed despite efforts to inform prescribers of the potentially unpredictable analgesia and serious side effects. A retrospective/prospective metric was introduced to determine the frequency of codeine orders as compared with similar institutions using Pediatric Health Information Systems data. Interventions included formal and informal education to prescribers, and replacing codeine with oxycodone for patients aged older than six months and an age-appropriate medication for those patients younger than six months within ordersets. Identifying and addressing the major barriers to change also was a key part of the process. Codeine use was reduced by 97% from the first quarter of 2008 through the third quarter of 2012. This was accomplished through orderset changes and education. Codeine was completely eliminated from the hospital formulary in January 2013. This quality improvement initiative was successful in eliminating codeine from the hospital formulary. Although education decreased codeine orders, understanding and addressing the barriers to change and directly changing the ordersets were the most effective and efficient for knowledge translation. Copyright © 2014 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

  16. Specific bronchial reactivity to toluene diisocyanate: relationship with baseline clinical findings.

    PubMed Central

    Paggiaro, P L; Innocenti, A; Bacci, E; Rossi, O; Talini, D

    1986-01-01

    One hundred and fourteen subjects with asthma induced by toluene diisocyanate were identified and the pattern of their bronchial responses to challenge with toluene diisocyanate was studied. An occupational type specific bronchial provocation test with toluene diisocyanate (10-25 parts per thousand million for 10-15 minutes) elicited an immediate response in 24, a late response in 50, and a dual response in 40 patients. Subjects with a dual response showed at diagnosis a longer duration of symptoms and a greater prevalence of airway obstruction; in these subjects FEV1 (percentage of predicted value) was lower than in subjects with immediate or late reactions to toluene diisocyanate. The percentage of current smokers and ex-smokers was significantly lower in subjects with a late response (26%) than in subjects with immediate or dual responses (56% and 57% respectively). In 27 of the 114 subjects a non-specific challenge test with methacholine was performed and subjects with dual responses showed greater non-specific bronchial hyperresponsiveness than the other groups. These results suggest that a dual response to specific challenge in bronchial asthma related to toluene diisocyanate may be associated with more severe disease than other types of response, as assessed by duration of symptoms, baseline airway obstruction, and non-specific bronchial hyperresponsiveness. The high prevalence of non-smokers and low prevalence of smokers in the group with a late response to specific challenge is so far unexplained. PMID:3016938

  17. The impact of case specificity and generalisable skills on clinical performance: a correlated traits-correlated methods approach.

    PubMed

    Wimmers, Paul F; Fung, Cha-Chi

    2008-06-01

    The finding of case or content specificity in medical problem solving moved the focus of research away from generalisable skills towards the importance of content knowledge. However, controversy about the content dependency of clinical performance and the generalisability of skills remains. This study aimed to explore the relative impact of both perspectives (case specificity and generalisable skills) on different components (history taking, physical examination, communication) of clinical performance within and across cases. Data from a clinical performance examination (CPX) taken by 350 Year 3 students were used in a correlated traits-correlated methods (CTCM) approach using confirmatory factor analysis, whereby 'traits' refers to generalisable skills and 'methods' to individual cases. The baseline CTCM model was analysed and compared with four nested models using structural equation modelling techniques. The CPX consisted of three skills components and five cases. Comparison of the four different models with the least-restricted baseline CTCM model revealed that a model with uncorrelated generalisable skills factors and correlated case-specific knowledge factors represented the data best. The generalisable processes found in history taking, physical examination and communication were responsible for half the explained variance, in comparison with the variance related to case specificity. Conclusions Pure knowledge-based and pure skill-based perspectives on clinical performance both seem too one-dimensional and new evidence supports the idea that a substantial amount of variance contributes to both aspects of performance. It could be concluded that generalisable skills and specialised knowledge go hand in hand: both are essential aspects of clinical performance.

  18. [Comparison of clinical characteristics and laboratory parameters of patients with dermatomyositis-specific autoantibodies and autoantibody-negative patients].

    PubMed

    Bodoki, Levente; Budai, Dóra; Nagy-Vincze, Melinda; Griger, Zoltán; Betteridge, Zoe; Dankó, Katalin

    2015-09-06

    Myositis is an autoimmune disease characterised by proximal muscle weakness. The aim of the authors was to determine the frequency of dermatomyositis-specific autoantibodies (anti-Mi-2, anti-transcriptional intermediary factor 1 gamma, anti-nuclear matrix protein 2, anti-small ubiquitin-like modifier activating enzyme, anti-melanoma differentiation-associated gene) in a Hungarian myositis population and to compare the clinical features with the characteristics of patients without myositis-specific antibodies. Antibodies were detected using immunoblot and immunoprecipitation. Of the 330 patients with myositis, 48 patients showed dermatomyositis-specific antibody positivity. The frequency of antibodies in these patients was lower than those published in literature Retrospective analysis of clinical findings and medical history revealed that patients with dermatomyositis-specific autoantibody had more severe muscle weakness and severe skin lesions at the beginning of the disease. Antibodies seem to be useful markers for distinct clinical subsets, for predicting the prognosis of myositis and the effectiveness of the therapy.

  19. Using Semantic Web technologies for the generation of domain-specific templates to support clinical study metadata standards.

    PubMed

    Jiang, Guoqian; Evans, Julie; Endle, Cory M; Solbrig, Harold R; Chute, Christopher G

    2016-01-01

    The Biomedical Research Integrated Domain Group (BRIDG) model is a formal domain analysis model for protocol-driven biomedical research, and serves as a semantic foundation for application and message development in the standards developing organizations (SDOs). The increasing sophistication and complexity of the BRIDG model requires new approaches to the management and utilization of the underlying semantics to harmonize domain-specific standards. The objective of this study is to develop and evaluate a Semantic Web-based approach that integrates the BRIDG model with ISO 21090 data types to generate domain-specific templates to support clinical study metadata standards development. We developed a template generation and visualization system based on an open source Resource Description Framework (RDF) store backend, a SmartGWT-based web user interface, and a "mind map" based tool for the visualization of generated domain-specific templates. We also developed a RESTful Web Service informed by the Clinical Information Modeling Initiative (CIMI) reference model for access to the generated domain-specific templates. A preliminary usability study is performed and all reviewers (n = 3) had very positive responses for the evaluation questions in terms of the usability and the capability of meeting the system requirements (with the average score of 4.6). Semantic Web technologies provide a scalable infrastructure and have great potential to enable computable semantic interoperability of models in the intersection of health care and clinical research.

  20. The Development of English as a Second Language with and without Specific Language Impairment: Clinical Implications

    ERIC Educational Resources Information Center

    Paradis, Johanne

    2016-01-01

    Purpose: The purpose of this research forum article is to provide an overview of typical and atypical development of English as a second language (L2) and to present strategies for clinical assessment with English language learners (ELLs). Method: A review of studies examining the lexical, morphological, narrative, and verbal memory abilities of…

  1. Pain and the brain: Specificity and plasticity of the brain in clinical chronic pain

    PubMed Central

    Apkarian, A.V.; Hashmi, J.A.; Baliki, M.N.

    2010-01-01

    We review recent advances in brain imaging in humans, concentrating on advances in our understanding of the human brain in clinical chronic pain. Understanding regarding anatomical and functional reorganization of the brain in chronic pain is emphasized. We conclude by proposing a brain model for the transition of the human from acute to chronic pain. PMID:21146929

  2. The Development of English as a Second Language with and without Specific Language Impairment: Clinical Implications

    ERIC Educational Resources Information Center

    Paradis, Johanne

    2016-01-01

    Purpose: The purpose of this research forum article is to provide an overview of typical and atypical development of English as a second language (L2) and to present strategies for clinical assessment with English language learners (ELLs). Method: A review of studies examining the lexical, morphological, narrative, and verbal memory abilities of…

  3. Verb Morphology as Clinical Marker of Specific Language Impairment: Evidence from First and Second Language Learners

    ERIC Educational Resources Information Center

    Verhoeven, Ludo; Steenge, Judit; van Balkom, Hans

    2011-01-01

    The goal of this study was to search for verb morphology characteristics as possible clinical markers of SLI in Dutch as a first and second language. We also wanted to find out to what extent bilingual children with SLI are additionally disadvantaged in comparison to monolingual children with SLI, on the one hand, and to typically developing…

  4. Instruments to assess the perception of physicians in the decision-making process of specific clinical encounters: a systematic review.

    PubMed

    Légaré, France; Moher, David; Elwyn, Glyn; LeBlanc, Annie; Gravel, Karine

    2007-10-15

    The measurement of processes and outcomes that reflect the complexity of the decision-making process within specific clinical encounters is an important area of research to pursue. A systematic review was conducted to identify instruments that assess the perception physicians have of the decision-making process within specific clinical encounters. For every year available up until April 2007, PubMed, PsycINFO, Current Contents, Dissertation Abstracts and Sociological Abstracts were searched for original studies in English or French. Reference lists from retrieved studies were also consulted. Studies were included if they reported a self-administered instrument evaluating physicians' perceptions of the decision-making process within specific clinical encounters, contained sufficient description to permit critical appraisal and presented quantitative results based on administering the instrument. Two individuals independently assessed the eligibility of the instruments and abstracted information on their conceptual underpinnings, main evaluation domain, development, format, reliability, validity and responsiveness. They also assessed the quality of the studies that reported on the development of the instruments with a modified version of STARD. Out of 3431 records identified and screened for evaluation, 26 potentially relevant instruments were assessed; 11 met the inclusion criteria. Five instruments were published before 1995. Among those published after 1995, five offered a corresponding patient version. Overall, the main evaluation domains were: satisfaction with the clinical encounter (n = 2), mutual understanding between health professional and patient (n = 2), mental workload (n = 1), frustration with the clinical encounter (n = 1), nurse-physician collaboration (n = 1), perceptions of communication competence (n = 2), degree of comfort with a decision (n = 1) and information on medication (n = 1). For most instruments (n = 10), some reliability and validity

  5. Instruments to assess the perception of physicians in the decision-making process of specific clinical encounters: a systematic review

    PubMed Central

    Légaré, France; Moher, David; Elwyn, Glyn; LeBlanc, Annie; Gravel, Karine

    2007-01-01

    Background The measurement of processes and outcomes that reflect the complexity of the decision-making process within specific clinical encounters is an important area of research to pursue. A systematic review was conducted to identify instruments that assess the perception physicians have of the decision-making process within specific clinical encounters. Methods For every year available up until April 2007, PubMed, PsycINFO, Current Contents, Dissertation Abstracts and Sociological Abstracts were searched for original studies in English or French. Reference lists from retrieved studies were also consulted. Studies were included if they reported a self-administered instrument evaluating physicians' perceptions of the decision-making process within specific clinical encounters, contained sufficient description to permit critical appraisal and presented quantitative results based on administering the instrument. Two individuals independently assessed the eligibility of the instruments and abstracted information on their conceptual underpinnings, main evaluation domain, development, format, reliability, validity and responsiveness. They also assessed the quality of the studies that reported on the development of the instruments with a modified version of STARD. Results Out of 3431 records identified and screened for evaluation, 26 potentially relevant instruments were assessed; 11 met the inclusion criteria. Five instruments were published before 1995. Among those published after 1995, five offered a corresponding patient version. Overall, the main evaluation domains were: satisfaction with the clinical encounter (n = 2), mutual understanding between health professional and patient (n = 2), mental workload (n = 1), frustration with the clinical encounter (n = 1), nurse-physician collaboration (n = 1), perceptions of communication competence (n = 2), degree of comfort with a decision (n = 1) and information on medication (n = 1). For most instruments (n = 10), some

  6. Identification of Mycobacterium bovis in bovine clinical samples by PCR species-specific primers.

    PubMed Central

    Romero, R E; Garzón, D L; Mejía, G A; Monroy, W; Patarroyo, M E; Murillo, L A

    1999-01-01

    Tuberculosis, caused by Mycobacterium bovis is emerging as the most important disease affecting cattle. Furthermore, it results in a major public health problem when transmitted to humans. Due to its difficult and non-specific diagnosis, M. bovis has been declared to be one of the etiologic agents causing significant economic loss in the cattle industry. Our group evaluated a more rapid and specific method, based on a new polymerase chain reaction species-specific primers, which amplifies a 470-base pair fragment of the M. bovis genome. A total of 275 milk-producing cows were studied by intradermal tuberculin test (ITT) which gave 184 positive and 91 negative cases. From them, 50 animals were taken from a cattle ranch free of tuberculosis. Three different samples were collected from each animal (blood, nasal mucus, and milk). Positive results were obtained from 26 animals by PCR (11.4%), 1 by bacteriological culturing (0.4%) and 1 by bacilloscopy (0.4%). This finding suggests, as in previous reports, that ITT, normally used for bovine tuberculosis detection, has the inconvenience of having a broad range of specificity and sensitivity, and the PCR technique is a more specific and sensitive test to detect infection associated with M. bovis. Therefore, we propose this PCR assay as a useful tool in the epidemiological characterization of infected animals in areas considered to be at high risk of transmission. Images Figure 1. PMID:10369566

  7. Identification of uterine leiomyoma-specific marker genes based on DNA methylation and their clinical application

    PubMed Central

    Sato, Shun; Maekawa, Ryo; Yamagata, Yoshiaki; Tamura, Isao; Lee, Lifa; Okada, Maki; Jozaki, Kosuke; Asada, Hiromi; Tamura, Hiroshi; Sugino, Norihiro

    2016-01-01

    Differential diagnosis of uterine leiomyomas and leiomyosarcomas is needed to determine whether the uterus can be retained. Therefore, biomarkers for uterine leiomyomas, and reliable and objective diagnostic methods have been desired besides the pathological diagnosis. In the present study, we identified 12 genes specific to uterine leiomyomas based on DNA methylation. Using these marker genes specific to uterine leiomyomas, we established a hierarchical clustering system based on the DNA methylation level of the marker genes, which could completely differentiate between uterine leiomyomas and normal myometrium. Furthermore, our hierarchical clustering system completely discriminated uterine cancers and differentiated between uterine leiomyosarcomas and leiomyomas with more than 70% accuracy. In conclusion, this study identified DNA methylation-based marker genes specific to uterine leiomyomas, and our hierarchical clustering system using these marker genes was useful for differential diagnosis of uterine leiomyomas and leiomyosarcomas. PMID:27498619

  8. Addressing Social Issues.

    ERIC Educational Resources Information Center

    Schoebel, Susan

    1991-01-01

    Maintains that advertising can help people become more aware of social responsibilities. Describes a successful nationwide newspaper advertising competition for college students in which ads address social issues such as literacy, drugs, teen suicide, and teen pregnancy. Notes how the ads have helped grassroots programs throughout the United…

  9. Addressivity in Cogenerative Dialogues

    ERIC Educational Resources Information Center

    Hsu, Pei-Ling

    2014-01-01

    Ashraf Shady's paper provides a first-hand reflection on how a foreign teacher used cogens as culturally adaptive pedagogy to address cultural misalignments with students. In this paper, Shady drew on several cogen sessions to showcase his journey of using different forms of cogens with his students. To improve the quality of cogens, one…

  10. Addressing Social Issues.

    ERIC Educational Resources Information Center

    Schoebel, Susan

    1991-01-01

    Maintains that advertising can help people become more aware of social responsibilities. Describes a successful nationwide newspaper advertising competition for college students in which ads address social issues such as literacy, drugs, teen suicide, and teen pregnancy. Notes how the ads have helped grassroots programs throughout the United…

  11. Invitational Addresses, 1965.

    ERIC Educational Resources Information Center

    Gates, Arthur I.; And Others

    The full texts of invitational addresses given at the 1965 International Reading Association (IRA) Convention in Detroit, Michigan, by six recipients of IRA citation awards are presented. Gates suggests steps IRA should take to revive and redirect reading research. McCallister discusses the implications of the changing and expanding vocabulary of…

  12. Addressing Sexual Harassment

    ERIC Educational Resources Information Center

    Young, Ellie L.; Ashbaker, Betty Y.

    2008-01-01

    This article discusses ways on how to address the problem of sexual harassment in schools. Sexual harassment--simply defined as any unwanted and unwelcome sexual behavior--is a sensitive topic. Merely providing students, parents, and staff members with information about the school's sexual harassment policy is insufficient; schools must take…

  13. Detection of Clostridium tetani in human clinical samples using tetX specific primers targeting the neurotoxin.

    PubMed

    Ganesh, Madhu; Sheikh, Nasira K; Shah, Pooja; Mehetre, Gajanan; Dharne, Mahesh S; Nagoba, Basavraj S

    2016-01-01

    Tetanus resulting from ear injury remains an important health problem, particularly in the developing world. We report the successful detection of Clostridium tetani using tetX specific primers targeting the Cl. tetani neurotoxin. The sample was obtained from an ear discharge of a case of otogenic tetanus in a 2-year-old male child. Based on the culture results of the ear discharge, Gram staining and virulence testing by genotyping, a diagnosis of tetanus was confirmed. This is the first report from India on the successful detection of Cl. tetani in a human clinical sample using tetX specific primers targeting the Cl. tetani neurotoxin.

  14. External Beam Radiotherapy for Clinically Localized Hormone-Refractory Prostate Cancer: Clinical Significance of Nadir Prostate-Specific Antigen Value Within 12 Months

    SciTech Connect

    Ogawa, Kazuhiko Nakamura, Katsumasa; Sasaki, Tomonari; Onishi, Hiroshi; Koizumi, Masahiko; Shioyama, Yoshiyuki; Araya, Masayuki; Mukumoto, Nobutaka M.S.; Mitsumori, Michihide; Teshima, Teruki

    2009-07-01

    Purpose: To analyze retrospectively the results of external beam radiotherapy for clinically localized hormone-refractory prostate cancer and investigate the clinical significance of nadir prostate-specific antigen (PSA) value within 12 months (nPSA12) as an early estimate of clinical outcomes after radiotherapy. Methods and Materials: Eighty-four patients with localized hormone-refractory prostate cancer treated with external beam radiotherapy were retrospectively reviewed. The total radiation doses ranged from 30 to 76 Gy (median, 66 Gy), and the median follow-up period for all 84 patients was 26.9 months (range, 2.7-77.3 months). Results: The 3-year actuarial overall survival, progression-free survival (PFS), and local control rates in all 84 patients after radiotherapy were 67%, 61%, and 93%, respectively. Although distant metastases and/or regional lymph node metastases developed in 34 patients (40%) after radiotherapy, local progression was observed in only 5 patients (6%). Of all 84 patients, the median nPSA12 in patients with clinical failure and in patients without clinical failure was 3.1 ng/mL and 0.5 ng/mL, respectively. When dividing patients according to low (<0.5 ng/mL) and high ({>=}0.5 ng/mL) nPSA12 levels, the 3-year PFS rate in patients with low nPSA12 and in those with high nPSA12 was 96% and 44%, respectively (p < 0.0001). In univariate analysis, nPSA12 and pretreatment PSA value had a significant impact on PFS, and in multivariate analysis nPSA12 alone was an independent prognostic factor for PFS after radiotherapy. Conclusions: External beam radiotherapy had an excellent local control rate for clinically localized hormone-refractory prostate cancer, and nPSA12 was predictive of clinical outcomes after radiotherapy.

  15. Sensitivity and specificity of clinical signs for assessment of dehydration in endurance athletes.

    PubMed

    McGarvey, J; Thompson, J; Hanna, C; Noakes, T D; Stewart, J; Speedy, D

    2010-08-01

    To investigate the diagnostic accuracy of commonly used signs of dehydration in marathon runners. The diagnostic accuracy of 5 clinical signs/symptoms thought to indicate dehydration (altered skin turgor, dry oral mucous membranes, sunken eyes, an inability to spit and the sensation of thirst) was assessed by comparing the presence of these markers with the criterion standard of body weight change over a marathon footrace. 2006 Auckland Marathon. 606 competitors in the full marathon. Body weight was measured before and immediately after the marathon. The 5 clinical signs/symptoms were assessed immediately after the marathon. Diagnostic accuracy of clinical signs/symptoms to detect dehydration greater than 3% of body weight. Results 606 complete data sets were obtained. 3 clinical signs were associated with greater percentage weight loss: sunken eyes (mean percentage weight loss with symptom 2.6% (standard deviation 1.5), without 2.3% (1.5)); decreased skin turgor (with 3.0% (1.4), without 2.3% (1.5)) and the sensation of thirst (with 2.5% (1.5), without 2.3% (1.5)). The ability to spit and dry oral mucous membranes were unrelated to percentage weight loss. No signs/symptoms showed acceptably high validity for detecting a weight loss equal to or greater than 3% of body weight. The 5 parameters (decreased skin turgor, sensation of thirst, sunken eyes, inability to spit and dry mucous membranes) tested in this study did not precisely identify runners with total weight loss >3% at the end of a marathon.

  16. Genetic and clinical specificity of 26 symptomatic carriers for dystrophinopathies at pediatric age.

    PubMed

    Mercier, Sandra; Toutain, Annick; Toussaint, Aurélie; Raynaud, Martine; de Barace, Claire; Marcorelles, Pascale; Pasquier, Laurent; Blayau, Martine; Espil, Caroline; Parent, Philippe; Journel, Hubert; Lazaro, Leila; Andoni Urtizberea, Jon; Moerman, Alexandre; Faivre, Laurence; Eymard, Bruno; Maincent, Kim; Gherardi, Romain; Chaigne, Denys; Ben Yaou, Rabah; Leturcq, France; Chelly, Jamel; Desguerre, Isabelle

    2013-08-01

    The molecular basis underlying the clinical variability in symptomatic Duchenne muscular dystrophy (DMD) carriers are still to be precised. We report 26 cases of early symptomatic DMD carriers followed in the French neuromuscular network. Clinical presentation, muscular histological analysis and type of gene mutation, as well as X-chromosome inactivation (XCI) patterns using DNA extracted from peripheral blood or muscle are detailed. The initial symptoms were significant weakness (88%) or exercise intolerance (27%). Clinical severity varied from a Duchenne-like progression to a very mild Becker-like phenotype. Cardiac dysfunction was present in 19% of the cases. Cognitive impairment was worthy of notice, as 27% of the carriers are concerned. The muscular analysis was always contributive, revealing muscular dystrophy (83%), mosaic in immunostaining (81%) and dystrophin abnormalities in western blot analysis (84%). In all, 73% had exonic deletions or duplications and 27% had point mutations. XCI pattern was biased in 62% of the cases. In conclusion, we report the largest series of manifesting DMD carriers at pediatric age and show that exercise intolerance and cognitive impairment may reveal symptomatic DMD carriers. The complete histological and immunohistological study of the muscle is the key of the diagnosis leading to the dystrophin gene analysis. Our study shows also that cognitive impairment in symptomatic DMD carriers is associated with mutations in the distal part of the DMD gene. XCI study does not fully explain the mechanisms as well as the wide spectrum of clinical phenotype, though a clear correlation between the severity of the phenotype and inactivation bias was observed.

  17. Clinical studies in oral allergen-specific immunotherapy: differences among allergens.

    PubMed

    Sato, Sakura; Yanagida, Noriyuki; Ogura, Kiyotake; Imai, Takanori; Utsunomiya, Tomohiro; Iikura, Katsuhito; Goto, Makiko; Asaumi, Tomoyuki; Okada, Yu; Koike, Yumi; Syukuya, Akinori; Ebisawa, Motohiro

    2014-01-01

    Oral immunotherapy (OIT) is a significant focus of treatment of food allergy. OIT appears to be effective in inducing desensitization, however, patients receiving OIT frequently developmild/moderate symptoms during the therapy. It has not been clearly established whether the clinical tolerance induced by OIT resembles natural tolerance. According to our data, the efficacy of OIT is different among food antigens, and it is comparatively difficult to achieve the clinical tolerance in milk OIT. Moreover, the definitive evidence of efficacy and safety with long-term therapy is limited. Further studies need to be offered to patients in clinical practice. Recently, novel treatments for food allergy, sublingual and epicutaneous immunotherapy, and combination treatment with an anti-IgE monoclonal antibody (omalizumab), have been examined in some studies. OIT combined with omalizumab increased the threshold doses of food without adverse reactions and may be of benefit in food allergy treatment. More studies are needed to demonstrate long-term safety and treatment benefits in a larger patient cohort. © 2014 S. Karger AG, Basel

  18. Use of patient specific 3D printed neurovascular phantoms to evaluate the clinical utility of a high resolution x-ray imager

    NASA Astrophysics Data System (ADS)

    Setlur Nagesh, S. V.; Russ, M.; Ionita, C. N.; Bednarek, D.; Rudin, S.

    2017-03-01

    Modern 3D printing technology can fabricate vascular phantoms based on an actual human patient with a high degree of precision facilitating a realistic simulation environment for an intervention. We present two experimental setups using 3D printed patient-specific neurovasculature to simulate different disease anatomies. To simulate the human neurovasculature in the Circle of Willis, patient-based phantoms with aneurysms were 3D printed using a Objet Eden 260V printer. Anthropomorphic head phantoms and a human skull combined with acrylic plates simulated human head bone anatomy and x-ray attenuation. For dynamic studies the 3D printed phantom was connected to a pulsatile flow loop with the anthropomorphic phantom underneath. By combining different 3D printed phantoms and the anthropomorphic phantoms, different patient pathologies can be simulated. For static studies a 3D printed neurovascular phantom was embedded inside a human skull and used as a positional reference for treatment devices such as stents. To simulate tissue attenuation acrylic layers were added. Different combinations can simulate different patient treatment procedures. The Complementary-Metal-Oxide-Semiconductor (CMOS) based High Resolution Fluoroscope (HRF) with 75μm pixels offers an advantage over the state-of-the-art 200 μm pixel Flat Panel Detector (FPD) due to higher Nyquist frequency and better DQE performance. Whether this advantage is clinically useful during an actual clinical neurovascular intervention can be addressed by qualitatively evaluating images from a cohort of various cases performed using both detectors. The above-mentioned method can offer a realistic substitute for an actual clinical procedure. Also a large cohort of cases can be generated and used for a HRF clinical utility determination study.

  19. Predicting Early Spelling Difficulties in Children with Specific Language Impairment: A Clinical Perspective

    ERIC Educational Resources Information Center

    Cordewener, Kim A. H.; Bosman, Anna M. T.; Verhoeven, Ludo

    2012-01-01

    This study focused on the precursors of spelling difficulties in first grade for children with specific language impairment (SLI). A sample of 58 second-year kindergartners in the Netherlands was followed until the end of first grade. Linguistic, phonological, orthographic, letter knowledge, memory, and nonverbal-reasoning skills were considered…

  20. Adiposity in children and adolescents: Correlates and clinical consequences of fat stored in specific body depots

    USDA-ARS?s Scientific Manuscript database

    The 2011 Pennington Biomedical Research Center's Scientific Symposium focused on adiposity in children and adolescents. The symposium was attended by 15 speakers and other invited experts. The specific objectives of the symposium were to (i) integrate the latest published and unpublished findings on...

  1. An audit of prostate-specific antigen and clinical symptoms in general practice.

    PubMed Central

    Ramachandran, S.; Foster, M. C.; Thomas, D. R.; Roalfe, A. K.; Hall, R. A.

    1998-01-01

    The objective was to devise local guidelines for the referral of patients with suspected prostatic carcinoma following evaluation by a retrospective audit of the value of the prostate-specific antigen concentration, together with age, urological symptoms, and digital rectal examination in the diagnosis of carcinoma of the prostate. Relevant details were collected from the notes of 582 patients from general practice and hospital. The significant diagnostic factors were ascertained by stepwise logistic regression. Prostate-specific antigen concentration, digital rectal examination and significant terminal dribbling were the most powerful factors in the diagnosis of carcinoma of the prostate. When prostate-specific antigen concentration was considered in isolation, a value of 6.5 ng/ml appeared appropriate for referral. Age was not significant, perhaps due to the narrow patient age range. The significant diagnostic factors were built into an algorithm calculating the probability of carcinoma of the prostate. This algorithm, together with prostate-specific antigen concentration results and digital rectal examination findings, forms the basis of the referral guidelines and a subsequent prospective study. PMID:9538483

  2. Specific Factors Influence Postconcussion Symptom Duration among Youth Referred to a Sports Concussion Clinic.

    PubMed

    Heyer, Geoffrey L; Schaffer, Caroline E; Rose, Sean C; Young, Julie A; McNally, Kelly A; Fischer, Anastasia N

    2016-07-01

    To identify the clinical factors that influence the duration of postconcussion symptoms among youth referred to a sports concussion clinic. A retrospective cohort study was conducted to evaluate several potential predictors of symptom duration via a Cox proportional hazards analyses. The individual postconcussion symptom scores were highly correlated, so these symptoms were analyzed in the statistical model as coefficients derived from principal component analyses. Among 1953 youth with concussion, 1755 (89.9%) had dates of reported symptom resolution. The remainder (10.1%) were lost to follow-up and censored. The median time to recovery was 18 days (range 1-353 days). By 30 days, 72.6% had recovered; by 60 days, 91.4% had recovered; and by 90 days, 96.8% had recovered. Several variables in a multivariate Cox model predicted postconcussion symptom duration: female sex (P < .001, hazard ratio [HR] = 1.28), continued activity participation (P = .02, HR = 1.13), loss of consciousness (P = .03, HR = 1.18), anterograde amnesia (P = .04, HR = 1.15), premorbid headaches (P = .03, HR = 1.15), symptom components from the day of concussion (emotion, P = .03, HR = 1.08), and the day of clinic evaluation (cognitive-fatigue, P < .001, HR = 1.22; cephalalgic, P < .001, HR = 1.27; emotional, P = .05, HR = 1.08; arousal-stimulation, P = .003, HR = 1.1). In univariate analyses, greater symptom scores generally predicted longer symptom durations. Worsening of symptoms from the day of concussion to the day of clinic evaluation also predicted longer recovery (P < .001, HR = 1.59). Several factors help to predict protracted postconcussion symptom durations among youth referred to a sports concussion clinic. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Dynamics of Leishmania-specific immunoglobulin isotypes in dogs with clinical leishmaniasis before and after treatment.

    PubMed

    Rodríguez, Alhelí; Solano-Gallego, Laia; Ojeda, Ana; Quintana, Josefina; Riera, Cristina; Gállego, Montserrat; Portús, Montserrat; Alberola, Jordi

    2006-01-01

    Concentrations of Leishmania-specific immunoglobulin G (IgG), immunoglobulin M (IgM), and immunoglobulin A (IgA) isotypes were analyzed by enzyme-linked immunosorbent assay (ELISA) in 23 dogs naturally infected with Leishmania infantum before and 1 year after initiating drug therapy. Results showed a high expression and prevalence of Leishmania-specific IgG (176.4 +/- 89 ELISA units [EU]), IgM (105.3 +/- 95.5 EU), and IgA (153.6 +/- 98 EU) in dogs before treatment (median +/- interquartile range EU). One year after treatment was started, dogs were classified as responsive dogs (RDs; n = 13) or unresponsive dogs (UDs; n = 10) based on clinicopathologic findings. Both groups of dogs experienced a statistically significant decrease (P < .05) in Leishmania-specific IgG (RDs = 27%, UDs = 41%), IgM (RDs = 42%, UDs = 29%), and IgA (RDs = 56%, UDs = 46%). Concentrations of specific IgG and IgM were not different at diagnosis or after treatment between the 2 groups. However, the median value for Leishmania-specific IgA 1 year after treatment was significantly lower (P < .05) in RDs (60.8 +/- 67 EU) than in UDs (117 +/- 54 EU). Examination of our data indicates that both the IgA isotype, which is mostly produced by mucosal plasma cells, and the IgM isotype are increased in infected symptomatic dogs, as previously reported for IgG. These 3 isotypes decreased significantly 1 year after initiation of medical treatment.

  4. Clinical Trials Using Adenovector-transduced AP1903-inducible MyD88/CD40-expressing Autologous PSMA-specific Prostate Cancer Vaccine BPX-201

    Cancer.gov

    NCI supports clinical trials that test new and more effective ways to treat cancer. Find clinical trials studying adenovector-transduced ap1903-inducible myd88/cd40-expressing autologous psma-specific prostate cancer vaccine bpx-201.

  5. A core outcome set for clinical trials on non-specific low back pain: study protocol for the development of a core domain set.

    PubMed

    Chiarotto, Alessandro; Terwee, Caroline B; Deyo, Richard A; Boers, Maarten; Lin, Chung-Wei Christine; Buchbinder, Rachelle; Corbin, Terry P; Costa, Leonardo O P; Foster, Nadine E; Grotle, Margreth; Koes, Bart W; Kovacs, Francisco M; Maher, Chris G; Pearson, Adam M; Peul, Wilco C; Schoene, Mark L; Turk, Dennis C; van Tulder, Maurits W; Ostelo, Raymond W

    2014-12-26

    Low back pain (LBP) is one of the most disabling and costly disorders affecting modern society, and approximately 90% of patients are labelled as having non-specific LBP (NSLBP). Several interventions for patients with NSLBP have been assessed in clinical trials, but heterogeneous reporting of outcomes in these trials has hindered comparison of results and performance of meta-analyses. Moreover, there is a risk of selective outcome reporting bias. To address these issues, the development of a core outcome set (COS) that should be measured in all clinical trials for a specific health condition has been recommended. A standardized set of outcomes for LBP was proposed in 1998, however, with evolution in COS development methodology, new instruments, interventions, and understanding of measurement properties, it is appropriate to update that proposal. This protocol describes the methods used in the initial step in developing a COS for NSLBP, namely, establishing a core domain set that should be measured in all clinical trials. An International Steering Committee including researchers, clinicians, and patient representatives from four continents was formed to guide the development of this COS. The approach of initiatives like Core Outcome Measures in Effectiveness Trials (COMET) and Outcome Measures in Rheumatology (OMERACT) was followed. Participants were invited to participate in a Delphi study aimed at generating a consensus-based core domain set for NSLBP. A list of potential core domains was drafted and presented to the Delphi participants who were asked to judge which domains were core. Participant suggestions about overlap, aggregation, or addition of potential core domains were addressed during the study. The patients' responses were isolated to assess whether there was substantial disagreement with the rest of the Delphi panel. A priori thresholds for consensus were established before each Delphi round. All participants' responses were analysed from a

  6. Development and Validation of Burkholderia pseudomallei-Specific Real-Time PCR Assays for Clinical, Environmental or Forensic Detection Applications

    PubMed Central

    Price, Erin P.; Dale, Julia L.; Cook, James M.; Sarovich, Derek S.; Seymour, Meagan L.; Ginther, Jennifer L.; Kaufman, Emily L.; Beckstrom-Sternberg, Stephen M.; Mayo, Mark; Kaestli, Mirjam; Glass, Mindy B.; Gee, Jay E.; Wuthiekanun, Vanaporn; Warner, Jeffrey M.; Baker, Anthony; Foster, Jeffrey T.; Tan, Patrick; Tuanyok, Apichai; Limmathurotsakul, Direk; Peacock, Sharon J.; Currie, Bart J.; Wagner, David M.; Keim, Paul; Pearson, Talima

    2012-01-01

    The bacterium Burkholderia pseudomallei causes melioidosis, a rare but serious illness that can be fatal if untreated or misdiagnosed. Species-specific PCR assays provide a technically simple method for differentiating B. pseudomallei from near-neighbor species. However, substantial genetic diversity and high levels of recombination within this species reduce the likelihood that molecular signatures will differentiate all B. pseudomallei from other Burkholderiaceae. Currently available molecular assays for B. pseudomallei detection lack rigorous validation across large in silico datasets and isolate collections to test for specificity, and none have been subjected to stringent quality control criteria (accuracy, precision, selectivity, limit of quantitation (LoQ), limit of detection (LoD), linearity, ruggedness and robustness) to determine their suitability for environmental, clinical or forensic investigations. In this study, we developed two novel B. pseudomallei specific assays, 122018 and 266152, using a dual-probe approach to differentiate B. pseudomallei from B. thailandensis, B. oklahomensis and B. thailandensis-like species; other species failed to amplify. Species specificity was validated across a large DNA panel (>2,300 samples) comprising Burkholderia spp. and non-Burkholderia bacterial and fungal species of clinical and environmental relevance. Comparison of assay specificity to two previously published B. pseudomallei-specific assays, BurkDiff and TTS1, demonstrated comparable performance of all assays, providing between 99.7 and 100% specificity against our isolate panel. Last, we subjected 122018 and 266152 to rigorous quality control analyses, thus providing quantitative limits of assay performance. Using B. pseudomallei as a model, our study provides a framework for comprehensive quantitative validation of molecular assays and provides additional, highly validated B. pseudomallei assays for the scientific research community. PMID:22624061

  7. Development and validation of Burkholderia pseudomallei-specific real-time PCR assays for clinical, environmental or forensic detection applications.

    PubMed

    Price, Erin P; Dale, Julia L; Cook, James M; Sarovich, Derek S; Seymour, Meagan L; Ginther, Jennifer L; Kaufman, Emily L; Beckstrom-Sternberg, Stephen M; Mayo, Mark; Kaestli, Mirjam; Glass, Mindy B; Gee, Jay E; Wuthiekanun, Vanaporn; Warner, Jeffrey M; Baker, Anthony; Foster, Jeffrey T; Tan, Patrick; Tuanyok, Apichai; Limmathurotsakul, Direk; Peacock, Sharon J; Currie, Bart J; Wagner, David M; Keim, Paul; Pearson, Talima

    2012-01-01

    The bacterium Burkholderia pseudomallei causes melioidosis, a rare but serious illness that can be fatal if untreated or misdiagnosed. Species-specific PCR assays provide a technically simple method for differentiating B. pseudomallei from near-neighbor species. However, substantial genetic diversity and high levels of recombination within this species reduce the likelihood that molecular signatures will differentiate all B. pseudomallei from other Burkholderiaceae. Currently available molecular assays for B. pseudomallei detection lack rigorous validation across large in silico datasets and isolate collections to test for specificity, and none have been subjected to stringent quality control criteria (accuracy, precision, selectivity, limit of quantitation (LoQ), limit of detection (LoD), linearity, ruggedness and robustness) to determine their suitability for environmental, clinical or forensic investigations. In this study, we developed two novel B. pseudomallei specific assays, 122018 and 266152, using a dual-probe approach to differentiate B. pseudomallei from B. thailandensis, B. oklahomensis and B. thailandensis-like species; other species failed to amplify. Species specificity was validated across a large DNA panel (>2,300 samples) comprising Burkholderia spp. and non-Burkholderia bacterial and fungal species of clinical and environmental relevance. Comparison of assay specificity to two previously published B. pseudomallei-specific assays, BurkDiff and TTS1, demonstrated comparable performance of all assays, providing between 99.7 and 100% specificity against our isolate panel. Last, we subjected 122018 and 266152 to rigorous quality control analyses, thus providing quantitative limits of assay performance. Using B. pseudomallei as a model, our study provides a framework for comprehensive quantitative validation of molecular assays and provides additional, highly validated B. pseudomallei assays for the scientific research community.

  8. Aquaporin-4 antibody isoform binding specificities do not explain clinical variations in NMO

    PubMed Central

    Kitley, Joanna; Woodhall, Mark; Leite, M. Isabel; Palace, Jackie; Waters, Patrick

    2015-01-01

    Objective: To assess the clinical relevance of the differential binding of antibodies against the 2 main aquaporin-4 (AQP4) isoforms in neuromyelitis optica (NMO) patient sera using stably transfected human embryonic kidney cells. Methods: Flow cytometry of human embryonic kidney cells stably transfected with either M23 or M1 AQP4 was used to measure antibody endpoint titers in 52 remission samples and 26 relapse samples from 34 patients with clinically well-characterized AQP4 antibody–positive NMO/NMO spectrum disorder. Results: The AQP4 M23 (40–61,440) and AQP4 M1 (<20–20,480) titers varied widely between patients, as did the M23:M1 antibody ratio (1–192). In 76 of 78 samples, binding to M23 was higher than binding to M1, including during relapses and remissions (p < 0.0001), and the M23:M1 ratio was relatively constant within an individual patient. Titers usually fell after immunosuppression, but the titers at which relapses occurred varied markedly; no threshold level for relapses could be identified, and relapses could occur without a rise in titers. Relapse severity did not correlate with M23 or M1 antibody titers, although there was a correlation between the earliest M23 titers and annualized relapse rates. The M23:M1 ratio and absolute M23 and M1 titers did not relate to age at disease onset, ethnicity, disease severity, phenotype, or relapses at different anatomical sites. Conclusion: Relative AQP4 antibody binding to M23 and M1 isoforms differs between patients but there is no consistent association between these differences and clinical characteristics of disease. Nevertheless, the M23 isoform provided a slightly more sensitive substrate for AQP4-antibody assays, particularly for follow-up studies. PMID:26140280

  9. Mutant allele specific imbalance in oncogenes with copy number alterations: Occurrence, mechanisms, and potential clinical implications.

    PubMed

    Yu, Chih-Chieh; Qiu, Wanglong; Juang, Caroline S; Mansukhani, Mahesh M; Halmos, Balazs; Su, Gloria H

    2017-01-01

    Mutant allele specific imbalance (MASI) was initially coined to describe copy number alterations associated with the mutant allele of an oncogene. The copy number gain (CNG) specific to the mutant allele can be readily observed in electropherograms. With the development of genome-wide analyses at base-pair resolution with copy number counts, we can now further differentiate MASI into those with CNG, with copy neutral alteration (also termed acquired uniparental disomy; UPD), or with loss of heterozygosity (LOH) due to the loss of the wild-type (WT) allele. Here we summarize the occurrence of MASI with CNG, aUPD, or MASI with LOH in some major oncogenes (such as EGFR, KRAS, PIK3CA, and BRAF). We also discuss how these various classifications of MASI have been demonstrated to impact tumorigenesis, progression, metastasis, prognosis, and potentially therapeutic responses in cancer, notably in lung, colorectal, and pancreatic cancers.

  10. Specific language impairment in Italian: the first steps in the search for a clinical marker.

    PubMed

    Bortolini, Umberta; Caselli, M Cristina; Deevy, Patricia; Leonard, Laurence B

    2002-01-01

    Recent studies of children with specific language impairment (SLI) have identified language measures that seem quite accurate in distinguishing preschool-age children with SLI from their normally developing peers. However, the studies have focussed exclusively on English, and it is clear from the literature that the SLI profile varies between languages. This paper reports on three studies designed to assess the utility of particular language measures for Italian. In the first two studies, it was found that a composite measure based on the use of definite singular articles and third-person plural inflections showed good sensitivity and specificity in distinguishing Italian-speaking children with SLI from their typically developing peers. The third study showed that the same composite can be applied successfully to individual cases of SLI. Some of the additional steps needed to evaluate this composite measure are discussed.

  11. Clinically Practical Magnetic Resonance Protocol for Improved Specificity in Breast Cancer Diagnosis

    DTIC Science & Technology

    2007-06-01

    method in breast cancer diagnosis. We have requested a no- cost extension of this grant to allow us to finish the recruitment of 150 patients as...demonstrates 100% sensitivity and 73% specificity. With the addition of the MRS and perfusion MRI results, assuming any negative finding from the two methods...Medicine. We are looking forward to the approval of the no- cost extension of the grant, which will allow us to finish the proposed accrual of 150

  12. Limitations of sensitivity, specificity, likelihood ratio, and bayes' theorem in assessing diagnostic probabilities: a clinical example.

    PubMed

    Moons, K G; van Es, G A; Deckers, J W; Habbema, J D; Grobbee, D E

    1997-01-01

    We evaluated the extent to which the sensitivity, specificity, and likelihood ratio of the exercise test to diagnose coronary artery disease vary across subgroups of a certain patient population. Among 295 patients suspected of coronary artery disease, as independently determined by coronary angiography, we assessed variation in sensitivity and specificity according to patient history, physical examination, exercise test results, and disease severity in 207 patients with and 88 patients without coronary artery disease, respectively. The sensitivity varied substantially according to sex (women 30% and men 64%), systolic blood pressure at baseline (53% to 65%), expected workload (50% to 64%), systolic blood pressure at peak exercise (50% to 67%), relative workload (33% to 68%), and number of diseased vessels (39% to 77%). The specificity varied across subgroups of sex (men 89% and women 97%) and relative workload (85% to 98%). The likelihood ratio varied (3.8 to 17.0) across the same patient subgroups, as did the sensitivity. As each population tends to be heterogeneous with respect to patient characteristics, no single level of these parameters can be given that is adequate for all subgroups. Use of these parameters as a basis for calculating diagnostic probabilities in individual patients using Bayes' theorem has serious limitations.

  13. Content Addressable Memory Project

    DTIC Science & Technology

    1990-11-01

    The Content Addressable M1-emory Project consists of the development of several experimental software systems on an AMT Distributed Array Processor...searching (database) compiler algorithms memory management other systems software) Linear C is an unlovely hybrid language which imports the CAM...memory from AMT’s operating system for the DAP; how- ever, other than this limitation, the memory management routines work exactly as their C counterparts

  14. Excerpts from keynote address

    SciTech Connect

    Creel, G.C.

    1995-06-01

    Excerpts from the keynote principally address emissions issues in the fossil power industry as related to heat rate improvements. Stack emissions of both sulfur and nitrogen oxides are discussed, and a number of examples are given: (1) PEPCO`s Potomac River Station, and (2) Morgantown station`s NOX reduction efforts. Circulating water emissions are also briefly discussed, as are O & M costs of emission controls.

  15. Holographic content addressable storage

    NASA Astrophysics Data System (ADS)

    Chao, Tien-Hsin; Lu, Thomas; Reyes, George

    2015-03-01

    We have developed a Holographic Content Addressable Storage (HCAS) architecture. The HCAS systems consists of a DMD (Digital Micromirror Array) as the input Spatial Light Modulator (SLM), a CMOS (Complementary Metal-oxide Semiconductor) sensor as the output photodetector and a photorefractive crystal as the recording media. The HCAS system is capable of performing optical correlation of an input image/feature against massive reference data set stored in the holographic memory. Detailed system analysis will be reported in this paper.

  16. KRAS analysis in colorectal carcinoma: Analytical aspects of Pyrosequencing and allele-specific PCR in clinical practice

    PubMed Central

    2010-01-01

    Background Epidermal growth factor receptor inhibitor therapy is now approved for treatment of metastatic colorectal carcinomas (CRC) in patients with tumors lacking KRAS mutations. Several procedures to detect KRAS mutations have been developed. However, the analytical sensitivity and specificity of these assays on routine clinical samples are not yet fully characterised. Methods The practical aspects and clinical applicability of a KRAS-assay based on Pyrosequencing were evaluated in a series of 314 consecutive CRC cases submitted for diagnostic KRAS analysis. The performance of Pyrosequencing compared to allele-specific, real-time PCR was then explored by a direct comparison of CE-IVD-marked versions of Pyrosequencing and TheraScreen (DxS) KRAS assays for a consecutive subset (n = 100) of the 314 clinical CRC samples. Results Using Pyrosequencing, 39% of the 314 CRC samples were found KRAS-mutated and several of the mutations (8%) were located in codon 61. To explore the analytical sensitivity of the Pyrosequencing assay, mutated patient DNA was serially diluted with wild-type patient DNA. Dilutions corresponding to 1.25-2.5% tumor cells still revealed detectable mutation signals. In clinical practice, our algorithm for KRAS analysis includes a reanalysis of samples with low tumor cell content (< 10%, n = 56) using an independent assay (allele-specific PCR, DxS). All mutations identified by Pyrosequencing were then confirmed and, in addition, one more mutated sample was identified in this subset of 56 samples. Finally, a direct comparison of the two technologies was done by re-analysis of a subset (n = 100) of the clinical samples using CE-IVD-marked versions of Pyrosequencing and TheraScreen KRAS assays in a single blinded fashion. The number of samples for which the KRAS codon 12/13 mutation status could be defined using the Pyrosequencing or the TheraScreen assay was 94 and 91, respectively, and both assays detected the same number of codon 12 and 13

  17. Randomised clinical trial investigating the specificity of a novel skin test (C-Tb) for diagnosis of M. tuberculosis infection.

    PubMed

    Aggerbeck, Henrik; Giemza, Rafaela; Joshi, Paulatsya; Tingskov, Pernille N; Hoff, Søren T; Boyle, Julia; Andersen, Peter; Lewis, David J M

    2013-01-01

    Tuberculin skin testing is simple and relatively inexpensive, but the specificity of PPD is affected by BCG vaccination. Determine optimal dose and specificity of recombinant ESAT-6 and CFP-10 (C-Tb) produced in Lactococcus lactis for diagnosis of M. tuberculosis infection. In a dose finding phase I trial 0.01 or 0.1 µg preserved and unpreserved C-Tb was injected by Mantoux technique in 38 patients with active tuberculosis and induration responses measured. In a phase II specificity trial in 151 uninfected, BCG vaccinated participants 0.1 µg C-Tb was compared to 2 TU PPD. 0.1 µg C-Tb gave a median induration of 15 mm after 2 days. Phenol preservation did not affect the response. The specificity of C-Tb was 99.3% (95% CI 96-100%) regarding indurations ≥5 mm as a positive outcome. This was higher than the specificity of PPD (63% using a cut-off of 5 mm or 92% using a cut-off of 15 mm to adjust for non-specific BCG responses). Local adverse reactions following C-Tb injection included transient itching and discomfort as expected components of the immune response. C-Tb offers a simple and convenient skin test to diagnose M. tuberculosis infection using a single, universal cut-off unaffected by BCG vaccination. ClinicalTrials.gov NCT01033929 and NCT01241188.

  18. Outcome tools for diabetes-specific quality of life: Study performed in a private family practice clinic.

    PubMed

    Nair, Rajesh; Kachan, Paul

    2017-06-01

    To critically review and evaluate the psychometric properties and practical considerations of administering generic and diabetes-specific quality-of-life (QoL) tools in the clinical environment and provide recommendations. A MEDLINE search was carried out from January 1950 to August 2015 using the MeSH terms diabetes, quality of life, and questionnaires. Four generic and 4 diabetes-specific tools were selected based on the frequency of their use and the existence of published evidence of strong psychometric properties in patients with diabetes (either type 1 or 2). The generic tools included the Short Form-36 (SF-36), Short Form-12 (SF-12), Sickness Impact Profile, and EuroQol EQ-5D instruments. Diabetes-specific tools included the Audit of Diabetes-Dependent Quality of Life, Diabetes Quality of Life, Appraisal of Diabetes Scale (ADS), and Diabetes Health Profile instruments. The SF-36 is one of the most widely used general health measures in QoL research and it has proven reliability and validity. However, the SF-12 is a better option for a family practice owing to its shorter length. The SF-12 has been shown to be closely correlated with the SF-36. Of the diabetes-specific measures, the ADS is known be valid, short, and relatively straightforward in terms of scoring, thereby increasing its usefulness in routine clinical practice. The Audit of Diabetes-Dependent Quality of Life and Diabetes Quality of Life tools have been widely tested and have generally been found to be more valid and reliable than the ADS, but specific issues with feasibility make them unappealing for the clinical setting. The rationale was to find the most rigorously tested instrument within the scientific literature in terms of validity, reliability, and responsiveness. However, this was not done, as judging the quality of a measure is not simply a matter of determining its psychometric properties but rather requires qualitative judgment about the entirety of the evidence. Finding ideal tools

  19. 16 CFR 0.2 - Official address.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Official address. 0.2 Section 0.2 Commercial Practices FEDERAL TRADE COMMISSION ORGANIZATION, PROCEDURES AND RULES OF PRACTICE ORGANIZATION § 0.2... 20580, unless otherwise specifically directed. The Commission's Web site address is www.ftc.gov....

  20. Ezetimibe: an update on its clinical usefulness in specific patient groups

    PubMed Central

    Hammersley, Daniel; Signy, Mark

    2016-01-01

    The aim of pharmacological lipid modification is to reduce low-density lipoprotein cholesterol (LDL-C) as a means of either secondary or primary prevention of cardiovascular disease. Statins are the first-line therapy for pharmacological lipid modification. Ezetimibe is a drug which reduces LDL-C by selectively inhibiting intestinal cholesterol absorption. This provides an alternative pharmacological approach to that of statin therapy to reduce LDL-C. Ezetimibe has been shown to significantly reduce levels of LDL-C and recently, as demonstrated in the IMPROVE-IT trial, to reduce the rate of cardiovascular events in high-risk patients. Ezetimibe therefore has an important role in pharmacological lipid modification. In this paper, we examine the body of research behind ezetimibe and assess its current clinical applications in different patient subgroups. PMID:28203346

  1. Site-specific chemokine expression regulates CNS inflammation and determines clinical phenotype in autoimmune encephalomyelitis1

    PubMed Central

    Stoolman, Joshua S.; Duncker, Patrick C.; Huber, Amanda K.; Segal, Benjamin M.

    2014-01-01

    The adoptive transfer of myelin-reactive T cells into wildtype (WT)2 hosts results in spinal cord inflammation and ascending paralysis, referred to as conventional experimental autoutoimmune encephalitis (EAE)3, as opposed to brainstem inflammation and ataxia, which characterize disease in IFNγRKO hosts (atypical EAE). Here we show that atypical EAE correlates with preferential upregulation of CXCL2 in the brainstem, and is driven by CXCR2 dependent recruitment of neutrophils. In contrast, conventional EAE is associated with upregulation of CCL2 in the spinal cord, and is driven by recruitment of monocytes via a partially CCR2-dependent pathway. This study illustrates how regional differences in chemokine expression within a target organ shape the spatial pattern and composition of autoimmune infiltrates, leading to disparate clinical outcomes. PMID:24928987

  2. [The immunological mechanisms contributing to the clinical efficacy of allergen specific immunotherapy (SIT) in allergic diseases].

    PubMed

    Asher, Ilan; Mahlab-Guri, Keren; Sthoeger, Zev

    2013-09-01

    The prevalence of allergic diseases has increased dramatically in the western world. In the last 2 decades, the frequency of asthma and allergic rhinitis has doubled. Allergen specific immunotherapy [SIT] has been used successfully for more than 100 years for the treatment of allergic disorders. Allergen SIT provides not only symptomatic relief, but it is potentially curative. The immunologic mechanisms of allergen SIT include all parts of the immune system. Regulatory T cells (TR1, Treg), have a major pivotal role in the success of immunotherapy. Along with the regulatory T cells, elevated suppressor cytokines (IL-10), suppression of TH2 cells, increasing titer of specific IgG4 and gradual decline in the number and function of basophils and mast cells also contribute to the success of the treatment (SIT). The above immune mechanisms are connected and related to each other acting at different times with the treatment with SIT. In this review we focused on the current knowledge and understanding of the different immune mechanisms which are involved in the success of SIT.

  3. [Specific developmental language disorder: a theoretical approach to its diagnosis, aetiology and clinical symptoms].

    PubMed

    Castro-Rebolledo, R; Giraldo-Prieto, M; Hincapié-Henao, L; Lopera, F; Pineda, D A

    This article presents an updated review about the definition, diagnostic criteria, classifications, etiology and the evolution of the specific language impairment (SLI). The specific language impairment is characterized by a developmental language delay and an impaired language, that persist over time and it is not explained by sensorial, motor and mental disabilities, neither by psycopathological disorders, socio-emotional deprivation, nor brain injury. The diagnosis is based on exclusional criteria. Some researchers propose different classifications considering the children performance in language comprehension and language production. Genetical linkage to the FOXP2 gen in the SPCH1 region of the chromosome 7 and to the chromosomes 13, 16 y 19 has been reported. The neuroimage studies have shown alterations in the volume and perfusion of some brain structures related to language. The manifestations of SLI may change during the development of the children and may disturb the self-esteem, the academic performance and the social abilities. The variability in the linguistic and cognitive performance, and the variety in the etiological findings in children with SLI, don't allow to settle the affected population as an homogeneous group. Different theoretical positions have emerged as a consequence of this condition.

  4. Clinical Control of HIV-1 by Cytotoxic T Cells Specific for Multiple Conserved Epitopes

    PubMed Central

    Murakoshi, Hayato; Akahoshi, Tomohiro; Koyanagi, Madoka; Chikata, Takayuki; Naruto, Takuya; Maruyama, Rie; Tamura, Yoshiko; Ishizuka, Naoki; Gatanaga, Hiroyuki; Oka, Shinichi

    2015-01-01

    ABSTRACT Identification and characterization of CD8+ T cells effectively controlling HIV-1 variants are necessary for the development of AIDS vaccines and for studies of AIDS pathogenesis, although such CD8+ T cells have been only partially identified. In this study, we sought to identify CD8+ T cells controlling HIV-1 variants in 401 Japanese individuals chronically infected with HIV-1 subtype B, in which protective alleles HLA-B*57 and HLA-B*27 are very rare, by using comprehensive and exhaustive methods. We identified 13 epitope-specific CD8+ T cells controlling HIV-1 in Japanese individuals, though 9 of these epitopes were not previously reported. The breadths of the T cell responses to the 13 epitopes were inversely associated with plasma viral load (P = 2.2 × 10−11) and positively associated with CD4 count (P = 1.2 × 10−11), indicating strong synergistic effects of these T cells on HIV-1 control in vivo. Nine of these epitopes were conserved among HIV-1 subtype B-infected individuals, whereas three out of four nonconserved epitopes were cross-recognized by the specific T cells. These findings indicate that these 12 epitopes are strong candidates for antigens for an AIDS vaccine. The present study highlighted a strategy to identify CD8+ T cells controlling HIV-1 and demonstrated effective control of HIV-1 by those specific for 12 conserved or cross-reactive epitopes. IMPORTANCE HLA-B*27-restricted and HLA-B*57-restricted cytotoxic T lymphocytes (CTLs) play a key role in controlling HIV-1 in Caucasians and Africans, whereas it is unclear which CTLs control HIV-1 in Asian countries, where HLA-B*57 and HLA-B*27 are very rare. A recent study showed that HLA-B*67:01 and HLA-B*52:01-C*12:02 haplotypes were protective alleles in Japanese individuals, but it is unknown whether CTLs restricted by these alleles control HIV-1. In this study, we identified 13 CTLs controlling HIV-1 in Japan by using comprehensive and exhaustive methods. They included 5 HLA-B*52

  5. Content addressable memory project

    NASA Technical Reports Server (NTRS)

    Hall, J. Storrs; Levy, Saul; Smith, Donald E.; Miyake, Keith M.

    1992-01-01

    A parameterized version of the tree processor was designed and tested (by simulation). The leaf processor design is 90 percent complete. We expect to complete and test a combination of tree and leaf cell designs in the next period. Work is proceeding on algorithms for the computer aided manufacturing (CAM), and once the design is complete we will begin simulating algorithms for large problems. The following topics are covered: (1) the practical implementation of content addressable memory; (2) design of a LEAF cell for the Rutgers CAM architecture; (3) a circuit design tool user's manual; and (4) design and analysis of efficient hierarchical interconnection networks.

  6. Bioreactors Addressing Diabetes Mellitus

    PubMed Central

    Minteer, Danielle M.; Gerlach, Jorg C.

    2014-01-01

    The concept of bioreactors in biochemical engineering is a well-established process; however, the idea of applying bioreactor technology to biomedical and tissue engineering issues is relatively novel and has been rapidly accepted as a culture model. Tissue engineers have developed and adapted various types of bioreactors in which to culture many different cell types and therapies addressing several diseases, including diabetes mellitus types 1 and 2. With a rising world of bioreactor development and an ever increasing diagnosis rate of diabetes, this review aims to highlight bioreactor history and emerging bioreactor technologies used for diabetes-related cell culture and therapies. PMID:25160666

  7. Bioreactors addressing diabetes mellitus.

    PubMed

    Minteer, Danielle M; Gerlach, Jorg C; Marra, Kacey G

    2014-11-01

    The concept of bioreactors in biochemical engineering is a well-established process; however, the idea of applying bioreactor technology to biomedical and tissue engineering issues is relatively novel and has been rapidly accepted as a culture model. Tissue engineers have developed and adapted various types of bioreactors in which to culture many different cell types and therapies addressing several diseases, including diabetes mellitus types 1 and 2. With a rising world of bioreactor development and an ever increasing diagnosis rate of diabetes, this review aims to highlight bioreactor history and emerging bioreactor technologies used for diabetes-related cell culture and therapies. © 2014 Diabetes Technology Society.

  8. Identification of H. pylori strain specific DNA sequences between two clinical isolates from NUD and gastric ulcer by SSH.

    PubMed

    Han, Feng-Chan; Gong, Min; Ng, Han-Chong; Ho, Bow

    2003-08-01

    The genomes of Helicobacter pylori (H. pylori) from different individuals are different. This project was to identify the strain specific DNA sequences between two clinical H. pylori isolates by suppression subtractive hybridization (SSH). Two clinical H. pylori isolates, one from gastric ulcer (GU, tester) and the other from non-ulcer dyspepsia (NUD, driver), were cultured and the genomic DNA was prepared and submitted to Alu I digestion. Then two different adaptors were ligated respectively to the 5'-end of two aliquots of the tester DNA fragments and SSH was made between the tester and driver DNA. The un-hybridized tester DNA sequences were amplified by two sequential PCR and cloned into pGEM-T-Easy Vector. The tester strain specific inserts were screened and disease related DNA sequences were identified by dot blotting. Among the 240 colonies randomly chosen, 50 contained the tester strain specific DNA sequences. Twenty three inserts were sequenced and the sizes ranged from 261 bp to 1 036 bp. Fifteen inserts belonged to the H.pylori plasmid pHPO100 that is about 3.5 kb and codes a replication protein A. Other inserts had patches of homologous to the genes of H.pylori in GenBank. Various patterns of dot blots were given and no GU strain unique DNA sequences were found when 4 inserts were used as probes to screen the genomic DNA from 27 clinical isolates, 8 from GU, 12 from duodenum ulcer (DU), 4 from GU-DU, 2 from NUD and 1 from gastric cancer (GC). But a 670 bp DNA fragment (GU198) that was a bit homologous to the 3'-end of the gene of thymidylate kinase was positive in 7 GU strains (7/8), 3 GU-DU strains (3/4) and 3 DU strains (3/12). A 384 bp fragment (GU79) of the replication gene A (repA) was positive only in 4 H.pylori isolates, 2 from GU and 2 from GU-DU. Differences exist in the genes of different H.pylori isolates. SSH is very effective to screen H.pylori strain specific DNA sequences between two clinical isolates, and some of these sequences may have

  9. Identification of H. pylori strain specific DNA sequences between two clinical isolates from NUD and gastric ulcer by SSH

    PubMed Central

    Han, Feng-Chan; Gong, Min; Ng, Han-Chong; Ho, Bow

    2003-01-01

    AIM: The genomes of Helicobacter pylori (H. pylori) from different individuals are different. This project was to identify the strain specific DNA sequences between two clinical H. pylori isolates by suppression subtractive hybridization (SSH). METHODS: Two clinical H. pylori isolates, one from gastric ulcer (GU, tester) and the other from non-ulcer dyspepsia (NUD, driver), were cultured and the genomic DNA was prepared and submitted to Alu I digestion. Then two different adaptors were ligated respectively to the 5’-end of two aliquots of the tester DNA fragments and SSH was made between the tester and driver DNA. The un-hybridized tester DNA sequences were amplified by two sequential PCR and cloned into pGEM-T-Easy Vector. The tester strain specific inserts were screened and disease related DNA sequences were identified by dot blotting. RESULTS: Among the 240 colonies randomly chosen, 50 contained the tester strain specific DNA sequences. Twenty three inserts were sequenced and the sizes ranged from 261 bp to 1036 bp. Fifteen inserts belonged to the H.pylori plasmid pHPO100 that is about 3.5 kb and codes a replication protein A. Other inserts had patches of homologous to the genes of H.pylori in GenBank. Various patterns of dot blots were given and no GU strain unique DNA sequences were found when 4 inserts were used as probes to screen the genomic DNA from 27 clinical isolates, 8 from GU, 12 from duodenum ulcer (DU), 4 from GU-DU, 2 from NUD and 1 from gastric cancer (GC). But a 670 bp DNA fragment (GU198) that was a bit homologous to the 3’-end of the gene of thymidylate kinase was positive in 7 GU strains (7/8), 3 GU-DU strains (3/4) and 3 DU strains (3/12). A 384 bp fragment (GU79) of the replication gene A (repA) was positive only in 4 H.pylori isolates, 2 from GU and 2 from GU-DU. CONCLUSION: Differences exist in the genes of different H.pylori isolates. SSH is very effective to screen H.pylori strain specific DNA sequences between two clinical isolates

  10. Predicting early spelling difficulties in children with specific language impairment: a clinical perspective.

    PubMed

    Cordewener, Kim A H; Bosman, Anna M T; Verhoeven, Ludo

    2012-01-01

    This study focused on the precursors of spelling difficulties in first grade for children with specific language impairment (SLI). A sample of 58 second-year kindergartners in The Netherlands was followed until the end of first grade. Linguistic, phonological, orthographic, letter knowledge, memory, and nonverbal-reasoning skills were considered as precursors, as was spelling level at an earlier point in time. Spelling difficulties at the end of first grade were most accurately identified by letter knowledge at the beginning of first grade and word spelling at the middle of first grade. It is concluded that spelling development in children with SLI can be seen as an autocatalytic process in which, without intervention, poor spellers generally remain poor spellers, and good spellers remain good spellers. A focus on early spelling intervention is thus emphasized. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Sensitivity and specificity of cone beam computed tomography in thin bony structures in maxillofacial surgery – A clinical trial.

    PubMed

    Thönissen, P; Ermer, M A; Schmelzeisen, R; Gutwald, R; Metzger, M C; Bittermann, G

    2015-09-01

    Cone-Beam Computed Tomography (CBCT) has become widely used in dentistry and maxillofacial surgery. Accuracy, sensitivity and specificity of thin bony structures below 0.5 mm have been subject of some in vitro studies. This prospective in vivo study investigates the correlation between preoperative CBCT-imaging and intraoperative clinical examination of thin bony structures. We hereby present results from daily clinical routine. A total number of 80 sites in 64 patients has been examined to differentiate between preoperative 3D imaging and clinical measurements on cystic lesions in maxilla and mandible. Different CBCT-devices with a voxel size ranging from 0.08 mm to 0.4 mm were used. Overall-specificity found for detecting thin bony structures of the human jaw is 13.89%, overall sensitivity is 100%, positive predictive value (PPV) is 58.67% and negative predictive value (NPV) is 100%. Image quality is the key to make use of additional information CBCT provides and depends on spatial, temporal and contrast resolution. CBCT does not depict reliably thin bony structures of the jaw, even if high voxel resolution is used. In selected cases using high resolution protocols should be considered despite affecting the patient with higher doses of radiation. Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  12. Performance-based quality specifications: the relationship between process critical control parameters, critical quality attributes, and clinical performance.

    PubMed

    Short, Steven M; Cogdill, Robert P; Drennen, James K; Anderson, Carl A

    2011-04-01

    The quality of pharmaceutical products is currently evaluated through a series of tests that do not explicitly communicate the clinical consequences of product variability. A previously published risk simulation platform was used to generate quantitative estimates of inefficacy and toxicity for 288 uniform lots of extended-release theophylline tablets displaying various levels of content uniformity and dissolution variability. These data were used to evaluate the univariate specifications utilized in the United States Pharmacopeia (USP) <711> and <905>. Simulation revealed that the specifications are too lenient for content uniformity, both in terms of inefficacy and toxicity, whereas the criteria for dissolution testing are too strict for inefficacy and inaccurate for toxicity. The USP tests also failed to pinpoint the clinical interaction between content uniformity and dissolution variability. Additionally, the simulation platform was used to define the underlying relationship between product quality attributes and clinical performance. Here, content uniformity and Weibull dissolution time constants were used as inputs to the design spaces, which were conditioned on quantitative estimates of inefficacy and toxicity. This methodology enhances the information content of the design space by omitting quality surrogates (e.g., dissolution, moisture content) that are utilized in current design space practices.

  13. Evaluation of Humoral Immunity to Mycobacterium tuberculosis-Specific Antigens for Correlation with Clinical Status and Effective Vaccine Development

    PubMed Central

    Niki, Mamiko; Suzukawa, Maho; Akashi, Shunsuke; Nagai, Hideaki; Ohta, Ken; Inoue, Manabu; Niki, Makoto; Kaneko, Yukihiro; Morimoto, Kozo; Kurashima, Atsuyuki; Kitada, Seigo; Matsumoto, Sohkichi; Suzuki, Koichi; Hoshino, Yoshihiko

    2015-01-01

    Although tuberculosis remains a major global health problem, Bacille Calmette-Guérin (BCG) is the only available vaccine. However, BCG has limited applications, and a more effective vaccine is needed. Cellular mediated immunity (CMI) is thought to be the most important immune response for protection against Mycobacterium tuberculosis (Mtb). However, the recent failure of a clinical trial for a booster BCG vaccine and increasing evidence of antibody-mediated immunity prompted us to evaluate humoral immunity to Mtb-specific antigens. Using Enzyme-Linked ImmunoSpot and Enzyme-Linked ImmunoSorbent Assays, we observed less correlation of both CMI and IgG titers with patient clinical status, including serum concentration of C reactive protein. However, IgA titers against Mtb were significantly correlated with clinical status, suggesting that specific IgA antibodies protect against Mtb proliferation. In addition, in some cases, IgA antibody titers were significantly associated with the serum concentration of total albumin, which supports the idea that humoral immunity can be influenced by the nutritional status. Based on these observations, we propose that the induction of humoral immunity should be included as an option in TB vaccine development strategies. PMID:26568961

  14. Specification of covariance structure in longitudinal data analysis for randomized clinical trials.

    PubMed

    Lu, Kaifeng; Mehrotra, Devan V

    2010-02-20

    Misspecification of the covariance structure for repeated measurements in longitudinal analysis may lead to biased estimates of the regression parameters and under or overestimation of the corresponding standard errors in the presence of missing data. The so-called sandwich estimator can 'correct' the variance, but it does not reduce the bias in point estimates. Removing all assumptions from the covariance structure (i.e. using an unstructured (UN) covariance) will remove such biases. However, an excessive amount of missing data may cause convergence problems for iterative algorithms, such as the default Newton-Raphson algorithm in the popular SAS PROC MIXED. This article examines, both through theory and simulations, the existence and the magnitude of these biases. We recommend the use of UN covariance as the default strategy for analyzing longitudinal data from randomized clinical trials with moderate to large number of subjects and small to moderate number of time points. We also present an algorithm to assist in the convergence when the UN covariance is used. (c) 2009 John Wiley & Sons, Ltd.

  15. Frequency-specific electric response audiometry (ERA) and its clinical application in the diagnosis of hearing defects in the dog.

    PubMed

    Schacks, S; Rohn, K; Hauschild, G

    2006-03-01

    Reference values were established for frequency-specific electric response audiometry (ERA) in dogs on the basis of the results of ERA examinations of 200 animals with normal hearing. Air-conducting acoustic tubes with foam stoppers were used in the determination of the following: the latencies of waves I, III and V; interpeak latencies (IPL) I-III, III-V and I-V; amplitudes I and V; and the amplitude difference I-V. A frequency-specific stimulus (tone pip) was used for frequency-specific examination (1 to 4 kHz) over the entire frequency range indicated. These reference values were then used for the clinical examination of 50 dogs with hearing defects. A frequency-specific ERA was conducted and the results evaluated. These findings made it possible to draw objective conclusions about the degree, type and site of the hearing defects. Frequency-specific electric response audiometry was shown to be an important diagnostic tool for the detection of partial high- and low-frequency hearing loss and for the characterisation of hearing defects of otological, otoneurological and neurological origin.

  16. Evidence of no protection for a recurrent case of pathogen specific clinical mastitis from a previous case.

    PubMed

    Cha, Elva; Hertl, Julia; Schukken, Ynte; Tauer, Loren; Welcome, Frank; Gröhn, Yrjö

    2016-02-01

    The objective of this study was to determine whether the occurrence of a previous case of pathogen-specific clinical mastitis (CM) protects Holstein dairy cows against a recurrent case. Pathogens studied were Escherichia coli, Staphylococcus aureus, Staphylococcus spp., Streptococcus spp., Klebsiella spp., and Trueperella pyogenes. A total of 40 864 lactations (17,265 primiparous and 23,599 multiparous) from 19 835 cows from 5 large, high milk producing New York State dairy herds were analysed. We estimated the effects of parity, calving diseases, milk yield, current season and number of CM cases in the previous lactation on the risk of a first CM case using generalised linear mixed models with a log link and Poisson error distribution. The aforementioned risk factors and the occurrence of previous cases of pathogen-specific CM within the current lactation were evaluated as risks for second and third cases of pathogen-specific CM. Cows with more CM cases in the previous lactation were at greater risk of pathogen-specific CM in the current lactation. Multiparous cows were at greater risk of a second CM case if they had suffered from a first CM case that was caused by the same pathogen as the second case. In contrast, a second CM case generally put cows at greater risk of a third case, irrespective of whether the third case was caused by the same or a different pathogen. Our results showed that a previous case of pathogen specific CM does not generally protect against a recurrent case.

  17. An "alternating instructions" version of the Autobiographical Memory Test for assessing autobiographical memory specificity in non-clinical populations.

    PubMed

    Dritschel, Barbara; Beltsos, Stamatis; McClintock, Shawn M; Beltosis, Stamatis

    2014-01-01

    There is limited research regarding how executive processes contribute to key cognitive deficits in depression, particularly impoverished retrieval of autobiographical memory. This study tested a novel version of the Autobiographical Memory Test (AMT), the "Alternating Instructions" AMT (AMT-AI), to determine how participants could flexibly retrieve specific and categoric autobiographical memories. The AMT-AI consisted of a standard AMT (AMT-S), a categoric version of the AMT (AMT-R), and a section of alternating instructions (AI) in which the rules required the participant to alternate between retrieval of categoric and specific memories. A total of 49 university students completed the AMT-AI, and self-report measures of depressive symptomatology and ruminative thinking. Results showed that the mean proportion of specific memories recalled on the AMT-AI was significantly lower than on the AMT-S. Also, reduced memory specificity on the AMT-AI, but not the AMT-S, was significantly negatively correlated with increased scores on measures of depressive symptomatology and ruminative thinking. Collectively the data suggested that the AMT-AI, relative to the traditional AMT, may be more sensitive to memory specificity in non-clinical populations. Future research is warranted to further determine the psychometric properties and utility of the AMT-AI.

  18. Site-specific mouth rinsing can improve oral odor by altering bacterial counts. Blind crossover clinical study.

    PubMed

    Alqumber, Mohammed A; Arafa, Khaled A

    2014-11-01

    To determine whether site-specific mouth rinsing with oral disinfectants can improve oral odor beyond the traditional panoral mouth disinfection with mouth rinses by targeting specifically oral malodor implicated anaerobic bacteria. Twenty healthy fasting subjects volunteered for a blinded prospective, descriptive correlational crossover cross-section clinical trial conducted during the month of Ramadan between July and August 2013 in Albaha province in Saudi Arabia involving the application of Listerine Cool Mint mouth rinse by either the traditional panoral rinsing method, or a site-specific disinfection method targeting the subgingival and supragingival plaque and the posterior third of the tongue dorsum, while avoiding the remaining locations within the oral cavity. The viable anaerobic and aerobic bacterial counts, volatile sulfur compounds (VSCs) levels, organoleptic assessment of oral odor, and the tongue-coating index were compared at baseline, one, 5, and 9 hours after the treatment. The site-specific disinfection method reduced the VSCs and anaerobic bacterial loads while keeping the aerobic bacterial numbers higher than the traditional panoral rinsing method. Site-specific disinfection can more effectively maintain a healthy oral cavity by predominantly disinfecting the niches of anaerobic bacteria within the oral cavity.

  19. Addressing Environmental Health Inequalities.

    PubMed

    Gouveia, Nelson

    2016-08-27

    Environmental health inequalities refer to health hazards disproportionately or unfairly distributed among the most vulnerable social groups, which are generally the most discriminated, poor populations and minorities affected by environmental risks. Although it has been known for a long time that health and disease are socially determined, only recently has this idea been incorporated into the conceptual and practical framework for the formulation of policies and strategies regarding health. In this Special Issue of the International Journal of Environmental Research and Public Health (IJERPH), "Addressing Environmental Health Inequalities-Proceedings from the ISEE Conference 2015", we incorporate nine papers that were presented at the 27th Conference of the International Society for Environmental Epidemiology (ISEE), held in Sao Paulo, Brazil, in 2015. This small collection of articles provides a brief overview of the different aspects of this topic. Addressing environmental health inequalities is important for the transformation of our reality and for changing the actual development model towards more just, democratic, and sustainable societies driven by another form of relationship between nature, economy, science, and politics.

  20. Addressing Environmental Health Inequalities

    PubMed Central

    Gouveia, Nelson

    2016-01-01

    Environmental health inequalities refer to health hazards disproportionately or unfairly distributed among the most vulnerable social groups, which are generally the most discriminated, poor populations and minorities affected by environmental risks. Although it has been known for a long time that health and disease are socially determined, only recently has this idea been incorporated into the conceptual and practical framework for the formulation of policies and strategies regarding health. In this Special Issue of the International Journal of Environmental Research and Public Health (IJERPH), “Addressing Environmental Health Inequalities—Proceedings from the ISEE Conference 2015”, we incorporate nine papers that were presented at the 27th Conference of the International Society for Environmental Epidemiology (ISEE), held in Sao Paulo, Brazil, in 2015. This small collection of articles provides a brief overview of the different aspects of this topic. Addressing environmental health inequalities is important for the transformation of our reality and for changing the actual development model towards more just, democratic, and sustainable societies driven by another form of relationship between nature, economy, science, and politics. PMID:27618906

  1. Patient-specific assessment of left ventricular thrombogenesis risk after acute myocardial infarction: a pilot clinical study

    NASA Astrophysics Data System (ADS)

    Rossini, L.; Khan, A.; Del Alamo, J. C.; Martinez-Legazpi, P.; Pérez Del Villar, C.; Benito, Y.; Yotti, R.; Barrio, A.; Delgado-Montero, A.; Gonzalez-Mansilla, A.; Fernandez-Avilés, F.; Bermejo, J.

    2016-11-01

    Left ventricular thrombosis (LVT) is a major complication of acute myocardial infarction (AMI). In these patients, the benefits of chronic anticoagulation therapy need to be balanced with its pro-hemorrhagic effects. Blood stasis in the cardiac chambers, a risk factor for LVT, is not addressed in current clinical practice. We recently developed a method to quantitatively assess the blood residence time (RT) inside the left ventricle (LV) based on 2D color-Doppler velocimetry (echo-CDV). Using time-resolved blood velocity fields acquired non-invasively, we integrate a modified advection equation to map intraventricular stasis regions. Here, we present how this tool can be used to estimate the risk of LVT in patients with AMI. 73 patients with a first anterior-AMI were studied by echo-CDV and RT analysis within 72h from admission and at a 5-month follow-up. Patients who eventually develop LVT showed early abnormalities of intraventricular RT: the apical region with RT>2s was significantly larger, had a higher RT and a longer wall contact length. Thus, quantitative analysis of intraventricular flow based on echocardiography may provide subclinical markers of LV thrombosis risk to guide clinical decision making.

  2. Tetramer guided, cell sorter assisted production of clinical grade autologous NY-ESO-1 specific CD8(+) T cells.

    PubMed

    Pollack, Seth M; Jones, Robin L; Farrar, Erik A; Lai, Ivy P; Lee, Sylvia M; Cao, Jianhong; Pillarisetty, Venu G; Hoch, Benjamin L; Gullett, Ashley; Bleakley, Marie; Conrad, Ernest U; Eary, Janet F; Shibuya, Kendall C; Warren, Edus H; Carstens, Jason N; Heimfeld, Shelly; Riddell, Stanley R; Yee, Cassian

    2014-01-01

    Adoptive T cell therapy represents an attractive modality for the treatment of patients with cancer. Peripheral blood mononuclear cells have been used as a source of antigen specific T cells but the very low frequency of T cells recognizing commonly expressed antigens such as NY-ESO-1 limit the applicability of this approach to other solid tumors. To overcome this, we tested a strategy combining IL-21 modulation during in vitro stimulation with first-in-class use of tetramer-guided cell sorting to generate NY-ESO-1 specific cytotoxic T lymphocytes (CTL). CTL generation was evaluated in 6 patients with NY-ESO-1 positive sarcomas, under clinical manufacturing conditions and characterized for phenotypic and functional properties. Following in vitro stimulation, T cells stained with NY-ESO-1 tetramer were enriched from frequencies as low as 0.4% to >90% after single pass through a clinical grade sorter. NY-ESO-1 specific T cells were generated from all 6 patients. The final products expanded on average 1200-fold to a total of 36 billion cells, were oligoclonal and contained 67-97% CD8(+), tetramer(+) T cells with a memory phenotype that recognized endogenous NY-ESO-1. This study represents the first series using tetramer-guided cell sorting to generate T cells for adoptive therapy. This approach, when used to target more broadly expressed tumor antigens such as WT-1 and additional Cancer-Testis antigens will enhance the scope and feasibility of adoptive T cell therapy.

  3. Qualified nurses' perceptions of nursing graduates' abilities vary according to specific demographic and clinical characteristics. A descriptive quantitative study.

    PubMed

    Missen, Karen; McKenna, Lisa; Beauchamp, Alison; Larkins, Jo-Ann

    2016-10-01

    Evidence from the literature and anecdotally from clinical settings suggests that newly graduated nurses are not fully prepared to be independent practitioners in healthcare settings. The aim of this study was to explore perceptions of qualified nurses in relation to the practice readiness of newly registered nursing graduates and determine whether these views differ according to specific demographic characteristics, clinical settings, and geographical locations. A descriptive quantitative design was used. An online survey tool was used to assess how qualified nurses (n=201) in Victoria, Australia, rated newly graduated nurses' abilities on 51 individual clinical skills/competencies in eight key skill areas. A composite score was calculated for each skill area and a comparative analysis was undertaken on the various cohorts of participants according to their demographic and clinical characteristics using one-way ANOVA and post hoc tests. Newly graduated nurses were found to be lacking competence in two key skill areas and were rated as performing adequately in the remaining six skill areas assessed. Significant differences (p≤0.05) in performance were found according to the age of the nurse, number of years registered, the educational setting in which they undertook their nurse education, their role, and the clinical area in which they worked. There were no significant differences according to whether the nurse worked in the private or public healthcare sector. Few differences were found between nurses working in a metropolitan vs. regional/rural healthcare setting. This is the first study to quantify the scale of this problem. Our findings serve as a reference for both nurse education providers and healthcare settings in better preparing nursing graduates to be competent, safe practitioners in all clinical areas. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Partial Diversity Generates Effector Immunity Specificity of the Bac41-Like Bacteriocins of Enterococcus faecalis Clinical Strains

    PubMed Central

    Kurushima, Jun; Ike, Yasuyoshi

    2016-01-01

    ABSTRACT Bacteriocin 41 (Bac41) is the plasmid-encoded bacteriocin produced by the opportunistic pathogen Enterococcus faecalis. Its genetic determinant consists of bacL1 (effector), bacL2 (regulator), bacA (effector), and bacI (immunity). The secreted effectors BacL1 and BacA coordinate to induce the lytic cell death of E. faecalis. Meanwhile, the immunity factor BacI provides self-resistance to the Bac41 producer, E. faecalis, against the action of BacL1 and BacA. In this study, we demonstrated that more than half of the 327 clinical strains of E. faecalis screened had functional Bac41 genes. Analysis of the genetic structure of the Bac41 genes in the DNA sequences of the E. faecalis strains revealed that the Bac41-like genes consist of a relatively conserved region and a variable region located downstream from bacA. Based on similarities in the variable region, the Bac41-like genes could be classified into type I, type IIa, and type IIb. Interestingly, the distinct Bac41 types had specific immunity factors for self-resistance, BacI1 or BacI2, and did not show cross-immunity to the other type of effector. We also demonstrated experimentally that the specificity of the immunity was determined by the combination of the C-terminal region of BacA and the presence of the unique BacI1 or BacI2 factor. These observations suggested that Bac41-like bacteriocin genes are extensively disseminated among E. faecalis strains in the clinical environment and can be grouped into at least three types. It was also indicated that the partial diversity results in specificity of self-resistance which may offer these strains a competitive advantage. IMPORTANCE Bacteriocins are antibacterial effectors produced by bacteria. In general, a bacteriocin-coding gene is accompanied by a cognate immunity gene that confers self-resistance on the bacteriocin-producing bacterium itself. We demonstrated that one of the bacteriocins, Bac41, is disseminated among E. faecalis clinical strains and the

  5. Clinical encounters in tactical medicine: a mission-specific analysis of the Maryland State Police experience.

    PubMed

    Levy, Matthew J; Smith, Rebecca; Gerold, Kevin B; Alves, Donald W; Tang, Nelson

    2014-01-01

    The Maryland State Police (MSP) Tactical Medical Unit (TMU) provides tactical emergency medical support (TEMS) through the deployment of specially trained state trooper tactical paramedics. The MSP TMU maintains an operational database of all mission related medical activity. This information constitutes a robust dataset derived from real world operational medicine experiences. A retrospective analysis of de-identified entries from the MSP TMU operational response database was performed for the 5-year period of 2007?2013. A summative analysis of missions, as well as a subgroup analysis of types of patients encountered, was performed to further characterize patient encounters based on the type of law enforcement tactical mission. Analysis was performed on 1,042 tactical missions, of which there were 367 total patient encounters during the study period. The majority (67%; 246/367) of patients encountered were law enforcement tactical team personnel. The most frequently occurring mission, by type, was high-risk warrant service, accounting for 45% (470/1,042) of all missions in this series. Law enforcement training support missions comprised 25% (259/1,042), and 15% (157/1,042) of all missions in the database were medical standbys for law enforcement operations. The highest number of patient contacts were associated with training activities, resulting in 29% (108/367) of clinical encounters. The next most common mission associated with patient encounters was high-risk warrant service (24%; 88/367). The 5-year analysis conducted in this study represents the largest known retrospective assessment of a state police tactical medical program. Training activities resulted in the highest number of patient encounters by this program, with law enforcement/tactical team personnel comprising the majority of patient encounters. The majority of chief complaints encountered were non?life threatening and reinforce the need for expanded scope of practice training and enhanced

  6. Two distinct symptom-based phenotypes of depression in epilepsy yield specific clinical and etiological insights.

    PubMed

    Rayner, Genevieve; Jackson, Graeme D; Wilson, Sarah J

    2016-11-01

    Depression is common but underdiagnosed in epilepsy. A quarter of patients meet criteria for a depressive disorder, yet few receive active treatment. We hypothesize that the presentation of depression is less recognizable in epilepsy because the symptoms are heterogeneous and often incorrectly attributed to the secondary effects of seizures or medication. Extending the ILAE's new phenomenological approach to classification of the epilepsies to include psychiatric comorbidity, we use data-driven profiling of the symptoms of depression to perform a preliminary investigation of whether there is a distinctive symptom-based phenotype of depression in epilepsy that could facilitate its recognition in the neurology clinic. The psychiatric and neuropsychological functioning of 91 patients with focal epilepsy was compared with that of 77 healthy controls (N=168). Cluster analysis of current depressive symptoms identified three clusters: one comprising nondepressed patients and two symptom-based phenotypes of depression. The 'Cognitive' phenotype (base rate=17%) was characterized by symptoms taking the form of self-critical cognitions and dysphoria and was accompanied by pervasive memory deficits. The 'Somatic' phenotype (7%) was characterized by vegetative depressive symptoms and anhedonia and was accompanied by greater anxiety. It is hoped that identification of the features of these two phenotypes will ultimately facilitate improved detection and diagnosis of depression in patients with epilepsy and thereby lead to appropriate and timely treatment, to the benefit of patient wellbeing and the potential efficacy of treatment of the seizure disorder. This article is part of a Special Issue entitled "The new approach to classification: Rethinking cognition and behavior in epilepsy". Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Rectal microbicides: clinically relevant approach to the design of rectal specific placebo formulations

    PubMed Central

    2011-01-01

    Background The objective of this study is to identify the critical formulation parameters controlling distribution and function for the rectal administration of microbicides in humans. Four placebo formulations were designed with a wide range of hydrophilic characteristics (aqueous to lipid) and rheological properties (Newtonian, shear thinning, thermal sensitive and thixotropic). Aqueous formulations using typical polymers to control viscosity were iso-osmotic and buffered to pH 7. Lipid formulations were developed from lipid solvent/lipid gelling agent binary mixtures. Testing included pharmaceutical function and stability as well as in vitro and in vivo toxicity. Results The aqueous fluid placebo, based on poloxamer, was fluid at room temperature, thickened and became shear thinning at 37°C. The aqueous gel placebo used carbopol as the gelling agent, was shear thinning at room temperature and showed a typical decrease in viscosity with an increase in temperature. The lipid fluid placebo, myristyl myristate in isopropyl myristate, was relatively thin and temperature independent. The lipid gel placebo, glyceryl stearate and PEG-75 stearate in caprylic/capric triglycerides, was also shear thinning at both room temperature and 37°C but with significant time dependency or thixotropy. All formulations showed no rectal irritation in rabbits and were non-toxic using an ex vivo rectal explant model. Conclusions Four placebo formulations ranging from fluid to gel in aqueous and lipid formats with a range of rheological properties were developed, tested, scaled-up, manufactured under cGMP conditions and enrolled in a formal stability program. Clinical testing of these formulations as placebos will serve as the basis for further microbicide formulation development with drug-containing products. PMID:21385339

  8. Body checking in non-clinical women: experimental evidence of a specific impact on fear of uncontrollable weight gain.

    PubMed

    Bailey, Natalie; Waller, Glenn

    2017-01-20

    Body checking is used widely among clinical and non-clinical individuals. It is suggested to be a safety behavior, reducing anxiety initially but potentially enhancing eating and shape concerns in the longer term. However, there is little causal evidence of those negative effects. This experimental study tests the potential negative impact of body checking. Fifty non-clinical women took part in a study of the effects of body checking in naturalistic settings. Each checked their wrist size every 15 minutes for eight hours on one day, then did not check the next day (order randomized). The impact on eating cognitions and body dissatisfaction was measured at the end of each day, and levels of change in those characteristics were also associated with eating pathology levels. Body checking did not result in more negative general eating attitudes or body dissatisfaction, but did result in a significant increase in a specific cognition that is hypothesised to be relevant to eating pathology - the fear of uncontrollable weight gain following eating. This impact was greater among those women with more negative existing eating attitudes. These findings add to the small experimental evidence base, demonstrating negative causal links between body checking and eating pathology. The findings need to be extended to clinical groups, but support the use of existing cognitive-behavioral methods to reduce body checking behavior.

  9. A Genotypic-Oriented View of CFTR Genetics Highlights Specific Mutational Patterns Underlying Clinical Macrocategories of Cystic Fibrosis

    PubMed Central

    Lucarelli, Marco; Bruno, Sabina Maria; Pierandrei, Silvia; Ferraguti, Giampiero; Stamato, Antonella; Narzi, Fabiana; Amato, Annalisa; Cimino, Giuseppe; Bertasi, Serenella; Quattrucci, Serena; Strom, Roberto

    2015-01-01

    Cystic fibrosis (CF) is a monogenic disease caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The genotype–phenotype relationship in this disease is still unclear, and diagnostic, prognostic and therapeutic challenges persist. We enrolled 610 patients with different forms of CF and studied them from a clinical, biochemical, microbiological and genetic point of view. Overall, there were 125 different mutated alleles (11 with novel mutations and 10 with complex mutations) and 225 genotypes. A strong correlation between mutational patterns at the genotypic level and phenotypic macrocategories emerged. This specificity appears to largely depend on rare and individual mutations, as well as on the varying prevalence of common alleles in different clinical macrocategories. However, 19 genotypes appeared to underlie different clinical forms of the disease. The dissection of the pathway from the CFTR mutated genotype to the clinical phenotype allowed to identify at least two components of the variability usually found in the genotype–phenotype relationship. One component seems to depend on the genetic variation of CFTR, the other component on the cumulative effect of variations in other genes and cellular pathways independent from CFTR. The experimental dissection of the overall biological CFTR pathway appears to be a powerful approach for a better comprehension of the genotype–phenotype relationship. However, a change from an allele-oriented to a genotypic-oriented view of CFTR genetics is mandatory, as well as a better assessment of sources of variability within the CFTR pathway. PMID:25910067

  10. Two Years Follow up of Domain Specific Cognitive Training in Relapsing Remitting Multiple Sclerosis: A Randomized Clinical Trial

    PubMed Central

    Mattioli, Flavia; Bellomi, Fabio; Stampatori, Chiara; Provinciali, Leandro; Compagnucci, Laura; Uccelli, Antonio; Pardini, Matteo; Santuccio, Giuseppe; Fregonese, Giuditta; Pattini, Marianna; Allegri, Beatrice; Clerici, Raffaella; Lattuada, Annalisa; Montomoli, Cristina; Corso, Barbara; Gallo, Paolo; Riccardi, Alice; Ghezzi, Angelo; Roscio, Marco; Tola, Maria Rosaria; Calanca, Chiara; Baldini, Daria; Trafficante, Debora; Capra, Ruggero

    2016-01-01

    Cognitive rehabilitation in multiple sclerosis (MS) has been reported to induce neuropsychological improvements, but the persistence of these effects has been scarcely investigated over long follow ups. Here, the results of a multicenter randomized clinical trial are reported, in which the efficacy of 15 week domain specific cognitive training was evaluated at 2 years follow up in 41 patients. Included patients were randomly assigned either to domain specific cognitive rehabilitation, or to aspecific psychological intervention. Patients who still resulted to be cognitively impaired at 1 year follow up were resubmitted to the same treatment, whereas the recovered ones were not. Neuropsychological tests and functional scales were administered at 2 years follow up to all the patients. Results revealed that both at 1 and at 2 years follow up more patients in the aspecific group (18/19, 94% and 13/17, 76% respectively) than in the specific group (11/22, 50% and 5/15, 33% respectively) resulted to be cognitively impaired. Furthermore patients belonging to the specific group showed significantly less impaired tests compared with the aspecific group ones (p = 0.02) and a significant amelioration in the majority of the tests. On the contrary patients in the aspecific group did not change. The specific group subjects also perceived a subjective improvement in their cognitive performance, while the aspecific group patients did not. These results showed that short time domain specific cognitive rehabilitation is a useful treatment for patients with MS, shows very long lasting effects, compared to aspecific psychological interventions. Also subjective cognitive amelioration was found in patients submitted to domain specific treatment after 2 years. PMID:26941630

  11. Envelope specific T cell responses & cytokine profiles in chikungunya patients hospitalized with different clinical presentations

    PubMed Central

    Tripathy, Anuradha S.; Tandale, Babasaheb V.; Balaji, Saravana S.; Hundekar, Supriya L.; Ramdasi, Ashwini Y.; Arankalle, Vidya A.

    2015-01-01

    Background & objectives: Since the 2006 massive outbreaks, chikungunya (CHIK) is a major public health concern in India. The aim of this study was to assess envelope specific immune responses in patients with chikungunya infection. Methods: This study included 46 hospitalized patients with chikungunya virus infection (encephalitis, n=22, other systemic involvement, OSI, n=12, classical, n=12) and six controls from Ahmedabad city, Gujarat, India. T cell responses and the levels of Th1, pro/ anti-inflammatory cytokines against the CHIK virus envelope antigens were assessed by lymphocyte proliferation assay and by cytometric bead array in flow cytometry, respectively. Results: Lymphoproliferative response was uniform among the patients. Comparisons of cytokines revealed significantly higher levels of interleukin (IL)-4 and IL-5 in encephalitis, OSI and classical patients versus controls. The levels of tumour necrosis factor (TNF)-α were higher in classical patients categories compared to the controls. Interferon (IFN)-γ levels were lower in encephalitis patients versus control. Interpretation & conclusions: Our findings showed recognition of T cell epitopes on the envelope region of chikungunya virus by all patient categories. Lower level of IFN-γ may be associated with the severity of disease in these patients. PMID:25900956

  12. Clinically used selective estrogen receptor modulators affect different steps of macrophage-specific reverse cholesterol transport

    PubMed Central

    Fernández-Suárez, María E.; Escolà-Gil, Joan C.; Pastor, Oscar; Dávalos, Alberto; Blanco-Vaca, Francisco; Lasunción, Miguel A.; Martínez-Botas, Javier; Gómez-Coronado, Diego

    2016-01-01

    Selective estrogen receptor modulators (SERMs) are widely prescribed drugs that alter cellular and whole-body cholesterol homeostasis. Here we evaluate the effect of SERMs on the macrophage-specific reverse cholesterol transport (M-RCT) pathway, which is mediated by HDL. Treatment of human and mouse macrophages with tamoxifen, raloxifene or toremifene induced the accumulation of cytoplasmic vesicles of acetyl-LDL-derived free cholesterol. The SERMs impaired cholesterol efflux to apolipoprotein A-I and HDL, and lowered ABCA1 and ABCG1 expression. These effects were not altered by the antiestrogen ICI 182,780 nor were they reproduced by 17β-estradiol. The treatment of mice with tamoxifen or raloxifene accelerated HDL-cholesteryl ester catabolism, thereby reducing HDL-cholesterol concentrations in serum. When [3H]cholesterol-loaded macrophages were injected into mice intraperitoneally, tamoxifen, but not raloxifene, decreased the [3H]cholesterol levels in serum, liver and feces. Both SERMs downregulated liver ABCG5 and ABCG8 protein expression, but tamoxifen reduced the capacity of HDL and plasma to promote macrophage cholesterol efflux to a greater extent than raloxifene. We conclude that SERMs interfere with intracellular cholesterol trafficking and efflux from macrophages. Tamoxifen, but not raloxifene, impair M-RCT in vivo. This effect is primarily attributable to the tamoxifen-mediated reduction of the capacity of HDL to promote cholesterol mobilization from macrophages. PMID:27601313

  13. Expression of specific inflammasome gene modules stratifies older individuals into two extreme clinical and immunological states.

    PubMed

    Furman, David; Chang, Junlei; Lartigue, Lydia; Bolen, Christopher R; Haddad, François; Gaudilliere, Brice; Ganio, Edward A; Fragiadakis, Gabriela K; Spitzer, Matthew H; Douchet, Isabelle; Daburon, Sophie; Moreau, Jean-François; Nolan, Garry P; Blanco, Patrick; Déchanet-Merville, Julie; Dekker, Cornelia L; Jojic, Vladimir; Kuo, Calvin J; Davis, Mark M; Faustin, Benjamin

    2017-02-01

    Low-grade, chronic inflammation has been associated with many diseases of aging, but the mechanisms responsible for producing this inflammation remain unclear. Inflammasomes can drive chronic inflammation in the context of an infectious disease or cellular stress, and they trigger the maturation of interleukin-1β (IL-1β). Here we find that the expression of specific inflammasome gene modules stratifies older individuals into two extremes: those with constitutive expression of IL-1β, nucleotide metabolism dysfunction, elevated oxidative stress, high rates of hypertension and arterial stiffness; and those without constitutive expression of IL-1β, who lack these characteristics. Adenine and N(4)-acetylcytidine, nucleotide-derived metabolites that are detectable in the blood of the former group, prime and activate the NLRC4 inflammasome, induce the production of IL-1β, activate platelets and neutrophils and elevate blood pressure in mice. In individuals over 85 years of age, the elevated expression of inflammasome gene modules was associated with all-cause mortality. Thus, targeting inflammasome components may ameliorate chronic inflammation and various other age-associated conditions.

  14. Patient-specific dosimetry in peptide receptor radionuclide therapy: a clinical review.

    PubMed

    Chalkia, M T; Stefanoyiannis, A P; Chatziioannou, S N; Round, W H; Efstathopoulos, E P; Nikiforidis, G C

    2015-03-01

    Neuroendocrine tumours (NETs) belong to a relatively rare class of neoplasms. Nonetheless, their prevalence has increased significantly during the last decades. Peptide receptor radionuclide therapy (PRRT) is a relatively new treatment approach for inoperable or metastasised NETs. The therapeutic effect is based on the binding of radiolabelled somatostatin analogue peptides with NETs' somatostatin receptors, resulting in internal irradiation of tumours. Pre-therapeutic patient-specific dosimetry is essential to ensure that a treatment course has high levels of safety and efficacy. This paper reviews the methods applied for PRRT dosimetry, as well as the dosimetric results presented in the literature. Focus is given on data concerning the therapeutic somatostatin analogue radiopeptides (111)In-[DTPA(0),D-Phe(1)]-octreotide ((111)In-DTPA-octreotide), (90)Y-[DOTA(0),Tyr(3)]-octreotide ((90)Y-DOTATOC) and (177)Lu-[DOTA(0),Tyr(3),Thr(8)]-octreotide ((177)Lu-DOTATATE). Following the Medical Internal Radiation Dose (MIRD) Committee formalism, dosimetric analysis demonstrates large interpatient variability in tumour and organ uptake, with kidneys and bone marrow being the critical organs. The results are dependent on the image acquisition and processing protocol, as well as the dosimetric imaging radiopharmaceutical.

  15. Female-specific pruritus from childhood to postmenopause: clinical features, hormonal factors, and treatment considerations.

    PubMed

    Rimoin, Lauren P; Kwatra, Shawn G; Yosipovitch, Gil

    2013-01-01

    There have been considerable advances in our understanding of the pathophysiology of pruritus in recent years. The purpose of this review was to highlight itch entities in women, and in particular pruritic vulvar dermatoses that women experience among different age groups. Unique temporal shifts may contribute to the etiology of many of these conditions. These changes lead to cyclical changes in the skin's basic composition. Specifically, estrogen receptors have been detected on keratinocytes that respond to rising and falling levels of estrogen. These receptors lead to changes in skin hydration, collagen content, and in the concentration of glycosaminoglycans that form the skin barrier. In addition, hormonal pH changes associated with the menstrual cycle may be an important factor in the aggravation of itch as increasing pH is known to activate the proteinase-activated receptor-2, a well-known itch mediator. Common pruritic conditions in women that will be discussed include atopic and irritant dermatitis, psoriasis, lichen sclerosus, infectious vulvovaginitis, vulvovaginal candidiasis, atrophic vulvovaginitis, squamous cell carcinoma, lichen simplex chronicus, and neuropathic itch. We also examine pruritic conditions associated with pregnancy including pemphigoid gestationis, polymorphic eruption of pregnancy, intrahepatic cholestasis of pregnancy and atopic eruption of pregnancy. Finally, acceptable and contraindicated antipruritic agents in pregnancy are examined.

  16. Antibodies specific for nucleic acids and applications in genomic detection and clinical diagnostics.

    PubMed

    Hu, Zonglin; Leppla, Stephen H; Li, Baoguang; Elkins, Christopher A

    2014-09-01

    Detection of nucleic acids using antibodies is uncommon. This is in part because nucleic acids are poor immunogens and it is difficult to elicit antibodies having high affinity to each type of nucleic acid while lacking cross-reactivity to others. We describe the origins and applications of a variety of anti-nucleic acid antibodies, including ones reacting with modified nucleosides and nucleotides, single-stranded DNA, double-stranded DNA, RNA, DNA:RNA hybrids, locked-nucleic acids or peptide nucleic acid:nucleic acid hybrids. Carefully selected antibodies can be excellent reagents for detecting bacteria, viruses, small RNAs, microRNAs, R-loops, cancer cells, stem cells, apoptotic cells and so on. The detection may be sensitive, simple, rapid, specific, reproducible, quantitative and cost-effective. Current microarray and diagnostic methods that depend on cDNA or cRNA can be replaced by using antibody detection of nucleic acids. Therefore, development should be encouraged to explore new utilities and create a robust arsenal of new anti-nucleic acid antibodies.

  17. [Clinical trial of non-specific immunotherapy using Lentinan in advanced or recurrent gastric cancer].

    PubMed

    Yoshino, Shigefumi; Oka, Masaaki

    2008-11-01

    Randomized phase III study of S-1 alone versus S-1 plus Lentinan (LNT) in advanced or recurrent gastric cancer started in February 2007 conducted by the Japanese Foundation for Multidisciplinary Treatment of Cancer. The objective of this study is to evaluate the superiority of S-1/LNT to S-1 alone. The primary end point is to compare over all survival between both treatment groups. Secondary end points include time to treatment failure, the grade and rate of the adverse events, the evaluation of quality of life (QOL), response rate evaluated by RECIST and immunological parameters. QOL is evaluated by Japanese version of FACT-BRM questionnaire. Immunological parameters include serum complements (CH50, C3) and beta-1, 3 binding monocytes. The sample size is estimated at 150 patients per arm. Registration period is 2 years with 2-year follow-up. This study has a chance to prove the efficacy of the non-specific biological response modifier. We will have to cooperate in order to make this study a success.

  18. Expression of specific inflammasome gene modules stratifies older individuals into two extreme clinical and immunological states

    PubMed Central

    Furman, David; Chang, Junlei; Lartigue, Lydia; Bolen, Christopher R; Haddad, François; Gaudilliere, Brice; Ganio, Edward A; Fragiadakis, Gabriela K; Spitzer, Matthew H; Douchet, Isabelle; Daburon, Sophie; Moreau, Jean-François; Nolan, Garry P; Blanco, Patrick; Déchanet-Merville, Julie; Dekker, Cornelia L; Jojic, Vladimir; Kuo, Calvin J; Davis, Mark M; Faustin, Benjamin

    2017-01-01

    Low-grade, chronic inflammation has been associated with many diseases of aging, but the mechanisms responsible for producing this inflammation remain unclear. Inflammasomes can drive chronic inflammation in the context of an infectious disease or cellular stress, and they trigger the maturation of interleukin-1β (IL-1β). Here we find that the expression of specific inflammasome gene modules stratifies older individuals into two extremes: those with constitutive expression of IL-1β, nucleotide metabolism dysfunction, elevated oxidative stress, high rates of hypertension and arterial stiffness; and those without constitutive expression of IL-1β, who lack these characteristics. Adenine and N4-acetylcytidine, nucleotide-derived metabolites that are detectable in the blood of the former group, prime and activate the NLRC4 inflammasome, induce the production of IL-1β, activate platelets and neutrophils and elevate blood pressure in mice. In individuals over 85 years of age, the elevated expression of inflammasome gene modules was associated with all-cause mortality. Thus, targeting inflammasome components may ameliorate chronic inflammation and various other age-associated conditions. PMID:28092664

  19. Interchangeable neck shape-specific coils for a clinically realizable anterior neck phased array system.

    PubMed

    Beck, Michael J; Parker, Dennis L; Bolster, Bradley D; Kim, Seong-Eun; McNally, J Scott; Treiman, Gerald S; Hadley, J Rock

    2017-02-10

    To demonstrate the interchangeable neck shape-specific (NSS) coil concept that supplements standard commercial spine and head/neck coils to provide simultaneous high-resolution (hi-res) head/neck imaging with high signal-to-noise ratio (SNR). Two NSS coils were constructed on formers designed to fit two different neck shapes. A 7-channel (7ch) ladder array was constructed on a medium neck former, and a 9-channel (9ch) ladder array was constructed on large neck former. Both coils were interchangeable with the same preamp housing. The 7ch and 9ch coils demonstrate SNR gains of approximately 4 times and 3 times over the Siemens 20-channel head/neck coil in the carotid arteries of our volunteers, respectively. Coupling between the Siemens 32-channel spine coil, Siemens 20-channel head/neck coil, and the NSS coils was negligible, allowing for simultaneous hi-res head/neck imaging with high SNR. This study demonstrates that supplementing existing commercial spine and head/neck coils with an NSS coil allows uniform simultaneous hi-res imaging with high SNR in the anterior neck, while maintaining SNR of the commercial coil in the head and posterior neck. Magn Reson Med, 2017. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

  20. Minimal brain dysfunction/specific learning disability: a clinical approach for the primary physician.

    PubMed

    Levy, H B

    1976-05-01

    Minimal brain dysfunction is a neurodevelopmental disorder which can be found in nearly 20% of school children. It is characterized by evidences of immaturity involving control of activity, emotions, and behavior, and by specific learning disabilities involving the communicating skills needed in reading, writing, and mathematics. The prime deficits in the classroom are an inability to maintain attention and concentration and an inability to skillfully blend the auditory and visual functions essential in language performance. Medical evaluation will reveal many of the "soft signs" of neurologic involvement, and educational appraisal will indicate a wide scatter in testing scores with a marked discrepancy between evaluated potential and actual classroom achievement. Remedial efforts directed at early detection, relief from pressure and unjust punishment or ridicule from parents and teachers, and adjustment of the educational environment with consideration of the child's individual talents, combined with the judicious use of medications to prolong attention span and improve neurodevelopmental maturity, hold promise of improving the lot of most involved children. There are valid indications that expansion of such programs can do much to prevent these youngsters from developing severe personality maladjustment and delinquent behavior, as well as emotional illness in later life.

  1. Clinically used selective estrogen receptor modulators affect different steps of macrophage-specific reverse cholesterol transport.

    PubMed

    Fernández-Suárez, María E; Escolà-Gil, Joan C; Pastor, Oscar; Dávalos, Alberto; Blanco-Vaca, Francisco; Lasunción, Miguel A; Martínez-Botas, Javier; Gómez-Coronado, Diego

    2016-09-07

    Selective estrogen receptor modulators (SERMs) are widely prescribed drugs that alter cellular and whole-body cholesterol homeostasis. Here we evaluate the effect of SERMs on the macrophage-specific reverse cholesterol transport (M-RCT) pathway, which is mediated by HDL. Treatment of human and mouse macrophages with tamoxifen, raloxifene or toremifene induced the accumulation of cytoplasmic vesicles of acetyl-LDL-derived free cholesterol. The SERMs impaired cholesterol efflux to apolipoprotein A-I and HDL, and lowered ABCA1 and ABCG1 expression. These effects were not altered by the antiestrogen ICI 182,780 nor were they reproduced by 17β-estradiol. The treatment of mice with tamoxifen or raloxifene accelerated HDL-cholesteryl ester catabolism, thereby reducing HDL-cholesterol concentrations in serum. When [(3)H]cholesterol-loaded macrophages were injected into mice intraperitoneally, tamoxifen, but not raloxifene, decreased the [(3)H]cholesterol levels in serum, liver and feces. Both SERMs downregulated liver ABCG5 and ABCG8 protein expression, but tamoxifen reduced the capacity of HDL and plasma to promote macrophage cholesterol efflux to a greater extent than raloxifene. We conclude that SERMs interfere with intracellular cholesterol trafficking and efflux from macrophages. Tamoxifen, but not raloxifene, impair M-RCT in vivo. This effect is primarily attributable to the tamoxifen-mediated reduction of the capacity of HDL to promote cholesterol mobilization from macrophages.

  2. Patient specific modeling of the HPA axis related to clinical diagnosis of depression.

    PubMed

    Bangsgaard, Elisabeth O; Ottesen, Johnny T

    2016-11-02

    A novel model of the hypothalamic-pituitary-adrenal axis is presented. The axis is an endocrine system responsible for coping with stress and it is likely to be involved in depression. The dynamics of the system is studied and existence, uniqueness and positivity of the solution and the existence of an attracting trapping region are proved. The model is calibrated and compared to data for healthy and depressed subjects. A sensitivity analysis resulting in a set of identifiable physiological parameters is provided. A subset is selected for parameter estimation and a reduced version of the model is stated and an approximated version is discussed. The model is physiologically based, thus parameters are representative for gland functions or elimination processes. Hence the model may be used for pointing out pathologies by parameter estimation and hypothesis testing whereby it may be used as an objective and refined method for diagnosing depression and suggesting individual treatment protocols. Finally, the method may inspire pharmaceutical companies to develop target specific psychopharmaca for more effective and individual treatment.

  3. [Middle-chain fatty acids: their dietary content, physiology, specific metabolism and clinical application].

    PubMed

    Titov, V N

    2012-01-01

    Fatty acids (FA) , keep in food and organisms divide on FA as saturated which have no double bonds (DB), monoenic (1 DB), unsaturated (2 or 3 DB) and polyenic (4, 5, or 6 DB). Saturated and monoenic FA are used predominantly as oxidation and energy substrate, unsaturated as plasma membrane constituents, polyenic as precursors in eicosanoid and aminophospholipid production. Bearing in mind specific features of metabolism and transport in vivo, FA can be regarded as short-chain (C4-C8) and middle-chain (C10-C14), their etherification with glycerol yielding short triglycerides (TG) which are not associated with apoproteins, while long-chain FA form long TG which in enterocytes are structured into chylomicrons by apoB-48. There are grounds to believe that a) outflow of middle-chain FA as short TG from enterocytes into the portal vein bed that includes the omentum veins and b) outflow of long-chain FA as chylomicron TG via d. thoracicus into major veins of systemic circulation are associated with pathogenesis of isolated omental obesity syndrome and metabolic syndrome, which wet by obesity.

  4. Clinical status of a cohort of patients with type 1 diabetes diagnosed more than 2 decades before. Results of a specific clinical follow-up program.

    PubMed

    Amor, Antonio J; Cabrer, Maria; Giménez, Marga; Vinagre, Irene; Ortega, Emilio; Conget, Ignacio

    2016-01-01

    The clinical course of type 1 diabetes mellitus (T1DM) has changed in recent decades. The aim of our study was to assess the long-term (> 20 years) clinical status of a patient cohort with T1DM under a specific treatment and follow-up program. A single center, observational, cross-sectional study was conducted of a patient cohort diagnosed with T1DM in the 1986-1994 period at our tertiary university hospital. Clinical characteristics, metabolic parameters, and occurrence of chronic complications and comorbidities after > 20 years of follow-up were collected. All subjects entered our specific program for patients with newly-diagnosed T1D and were followed up using the same clinical protocol. Data are shown as mean (standard deviation) or as number of patients and percentage. The appropriate test was used to compare quantitative and qualitative data. A P value <0.05 was considered statistically significant. A total of 279 patients were recorded, of whom 153 (53.6% women; mean age 46.6±8.6 years; age at onset 23.3±8.8 years; disease duration, 23.3±2.6 years) continued to attend our diabetes unit at the time of the analysis. Of these patients, 24.8% were administered continuous subcutaneous insulin infusion (CSII). Mean HbA1c in the past 5 years and in the last year were7.8±0.9% and 7.7±1.1% respectively (7.3±1.5% in those given CSII). Smoking was reported by 19.6% of patients, while 15.7% had high blood pressure and 37.9% dyslipidemia. Diabetic retinopathy was diagnosed in 20.4%, and 11.3% of the total cohort had nephropathy. Only 1.3% of our patients had a history of CVD. Data collected from a cohort of patients with T1DM for more than 2 decades regularly followed up with a specific program in a tertiary university hospital suggest a remarkably low prevalence of diabetic complications. Copyright © 2016 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

  5. Disease-specific dynamic biomarkers selected by integrating inflammatory mediators with clinical informatics in ARDS patients with severe pneumonia.

    PubMed

    Chen, Chengshui; Shi, Lin; Li, Yuping; Wang, Xiangdong; Yang, Shuanying

    2016-06-01

    Acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome that occurs as a result of various risk factors, including either direct or indirect lung injury, and systemic inflammation triggered also by severe pneumonia (SP). SP-ARDS-associated morbidity and mortality remains high also due to the lack of disease-specific biomarkers. The present study aimed at identifying disease-specific biomarkers in SP or SP-ARDS by integrating proteomic profiles of inflammatory mediators with clinical informatics. Plasma was sampled from the healthy as controls or patients with SP infected with bacteria or infection-associated SP-ARDS on the day of admission, day 3, and day 7. About 15 or 52 cytokines showed significant difference between SP and SP-ARDS patients with controls or 13 between SP-ARDS with SP alone and controls, including bone morphogenetic protein-15 (BMP-15), chemokine (C-X-C motif) ligand 16 (CXCL16), chemokine (C-X-C motif) receptor 3 (CXCR3), interleukin-6 (IL-6), protein NOV homolog (NOV/CCN3), glypican 3, insulin-like growth factor binding protein 4 (IGFBP-4), IL-5, IL-5 R alpha, IL-22 BP, leptin, MIP-1d, and orexin B with a significant correlation with Digital Evaluation Score System (DESS) scores. ARDS patients with overexpressed IL-6, CXCL16, or IGFBP-4 had significantly longer hospital stay and higher incidence of secondary infection. We also found higher levels of those mediators were associated with poor survival rates in patients with lung cancer and involved in the process of the epithelial mesenchymal transition of alveolar epithelial cells. Our preliminary study suggested that integration of proteomic profiles with clinical informatics as part of clinical bioinformatics is important to validate and optimize disease-specific and disease-staged biomarkers.

  6. Specificity of lectin-immobilized fluorescent nanospheres for colorectal tumors in a mouse model which more resembles the clinical disease

    PubMed Central

    Kitamura, Tokio; Sakuma, Shinji; Shimosato, Moe; Higashino, Haruki; Masaoka, Yoshie; Kataoka, Makoto; Yamashita, Shinji; Hiwatari, Ken-ichiro; Kumagai, Hironori; Morimoto, Naoki; Koike, Seiji; Tobita, Etsuo; Hoffman, Robert M.; Gore, John C.; Pham, Wellington

    2014-01-01

    We are investigating an imaging agent that enables real-time and accurate diagnosis of early colorectal cancer at the intestinal mucosa by colonoscopy. The imaging agent is peanut agglutinin-immobilized polystyrene nanospheres with surface poly(N-vinylacetamide) chains encapsulating coumarin 6. Intracolonically-administered lectin-immobilized fluorescent nanospheres detect tumor-derived changes through molecular recognition of lectin for the terminal sugar of cancer-specific antigens on the mucosal surface. The focus of this study was to evaluate imaging abilities of the nanospheres in animal models that reflect clinical environments. We previously developed an orthotopic mouse model with human colorectal tumors growing on the mucosa of the descending colon to more resemble the clinical disease. The entire colon of the mice in the exposed abdomen was monitored in real-time with an in vivo imaging apparatus. Fluorescence from the nanospheres was observed along the entire descending colon after intracolonical administration of them from the anus. When the luminal side of the colon was washed with PBS, most of the nanospheres drained away. However, fluorescence persisted in areas where the cancer cells were implanted. Histological evaluation demonstrated that tumors were present in the mucosal epithelia where the nanospheres fluoresced. In contrast, no fluorescence was observed when control mice without tumors were tested. The lectin-immobilized fluorescent nanospheres were tumor specific and bound to tumors even after vigorously washing. The nanospheres non-specifically bound to normal mucosa were easily removed through mild washing. Results indicate that the nanospheres accompanied by colonoscopy will be a clinically-valuable diagnostic tool for the early stage primary colon carcinoma. PMID:24976331

  7. Gender-Specific Molecular and Clinical Features underlie Malignant Pleural Mesothelioma

    PubMed Central

    Rienzo, Assunta De; Archer, Michael A.; Yeap, Beow Y.; Dao, Nhien; Sciaranghella, Daniele; Sideris, Antonios C.; Zheng, Yifan; Holman, Alexander G.; Wang, Yaoyu E.; Dal Cin, Paola S.; Fletcher, Jonathan A.; Rubio, Renee; Croft, Larry; Quackenbush, John; Sugarbaker, Peter E.; Munir, Kiara J.; Battilana, Jesse R.; Gustafson, Corinne E.; Chirieac, Lucian R.; Ching, Soo Meng; Wong, James; Tay, Liang Chung; Rudd, Stephen; Hercus, Robert; Sugarbaker, David J.; Richards, William G.; Bueno, Raphael

    2015-01-01

    Malignant pleural mesothelioma (MPM) is an aggressive cancer that occurs more frequently in men, but is associated with longer survival in women. Insight into the survival advantage of female patients may advance the molecular understanding of MPM and identify therapeutic interventions that will improve the prognosis for all MPM patients. In this study, we performed whole-genome sequencing of tumor specimens from 10 MPM patients and matched control samples to identify potential driver mutations underlying MPM. We identified molecular differences associated with gender and histology. Specifically, single-nucleotide variants of BAP1 were observed in 21% of cases, with lower mutation rates observed in sarcomatoid MPM (p<0.001). Chromosome 22q loss was more frequently associated with the epithelioid than that non-epitheliod histology (p=0.037), whereas CDKN2A deletions occurred more frequently in non-epithelioid subtypes among men (p=0.021) and were correlated with shorter overall survival for the entire cohort (p=0.002) and for men (p=0.012). Furthermore, women were more likely to harbor TP53 mutations (p=0.004). Novel mutations were found in genes associated with the integrin-linked kinase pathway, including MYH9 and RHOA. Moreover, expression levels of BAP1, MYH9, and RHOA were significantly higher in non-epithelioid tumors, and were associated with significant reduction in survival of the entire cohort and across gender subgroups. Collectively, our findings indicate that diverse mechanisms highly related to gender and histology appear to drive MPM. PMID:26554828

  8. Molecular and clinical dissection of CD24 antibody specificity by a comprehensive comparative analysis.

    PubMed

    Kristiansen, Glen; Machado, Eda; Bretz, Niko; Rupp, Christian; Winzer, Klaus-Jürgen; König, Anne-Kathleen; Moldenhauer, Gerhard; Marmé, Frederik; Costa, Julia; Altevogt, Peter

    2010-07-01

    CD24 is a small, highly glycosylated cell surface protein that is linked to the membrane through a glycosyl-phosphatidylinositol anchor. It is overexpressed in many human carcinomas and its expression is linked to bad prognosis. Lately, lack or low expression of CD24 was used to identify tumor stem cells resulting in conflicting data on the usefulness of this marker. In many immunohistochemical studies, the mAb SN3b was used but the epitope and specificity of this antibody have never been thoroughly investigated. In other studies based mainly on cytofluorographic analysis, the mAb ML-5 was applied. In this study, we compared the epitope of mAb SN3b to the CD24 mAbs SWA-11 and ML-5 that both bind to the core protein of CD24. Using tissue microarrays and affinity-purified CD24 glycoforms, we observed only a partial overlap of SN3b and SWA11 reactivity. The mAb SN3b recognizes sialic acid most likely on O-linked glycans that can occur independently of the CD24 protein backbone. The SN3b epitope was not related to common sialylated cancer-associated glycan structures. Both SN3b epitope positive or negative CD24 glycoforms supported the binding of P-selectin and Siglec-5. In breast cancer, the SN3b reactivity was associated with bad prognosis, whereas SWA11 was not. In renal cell cancer, the SN3b epitope was completely absent but SWA11 reactivity was a prognostic factor. Our results shed new light on the tumorbiological role of CD24 and resolve discrepancies in the literature related to the use of different CD24 mAbs.

  9. [Clinical significance of ID4 methylation detection by quantitative methylation-specific PCR in acute leukemia].

    PubMed

    Liu, Yang; Zhong, Wen-Wen; Kang, Hui-Yuan; Wang, Li-Li; Lu, Xue-Chun; Yu, Li; Zhu, Hong-Li

    2014-06-01

    The advances of treatment improved the prognosis of the patients with acute leukemia (AL) in the last decade, but the lack of general biomarker for predicting relapse in AL, which is one of the most important factors influencing the survival and prognosis. DNA methylation of ID4 gene promoter occurred frequently in patients with AL and was found to be highly related to the tumor progression. Based on the previous work of the setup of methylation-specific quantitative PCR system for ID4 gene, this study was designed to investigate the relation between the quantitative indicator of methylation density, percentage of methylation reference(PMR) value, and different disease status of AL. PMR of ID4 was detected by MS-PCR in bone marrow (BM) samples of 17 healthy persons and 54 AL patients in the status of newly diagnosis, complete remission and disease relapse. The results showed that at different disease status, PMR value in newly diagnosed group was significantly lower than that in complete remission group (P = 0.031). Among serial samples, PMR value remained very low at the status of patients with continuous complete remission (<1.5‰), and increased along with the accumulation of tumor cells at relapse. In 1 relapse case, the abnormal rise of PMR value occurred prior to morphological relapse. PMR value seemed to be related to body tumor cell load. It is concluded that the quantitative indicator of methylation density and PMR value may reflect the change of tumor cell load in acute leukemia patients. Dynamic monitoring of PMR maybe predict leukemia relapse.

  10. [Specific clinical and functional features in the patients presenting with neurologic manifestations of deforming dorsopathies and concomitant osteoarthrosis].

    PubMed

    Miriutova, N F; Zaĭtsev, A A; Popova, A V

    2012-01-01

    The present study has revealed some specific clinical and functional features in the patients presenting with neurologic manifestations of deforming dorsopathies and concomitant osteoarthrosis. The negative influence of the latter condition on the pain intensity, microcirculation, and duration of the exacerbation of neurologic syndrome has been demonstrated based on the analysis of correlational relationships between the severity of referred projectional nerve root pain and articular pain syndrome. Special emphasis is laid on the interrelation between the duration of pain syndrome and characteristics of microcirculation.

  11. Development of Specific Sequence-Characterized Amplified Region Markers for Detecting Histoplasma capsulatum in Clinical and Environmental Samples

    PubMed Central

    Frías De León, María Guadalupe; Arenas López, Gabina; Taylor, Maria Lucia; Acosta Altamirano, Gustavo

    2012-01-01

    Sequence-characterized amplified region (SCAR) markers, generated by randomly amplified polymorphic DNA (RAPD)-PCR, were developed to detect Histoplasma capsulatum selectively in clinical and environmental samples. A 1,200-bp RAPD-PCR-specific band produced with the 1281-1283 primers was cloned, sequenced, and used to design two SCAR markers, 1281-1283220 and 1281-1283230. The specificity of these markers was confirmed by Southern hybridization. To evaluate the relevance of the SCAR markers for the diagnosis of histoplasmosis, another molecular marker (M antigen probe) was used for comparison. To validate 1281-1283220 and 1281-1283230 as new tools for the identification of H. capsulatum, the specificity and sensitivity of these markers were assessed for the detection of the pathogen in 36 clinical (17 humans, as well as 9 experimentally and 10 naturally infected nonhuman mammals) and 20 environmental (10 contaminated soil and 10 guano) samples. Although the two SCAR markers and the M antigen probe identified H. capsulatum isolates from different geographic origins in America, the 1281-1283220 SCAR marker was the most specific and detected the pathogen in all samples tested. In contrast, the 1281-1283230 SCAR marker and the M antigen probe also amplified DNA from Aspergillus niger and Cryptococcus neoformans, respectively. Both SCAR markers detected as little as 0.001 ng of H. capsulatum DNA, while the M antigen probe detected 0.5 ng of fungal DNA. The SCAR markers revealed the fungal presence better than the M antigen probe in contaminated soil and guano samples. Based on our results, the 1281-1283220 marker can be used to detect and identify H. capsulatum in samples from different sources. PMID:22189121

  12. Prevalence and predictors of infertility-specific stress in women diagnosed with primary infertility: A clinic-based study

    PubMed Central

    Patel, Ansha; Sharma, P. S. V. N.; Narayan, Pratapkumar; Binu, V. S.; Dinesh, N.; Pai, Praveena Joglekar

    2016-01-01

    BACKGROUND: According to the existing literature on infertility, stress appears to be inevitably associated with infertility diagnosis and treatment in sub-fertile individuals. The epidemiological data on the prevalence and predictors of infertility-specific stress in cultural specific scenario are scarce. The objective of the present study was to estimate the prevalence of infertility-specific stress and identify predictors of infertility-specific stress in women diagnosed with primary infertility. MATERIALS AND METHODS: This cross-sectional study was conducted on 300 infertile married women, diagnosed with primary infertility. The tools used for the assessment were “semi-structured questionnaire” compiled by the authors, “ICD-10 Classification of Mental and Behavioral Disorders (Clinical Descriptions and Diagnostic Guidelines),” and “Psychological Evaluation Test for infertility.” STATISTICAL ANALYSIS: Data were analyzed using SPSS (version 15). Chi-square test was used for univariate analysis followed by multiple logistic regressions between stress and the predictor variables. RESULTS AND DISCUSSION: The prevalence of stress among women was 80%. Univariate analysis revealed that predictors of stress were years of marital life, duration of infertility, infertility type, history of gynecological surgery, cycles of ovulation induction with timed intercourse and intra-uterine inseminations, present and past psychiatric morbidity, coping difficulties, gynecological diagnosis, and severity of premenstrual dysphoria. Multivariate analysis showed leading associations of stress with infertility type and coping difficulties. PMID:27110075

  13. Automated Cell Enrichment of Cytomegalovirus-specific T cells for Clinical Applications using the Cytokine-capture System.

    PubMed

    Kumaresan, Pappanaicken; Figliola, Mathew; Moyes, Judy S; Huls, M Helen; Tewari, Priti; Shpall, Elizabeth J; Champlin, Richard; Cooper, Laurence J N

    2015-10-05

    The adoptive transfer of pathogen-specific T cells can be used to prevent and treat opportunistic infections such as cytomegalovirus (CMV) infection occurring after allogeneic hematopoietic stem-cell transplantation. Viral-specific T cells from allogeneic donors, including third party donors, can be propagated ex vivo in compliance with current good manufacturing practice (cGMP), employing repeated rounds of antigen-driven stimulation to selectively propagate desired T cells. The identification and isolation of antigen-specific T cells can also be undertaken based upon the cytokine capture system of T cells that have been activated to secrete gamma-interferon (IFN-γ). However, widespread human application of the cytokine capture system (CCS) to help restore immunity has been limited as the production process is time-consuming and requires a skilled operator. The development of a second-generation cell enrichment device such as CliniMACS Prodigy now enables investigators to generate viral-specific T cells using an automated, less labor-intensive system. This device separates magnetically labeled cells from unlabeled cells using magnetic activated cell sorting technology to generate clinical-grade products, is engineered as a closed system and can be accessed and operated on the benchtop. We demonstrate the operation of this new automated cell enrichment device to manufacture CMV pp65-specific T cells obtained from a steady-state apheresis product obtained from a CMV seropositive donor. These isolated T cells can then be directly infused into a patient under institutional and federal regulatory supervision. All the bio-processing steps including removal of red blood cells, stimulation of T cells, separation of antigen-specific T cells, purification, and washing are fully automated. Devices such as this raise the possibility that T cells for human application can be manufactured outside of dedicated good manufacturing practice (GMP) facilities and instead be produced

  14. Reporting of cause-specific treatment effects in cancer clinical trials with competing risks: a systematic review.

    PubMed

    Mell, Loren K; Lau, Steven K; Rose, Brent S; Jeong, Jong-Hyeon

    2012-09-01

    Separate analysis of cause-specific treatment effects is important for interpreting results of randomized trials. We sought to determine the extent to which cause-specific effects on primary events are reported in contemporary randomized controlled trials in oncology. We screened 833 randomized trials published in eight leading medical journals between January 2006 and December 2009. We excluded prevention studies (n=52), secondary reports (n=100), and one retracted study. Analysis was further restricted to 116 trials in non-metastatic/recurrent cancer that used an event-free survival primary endpoint. For each study included in the analysis, we evaluated whether treatment effects on both cancer and non-cancer events comprising the primary endpoint were reported separately and whether statistical analysis was provided. Of the 116 randomized trials, 47 (40%; 95% confidence interval (CI), 32-50%) reported effects on both cancer and non-cancer events comprising the primary endpoint, with statistical analysis provided in 13 (11%; 95% CI, 7-19%). Twenty-six trials (22%; 95% CI, 15-31%) reported effects on cancer but not non-cancer events, with statistical analysis provided in 11 (9%; 95% CI, 5-17%). In 43 studies (37%; 95% CI, 28-47%), no effects on cancer-specific components of the primary endpoint were given. Of these, 33 studies (28%; 95% CI, 21-38%) did report effects on some cancer-specific event, while ten (9%; 95% CI, 4-16%) did not report effects of treatment on any cancer event. Many randomized trials in oncology do not report cause-specific effects on primary events. Increased specificity is needed in the design and reporting of cancer clinical trials. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Disease Type- and Status-Specific Alteration of CSF Metabolome Coordinated with Clinical Parameters in Inflammatory Demyelinating Diseases of CNS

    PubMed Central

    Kong, Byung Soo; Lee, Jung-Eun; Kim, Kyoung Heon; Lee, Do Yup; Kim, Ho Jin

    2016-01-01

    Central nervous system (CNS) inflammatory demyelinating diseases (IDDs) are a group of disorders with different aetiologies, characterized by inflammatory lesions. These disorders include multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and idiopathic transverse myelitis (ITM). Differential diagnosis of the CNS IDDs still remains challenging due to frequent overlap of clinical and radiological manifestation, leading to increased demands for new biomarker discovery. Since cerebrospinal fluid (CSF) metabolites may reflect the status of CNS tissues and provide an interfacial linkage between blood and CNS tissues, we explored multi-component biomarker for different IDDs from CSF samples using gas chromatography mass spectrometry-based metabolite profiling coupled to multiplex bioinformatics approach. We successfully constructed the single model with multiple metabolite variables in coordinated regression with clinical characteristics, expanded disability status scale, oligoclonal bands, and protein levels. The multi-composite biomarker simultaneously discriminated four different immune statuses (a total of 145 samples; 54 MS, 49 NMOSD, 30 ITM, and 12 normal controls). Furthermore, systematic characterization of transitional metabolic modulation identified relapse-associated metabolites and proposed insights into the disease network underlying type-specific metabolic dysfunctionality. The comparative analysis revealed the lipids, 1-monopalmitin and 1-monostearin were common indicative for MS, NMOSD, and ITM whereas fatty acids were specific for the relapse identified in all types of IDDs. PMID:27855220

  16. Identification of ssDNA aptamers specific to clinical isolates of Streptococcus mutans strains with different cariogenicity.

    PubMed

    Cui, Wei; Liu, Jiaojiao; Su, Donghua; Hu, Danyang; Hou, Shuai; Hu, Tongnan; Yang, Jiyong; Luo, Yanping; Xi, Qing; Chu, Bingfeng; Wang, Chenglong

    2016-06-01

    Streptococcus mutans, a Gram-positive facultative anaerobic bacterium, is considered to be a major etiological factor for dental caries. In this study, plaques from dental enamel surfaces of caries-active and caries-free individuals were obtained and cultivated for S. mutans isolation. Morphology examination, biochemical characterization, and polymerase chain reaction were performed to identify S. mutans The cariogenicity of S. mutans strains isolated from clinical specimens was evaluated by testing the acidogenicity, aciduricity, extracellular polysaccharide production, and adhesion ability of the bacteria. Finally, subtractive SELEX (systematic evolution of ligands by exponential enrichment) technology targeting whole intact cells was used to screen for ssDNA aptamers specific to the strains with high cariogenicity. After nine rounds of subtractive SELEX, sufficient pool enrichment was achieved as shown by radioactive isotope analysis. The enriched pool was cloned and sequenced randomly, followed by MEME online and RNA structure software analysis of the sequences. Results from the flow cytometry indicated that aptamers H1, H16, H4, L1, L10, and H19 could discriminate highly cariogenic S. mutans strains from poorly cariogenic strains. Among these, Aptamer H19 had the strongest binding capacity with cariogenic S. mutans strains with a dissociation constant of 69.45 ± 38.53 nM. In conclusion, ssDNA aptamers specific to highly cariogenic clinical S. mutans strains were successfully obtained. These ssDNA aptamers might be used for the early diagnosis and treatment of dental caries.

  17. Accelerated production of antigen-specific T-cells for pre-clinical and clinical applications using Gas-permeable Rapid Expansion cultureware (G-Rex)

    PubMed Central

    Vera, Juan F.; Brenner, Lara J.; Gerdemann, Ulrike; Ngo, Minhtran C.; Sili, Uluhan; Liu, Hao; Wilson, John; Dotti, Gianpietro; Heslop, Helen E.; Leen, Ann M.; Rooney, Cliona M.

    2009-01-01

    The clinical manufacture of antigen-specific cytotoxic T lymphocytes (CTL) for adoptive immunotherapy is limited by the complexity and time required to produce large numbers with the desired function and specificity. The culture conditions required are rigorous, and in some cases only achieved in 2cm2 wells in which cell growth is limited by gas exchange, nutrients and waste accumulation. Bioreactors developed to overcome these issues tend to be complex, expensive and not always conducive to CTL growth. We observed that antigen-specific CTL undergo seven to ten divisions post-stimulation. However the expected CTL numbers were achieved only in the first week of culture. By recreating the culture conditions present during this first week - low frequency of antigen-specific T-cells and high frequency of feeder cells - we were able to increase CTL expansion to expected levels which could be sustained for several weeks without affecting phenotype or function. However, the number of 24-well plates needed was excessive and cultures required frequent media changes, increasing complexity and manufacturing costs. Therefore, we evaluated novel gas-permeable culture devices (G-Rex) with a silicone membrane at the base allowing gas exchange to occur uninhibited by depth of medium above. This system effectively supports the expansion of CTL and actually increases output by up to 20-fold while decreasing required technician time. Importantly, this amplified cell expansion is not due to more cell divisions but to reduced cell death. This bioprocess optimization increased T-cell output while decreasing the complexity and cost of CTL manufacture, making cell therapy more accessible. PMID:20445351

  18. [Keynote address: Climate change

    SciTech Connect

    Forrister, D.

    1994-12-31

    Broadly speaking, the climate issue is moving from talk to action both in the United States and internationally. While few nations have adopted strict controls or stiff new taxes, a number of them are developing action plans that are making clear their intention to ramp up activity between now and the year 2000... and beyond. There are sensible, economically efficient strategies to be undertaken in the near term that offer the possibility, in many countries, to avoid more draconian measures. These strategies are by-and-large the same measures that the National Academy of Sciences recommended in a 1991 report called, Policy Implications of Greenhouse Warming. The author thinks the Academy`s most important policy contribution was how it recommended the nations act in the face of uncertain science and high risks--that cost effective measures are adopted as cheap insurance... just as nations insure against other high risk, low certainty possibilities, like catastrophic health insurance, auto insurance, and fire insurance. This insurance theme is still right. First, the author addresses how the international climate change negotiations are beginning to produce insurance measures. Next, the author will discuss some of the key issues to watch in those negotiations that relate to longer-term insurance. And finally, the author will report on progress in the United States on the climate insurance plan--The President`s Climate Action Plan.

  19. Towards personalised management of atherosclerosis via computational models in vascular clinics: technology based on patient-specific simulation approach.

    PubMed

    Díaz-Zuccarini, Vanessa; Di Tomaso, Giulia; Agu, Obiekezie; Pichardo-Almarza, Cesar

    2014-01-01

    The development of a new technology based on patient-specific modelling for personalised healthcare in the case of atherosclerosis is presented. Atherosclerosis is the main cause of death in the world and it has become a burden on clinical services as it manifests itself in many diverse forms, such as coronary artery disease, cerebrovascular disease/stroke and peripheral arterial disease. It is also a multifactorial, chronic and systemic process that lasts for a lifetime, putting enormous financial and clinical pressure on national health systems. In this Letter, the postulate is that the development of new technologies for healthcare using computer simulations can, in the future, be developed as in-silico management and support systems. These new technologies will be based on predictive models (including the integration of observations, theories and predictions across a range of temporal and spatial scales, scientific disciplines, key risk factors and anatomical sub-systems) combined with digital patient data and visualisation tools. Although the problem is extremely complex, a simulation workflow and an exemplar application of this type of technology for clinical use is presented, which is currently being developed by a multidisciplinary team following the requirements and constraints of the Vascular Service Unit at the University College Hospital, London.

  20. Quality of life after traumatic brain injury: the clinical use of the QOLIBRI, a novel disease-specific instrument.

    PubMed

    Truelle, Jean-Luc; Koskinen, Sanna; Hawthorne, Graeme; Sarajuuri, Jaana; Formisano, Rita; Von Wild, Klaus; Neugebauer, Edmund; Wilson, Lindsay; Gibbons, Henning; Powell, Jane; Bullinger, Monika; Höfer, Stefan; Maas, Andrew; Zitnay, George; Von Steinbuechel, Nicole

    2010-01-01

    To report the clinical use of the QOLIBRI, a disease-specific measure of health-related quality-of-life (HRQoL) after traumatic brain injury (TBI). The QOLIBRI, with 37 items in six scales (cognition, self, daily life and autonomy, social relationships, emotions and physical problems) was completed by 795 patients in six languages (Finnish, German, Italian, French, English and Dutch). QOLIBRI scores were examined by variables likely to be influenced by rehabilitation interventions and included socio-demographic, functional outcome, health status and mental health variables. The QOLIBRI was self-completed by 73% of participants and 27% completed it in interview. It was sensitive to areas of life amenable to intervention, such as accommodation, work participation, health status (including mental health) and functional outcome. The QOLIBRI provides information about patient's subjective perception of his/her HRQoL which supplements clinical measures and measures of functional outcome. It can be applied across different populations and cultures. It allows the identification of personal needs, the prioritization of therapeutic goals and the evaluation of individual progress. It may also be useful in clinical trials and in longitudinal studies of TBI recovery.

  1. Effects of Popular Diets without Specific Calorie Targets on Weight Loss Outcomes: Systematic Review of Findings from Clinical Trials.

    PubMed

    Anton, Stephen D; Hida, Azumi; Heekin, Kacey; Sowalsky, Kristen; Karabetian, Christy; Mutchie, Heather; Leeuwenburgh, Christiaan; Manini, Todd M; Barnett, Tracey E

    2017-07-31

    The present review examined the evidence base for current popular diets, as listed in the 2016 U.S. News & World Report, on short-term (≤six months) and long-term (≥one year) weight loss outcomes in overweight and obese adults. For the present review, all diets in the 2016 U.S. News & World Report Rankings for "Best Weight-Loss Diets", which did not involve specific calorie targets, meal replacements, supplementation with commercial products, and/or were not categorized as "low-calorie" diets were examined. Of the 38 popular diets listed in the U.S. News & World Report, 20 met our pre-defined criteria. Literature searches were conducted through PubMed, Cochrane Library, and Web of Science using preset key terms to identify all relevant clinical trials for these 20 diets. A total of 16 articles were identified which reported findings of clinical trials for seven of these 20 diets: (1) Atkins; (2) Dietary Approaches to Stop Hypertension (DASH); (3) Glycemic-Index; (4) Mediterranean; (5) Ornish; (6) Paleolithic; and (7) Zone. Of the diets evaluated, the Atkins Diet showed the most evidence in producing clinically meaningful short-term (≤six months) and long-term (≥one-year) weight loss. Other popular diets may be equally or even more effective at producing weight loss, but this is unknown at the present time since there is a paucity of studies on these diets.

  2. Effects of Popular Diets without Specific Calorie Targets on Weight Loss Outcomes: Systematic Review of Findings from Clinical Trials

    PubMed Central

    Anton, Stephen D.; Hida, Azumi; Heekin, Kacey; Sowalsky, Kristen; Karabetian, Christy; Mutchie, Heather; Leeuwenburgh, Christiaan; Manini, Todd M.; Barnett, Tracey E.

    2017-01-01

    The present review examined the evidence base for current popular diets, as listed in the 2016 U.S. News & World Report, on short-term (≤six months) and long-term (≥one year) weight loss outcomes in overweight and obese adults. For the present review, all diets in the 2016 U.S. News & World Report Rankings for “Best Weight-Loss Diets”, which did not involve specific calorie targets, meal replacements, supplementation with commercial products, and/or were not categorized as “low-calorie” diets were examined. Of the 38 popular diets listed in the U.S. News & World Report, 20 met our pre-defined criteria. Literature searches were conducted through PubMed, Cochrane Library, and Web of Science using preset key terms to identify all relevant clinical trials for these 20 diets. A total of 16 articles were identified which reported findings of clinical trials for seven of these 20 diets: (1) Atkins; (2) Dietary Approaches to Stop Hypertension (DASH); (3) Glycemic-Index; (4) Mediterranean; (5) Ornish; (6) Paleolithic; and (7) Zone. Of the diets evaluated, the Atkins Diet showed the most evidence in producing clinically meaningful short-term (≤six months) and long-term (≥one-year) weight loss. Other popular diets may be equally or even more effective at producing weight loss, but this is unknown at the present time since there is a paucity of studies on these diets. PMID:28758964

  3. Preclinical and clinical performance of the Efoora test, a rapid test for detection of human immunodeficiency virus-specific antibodies.

    PubMed

    Arens, Max Q; Mundy, Linda M; Amsterdam, Daniel; Barrett, J Tom; Bigg, Dan; Bruckner, David; Hanna, Bruce; Prince, Harry; Purington, Timothy; Hanna, Todd; Hewitt, Ross; Kalinka, Carolyn; Koppes, Thomas; Maxwell, Sarz; Moe, Ardis; Doymaz, Mehmet; Poulter, Melinda; Saber-Tehrani, Maryam; Simard, Lorenzo; Wilkins-Carmody, Donna; Vidaver, John; Berger, Cheryl; Davis, Alan H; Alzona, Mortimer T

    2005-05-01

    Barriers to effective diagnostic testing for human immunodeficiency virus type 1 (HIV-1) infection can be reduced with simple, reliable, and rapid detection methods. Our objective was to determine the accuracy, sensitivity, and specificity of a new rapid, lateral-flow immunochromatographic HIV-1 antibody detection device. Preclinical studies were performed using seroconversion, cross-reaction, and interference panels, archived clinical specimens, and fresh whole blood. In a multicenter, prospective clinical trial, a four-sample matrix of capillary (fingerstick) whole-blood specimens and venous whole blood, plasma, and serum was tested for HIV-1 antibodies with the Efoora HIV rapid test (Efoora Inc., Buffalo Grove, IL) and compared with an enzyme immunoassay (EIA) (Abbott Laboratories) licensed by the Food and Drug Administration. Western blot and nucleic acid test supplemental assays were employed to adjudicate discordant samples. Preclinical testing of seroconversion panels showed that antibodies were often detected earlier by the rapid test than by a reference EIA. No significant interference or cross-reactions were observed. Testing of 4,984 archived specimens yielded a sensitivity of 99.2% and a specificity of 99.7%. A prospective multicenter clinical study with 2,954 adult volunteers demonstrated sensitivity and specificity for the Efoora HIV rapid test of 99.8% (95% confidence interval [CI], 99.3 and 99.98%) and 99.0% (95% CI, 98.5 and 99.4%), respectively. Reactive rapid HIV-1 antibody detection was confirmed in 99.6% of those with a known HIV infection (n = 939), 5.2% of those in the high-risk group (n = 1,003), and 0.1% of those in the low-risk group (n = 1,012). For 21 (0.71%) patients, there was discordance between the results of the rapid test and the confirmatory EIA/Western blot tests. We conclude that the Efoora HIV rapid test is a simple, rapid assay for detection of HIV-1 antibodies, with high sensitivity and specificity compared to a standardized

  4. SU-C-201-07: Towards Clinical Cherenkov Emission Dosimetry: Stopping Power-To-Cherenkov Power Ratios and Beam Quality Specification of Clinical Electron Beams

    SciTech Connect

    Zlateva, Y; Seuntjens, J; El Naqa, I

    2016-06-15

    Purpose: We propose a Cherenkov emission (CE)-based reference dosimetry method, which in contrast to ionization chamber-based dosimetry, employs spectrum-averaged electron restricted mass collision stopping power-to-Cherenkov power ratios (SCRs), and we examine Monte Carlo-calculated SCRs and beam quality specification of clinical electron beams. Methods: The EGSnrc user code SPRRZnrc was modified to compute SCRs instead of stopping-power ratios (single medium: water; cut-off: CE threshold (observing Spencer-Attix conditions); CE power: Frank-Tamm). SCRs are calculated with BEAMnrc for realistic electron beams with nominal energies of 6–22 MeV from three Varian accelerators (TrueBeam Clinac 21EX, Clinac 2100C/D) and for mono-energetic beams of energies equal to the mean electron energy at the water surface. Sources of deviation between clinical and mono-energetic SCRs are analyzed quantitatively. A universal fit for the beam-quality index R{sub 50} in terms of the depth of 50% CE C{sub 50} is carried out. Results: SCRs at reference depth are overestimated by mono-energetic values by up to 0.2% for a 6-MeV beam and underestimated by up to 2.3% for a 22-MeV beam. The variation is mainly due to the clinical beam spectrum and photon contamination. Beam angular spread has a small effect across all depths and energies. The influence of the electron spectrum becomes increasingly significant at large depths, while at shallow depths and high beam energies photon contamination is predominant (up to 2.0%). The universal data fit reveals a strong linear correlation between R{sub 50} and C{sub 50} (ρ > 0.99999). Conclusion: CE is inherent to radiotherapy beams and can be detected outside the beam with available optical technologies, which makes it an ideal candidate for out-of-beam high-resolution 3D dosimetry. Successful clinical implementation of CE dosimetry hinges on the development of robust protocols for converting measured CE to radiation dose. Our findings constitute

  5. Clinical Value of Specific Immunoglobulin E Detection by Enzyme-Linked Immunosorbent Assay in Cases of Acquired and Congenital Toxoplasmosis

    PubMed Central

    Foudrinier, F.; Villena, I.; Jaussaud, R.; Aubert, D.; Chemla, C.; Martinot, F.; Pinon, J. M.

    2003-01-01

    The clinical value of immunoenzymatic (enzyme-linked immunosorbent assay) detection of anti-Toxoplasma immunoglobulin E (IgE) was assessed by studying 2,036 sera from 792 subjects, comprising seronegative controls and subjects with acute, active, reactivated, or congenital toxoplasmosis. Included were nonimmunized adults; pregnant women with recently acquired infection (acute toxoplasmosis); immunocompetent subjects with recently acquired severe infection (active toxoplasmosis) expressed as fever, adenopathies, splenomegaly, pneumonia, meningitis, or disseminated infection; subjects—some of them immunocompromised—whose previously moderate IgG antibody levels rose, suggesting a reactivation of quiescent toxoplasmosis; and infants born to seroconverted mothers and evaluated for diagnosis of congenital infection and therapeutic management. Specific IgE antibodies were never detected in seronegative subjects. They were present in 85.7% of asymptomatic seroconverters and in 100% of seroconverters with overt toxoplasmosis, following two different kinetics: in the former, the specific IgE titer generally presented a brief peak 2 to 3 months postinfection and then fell rapidly, whereas specific IgE persisted at a very high titer for several months in the latter. IgE emerged concomitantly with the increase in IgG during toxoplasmic reactivation. For neonatal diagnosis of congenital toxoplasmosis, IgE was less informative than IgM and IgA (sensitivities, 59.5, 64.3, and 76.2%, respectively) and had a specificity of 91.9%. Nevertheless, simultaneous measurement of the three isotypes at birth improved the diagnostic yield to 81% relative to the combination of IgA and IgM. Emergence of specific IgE during postnatal treatment for congenital toxoplasmosis is a sign of poor adherence or inadequate dosing. PMID:12682160

  6. A biomarker of mercury body-burden correlated with diagnostic domain specific clinical symptoms of autism spectrum disorder.

    PubMed

    Kern, Janet K; Geier, David A; Adams, James B; Geier, Mark R

    2010-12-01

    The study purpose was to compare the quantitative results from tests for urinary porphyrins, where some of these porphyrins are known biomarkers of heavy metal toxicity, to the independent assessments from a recognized quantitative measurement, the Autism Treatment Evaluation Checklist (ATEC), of specific domains of autistic disorders symptoms (Speech/Language, Sociability, Sensory/Cognitive Awareness, and Health/Physical/Behavior) in a group of children having a clinical diagnosis of autism spectrum disorder (ASD). After a Childhood Autism Rating Scale (CARS) evaluation to assess the development of each child in this study and aid in confirming their classification, and an ATEC was completed by a parent, a urinary porphyrin profile sample was collected and sent out for blinded analysis. Urinary porphyrins from twenty-four children, 2-13 years of age, diagnosed with autism or PDD-NOS were compared to their ATEC scores as well as their scores in the specific domains (Speech/Language, Sociability, Sensory/Cognitive Awareness, and Health/Physical/Behavior) assessed by ATEC. Their urinary porphyrin samples were evaluated at Laboratoire Philippe Auguste (which is an ISO-approved clinical laboratory). The results of the study indicated that the participants' overall ATEC scores and their scores on each of the ATEC subscales (Speech/Language, Sociability, Sensory/Cognitive Awareness, and Health/Physical/Behavior) were linearly related to urinary porphyrins associated with mercury toxicity. The results show an association between the apparent level of mercury toxicity as measured by recognized urinary porphyrin biomarkers of mercury toxicity and the magnitude of the specific hallmark features of autism as assessed by ATEC.

  7. The clinical recovery of tuberculosis patients undergoing specific treatment is associated with changes in the immune and neuroendocrine responses.

    PubMed

    Díaz, Ariana; Bongiovanni, Bettina; D'Attilio, Luciano; Santucci, Natalia; Dídoli, Griselda; Fernández, Rocío Del Valle; Kovalevski, Leandro; Lioi, Susana; Gardeñez, Walter; Brandan, Nadia; Nannini, Luis J; Besedovsky, Hugo; Del Rey, Adriana; Bottasso, Oscar; Bay, María Luisa

    2017-09-29

    Tuberculosis (TB) caused by Mycobacterium tuberculosis is a health problem worldwide. Patients with pulmonary TB show a neuro-immune-endocrine imbalance characterized by an impaired cellular immunity together with increased plasma levels of cortisol, pro- and anti-inflammatory cytokines and markedly decreased dehydroepiandrosterone (DHEA) levels. Extending these findings, we now investigated the immune-endocrine profile of TB patients undergoing specific treatment. Patients (n = 24) were bled at diagnosis (T0), 2, 4, 6 months after treatment initiation and 3 months following its completion. At T0, TB patients showed increased plasma levels of interleukin-6 (IL-6), C reactive protein, interferon-gamma (IFN-γ) and transforming growth factor beta (TGF-β). These mediators decreased during treatment, reaching levels similar to those from healthy controls (n = 26). Specific treatment led to an increased lymphoproliferative response along with clinical improvement. Newly diagnosed patients had low levels of DHEA, with increased cortisol amounts and cortisol/DHEA ratio, which normalized upon specific treatment. As regards glucocorticoid receptors (GR), TB patients at diagnosis presented a reduced mRNA GRα/GRβ ratio in their peripheral blood mononuclear cells. Furthermore, multivariate analysis showed that cortisol/DHEA ratio was positively associated with inflammatory mediators for which this ratio may constitute a disease biomarker. Anti-mycobacterial treatment results in a better immune-endocrine scenario for the control of physiopathological processes accompanying disease development and hence implied in clinical recovery. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. CMV-specific T-cell immunity, viral load, and clinical outcome in seropositive renal transplant recipients: a pilot study.

    PubMed

    Sund, Fredrik; Lidehäll, Anna-Karin; Claesson, Kerstin; Foss, Aksel; Tötterman, Thomas H; Korsgren, Olle; Eriksson, Britt-Marie

    2010-01-01

    Cytomegalovirus (CMV) infection is still the leading opportunistic infection following solid organ transplantation. The aim of this prospective study of renal transplant recipients was to evaluate the dynamics of CMV-specific T-cells, viral load, and clinical symptoms of CMV infection. Levels of tetramer-selected CD8(+) T-cells (TetraCD8), CMV-specific interferon-gamma producing CD8(+) T-cells (IFNgammaCD8), and CD4(+) T-cells (IFNgammaCD4), measured using major histocompatibility complex-tetramer and cytokine flow cytometry techniques, and CMV DNA were monitored monthly in 17 CMV-seropositive patients up to one yr (median 12 months, range 3-12) after transplantation and correlated to clinical outcome. CMV DNAemia was detected in 94% of the patients, but only one patient developed CMV disease. CMV DNAemia >1 million copies/mL was seen in asymptomatic patients. CMV-specific T-cells decreased rapidly after transplantation. TetraCD8 and IFNgammaCD8 regenerated within three months, whereas IFNgammaCD4 recovery was impaired up to one yr after transplantation. The proportion of IFNgammaCD4 at two months post-transplantation as compared with baseline, correlated strongly with the magnitude of the CMV DNAemia. Monitoring the reduction of IFNgammaCD4 compared with baseline during the first months after transplantation could be considered in predicting risk for high-grade CMV DNAemia and in deciding strategic approaches for pre-emptive and prophylactic therapy.

  9. Clinical breakpoints for voriconazole and Candida spp. revisited: review of microbiologic, molecular, pharmacodynamic, and clinical data as they pertain to the development of species-specific interpretive criteria.

    PubMed

    Pfaller, Michael A; Andes, David; Arendrup, Maiken C; Diekema, Daniel J; Espinel-Ingroff, Ana; Alexander, Barbara D; Brown, Steven D; Chaturvedi, Vishnu; Fowler, Cynthia L; Ghannoum, Mahmoud A; Johnson, Elizabeth M; Knapp, Cynthia C; Motyl, Mary R; Ostrosky-Zeichner, Luis; Walsh, Thomas J

    2011-07-01

    We reassessed the Clinical and Laboratory Standards Institute (CLSI) clinical breakpoints (CBPs) for voriconazole. We examined i) the essential (EA: ±2 dilutions) and categorical agreement between 24-h CLSI and EUCAST methods for voriconazole testing of Candida, ii) wild-type (WT) MICs and epidemiologic cutoff values (ECVs) for voriconazole by both CLSI and EUCAST methods, and iii) correlation of MICs with outcomes from previously published data using CLSI methods. We applied these findings to propose new 24-h species-specific CLSI CBPs. Adjusted 24-h CBPs for voriconazole and C. albicans, C. tropicalis, and C. parapsilosis (susceptible, ≤ 0.125 μg/mL; intermediate, 0.25-0.5 μg/mL; resistant, ≥ 1 μg/mL) should be more sensitive for detecting emerging resistance among common Candida species and provide consistency with EUCAST CBPs. In the absence of CBPs for voriconazole and C. glabrata (and less common species), we recommend that their respective ECVs be used to detect the emergence of non-WT strains.

  10. No benefit of patient-specific instrumentation in TKA on functional and gait outcomes: a randomized clinical trial.

    PubMed

    Abdel, Matthew P; Parratte, Sébastien; Blanc, Guillaume; Ollivier, Matthieu; Pomero, Vincent; Viehweger, Elke; Argenson, Jean-Noël A

    2014-08-01

    Although some clinical reports suggest patient-specific instrumentation in TKA may improve alignment, reduce surgical time, and lower hospital costs, it is unknown whether it improves pain- and function-related outcomes and gait. We hypothesized that TKA performed with patient-specific instrumentation would improve patient-reported outcomes measured by validated scoring tools and level gait as ascertained with three-dimensional (3-D) analysis compared with conventional instrumentation 3 months after surgery. We randomized 40 patients into two groups using either patient-specific instrumentation or conventional instrumentation. Patients were evaluated preoperatively and 3 months after surgery. Assessment tools included subjective functional outcome and quality-of-life (QOL) scores using validated questionnaires (New Knee Society Score(©) [KSS], Knee Injury and Osteoarthritis Outcome Score [KOOS], and SF-12). In addition, gait analysis was evaluated with a 3-D system during level walking. The study was powered a priori at 90% to detect a difference in walking speed of 0.1 m/second, which was considered a clinically important difference, and in a post hoc analysis at 80% to detect a difference of 10 points in KSS. There were improvements from preoperatively to 3 months postoperatively in functional scores, QOL, and knee kinematic and kinetic gait parameters during level walking. However, there was no difference between the patient-specific instrumentation and conventional instrumentation groups in KSS, KOOS, SF-12, or 3-D gait parameters. Our observations suggest that patient-specific instrumentation does not confer a substantial advantage in early functional or gait outcomes after TKA. It is possible that differences may emerge, and this study does not allow one to predict any additional variances in the intermediate followup period from 6 months to 1 year postoperatively. However, the goals of the study were to investigate the recovery period as early pain and

  11. Imaging, virtual planning, design, and production of patient-specific implants and clinical validation in craniomaxillofacial surgery.

    PubMed

    Dérand, Per; Rännar, Lars-Erik; Hirsch, Jan-M

    2012-09-01

    The purpose of this article was to describe the workflow from imaging, via virtual design, to manufacturing of patient-specific titanium reconstruction plates, cutting guide and mesh, and its utility in connection with surgical treatment of acquired bone defects in the mandible using additive manufacturing by electron beam melting (EBM). Based on computed tomography scans, polygon skulls were created. Following that virtual treatment plans entailing free microvascular transfer of fibula flaps using patient-specific reconstruction plates, mesh, and cutting guides were designed. The design was based on the specification of a Compact UniLOCK 2.4 Large (Synthes(®), Switzerland). The obtained polygon plates were bent virtually round the reconstructed mandibles. Next, the resections of the mandibles were planned virtually. A cutting guide was outlined to facilitate resection, as well as plates and titanium mesh for insertion of bone or bone substitutes. Polygon plates and meshes were converted to stereolithography format and used in the software Magics for preparation of input files for the successive step, additive manufacturing. EBM was used to manufacture the customized implants in a biocompatible titanium grade, Ti6Al4V ELI. The implants and the cutting guide were cleaned and sterilized, then transferred to the operating theater, and applied during surgery. Commercially available software programs are sufficient in order to virtually plan for production of patient-specific implants. Furthermore, EBM-produced implants are fully usable under clinical conditions in reconstruction of acquired defects in the mandible. A good compliance between the treatment plan and the fit was demonstrated during operation. Within the constraints of this article, the authors describe a workflow for production of patient-specific implants, using EBM manufacturing. Titanium cutting guides, reconstruction plates for fixation of microvascular transfer of osteomyocutaneous bone grafts, and

  12. Imaging, Virtual Planning, Design, and Production of Patient-Specific Implants and Clinical Validation in Craniomaxillofacial Surgery

    PubMed Central

    Dérand, Per; Rännar, Lars-Erik; Hirsch, Jan-M

    2012-01-01

    The purpose of this article was to describe the workflow from imaging, via virtual design, to manufacturing of patient-specific titanium reconstruction plates, cutting guide and mesh, and its utility in connection with surgical treatment of acquired bone defects in the mandible using additive manufacturing by electron beam melting (EBM). Based on computed tomography scans, polygon skulls were created. Following that virtual treatment plans entailing free microvascular transfer of fibula flaps using patient-specific reconstruction plates, mesh, and cutting guides were designed. The design was based on the specification of a Compact UniLOCK 2.4 Large (Synthes®, Switzerland). The obtained polygon plates were bent virtually round the reconstructed mandibles. Next, the resections of the mandibles were planned virtually. A cutting guide was outlined to facilitate resection, as well as plates and titanium mesh for insertion of bone or bone substitutes. Polygon plates and meshes were converted to stereolithography format and used in the software Magics for preparation of input files for the successive step, additive manufacturing. EBM was used to manufacture the customized implants in a biocompatible titanium grade, Ti6Al4V ELI. The implants and the cutting guide were cleaned and sterilized, then transferred to the operating theater, and applied during surgery. Commercially available software programs are sufficient in order to virtually plan for production of patient-specific implants. Furthermore, EBM-produced implants are fully usable under clinical conditions in reconstruction of acquired defects in the mandible. A good compliance between the treatment plan and the fit was demonstrated during operation. Within the constraints of this article, the authors describe a workflow for production of patient-specific implants, using EBM manufacturing. Titanium cutting guides, reconstruction plates for fixation of microvascular transfer of osteomyocutaneous bone grafts, and

  13. Towards the Personalized Treatment of Glioblastoma: Integrating Patient-Specific Clinical Data in a Continuous Mechanical Model

    PubMed Central

    Faggiano, Elena; Boffano, Carlo; Acerbi, Francesco; Ciarletta, Pasquale

    2015-01-01

    Glioblastoma multiforme (GBM) is the most aggressive and malignant among brain tumors. In addition to uncontrolled proliferation and genetic instability, GBM is characterized by a diffuse infiltration, developing long protrusions that penetrate deeply along the fibers of the white matter. These features, combined with the underestimation of the invading GBM area by available imaging techniques, make a definitive treatment of GBM particularly difficult. A multidisciplinary approach combining mathematical, clinical and radiological data has the potential to foster our understanding of GBM evolution in every single patient throughout his/her oncological history, in order to target therapeutic weapons in a patient-specific manner. In this work, we propose a continuous mechanical model and we perform numerical simulations of GBM invasion combining the main mechano-biological characteristics of GBM with the micro-structural information extracted from radiological images, i.e. by elaborating patient-specific Diffusion Tensor Imaging (DTI) data. The numerical simulations highlight the influence of the different biological parameters on tumor progression and they demonstrate the fundamental importance of including anisotropic and heterogeneous patient-specific DTI data in order to obtain a more accurate prediction of GBM evolution. The results of the proposed mathematical model have the potential to provide a relevant benefit for clinicians involved in the treatment of this particularly aggressive disease and, more importantly, they might drive progress towards improving tumor control and patient’s prognosis. PMID:26186462

  14. Addressing viral resistance through vaccines

    PubMed Central

    Laughlin, Catherine; Schleif, Amanda; Heilman, Carole A

    2015-01-01

    Antimicrobial resistance is a serious healthcare concern affecting millions of people around the world. Antiviral resistance has been viewed as a lesser threat than antibiotic resistance, but it is important to consider approaches to address this growing issue. While vaccination is a logical strategy, and has been shown to be successful many times over, next generation viral vaccines with a specific goal of curbing antiviral resistance will need to clear several hurdles including vaccine design, evaluation and implementation. This article suggests that a new model of vaccination may need to be considered: rather than focusing on public health, this model would primarily target sectors of the population who are at high risk for complications from certain infections. PMID:26604979

  15. Using pathology-specific laboratory profiles in clinical pathology to reduce inappropriate test requesting: two completed audit cycles.

    PubMed

    Baricchi, Roberto; Zini, Michele; Nibali, Maria Grazia; Vezzosi, Walter; Insegnante, Vincenzo; Manfuso, Clotilde; Polese, Alessandra; Costoli, Valmer; Spelti, Antonio; Formisano, Debora; Orlandini, Danilo; Nicolini, Fausto; Poli, Antonio

    2012-07-03

    Systematic reviews have shown that, although well prepared, the Consensus Guidelines have failed to change clinical practice. In the healthcare district of Castelnovo né Monti (Reggio Emilia, Italy), it became necessary for the GPs and Clinical Pathologists to work together to jointly define laboratory profiles. Observational study with two cycles of retrospective audit on test request forms, in a primary care setting. Objectives of the study were to develop pathology-specific laboratory profiles and to increase the number of provisional diagnoses on laboratory test request forms. A Multiprofessional Multidisciplinary Inter-hospital Work Team developed pathology-specific laboratory profiles for more effective test requesting. After 8 training sessions that used a combined strategy with multifaceted interventions, the 23 General Practitioners (GPs) in the trial district (Castelnovo nè Monti) tested the profiles; the 21 GPs in the Puianello district were the control group; all GPs in both districts participated in the trial. All laboratory tests for both healthcare districts are performed at the Laboratory located in the trial district. A baseline and a 1-year audit were performed in both districts on the GPs' request forms. Seven pathology-specific laboratory profiles for outpatients were developed. In the year after the first audit cycle: 1) the number of tests requested in the trial district was distinctly lower than that in the previous year, with a decrease of about 5% (p < 0.001); 2) the provisional diagnosis on the request forms was 52.8% in the trial district and 42% in the control district (P < 0.001); 3) the decrease of the number of tests on each request form was much more marked in the trial district (8.73 vs. 10.77; p < 0.001). The first audit cycle showed a significant decrease in the number of tests ordered only in the trial district. The combined strategy used in this study improved the prescriptive compliance of most of the GPs involved

  16. Estimation of left ventricular blood flow parameters: clinical application of patient-specific CFD simulations from 4D echocardiography

    NASA Astrophysics Data System (ADS)

    Larsson, David; Spühler, Jeannette H.; Günyeli, Elif; Weinkauf, Tino; Hoffman, Johan; Colarieti-Tosti, Massimiliano; Winter, Reidar; Larsson, Matilda

    2017-03-01

    Echocardiography is the most commonly used image modality in cardiology, assessing several aspects of cardiac viability. The importance of cardiac hemodynamics and 4D blood flow motion has recently been highlighted, however such assessment is still difficult using routine echo-imaging. Instead, combining imaging with computational fluid dynamics (CFD)-simulations has proven valuable, but only a few models have been applied clinically. In the following, patient-specific CFD-simulations from transthoracic dobutamin stress echocardiography have been used to analyze the left ventricular 4D blood flow in three subjects: two with normal and one with reduced le