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Sample records for achieved clinical response

  1. Adalimumab induction and maintenance therapy achieve clinical remission and response in Chinese patients with Crohn's disease

    PubMed Central

    Ran, Zhi Hua; Gao, Xiang; Chen, Minhu; Zhong, Jie; Sheng, Jian-Qiu; Kamm, Michael A; Travis, Simon; Wallace, Kori; Mostafa, Nael M; Shapiro, Marisa; Li, Yao; Thakkar, Roopal B; Robinson, Anne M

    2016-01-01

    Background/Aims This was a Phase 2 study (NCT02015793) to evaluate the pharmacokinetics, safety, and efficacy of adalimumab in Chinese patients with Crohn's disease (CD). Methods Thirty, adult Chinese patients with CD (CD Activity Index [CDAI] 220–450; high-sensitivity [hs]-C-reactive protein [CRP] ≥3 mg/L) received double-blind adalimumab 160/80 mg or 80/40 mg at weeks 0/2, followed by 40 mg at weeks 4 and 6. An open-label extension period occurred from weeks 8–26; patients received 40 mg adalimumab every other week. Serum adalimumab concentration and change from baseline in fecal calprotectin (FC) were measured during the double-blind period. Clinical remission (CDAI <150), response (decrease in CDAI ≥70 points from baseline), and change from baseline in hs-CRP were assessed through week 26. Nonresponder imputation was used for missing categorical data and last observation carried forward for missing hs-CRP/FC values. No formal hypothesis was tested. Adverse events were monitored. Results Mean adalimumab serum concentrations during the induction phase were 13.9–18.1 µg/mL (160/80 mg group) and 7.5−9.5 µg/mL (80/40 mg group). During the double-blind period, higher remission/response rates and greater reductions from baseline in hs-CRP and FC were observed with adalimumab 160/80 mg compared to that with 80/40 mg. Adverse event rates were similar among all treatment groups. Conclusions Adalimumab serum concentrations in Chinese patients with CD were comparable to those observed previously in Western and Japanese patients. Clinically meaningful remission rates and improvement in inflammatory markers were achieved with both dosing regimens; changes occurred rapidly with adalimumab 160/80 mg induction therapy. No new safety signals were reported. PMID:27175116

  2. Achieving clinical integration.

    PubMed

    Redding, John

    2013-11-01

    To develop an effective and sustainable clinically integrated network (CIN) that positions a healthcare organization for value-based payment and other effects of healthcare reform, leaders of CIN initiatives should: Embrace progress rather than perfection; Constrain the development timeline by project managing in reverse; Ensure that physician leaders play an oversight role in the development process. PMID:24340650

  3. Clinically significant responses achieved with romidepsin across disease compartments in patients with cutaneous T-cell lymphoma

    PubMed Central

    Kim, Ellen J.; Kim, Youn H.; Rook, Alain H.; Lerner, Adam; Duvic, Madeleine; Reddy, Sunil; Robak, Tadeusz; Becker, Jürgen C.; Samtsov, Alexey; McCulloch, William; Waksman, Joel; Whittaker, Sean

    2015-01-01

    Cutaneous T-cell lymphoma (CTCL) is a rare heterogeneous group of non-Hodgkin lymphomas that arises in the skin but can progress to systemic disease (lymph nodes, blood, viscera). Historically, in clinical trials of CTCL there has been little consistency in how responses were defined in each disease “compartment”; some studies only assessed responses in the skin. The histone deacetylase inhibitor romidepsin is approved by the US Food and Drug Administration for the treatment of CTCL in patients who have received at least one prior systemic therapy. Phase II studies that led to approval used rigorous composite end points that incorporated disease assessments in all compartments. The objective of this analysis was to thoroughly examine the activity of romidepsin within each disease compartment in patients with CTCL. Romidepsin was shown to have clinical activity across disease compartments and is suitable for use in patients with CTCL having skin involvement only, erythroderma, lymphadenopathy and/or blood involvement. PMID:25791237

  4. Prediction of Achievement in Clinical Pharmacy Courses

    ERIC Educational Resources Information Center

    Simon, Lee S.

    1978-01-01

    A study sought to identify student characteristics which account for academic achievement in clinical pharmacy courses. Preclinical grade point average was the best predictor. Subscales of the California Personality Inventory and the Myers-Briggs Type Indicator, work experience, sex, and age were the other predictor variables. (SW)

  5. Sharing Leadership Responsibilities Results in Achievement Gains

    ERIC Educational Resources Information Center

    Armistead, Lew

    2010-01-01

    Collective, not individual, leadership in schools has a greater impact on student achievement; when principals and teachers share leadership responsibilities, student achievement is higher; and schools having high student achievement also display a vision for student achievement and teacher growth. Those are just a few of the insights into school…

  6. Different clinical electrodes achieve similar electrical nerve conduction block

    NASA Astrophysics Data System (ADS)

    Boger, Adam; Bhadra, Narendra; Gustafson, Kenneth J.

    2013-10-01

    Objective. We aim to evaluate the suitability of four electrodes previously used in clinical experiments for peripheral nerve electrical block applications. Approach. We evaluated peripheral nerve electrical block using three such clinical nerve cuff electrodes (the Huntington helix, the Case self-sizing Spiral and the flat interface nerve electrode) and one clinical intramuscular electrode (the Memberg electrode) in five cats. Amplitude thresholds for the block using 12 or 25 kHz voltage-controlled stimulation, onset response, and stimulation thresholds before and after block testing were determined. Main results. Complete nerve block was achieved reliably and the onset response to blocking stimulation was similar for all electrodes. Amplitude thresholds for the block were lowest for the Case Spiral electrode (4 ± 1 Vpp) and lower for the nerve cuff electrodes (7 ± 3 Vpp) than for the intramuscular electrode (26 ± 10 Vpp). A minor elevation in stimulation threshold and reduction in stimulus-evoked urethral pressure was observed during testing, but the effect was temporary and did not vary between electrodes. Significance. Multiple clinical electrodes appear suitable for neuroprostheses using peripheral nerve electrical block. The freedom to choose electrodes based on secondary criteria such as ease of implantation or cost should ease translation of electrical nerve block to clinical practice.

  7. Achieving reliable communication in dynamic emergency responses.

    PubMed

    Chipara, Octav; Plymoth, Anders N; Liu, Fang; Huang, Ricky; Evans, Brian; Johansson, Per; Rao, Ramesh; Griswold, William G

    2011-01-01

    Emergency responses require the coordination of first responders to assess the condition of victims, stabilize their condition, and transport them to hospitals based on the severity of their injuries. WIISARD is a system designed to facilitate the collection of medical information and its reliable dissemination during emergency responses. A key challenge in WIISARD is to deliver data with high reliability as first responders move and operate in a dynamic radio environment fraught with frequent network disconnections. The initial WIISARD system employed a client-server architecture and an ad-hoc routing protocol was used to exchange data. The system had low reliability when deployed during emergency drills. In this paper, we identify the underlying causes of unreliability and propose a novel peer-to-peer architecture that in combination with a gossip-based communication protocol achieves high reliability. Empirical studies show that compared to the initial WIISARD system, the redesigned system improves reliability by as much as 37% while reducing the number of transmitted packets by 23%. PMID:22195075

  8. Achieving Reliable Communication in Dynamic Emergency Responses

    PubMed Central

    Chipara, Octav; Plymoth, Anders N.; Liu, Fang; Huang, Ricky; Evans, Brian; Johansson, Per; Rao, Ramesh; Griswold, William G.

    2011-01-01

    Emergency responses require the coordination of first responders to assess the condition of victims, stabilize their condition, and transport them to hospitals based on the severity of their injuries. WIISARD is a system designed to facilitate the collection of medical information and its reliable dissemination during emergency responses. A key challenge in WIISARD is to deliver data with high reliability as first responders move and operate in a dynamic radio environment fraught with frequent network disconnections. The initial WIISARD system employed a client-server architecture and an ad-hoc routing protocol was used to exchange data. The system had low reliability when deployed during emergency drills. In this paper, we identify the underlying causes of unreliability and propose a novel peer-to-peer architecture that in combination with a gossip-based communication protocol achieves high reliability. Empirical studies show that compared to the initial WIISARD system, the redesigned system improves reliability by as much as 37% while reducing the number of transmitted packets by 23%. PMID:22195075

  9. Clinical ethics revisited: responses

    PubMed Central

    Benatar, Solomon R; Bhutta, Zulfiqar A; Daar, Abdallah S; Hope, Tony; MacRae, Sue; Roberts, Laura W; Sharpe, Virginia A

    2001-01-01

    This series of responses was commissioned to accompany the article by Singer et al, which can be found at . If you would like to comment on the article by Singer et al or any of the responses, please email us on editorial@biomedcentral.com. PMID:11346457

  10. Variability in Clinical Integration Achieved by Athletic Training Students across Different Clinical Sport Assignments

    ERIC Educational Resources Information Center

    Dodge, Thomas M.; Mazerolle, Stephanie M.; Bowman, Thomas G.

    2015-01-01

    Context: Clinical integration impacts athletic training students' (ATSs) motivation and persistence. Research has yet to elucidate the manner in which different clinical placements can influence clinical integration. Objective: To examine differences in the levels of clinical integration achieved by ATSs across various clinical sport assignments.…

  11. Achieving clinical equality in an influenza pandemic: patent realities.

    PubMed

    Kane, Eileen M

    2009-01-01

    A twenty-first century novel influenza A (H1N1) pandemic is currently unfolding, and the eventual scope of this public health crisis is not clear. In addition, ongoing surveillance of the avian influenza A (H5N1) virus reveals outbreaks of human-to-human transmission of the virus, with significant mortality. Effective pandemic management depends on pharmaceutical intervention with two different clinical objectives: the generation of an immune response to specific viral strains (vaccination) and the reduction of viral replication in an infected individual (antiviral administration). The ability to offer pharmaceutical interventions for a public health crisis depends on three factors: development, capacity, and access. Pharmaceutical measures must be developed, capacity must be established, and access must be ensured. The article discusses the three nodes of patenting that influence the availability of pharmaceutical countermeasures in an influenza pandemic. Identification of the causative influenza virus is the first step in pandemic management and precedes vaccine design, and the virus and its RNA sequence are both knowledge assets and inputs for vaccine design. Vaccine development, therefore, will be influenced by any patents on the genetic sequences or proteins of the pandemic virus, as well as on novel methods for vaccine production, the actual vaccine or adjuvant technology, all of which are relevant to the assembly of a working vaccine on short notice. Pharmaceutical treatment of influenza infection during a pandemic could also rely on use of patented antiviral drugs, whose efficacy may be revealed as the pandemic unfolds. Unlike vaccines, these are not generally developed de novo for a pandemic, but their availability could be dependent on the exercise of patent rights by market incumbents. Patent rights could control capacity, which may determine access. Pandemic planning must consider how patenting can influence development, capacity and access to

  12. Improving International Research with Clinical Specimens: 5 Achievable Objectives

    PubMed Central

    LaBaer, Joshua

    2012-01-01

    Our increased interest in translational research has created a large demand for blood, tissue and other clinical samples, which find use in a broad variety of research including genomics, proteomics, and metabolomics. Hundreds of millions of dollars have been invested internationally on the collection, storage and distribution of samples. Nevertheless, many researchers complain in frustration about their inability to obtain relevant and/or useful samples for their research. Lack of access to samples, poor condition of samples, and unavailability of appropriate control samples have slowed our progress in the study of diseases and biomarkers. In this editorial, I focus on five major challenges that thwart clinical sample use for translational research and propose near term objectives to address them. They include: (1) defining our biobanking needs; (2) increasing the use of and access to standard operating procedures; (3) mapping inter-observer differences for use in normalizing diagnoses; (4) identifying natural internal protein controls; and (5) redefining the clinical sample paradigm by building partnerships with the public. In each case, I believe that we have the tools at hand required to achieve the objective within 5 years. Potential paths to achieve these objectives are explored. However we solve these problems, the future of proteomics depends on access to high quality clinical samples, collected under standardized conditions, accurately annotated and shared under conditions that promote the research we need to do. PMID:22998582

  13. Are Teachers Responsible for Low Achievement by Poor Students?

    ERIC Educational Resources Information Center

    Berliner, David C.

    2009-01-01

    Backers of the No Child Left Behind (NCLB) law based their support on the belief that teachers and administrators primarily were responsible for low levels of achievement by America's poor. This one-sided view about who is responsible for the nation's achievement gap is both inadequate and unsupported by the evidence. The author argues that harsh…

  14. Identifying and managing clinical responsibility.

    PubMed

    Armitage, Mary; Shaw, Kirstyn; Drew, Peter

    2008-04-01

    Clinical responsibility is an area that requires extensive consideration and development to align with other changes in healthcare in the NHS. Increasing levels of litigation and investigation into the practice of medical practitioners have highlighted the need for clearer guidance for doctors. Using hypothetical case studies, this project explored the understandings and experiences of physicians and potential solutions in areas where there was ambiguity in clinical responsibility. In addition, existing policy and practice within trusts throughout the UK was analysed. The output from the focus group discussion and policy analysis led to the recommendations and guidance for doctors outlined in this paper, with the aim of illustrating the central themes that both doctors and trusts need to address in the future. PMID:18478855

  15. Identification of Synergistic, Clinically Achievable, Combination Therapies for Osteosarcoma

    PubMed Central

    Yu, Diana; Kahen, Elliot; Cubitt, Christopher L.; McGuire, Jeremy; Kreahling, Jenny; Lee, Jae; Altiok, Soner; Lynch, Conor C.; Sullivan, Daniel M.; Reed, Damon R.

    2015-01-01

    Systemic therapy has improved osteosarcoma event-free and overall survival, but 30–50% of patients originally diagnosed will have progressive or recurrent disease, which is difficult to cure. Osteosarcoma has a complex karyotype, with loss of p53 in the vast majority of cases and an absence of recurrent, targetable pathways. In this study, we explored 54 agents that are clinically approved for other oncologic indications, agents in active clinical development, and others with promising preclinical data in osteosarcoma at clinically achievable concentrations in 5 osteosarcoma cell lines. We found significant single-agent activity of multiple agents and tested 10 drugs in all permutations of two-drug combinations to define synergistic combinations by Chou and Talalay analysis. We then evaluated order of addition to choose the combinations that may be best to translate to the clinic. We conclude that the repurposing of chemotherapeutics in osteosarcoma by using an in vitro system may define novel drug combinations with significant in vivo activity. In particular, combinations of proteasome inhibitors with histone deacetylase inhibitors and ixabepilone and MK1775 demonstrated excellent activity in our assays. PMID:26601688

  16. Culturally Responsive Pedagogies in Arizona and Latino Students' Achievement

    ERIC Educational Resources Information Center

    López, Francesca A.

    2016-01-01

    Background: Despite numerous educational reform efforts aimed at aggressively addressing achievement disparities, Latinos continue to underperform in school. In sharp contrast to the belief that the inordinate achievement disparities among Latino students stem from deficiencies, some researchers assert that culturally responsive teaching (CRT)…

  17. Superintendents' Responses to the Achievement Gap: An Ethical Critique.

    ERIC Educational Resources Information Center

    Sherman, Whitney H.; Grogan, Margaret

    2003-01-01

    Uses multidimensional ethical framework to critique 15 Virginia superintendents' responses to the achievement gap as measured by the Standards of Learning (SOL) tests. Questions majority of superintendents' readiness to deal with moral and ethical issues related to achievement gap. (Contains 24 references.) (PKP)

  18. Are Teachers Responsible for Low Achievement by Poor Students?

    ERIC Educational Resources Information Center

    Berliner, David C.

    2010-01-01

    Backers of No Child Left Behind (NCLB) based their support on the belief that teachers and administrators primarily were responsible for low levels of achievement by America's poor. But this one-sided view is both inadequate and unsupported by the evidence. The author argues that harsh social policies and the pernicious effects of poverty are more…

  19. Response to Intervention (RTI) Effectiveness in Kindergarten Reading Achievement

    ERIC Educational Resources Information Center

    Whittaker, Susan

    2013-01-01

    The purpose of this quantitative study was to determine whether kindergarten-reading achievement could be increased by implementing Response to Intervention (RtI) strategies. Kindergarten children (N = 290) who were identified as at-risk for reading difficulties were assigned to receive intervention through a) small reading groups (SRG), b)…

  20. Middle School Response to Intervention and Student Achievement

    ERIC Educational Resources Information Center

    Smith, Kelly A. Obrion

    2013-01-01

    This ex post facto descriptive-comparative quantitative study compared the differences in reading achievement between groups of 6th- through 8th-grade students enrolled in a response to intervention (RtI) classroom against groups of students enrolled in a general education classroom. Students across English language learner and low socioeconomic…

  1. The Interim : until you achieve an operationally responsive ground system

    NASA Technical Reports Server (NTRS)

    Wendlandt, Bob; Clarke, Kelly; Lei, Jordan; Miyamoto, Charles; Owen-Mankovich, Kyran

    2008-01-01

    Everyone wants to achieve a 'Responsive' Ground Data System (GDS), but that takes time. What do you do in the interim? Our group, called the Integration, Test and Deployment Team (ITD), is a group of responsive engineers whose primary focus is to assist JPL projects to successfully adapt, test, integrate and deploy their ground data system. The team configures and adapts the GDS for a project, so that analysts, engineers and scientist do not need to be experts in the GDS to operate it. The team has developed a human interface to accommodate all types of users. It provides Graphical User Interfaces (GUI's) for those that want GUI's, command line interfaces for those that want control, and selection button interfaces for other users. The cornerstone of a responsive Ground Data System is responsive people. Without individuals who can be aware of a project's changing needs and requirements, how can the GDS become responsive

  2. The Interim: Until You Achieve an Operationally Responsive Ground System

    NASA Technical Reports Server (NTRS)

    Wendlandt, Bob; Clarke, Kelly; Miyamoto, Charles; Lei, Jordan; Owen-Mankovich, Kyran

    2008-01-01

    Everyone wants to achieve a 'Responsive' Ground Data System (GDS), but that takes time. What do you do in the interim? Our group, called the Integration, Test and Deployment Team (ITD), is a group of responsive engineers whose primary focus is to assist JPL projects to successfully adapt, test, integrate and deploy their ground data system. The team configures and adapts the GDS for a project, so that analysts, engineers and scientist do not need to be experts in the GDS to operate it. The team has developed a human interface to accommodate all types of users. It provides Graphical User Interfaces (GUI's) for those that want GUI's, command line interfaces for those that want control, and selection button interfaces for other users. The cornerstone of a responsive Ground Data System is responsive people. Without individuals who can be aware of a project's changing needs and requirements, how can the GDS become responsive?.

  3. Achieving the World Health Organization's vision for clinical pharmacology.

    PubMed

    Martin, Jennifer H; Henry, David; Gray, Jean; Day, Richard; Bochner, Felix; Ferro, Albert; Pirmohamed, Munir; Mörike, Klaus; Schwab, Matthias

    2016-02-01

    Clinical pharmacology is a medical specialty whose practitioners teach, undertake research, frame policy, give information and advice about the actions and proper uses of medicines in humans and implement that knowledge in clinical practice. It involves a combination of several activities: drug discovery and development, training safe prescribers, providing objective and evidence-based therapeutic information to ethics, regulatory and pricing bodies, supporting patient care in an increasingly subspecialized arena where co-morbidities, polypharmacy, altered pharmacokinetics and drug interactions are common and developing and contributing to medicines policies for Governments. Clinical pharmacologists must advocate drug quality and they must also advocate for sustainability of the Discipline. However for this they need appropriate clinical service and training support. This Commentary discusses strategies to ensure the Discipline is supported by teaching, training and policy organizations, to communicate the full benefits of clinical pharmacology services, put a monetary value on clinical pharmacology services and to grow the clinical pharmacology workforce to support a growing clinical, academic and regulatory need. PMID:26466826

  4. Expertise, Ethics Expertise, and Clinical Ethics Consultation: Achieving Terminological Clarity.

    PubMed

    Iltis, Ana S; Sheehan, Mark

    2016-08-01

    The language of ethics expertise has become particularly important in bioethics in light of efforts to establish the value of the clinical ethics consultation (CEC), to specify who is qualified to function as a clinical ethics consultant, and to characterize how one should evaluate whether or not a person is so qualified. Supporters and skeptics about the possibility of ethics expertise use the language of ethics expertise in ways that reflect competing views about what ethics expertise entails. We argue for clarity in understanding the nature of expertise and ethics expertise. To be an ethics expert, we argue, is to be an expert in knowing what ought to be done. Any attempt to articulate expertise with respect to knowing what ought to be done must include an account of ethics that specifies the nature of moral truth and the means by which we access this truth or a theoretical account of ethics such that expertise in another domain is linked to knowing or being better at judging what ought to be done and the standards by which this "knowing" or "being better at judging" is determined. We conclude with a discussion of the implications of our analysis for the literature on ethics expertise in CEC. We do think that there are clear domains in which a clinical ethics consultant might be expert but we are skeptical about the possibility that this includes ethics expertise. Clinical ethics consultants should not be referred to as ethics experts. PMID:27256848

  5. Ethical responsibilities of the clinical engineer.

    PubMed

    Saha, P; Saha, S

    1986-01-01

    Because of the growth of medical technology, Clinical Engineers have increased responsibilities in respect to this new technology and so to modern medicine itself. This results in a need to ensure that an ethical consciousness of responsibilities to patients, physicians, and institutions grows within Clinical Engineers as they move into evermore important roles within the health care system. Clinical Engineers must have clearly defined roles, as well as authority acknowledged and supported by other health care professionals. Most importantly, Clinical Engineers themselves must recognize the seriousness of their professional responsibilities as they contribute to the maintenance of equipment, use and design instrumentation, and fulfill roles in administration, management, and research. As members of the health care team, Clinical Engineers must be prepared to face ethical issues arising from defective or inadequate equipment, hazards and incidents, scarcity and resources, conflict of interest, confidentiality, clinical research, "truth-telling," and care of the terminally ill. PMID:10275911

  6. Feedback and assessment for clinical placements: achieving the right balance

    PubMed Central

    Burgess, Annette; Mellis, Craig

    2015-01-01

    During clinical placements, the provision of feedback forms an integral part of the learning process and enriches students’ learning experiences. The purpose of feedback is to improve the learner’s knowledge, skills, or behavior. Receipt of accurate feedback can help to narrow the gap between actual and desired performance. Effective and regular feedback has the potential to reinforce good practice and motivate the learner toward the desired outcome. Despite the obvious role of feedback in effective teaching and learning, a common complaint from students is that they do not receive adequate feedback. Unfortunately, skills in giving and receiving feedback are rarely taught to students or clinicians. This study aims to provide an understanding of the role of feedback within the learning process, consider consequences of inadequate or poorly given feedback, consider the barriers to the feedback process, provide practical guidelines for providing feedback, and consider the need for student and faculty development in feedback skills. PMID:26056511

  7. Toward achieving optimal response: understanding and managing antidepressant side effects

    PubMed Central

    Kelly, Karen; Posternak, Michael; Jonathan, E. Alpert

    2008-01-01

    The safety and tolerability of antidepressants have improved considerably over the past two decades, Nevertheless, antidepressant side effects are still common and problematic. The majority of patients treated with contemporary agents experience one or more bothersome side effects. These side effects often create barriers to achieving depressive remission, as well as to preventing relapse and recurrence. Clinicians tend to underestimate the prevalence of side effects, and as many as one quarter of patients discontinue their antidepressants because of difficult-to-tolerate side effects; others may continue on antidepressant therapy but experience diminished quality of life related to troublesome side effects. This article reviews the prevalence of side effects, the impact of side effects on treatment adherence, and methodological issues including the challenge of distinguishing side effects from residual depressive symptoms, discontinuation effects, and general medical problems. In addition, we address the most common side effects such as sexual dysfunction, gastrointestinal problems, sleep disturbance, apathy, and fatigue, and offer strategies for management that may help patients achieve optimal response to pharmacotherapy. PMID:19170398

  8. Achieving consensus for clinical trials: the REiNS International Collaboration.

    PubMed

    Plotkin, Scott R; Blakeley, Jaishri O; Dombi, Eva; Fisher, Michael J; Hanemann, C Oliver; Walsh, Karin S; Wolters, Pamela L; Widemann, Brigitte C

    2013-11-19

    The neurofibromatoses (NF)--including neurofibromatosis 1 (NF1), neurofibromatosis 2 (NF2), and schwannomatosis--are related tumor-suppressor syndromes characterized by a predisposition to multiple tumor types and other disease manifestations, which often result in functional disability, reduced quality of life, pain, and, in some cases, malignancy. With increasing knowledge of the biology and pathogenesis of NF, clinical trials with targeted agents directed at NF tumors have become available. Most clinical trials for patients with NF have used designs and endpoints similar to oncology trials. However, differences in the disease manifestations and natural history of NF (compared to cancers) require the development of new designs and endpoints to perform meaningful NF clinical trials. The Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration was established in 2011 at the Children's Tumor Foundation meeting to achieve consensus within the NF community about the design of future clinical trials, with a specific emphasis on endpoints. The REiNS Collaboration includes 7 working groups that focus on imaging of tumor response; functional, visual, patient-reported, and neurocognitive outcomes; whole-body MRI; and disease biomarkers. This supplement includes the first series of recommendations by the REiNS Collaboration. The hope is that these recommendations will be used by members of the group and by researchers outside of the REiNS International Collaboration to standardize the measurement of outcomes and thus improve clinical trials for patients with NF. Ultimately, we plan to engage industry partners and national regulatory agencies in this process to facilitate the approval of drugs for patients with NF. PMID:24249801

  9. Using Visual and Narrative Methods to Achieve Fair Process in Clinical Care

    PubMed Central

    2011-01-01

    The Institute of Medicine has targeted patient-centeredness as an important area of quality improvement. A major dimension of patient-centeredness is respect for patient's values, preferences, and expressed needs. Yet specific approaches to gaining this understanding and translating it to quality care in the clinical setting are lacking. From a patient perspective quality is not a simple concept but is best understood in terms of five dimensions: technical outcomes; decision-making efficiency; amenities and convenience; information and emotional support; and overall patient satisfaction. Failure to consider quality from this five-pronged perspective results in a focus on medical outcomes, without considering the processes central to quality from the patient's perspective and vital to achieving good outcomes. In this paper, we argue for applying the concept of fair process in clinical settings. Fair process involves using a collaborative approach to exploring diagnostic issues and treatments with patients, explaining the rationale for decisions, setting expectations about roles and responsibilities, and implementing a core plan and ongoing evaluation. Fair process opens the door to bringing patient expertise into the clinical setting and the work of developing health care goals and strategies. This paper provides a step by step illustration of an innovative visual approach, called photovoice or photo-elicitation, to achieve fair process in clinical work with acquired brain injury survivors and others living with chronic health conditions. Applying this visual tool and methodology in the clinical setting will enhance patient-provider communication; engage patients as partners in identifying challenges, strengths, goals, and strategies; and support evaluation of progress over time. Asking patients to bring visuals of their lives into the clinical interaction can help to illuminate gaps in clinical knowledge, forge better therapeutic relationships with patients living

  10. Using visual and narrative methods to achieve fair process in clinical care.

    PubMed

    Lorenz, Laura S; Chilingerian, Jon A

    2011-01-01

    The Institute of Medicine has targeted patient-centeredness as an important area of quality improvement. A major dimension of patient-centeredness is respect for patient's values, preferences, and expressed needs. Yet specific approaches to gaining this understanding and translating it to quality care in the clinical setting are lacking. From a patient perspective quality is not a simple concept but is best understood in terms of five dimensions: technical outcomes; decision-making efficiency; amenities and convenience; information and emotional support; and overall patient satisfaction. Failure to consider quality from this five-pronged perspective results in a focus on medical outcomes, without considering the processes central to quality from the patient's perspective and vital to achieving good outcomes. In this paper, we argue for applying the concept of fair process in clinical settings. Fair process involves using a collaborative approach to exploring diagnostic issues and treatments with patients, explaining the rationale for decisions, setting expectations about roles and responsibilities, and implementing a core plan and ongoing evaluation. Fair process opens the door to bringing patient expertise into the clinical setting and the work of developing health care goals and strategies. This paper provides a step by step illustration of an innovative visual approach, called photovoice or photo-elicitation, to achieve fair process in clinical work with acquired brain injury survivors and others living with chronic health conditions. Applying this visual tool and methodology in the clinical setting will enhance patient-provider communication; engage patients as partners in identifying challenges, strengths, goals, and strategies; and support evaluation of progress over time. Asking patients to bring visuals of their lives into the clinical interaction can help to illuminate gaps in clinical knowledge, forge better therapeutic relationships with patients living

  11. Raising Black Students' Achievement through Culturally Responsive Teaching

    ERIC Educational Resources Information Center

    McKinley, Johnnie H.

    2010-01-01

    While there are theories about how to close the achievement gap between black students and their white peers, what you need is the real low-down from frontline educators who know what works. Here's a book that gives you that plus a whole-school plan for raising the achievement of these chronically underserved students. Drawing from her work with…

  12. Clinically achievable plasma deferoxamine concentrations are therapeutic in a rat model of Pneumocystis carinii pneumonia.

    PubMed Central

    Merali, S; Chin, K; Del Angel, L; Grady, R W; Armstrong, M; Clarkson, A B

    1995-01-01

    The iron-chelating drug deferoxamine (DFO) has been shown to be active in animal models of Pneumocystis carinii pneumonia (PCP), with effective daily intraperitoneal bolus dosages being 400 and 1,000 mg of DFO mesylate kg of body weight-1 in mouse and rat models, respectively. Continuous infusion produced a moderately improved response in a rat model. The data reported here demonstrate that the response achieved by continuous infusion of 195 and 335 mg of DFO mesylate kg-1 day-1 in the rat model is associated with mean concentrations in plasma of 1.3 and 2.5 micrograms of DFO ml-1 and mean concentrations in lung tissue of 4.9 and 6.0 micrograms of DFO g of lung tissue-1, respectively. Since current clinical use of DFO mesylate for the treatment of iron overload produces higher concentrations in the plasma of patients, DFO may prove to be a useful anti-PCP treatment. The 2.4- to 3.8-fold higher DFO concentration observed in lung tissue compared with that observed in plasma may be important in the response of PCP to DFO. PMID:8540710

  13. Roles and Responsibilities of Clinical Nurse Researchers.

    ERIC Educational Resources Information Center

    Kirchhoff, Karin T.; Mateo, Magdelena A.

    1996-01-01

    A follow-up survey of 142 nurse researchers employed in clinical settings (75% response) found that fewer than half have a budget, 52% have secretarial support, 82% have a research committee, and 71% report to the chief nurse executive. Although their positions were primarily research, the average time spent on research was 50%. (JOW)

  14. [Clinical Responses To Infants and Families.

    ERIC Educational Resources Information Center

    Fenichel, Emily, Ed.

    1995-01-01

    This journal issue focuses on family service clinical responses to infants and families. In "The Therapeutic Relationship as Human Connectedness," Jeree H. Pawl stresses the importance of caregivers creating in children the sense and experience of human connectedness that arises from the feeling of existing in the mind of someone else--that is,…

  15. A Comparison of Responsive Interventions on Kindergarteners' Early Reading Achievement

    ERIC Educational Resources Information Center

    Little, Mary E.; Rawlinson, D'Ann; Simmons, Deborah C.; Kim, Minjung; Kwok, Oi-man; Hagan-Burke, Shanna; Simmons, Leslie E.; Fogarty, Melissa; Oslund, Eric; Coyne, Michael D.

    2012-01-01

    This study compared the effects of Tier 2 reading interventions that operated in response-to-intervention contexts. Kindergarten children (N = 90) who were identified as at risk for reading difficulties were stratified by school and randomly assigned to receive (a) Early Reading Intervention (ERI; Pearson/Scott Foresman, 2004) modified in response…

  16. Roles and responsibilities of clinical nurse researchers.

    PubMed

    Kirchhoff, K T; Mateo, M A

    1996-01-01

    A follow-up survey of 142 nurse researchers employed in clinical settings (NRECS) was conducted 10 years after the first one conducted by Knafl, Bevis, and Kirchhoff in which only 34 individuals qualified for inclusion. An 80-item questionnaire included items about the structure of the position, processes used, variables that may influence outcomes, and outside activities. When ineligible persons were excluded, the response rate was 75 per cent. Most commonly NRECS had positions in clinical settings only (55.7 per cent), offices (75.5 per cent), some staff (72.6 per cent), and secretarial support (52.8 per cent), and they usually reported to the chief nurse executives (71.7 per cent). Although the majority of NRECS reported responsibility for research activities, the average time spent on research is only 50 per cent. Most (82 per cent) have a nursing research committee, but NRECS also sit on other research-related committees in the department or hospital. Details about salary, responsibilities, and processes will be helpful to those preparing themselves or others for this role, for those who wish to start such a position for themselves or another, or for those in the role wanting to know how other NRECS perform. PMID:8632106

  17. Clinical and Immunological Responses in Ocular Demodecosis

    PubMed Central

    Kim, Jae Hoon; Chun, Yeoun Sook

    2011-01-01

    The purpose of this study was to investigate clinical and immunological responses to Demodex on the ocular surface. Thirteen eyes in 10 patients with Demodex blepharitis and chronic ocular surface disorders were included in this study and treated by lid scrubbing with tea tree oil for the eradication of Demodex. We evaluated ocular surface manifestations and Demodex counts, and analyzed IL-1β, IL-5, IL-7, IL-12, IL-13, IL-17, granulocyte colony-stimulating factor, and macrophage inflammatory protein-1β in tear samples before and after the treatment. All patients exhibited ocular surface manifestations including corneal nodular opacity, peripheral corneal vascularization, refractory corneal erosion and infiltration, or chronic conjunctival inflammatory signs before treatment. After treatment, Demodex was nearly eradicated, tear concentrations of IL-1β and IL-17 were significantly reduced and substantial clinical improvement was observed in all patients. In conclusion, we believe that Demodex plays an aggravating role in inflammatory ocular surface disorders. PMID:21935281

  18. Graduate-Entry Medical Student Variables that Predict Academic and Clinical Achievement

    ERIC Educational Resources Information Center

    Blackman, Ian; Darmawan, I Gusti Ngurah

    2004-01-01

    A hypothetical model was formulated to explore factors that influenced academic and clinical achievement for graduate-entry medical students completing their third year of university studies. Nine latent variables were considered including the students' background, previous successes with their undergraduate and postgraduate studies and their…

  19. Undergraduate Nurse Variables that Predict Academic Achievement and Clinical Competence in Nursing

    ERIC Educational Resources Information Center

    Blackman, Ian; Hall, Margaret; Darmawan, I Gusti Ngurah.

    2007-01-01

    A hypothetical model was formulated to explore factors that influenced academic and clinical achievement for undergraduate nursing students. Sixteen latent variables were considered including the students' background, gender, type of first language, age, their previous successes with their undergraduate nursing studies and status given for…

  20. Cultural Competency and Achieving Styles in Clinical Social Work: A Conceptual and Empirical Exploration.

    ERIC Educational Resources Information Center

    Lu, Yuhwa Eva; Lum, Doman; Chen, Sheying

    2001-01-01

    A study explored the relationship between linguistic/cultural differences and individual achieving styles among 900 clinical social workers, including Asian Americans, Latinos, American Indians, African Americans, Jewish Americans, and Whites. Findings are related to a model of cultural competency in which cross-cultural counselor-client…

  1. Achieving quality in a government hospital: departmental responsibility.

    PubMed

    Haron, Yafa; Segal, Zvi; Barhoum, Masad

    2009-01-01

    Quality improvement in health care organizations requires structural reorganization and system reform and the development of an appropriate organizational "culture." In 2007, the Division of Quality and Excellence in Civil Service in Israel developed a concept to improve quality management in governmental institutions throughout the country. To put this strategy into practice, Western Galilee Hospital, a governmental hospital, in northern Israel, developed a plan to advance the quality management system where each department and unit is autonomously responsible for its own quality and excellence. Since the hospital has been certificated by ISO 9001 for more than 10 years (the only hospital in Israel to have this certificate), the main challenge now is to improve the quality and excellence system in every department. The aim of this article is to describe the implementation of a comprehensive program designed to raise the ability of managers and workers in Western Galilee Hospital in addressing all of the government's requirements for quality and excellence in service in Israel. PMID:19369858

  2. The Relationships between Teacher Empowerment, Teachers' Sense of Responsibility for Student Outcomes, and Student Achievement.

    ERIC Educational Resources Information Center

    Martin, Barbara N.; Crossland, Barbara J.

    Relationships between the level of teachers' perceived empowerment, the degree of teachers' perceived responsibility for student outcomes, and student achievement were studied with 271 elementary school teachers. The Responsibility for Student Achievement Scale (RSA) (T. Guskey, 1981) and the School Participant Empowerment Scales (SPES) (P. Short…

  3. High-fidelity simulation: Assessment of student nurses' team achievements of clinical judgment.

    PubMed

    Hallin, Karin; Bäckström, Britt; Häggström, Marie; Kristiansen, Lisbeth

    2016-07-01

    Nursing educators have the challenge of preparing nursing students to handle complex patient care situations in real life, but much remains unknown about the ability to make clinical judgments. In this study, high-fidelity simulation (HFS) was used at a Swedish university to find answers about pre-licensure nursing students' success in clinical judgment in terms of team ability and relationships with theoretical achievements, and personal and scenario circumstances. The matrix Lasater Clinical Judgment Rubric (LCJR) was used to analyze and score the students' ability in teams to notice, interpret and respond to complex care situations. Overall, the results showed the student teams in their first meeting with HFS in a complex care situation achieved low clinical judgment points; most teams were in the stages of Beginning and Developing. For attaining high team achievements the majority of the students in the team should theoretically be "high performance". Being observers and having HFS experience before nursing education was significant too. However, age, health care experience, and assistant nurse degrees were of secondary importance. Further research at universities regionally, nationally, and internationally is needed. PMID:27428686

  4. Prognostic impact of immunophenotypic complete response in patients with multiple myeloma achieving better than complete response.

    PubMed

    Fukumoto, Kota; Fujisawa, Manabu; Suehara, Yasuto; Narita, Ken-Taro; Usui, Yoshiaki; Takeuchi, Masami; Matsue, Kosei

    2016-08-01

    To investigate the impact of immunophenotypic complete response [iCR, ≤10(-4) multiple myeloma (MM) cells defined by multicolor flow cytometry (MFC)] on survival in patients with MM, we retrospectively analyzed 78 patients that obtained conventional CR at our hospital. Survivals were landmarked at achievement of CR. The rate of stringent CR (sCR) among patients with CR was 88%, and iCR for CR and sCR patients were 44% and 49%, respectively. Achievement of iCR was associated with significantly longer disease-free survival (DFS) not only in CR patients (p = 0.009) but also in sCR patients (p = 0.002), while sCR attainment per se did not have statistically significant impact on DFS (p = 0.06) or overall survival (OS) (p = 0.587). Univariate and multivariate analyses indicated that attainment of iCR was independently associated with longer 2-year DFS in addition to creatinine (≤2.0 mg/dL) and maintenance therapy. This study highlights the importance of pursuing iCR even in patients with sCR. PMID:26764045

  5. Clinical importance of achieving biochemical control with medical therapy in adult patients with acromegaly

    PubMed Central

    Christofides, Elena A

    2016-01-01

    In acromegaly, achieving biochemical control (growth hormone [GH] level <1.0 ng/mL and age- and sex-normalized levels of insulin-like growth factor 1 [IGF-1]) through timely diagnosis and appropriate treatment provides an opportunity to improve patient outcomes. Diagnosis of acromegaly is challenging because it is rooted in observing subtle clinical manifestations, and it is typical for acromegaly to evolve for up to 10 years before it is recognized. This results in chronic exposure to elevated levels of GH and IGF-1 and delay in patients receiving appropriate treatment, which consequently increases mortality risk. In this review, the clinical impact of elevated GH and IGF-1 levels, the effectiveness of current therapies, and the potential role of novel treatments for acromegaly will be discussed. Clinical burden of acromegaly and benefits associated with management of GH and IGF-1 levels will be reviewed. Major treatment paradigms in acromegaly include surgery, medical therapy, and radiotherapy. With medical therapies, such as somatostatin analogs, dopamine agonists, and GH receptor antagonists, a substantial proportion of patients achieve reduced GH and normalized IGF-1 levels. In addition, signs and symptoms, quality of life, and comorbidities have also been reported to improve to varying degrees in patients who achieve biochemical control. Currently, there are several innovative therapies in development to improve patient outcomes, patient use, and access. Timely biochemical control of acromegaly ensures that the patient can ultimately improve morbidity and mortality from this disease and its extensive consequences. PMID:27471378

  6. Clinical decision support systems for improving diagnostic accuracy and achieving precision medicine.

    PubMed

    Castaneda, Christian; Nalley, Kip; Mannion, Ciaran; Bhattacharyya, Pritish; Blake, Patrick; Pecora, Andrew; Goy, Andre; Suh, K Stephen

    2015-01-01

    As research laboratories and clinics collaborate to achieve precision medicine, both communities are required to understand mandated electronic health/medical record (EHR/EMR) initiatives that will be fully implemented in all clinics in the United States by 2015. Stakeholders will need to evaluate current record keeping practices and optimize and standardize methodologies to capture nearly all information in digital format. Collaborative efforts from academic and industry sectors are crucial to achieving higher efficacy in patient care while minimizing costs. Currently existing digitized data and information are present in multiple formats and are largely unstructured. In the absence of a universally accepted management system, departments and institutions continue to generate silos of information. As a result, invaluable and newly discovered knowledge is difficult to access. To accelerate biomedical research and reduce healthcare costs, clinical and bioinformatics systems must employ common data elements to create structured annotation forms enabling laboratories and clinics to capture sharable data in real time. Conversion of these datasets to knowable information should be a routine institutionalized process. New scientific knowledge and clinical discoveries can be shared via integrated knowledge environments defined by flexible data models and extensive use of standards, ontologies, vocabularies, and thesauri. In the clinical setting, aggregated knowledge must be displayed in user-friendly formats so that physicians, non-technical laboratory personnel, nurses, data/research coordinators, and end-users can enter data, access information, and understand the output. The effort to connect astronomical numbers of data points, including '-omics'-based molecular data, individual genome sequences, experimental data, patient clinical phenotypes, and follow-up data is a monumental task. Roadblocks to this vision of integration and interoperability include ethical, legal

  7. Response to Marie Paz Morales' ``Influence of culture and language sensitive physics on science attitude achievement''

    NASA Astrophysics Data System (ADS)

    Cole, Mikel Walker

    2015-12-01

    This response to Marie Paz Morales' "Influence of culture and language sensitive physics on science attitude achievement" explores the ideas of culturally responsive pedagogy and critical literacy to examine some implications for culturally responsive science instruction implicit in the original manuscript.

  8. Response to Marie Paz Morales' "Influence of Culture and Language Sensitive Physics on Science Attitude Achievement"

    ERIC Educational Resources Information Center

    Cole, Mikel Walker

    2015-01-01

    This response to Marie Paz Morales' "Influence of culture and language sensitive physics on science attitude achievement" explores the ideas of culturally responsive pedagogy and critical literacy to examine some implications for culturally responsive science instruction implicit in the original manuscript. [For "Influence of…

  9. 42 CFR 493.1457 - Standard; Clinical consultant responsibilities.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 5 2011-10-01 2011-10-01 false Standard; Clinical consultant responsibilities. 493... Testing Laboratories Performing High Complexity Testing § 493.1457 Standard; Clinical consultant responsibilities. The clinical consultant provides consultation regarding the appropriateness of the...

  10. 42 CFR 493.1419 - Standard; Clinical consultant responsibilities.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 5 2011-10-01 2011-10-01 false Standard; Clinical consultant responsibilities. 493... Testing Laboratories Performing Moderate Complexity Testing § 493.1419 Standard; Clinical consultant responsibilities. The clinical consultant provides consultation regarding the appropriateness of the...

  11. Evaluation of preceptors and skills achievement by clinical pharmacy clerkship students during their clinical rotations at University of Gondar, Ethiopia

    PubMed Central

    Belachew, Sewunet Admasu; Abegaz, Tadesse Melaku; Bhagavathula, Akshaya Srikanth; Getachew, Henok; Tefera, Yonas Getaye

    2016-01-01

    Aim To investigate the overall experiences of clinical pharmacy students during their clinical attachments and to understand the breadth and depth of clinical skills provided by their preceptors. Methods A cross-sectional study using a self-administered questionnaire containing 34 items to obtain feedback from the clerkship students from June to July 2015. Data analysis was performed to calculate mean, standard deviation, percentages, and multiple logistic regression using Statistical Package for the Social Sciences (SPSS) software Version 22. Statistical significance was set at P<0.01. Results All 58 clerkship students actively participated in the study, yielding a response rate of 100%. While students ranked their clerkship experience as moderate, >15% remarked that they did not receive enough opportunities to hone their pharmaceutical care documentation skills. A relatively high percentage of students (32.8%) strongly agreed that their preceptors had provided ample opportunity to discuss the patient problems at the bedside and encouraged them to express their opinions regarding patients’ drug therapeutic issues. This study also revealed that students’ continuity in developing their therapeutic and disease process knowledge was significantly associated with the preceptor’s ability to provide adequate training and orientation (P =0.01), engagement in clinical pharmacy activities (P =0.01), regular review of students’ work (P =0.01), and instruction to students before entering clinical sites (P =0.00). Conclusion The findings of this study reveal that a majority of the students were moderately satisfied with the clinical training program and preceptors need to demonstrate effective pharmaceutical care processes in their clinical sites. PMID:27099540

  12. Response to clozapine in a clinically identifiable subtype of schizophrenia

    PubMed Central

    Butcher, Nancy J.; Fung, Wai Lun Alan; Fitzpatrick, Laura; Guna, Alina; Andrade, Danielle M.; Lang, Anthony E.; Chow, Eva W. C.; Bassett, Anne S.

    2015-01-01

    Background Genetic testing in psychiatry promises to improve patient care through advances in personalised medicine. However, there are few clinically relevant examples. Aims To determine whether patients with a well-established genetic subtype of schizophrenia show a different response profile to the antipsychotic clozapine than those with idiopathic schizophrenia. Method We retrospectively studied the long-term safety and efficacy of clozapine in 40 adults with schizophrenia, half with a 22q11.2 deletion (22q11.2DS group) and half matched for age and clinical severity but molecularly confirmed to have no pathogenic copy number variant (idiopathic group). Results Both groups showed similar clinical improvement and significant reductions in hospitalisations, achieved at a lower median dose for those in the 22q11.2DS group. Most common side-effects were similarly prevalent between the two groups, however, half of the 22q11.2DS group experienced at least one rare serious adverse event compared with none of the idiopathic group. Many were successfully retried on clozapine. Conclusions Individuals with 22q11.2DS-schizophrenia respond as well to clozapine treatment as those with other forms of schizophrenia, but may represent a disproportionate number of those with serious adverse events, primarily seizures. Lower doses and prophylactic (for example anticonvulsant) management strategies can help ameliorate side-effect risks. This first systematic evaluation of antipsychotic response in a genetic subtype of schizophrenia provides a proof-of-principle for personalised medicine and supports the utility of clinical genetic testing in schizophrenia. PMID:25745132

  13. Diabetic gastrointestinal autonomic neuropathy: current status and new achievements for everyday clinical practice.

    PubMed

    Gatopoulou, A; Papanas, N; Maltezos, E

    2012-09-01

    Gastrointestinal symptoms occur frequently among patients with diabetes mellitus and are associated with considerable morbidity. Diabetic gastrointestinal autonomic neuropathy represents a complex disorder with multifactorial pathogenesis, which is still not well understood. It appears to involve a spectrum of metabolic and cellular changes that affect gastrointestinal motor and sensory control. It may affect any organ in the digestive system. Clinical manifestations are often underestimated, and therefore autonomic neuropathy should be suspected in all diabetic patients with unexplained gastrointestinal symptoms. Advances in technology have now enabled assessment of gastrointestinal motor function. Moreover, novel pharmacological approaches, along with endoscopic and surgical treatment options, contribute to improved outcomes. This review summarises the progress achieved in diabetic gastrointestinal autonomic neuropathy during the last years, focusing on clinical issues of practical importance to the everyday clinician. PMID:22863425

  14. Relationship of Children's Social Desirability Response Tendencies to Their Expectations of Response to Achievement Behaviors in Classrooms.

    ERIC Educational Resources Information Center

    Potter, Ellen F.

    This study clarifies the relationship between children's social desirability (CSD) response tendencies and their withdrawal from classroom achievement situations by investigating the effects of the child's expectations of peer response. Data gathered included scores on the Children's Social Desirability Scale, scores on an expectancy of response…

  15. Using Culturally Competent Responsive Services to Improve Student Achievement and Behavior

    ERIC Educational Resources Information Center

    Schellenberg, Rita; Grothaus, Tim

    2011-01-01

    This article illustrates standards blending, the integration of core academic and school counseling standards, as a culturally alert responsive services strategy to assist in closing the achievement gap while also enhancing employability skills and culturally salient career competencies. The responsive services intervention described in this…

  16. Using Explanatory Item Response Models to Analyze Group Differences in Science Achievement

    ERIC Educational Resources Information Center

    Briggs, Derek C.

    2008-01-01

    This article illustrates the use of an explanatory item response modeling (EIRM) approach in the context of measuring group differences in science achievement. The distinction between item response models and EIRMs, recently elaborated by De Boeck and Wilson (2004), is presented within the statistical framework of generalized linear mixed models.…

  17. Reductions in disease activity in the AMPLE trial: clinical response by baseline disease duration

    PubMed Central

    Schiff, Michael; Weinblatt, Michael E; Valente, Robert; Citera, Gustavo; Maldonado, Michael; Massarotti, Elena; Yazici, Yusuf; Fleischmann, Roy

    2016-01-01

    Objectives To evaluate clinical response by baseline disease duration using 2-year data from the AMPLE trial. Methods Patients were randomised to subcutaneous abatacept 125 mg weekly or adalimumab 40 mg bi-weekly, with background methotrexate. As part of a post hoc analysis, the achievement of validated definitions of remission (Clinical Disease Activity Index (CDAI) ≤2.8, Simplified Disease Activity Index (SDAI) ≤3.3, Routine Assessment of Patient Index Data 3 (RAPID3) ≤3.0, Boolean score ≤1), low disease activity (CDAI <10, SDAI <11, RAPID3 ≤6.0), Health Assessment Questionnaire-Disability Index response and American College of Rheumatology responses were evaluated by baseline disease duration (≤6 vs >6 months). Disease Activity Score 28 (C-reactive protein) <2.6 or ≤3.2 and radiographic non-progression in patients achieving remission were also evaluated. Results A total of 646 patients were randomised and treated (abatacept, n=318; adalimumab, n=328). In both treatment groups, comparable responses were achieved in patients with early rheumatoid arthritis (≤6 months) and in those with later disease (>6 months) across multiple clinical measures. Conclusions Abatacept or adalimumab with background methotrexate were associated with similar onset and sustainability of response over 2 years. Patients treated early or later in the disease course achieved comparable clinical responses. Trial registration number NCT00929864, Post-results. PMID:27110385

  18. A Pharmacist-Staffed, Virtual Gout Management Clinic for Achieving Target Serum Uric Acid Levels: A Randomized Clinical Trial

    PubMed Central

    Goldfien, Robert; Pressman, Alice; Jacobson, Alice; Ng, Michele; Avins, Andrew

    2016-01-01

    Context: Relatively few patients with gout receive appropriate treatment. Objective: To determine whether a pharmacist-staffed gout management program is more effective than usual care in achieving target serum uric acid (sUA) levels in gout patients. Design: A parallel-group, randomized controlled trial of a pharmacist-staffed, telephone-based program for managing hyperuricemia vs usual care. Trial duration was 26 weeks. Main Outcome Measures: Primary outcome measure was achieving sUA levels at or below 6 mg/dL at the 26-week visit. Secondary outcome was mean change in sUA levels in the control and intervention groups. Participants were adults with recurrent gout and sUA levels above 6.0 mg/dL. Participants were randomly assigned to management by a clinical pharmacist following protocol or to monitoring of sUA levels but management of their gout by their usual treating physician. Results: Of 102 patients who met eligibility criteria, 77 subjects obtained a baseline sUA measurement and were entered into the trial. Among 37 participants in the intervention group, 13 (35%) had sUA levels at or below 6.0 mg/dL at 26 weeks, compared with 5 (13%) of 40 participants in the control group (risk ratio = 2.8, 95% confidence interval [CI] = 1.1 to 7.1, p = 0.03). The mean change in sUA levels among controls was +0.1 mg/dL compared with −1.5 mg/dL in the intervention group (sUA difference = −1.6, 95% CI = −0.9 to −2.4, p < 0.001). Conclusions: A structured pharmacist-staffed program was more effective than usual care for achieving target sUA levels. These results suggest a structured program could greatly improve gout management. PMID:27352414

  19. The relationship between medical students’ epistemological beliefs and achievement on a clinical performance examination

    PubMed Central

    Oh, Sun-A; Chung, Eun-Kyung; Han, Eui-Ryoung; Woo, Young-Jong; Kevin, Deiter

    2016-01-01

    Purpose: This study was to explore the relationship between clinical performance examination (CPX) achievement and epistemological beliefs to investigate the potentials of epistemological beliefs in ill-structured medical problem solving tasks. Methods: We administered the epistemological beliefs questionnaire (EBQ) to fourth-year medical students and correlated the results with their CPX scores. The EBQ comprised 61 items reflecting five belief systems: certainty of knowledge, source of knowledge, rigidity of learning, ability to learn, and speed of knowledge acquisition. The CPX included scores for history taking, physical examination, and patient-physician interaction. Results: The higher epistemological beliefs group obtained significantly higher scores on the CPX with regard to history taking and patient-physician interaction. The epistemological beliefs scores on certainty of knowledge and source of knowledge were significantly positively correlated with patient-physician interaction. The epistemological beliefs scores for ability to learn were significantly positively correlated with those for history taking, physical examination, and patient-physician interaction. Conclusion: Students with more sophisticated and advanced epistemological beliefs stances used more comprehensive and varied approaches in the patient-physician interaction. Therefore, educational efforts that encourage discussions pertaining to epistemological views should be considered to improve clinical reasoning and problem-solving competence in the clinic setting. PMID:26838566

  20. A Model of Placebo Response in Antidepressant Clinical Trials

    PubMed Central

    Rutherford, Bret R; Roose, Steven P.

    2012-01-01

    Placebo response in clinical trials of antidepressant medications is substantial and increasing. High placebo response rates hamper efforts to detect signals of efficacy for new antidepressant medications, contributing to more failed trials and delaying the delivery of new treatments to market. Media reports seize upon increasing placebo response and modest advantages for active drugs as reasons to question the value of antidepressant medication, which may further stigmatize treatments for depression and dissuade patients from accessing mental health care. Conversely, enhancing the factors responsible for placebo response may represent a strategy for improving available treatments for Major Depressive Disorder. A conceptual framework describing the causes of placebo response is needed in order to develop strategies for minimizing placebo response in clinical trials, maximizing placebo response in clinical practice, and talking with depressed patients about the risks and benefits of antidepressant medications. This review examines contributors to placebo response in antidepressant clinical trials and proposes an explanatory model. Research aimed at reducing placebo response should focus on limiting patient expectancy and the intensity of therapeutic contact in antidepressant clinical trials, while the optimal strategy in clinical practice may be to combine active medication with a presentation and level of therapeutic contact that enhances treatment response. PMID:23318413

  1. Pre-operative Thresholds for Achieving Meaningful Clinical Improvement after Arthroscopic Treatment of Femoroacetabular Impingement

    PubMed Central

    Nwachukwu, Benedict U.; Fields, Kara G.; Nawabi, Danyal H.; Kelly, Bryan T.; Ranawat, Anil S.

    2016-01-01

    Objectives: Knowledge of the thresholds and determinants for successful femoroacetabular impingement (FAI) treatment is evolving. The primary purpose of this study was to define pre-operative outcome score thresholds that can be used to predict patients most likely to achieve meaningful clinically important difference (MCID) after arthroscopic FAI treatment. Secondarily determinants of achieving MCID were evaluated. Methods: A prospective institutional hip arthroscopy registry was reviewed to identify patients with FAI treated with arthroscopic labral surgery, acetabular rim trimming, and femoral osteochondroplasty. The modified Harris Hip Score (mHHS), the Hip Outcome Score (HOS) and the international Hip Outcome Tool (iHOT-33) tools were administered at baseline and at one year post-operatively. MCID was calculated using a distribution-based method. A receiver operating characteristic (ROC) analysis was used to calculate cohort-based threshold values predictive of achieving MCID. Area under the curve (AUC) was used to define predictive ability (strength of association) with AUC >0.7 considered acceptably predictive. Univariate and multivariable analyses were used to analyze demographic, radiographic and intra-operative factors associated with achieving MCID. Results: There were 374 patients (mean + SD age, 32.9 + 10.5) and 56.4% were female. The MCID for mHHS, HOS activities of daily living (HOS-ADL), HOS Sports, and iHOT-33 was 8.2, 8.4,14.5, and 12.0 respectively. ROC analysis (threshold, % achieving MCID, strength of association) for these tools in our population was: mHHS (61.6, 78%, 0.68), HOS-ADL (83.8, 68%, 0.84), HOS-Sports (63.9, 64%, 0.74), and iHOT-33 (54.3, 82%, 0.65). Likelihood for achieving MCID declined above and increased below these thresholds. In univariate analysis female sex, femoral version, lower acetabular outerbridge score and increasing CT sagittal center edge angle (CEA) were predictive of achieving MCID. In multivariable analysis

  2. X-linked acrogigantism syndrome: clinical profile and therapeutic responses.

    PubMed

    Beckers, Albert; Lodish, Maya Beth; Trivellin, Giampaolo; Rostomyan, Liliya; Lee, Misu; Faucz, Fabio R; Yuan, Bo; Choong, Catherine S; Caberg, Jean-Hubert; Verrua, Elisa; Naves, Luciana Ansaneli; Cheetham, Tim D; Young, Jacques; Lysy, Philippe A; Petrossians, Patrick; Cotterill, Andrew; Shah, Nalini Samir; Metzger, Daniel; Castermans, Emilie; Ambrosio, Maria Rosaria; Villa, Chiara; Strebkova, Natalia; Mazerkina, Nadia; Gaillard, Stéphan; Barra, Gustavo Barcelos; Casulari, Luis Augusto; Neggers, Sebastian J; Salvatori, Roberto; Jaffrain-Rea, Marie-Lise; Zacharin, Margaret; Santamaria, Beatriz Lecumberri; Zacharieva, Sabina; Lim, Ee Mun; Mantovani, Giovanna; Zatelli, Maria Chaira; Collins, Michael T; Bonneville, Jean-François; Quezado, Martha; Chittiboina, Prashant; Oldfield, Edward H; Bours, Vincent; Liu, Pengfei; W de Herder, Wouter; Pellegata, Natalia; Lupski, James R; Daly, Adrian F; Stratakis, Constantine A

    2015-06-01

    X-linked acrogigantism (X-LAG) is a new syndrome of pituitary gigantism, caused by microduplications on chromosome Xq26.3, encompassing the gene GPR101, which is highly upregulated in pituitary tumors. We conducted this study to explore the clinical, radiological, and hormonal phenotype and responses to therapy in patients with X-LAG syndrome. The study included 18 patients (13 sporadic) with X-LAG and microduplication of chromosome Xq26.3. All sporadic cases had unique duplications and the inheritance pattern in two families was dominant, with all Xq26.3 duplication carriers being affected. Patients began to grow rapidly as early as 2-3 months of age (median 12 months). At diagnosis (median delay 27 months), patients had a median height and weight standard deviation scores (SDS) of >+3.9 SDS. Apart from the increased overall body size, the children had acromegalic symptoms including acral enlargement and facial coarsening. More than a third of cases had increased appetite. Patients had marked hypersecretion of GH/IGF1 and usually prolactin, due to a pituitary macroadenoma or hyperplasia. Primary neurosurgical control was achieved with extensive anterior pituitary resection, but postoperative hypopituitarism was frequent. Control with somatostatin analogs was not readily achieved despite moderate to high levels of expression of somatostatin receptor subtype-2 in tumor tissue. Postoperative use of adjuvant pegvisomant resulted in control of IGF1 in all five cases where it was employed. X-LAG is a new infant-onset gigantism syndrome that has a severe clinical phenotype leading to challenging disease management. PMID:25712922

  3. Relationship between Achievement Goals and Students' Self-Reported Personal and Social Responsibility Behaviors.

    PubMed

    Agbuga, Bulent; Xiang, Ping; McBride, Ron E

    2015-01-01

    This study utilized the 2x2 achievement goal model (mastery-approach, mastery-avoidance, performance-approach, performance-avoidance goals) to explore the relationships between achievement goals and self-reported personal and social responsibility behaviors in high school physical education settings. Two hundred and twenty one Turkish students completed questionnaires assessing their achievement goals, personal and social responsibility behaviors. Results of the one-way repeated measures ANOVA revealed significant differences among the four achievement goals, F(3, 660) = 137.05, p < .001, η2 = .39. The result also revealed that students were more likely to endorse the mastery-approach goal than three other goals. The simple correlations revealed mastery-approach and performance-approach goals were positively related to students' self-reported personal (r = .54, p < .001; r = .37, p < .001, respectively) and social responsibility (r = .38, p < .001; r = .22, p < .001, respectively) behaviors. However, hierarchical regression analyses indicated only the mastery-approach goal emerged as the significant positive predictor, b = .52, t(216) = 7.19, p < .001 for personal responsibility behaviors, and b = .41, t(216) = 5.23, p < .001 for social responsibility behaviors. These findings seem to provide convergent evidence that mastery-approach goals are positively related to positive educational outcomes. PMID:25896600

  4. The Value of Item Response Theory in Clinical Assessment: A Review

    ERIC Educational Resources Information Center

    Thomas, Michael L.

    2011-01-01

    Item response theory (IRT) and related latent variable models represent modern psychometric theory, the successor to classical test theory in psychological assessment. Although IRT has become prevalent in the measurement of ability and achievement, its contributions to clinical domains have been less extensive. Applications of IRT to clinical…

  5. The Accountability System: Defining Responsibility for Student Achievement. Children Achieving: Philadelphia's Education Reform. Progress Report Series 1996-1997.

    ERIC Educational Resources Information Center

    Luhm, Theresa; Foley, Ellen; Corcoran, Tom

    This report explores issues related to accountability in the context of Children Achieving, the school reform effort of Philadelphia (Pennsylvania). The accountability system begins with content standards in English/language arts, mathematics, science, and the arts. The Stanford-9 Achievement Test has been designated to assess how students are…

  6. Impairing loyalty: corporate responsibility for clinical misadventure.

    PubMed

    Kipnis, Kenneth

    2011-09-01

    A medical device manufacturer pays a surgeon to demonstrate a novel medical instrument in a live broadcast to an audience of specialists in another city. The surgical patient is unaware of the broadcast and unaware of the doctor's relationship with the manufacturer. It turns out that the patient required a different surgical approach to her condition-one that would not have allowed a demonstration of the instrument--and she later dies. The paper is an exploration of whether the manufacturer shares, along with the doctor, responsibility for the death of the patient. Three arguments for corporate responsibility are considered; two are criticized and the third is offered as sound. PMID:21877962

  7. The Effects of Response to Intervention on Third Graders' Reading Achievement

    ERIC Educational Resources Information Center

    King, Marlon Demetrius

    2012-01-01

    The purpose of this quantitative study was to examine the effects of the Response to Intervention Three Tier Model on third graders' reading achievement. Two hundred forty-three students participated in this study. Students were from an elementary school in the southeastern region of the United States. The data on the students was collected…

  8. The Effect of a Student Response System on Student Achievement in Mathematics within an Elementary Classroom

    ERIC Educational Resources Information Center

    Dix, Yvette Ellsworth

    2013-01-01

    The objective of this quasi-experimental quantitative study was to determine if the use of a student response system, combined with an interactive whiteboard, led to increased student achievement in mathematics within a fifth grade classroom as measured by a district benchmark assessment and the annual Arizona Instrument to Measure Standards…

  9. Addressing the Achievement Gap and Disproportionality through the Use of Culturally Responsive Teaching Practices

    ERIC Educational Resources Information Center

    Griner, Angela Christine; Stewart, Martha Lue

    2013-01-01

    Culturally responsive practices in schools and classrooms have been shown to be an effective means of addressing the achievement gap as well as the disproportionate representation of racially, culturally, ethnically, and linguistically diverse students in programs serving students with special needs. While there has been much research discussing…

  10. The Impact of Anonymous and Assigned Use of Student Response Systems on Student Achievement

    ERIC Educational Resources Information Center

    Poole, Dawn

    2012-01-01

    This study examined the impact of two approaches to use of student response systems (SRSs) on achievement in a study designed to better understand effective use of the devices. One condition was anonymous use of SRSs, in which graduate students selected a random clicker when entering the classroom. The second condition assigned devices to students…

  11. The Effects of Response to Intervention on the Mathematics Achievement of Seventh and Eighth Grade Students

    ERIC Educational Resources Information Center

    Cornelius, Annette Sargent

    2013-01-01

    The purpose of this quantitative study was to investigate the effectiveness of a system-wide Response to Intervention (RTI) program on the mathematical achievement of seventh and eighth grade students. The study consisted of five district schools with a total of 502 participants. The students were identified as belonging to one of two tiers, which…

  12. Culturally Responsive Caring and Expectations for Academic Achievement in a Catholic School

    ERIC Educational Resources Information Center

    Dallavis, Christian

    2014-01-01

    This article draws from a larger dissertation study that applied ethnographic and historical research methods to explore the intersection of culturally responsive pedagogy and Catholic schooling in immigrant communities. In particular, this article presents qualitative data analysis to describe student achievement expectations at a contemporary…

  13. Promoting Cultural Responsiveness and Closing the Achievement Gap with Standards Blending

    ERIC Educational Resources Information Center

    Schellenberg, Rita; Grothaus, Timothy

    2009-01-01

    In this article, "standards blending"--the integration of core academic and school counseling standards--is demonstrated as a culturally responsive strategy to assist in closing the achievement gap for a group of third-grade African American males. The small-group intervention described resulted in knowledge gains in both the school counseling and…

  14. Clinical applications of the human brainstem responses to auditory stimuli

    NASA Technical Reports Server (NTRS)

    Galambos, R.; Hecox, K.

    1975-01-01

    A technique utilizing the frequency following response (FFR) (obtained by auditory stimulation, whereby the stimulus frequency and duration are mirror-imaged in the resulting brainwaves) as a clinical tool for hearing disorders in humans of all ages is presented. Various medical studies are discussed to support the clinical value of the technique. The discovery and origin of the FFR and another significant brainstem auditory response involved in studying the eighth nerve is also discussed.

  15. 42 CFR 493.1457 - Standard; Clinical consultant responsibilities.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Standard; Clinical consultant responsibilities. 493... HUMAN SERVICES (CONTINUED) STANDARDS AND CERTIFICATION LABORATORY REQUIREMENTS Personnel for Nonwaived Testing Laboratories Performing High Complexity Testing § 493.1457 Standard; Clinical...

  16. 42 CFR 493.1419 - Standard; Clinical consultant responsibilities.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... clinical consultation to the laboratory's clients; (b) Be available to assist the laboratory's clients in... 42 Public Health 5 2010-10-01 2010-10-01 false Standard; Clinical consultant responsibilities. 493... HUMAN SERVICES (CONTINUED) STANDARDS AND CERTIFICATION LABORATORY REQUIREMENTS Personnel for...

  17. [Clinical efficacy and achievement of a complete remission in depression: increasing interest in treatment with escitalopram].

    PubMed

    Favré, P

    2012-02-01

    Such a prevalent disease as Major Depressive Disorder (MDD), associated with prominent impairment in physical and social functioning, implies as well an increased morbidity and mortality. Long-term treatments are required due to the frequent occurrence of relapses. Patient compliance is a core factor in both acute and continuation treatment, closely related to tolerability issues. We have partially reviewed the literature published on PubMed since 2004 which assess the relative antidepressant efficacy of escitalopram and comparator antidepressants in adult patients who met DSM-IV criteria for major depressive disorder (MDD). Clinically important differences exist between commonly prescribed antidepressants. These analyses are in favor of a superior efficacy and tolerability of long-term escitalopram treatment (10 to 20mg/day) compared with active controls, including selective serotonin re-uptake inhibitors (SSRIs) (paroxetine, citalopram, bupropion, fluoxetine, fluvoxamine, sertraline), serotonin/noradrenaline reuptake inhibitors (SNRIs) (venlafaxine, milnacipran and duloxetine) and noradrenergic and specific serotonergic antidepressants (NaSSAs) (mirtazapine). Cipriani et al. (2009) have performed a network meta-analysis of 12 new generation antidepressants. They have shown that clinically important differences exist between commonly prescribed antidepressants for both efficacy and acceptability in favor of escitalopram and sertraline in acute treatment, defined as 8-week treatment. Kasper et al. (2009) conducted a post-hoc pooled analysis of data from two 6-month randomized controlled trials that revealed superior efficacy and tolerability of escitalopram when compared with paroxetine. The pooled analysis of four randomized, double-blind, active comparator, 6-month trials in MDD, by Wade et al. (2009), showed that short-term outcomes may predict long-term treatment compliance and outcomes. A higher probability of achieving remission was associated with responding

  18. Clinical and EEG response to anticonvulsants in neonatal seizures.

    PubMed Central

    Connell, J; Oozeer, R; de Vries, L; Dubowitz, L M; Dubowitz, V

    1989-01-01

    During a two year period prospective continuous electroencephalographic (EEG) monitoring of 275 infants identified seizure activity in 55 cases, 31 of whom were treated with anticonvulsant drugs on clinical grounds. EEG and clinical response was complete in only two and equivocal in another six. Clinical response with persistent EEG seizures occurred in 13 and neither clinical nor EEG response in 10. There was no significant improvement in the generally poor neurological outcome compared with that in 24 infants whose seizures were not treated because of limited or absent clinical manifestations. Background EEG abnormality (as an index of associated cerebral dysfunction) was a guide to potential lack of response to anticonvulsant drugs; it was also predictive of subsequent clinical outcome irrespective of treatment. This study shows that commonly used anticonvulsant drugs (phenobarbitone, paraldehyde, phenytoin, and diazepam) have little effect on seizure control or neurological outcome in neonatal seizures associated with haemorrhagic, hypoxic, or ischaemic cerebral lesions. In view of the variable clinical appearance of EEG seizure activity, continuous EEG monitoring should be an essential feature of further study of neonatal anticonvulsant treatment. PMID:2730114

  19. Achieving progress through clinical governance? A national study of health care managers' perceptions in the NHS in England

    PubMed Central

    Freeman, T; Walshe, K

    2004-01-01

    Background: A national cross sectional study was undertaken to explore the perceptions concerning the importance of, and progress in, aspects of clinical governance among board level and directorate managers in English acute, ambulance, and mental health/learning disabilities (MH/LD) trusts. Participants: A stratified sample of acute, ambulance, and mental health/learning disabilities trusts in England (n = 100), from each of which up to 10 board level and 10 directorate level managers were randomly sampled. Methods: Fieldwork was undertaken between April and July 2002 using the Organisational Progress in Clinical Governance (OPCG) schedule to explore managers' perceptions of the importance of, and organisational achievement in, 54 clinical governance competency items in five aggregated domains: improving quality; managing risks; improving staff performance; corporate accountability; and leadership and collaboration. The difference between ratings of importance and achievement was termed a shortfall. Results: Of 1916 individuals surveyed, 1177 (61.4%) responded. The competency items considered most important and recording highest perceived achievement related to corporate accountability structures and clinical risks. The highest shortfalls between perceived importance and perceived achievement were reported in joint working across local health communities, feedback of performance data, and user involvement. When aggregated into domains, greatest achievement was perceived in the assurance related areas of corporate accountability and risk management, with considerably less perceived achievement and consequently higher shortfalls in quality improvement and leadership and collaboration. Directorate level managers' perceptions of achievement were found to be significantly lower than those of their board level colleagues on all domains other than improving performance. No differences were found in perceptions of achievement between different types of trusts, or between

  20. Achievable Convergence Angle and the Effect of Preparation Design on the Clinical Outcome of Full Veneer Crowns in Dogs

    PubMed Central

    Soukup, Jason W.; Snyder, Christopher J.; Karls, Tina L.; Riehl, Jessica

    2012-01-01

    Summary It is widely accepted that the convergence angle of a full veneer crown preparation should be as close to parallel as possible to attain adequate retention/resistance. The shape of the dog’s canine tooth limits the veterinary dentists’ ability to achieve the recommended convergence angle. However, the clinically achievable convergence angle of the canine tooth in dogs has not been evaluated. In addition, the convergence angle and other physical properties of a preparation, such as height and base diameter, have been shown to affect the retention/resistance of full veneer crowns, in vitro. This effect has not been evaluated clinically in the dog. Physical properties of 32 stone dies from full veneer crowns of canine teeth were studied to evaluate the clinically achievable convergence angle and the potential effect physical properties of the preparation had on the clinical outcome of the restoration. The clinically achievable convergence angle was much higher than the current recommendation. There was an association, albeit not statistically significant, between physical properties of a preparation (convergence angle, height, base diameter) and the clinical outcome of the restoration. PMID:21916370

  1. Physicians' Professionally Responsible Power: A Core Concept of Clinical Ethics.

    PubMed

    McCullough, Laurence B

    2016-02-01

    The gathering of power unto themselves by physicians, a process supported by evidence-based practice, clinical guidelines, licensure, organizational culture, and other social factors, makes the ethics of power--the legitimation of physicians' power--a core concept of clinical ethics. In the absence of legitimation, the physician's power over patients becomes problematic, even predatory. As has occurred in previous issues of the Journal, the papers in the 2016 clinical ethics issue bear on the professionally responsible deployment of power by physicians. This introduction explores themes of physicians' power in papers from an international group of authors who address autonomy and trust, the virtues of perinatal hospice, conjoined twins in ethics and law, addiction and autonomy in clinical research on addicting substances, euthanasia of patients with dementia in Belgium, and a pragmatic approach to clinical futility. PMID:26671961

  2. Failure of Ivermectin per Rectum to Achieve Clinically Meaningful Serum Levels in Two Cases of Strongyloides Hyperinfection

    PubMed Central

    Bogoch, Isaac I.; Khan, Kamran; Abrams, Howard; Nott, Caroline; Leung, Elizabeth; Fleckenstein, Lawrence; Keystone, Jay S.

    2015-01-01

    Two cases of Strongyloides hyperinfection are presented. Ivermectin was initially administered orally and per rectum pending the availability of subcutaneous (SC) preparations. In neither case did rectal suppositories of ivermectin achieve clinically meaningful serum values. Clinicians should use SC preparations of ivermectin as early as possible in Strongyloides hyperinfection and dissemination. PMID:25918215

  3. Decitabine Can Be Safely Reduced after Achievement of Best Objective Response in Patients with Myelodysplastic Syndrome

    PubMed Central

    Ghanem, Hady; Cornelison, A. Megan; Garcia-Manero, Guillermo; Kantarjian, Hagop; Ravandi, Farhad; Kadia, Tapan; Cortes, Jorge; O’Brien, Susan; Brandt, Mark; Borthakur, Gautam; Jabbour, Elias

    2014-01-01

    Decitabine is standard therapy in patients with myelodysplastic syndrome (MDS). Current recommendations suggest a dose of 20 mg/m2 IV daily for 5 days every 4 weeks. However, this therapy is associated with frequent grade 3–4 hematologic toxicity, requiring dose reductions (DR) and/or dose delays (DD). We investigated the outcome of 122 MDS patients who had DD/DR of frontline decitabine therapy. Sixty five patients (53%) had DR by at least 25% or DD (defined as a delay beyond 5 weeks between cycles). Thirty-five patients (29%) underwent DD/DR after achieving best objective response (BOR), 30 patients (25%) before BOR and 57 (54%) had no DD/DR. There was a trend for more durable responses in favor of patients requiring DD/DR after the achievement of BOR (median not reached) (p=0.161). Overall survival rates were significantly higher for patients who had DD/DR after BOR compared to those who had DD/DR prior to BOR or those with no DD/DR (30 v/s 22 v/s 11 months, respectively, p<0.001). Progression-free survival rates also trended higher for those with DD/DR after BOR (median not reached) compared to those who required DD/DR before (median of 15 months) (p=0.285). In conclusion, DD/DR may be safely accomplished once the patient has achieved BOR (preferably complete remission) without impacting outcome. Prospective evaluation of an approach conceiving a loading dose for induction of a best objective response followed by a maintenance schedule is to be considered. PMID:23969308

  4. A new method for achieving enhanced dielectric response over a wide temperature range

    PubMed Central

    Maurya, Deepam; Sun, Fu-Chang; Pamir Alpay, S.; Priya, Shashank

    2015-01-01

    We report a novel approach for achieving high dielectric response over a wide temperature range. In this approach, multilayer ceramic heterostructures with constituent compositions having strategically tuned Curie points (TC) were designed and integrated with varying electrical connectivity. Interestingly, these multilayer structures exhibited different dielectric behavior in series and parallel configuration due to variations in electrical boundary conditions resulting in the differences in the strength of the electrostatic coupling. The results are explained using nonlinear thermodynamic model taking into account electrostatic interlayer interaction. We believe that present work will have huge significance in design of high performance ceramic capacitors. PMID:26477391

  5. A new method for achieving enhanced dielectric response over a wide temperature range

    NASA Astrophysics Data System (ADS)

    Maurya, Deepam; Sun, Fu-Chang; Pamir Alpay, S.; Priya, Shashank

    2015-10-01

    We report a novel approach for achieving high dielectric response over a wide temperature range. In this approach, multilayer ceramic heterostructures with constituent compositions having strategically tuned Curie points (TC) were designed and integrated with varying electrical connectivity. Interestingly, these multilayer structures exhibited different dielectric behavior in series and parallel configuration due to variations in electrical boundary conditions resulting in the differences in the strength of the electrostatic coupling. The results are explained using nonlinear thermodynamic model taking into account electrostatic interlayer interaction. We believe that present work will have huge significance in design of high performance ceramic capacitors.

  6. A new method for achieving enhanced dielectric response over a wide temperature range

    DOE PAGESBeta

    Maurya, Deepam; Sun, Fu -Chang; Pamir Alpay, S.; Priya, Shashank

    2015-10-19

    We report a novel approach for achieving high dielectric response over a wide temperature range. In this approach, multilayer ceramic heterostructures with constituent compositions having strategically tuned Curie points (TC) were designed and integrated with varying electrical connectivity. Interestingly, these multilayer structures exhibited different dielectric behavior in series and parallel configuration due to variations in electrical boundary conditions resulting in the differences in the strength of the electrostatic coupling. The results are explained using nonlinear thermodynamic model taking into account electrostatic interlayer interaction. We believe that present work will have huge significance in design of high performance ceramic capacitors.

  7. Clinical manifestations, response to treatment, and clinical outcome for Weimaraners with hypertrophic osteodystrophy: 53 cases (2009–2011)

    PubMed Central

    Safra, Noa; Johnson, Eric G.; Lit, Lisa; Foreman, Oded; Wolf, Zena T.; Aguilar, Miriam; Karmi, Nili; Finno, Carrie J.; Bannasch, Danika L.

    2014-01-01

    Objective To evaluate clinical manifestations, response to treatment, and outcome for Weimaraners with hypertrophic osteodystrophy (HOD). Design Retrospective case series. Animals 53 dogs. Procedures Medical records were reviewed for signalment, vaccination history, clinical signs, laboratory test results, response to treatment, and relapses. Radiographs were reviewed. Results Clinical signs included pyrexia, lethargy, and ostealgia; signs involving the gastrointestinal, ocular, or cutaneous systems were detected. Of the 53 dogs, 28 (52.8%) had HOD-affected littermates. Dogs with HOD-affected littermates were more likely to relapse, compared with the likelihood of relapse for dogs with no HOD-affected littermates. All 53 dogs had been vaccinated 1 to 30 days before HOD onset; no difference was found between the number of dogs with a history of vaccination with a recombinant vaccine (n = 21) versus a nonrecombinant vaccine (32). Fifty (94.3%) dogs had radiographic lesions compatible with HOD at disease onset, and the other 3 (5.7%) had HOD lesions 48 to 72 hours after the onset of clinical signs. Twelve of 22 (54.5%) dogs treated with NSAIDs did not achieve remission by 7 days after initiation of treatment. All dogs treated initially with corticosteroids achieved remission within 8 to 48 hours. Of the 33 dogs that reached adulthood, 28 (84.8%) were healthy and 5 (15.2%) had episodes of pyrexia and malaise. Conclusions and Clinical Relevance Treatment with corticosteroids was superior to treatment with NSAIDs in Weimaraners with HOD. It may be necessary to evaluate repeated radiographs to establish a diagnosis of HOD. Most HOD-affected Weimaraners had resolution of the condition with physeal closure. PMID:23600784

  8. Piloted Simulator Investigation of Techniques to Achieve Attitude Command Response with Limited Authority Servos

    NASA Technical Reports Server (NTRS)

    Key, David L.; Heffley, Robert K.

    2002-01-01

    The purpose of the study was to develop generic design principles for obtaining attitude command response in moderate to aggressive maneuvers without increasing SCAS series servo authority from the existing +/- 10%. In particular, to develop a scheme that would work on the UH-60 helicopter so that it can be considered for incorporation in future upgrades. The basic math model was a UH-60A version of GENHEL. The simulation facility was the NASA-Ames Vertical Motion Simulator (VMS). Evaluation tasks were Hover, Acceleration-Deceleration, and Sidestep, as defined in ADS-33D-PRF for Degraded Visual Environment (DVE). The DVE was adjusted to provide a Usable Cue Environment (UCE) equal to two. The basic concept investigated was the extent to which the limited attitude command authority achievable by the series servo could be supplemented by a 10%/sec trim servo. The architecture used provided angular rate feedback to only the series servo, shared the attitude feedback between the series and trim servos, and when the series servo approached saturation the attitude feedback was slowly phased out. Results show that modest use of the trim servo does improve pilot ratings, especially in and around hover. This improvement can be achieved with little degradation in response predictability during moderately aggressive maneuvers.

  9. Admission Privileges and Clinical Responsibilities for Interventional Radiologists

    SciTech Connect

    Al-Kutoubi, Aghiad

    2015-04-15

    Although clinical involvement by interventional radiologists in the care of their patients was advocated at the inception of the specialty, the change into the clinical paradigm has been slow and patchy for reasons related to pattern of practice, financial remuneration or absence of training. The case for the value of clinical responsibilities has been made in a number of publications and the consequences of not doing so have been manifest in the erosion of the role of the interventional radiologists particularly in the fields of peripheral vascular and neuro intervention. With the recent recognition of interventional radiology (IR) as a primary specialty in the USA and the formation of IR division in the Union of European Medical Specialists and subsequent recognition of the subspecialty in many European countries, it is appropriate to relook at the issue and emphasize the need for measures to promote the clinical role of the interventional radiologist.

  10. Exposure–Response Modeling of Clinical End Points Using Latent Variable Indirect Response Models

    PubMed Central

    Hu, C

    2014-01-01

    Exposure–response modeling facilitates effective dosing regimen selection in clinical drug development, where the end points are often disease scores and not physiological variables. Appropriate models need to be consistent with pharmacology and identifiable from the time courses of available data. This article describes a general framework of applying mechanism-based models to various types of clinical end points. Placebo and drug model parameterization, interpretation, and assessment are discussed with a focus on the indirect response models. PMID:24897307

  11. Clinical spectrum of dopa-responsive dystonia and related disorders.

    PubMed

    Lee, Woong-Woo; Jeon, Beom Seok

    2014-07-01

    Dopa-responsive dystonia (DRD) has a classic presentation of childhood or adolescent-onset dystonia, mild parkinsonism, marked diurnal fluctuations, improvement with sleep or rest, and a dramatic and sustained response to low doses of L-dopa without motor fluctuations or dyskinesias. However, there have been many papers on patients with a wide range of features, which report them as DRD mainly because they had dystonic syndromes with L-dopa responsiveness. Many mutations in the dopaminergic system have been found as molecular genetic defects. Therefore, the clinical and genetic spectra of DRD are unclear, which lead to difficulties in diagnostic work-ups and planning treatments. We propose the concept of DRD and DRD-plus to clarify the confusion in this area and to help understand the pathophysiology and clinical features, which will help in guiding diagnostic investigations and planning treatments. We critically reviewed the literature on atypical cases and discussed the limitations of the gene study. PMID:24844652

  12. [Legal responsibility in the exercising of the neurology clinical practice].

    PubMed

    Siso Martín, J

    2004-12-01

    The importance of responsibility in the clinical practice is derived from the transcendency of what they affect (life and health) and the risk implicit to it. The clinical performance does not require curing. The obligations that are derived from them are means and not results. It is also not correct to associate error and responsibility. Responsibility of the professional may be claimed by civil, patrimony, corporative, disciplinary and penal routes based on the reasons and according to who is making the claim. These claims may be presented individually or jointly based on whether the modality of the professional practice is free or carried out by others, whether in public health or private health care. The professional has different alternatives to respond to the possible lawsuits that are presented, both penal and civil action or protection have the common problem of the difficulty of proof. PMID:15719285

  13. Monitoring Regulatory Immune Responses in Tumor Immunotherapy Clinical Trials

    PubMed Central

    Olson, Brian M.; McNeel, Douglas G.

    2013-01-01

    While immune monitoring of tumor immunotherapy often focuses on the generation of productive Th1-type inflammatory immune responses, the importance of regulatory immune responses is often overlooked, despite the well-documented effects of regulatory immune responses in suppressing anti-tumor immunity. In a variety of malignancies, the frequency of regulatory cell populations has been shown to correlate with disease progression and a poor prognosis, further emphasizing the importance of characterizing the effects of immunotherapy on these populations. This review focuses on the role of suppressive immune populations (regulatory T cells, myeloid-derived suppressor cells, and tumor-associated macrophages) in inhibiting anti-tumor immunity, how these populations have been used in the immune monitoring of clinical trials, the prognostic value of these responses, and how the monitoring of these regulatory responses can be improved in the future. PMID:23653893

  14. Paving the critical path: how can clinical pharmacology help achieve the vision?

    PubMed

    Lesko, L J

    2007-02-01

    It has been almost 3 years since the launch of the FDA critical path initiative following the publication of the paper "Innovation or Stagnation: Challenges and Opportunities on the Critical Path of New Medical Product Development." The initiative was intended to create an urgency with the drug development enterprise to address the so-called "productivity problem" in modern drug development. Clinical pharmacologists are strategically aligned with solutions designed to reduce late phase clinical trial failures to show adequate efficacy and/or safety. This article reviews some of the ways that clinical pharmacologists can lead and implement change in the drug development process. It includes a discussion of model-based, semi-mechanistic drug development, drug/disease models that facilitate informed clinical trial designs and optimal dosing, the qualification process and criteria for new biomarkers and surrogate endpoints, approaches to streamlining clinical trials and new types of interaction between industry and FDA such as the end-of-phase 2A and voluntary genomic data submission meetings respectively. PMID:17259944

  15. Initial Stage Affects Survival Even After Complete Pathologic Remission is Achieved in Locally Advanced Esophageal Cancer: Analysis of 70 Patients With Pathologic Major Response After Preoperative Chemoradiotherapy

    SciTech Connect

    Kim, Min Kyoung; Cho, Kyung-Ja; Park, Seung-Il; Kim, Yong Hee; Kim, Jong Hoon; Song, Ho-Young; Shin, Ji Hoon; Jung, Hwoon Yong; Lee, Gin Hyug; Choi, Kee Don; Song, Ho June; Ryu, Jin-Sook; Kim, Sung-Bae

    2009-09-01

    Purpose: To analyze outcomes and factors predictive for recurrence and survival in patients with operable esophageal carcinoma who achieved pathologic complete response (PCR) or microscopic residual disease (MRD) after preoperative chemoradiotherapy (CRT). Materials and Methods: Outcomes were assessed in 70 patients with locally advanced esophageal cancer who achieved pathologic major response (53 with PCR and 17 with MRD) after preoperative CRT. Results: At a median follow-up of 38.6 months for surviving patients, 17 of 70 patients (24.3%) experienced disease recurrence and 31 (44.3%) died. Clinical stage (II vs III; p = 0.013) and pathologic response (PCR vs. MRD; p = 0.014) were independent predictors of disease recurrence. Median overall survival (OS) was 99.6 months (95% CI, 44.1-155.1 months) and the 5-year OS rate was 57%. Median recurrence-free survival (RFS) was 71.5 months (95% CI, 39.5-103.6 months) and the 5-year RFS rate was 51.3%. Median OS of patients with Stage II and Stage III disease was 108.8 months and 39.9 months, respectively, and the 5-year OS rates were 68.2% and 27.0%, respectively (p = 0.0003). In a subgroup of patients with PCR, median OS and RFS were also significantly different according to clinical stage. Multivariate analysis showed that clinical stage was an independent predictor of RFS (p = 0.01) and OS (p = 0.008). Conclusions: Even though patients achieved major response after preoperative CRT, pretreatment clinical stage is an important prognostic marker for recurrence and survival. Patients with MRD have an increased recurrence risk but similar survival compared with patients achieved PCR.

  16. Nursing Students Achieving Community Health Competencies through Undergraduate Clinical Experiences: A Gap Analysis.

    PubMed

    Pijl-Zieber, Em M; Barton, Sylvia; Awosoga, Oluwagbohunmi A; Konkin, Jill

    2015-01-01

    In Canada, it is widely believed that nursing practice and health care will move from acute care into the community. At the same time, increasing numbers of nursing students are engaged in non-traditional clinical experiences for their community health rotation. These clinical experiences occur at agencies not organizationally affiliated with the health care system and typically do not employ registered nurses (RNs). What has yet to be established is the degree to which nursing students are actually being prepared for community health nursing roles through their community health clinical rotations. In this paper we report the findings of a mixed method study that explored the gap between desired and observed levels of competence in community health of senior nursing students and new graduates. The gap was quantified and then the nature of the gap further explored through focus groups. PMID:26461843

  17. WISC-III and CAS: Which Correlates Higher with Achievement for a Clinical Sample?

    ERIC Educational Resources Information Center

    Naglieri, Jack A.; De Lauder, Brianna Y.; Goldstein, Sam; Schwebech, Adam

    2006-01-01

    The relationships between Wechsler Intelligence Scale for Children-Third Edition (WISC-III) and the Cognitive Assessment System (CAS) with the Woodcock-Johnson Tests of Achievement (WJ-III) were examined for a sample of 119 children (87 males and 32 females) ages 6 to 16. The sample was comprised of children who were referred to a specialty clinic…

  18. Optimal microelectromechanical systems (MEMS) device for achieving high pyroelectric response of AlN

    NASA Astrophysics Data System (ADS)

    Kebede, Bemnnet; Coutu, Ronald A.; Starman, LaVern

    2014-03-01

    This paper discusses research being conducted on aluminum nitride (AlN) as a pyroelectric material for use in detecting applications. AlN is being investigated because of its high pyroelectric coefficient, thermal stability, and high Curie temperature. In order to determine suitability of the pyroelectric properties of AlN for use as a detector, testing of several devices was conducted. These devices were fabricated using microelectromechanical systems (MEMS) fabrication processes; the devices were also designed to allow for voltage and current measurements. The deposited AlN films used were 150 nm - 300 nm in thickness. Thin-films were used to rapidly increase the temperature response after the thermal stimulus was applied to the pyroelectric material. This is important because the pyroelectric effect is directly proportional to the rate of temperature change. The design used was a face-electrode bridge that provides thermal isolation which minimizes heat loss to the substrate, thereby increasing operation frequency of the pyroelectric device. A thermal stimulus was applied to the pyroelectric material and the response was measured across the electrodes. A thermal imaging camera was used to monitor the changes in temperature. Throughout the testing process, the annealing temperatures, type of layers, and thicknesses were also varied. These changes resulted in improved MEMS designs, which were fabricated to obtain an optimal design configuration for achieving a high pyroelectric response. A pyroelectric voltage response of 38.9 mVp-p was measured without filtering, 12.45 mVp-p was measured in the infrared (IR) region using a Si filter, and 6.38 mVp-p was measured in the short wavelength IR region using a long pass filter. The results showed that AlN's pyroelectric properties can be used in detecting applications.

  19. Nuclear imaging of the breast: Translating achievements in instrumentation into clinical use

    PubMed Central

    Hruska, Carrie B.; O'Connor, Michael K.

    2013-01-01

    Approaches to imaging the breast with nuclear medicine and/or molecular imaging methods have been under investigation since the late 1980s when a technique called scintimammography was first introduced. This review charts the progress of nuclear imaging of the breast over the last 20 years, covering the development of newer techniques such as breast specific gamma imaging, molecular breast imaging, and positron emission mammography. Key issues critical to the adoption of these technologies in the clinical environment are discussed, including the current status of clinical studies, the efforts at reducing the radiation dose from procedures associated with these technologies, and the relevant radiopharmaceuticals that are available or under development. The necessary steps required to move these technologies from bench to bedside are also discussed. PMID:23635248

  20. Nuclear imaging of the breast: Translating achievements in instrumentation into clinical use

    SciTech Connect

    Hruska, Carrie B.; O'Connor, Michael K.

    2013-05-15

    Approaches to imaging the breast with nuclear medicine and/or molecular imaging methods have been under investigation since the late 1980s when a technique called scintimammography was first introduced. This review charts the progress of nuclear imaging of the breast over the last 20 years, covering the development of newer techniques such as breast specific gamma imaging, molecular breast imaging, and positron emission mammography. Key issues critical to the adoption of these technologies in the clinical environment are discussed, including the current status of clinical studies, the efforts at reducing the radiation dose from procedures associated with these technologies, and the relevant radiopharmaceuticals that are available or under development. The necessary steps required to move these technologies from bench to bedside are also discussed.

  1. Clinical and electrophysiological responses to dietary challenge in migraineurs.

    PubMed

    Lai, C W; Dean, P; Ziegler, D K; Hassanein, R S

    1989-03-01

    Thirty eight patients with a history of diet-induced migraine were studied with recording of clinical responses, electroencephalography in resting state, in response to photic stimulation, and to hyperventilation and visual evoked potentials. Tests were carried out on an initial baseline day and on a second day, after challenge with chocolate, red wine, cheese, and fasting. Lateralized headache occurred in sixteen subjects (42%), four with scintillating scotomata. Electroencephalograms were abnormal on Day 1 and/or Day 2 in twelve subjects (32%), most abnormalities being non-specific slow waves. In three cases there were paroxysmal features. Electroencephalographic response to hyperventilation was calibrated and was found to be exaggerated in eight subjects (21%) on either Day 1 or Day 2; such response was not related to the occurrence of a headache. Photic simulation showed high frequency driving response (so called "H" response) in all 16 individuals who developed headache but in only 14 out of 22 (64%) who did not (p less than 0.01). Pattern reversal visual evoked responses were normal and failed to show any difference in latency or amplitude between headache responders and non-responders. PMID:2708047

  2. Modeling Clinical Radiation Responses in the IMRT Era

    NASA Astrophysics Data System (ADS)

    Schwartz, J. L.; Murray, D.; Stewart, R. D.; Phillips, M. H.

    2014-03-01

    The purpose of this review is to highlight the critical issues of radiobiological models, particularly as they apply to clinical radiation therapy. Developing models of radiation responses has a long history that continues to the present time. Many different models have been proposed, but in the field of radiation oncology, the linear-quadratic (LQ) model has had the most impact on the design of treatment protocols. Questions have been raised as to the value of the LQ model given that the biological assumption underlying it has been challenged by molecular analyses of cell and tissue responses to radiation. There are also questions as to use of the LQ model for hypofractionation, especially for high dose treatments using a single fraction. While the LQ model might over-estimate the effects of large radiation dose fractions, there is insufficient information to fully justify the adoption of alternative models. However, there is increasing evidence in the literature that non-targeted and other indirect effects of radiation sometimes produce substantial deviations from LQ-like dose-response curves. As preclinical and clinical hypofractionation studies accumulate, new or refined dose-response models that incorporate high-dose/fraction non-targeted and indirect effects may be required, but for now the LQ model remains a simple, useful tool to guide the design of treatment protocols.

  3. Towards Achieving the Full Clinical Potential of Proton Therapy by Inclusion of LET and RBE Models

    PubMed Central

    Jones, Bleddyn

    2015-01-01

    Despite increasing use of proton therapy (PBT), several systematic literature reviews show limited gains in clinical outcomes, with publications mostly devoted to recent technical developments. The lack of randomised control studies has also hampered progress in the acceptance of PBT by many oncologists and policy makers. There remain two important uncertainties associated with PBT, namely: (1) accuracy and reproducibility of Bragg peak position (BPP); and (2) imprecise knowledge of the relative biological effect (RBE) for different tissues and tumours, and at different doses. Incorrect BPP will change dose, linear energy transfer (LET) and RBE, with risks of reduced tumour control and enhanced toxicity. These interrelationships are discussed qualitatively with respect to the ICRU target volume definitions. The internationally accepted proton RBE of 1.1 was based on assays and dose ranges unlikely to reveal the complete range of RBE in the human body. RBE values are not known for human (or animal) brain, spine, kidney, liver, intestine, etc. A simple efficiency model for estimating proton RBE values is described, based on data of Belli et al. and other authors, which allows linear increases in α and β with LET, with a gradient estimated using a saturation model from the low LET α and β radiosensitivity parameter input values, and decreasing RBE with increasing dose. To improve outcomes, 3-D dose-LET-RBE and bio-effectiveness maps are required. Validation experiments are indicated in relevant tissues. Randomised clinical studies that test the invariant 1.1 RBE allocation against higher values in late reacting tissues, and lower tumour RBE values in the case of radiosensitive tumours, are also indicated. PMID:25790470

  4. Clinical predictors of therapeutic response to antipsychotics in schizophrenia

    PubMed Central

    Carbon, Maren; Correll, Christoph U.

    2014-01-01

    The search for clinical outcome predictors for schizophrenia is as old as the field of psychiatry. However, despite a wealth of large, longitudinal studies into prognostic factors, only very few clinically useful outcome predictors have been identified. The goal of future treatment is to either affect modifiable risk factors, or use nonmodifiable factors to parse patients into therapeutically meaningful subgroups. Most clinical outcome predictors are nonspecific and/or nonmodifiable. Nonmodifiable predictors for poor odds of remission include male sex, younger age at disease onset, poor premorbid adjustment, and severe baseline psychopathology. Modifiable risk factors for poor therapeutic outcomes that clinicians can act upon include longer duration of untreated illness, nonadherence to antipsychotics, comorbidities (especially substance-use disorders), lack of early antipsychotic response, and lack of improvement with non-clozapine antipsychotics, predicting clozapine response. It is hoped that this limited capacity for prediction will improve as pathophysiological understanding increases and/or new treatments for specific aspects of schizophrenia become available. PMID:25733955

  5. Dopa-responsive dystonia--clinical and genetic heterogeneity.

    PubMed

    Wijemanne, Subhashie; Jankovic, Joseph

    2015-07-01

    Dopa-responsive dystonia (DRD) encompasses a group of clinically and genetically heterogeneous disorders that typically manifest as limb-onset, diurnally fluctuating dystonia and exhibit a robust and sustained response to levodopa treatment. Autosomal dominant GTP cyclohydrolase 1 deficiency, also known as Segawa disease, is the most common and best-characterized condition that manifests as DRD, but a similar presentation can be seen with genetic abnormalities that lead to deficiencies in tyrosine hydroxylase, sepiapterin reductase or other enzymes that are involved in the biosynthesis of dopamine. In rare cases, DRD can result from conditions that do not affect the biosynthesis of dopamine; single case reports have shown that DRD can be a manifestation of hereditary spastic paraplegia type 11, spinocerebellar ataxia type 3 and ataxia telangiectasia. This heterogeneity of conditions that underlie DRD frequently leads to misdiagnosis, which delays the appropriate treatment with levodopa. Correct diagnosis at an early stage requires use of the appropriate diagnostic tests, which include a levodopa trial, genetic testing (including whole-exome sequencing), cerebrospinal fluid neurotransmitter analysis, the phenylalanine loading test, and enzyme activity measurements. The selection of tests for use depends on the clinical presentation and level of complexity. This Review presents the common and rarer causes of DRD and their clinical features, and considers the most appropriate approaches to ensure early diagnosis and treatment. PMID:26100751

  6. Predicting clinical responses in major depression using intrinsic functional connectivity.

    PubMed

    Qin, Jian; Shen, Hui; Zeng, Ling-Li; Jiang, Weixiong; Liu, Li; Hu, Dewen

    2015-08-19

    There has been increasing interest in multivariate pattern analysis (MVPA) as a means of distinguishing psychiatric patients from healthy controls using brain imaging. However, it remains unclear whether MVPA methods can accurately estimate the medication status of psychiatric patients. This study aims to develop an MVPA approach to accurately predict the antidepressant medication status of individuals with major depression on the basis of whole-brain resting-state functional connectivity MRI (rs-fcMRI). We investigated data from rs-fcMRI of 24 medication-naive depressed patients, 16 out of whom subsequently underwent antidepressant treatment and achieved clinical recovery, and 29 demographically similar controls. By training a linear support vector machine classifier and combining it with principal component analysis, the medication-naive patients were identified from the healthy controls with 100% accuracy. In addition, we found reliable correlations between MVPA prediction scores and clinical symptom severity. Moreover, the most discriminative functional connections were located within or across the cerebellum and default mode, affective, and sensorimotor networks, indicating that these networks may play important roles in major depression. Most importantly, only ∼30% of these discriminative connections were normalized in clinically recovered patients after antidepressant treatment. The current study may not only show the feasibility of estimating medication status by MVPA of whole-brain rs-fcMRI data in major depression but also shed new light on the pathological mechanism of this disorder. PMID:26164454

  7. Responses of rat lungs following inhalation of beryllium metal particles to achieve relatively low lung burdens

    SciTech Connect

    Finch, G.L.; Haley, P.J.; Hoover, M.D.; Cuddihy, R.G.

    1991-01-01

    Potential health effects resulting from the accidental exposure of people to beryllium metal are of concern. To investigate the effects of relatively low levels of beryllium metal on lung clearance, we simultaneously exposed rats to beryllium metal and radioactive tracer particles. Exposure to beryllium metal aerosol to achieve estimated lung burdens of 9 or 52 {mu}g significantly retarded clearance up to 365 days after exposure compared to controls, whereas lung burdens of 1.5 or 2 {mu}g had no significant effect on clearance. Groups of rats were sacrificed at 8, 16, 40, 90, 210 and 365 days after exposure for bronchoalveolar lavage. The total numbers of cells, incidence of neutrophils, the levels of total protein, and the enzymes lactate dehydrogenase and {beta}-glucuronidase were generally elevated in lavage fluids from groups of rats that also had impaired lung clearance. This study serves to further define the levels of beryllium metal required to retard lung clearance and induce accompanying pathological responses in the lungs of rats. 11 refs., 5 figs., 1 tab.

  8. [Langerhans cell sarcoma developing acute myeloid leukemia after achieving complete response by THP-COP].

    PubMed

    Hamaguchi, Kota; Hashimoto, Akari; Fujimi, Akihito; Kanisawa, Yuji; Shibata, Takanori; Nakajima, Chisa; Hayasaka, Naotaka; Yamada, Shota; Okuda, Toshinori; Minami, Shinya; Kamihara, Yusuke; Ohshima, Koichi; Kato, Junji

    2015-12-01

    An 86-year-old man presented with enlarged left submandibular, left inguinal, and superficial femoral lymph nodes. He was diagnosed with Langerhans cell sarcoma (LCS) on the basis of the histopathological findings of the left inguinal lymph node biopsy. In addition, laboratory examinations revealed normocytic normochromic anemia, and bone marrow aspiration and biopsy led to a diagnosis of idiopathic cytopenia of undetermined significance (ICUS). Because of the patient's age, he was administered a regimen of cyclophosphamide, pirarubicin, vincristine, and prednisolone (THP-COP), and achieved a partial response after six courses. However, he developed acute myeloid leukemia (AML) 11 months after completion of the THP-COP therapy, and received only supportive care until his death. LCS is an extremely rare and aggressive dendritic cell neoplasm. To the best of our knowledge, only 67 cases have been reported in the literature. There are case reports describing the concurrence of hematological malignancies. Herein, we report the first documented development of LCS in a patient with ICUS who progressed to AML, and summarize the published data on the epidemiology of and therapeutic options for LCS. PMID:26725355

  9. Fostering Dental Students' Academic Achievements and Reflection Skills Through Clinical Peer Assessment and Feedback.

    PubMed

    Tricio, Jorge A; Woolford, Mark J; Escudier, Michael P

    2016-08-01

    Peer assessment is increasingly being encouraged to enhance dental students' learning. The aim of this study was to evaluate the educational impact in terms of academic achievements and reflective thinking of a formative prospective peer assessment and feedback protocol. Volunteer final-year dental students at King's College London Dental Institute, UK, received training on peer assessment, peer feedback, and self-reflection. At the beginning (baseline) and end (resultant) of the 2012-13 academic year, 86 students (55% of the year group) completed a reflection questionnaire (RQ). Sixty-eight of those students used a modified Direct Observation of Procedural Skills (DOPS) as a framework for peer assessment and peer feedback during a complete academic year. End-of-year, high-stakes examination grades and RQ scores from the participants and nonparticipants were statistically compared. The participants completed 576 peer DOPS. Those 22 students who peer assessed each other ≥10 times exhibited highly statistically significant differences and powerful positive effect sizes in their high-stakes exam grades (p=0.0001, d=0.74) and critical reflection skills (p=0.005, d=1.41) when compared to those who did not assess one another. Furthermore, only the same 22 students showed a statistically significant increase and positive effect size in their critical reflection skills from baseline to resultant (p=0.003, d=1.04). The results of this study suggest that the protocol used has the potential to impact dental students' academic and reflection skills, provided it is practiced in ten or more peer encounters and ensuring peer feedback is provided followed by self-reflection. PMID:27480702

  10. Corticosteroid responsiveness and clinical characteristics in childhood difficult asthma

    PubMed Central

    Bossley, C.J.; Saglani, S.; Kavanagh, C.; Payne, D.N.R.; Wilson, N.; Tsartsali, L.; Rosenthal, M.; Balfour-Lynn, I.M.; Nicholson, A.G.; Bush, A.

    2012-01-01

    This study describes the clinical characteristics and corticosteroid responsiveness of children with difficult asthma (DA). We hypothesised that complete corticosteroid responsiveness (defined as improved symptoms, normal spirometry, normal exhaled nitric oxide fraction (FeNO) and no bronchodilator responsiveness (BDR <12%)) is uncommon in paediatric DA. We report on 102 children, mean±SD age 11.6±2.8 yrs, with DA in a cross-sectional study. 89 children underwent spirometry, BDR and FeNO before and after 2 weeks of systemic corticosteroids (corticosteroid response study). Bronchoscopy was performed after the corticosteroid trial. Of the 102 patients in the cross-sectional study, 88 (86%) were atopic, 60 (59%) were male and 52 (51%) had additional or alternative diagnoses. Out of the 81 patients in the corticosteroid response study, nine (11%) were complete responders. Of the 75 patients with symptom data available, 37 (49%) responded symptomatically, which was less likely if there were smokers in the home (OR 0.31, 95% CI 0.02–0.82). Of the 75 patients with available spirometry data, 35 (46%) had normal spirometry, with associations being BAL eosinophilia (OR 5.43, 95% CI 1.13–26.07) and high baseline forced expiratory volume in 1 s (FEV1) (OR 1.08, 95% CI 1.02–1.12). Of these 75 patients, BDR data were available in 64, of whom 36 (56%) had <12% BDR. FeNO data was available in 70 patients, of whom 53 (75%) had normal FeNO. Airflow limitation data was available in 75 patients, of whom 17 (26%) had persistent airflow limitation, which was associated with low baseline FEV1 (OR 0.93, 95% CI 0.90–0.97). Only 11% of DA children exhibited complete corticosteroid responsiveness. The rarity of complete corticosteroid responsiveness suggests alternative therapies are needed for children with DA. PMID:19541710

  11. Interactive Voice/Web Response System in clinical research

    PubMed Central

    Ruikar, Vrishabhsagar

    2016-01-01

    Emerging technologies in computer and telecommunication industry has eased the access to computer through telephone. An Interactive Voice/Web Response System (IxRS) is one of the user friendly systems for end users, with complex and tailored programs at its backend. The backend programs are specially tailored for easy understanding of users. Clinical research industry has experienced revolution in methodologies of data capture with time. Different systems have evolved toward emerging modern technologies and tools in couple of decades from past, for example, Electronic Data Capture, IxRS, electronic patient reported outcomes, etc. PMID:26952178

  12. Interactive Voice/Web Response System in clinical research.

    PubMed

    Ruikar, Vrishabhsagar

    2016-01-01

    Emerging technologies in computer and telecommunication industry has eased the access to computer through telephone. An Interactive Voice/Web Response System (IxRS) is one of the user friendly systems for end users, with complex and tailored programs at its backend. The backend programs are specially tailored for easy understanding of users. Clinical research industry has experienced revolution in methodologies of data capture with time. Different systems have evolved toward emerging modern technologies and tools in couple of decades from past, for example, Electronic Data Capture, IxRS, electronic patient reported outcomes, etc. PMID:26952178

  13. Rapid-Response Impulsivity: Definitions, Measurement Issues, and Clinical Implications

    PubMed Central

    Hamilton, Kristen R.; Littlefield, Andrew K.; Anastasio, Noelle C.; Cunningham, Kathryn A.; Fink, Latham H.; Wing, Victoria C.; Mathias, Charles W.; Lane, Scott D.; Schutz, Christian; Swann, Alan C.; Lejuez, C.W.; Clark, Luke; Moeller, F. Gerard; Potenza, Marc N.

    2015-01-01

    Impulsivity is a multi-faceted construct that is a core feature of multiple psychiatric conditions and personality disorders. However, progress in understanding and treating impulsivity in the context of these conditions is limited by a lack of precision and consistency in its definition and assessment. Rapid-response-impulsivity (RRI) represents a tendency toward immediate action that occurs with diminished forethought and is out of context with the present demands of the environment. Experts from the International Society for Research on Impulsivity (InSRI) met to discuss and evaluate RRI-measures in terms of reliability, sensitivity, and validity with the goal of helping researchers and clinicians make informed decisions about the use and interpretation of findings from RRI-measures. Their recommendations are described in this manuscript. Commonly-used clinical and preclinical RRI-tasks are described, and considerations are provided to guide task selection. Tasks measuring two conceptually and neurobiologically distinct types of RRI, “refraining from action initiation” (RAI) and “stopping an ongoing action” (SOA) are described. RAI and SOA-tasks capture distinct aspects of RRI that may relate to distinct clinical outcomes. The InSRI group recommends that: 1) selection of RRI-measures should be informed by careful consideration of the strengths, limitations, and practical considerations of the available measures; 2) researchers use both RAI and SOA tasks in RRI studies to allow for direct comparison of RRI types and examination of their associations with clinically relevant measures; and, 3) similar considerations should be made for human and non-human studies in an effort to harmonize and integrate pre-clinical and clinical research. PMID:25867840

  14. [Responsible dealing with sexuality. Recommendations in a clinical institution].

    PubMed

    Steinberg, R; Rittner, C; Dormann, S; Spengler-Katerndahl, D

    2012-03-01

    Sexuality is excluded in house regulations, guidelines, instructions and regulations in German hospitals. The English literature does not show much more, but more often the wish for clear guidelines is formulated. Under the guidance of the clinical Ethics Committee a paper with recommendations was prepared, which comprises regulations for responsible handling of sexuality in the Pfalzklinikum. This includes sexuality of acute patients in psychiatry, nursing home inhabitants, forensic patients and above all patients in the department of child and youth psychiatry. The right of self-realization on the one hand, the staff's responsibility for patients with limitations in the determination of one's intent on the other hand and the rules for staff members define the range of the paper. PMID:21607802

  15. Laser thermokeratoplasty: analysis of in-vitro results and refractive changes achieved in a first clinical study

    NASA Astrophysics Data System (ADS)

    Brinkmann, Ralf; Geerling, Gerd; Kampmeier, Juergen; Koop, Norbert; Radt, Benno; Birngruber, Reginald

    1997-12-01

    Laser thermokeratoplasty (LTK) is a minimally invasive method to correct hyperopia and astigmatism. A cw mid-IR laser diode emitting at wavelengths around 1.86 micrometers was used to perform LTK on a first clinical trial. The coagulations were applied to the cornea by means of a specially designed focusing handpiece which was introduced into a corneal application mask fixed by a suction ring. Coagulation patterns consisting of 8 spots per ring were performed with a laser power between 100 - 150 mW and an irradiation time of 10 seconds both on single and on double rings. Significant refractive changes up to 19 D could initially be achieved followed by a strong regression within the first month. Three months post LTK, refractive changes achieved with the single and double ring have stabilized, yielding 1.2 and 1.8 D on the average, respectively. The method reveals only little adverse effects limited to the first days post-op. Force measurements were performed on corneal stripes, which were submerged for 10 s into an oil bath of constant temperature in order to investigate the absolute temperatures required for corneal collagen contraction. Only temperatures exceeding 90 degree(s)C induced a significant force. Analyzing the clinically used LTK parameters by temperature calculations revealed that only a small part of the heated stromal volume experienced sufficient high temperatures to induce significant collagen shrinkage.

  16. JAK INHIBITOR CLINICAL RESPONSE IN POLYARTHRITIS: CASE REPORT.

    PubMed

    Stipić-Marković, Asja; Ferček, Iva; Čubela, Marta; Artuković, Marinko; Radončić, Ksenija Maštrović; Lugović-Mihić, Liborija

    2015-06-01

    The heterogeneity of rheumatoid arthritis (RA) presentation and molecular signature of RA subclasses in patients with early changes of small peripheral joints still remains a challenging problem. In clinical setting, classification of the disease subtypes is not possible and treatment adjustment is based on the continuous Disease Activity Score for disease severity recognition. A new approach in the treatment appears with the novel non biologic targeted synthetic disease-modifying antirheumatic drugs from the group of Janus kinase 1 and 3 (JAKI and JAK3), blocking interleukin (IL)-2, IL-4, IL-7, IL-9, IL-15 and IL-21. We report a case of a 48-year-old patient who had suffered from polyarthritis from his age 40. Initial laboratory tests showed low inflammatory parameters and magnetic resonance imaging of both hands indicated an early stage of RA. Methylprednisolone and methotrexate therapy was initiated. The patient underwent additional tests, but there was not sufficient evidence for a precise diagnosis. According to the European League Against Rheumatism/American College of Rheumatology score-based algorithm, the patient was classified as seronegative RA based on joint involvement, duration of the disease, and synovitis not better explained by another disease. A partial clinical effect of the administered therapy (steroids as monotherapy and in combination, methotrexate and leflunomide) was noticed with the use of systemic steroids, but dramatic improvement was only achieved with a JAK inhibitor targeted therapy. Although the use of anti TNF-α blocker is a proposed procedure and the drug has not yet been registered in Europe, we took the opportunity to apply this new medication option. The patient, a construction worker, was treated for 20 months, which led to complete remission of the disease, without the need of basic or corticosteroid therapy. Full functional capacity necessary in his demanding job was also achieved. This result raised a question of timely

  17. Clinical factors of post-chemoradiotherapy as valuable indicators for pathological complete response in locally advanced rectal cancer

    PubMed Central

    Peng, Jianhong; Lin, Junzhong; Qiu, Miaozhen; Wu, Xiaojun; Lu, Zhenhai; Chen, Gong; Li, Liren; Ding, Peirong; Gao, Yuanhong; Zeng, Zhifan; Zhang, Huizhong; Wan, Desen; Pan, Zhizhong

    2016-01-01

    OBJECTIVES: Pathological complete response has shown a better prognosis for patients with locally advanced rectal cancer after preoperative chemoradiotherapy. However, correlations between post-chemoradiotherapy clinical factors and pathologic complete response are not well confirmed. The aim of the current study was to identify post-chemoradiotherapy clinical factors that could serve as indicators of pathologic complete response in locally advanced rectal cancer. METHODS: This study retrospectively analyzed 544 consecutive patients with locally advanced rectal cancer treated at Sun Yat-sen University Cancer Center from December 2003 to June 2014. All patients received preoperative chemoradiotherapy followed by surgery. Univariate and multivariate regression analyses were performed to identify post-chemoradiotherapy clinical factors that are significant indicators of pathologic complete response. RESULTS: In this study, 126 of 544 patients (23.2%) achieved pathological complete response. In multivariate analyses, increased pathological complete response rate was significantly associated with the following factors: post-chemoradiotherapy clinical T stage 0-2 (odds ratio=2.098, 95% confidence interval=1.023-4.304, p=0.043), post-chemoradiotherapy clinical N stage 0 (odds ratio=2.011, 95% confidence interval=1.264-3.201, p=0.003), interval from completion of preoperative chemoradiotherapy to surgery of >7 weeks (odds ratio=1.795, 95% confidence interval=1.151-2.801, p=0.010) and post-chemoradiotherapy carcinoembryonic antigen ≤2 ng/ml (odds ratio=1.579, 95% confidence interval=1.026-2.432, p=0.038). CONCLUSIONS: Post-chemoradiotherapy clinical T stage 0-2, post-chemoradiotherapy clinical N stage 0, interval from completion of chemoradiotherapy to surgery of >7 weeks and post-chemoradiotherapy carcinoembryonic antigen ≤2 ng/ml were independent clinical indicators for pathological complete response. These findings demonstrate that post-chemoradiotherapy clinical

  18. Acute Pelvic Inflammatory Disease and Clinical Response to Parenteral Doxycycline

    PubMed Central

    Chow, Anthony W.; Malkasian, Kay L.; Marshall, John R.; Guze, Lucien B.

    1975-01-01

    The bacteriology of acute pelvic inflammatory disease (PID) and clinical response to parenteral doxycycline were evaluated in 30 patients. Only 3 of 21 cul-de-sac cultures from PID patients were sterile, whereas all 8 normal control subjects yielded negative results (P< 0.005). Poor correlation was observed between cervical and cul-de-sac cultures. Neisseria gonorrhoeae, isolated from the cervix in 17 patients (57%), was recovered from the cul-de-sac only once. Streptococcus, Peptococcus, Peptostreptococcus, coliforms, and other organisms normally present in the vagina were the predominant isolates recovered from the cul-de-sac. Parenteral doxycycline resulted in rapid resolution of signs and symptoms (within 48 h) in 20 of 27 evaluable patients (74%). In five others, signs and symptoms of infection abated within 4 days. The remaining two patients failed to respond; in both cases, adnexal masses developed during doxycycline therapy. Gonococci were eradicated from the cervix in all but one patient who, nevertheless, had a rapid defervescence of symptoms. There was no clear-cut correlation between the clinical response and in vitro susceptibility of cul-de-sac isolates to doxycycline. These data confirm the usefulness of broad-spectrum antibiotics in acute PID. Culdocentesis is a reliable means of obtaining material for the bacteriological diagnosis of acute PID; however, the pathogenetic role and relative importance of gonococci and various other bacteria in acute PID need to be clarified further. PMID:1169908

  19. Clinical iron deficiency disturbs normal human responses to hypoxia

    PubMed Central

    Frise, Matthew C.; Cheng, Hung-Yuan; Nickol, Annabel H.; Curtis, M. Kate; Pollard, Karen A.; Roberts, David J.; Ratcliffe, Peter J.; Dorrington, Keith L.; Robbins, Peter A.

    2016-01-01

    BACKGROUND. Iron bioavailability has been identified as a factor that influences cellular hypoxia sensing, putatively via an action on the hypoxia-inducible factor (HIF) pathway. We therefore hypothesized that clinical iron deficiency would disturb integrated human responses to hypoxia. METHODS. We performed a prospective, controlled, observational study of the effects of iron status on hypoxic pulmonary hypertension. Individuals with absolute iron deficiency (ID) and an iron-replete (IR) control group were exposed to two 6-hour periods of isocapnic hypoxia. The second hypoxic exposure was preceded by i.v. infusion of iron. Pulmonary artery systolic pressure (PASP) was serially assessed with Doppler echocardiography. RESULTS. Thirteen ID individuals completed the study and were age- and sex-matched with controls. PASP did not differ by group or study day before each hypoxic exposure. During the first 6-hour hypoxic exposure, the rise in PASP was 6.2 mmHg greater in the ID group (absolute rises 16.1 and 10.7 mmHg, respectively; 95% CI for difference, 2.7–9.7 mmHg, P = 0.001). Intravenous iron attenuated the PASP rise in both groups; however, the effect was greater in ID participants than in controls (absolute reductions 11.1 and 6.8 mmHg, respectively; 95% CI for difference in change, –8.3 to –0.3 mmHg, P = 0.035). Serum erythropoietin responses to hypoxia also differed between groups. CONCLUSION. Clinical iron deficiency disturbs normal responses to hypoxia, as evidenced by exaggerated hypoxic pulmonary hypertension that is reversed by subsequent iron administration. Disturbed hypoxia sensing and signaling provides a mechanism through which iron deficiency may be detrimental to human health. TRIAL REGISTRATION. ClinicalTrials.gov (NCT01847352). FUNDING. M.C. Frise is the recipient of a British Heart Foundation Clinical Research Training Fellowship (FS/14/48/30828). K.L. Dorrington is supported by the Dunhill Medical Trust (R178/1110). D.J. Roberts was

  20. Exemplary Care and Learning Sites: A Model for Achieving Continual Improvement in Care and Learning in the Clinical Setting

    PubMed Central

    Ogrinc, Greg; Hoffman, Kimberly G.; Stevenson, Katherine M.; Shalaby, Marc; Beard, Albertine S.; Thörne, Karin E.; Coleman, Mary T.; Baum, Karyn D.

    2016-01-01

    Problem Current models of health care quality improvement do not explicitly describe the role of health professions education. The authors propose the Exemplary Care and Learning Site (ECLS) model as an approach to achieving continual improvement in care and learning in the clinical setting. Approach From 2008–2012, an iterative, interactive process was used to develop the ECLS model and its core elements—patients and families informing process changes; trainees engaging both in care and the improvement of care; leaders knowing, valuing, and practicing improvement; data transforming into useful information; and health professionals competently engaging both in care improvement and teaching about care improvement. In 2012–2013, a three-part feasibility test of the model, including a site self-assessment, an independent review of each site’s ratings, and implementation case stories, was conducted at six clinical teaching sites (in the United States and Sweden). Outcomes Site leaders reported the ECLS model provided a systematic approach toward improving patient (and population) outcomes, system performance, and professional development. Most sites found it challenging to incorporate the patients and families element. The trainee element was strong at four sites. The leadership and data elements were self-assessed as the most fully developed. The health professionals element exhibited the greatest variability across sites. Next Steps The next test of the model should be prospective, linked to clinical and educa tional outcomes, to evaluate whether it helps care delivery teams, educators, and patients and families take action to achieve better patient (and population) outcomes, system performance, and professional development. PMID:26760058

  1. Improving Upper Grade Math Achievement via the Integration of a Culturally Responsive Curriculum.

    ERIC Educational Resources Information Center

    Pajkos, Diane; Klein-Collins, John

    This report describes an intervention program for increasing mathematical achievement of African American students. Within the targeted population, it was evident that the disparity in math achievement between African American and White students was increasing each year. The targeted population consisted of sixth, seventh, and eighth grade…

  2. Teaching Low-Achieving Students to Self-Regulate Persuasive Quick Write Responses

    ERIC Educational Resources Information Center

    Mason, Linda H.; Benedek-Wood, Elizabeth; Valasa, Lauren

    2009-01-01

    Students' academic achievement across content areas is often dependent on their ability to express knowledge through written expression. Many adolescent students lack the skills to write efficiently and effectively. These low-achieving writers can benefit from instruction in self-regulating the writing process. One approach, Self-Regulated…

  3. [Achievement of deep molecular response in an elderly chronic myeloid leukemia patient intolerant to imatinib and nilotinib].

    PubMed

    Kurimoto, Miwa; Nagata, Akihisa; Sekiguchi, Naohiro; Noto, Satoshi; Takezako, Naoki

    2015-12-01

    A 90-year-old woman was diagnosed with chronic myeloid leukemia (CML) of the high risk type (Sokal score 1.5), and was administered imatinib (400 mg/day). However, imatinib had to be switched to nilotinib because she suffered persistent vomiting and nausea. Although a cytogenetic response was achieved, the nilotinib administration also had to be stopped because the patient developed QTc prolongation and heart failure. After she had recovered from heart failure, the patient was given dasatinib (50 mg/day). No non-hematological adverse events occurred and she achieved a molecular response with administration of dasatinib. A molecular response can be achieved through appropriate supportive care and careful selection of tyrosine kinase inhibitors, with adjustments in the doses of these drugs administered to patients with the high-risk form of CML who are intolerant to imatinib. PMID:26725357

  4. Dendritic Cell Responses to Surface Properties of Clinical Titanium Surfaces

    PubMed Central

    Kou, Peng Meng; Schwartz, Zvi; Boyan, Barbara D.

    2010-01-01

    Dendritic cells (DCs) play pivotal roles in responding to foreign entities during an innate immune response and initiating effective adaptive immunity as well as maintaining immune tolerance. The sensitivity of DCs to foreign stimuli also makes them useful cells to assess the inflammatory response to biomaterials. Elucidating the material property-DC phenotype relationships using a well-defined biomaterial system is expected to provide criteria for immuno-modulatory biomaterial design. Clinical titanium (Ti) substrates, including pretreatment (PT), sand-blasted and acid-etched (SLA), and modified SLA (modSLA), with different roughness and surface energy were used to treat DCs and resulted in differential DC responses. PT and SLA induced a mature DC (mDC) phenotype, while modSLA promoted a non-inflammatory environment by supporting an immature DC (iDC) phenotype based on surface marker expression, cytokine production profiles and cell morphology. Principal component analysis (PCA) confirmed these experimental results, and it also indicated that the non-stimulating property of modSLA covaried with certain surface properties, such as high surface hydrophilicity, % oxygen and % Ti of the substrates. In addition to the previous research that demonstrated the superior osteogenic property of modSLA compared to PT and SLA, the result reported herein indicates that modSLA may further benefit implant osteo-integration by reducing local inflammation and its associated osteoclastogenesis. PMID:20977948

  5. Inflammatory mammary carcinoma in 12 dogs: Clinical features, cyclooxygenase-2 expression, and response to piroxicam treatment

    PubMed Central

    de M. Souza, Carlos H.; Toledo-Piza, Evandro; Amorin, Renee; Barboza, Andrigo; Tobias, Karen M.

    2009-01-01

    Canine inflammatory mammary carcinoma (IMC) is a rare, locally aggressive, highly metastatic tumor that is poorly responsive to treatment. The purposes of this study were to retrospectively evaluate the history, signalment, and clinical signs of dogs with IMC; compare the outcome of affected dogs treated with traditional chemotherapy with those treated with piroxicam; evaluate Cox-2 expression of IMC cells; and correlate Cox-2 expression with outcome based on treatment. Strong cyclooxygenase-2 expression was present in all tumors. Improvement in clinical condition and disease stability was achieved in all dogs treated with piroxicam, with mean and median progression-free survival of 171 and 183 days, respectively. Median survival time of 3 dogs treated with doxorubicin-based protocols was 7 days, which was significantly less than that of dogs treated with piroxicam (median, 185 days). In conclusion, piroxicam should be considered as a single agent for the treatment of dogs with inflammatory mammary carcinoma. PMID:19436636

  6. Strategic Clinical Networks: Alberta's Response to Triple Aim.

    PubMed

    Noseworthy, Tom; Wasylak, Tracy; O'Neill, Blair J

    2016-01-01

    Verma and Bhatia make a compelling case for the Triple Aim to promote health system innovation and sustainability. We concur. Moreover, the authors offer a useful categorization of policies and actions to advance the Triple Aim under the "classic functions" of financing, stewardship and resource generation (Verma and Bhatia 2016). The argument is tendered that provincial governments should embrace the Triple Aim in the absence of federal government leadership, noting that, by international standards, we are at best mediocre and, more realistically, fighting for the bottom in comparative, annual cross-country surveys. Ignoring federal government participation in Medicare and resorting solely to provincial leadership seems to make sense for the purposes of this discourse; but, it makes no sense at all if we are attempting to achieve high performance in Canada's non-system (Canada Health Action: Building on the Legacy 1997; Commission on the Future of Health Care in Canada 2002; Lewis 2015). As for enlisting provincial governments, we heartily agree. A great deal can be accomplished by the Council of the Federation of Canadian Premiers. But, the entire basis for this philosophy and the reference paper itself assumes a top-down approach to policy and practice. That is what we are trying to change in Alberta and we next discuss. Bottom-up clinically led change, driven by measurement and evidence, has to meet with the top-down approach being presented and widely practiced. While true for each category of financing, stewardship and resource generation, in no place is this truer than what is described and included in "health system stewardship." This commentary draws from Verma and Bhatia (2016) and demonstrates how Alberta, through the use of Strategic Clinical Networks (SCNs), is responding to the Triple Aim. We offer three examples of provincially scaled innovations, each representing one or more arms of the Triple Aim. PMID:27009587

  7. The "How" and "For Whom" of Program Effectiveness: Dissecting the "Responsive Classroom"[R] Approach in Relation to Academic Achievement

    ERIC Educational Resources Information Center

    Abry, Tashia; Rimm-Kaufman, Sara E.; Hulleman, Chris S.; Thomas, Julie; Ko, Michelle

    2012-01-01

    In the context of an experimental trial, the authors examined variability in treatment and control teachers' use of several "Responsive Classroom" (RC) practices to predict students' 4th grade academic achievement. Further, they examined the extent to which use of the "RC" practices is differentially important for subgroups of students. They…

  8. The Grasshopper and the Ant: Motivational Responses of Low-Achieving Students to High-Stakes Testing.

    ERIC Educational Resources Information Center

    Roderick, Melissa; Engel, Mimi

    2001-01-01

    Examined the responses of 102 low achieving sixth and eighth graders to Chicago's highly publicized efforts to end social promotion. Students generally described increased work efforts, and students with high levels of work effort generally had greater than average learning gains and positive outcomes in terms of promotion. About one-third of…

  9. Mothers' Expressive Style and Emotional Responses to Children's Behavior Predict Children's Prosocial and Achievement-Related Self-Ratings

    ERIC Educational Resources Information Center

    Dunsmore, Julie C.; Bradburn, Isabel S.; Costanzo, Philip R.; Fredrickson, Barbara L.

    2009-01-01

    In this study we investigated whether mothers' typical expressive style and specific emotional responses to children's behaviors are linked to children's prosocial and competence self-ratings. Eight- to 12-year-old children and their mothers rated how mothers had felt when children behaved prosocially and antisocially, achieved and failed to…

  10. Effects of Science Interest and Environmental Responsibility on Science Aspiration and Achievement: Gender Differences and Cultural Supports

    ERIC Educational Resources Information Center

    Chiu, Mei-Shiu

    2010-01-01

    The aim of the present study is twofold: (1) to investigate gender differences in the effects of science interest and environmental responsibility on science aspiration and achievement and (2) to explore the relations between cultural supports (macroeconomic and gender equality) and both boys' and girls' tendencies to integrate the aforementioned…

  11. Sex Offender Populations and Clinical Efficacy: A Response to Rosky.

    PubMed

    Jensen, Todd M; Shafer, Kevin; Roby, C Y; Roby, Jini L

    2016-06-01

    We provide a brief response to a commentary submitted by Rosky in which he questions the rationale and methodological merits of our original study about full-disclosure polygraph outcome differences between juvenile and adult sex offenders. At the heart of Rosky's substantive concerns is the premise that only research tying polygraphy outcomes to actual recidivism is useful or worthwhile. He also questions the overall utility and validity of polygraphy. We acknowledge and challenge these two points. Furthermore, many of the methodological concerns expressed by Rosky represent either a misunderstanding of our research question, study design, and sample, or a disregard for the explicit declarations we made with respect to our study limitations. Overall, it appears Rosky has accused us of not answering well a question we were not trying to ask. Our response addresses the key substantive and methodological concerns extended by Rosky and clarifies the actual aims and scope of our original study. We also argue that a calm, rational, and scientific discussion is the best approach to understanding how to improve clinical methods used in sex offender treatment. PMID:25670743

  12. Two Flavonolignans from Milk Thistle (Silybum marianum) Inhibit CYP2C9-Mediated Warfarin Metabolism at Clinically Achievable Concentrations

    PubMed Central

    Brantley, Scott J.; Oberlies, Nicholas H.; Kroll, David J.

    2010-01-01

    Milk thistle (Silybum marianum) is a popular herbal product used for hepatoprotection and chemoprevention. Two commercially available formulations are the crude extract, silymarin, and the semipurified product, silibinin. Silymarin consists of at least seven flavonolignans, of which the most prevalent are the diastereoisomers silybin A and silybin B; silibinin consists only of silybin A and silybin B. Based on a recent clinical study showing an interaction between a silymarin product and the CYP2C9 substrate losartan, the CYP2C9 inhibition properties of silybin A and silybin B and corresponding regioisomers, isosilybin A and isosilybin B, were evaluated using human liver microsomes (HLMs), recombinant CYP2C9 (rCYP2C9) enzymes, and the clinically relevant probe, (S)-warfarin. Silybin B was the most potent inhibitor in HLMs, followed by silybin A, isosilybin B, and isosilybin A (IC50 of 8.2, 18, 74, and >100 μM, respectively). Next, silybin A and silybin B were selected for further characterization. As with HLMs, silybin B was more potent than silybin A toward rCYP2C9*1 (6.7 versus 12 μM), rCYP2C9*2 (9.3 versus 19 μM), and rCYP2C9*3 (2.4 versus 9.3 μM). Using a matrix of five substrate (1–15 μM) and six inhibitor (1–80 μM) concentrations and HLMs, both diastereoisomers inhibited (S)-warfarin 7-hydroxylation in a manner described best by a mixed-type inhibition model (Ki values of 4.8 and 10 μM for silybin B and silybin A, respectively). These observations, combined with the high systemic silibinin concentrations (>5–75 μM) achieved in a phase I study involving prostate cancer patients, prompt clinical evaluation of a potential warfarin-milk thistle interaction. PMID:19934397

  13. Two flavonolignans from milk thistle (Silybum marianum) inhibit CYP2C9-mediated warfarin metabolism at clinically achievable concentrations.

    PubMed

    Brantley, Scott J; Oberlies, Nicholas H; Kroll, David J; Paine, Mary F

    2010-03-01

    Milk thistle (Silybum marianum) is a popular herbal product used for hepatoprotection and chemoprevention. Two commercially available formulations are the crude extract, silymarin, and the semipurified product, silibinin. Silymarin consists of at least seven flavonolignans, of which the most prevalent are the diastereoisomers silybin A and silybin B; silibinin consists only of silybin A and silybin B. Based on a recent clinical study showing an interaction between a silymarin product and the CYP2C9 substrate losartan, the CYP2C9 inhibition properties of silybin A and silybin B and corresponding regioisomers, isosilybin A and isosilybin B, were evaluated using human liver microsomes (HLMs), recombinant CYP2C9 (rCYP2C9) enzymes, and the clinically relevant probe, (S)-warfarin. Silybin B was the most potent inhibitor in HLMs, followed by silybin A, isosilybin B, and isosilybin A (IC(50) of 8.2, 18, 74, and >100 microM, respectively). Next, silybin A and silybin B were selected for further characterization. As with HLMs, silybin B was more potent than silybin A toward rCYP2C9 1 (6.7 versus 12 microM), rCYP2C9 2 (9.3 versus 19 microM), and rCYP2C9 3 (2.4 versus 9.3 microM). Using a matrix of five substrate (1-15 microM) and six inhibitor (1-80 microM) concentrations and HLMs, both diastereoisomers inhibited (S)-warfarin 7-hydroxylation in a manner described best by a mixed-type inhibition model (K(i) values of 4.8 and 10 microM for silybin B and silybin A, respectively). These observations, combined with the high systemic silibinin concentrations (>5-75 microM) achieved in a phase I study involving prostate cancer patients, prompt clinical evaluation of a potential warfarin-milk thistle interaction. PMID:19934397

  14. Steroid-responsive and nephrotic syndrome and allergy: clinical studies.

    PubMed Central

    Meadow, S R; Sarsfield, J K

    1981-01-01

    Eighty-four children with steroid-responsive nephrotic syndrome who had been shown to have, or were believed to have, minimal change histology were investigated to study the relationship between steroid-responsive nephrotic syndrome and allergy. They were found to have a greater incidence of the standard atopic disorders--asthma, eczema, recurrent urticaria, and hay fever. Their 1st-degree relatives had an increased incidence of these atopic disorders too. A nasal discharge was a frequent precursor or an accompaniment of nephrotic syndrome, but an overt atrophic disorder at the same time was rare. Such disorders, related to relapse, occurred in only 5 children; in none was it a consistent or recurrent happening at the time of each relapse. No example of pollen hypersensitivity nephrotic syndrome was found, and no particular allergen could be identified with certainty as responsible for a child's nephrotic syndrome. No association was found between the time of relapse and the season of the year, or the season in which the child was born. Children with nephrotic syndrome had a greater incidence of positive skin tests to common antigens, the comparative frequency of positive reactions to different antigens being similar to that found in children with asthma, although the total frequency was about half that of children with asthma. Despite the increased incidence of clinical features of atopy, measures to reduce the frequency of relapse of nephrotic syndrome by allergen avoidance, the use of sodium cromoglycate, and the use of a new oral antiallergic drug were unsuccessful. PMID:6791592

  15. Steroid-responsive and nephrotic syndrome and allergy: clinical studies.

    PubMed

    Meadow, S R; Sarsfield, J K

    1981-07-01

    Eighty-four children with steroid-responsive nephrotic syndrome who had been shown to have, or were believed to have, minimal change histology were investigated to study the relationship between steroid-responsive nephrotic syndrome and allergy. They were found to have a greater incidence of the standard atopic disorders--asthma, eczema, recurrent urticaria, and hay fever. Their 1st-degree relatives had an increased incidence of these atopic disorders too. A nasal discharge was a frequent precursor or an accompaniment of nephrotic syndrome, but an overt atrophic disorder at the same time was rare. Such disorders, related to relapse, occurred in only 5 children; in none was it a consistent or recurrent happening at the time of each relapse. No example of pollen hypersensitivity nephrotic syndrome was found, and no particular allergen could be identified with certainty as responsible for a child's nephrotic syndrome. No association was found between the time of relapse and the season of the year, or the season in which the child was born. Children with nephrotic syndrome had a greater incidence of positive skin tests to common antigens, the comparative frequency of positive reactions to different antigens being similar to that found in children with asthma, although the total frequency was about half that of children with asthma. Despite the increased incidence of clinical features of atopy, measures to reduce the frequency of relapse of nephrotic syndrome by allergen avoidance, the use of sodium cromoglycate, and the use of a new oral antiallergic drug were unsuccessful. PMID:6791592

  16. Who Is to Blame? Students, Teachers and Parents Views on Who Is Responsible for Student Achievement

    ERIC Educational Resources Information Center

    Peterson, Elizabeth R.; Rubie-Davies, Christine M.; Elley-Brown, Margaret J.; Widdowson, Deborah A.; Dixon, Robyn S.; Irving, Earl S.

    2011-01-01

    This research investigates who students, parents and teachers believe is responsible for student learning. Thirteen focus groups were conducted with Year 9 and 10 students, and parents and teachers from three diverse New Zealand secondary schools. Differences were found with respect to whom the three stakeholders thought were responsible for…

  17. Response to Intervention and Its Effects on Achievement of Students Who Live in Poverty

    ERIC Educational Resources Information Center

    Guerin, Kimberly A.

    2013-01-01

    The gap in achievement between students from different socioeconomic backgrounds continues to challenge educators. As schools with high poverty populations continue to struggle, many disadvantaged students are subsequently referred for special education services. Educators today are faced with the problem of disproportionality, an over…

  18. Response to Comment on "Math at home adds up to achievement in school".

    PubMed

    Berkowitz, Talia; Schaeffer, Marjorie W; Rozek, Christopher S; Maloney, Erin A; Levine, Susan C; Beilock, Sian L

    2016-03-11

    Frank presents an alternative interpretation of our data, yet reports largely similar results to those in our original Report. A critical difference centers on how to interpret and test interaction effects. Frank finds no mistakes in our analyses. We stand by our original conclusions of meaningful effects of the Bedtime Learning Together (BLT) math app on children's math achievement. PMID:26965620

  19. Friends' Responses to Children's Disclosure of an Achievement-Related Success: An Observational Study

    ERIC Educational Resources Information Center

    Altermatt, Ellen Rydell; Ivers, Ivy E.

    2011-01-01

    This study examined social support processes in the context of positive events. The conversations of fourth-grade through sixth-grade focal children and their friends (N = 116) were observed after focal children outperformed their friend on an achievement-related task. Changes in focal children's performance-related positive affect from…

  20. The Role of Temperament in Children's Affective and Behavioral Responses in Achievement Situations

    ERIC Educational Resources Information Center

    Hirvonen, Riikka; Aunola, Kaisa; Alatupa, Saija; Viljaranta, Jaana; Nurmi, Jari-Erik

    2013-01-01

    Although students' affects and behaviors in achievement situations have been shown to be influenced by their previous learning experiences, less is known about how they relate to students' dispositional characteristics, such as temperament. This study examined to what extent children's temperament is related to their affective and behavioral…

  1. Performance Concern, Contingent Self-Worth, and Responses to Repeated Achievement Failure in Second Graders

    ERIC Educational Resources Information Center

    Smiley, Patricia A.; Coulson, Sheri L.; Greene, Joelle K.; Bono, Katherine L.

    2010-01-01

    Individual differences in emotion, cognitions, and task choice following achievement failure are found among four- to seven-year-olds. However, neither performance deterioration during failure nor generalization after failure--aspects of the helpless pattern in 10-year-olds--have been reliably demonstrated in this age group. In the present study,…

  2. Collective Responsibility, Academic Optimism, and Student Achievement in Taiwan Elementary Schools

    ERIC Educational Resources Information Center

    Wu, Hsin-Chieh

    2012-01-01

    Previous research indicates that collective efficacy, faculty trust in students and parents, and academic emphasis together formed a single latent school construct, called academic optimism. In the U.S., academic optimism has been proven to be a powerful construct that could effectively predict student achievement even after controlling for…

  3. Multilevel Item Response Modeling: Applications to Large-Scale Assessment of Academic Achievement

    ERIC Educational Resources Information Center

    Zheng, Xiaohui

    2009-01-01

    The call for standards-based reform and educational accountability has led to increased attention to large-scale assessments. Over the past two decades, large-scale assessments have been providing policymakers and educators with timely information about student learning and achievement to facilitate their decisions regarding schools, teachers and…

  4. A Model for Incorporating Response-Time Data in Scoring Achievement Tests. Research Report No. 3.

    ERIC Educational Resources Information Center

    Tatsuoka, Kikumi; Tatsuoka, Maurice

    The differences in types of information-processing skills developed by different instructional backgrounds affect, negatively or positively, the learning of further advanced instructional materials. If prior and subsequent instructional methods are different, a proactive inhibition effect produces low achievement scores on a post test. This poses…

  5. Clinical and molecular response to interferon-α therapy in essential thrombocythemia patients with CALR mutations.

    PubMed

    Verger, Emmanuelle; Cassinat, Bruno; Chauveau, Aurélie; Dosquet, Christine; Giraudier, Stephane; Schlageter, Marie-Hélène; Ianotto, Jean-Christophe; Yassin, Mohammed A; Al-Dewik, Nader; Carillo, Serge; Legouffe, Eric; Ugo, Valerie; Chomienne, Christine; Kiladjian, Jean-Jacques

    2015-12-10

    Myeloproliferative neoplasms are clonal disorders characterized by the presence of several gene mutations associated with particular hematologic parameters, clinical evolution, and prognosis. Few therapeutic options are available, among which interferon α (IFNα) presents interesting properties like the ability to induce hematologic responses (HRs) and molecular responses (MRs) in patients with JAK2 mutation. We report on the response to IFNα therapy in a cohort of 31 essential thrombocythemia (ET) patients with CALR mutations (mean follow-up of 11.8 years). HR was achieved in all patients. Median CALR mutant allelic burden (%CALR) significantly decreased from 41% at baseline to 26% after treatment, and 2 patients even achieved complete MR. In contrast, %CALR was not significantly modified in ET patients treated with hydroxyurea or aspirin only. Next-generation sequencing identified additional mutations in 6 patients (affecting TET2, ASXL1, IDH2, and TP53 genes). The presence of additional mutations was associated with poorer MR on CALR mutant clones, with only minor or no MRs in this subset of patients. Analysis of the evolution of the different variant allele frequencies showed that the mutated clones had a differential sensitivity to IFNα in a given patient, but no new mutation emerged during treatment. In all, this study shows that IFNα induces high rates of HRs and MRs in CALR-mutated ET, and that the presence of additional nondriver mutations may influence the MR to therapy. PMID:26486786

  6. Modeling HIV Immune Response and Validation with Clinical Data

    PubMed Central

    Banks, H. T.; Davidian, M.; Hu, Shuhua; Kepler, Grace M.; Rosenberg, E.S.

    2009-01-01

    A system of ordinary differential equations is formulated to describe the pathogenesis of HIV infection, wherein certain features that have been shown to be important by recent experimental research are incorporated in the model. These include the role of CD4+ memory cells that serve as a major reservoir of latently infected cells, a critical role for T-helper cells in the generation of CD8 memory cells capable of efficient recall response, and stimulation by antigens other than HIV. A stability analysis illustrates the capability of this model in admitting multiple locally asymptotically stable (locally a.s.) off-treatment equilibria. We show that this more biologically-detailed model can exhibit the phenomenon of transient viremia experienced by some patients on therapy with viral load levels suppressed below the detection limit. We also show that the loss of CD4+ T-cell help in the generation of CD8+ memory cells leads to larger peak values for the viral load during transient viremia. Censored clinical data is used to obtain parameter estimates. We demonstrate that using a reduced set of 16 free parameters, obtained by fixing some parameters at their population averages, the model provides reasonable fits to the patient data and, moreover, that it exhibits good predictive capability. We further show that parameter values obtained for most clinical patients do not admit multiple locally a.s off-treatment equilibria. This suggests that treatment to move from a high viral load equilibrium state to an equilibrium state with a lower (or zero) viral load is not possible for these patients. PMID:19495424

  7. Responses of blind fish to gravitational changes as achieved in parabolic flight

    NASA Technical Reports Server (NTRS)

    Vonbaumgarten, R. J.; Shillinger, G. L., Jr.; Baldright, G.

    1972-01-01

    Blind fish, during parabolic flight, display a measurable and consistent behavior. The most spectacular new behavioral response is the forward looping of blind fish in or near weightlessness. This response shows no measurable adaptation during the entire period of weightlessness of about 30 sec. During the entrance and exit of weightless parabolas (pushover and pullout) respectively, the fish assumes a forward tilted diving position. Parabolic flight with negative g in the range between 0g and -1g causes similar diving responses of the fish with the only difference being that the dive is directed toward the top of the fish tank. When the response to a g value less than 1g is compared to the response to increased g load on the ground (escape of darting response) an essential difference is seen: higher horizontal acceleration or jerk on the ground causes fish to swim, or even dart, against the direction of inertial force; fish during weightless parabolas move into the direction of the inertial or gravitational force. Since the vestibular system of fish is homologous to that of man, the observed behavior of fish in weightless flight could help to better understand human performance and sensations in comparable situations.

  8. Achievement of controlled resistive response of nanogapped palladium film to hydrogen

    SciTech Connect

    Zhao, M.; Wong, M. H.; Ong, C. W.

    2015-07-20

    Palladium (Pd) film containing nanogaps of well controlled dimension was fabricated on a Si wafer having a high-aspect-ratio micropillar. The Pd film was arranged to experience hydrogen (H{sub 2})-induced volume expansion. (i) If the nanogap is kept open, its width is narrowed down. A discharge current was generated to give a strong, fast, and repeatable on-off type resistive switching response. (ii) If the nanogap is closed, the cross section of the conduction path varies to give continuous H{sub 2}-concentration dependent resistive response. The influence of stresses and related physical mechanisms are discussed.

  9. Accreditation Stimuli and Evaluation Responses in a Clinical Training Program.

    ERIC Educational Resources Information Center

    Wood, David; And Others

    Assessment and evaluation skills are significant goals of clinical training, yet many clinical and counseling students lack personal experiences with applied program evaluation. Clinical psychology graduate students responded to successive impending accreditation visits by conducting in-house evaluations. Students in 1977 (N=38) and 1980 (N=35)…

  10. Work and Family Responsibilities: Achieving a Balance. A Program Paper of the Ford Foundation.

    ERIC Educational Resources Information Center

    Ford Foundation, New York, NY.

    The relationship between work and family is an issue of growing concern in the United States. The increasing participation of women in the labor force has created new demands for services, especially for low-income families, to offset women's dual responsibilities at work and home. This paper describes a Ford Foundation program to study the place…

  11. Academic Optimism and Collective Responsibility: An Organizational Model of the Dynamics of Student Achievement

    ERIC Educational Resources Information Center

    Wu, Jason H.

    2013-01-01

    This study was designed to examine the construct of academic optimism and its relationship with collective responsibility in a sample of Taiwan elementary schools. The construct of academic optimism was tested using confirmatory factor analysis, and the whole structural model was tested with a structural equation modeling analysis. The data were…

  12. The Reading Response E-Journal: An Alternative Way to Engage Low-Achieving EFL Students

    ERIC Educational Resources Information Center

    Lee, Hsiao-Chien

    2013-01-01

    The reading response journal has been valued as an effective tool for involving students in authentic reading and writing activities. As the internet has become an essential medium in today's English classroom, it is advisable to integrate both the web and the journal when approaching our EFL students. In order to motivate and engage my…

  13. Effectiveness of Student Response Systems in Terms of Learning Environment, Attitudes and Achievement

    ERIC Educational Resources Information Center

    Cohn, Stephen T.; Fraser, Barry J.

    2016-01-01

    In order to investigate the effectiveness of using Student Response Systems (SRS) among grade 7 and 8 science students in New York, the How Do You Feel About This Class? (HDYFATC) questionnaire was administered to 1097 students (532 students did use SRS and 565 students who did not use SRS). Data analyses attested to the sound factorial validity…

  14. VSL#3 induces and maintains short-term clinical response in patients with active microscopic colitis: a two-phase randomised clinical trial

    PubMed Central

    Rohatgi, Sarika; Ahuja, Vineet; Makharia, Govind K; Rai, Tarun; Das, Prasenjit; Dattagupta, Siddharth; Mishra, Veena; Garg, Sushil Kumar

    2015-01-01

    Background The probiotic mixture VSL#3 has proven efficacious in inflammatory bowel diseases and irritable bowel syndrome; however, its efficacy in microscopic colitis (MC) is being investigated. Objective To evaluate the safety and efficacy of a multistrain probiotic, VSL#3, in inducing clinical remission and achieving clinical response, as compared with mesalamine, in patients with active MC. Methods A randomised, open labelled study comparing the efficacy of 900 billion colony-forming units/day of VSL#3 (group (Gp) A) or 1.6 g of mesalamine/day (Gp B) for 8 weeks in 30 patients with MC was conducted. After a washout period of 2 weeks, Gp B received 8 weeks of VSL#3 and Gp A was off medication for the next 8 weeks. The primary end points were clinical remission and clinical response at 8 weeks. Results Of 30 patients, 15 were randomised in each arm. 11 patients in Gp A and 13 patients in Gp B completed 8 weeks of treatment. 5 (46%) of 11 patients in Gp A and 1 (8%) of 13 patients in Gp B attained clinical remission (p=0.022). Clinical response was seen in Gp A, as evidenced by a lower stool weight (377.6±104.5 g) as compared with Gp B (507±168.2 g; p=0.03). VSL#3 was effective in maintaining clinical response up to 10 weeks, even after discontinuation of therapy. Secondary end points like stool parameters, histology and well-being improved in both treatment groups. Conclusions The probiotic VSL#3 was found to offer the benefit of inducing as well as maintaining short-term clinical response in patients with active MC. Trial registration number The clinical trial is registered with CLINICAL TRIAL REGISTRY INDIA; http://ctri.nic.in, CTRI No. “CTRI/2008/091/000086” (registered on: 23/06/2008). PMID:26462271

  15. Science, technology, and innovation: nursing responsibilities in clinical research.

    PubMed

    Grady, Christine; Edgerly, Maureen

    2009-12-01

    Clinical research is a systematic investigation of human biology, health, or illness involving human beings. It builds on laboratory and animal studies and often involves clinical trials, which are specifically designed to test the safety and efficacy of interventions in humans. Nurses are critical to the conduct of ethical clinical research and face clinical, ethical, and regulatory challenges in research in many diverse roles. Understanding and addressing the ethical challenges that complicate clinical research is integral to upholding the moral commitment that nurses make to patients, including protecting their rights and ensuring their safety as patients and as research participants. PMID:19850183

  16. Postmastectomy Radiation Improves the Outcome of Patients With Locally Advanced Breast Cancer Who Achieve a Pathologic Complete Response to Neoadjuvant Chemotherapy

    SciTech Connect

    McGuire, Sean E.; Gonzalez-Angulo, Ana M.; Huang, Eugene H.; Tucker, Susan L.; Kau, S.-W.C.; Yu, T.-K.; Strom, Eric A.; Oh, Julia L.; Woodward, Wendy A.; Tereffe, Welela; Hunt, Kelly K.; Kuerer, Henry M.; Sahin, Aysegul A.; Hortobagyi, Gabriel N.; Buchholz, Thomas A. . E-mail: tbuchhol@mdanderson.org

    2007-07-15

    Purpose: The aim of this study was to investigate the role of postmastectomy radiation therapy in women with breast cancer who achieved a pathologic complete response (pCR) to neoadjuvant chemotherapy. Methods and Materials: We retrospectively identified 226 patients treated at our institution who achieved a pCR at surgery after receiving neoadjuvant chemotherapy. Of these, the 106 patients without inflammatory breast cancer who were treated with mastectomy were analyzed. The patients' clinical stages at diagnosis were I in 2%, II in 31%, IIIA in 30%, IIIB in 25%, and IIIC in 11% (American Joint Committee on Cancer 2003 system). Of the patients, 92% received anthracycline-based chemotherapy, and 38% also received a taxane. A total of 72 patients received postmastectomy radiation therapy, and 34 did not. The actuarial rates of local-regional recurrence (LRR) and survival of the two groups were compared using the log-rank test. Results: The median follow-up of surviving patients was 62 months. Use of radiation therapy did not affect the 10-year rates of LRR for patients with Stage I or II disease (the 10-year LRR rates were 0% for both groups). However, the 10-year LRR rate for patients with Stage III disease was significantly improved with radiation therapy (7.3% {+-} 3.5% with vs. 33.3% {+-} 15.7% without; p 0.040). Within this cohort, use of radiation therapy was also associated with improved disease-specific and overall survival. Conclusion: Postmastectomy radiation therapy provides a significant clinical benefit for breast cancer patients who present with clinical Stage III disease and achieve a pCR after neoadjuvant chemothearpy.

  17. Petit receives Robert C. Cowen Award for Sustained Achievement in Science Journalism: Response

    NASA Astrophysics Data System (ADS)

    Petit, Charles W.

    2012-01-01

    Charles W. Petit, a veteran science writer, received the 2011 Robert C. Cowan Award for Sustained Achievement in Science Journalism at the AGU Fall Meeting Honors Ceremony, held on 7 December 2011 in San Francisco, Calif. Petit covered earthquakes for the San Francisco Chronicle during the 1980s and 1990s and has recently served as "head tracker" for the Knight Science Journalism Tracker, a Massachusetts Institute of Technology-based daily blog that compiles and critiques science reporting worldwide. Petit was previously honored by AGU in 2003 when he received the David Perlman Award for an article about a new finding in oceanography. The Cowan Award, named for a former science editor of the Christian Science Monitor, is given no more than every 2 years and recognizes a journalist who has made "significant, lasting, and consistent contributions to accurate reporting or writing" on the Earth and space sciences for the general public.

  18. The medical ethos and social responsibility in clinical medicine.

    PubMed Central

    Francis, C. K.

    2001-01-01

    The medical profession will face many challenges in the new millennium. As medicine looks forward to advances in molecular genetics and the prospect of unprecedented understanding of the causes and cures of human disease, clinicians, scientists and bioethicists may benefit from reflection upon the origins of the medical ethos and its relevance to postmodern medicine. Past distortions of the medical ethos, such as Nazism and the Tuskegee Syphilis Study, as well as more recent experience with the ethical challenges of employer-based market driven managed care, provide important lessons as medicine contemplates the future. Racial and ethnic disparities in health status and access to care serve as a reminders that the racial doctrines that fostered the horrors of the Holocaust and the Tuskegee Syphilis Study have not been completely removed from contemporary thinking. Inequalities in health status based on race and ethnicity, as well as socioeconomic status, attest to the inescapable reality of racism in America. When viewed against a background of historical distortions and disregard for the traditional tenets of the medical ethos, persistent racial and ethnic disparities and health and the prospect of genetic engineering raise the specter of discrimination because of genotype, a postmodern version of "racist medicine" or of a "new eugenics." There is a need to balance medicine's devotion to the wellbeing of the patient and the primacy of the patient-physician relationship against with the need to meet the health care needs of society. The challenge facing the medical profession in the new millennium is to establish an equilibrium between the responsibility to assure quality health care for the individual patient while affecting societal changes to achieve "health for all." PMID:11405593

  19. Integrative Analysis of Epigenetic Modulation in Melanoma Cell Response to Decitabine: Clinical Implications

    PubMed Central

    Halaban, Ruth; Krauthammer, Michael; Pelizzola, Mattia; Cheng, Elaine; Kovacs, Daniela; Sznol, Mario; Ariyan, Stephan; Narayan, Deepak; Bacchiocchi, Antonella; Molinaro, Annette; Kluger, Yuval; Deng, Min; Tran, Nam; Zhang, Wengeng; Picardo, Mauro; Enghild, Jan J.

    2009-01-01

    Decitabine, an epigenetic modifier that reactivates genes otherwise suppressed by DNA promoter methylation, is effective for some, but not all cancer patients, especially those with solid tumors. It is commonly recognized that to overcome resistance and improve outcome, treatment should be guided by tumor biology, which includes genotype, epigenotype, and gene expression profile. We therefore took an integrative approach to better understand melanoma cell response to clinically relevant dose of decitabine and identify complementary targets for combined therapy. We employed eight different melanoma cell strains, determined their growth, apoptotic and DNA damage responses to increasing doses of decitabine, and chose a low, clinically relevant drug dose to perform whole-genome differential gene expression, bioinformatic analysis, and protein validation studies. The data ruled out the DNA damage response, demonstrated the involvement of p21Cip1 in a p53-independent manner, identified the TGFβ pathway genes CLU and TGFBI as markers of sensitivity to decitabine and revealed an effect on histone modification as part of decitabine-induced gene expression. Mutation analysis and knockdown by siRNA implicated activated β-catenin/MITF, but not BRAF, NRAS or PTEN mutations as a source for resistance. The importance of protein stability predicted from the results was validated by the synergistic effect of Bortezomib, a proteasome inhibitor, in enhancing the growth arrest of decitabine in otherwise resistant melanoma cells. Our integrative analysis show that improved therapy can be achieved by comprehensive analysis of cancer cells, identified biomarkers for patient's selection and monitoring response, as well as targets for improved combination therapy. PMID:19234609

  20. Selective inhibition of a multicomponent response can be achieved without cost.

    PubMed

    Xu, Jing; Westrick, Zachary; Ivry, Richard B

    2015-01-15

    Behavioral flexibility frequently requires the ability to modify an on-going action. In some situations, optimal performance requires modifying some components of an on-going action without interrupting other components of that action. This form of control has been studied with the selective stop-signal task, in which participants are instructed to abort only one movement of a multicomponent response. Previous studies have shown a transient disruption of the nonaborted component, suggesting limitations in our ability to use selective inhibition. This cost has been attributed to a structural limitation associated with the recruitment of a cortico-basal ganglia pathway that allows for the rapid inhibition of action but operates in a relatively generic manner. Using a model-based approach, we demonstrate that, with a modest amount of training and highly compatible stimulus-response mappings, people can perform a selective-stop task without any cost on the nonaborted component. Prior reports of behavioral costs in selective-stop tasks reflect, at least in part, a sampling bias in the method commonly used to estimate such costs. These results suggest that inhibition can be selectively controlled and present a challenge for models of inhibitory control that posit the operation of generic processes. PMID:25339712

  1. X-linked Acrogigantism (X-LAG) Syndrome: Clinical Profile and Therapeutic Responses

    PubMed Central

    Beckers, Albert; Lodish, Maya Beth; Trivellin, Giampaolo; Rostomyan, Liliya; Lee, Misu; Faucz, Fabio R; Yuan, Bo; Choong, Catherine S; Caberg, Jean-Hubert; Verrua, Elisa; Naves, Luciana Ansaneli; Cheetham, Tim D; Young, Jacques; Lysy, Philippe A; Petrossians, Patrick; Cotterill, Andrew; Shah, Nalini Samir; Metzger, Daniel; Castermans, Emilie; Ambrosio, Maria Rosaria; Villa, Chiara; Strebkova, Natalia; Mazerkina, Nadia; Gaillard, Stéphan; Barra, Gustavo Barcelos; Casulari, Luis Augusto; Neggers, Sebastian J.; Salvatori, Roberto; Jaffrain-Rea, Marie-Lise; Zacharin, Margaret; Santamaria, Beatriz Lecumberri; Zacharieva, Sabina; Lim, Ee Mun; Mantovani, Giovanna; Zatelli, Maria Chaira; Collins, Michael T; Bonneville, Jean-François; Quezado, Martha; Chittiboina, Prashant; Oldfield, Edward H.; Bours, Vincent; Liu, Pengfei; De Herder, Wouter; Pellegata, Natalia; Lupski, James R.; Daly, Adrian F.; Stratakis, Constantine A.

    2015-01-01

    X-linked acro-gigantism (X-LAG) is a new syndrome of pituitary gigantism, caused by microduplications on chromosome Xq26.3, encompassing the gene GPR101, which is highly upregulated in pituitary tumors. We conducted this study to explore the clinical, radiological and hormonal phenotype and responses to therapy in patients with X-LAG syndrome. The study included 18 patients (13 sporadic) with X-LAG and a microduplication in chromosome Xq26.3. All sporadic cases had unique duplications and the inheritance pattern in 2 families was dominant with all Xq26.3 duplication carriers being affected. Patients began to grow rapidly as early as 2–3 months of age (median 12 months). At diagnosis (median delay 27 months), patients had a median height and weight SDS score of >+3.9 SDS. Apart from the increased overall body size, the children had acromegalic symptoms including acral enlargement and facial coarsening. More than a third of cases had increased appetite. Patients had marked hypersecretion of GH/IGF-1 and prolactin, usually due to a pituitary macroadenoma or hyperplasia. Primary neurosurgical control was achieved with extensive anterior pituitary resection but postoperative hypopituitarism was frequent. Control with somatostatin analogs was not readily achieved despite moderate to high somatostatin receptor subtype-2 expression in tumor tissue. Postoperative adjuvant pegvisomant achieved control of IGF-1 all 5 cases in which it was employed. X-LAG is a new infant-onset gigantism syndrome that has a severe clinical phenotype leading to challenging disease management. PMID:25712922

  2. Early treatment response predicted subsequent clinical response in patients with schizophrenia taking paliperidone extended-release.

    PubMed

    Yeh, En-Chi; Huang, Ming-Chyi; Tsai, Chang-Jer; Chen, Chun-Tse; Chen, Kuan-Yu; Chiu, Chih-Chiang

    2015-11-30

    This 6-week open-labeled study investigated whether early treatment response in patients receiving paliperidone extended-release (paliperidone ER) can facilitate prediction of responses at Week 6. Patients with schizophrenia or schizoaffective disorder were administered 9mg/day of paliperidone ER during the first 2 weeks, after which the dose was adjusted clinically. They were assessed on Days 0, 4, 7, 14, 28, and 42 by the Positive and Negative Syndrome Scale (PANSS). The serum concentrations of 9-hydroxyrisperidone were examined on Days 14 and 42. Among the 41 patients enrolled, 26 were classified as responders (≧50% improvement on total PANSS scores at Week 6). In the receiver-operator curves (ROC) analyses, the changes in total PANSS scores at Week 2 appeared to show more accurate predictability compared to Day 4 and Day 7. At Week 6, no significant correlation was observed between blood 9-hydroxyrisperidone concentration and the total score or changes of PANSS scores. The results suggest that early treatment response to paliperidone ER, particularly at Week 2, can serve as a suitable outcome predictor at Week 6. Using 9mg/day paliperidone ER as an initial dose for schizophrenia treatment exhibited relatively favorable tolerability and feasibility. PMID:26319696

  3. Application and Refinement of a Method to Achieve Uniform Convective Response on Variable-Resolution Meshes

    NASA Astrophysics Data System (ADS)

    Walko, R. L.; Medvigy, D.; Avissar, R.

    2013-12-01

    Variable-resolution computational grids can substantially improve the benefit-to-cost ratio in many environmental modeling applications, but they can also introduce unwanted and unrealistic numerical anomalies if not properly utilized. For example, we showed in previous studies that resolved (non-parameterized) atmospheric convection develops more quickly as resolution increases. Furthermore, on variable grids that transition from resolved to parameterized convection, timing and intensity of the convection in both regimes is generally disparate unless special care is taken to tune the parameterization. In both cases, the convection that develops first (due to purely numerical reasons) tends to suppress convection elsewhere by inducing subsidence in the surrounding environment. This highly nonlinear competition, while desirable when induced by natural causes such as surface inhomogeneity, is highly undesirable when it is a numerical artifact of variable grid resolution and/or selective application of convective parameterization. Our current research is aimed at leveling the playing field for convection across a variable resolution grid so that the above problems are avoided. The underlying idea is to apply the same or very similar 'convective machinery' to all areas of the grid. For convection-resolving regions of the grid, this machinery is simply the model grid itself, along with explicit representation of dynamics and a bulk microphysics parameterization. For coarser regions of the grid, the local environment is sampled from one or more grid columns (depending on local resolution) and fed to a separate 'convective processor', which determines the convective response to that environment and feeds the result back to the host grid. The convective processor chooses to either (1) explicitly resolve convective activity in the given environment on a separate (independent) limited-area 3D computational grid of comparable resolution to the convection-resolving part of the

  4. Achieving standardized medication data in clinical research studies: two approaches and applications for implementing RxNorm.

    PubMed

    Richesson, Rachel L; Smith, Susan B; Malloy, Jamie; Krischer, Jeffrey P

    2010-08-01

    The National Institutes of Health has proposed a roadmap for clinical research. Test projects of this roadmap include centralized data management for distributed research, the harmonization of clinical and research data, and the use of data standards throughout the research process. In 2003, RxNorm was named as a standard for codifying clinical drugs. Clinical researchers looking to implement RxNorm have few template implementation plans. Epidemiological studies and clinical trials (types of clinical research) have different requirements for model standards and best implementation tools. This paper highlights two different (epidemiological and intervention) clinical research projects, their unique requirements for a medication standard, the suitability of RxNorm as a standard for each, and application and process requirements for implementation. It is hoped that our experience of selecting and implementing the RxNorm standard to address varying study requirements in both domestic and international settings will be of value to other efforts. PMID:20703919

  5. Achieving high quality long-term care for elderly people: consumers' wishes and providers' responsibilities.

    PubMed

    Morse, R; Jenkinson, D

    1995-01-01

    The organisation of long-term care for older people has major implications for all hospital and community health services. However, even health professionals have a poor understanding of the structure and purpose of long-term care and national professional bodies are still not giving enough attention to the issues involved. In the wider context, care of disabled older people has received little public debate in the UK despite the ethical, social, and financial issues involved and despite the recent major organisational changes in the health service. The past ten years have seen a huge expansion in private residential and nursing homes with a concomitant fall in NHS long-stay beds. Currently, approximately 500,000 elderly people in the UK are living in some form of long-stay care facility, and many other elderly people with multiple disabilities are being supported at home and should also be included under the umbrella of long-term care. Ensuring appropriate, equitable, and high-quality care is a responsibility not only for health and social services but also for society as a whole. This conference, organised jointly by the Royal College of Physicians, the British Geriatrics Society, and Age Concern England, with support from the Department of Health, was a much-needed and welcomed initiative. Over 200 delegates attended, consisting of doctors (geriatricians, psychiatrists, general practitioners), nurses (public and private sector), social services representatives, Department of Health representatives, managers of nursing homes, and members of charities such as Age Concern and the Relatives Association. PMID:7658422

  6. Empirically and Clinically Useful Decision Making in Psychotherapy: Differential Predictions with Treatment Response Models

    ERIC Educational Resources Information Center

    Lutz, Wolfgang; Saunders, Stephen M.; Leon, Scott C.; Martinovich, Zoran; Kosfelder, Joachim; Schulte, Dietmar; Grawe, Klaus; Tholen, Sven

    2006-01-01

    In the delivery of clinical services, outcomes monitoring (i.e., repeated assessments of a patient's response to treatment) can be used to support clinical decision making (i.e., recurrent revisions of outcome expectations on the basis of that response). Outcomes monitoring can be particularly useful in the context of established practice research…

  7. Alopecia of myxedema: clinical response to levothyroxine sodium.

    PubMed

    Signore, R J; von Weiss, J

    1991-11-01

    Noncicatricial alopecia resulting from myxedema developed in a 58-year-old woman. We report the response of her alopecia to treatment with levothyroxine sodium and review the literature on the subject. PMID:1761768

  8. High-throughput screening using patient-derived tumor xenografts to predict clinical trial drug response.

    PubMed

    Gao, Hui; Korn, Joshua M; Ferretti, Stéphane; Monahan, John E; Wang, Youzhen; Singh, Mallika; Zhang, Chao; Schnell, Christian; Yang, Guizhi; Zhang, Yun; Balbin, O Alejandro; Barbe, Stéphanie; Cai, Hongbo; Casey, Fergal; Chatterjee, Susmita; Chiang, Derek Y; Chuai, Shannon; Cogan, Shawn M; Collins, Scott D; Dammassa, Ernesta; Ebel, Nicolas; Embry, Millicent; Green, John; Kauffmann, Audrey; Kowal, Colleen; Leary, Rebecca J; Lehar, Joseph; Liang, Ying; Loo, Alice; Lorenzana, Edward; Robert McDonald, E; McLaughlin, Margaret E; Merkin, Jason; Meyer, Ronald; Naylor, Tara L; Patawaran, Montesa; Reddy, Anupama; Röelli, Claudia; Ruddy, David A; Salangsang, Fernando; Santacroce, Francesca; Singh, Angad P; Tang, Yan; Tinetto, Walter; Tobler, Sonja; Velazquez, Roberto; Venkatesan, Kavitha; Von Arx, Fabian; Wang, Hui Qin; Wang, Zongyao; Wiesmann, Marion; Wyss, Daniel; Xu, Fiona; Bitter, Hans; Atadja, Peter; Lees, Emma; Hofmann, Francesco; Li, En; Keen, Nicholas; Cozens, Robert; Jensen, Michael Rugaard; Pryer, Nancy K; Williams, Juliet A; Sellers, William R

    2015-11-01

    Profiling candidate therapeutics with limited cancer models during preclinical development hinders predictions of clinical efficacy and identifying factors that underlie heterogeneous patient responses for patient-selection strategies. We established ∼1,000 patient-derived tumor xenograft models (PDXs) with a diverse set of driver mutations. With these PDXs, we performed in vivo compound screens using a 1 × 1 × 1 experimental design (PDX clinical trial or PCT) to assess the population responses to 62 treatments across six indications. We demonstrate both the reproducibility and the clinical translatability of this approach by identifying associations between a genotype and drug response, and established mechanisms of resistance. In addition, our results suggest that PCTs may represent a more accurate approach than cell line models for assessing the clinical potential of some therapeutic modalities. We therefore propose that this experimental paradigm could potentially improve preclinical evaluation of treatment modalities and enhance our ability to predict clinical trial responses. PMID:26479923

  9. Is Radiotherapy an Option for Early Breast Cancers With Complete Clinical Response After Neoadjuvant Chemotherapy?

    SciTech Connect

    Daveau, Caroline; Savignoni, Alexia; Abrous-Anane, Soumya; Pierga, Jean-Yves; Reyal, Fabien; Gautier, Chantal; Kirova, Youlia M.; Dendale, Remi; Campana, Francois; Fourquet, Alain; Bollet, Marc A.

    2011-04-01

    Purpose: To determine whether the exclusive use of radiotherapy (ERT) could be a treatment option after complete clinical response (cCR) to neoadjuvant chemotherapy (NCT) for early breast cancer (EBC). Methods and Materials: Between 1985 and 1999, 1,477 patients received NCT for EBC considered too large for primary conservative surgery. Of 165 patients with cCR, 65 patients were treated with breast surgery (with radiotherapy) and 100 patients were treated with ERT. Results: The two groups were comparable in terms of baseline characteristics, except for larger initial tumor sizes in the ERT group. There were no significant differences in overall, disease-free and metastasis-free survival rates. Five-year and 10-year overall survival rates were 91% and 77% in the no-surgery group and 82% and 79% in the surgery group, respectively (p = 0.9). However, a nonsignificant trend toward higher locoregional recurrence rates (LRR) was observed in the no-surgery group (31% vs. 17% at 10 years; p = 0.06). In patients with complete responses on mammography and/or ultrasound, LRR were not significantly different (p = 0.45, 10-year LRR: 21% in surgery vs. 26% in ERT). No significant differences were observed in terms of the rate of cutaneous, cardiac, or pulmonary toxicities. Conclusions: Surgery is a key component of locoregional treatment for breast cancers that achieved cCR to NCT.

  10. Clinical utility and validity of minoxidil response testing in androgenetic alopecia.

    PubMed

    Goren, Andy; Shapiro, Jerry; Roberts, Janet; McCoy, John; Desai, Nisha; Zarrab, Zoulikha; Pietrzak, Aldona; Lotti, Torello

    2015-01-01

    Clinical response to 5% topical minoxidil for the treatment of androgenetic alopecia (AGA) is typically observed after 3-6 months. Approximately 40% of patients will regrow hair. Given the prolonged treatment time required to elicit a response, a diagnostic test for ruling out nonresponders would have significant clinical utility. Two studies have previously reported that sulfotransferase enzyme activity in plucked hair follicles predicts a patient's response to topical minoxidil therapy. The aim of this study was to assess the clinical utility and validity of minoxidil response testing. In this communication, the present authors conducted an analysis of completed and ongoing studies of minoxidil response testing. The analysis confirmed the clinical utility of a sulfotransferase enzyme test in successfully ruling out 95.9% of nonresponders to topical minoxidil for the treatment of AGA. PMID:25112173

  11. A method for achieving monotonic frequency-temperature response for langasite surface-acoustic-wave high-temperature sensor

    NASA Astrophysics Data System (ADS)

    Shaoming, Bao; Yabing, Ke; Yanqing, Zheng; Lina, Cheng; Honglang, Li

    2016-02-01

    To achieve the monotonic frequency-temperature response for a high-temperature langasite (LGS) surface-acoustic-wave (SAW) sensor in a wide temperature range, a method utilizing two substrate cuts with different propagation angles on the same substrate plane was proposed. In this method, the theory of effective permittivity is adopted to calculate the temperature coefficients of frequency (TCF), electromechanical coupling coefficients (k2), and power flow angle (PFA) for different propagation angles on the same substrate plane, and then the two substrate cuts were chosen to have large k2 and small PFA, as well as the difference in their TCFs (ΔTCF) to always have the same sign of their values. The Z-cut LGS substrate plane was taken as an example, and the two suitable substrate cuts with propagation angles of 74 and 80° were chosen to derive a monotonic frequency-temperature response for LGS SAW sensors at -50 to 540 °C. Experiments on a LGS SAW sensor using the above two substrate cuts were designed, and its measured frequency-temperature response at -50 to 540 °C agreed well with the theory, demonstrating the high accuracy of the proposed method.

  12. The Encapsulation of Hemagglutinin in Protein Bodies Achieves a Stronger Immune Response in Mice than the Soluble Antigen

    PubMed Central

    Hofbauer, Anna; Melnik, Stanislav; Tschofen, Marc; Arcalis, Elsa; Phan, Hoang T.; Gresch, Ulrike; Lampel, Johannes; Conrad, Udo; Stoger, Eva

    2016-01-01

    Zein is a water-insoluble polymer from maize seeds that has been widely used to produce carrier particles for the delivery of therapeutic molecules. We encapsulated a recombinant model vaccine antigen in newly formed zein bodies in planta by generating a fusion construct comprising the ectodomain of hemagglutinin subtype 5 and the N-terminal part of γ-zein. The chimeric protein was transiently produced in tobacco leaves, and H5-containing protein bodies (PBs) were used to immunize mice. An immune response was achieved in all mice treated with H5-zein, even at low doses. The fusion to zein markedly enhanced the IgG response compared the soluble H5 control, and the effect was similar to a commercial adjuvant. The co-administration of adjuvants with the H5-zein bodies did not enhance the immune response any further, suggesting that the zein portion itself mediates an adjuvant effect. While the zein portion used to induce protein body formation was only weakly immunogenic, our results indicate that zein-induced PBs are promising production and delivery vehicles for subunit vaccines. PMID:26909090

  13. Early responses in randomized clinical trials of triptans in acute migraine treatment. Are they clinically relevant? A comment.

    PubMed

    Tfelt-Hansen, Peer

    2010-07-01

    One can question the clinical relevance of early headache responses after oral and intranasal triptans. Thus, for pain-free the early responses were significant but in absolute values they were only a few percentages: the therapeutic gains (TGs) were 1.8% (95% CI = 0.3-3%) for oral almotriptan 12.5 after 30 minutes and 1.0% (95% CI = 0-2%) after intranasal zolmitriptan 5 mg after 15 minutes. These results are compared with subcutaneous sumatriptan 6 mg which has TGs of 11% (95% CI = 7-15%) to 14% (95% CI = 11-17%) for pain-free after 30 minutes. Subcutaneous sumatriptan has a 2 times higher response rate than intranasal zolmitriptan and is 5 times more effective than oral almotriptan at these early time points. It is concluded that if a very early and clinically relevant effect is desired then the migraine patient should use the subcutaneous administration form of sumatriptan. PMID:19178578

  14. Exploratory studies of new avenues to achieve high electromechanical response and high dielectric constant in polymeric materials

    NASA Astrophysics Data System (ADS)

    Huang, Cheng

    High performance soft electronic materials are key elements in advanced electronic devices for broad range applications including capacitors, actuators, artificial muscles and organs, smart materials and structures, microelectromechanical (MEMS) and microfluidic devices, acoustic devices and sensors. This thesis exploits new approaches to improve the electromechanical response and dielectric response of these materials. By making use of novel material phenomena such as large anisotropy in dipolar response in liquid crystals (LCs) and all-organic composites in which high dielectric constant organic solids and conductive polymers are either physically blended into or chemically grafted to a polymer matrix, we demonstrate that high dielectric constant and high electromechanical conversion efficiency comparable to that in ceramic materials can be achieved. Nano-composite approach can also be utilized to improve the performance of the electronic electroactive polymers (EAPs) and composites, for example, exchange coupling between the fillers and matrix with very large dielectric contrast can lead to significantly enhance the dielectric response as well as electromechanical response when the heterogeneity size of the composite is comparable to the exchange length. In addition to the dielectric composites, in which high dielectric constant fillers raise the dielectric constant of composites, conductive percolation can also lead to high dielectric constant in polymeric materials. An all-polymer percolative composite is introduced which exhibits very high dielectric constant (>7,000). The flexible all-polymer composites with a high dielectric constant make it possible to induce a high electromechanical response under a much reduced electric field in the field effect electroactive polymer (EAP) actuators (a strain of 2.65% with an elastic energy density of 0.18 J/cm3 can be achieved under a field of 16 V/mum). Agglomeration of the particles can also be effectively prevented

  15. Assessment of treatment response in chronic constipation clinical trials

    PubMed Central

    Ervin, Claire M; Fehnel, Sheri E; Baird, Mollie J; Carson, Robyn T; Johnston, Jeffrey M; Shiff, Steven J; Kurtz, Caroline B; Mangel, Allen W

    2014-01-01

    Background While chronic constipation (CC) clinical trials have focused primarily on bowel symptoms (symptoms directly related to bowel movements), abdominal symptoms are also prevalent among patients. The United States Food and Drug Administration’s (FDA’s) guidance on the use of patient-reported outcome measures to support product approvals or labeling claims recommends that endpoints be developed with direct patient input and include all symptoms important to patients. Aim To identify a comprehensive set of CC symptoms that are important to patients for measurement in clinical trials. Methods Following a targeted literature review to identify CC symptoms previously reported by patients, 28 patient interviews were conducted consistent with the FDA’s guidance on patient-reported outcomes. Subsequent to open-ended questions eliciting descriptions of all symptoms, rating and ranking methods were used to identify those of greatest importance to patients. Results All 67 studies reviewed included bowel symptoms; more than half also addressed at least one abdominal symptom. Interview participants reported 62 potentially distinct concepts: 12 bowel symptoms; 21 abdominal symptoms; and 29 additional symptoms/impacts. Patients’ descriptions revealed that many symptom terms were highly related and/or could be considered secondary to CC. The rating and ranking task results suggest that both bowel (for example, stool frequency and consistency) and abdominal symptoms (for example, bloating, abdominal pain) comprise patients’ most important symptoms. Further, improvements in both bowel and abdominal symptoms would constitute an improvement in patients’ CC overall. Conclusion Abdominal symptoms in CC patients are equal in relevance to bowel symptoms and should also be addressed in clinical trials to fully evaluate treatment benefit. PMID:24940076

  16. Host response to laparoscopic surgery: mechanisms and clinical correlates

    PubMed Central

    Hackam, David J.; Rotstein, Ori D.

    1998-01-01

    Minimal access surgery has revolutionized the treatment of a variety of surgical diseases, partly because it is associated with less patient morbidity than nonlaparoscopic surgical procedures. Emerging evidence suggests that alteration in the host response after laparoscopic procedures has significantly contributed to the improved postoperative course. Laparoscopy modulates both afferent stimuli (including tissue trauma, pain and wound size) and efferent responses (via neuroendocrine, metabolic, immunologic and cardiorespiratory systems). These effects lead to a decrease in postoperative pain, fever and disability. Laparoscopy mediates these effects through reduced wound size, the activities of endotoxin and immunomodulatory actions of the insufflated gas, resulting in impaired macrophage activity. Although clearly beneficial in reducing postoperative morbidity after elective surgery, this immunosuppression could increase the risk of complications during procedures for infection or neoplasia. PMID:9575992

  17. Host Response to Nontuberculous Mycobacterial Infections of Current Clinical Importance

    PubMed Central

    Orme, Ian M.

    2014-01-01

    The nontuberculous mycobacteria are a large group of acid-fast bacteria that are very widely distributed in the environment. While Mycobacterium avium was once regarded as innocuous, its high frequency as a cause of disseminated disease in HIV-positive individuals illustrated its potential as a pathogen. Much more recently, there is growing evidence that the incidence of M. avium and related nontuberculous species is increasing in immunocompetent individuals. The same has been observed for M. abscessus infections, which are very difficult to treat; accordingly, this review focuses primarily on these two important pathogens. Like the host response to M. tuberculosis infections, the host response to these infections is of the TH1 type but there are some subtle and as-yet-unexplained differences. PMID:24914222

  18. Radiation-Induced Bystander Response: Mechanism and Clinical Implications

    PubMed Central

    Suzuki, Keiji; Yamashita, Shunichi

    2014-01-01

    Significance: Absorption of energy from ionizing radiation (IR) to the genetic material in the cell gives rise to damage to DNA in a dose-dependent manner. There are two types of DNA damage; by a high dose (causing acute or deterministic effects) and by a low dose (related to chronic or stochastic effects), both of which induce different health effects. Among radiation effects, acute cutaneous radiation syndrome results from cell killing as a consequence of high-dose exposure. Recent advances: Recent advances in radiation biology and oncology have demonstrated that bystander effects, which are emerged in cells that have never been exposed, but neighboring irradiated cells, are also involved in radiation effects. Bystander effects are now recognized as an indispensable component of tissue response related to deleterious effects of IR. Critical issues: Evidence has indicated that nonapoptotic premature senescence is commonly observed in various tissues and organs. Senesced cells were found to secrete various proteins, including cytokines, chemokines, and growth factors, most of which are equivalent to those identified as bystander factors. Secreted factors could trigger cell proliferation, angiogenesis, cell migration, inflammatory response, etc., which provide a tissue microenvironment assisting tissue repair and remodeling. Future directions: Understandings of the mechanisms and physiological relevance of radiation-induced bystander effects are quite essential for the beneficial control of wound healing and care. Further studies should extend our knowledge of the mechanisms of bystander effects and mode of cell death in response to IR. PMID:24761341

  19. Enhanced loading regimen of teicoplanin is necessary to achieve therapeutic pharmacokinetics levels for the improvement of clinical outcomes in patients with renal dysfunction.

    PubMed

    Ueda, T; Takesue, Y; Nakajima, K; Ichiki, K; Doita, A; Wada, Y; Tsuchida, T; Takahashi, Y; Ishihara, M; Ikeuchi, H; Uchino, M; Kimura, T

    2016-09-01

    We evaluated the clinical efficacy and safety of teicoplanin according to the pharmacokinetics (PK) therapeutic level achieved in patients with renal dysfunction. Target trough concentration (Cmin) was ≥15-30 μg/ml which has been recommended in patients with normal renal function. Adult patients (estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2)) who were treated by teicoplanin were included in the study. We adopted two types of regimen for the initial 3 days: the conventional regimen, and the enhanced loading regimen (10 mg/kg twice daily on the 1st day, followed by 6.7-10 mg/kg once daily for the 2nd and 3rd days]. Two hundred and eighty-eight patients were evaluated for safety, and 106 patients with methicillin-resistant Staphylococcus aureus (MRSA) infections were evaluated for clinical efficacy. A significantly higher success rate was obtained in patients who achieved the target initial Cmin compared with those that did not (75.0 % vs 50.0 %, p = 0.008). In a multivariate analysis, initial Cmin ≥15 μg/ml was an independent factor for clinical success (adjusted odds ratio: 4.20, 95 % confidence interval: 1.34-13.15). In patients with 15-30 μg/ml of maximal Cmin during therapy, nephrotoxicity occurred in 13.1 %, and hepatotoxicity in 2.6 %, and these incidences were not significantly higher compared with those patients with <15 μg/ml. In conclusion, achievement of Cmin of 15-30 μg/ml without delay was necessary to improve clinical outcomes for the treatment by teicoplanin in patients with renal dysfunction. Further investigation is required regarding the optimal loading regimen to achieve the therapeutic levels in those patients. PMID:27278654

  20. Placebo Response in Antipsychotic Clinical Trials: A Meta-Analysis

    PubMed Central

    Rutherford, Bret R; Pott, Emily; Tandler, Jane M.; Wall, Melanie M.; Roose, Steven P.; Lieberman, Jeffrey A.

    2014-01-01

    Importance Because rising placebo response decreases drug-placebo differences and increases failed trials, it is imperative to determine what is causing this trend. Objective We investigated the relationships of antipsychotic medication/placebo response with publication year and identified associated study design and implementation variables. Data Sources Medline, PsycINFO, and PubMed were searched in July 2013 to identify randomized controlled trials (RCTs) of antipsychotic medications published from 1960-present. Study Selection Included were RCTs lasting 4–24 weeks, contrasting antipsychotic medication with placebo or active comparator, and enrolling patients ≥18 years with schizophrenia or schizoaffective disorder. Data Extraction and Synthesis Standardized mean change scores were calculated for each treatment cell, plotted against publication year, and tested with Spearman rank-order correlation coefficients. Hierarchical linear modeling identified factors associated with the standardized mean change across medication and placebo treatment cells. Main Outcome Measure We hypothesized that the mean change in placebo-treated patients would significantly increase from 1960-present, that greater change would be observed in active comparator vs. placebo-controlled trials, and that more protocol visits would increase the symptom change observed. Results In 106 trials examined, the mean change observed in placebo cells increased significantly with year of publication (N = 39, r = 0.52, p = 0.001), while the mean change in effective dose medication cells decreased significantly (N = 208, r = −0.26, p < 0.001). Significant interactions were found between assignment to effective dose medication and publication year (t = −5.55, df 260, p < 0.001), baseline severity (t = 5.08, df 260, p < 0.001), and study duration (t = −3.76, df 260, p < 0.001), indicating that the average drug-placebo difference significantly decreased over time, with decreasing baseline

  1. Clinical Significance of the Humoral Immune Response to Modified LDL

    PubMed Central

    Lopes-Virella, MF; Virella, G

    2009-01-01

    Human low density lipoprotein (LDL) undergoes oxidation and glycation in vivo. By themselves, oxidized LDL (oxLDL) and AGE-LDL have proinflammatory properties and are considered atherogenic. But the atherogenicity of these lipoproteins are significantly increased as a consequence of the formation of immune complexes (IC) involving autoantibodies spontaneously formed. OxLDL and AGE antibodies have been shown to be predominantly of the IgG1 and IgG3 isotypes. OxLDL antibodies are able to activate the complement system by the classical pathway and to induce FcR-mediated phagocytosis. In vitro and ex vivo studies performed with modified LDL-IC have proven their pro-inflammatory and atherogenic properties. Clinical studies have demonstrated that the levels of circulating modified LDL-IC correlate with parameters indicative of cardiovascular and renal disease in diabetic patients and other patient populations. The possibility that spontaneously formed or induced modified LDL antibodies (particularly IgM oxLDL antibodies) may have a protective effect has been suggested, but the data is unclear and needs to be further investigated. PMID:19427818

  2. The antibody response to methyl isocyanate: experimental and clinical findings.

    PubMed

    Karol, M H; Kamat, S R

    1987-01-01

    Sera from 99 subjects exposed to the industrial gas leak in Bhopal on December 2, 1984 were studied along with sera from guinea pigs exposed to methyl isocyanate (MIC) to determine the production of antibodies specific to (MIC). Each of the four guinea pigs injected with the reactive isocyanate produced MIC-specific antibodies in titres of 1:5120 to 1:10240, when tested with MIC-guinea pig albumin antigen conjugate. Analogous antigens prepared by reaction of MIC with human serum albumin were used to probe production of antibodies in 264 serially obtained human sera from 99 subjects from Bhopal. MIC-specific antibodies belonging to IgG, IgM and IgE classes were detected in eleven subjects. Though titres were low and transient (declining after several months) these findings indicate that the single large exposure to MIC resulted in an immunologic response. This finding was concomitant with chronic respiratory effects following MIC exposure. PMID:3453753

  3. Rebuttal to Nelson et al. 'Response to Bodin and Grote regarding postdoctoral recruitment in clinical neuropsychology'.

    PubMed

    Bodin, Doug; Grote, Christopher L

    2016-07-01

    Nelson et al. provided a response to our commentary on the postdoctoral match in clinical neuropsychology. In this brief rebuttal, we will focus on statements from Nelson et al. that we believe are factual inaccuracies or misunderstandings of some of the points we made in our commentary. In addition, we will comment briefly on the proposed guidelines offered in their response. PMID:27348786

  4. In Silico Simulation of a Clinical Trial Concerning Tumour Response to Radiotherapy

    SciTech Connect

    Dionysiou, Dimitra D.; Stamatakos, Georgios S.; Athanaileas, Theodoras E.; Merrychtas, Andreas; Kaklamani, Dimitra; Varvarigou, Theodora; Uzunoglu, Nikolaos

    2008-11-06

    The aim of this paper is to demonstrate how multilevel tumour growth and response to therapeutic treatment models can be used in order to simulate clinical trials, with the long-term intention of both better designing clinical studies and understanding their outcome based on basic biological science. For this purpose, an already developed computer simulation model of glioblastoma multiforme response to radiotherapy has been used and a clinical study concerning glioblastoma multiforme response to radiotherapy has been simulated. In order to facilitate the simulation of such virtual trials, a toolkit enabling the user-friendly execution of the simulations on grid infrastructures has been designed and developed. The results of the conducted virtual trial are in agreement with the outcome of the real clinical study.

  5. The role, responsibilities and status of the clinical medical physicist in AFOMP.

    PubMed

    Ng, K H; Cheung, K Y; Hu, Y M; Inamura, K; Kim, H J; Krisanachinda, A; Leung, J; Pradhan, A S; Round, H; van Doomo, T; Wong, T J; Yi, B Y

    2009-12-01

    This document is the first of a series of policy statements being issued by the Asia-Oceania Federation of Organizations for Medical Physics (AFOMP). The document was developed by the AFOMP Professional Development Committee (PDC) and was endorsed for official release by AFOMP Council in 2006. The main purpose of the document was to give guidance to AFOMP member organizations on the role and responsibilities of clinical medical physicists. A definition of clinical medical physicist has also been provided. This document discusses the following topics: professional aspects of education and training; responsibilities of the clinical medical physicist; status and organization of the clinical medical physics service and the need for clinical medical physics service. PMID:20169835

  6. Serum phenytoin concentration and clinical response in patients with epilepsy.

    PubMed Central

    Gannaway, D J; Mawer, G E

    1981-01-01

    1 Patients with poorly controlled epilepsy were cautiously transferred from multiple drug therapy to treatment with phenytoin sodium alone. One patient suffered more severe seizures and the initial treatment was restarted. The remainder showed no deterioration. 2 The daily dose of phenytoin was then increased by a small increment at intervals of 2 or more months. The serum phenytoin concentration (total and free) was measured regularly and response was assessed by records of seizure frequency and tests of speech, handwriting, short-term memory and coordination. 3 Patients (n = 11) with partial seizures showed no consistent improvement with increased phenytoin concentration within the range 15 mg/l (60 mumol/l) to the individual threshold for intoxication, greater than or equal to 35 mg/l (140 mumol/l). Patients (n = 4) with generalized seizures however were consistently improved at higher concentrations. 4 Tolerance to phenytoin varied, the threshold for symptomatic intoxication ranging from 35-60 mg/l (140-240 mumol/l) total and 2.7-5.2 mg/l (10.8-20.8 mumol/l) free. Ataxia was the commonest symptom and in some cases this was manifest by worsening of performance on the test of coordination (pursuit rotor). Even at lower phenytoin concentrations the patients performed less well on this test than control subjects. Other tests of performance showed no evidence of impairment at higher phenytoin concentrations. 5 The same daily dose of phenytoin tended to give higher serum drug concentrations after intoxication than before. PMID:7340885

  7. Clinical Evaluation of Tuberculosis Viability Microscopy for Assessing Treatment Response

    PubMed Central

    Datta, Sumona; Sherman, Jonathan M.; Bravard, Marjory A.; Valencia, Teresa; Gilman, Robert H.; Evans, Carlton A.

    2015-01-01

    Background. It is difficult to determine whether early tuberculosis treatment is effective in reducing the infectiousness of patients' sputum, because culture takes weeks and conventional acid-fast sputum microscopy and molecular tests cannot differentiate live from dead tuberculosis. Methods. To assess treatment response, sputum samples (n = 124) from unselected patients (n = 35) with sputum microscopy–positive tuberculosis were tested pretreatment and after 3, 6, and 9 days of empiric first-line therapy. Tuberculosis quantitative viability microscopy with fluorescein diacetate, quantitative culture, and acid-fast auramine microscopy were all performed in triplicate. Results. Tuberculosis quantitative viability microscopy predicted quantitative culture results such that 76% of results agreed within ±1 logarithm (rS = 0.85; P < .0001). In 31 patients with non-multidrug-resistant (MDR) tuberculosis, viability and quantitative culture results approximately halved (both 0.27 log reduction, P < .001) daily. For patients with non-MDR tuberculosis and available data, by treatment day 9 there was a >10-fold reduction in viability in 100% (24/24) of cases and quantitative culture in 95% (19/20) of cases. Four other patients subsequently found to have MDR tuberculosis had no significant changes in viability (P = .4) or quantitative culture (P = .6) results during early treatment. The change in viability and quantitative culture results during early treatment differed significantly between patients with non-MDR tuberculosis and those with MDR tuberculosis (both P < .001). Acid-fast microscopy results changed little during early treatment, and this change was similar for non-MDR tuberculosis vs MDR tuberculosis (P = .6). Conclusions. Tuberculosis quantitative viability microscopy is a simple test that within 1 hour predicted quantitative culture results that became available weeks later, rapidly indicating whether patients were responding to tuberculosis therapy

  8. Linear Discriminant Analysis Achieves High Classification Accuracy for the BOLD fMRI Response to Naturalistic Movie Stimuli.

    PubMed

    Mandelkow, Hendrik; de Zwart, Jacco A; Duyn, Jeff H

    2016-01-01

    Naturalistic stimuli like movies evoke complex perceptual processes, which are of great interest in the study of human cognition by functional MRI (fMRI). However, conventional fMRI analysis based on statistical parametric mapping (SPM) and the general linear model (GLM) is hampered by a lack of accurate parametric models of the BOLD response to complex stimuli. In this situation, statistical machine-learning methods, a.k.a. multivariate pattern analysis (MVPA), have received growing attention for their ability to generate stimulus response models in a data-driven fashion. However, machine-learning methods typically require large amounts of training data as well as computational resources. In the past, this has largely limited their application to fMRI experiments involving small sets of stimulus categories and small regions of interest in the brain. By contrast, the present study compares several classification algorithms known as Nearest Neighbor (NN), Gaussian Naïve Bayes (GNB), and (regularized) Linear Discriminant Analysis (LDA) in terms of their classification accuracy in discriminating the global fMRI response patterns evoked by a large number of naturalistic visual stimuli presented as a movie. Results show that LDA regularized by principal component analysis (PCA) achieved high classification accuracies, above 90% on average for single fMRI volumes acquired 2 s apart during a 300 s movie (chance level 0.7% = 2 s/300 s). The largest source of classification errors were autocorrelations in the BOLD signal compounded by the similarity of consecutive stimuli. All classifiers performed best when given input features from a large region of interest comprising around 25% of the voxels that responded significantly to the visual stimulus. Consistent with this, the most informative principal components represented widespread distributions of co-activated brain regions that were similar between subjects and may represent functional networks. In light of these

  9. Linear Discriminant Analysis Achieves High Classification Accuracy for the BOLD fMRI Response to Naturalistic Movie Stimuli

    PubMed Central

    Mandelkow, Hendrik; de Zwart, Jacco A.; Duyn, Jeff H.

    2016-01-01

    Naturalistic stimuli like movies evoke complex perceptual processes, which are of great interest in the study of human cognition by functional MRI (fMRI). However, conventional fMRI analysis based on statistical parametric mapping (SPM) and the general linear model (GLM) is hampered by a lack of accurate parametric models of the BOLD response to complex stimuli. In this situation, statistical machine-learning methods, a.k.a. multivariate pattern analysis (MVPA), have received growing attention for their ability to generate stimulus response models in a data-driven fashion. However, machine-learning methods typically require large amounts of training data as well as computational resources. In the past, this has largely limited their application to fMRI experiments involving small sets of stimulus categories and small regions of interest in the brain. By contrast, the present study compares several classification algorithms known as Nearest Neighbor (NN), Gaussian Naïve Bayes (GNB), and (regularized) Linear Discriminant Analysis (LDA) in terms of their classification accuracy in discriminating the global fMRI response patterns evoked by a large number of naturalistic visual stimuli presented as a movie. Results show that LDA regularized by principal component analysis (PCA) achieved high classification accuracies, above 90% on average for single fMRI volumes acquired 2 s apart during a 300 s movie (chance level 0.7% = 2 s/300 s). The largest source of classification errors were autocorrelations in the BOLD signal compounded by the similarity of consecutive stimuli. All classifiers performed best when given input features from a large region of interest comprising around 25% of the voxels that responded significantly to the visual stimulus. Consistent with this, the most informative principal components represented widespread distributions of co-activated brain regions that were similar between subjects and may represent functional networks. In light of these

  10. Relationship between placebo response rate and clinical trial outcome in bipolar depression.

    PubMed

    Iovieno, Nadia; Nierenberg, Andrew A; Parkin, Susannah R; Hyung Kim, Daniel Ju; Walker, Rosemary S W; Fava, Maurizio; Papakostas, George I

    2016-03-01

    The aim of this work is to investigate the impact of placebo response rates on the relative risk of response to drug versus placebo in randomized, double-blind, placebo-controlled clinical trials of pharmacological therapy in Bipolar Depression (BPD). Medline/PubMed publication databases were searched for randomized, double-blind, placebo-controlled trials of oral drugs used as monotherapy for the treatment of BPD. The search was limited to articles published between January 1980 and September 2015. Data extracted from 12 manuscripts and one poster with yet unpublished results, representing a total of 17 clinical trials were pooled (n = 6578). Pooled response rates for drug and placebo were 55.1% and 39.2%, corresponding to a risk ratio (RR) for responding to active treatment versus placebo of 1.29 (p < 0.001). Clinical response was defined as a 50% or greater reduction in depression scores, baseline to endpoint. A higher placebo response rate correlated with a significantly lower RR of responding to pharmacotherapy versus placebo (p = 0.002). The pooled drug and placebo response rates for studies with a placebo response rate ≤ 30% were 50.5% versus 26.6%, while corresponding values from studies with a placebo response rate >30 were 55.0% versus 41.6%. These results suggest that the relative efficacy of the active drug compared to placebo in clinical trials for BPD is highly heterogeneous across studies with different placebo response rates, with a worse performance in showing a superiority of the drug versus placebo for studies with placebo response rates >30%. It is important to maintain placebo response rates below this critical threshold, since this is one of the most challenging obstacles for new treatment development in BPD. PMID:26736040

  11. Responders vs clinical response: a critical analysis of data from linaclotide phase 3 clinical trials in IBS-C

    PubMed Central

    Lacy, B E; Lembo, A J; MacDougall, J E; Shiff, S J; Kurtz, C B; Currie, M G; Johnston, J M

    2014-01-01

    Background US Food and Drug Administration (FDA) set a rigorous standard for defining patient responders in irritable bowel syndrome-C (IBS-C; i.e., FDA's Responder Endpoint) for regulatory approval. However, this endpoint's utility for health-care practitioners to assess clinical response has not been determined. We analyzed pooled IBS-C linaclotide trial data to evaluate clinically significant responses in linaclotide-treated patients who did not meet the FDA responder definition. Methods Percentages of FDA non-responders reporting improvement in abdominal pain, bowel function and/or global relief measures were determined using pooled data from two linaclotide Phase 3 IBS-C trials. Key Results 1602 IBS-C patients enrolled; 34% of linaclotide-treated and 17% of placebo-treated patients met the FDA Responder Endpoint (p < 0.0001). Among FDA non-responders at week 12, 63% of linaclotide-treated patients reported their abdominal pain was at least somewhat relieved, compared with 48% of placebo-treated patients. For stool frequency, 62% of linaclotide-treated patients reported that they were at least somewhat improved at week 12, compared with 46% of placebo-treated patients. For global IBS symptoms, 65% of linaclotide-treated patients reported at least some IBS-symptom relief, 43% reported adequate relief of IBS symptoms, and 57% reported being satisfied with linaclotide treatment, vs placebo rates of 48%, 34%, and 41% respectively. Conclusions & Inferences Most linaclotide-treated IBS-C patients who were FDA non-responders reported some improvement in abdominal pain and stool frequency, and global relief/satisfaction. In addition to the FDA Responder Endpoint, differing response thresholds and symptom-specific change from baseline should be considered by clinicians for a complete understanding of clinical response to linaclotide and other IBS-C therapies. PMID:24382134

  12. Assessing eating disorder risk: the pivotal role of achievement anxiety, depression and female gender in non-clinical samples.

    PubMed

    Fragkos, Konstantinos C; Frangos, Christos C

    2013-03-01

    The objective of the present study was to assess factors predicting eating disorder risk in a sample of undergraduate students. A structured questionnaire was employed on a random sample (n = 1865) consisting of the following sections: demographics, SCOFF (Sick, Control, One stone, Fat, Food) questionnaire for screening eating disorders and the Achievement Anxiety Test and the Depression, Anxiety and Stress Scale. The students at risk for eating disorders (SCOFF score ≥2) were 39.7%. Eating disorder risk was more frequent in females, students with divorced parents, students who lived alone, students who were seeking a romantic relationship or were married, students who were at a post-secondary vocational institute/college (private-public) educational level and who were more likely to have marks under merit level. Also, the mean scores for the psychological factors of depression, stress and anxiety were higher in students with eating disorder risk. A logistic regression model was produced depicting that depression, stress, female gender, being married and searching for a romantic relationship were risk factors of having an eating disorder risk. The suggested psychological model examined with structural equation modelling signified the role of academic anxiety as an immediate precursor of general anxiety. Hence, college populations in Greece need organized infrastructures of nutrition health services and campaigns to assist in reducing the risk of eating disorders. PMID:23482057

  13. Primary TKA Patients with Quantifiably Balanced Soft-Tissue Achieve Significant Clinical Gains Sooner than Unbalanced Patients

    PubMed Central

    Gustke, Kenneth A.; Golladay, Gregory J.; Roche, Martin W.; Elson, Leah C.; Anderson, Christopher R.

    2014-01-01

    Although total knee arthroplasty has a high success rate, poor outcomes and early revision are associated with ligament imbalance. This multicenter evaluation was performed in order to provide 1-year followup of a previously reported group of patients who had sensor-assisted TKA, comparing the clinical outcomes of quantitatively balanced versus unbalanced patients. At 1 year, the balanced cohort scored 179.3 and 10.4 in KSS and WOMAC, respectively; the unbalanced cohort scored 156.1 and 17.9 in KSS and WOMAC (P < 0.001; P = 0.085). The average activity level scores of quantitatively balanced patients were 68.6 (corresponding to tennis, light jogging, and heavy yard work), while the average activity level of unbalanced patients was 46.7 (corresponding to light housework, and limited walking distances) (P = 0.015). Out of all confounding variables, a balanced articulation was the most significant contributing factor to improved postoperative outcomes (P < 0.001). PMID:25210632

  14. Clinical phenotype clustering in cardiovascular risk patients for the identification of responsive metabotypes after red wine polyphenol intake.

    PubMed

    Vázquez-Fresno, Rosa; Llorach, Rafael; Perera, Alexandre; Mandal, Rupasri; Feliz, Miguel; Tinahones, Francisco J; Wishart, David S; Andres-Lacueva, Cristina

    2016-02-01

    This study aims to evaluate the robustness of clinical and metabolic phenotyping through, for the first time, the identification of differential responsiveness to dietary strategies in the improvement of cardiometabolic risk conditions. Clinical phenotyping of 57 volunteers with cardiovascular risk factors was achieved using k-means cluster analysis based on 69 biochemical and anthropometric parameters. Cluster validation based on Dunn and Figure of Merit analysis for internal coherence and external homogeneity were employed. k-Means produced four clusters with particular clinical profiles. Differences on urine metabolomic profiles among clinical phenotypes were explored and validated by multivariate orthogonal signal correction partial least-squares discriminant analysis (OSC-PLS-DA) models. OSC-PLS-DA of (1)H-NMR data revealed that model comparing "obese and diabetic cluster" (OD-c) against "healthier cluster" (H-c) showed the best predictability and robustness in terms of explaining the pairwise differences between clusters. Considering these two clusters, distinct groups of metabolites were observed following an intervention with wine polyphenol intake (WPI; 733 equivalents of gallic acid/day) per 28days. Glucose was significantly linked to OD-c metabotype (P<.01), and lactate, betaine and dimethylamine showed a significant trend. Tartrate (P<.001) was associated with wine polyphenol intervention (OD-c_WPI and H-c_WPI), whereas mannitol, threonine methanol, fucose and 3-hydroxyphenylacetate showed a significant trend. Interestingly, 4-hydroxyphenylacetate significantly increased in H-c_WPI compared to OD-c_WPI and to basal groups (P<.05)-gut microbial-derived metabolite after polyphenol intake-, thereby exhibiting a clear metabotypic intervention effect. Results revealed gut microbiota responsive phenotypes to wine polyphenols intervention. Overall, this study illustrates a novel metabolomic strategy for characterizing interindividual responsiveness to dietary

  15. Clinically relevant exaggerated pharmacodynamic response to dual antiplatelet therapy detected by Thromboelastogram® Platelet Mapping™

    PubMed Central

    Hiller, Kenneth N.

    2016-01-01

    Dual antiplatelet therapy (DAPT) is the standard of care for primary and secondary prevention strategies in patients with coronary artery disease after stenting. Current guidelines recommend that DAPT be continued for 12 months in patients after receiving drug eluting stents. Approximately 5% of these patients will present within this 12-month period for noncardiac surgery. This case report describes a clinically relevant exaggerated pharmacodynamic response to DAPT detected by preoperative assessment of platelet function. Based on the clinical history and physical exam and subsequent lab results, a general anesthetic was performed rather than a spinal anesthetic and the surgical procedure was changed. An exaggerated pharmacodynamic response to DAPT poses its own set of risks (unexpected uncontrolled bleeding, epidural hematoma following neuraxial block placement) that point-of-care aggregation testing may decrease or mitigate by altering clinical decision making. If the clinical history and physical exam reveal possible platelet dysfunction in patients receiving DAPT, preoperative platelet function testing should be considered. PMID:27006555

  16. Establishing Good Practices for Exposure–Response Analysis of Clinical Endpoints in Drug Development

    PubMed Central

    Overgaard, RV; Ingwersen, SH; Tornøe, CW

    2015-01-01

    This tutorial aims at promoting good practices for exposure–response (E-R) analyses of clinical endpoints in drug development. The focus is on practical aspects of E-R analyses to assist modeling scientists with a process of performing such analyses in a consistent manner across individuals and projects and tailored to typical clinical drug development decisions. This includes general considerations for planning, conducting, and visualizing E-R analyses, and how these are linked to key questions. PMID:26535157

  17. Protracted Hypofractionated Radiotherapy for Graves' Ophthalmopathy: A Pilot Study of Clinical and Radiologic Response

    SciTech Connect

    Casimiro de Deus Cardoso, Cejana; Giordani, Adelmo Jose; Borri Wolosker, Angela Maria; Souhami, Luis; Gois Manso, Paulo; Souza Dias, Rodrigo; Comodo Segreto, Helena Regina; Araujo Segreto, Roberto

    2012-03-01

    Purpose: To evaluate the clinical and radiologic response of patients with Graves' ophthalmopathy given low-dose orbital radiotherapy (RT) with a protracted fractionation. Methods and Materials: Eighteen patients (36 orbits) received orbital RT with a total dose of 10 Gy, fractionated in 1 Gy once a week over 10 weeks. Of these, 9 patients received steroid therapy as well. Patients were evaluated clinically and radiologically at 6 months after treatment. Clinical response assessment was carried out using three criteria: by physical examination, by a modified clinical activity score, and by a verbal questionnaire considering the 10 most common signs and symptoms of the disease. Radiologic response was assessed by magnetic resonance imaging. Results: Improvement in ocular pain, palpebral edema, visual acuity, and ocular motility was observed in all patients. Significant decrease in symptoms such as tearing (p < 0.001) diplopia (p = 0.008), conjunctival hyperemia (p = 0.002), and ocular grittiness (p = 0.031) also occurred. Magnetic resonance imaging showed decrease in ocular muscle thickness and in the intensity of the T2 sequence signal in the majority of patients. Treatments were well tolerated, and to date no complications from treatment have been observed. There was no statistical difference in clinical and radiologic response between patients receiving RT alone and those receiving RT plus steroid therapy. Conclusion: RT delivered in at a low dose and in a protracted scheme should be considered as a useful therapeutic option for patients with Graves' ophthalmopathy.

  18. The role, duties and responsibilities of technologists in the clinical laboratory.

    PubMed

    Wood, John

    2002-05-21

    Within the United Kingdom, the job functions of the technologist are carried out by Biomedical Scientists who account for the greater proportion of staff employed within clinical laboratories. Their traditional responsibilities have involved providing a quality service through their scientific, technical and clinical skills. During the 1990s, a number of factors combined, leading to a change in the way which quality was viewed within the National Health Service (NHS). This has changed the role of the technologist, encouraging them to broaden their knowledge and take on new skills and responsibility. PMID:11955489

  19. Quantification of clinical scores through physiological recordings in low-responsive patients: a feasibility study.

    PubMed

    Wieser, Martin; Buetler, Lilith; Vallery, Heike; Schaller, Judith; Mayr, Andreas; Kofler, Markus; Saltuari, Leopold; Zutter, Daniel; Riener, Robert

    2012-01-01

    Clinical scores represent the gold standard in characterizing the clinical condition of patients in vegetative or minimally conscious state. However, they suffer from problems of sensitivity, specificity, subjectivity and inter-rater reliability.In this feasibility study, objective measures including physiological and neurophysiological signals are used to quantify the clinical state of 13 low-responsive patients. A linear regression method was applied in nine patients to obtain fixed regression coefficients for the description of the clinical state. The statistical model was extended and evaluated with four patients of another hospital. A linear mixed models approach was introduced to handle the challenges of data sets obtained from different locations.Using linear backward regression 12 variables were sufficient to explain 74.4% of the variability in the change of the clinical scores. Variables based on event-related potentials and electrocardiogram account for most of the variability.These preliminary results are promising considering that this is the first attempt to describe the clinical state of low-responsive patients in such a global and quantitative way. This new model could complement the clinical scores based on objective measurements in order to increase diagnostic reliability. Nevertheless, more patients are necessary to prove the conclusions of a statistical model with 12 variables. PMID:22647145

  20. Pharmacogenomics of Methotrexate Membrane Transport Pathway: Can Clinical Response to Methotrexate in Rheumatoid Arthritis Be Predicted?

    PubMed Central

    Lima, Aurea; Bernardes, Miguel; Azevedo, Rita; Medeiros, Rui; Seabra, Vitor

    2015-01-01

    Background: Methotrexate (MTX) is widely used for rheumatoid arthritis (RA) treatment. Single nucleotide polymorphisms (SNPs) could be used as predictors of patients’ therapeutic outcome variability. Therefore, this study aims to evaluate the influence of SNPs in genes encoding for MTX membrane transport proteins in order to predict clinical response to MTX. Methods: Clinicopathological data from 233 RA patients treated with MTX were collected, clinical response defined, and patients genotyped for 23 SNPs. Genotype and haplotype analyses were performed using multivariate methods and a genetic risk index (GRI) for non-response was created. Results: Increased risk for non-response was associated to SLC22A11 rs11231809 T carriers; ABCC1 rs246240 G carriers; ABCC1 rs3784864 G carriers; CGG haplotype for ABCC1 rs35592, rs2074087 and rs3784864; and CGG haplotype for ABCC1 rs35592, rs246240 and rs3784864. GRI demonstrated that patients with Index 3 were 16-fold more likely to be non-responders than those with Index 1. Conclusions: This study revealed that SLC22A11 and ABCC1 may be important to identify those patients who will not benefit from MTX treatment, highlighting the relevance in translating these results to clinical practice. However, further validation by independent studies is needed to develop the field of personalized medicine to predict clinical response to MTX treatment. PMID:26086825

  1. Clinicians' emotional responses and Psychodynamic Diagnostic Manual adult personality disorders: A clinically relevant empirical investigation.

    PubMed

    Gazzillo, Francesco; Lingiardi, Vittorio; Del Corno, Franco; Genova, Federica; Bornstein, Robert F; Gordon, Robert M; McWilliams, Nancy

    2015-06-01

    The aim of this study is to explore the relationship between level of personality organization and type of personality disorder as assessed with the categories in the Psychodynamic Diagnostic Manual (PDM; PDM Task Force, 2006) and the emotional responses of treating clinicians. We asked 148 Italian clinicians to assess 1 of their adult patients in treatment for personality disorders with the Psychodiagnostic Chart (PDC; Gordon & Bornstein, 2012) and the Personality Diagnostic Prototype (PDP; Gazzillo, Lingiardi, & Del Corno, 2012) and to complete the Therapist Response Questionnaire (TRQ; Betan, Heim, Zittel-Conklin, & Westen, 2005). The patients' level of overall personality pathology was positively associated with helpless and overwhelmed responses in clinicians and negatively associated with positive emotional responses. A parental and disengaged response was associated with the depressive, anxious, and dependent personality disorders; an exclusively parental response with the phobic personality disorder; and a parental and criticized response with narcissistic disorder. Dissociative disorder evoked a helpless and parental response in the treating clinicians whereas somatizing disorder elicited a disengaged reaction. An overwhelmed and disengaged response was associated with sadistic and masochistic personality disorders, with the latter also associated with a parental and hostile/criticized reaction; an exclusively overwhelmed response with psychopathic patients; and a helpless response with paranoid patients. Finally, patients with histrionic personality disorder evoked an overwhelmed and sexualized response in their clinicians whereas there was no specific emotional reaction associated with the schizoid and the obsessive-compulsive disorders. Clinical implications of these findings were discussed. PMID:25868053

  2. Typhoid Fever in Young Children in Bangladesh: Clinical Findings, Antibiotic Susceptibility Pattern and Immune Responses

    PubMed Central

    Khanam, Farhana; Sayeed, Md. Abu; Choudhury, Feroza Kaneez; Sheikh, Alaullah; Ahmed, Dilruba; Goswami, Doli; Hossain, Md. Lokman; Brooks, Abdullah; Calderwood, Stephen B.; Charles, Richelle C.; Cravioto, Alejandro; Ryan, Edward T.; Qadri, Firdausi

    2015-01-01

    Background Children bear a large burden of typhoid fever caused by Salmonella enterica serotype Typhi (S. Typhi) in endemic areas. However, immune responses and clinical findings in children are not well defined. Here, we describe clinical and immunological characteristics of young children with S. Typhi bacteremia, and antimicrobial susceptibility patterns of isolated strains. Methods As a marker of recent infection, we have previously characterized antibody-in-lymphocyte secretion (TPTest) during acute typhoid fever in adults. We similarly assessed membrane preparation (MP) IgA responses in young children at clinical presentation, and then 7-10 days and 21-28 days later. We also assessed plasma IgA, IgG and IgM responses and T cell proliferation responses to MP at these time points. We compared responses in young children (1-5 years) with those seen in older children (6-17 years), adults (18-59 years), and age-matched healthy controls. Principal Findings We found that, compared to age-matched controls patients in all age cohorts had significantly more MP-IgA responses in lymphocyte secretion at clinical presentation, and the values fell in all groups by late convalescence. Similarly, plasma IgA responses in patients were elevated at presentation compared to controls, with acute and convalescent IgA and IgG responses being highest in adults. T cell proliferative responses increased in all age cohorts by late convalescence. Clinical characteristics were similar in all age cohorts, although younger children were more likely to present with loss of appetite, less likely to complain of headache compared to older cohorts, and adults were more likely to have ingested antibiotics. Multi-drug resistant strains were present in approximately 15% of each age cohort, and 97% strains had resistance to nalidixic acid. Conclusions This study demonstrates that S. Typhi bacteremia is associated with comparable clinical courses, immunologic responses in various age cohorts

  3. PET Parametric Response Mapping for Clinical Monitoring and Treatment Response Evaluation in Brain Tumors.

    PubMed

    Ellingson, Benjamin M; Chen, Wei; Harris, Robert J; Pope, Whitney B; Lai, Albert; Nghiemphu, Phioanh L; Czernin, Johannes; Phelps, Michael E; Cloughesy, Timothy F

    2013-04-01

    PET parametric response maps (PRMs) are a provocative new molecular imaging technique for quantifying brain tumor response to therapy in individual patients. By aligning sequential PET scans over time using anatomic MR imaging information, the voxel-wise change in radiotracer uptake can be quantified and visualized. PET PRMs can be performed before and after a particular therapy to test whether the tumor is responding favorably, or performed relative to a distant time point to monitor changes through the course of a treatment. This article focuses on many of the technical details involved in generating, visualizing, and quantifying PET PRMs, and practical applications and example case studies. PMID:27157948

  4. Predictors of Individual Response to Placebo or Tadalafil 5mg among Men with Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia: An Integrated Clinical Data Mining Analysis

    PubMed Central

    Fusco, Ferdinando; D’Anzeo, Gianluca; Henneges, Carsten; Rossi, Andrea; Büttner, Hartwig; Nickel, J. Curtis

    2015-01-01

    Background A significant percentage of patients with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) achieve clinically meaningful improvement when receiving placebo or tadalafil 5mg once daily. However, individual patient characteristics associated with treatment response are unknown. Methods This integrated clinical data mining analysis was designed to identify factors associated with a clinically meaningful response to placebo or tadalafil 5mg once daily in an individual patient with LUTS-BPH. Analyses were performed on pooled data from four randomized, placebo-controlled, double-blind, clinical studies, including about 1,500 patients, from which 107 baseline characteristics were selected and 8 response criteria. The split set evaluation method (1,000 repeats) was used to estimate prediction accuracy, with the database randomly split into training and test subsets. Logistic Regression (LR), Decision Tree (DT), Support Vector Machine (SVM) and Random Forest (RF) models were then generated on the training subset and used to predict response in the test subset. Prediction models were generated for placebo and tadalafil 5mg once daily Receiver Operating Curve (ROC) analysis was used to select optimal prediction models lying on the ROC surface. Findings International Prostate Symptom Score (IPSS) baseline group (mild/moderate vs. severe) for active treatment and placebo achieved the highest combined sensitivity and specificity of 70% and ~50% for all analyses, respectively. This was below the sensitivity and specificity threshold of 80% that would enable reliable allocation of an individual patient to either the responder or non-responder group Conclusions This extensive clinical data mining study in LUTS-BPH did not identify baseline clinical or demographic characteristics that were sufficiently predictive of an individual patient response to placebo or once daily tadalafil 5mg. However, the study reaffirms the efficacy of

  5. Long-Term Clinical Responses of Neoadjuvant Dendritic Cell Infusions and Radiation in Soft Tissue Sarcoma

    PubMed Central

    Raj, Shailaja; Bui, Marilyn M.; Springett, Gregory; Conley, Anthony; Lavilla-Alonso, Sergio; Zhao, Xiuhua; Chen, Dungsa; Haysek, Randy; Gonzalez, Ricardo; Letson, G. Douglas; Finkelstein, Steven Eric; Chiappori, Alberto A.; Gabrilovitch, Dmitry I.; Antonia, Scott J.

    2015-01-01

    Purpose. Patients with large >5 cm, high-grade resectable soft tissue sarcomas (STS) have the highest risk of distant metastases. Previously we have shown that dendritic cell (DC) based vaccines show consistent immune responses. Methods. This was a Phase I single institution study of neoadjuvant radiation with DC injections on 18 newly diagnosed high-risk STS patients. Neoadjuvant treatment consisted of 50 Gy of external beam radiation (EBRT), given in 25 fractions delivered five days/week, combined with four intratumoral injections of DCs followed by complete resection. The primary endpoint was to establish the immunological response to neoadjuvant therapy and obtain data on its clinical safety and outcomes. Results. There were no unexpected toxicities or serious adverse events. Twelve out of 18 (67%) patients were alive, of which an encouraging 11/18 (61%) were alive with no systemic recurrence over a period of 2–8 years. Favorable immunological responses correlated with clinical responses in some cases. Conclusions. This study provides clinical support to using dendritic cell injections along with radiation in sarcomas, which when used optimally in combination can help clinical outcomes in soft tissue sarcoma. Study registration number is NCT00365872. PMID:26880867

  6. Responsibility Attributions for Clients Working with a Counselor, Clinical Psychologist, or Psychiatrist on Various Problems.

    ERIC Educational Resources Information Center

    Kleinke, Chris L.; Kane, Joseph C.

    1998-01-01

    Participants in Study 1 rated the appropriateness of four models of responsibility to a man or woman seeking psychotherapy for uncontrolled anger or depression. In Study 2, appropriateness of these models was related to three types of counselor and problems of personal adjustment, anxiety, schizophrenia. Results, clinical implications are…

  7. Refining Video Game Use Questionnaires for Research and Clinical Application: Detection of Problematic Response Sets

    ERIC Educational Resources Information Center

    Faust, Kyle A.; Faust, David; Baker, Aaron M.; Meyer, Joseph F.

    2012-01-01

    Even when relatively infrequent, deviant response sets, such as defensive and careless responding, can have remarkably robust effects on individual and group data and thereby distort clinical evaluations and research outcomes. Given such potential adverse impacts and the widespread use of self-report measures when appraising addictions and…

  8. In vivo/In vitro immune responses to L. major isolates from patients with no clinical response to Glucantime

    PubMed Central

    Saberi, Sedigheh; Arjmand, Reza; Soleimanifard, Simindokht; Khamesipour, Ali; Hosseini, Seyed Mohsen; Salehi, Mansoor; Varshosaz, Jaleh; Palizban, Abbas Ali; Hejazi, Seyed Hossein

    2016-01-01

    Background: Leishmaniasis is a major health problem in some endemic areas of tropical and subtropical areas of the world. Interleukin-12 (IL-12) and interferon gamma (IFN-γ) are essential cytokines associated with initiation of Th1 response. The main objective of this study was to evaluate of the type of immune response to L. major isolates from patients with no clinical response to antimonite (Glucantime). Materials and Methods: This experimental study was carried out during 2013–2014. In the current study Leishmania major were isolated from 10 CL patients with a history of at least one course of treatment with Meglumine antimonate (Sb5). The isolates were used to evaluate in vitro and in vivo response to Sb5. J774 murine macrophage cell line was used for in vitro tests and Balb/c mice was used for in vivo studies. IL-12 gene expression was evaluated using Real-time PCR and IFN-γ serum level was quantified using ELISA technique. SPSS (version: 20), analysis of Covariance (ANCOVA) was used for statistical analysis. Results: PCR results confirmed that all 10 isolates were L. major. The mean of IL-12 gene expression in vitro, in vivo and IFN-γ serum levels (pg/ml) after 2 and 3 weeks treatment in vivo, increased significantly following the treatment with Glucantime in the two groups of Balb/c mice infected either with patients' isolates or standard L. major. No significant difference was seen between the patients' isolates and standard species. Conclusions: Although the L. major were isolated from patients with active lesion and no clinical response to Glucantime after at least one courses of Glucantime treatment but in vivo and in vitro immune response of L. major isolates showed no difference between the patients' isolates and standard L. major. PMID:27563636

  9. Infliximab Preferentially Induces Clinical Remission and Mucosal Healing in Short Course Crohn's Disease with Luminal Lesions through Balancing Abnormal Immune Response in Gut Mucosa

    PubMed Central

    Yu, Lijuan; Yang, Xuehua; Xia, Lu; Zhong, Jie; Ge, Wensong; Wu, Jianxin; Liu, Hongchun; Liu, Fei; Liu, Zhanju

    2015-01-01

    This study was undertaken to evaluate the efficacy of infliximab (IFX) in treatment of Crohn's disease (CD) patients. 106 CD patients were undergoing treatment with IFX from five hospitals in Shanghai, China. Clinical remission to IFX induction therapy was defined as Crohn's disease activity index (CDAI) < 150. Clinical response was assessed by a decrease in CDAI ≥ 70, and the failure as a CDAI was not significantly changed or increased. Ten weeks after therapy, 61 (57.5%) patients achieved clinical remission, 17 (16.0%) had clinical response, and the remaining 28 (26.4%) were failed. In remission group, significant changes were observed in CDAI, the Simple Endoscopic Score for Crohn's Disease (SES-CD), and serum indexes. Patients with short disease duration (22.2 ± 23.2 months) and luminal lesions showed better effects compared to those with long disease duration (71.0 ± 58.2 months) or stricturing and penetrating lesions. IFX markedly downregulated Th1/Th17-mediated immune response but promoted IL-25 production in intestinal mucosa from remission group. No serious adverse events occurred to terminate treatment. Taken together, our studies demonstrated that IFX is efficacious and safe in inducing clinical remission, promoting mucosal healing, and downregulating Th1/Th17-mediated immune response in short course CD patients with luminal lesions. PMID:25873771

  10. Ethical responsibilities toward indirect and collateral participants in pragmatic clinical trials.

    PubMed

    Smalley, Jaye Bea; Merritt, Maria W; Al-Khatib, Sana M; McCall, Debbe; Staman, Karen L; Stepnowsky, Carl

    2015-10-01

    Pragmatic clinical trials are designed to inform decision makers about the benefits, burdens, and risks of health interventions in real-world settings. Pragmatic clinical trials often use for research purposes data collected in the course of clinical practice. The distinctive features of pragmatic clinical trials demand fresh thinking about what is required to act properly toward people affected by their conduct, in ways that go beyond ensuring the protection of rights and welfare for "human research subjects" under conventional research ethics regulations. To stimulate such work, we propose to distinguish among categories of research participants in pragmatic clinical trials as follows: Direct participants: (1) individuals being directly intervened upon and/or (2) individuals from whom personal identifiable data are being collected for the purposes of the pragmatic clinical trial. Indirect participants: individuals who are (1) not identified as direct participants and (2) whose rights and welfare may be affected by the intervention through their routine exposure to the environment in which the intervention is being deployed. Collateral participants: patient groups and other stakeholder communities who may be otherwise affected by the occurrence and findings of the pragmatic clinical trial. We illustrate these distinctions with case examples and discuss the distinctive responsibilities of researchers and pragmatic clinical trial leadership toward each type of participant. We suggest that pragmatic clinical trial investigators, institutional review boards, health systems leaders, and others engaged in the research enterprise work together to identify these participants. For indirect participants, risks and benefits to which they are exposed should be weighed to ensure that their rights and welfare are protected accordingly, and communication strategies should be considered to help them make well-informed decisions. Collateral participants could provide input on the

  11. [Responsibilities of clinical pharmacology in the early phase of drug development].

    PubMed

    Kuhlmann, J

    2000-05-01

    The path of a new drug from the idea to the product may be divided into 2 phases, namely drug discovery and drug development. Due to the scientific progress new and simple methods could be developed to determine the biological efficacy of a large number of compounds. During the first part of drug development necessary requirements for the first use in man are met by performing preclinical pharmacological, toxicological and pharmacokinetic investigations in the animal and in in-vitro testing. After a first clinical-pharmacological profile of the new substance has been established during phase I on the basis of which a decision for the continuation of the clinical trial is made, the aim of phases II and III is now to answer the important questions of the therapeutic efficacy and tolerability in a large number of patients with the target indication. Due to the continuously increasing time and costs of drug development, drug development should be streamlined combining preclinical and early clinical phases as an exploratory stage and later clinical development as a confirmatory stage. The development and appropriate use of surrogates and models may be helpful to determine drug actions in human and to assist in dose selection as the main requirement for a successful large clinical trial in the confirmatory stage. Identifying the genes responsible for the huge variations in how different patients respond to a drug, in terms of both the product's effectiveness and its side effects, and genotyping patients before including in large clinical trials may prevent selecting the wrong patient population and avoid expensive repetition of these studies. Taking responsibility as the link between research and development gives clinical pharmacology a major opportunity to assume a pivotal role in drug development. To reach this goal, clinical pharmacology must be fully integrated in the whole process of drug development from the candidate selection until the approval. PMID:10851846

  12. [Responsibilities of clinical pharmacology in the early phase of drug development].

    PubMed

    Kuhlmann, J

    1999-05-15

    The path of a new drug from the idea to the product may be divided into 2 phases, namely drug discovery and drug development. Due to the scientific progress new and simple methods could be developed to determine the biological efficacy of a large number of compounds. During the first part of drug development necessary requirements for the first use in man are met by performing preclinical pharmacological, toxicological and pharmacokinetic investigations in the animal and in in-vitro testing. After a first clinical-pharmacological profile of the new substance has been established during phase I on the basis of which a decision for the continuation of the clinical trial is made, the aim of phases II and III is now to answer the important questions of the therapeutic efficacy and tolerability in a large number of patients with the target indication. Due to the continuously increasing time and costs of drug development, drug development should be streamlined combining preclinical and early clinical phases as an exploratory stage and later clinical development as a confirmatory stage. The development and appropriate use of surrogates and models may be helpful to determine drug actions in human and to assist in dose selection as the main requirement for a successful large clinical trial in the confirmatory stage. Identifying the genes responsible for the huge variations in how different patients respond to a drug, in terms of both the product's effectiveness and its side effects, and genotyping patients before including in large clinical trials may prevent selecting the wrong patient population and avoid expensive repetition of these studies. Taking responsibility as the link between research and development gives clinical pharmacology a major opportunity to assume a pivotal role in drug development. To reach this goal, clinical pharmacology must be fully integrated in the whole process of drug development from the candidate selection until the approval. PMID:10408193

  13. Mathematical Knowledge for Teaching, Standards-Based Mathematics Teaching Practices, and Student Achievement in the Context of the "Responsive Classroom Approach"

    ERIC Educational Resources Information Center

    Ottmar, Erin R.; Rimm-Kaufman, Sara E.; Larsen, Ross A.; Berry, Robert Q.

    2015-01-01

    This study investigates the effectiveness of the Responsive Classroom (RC) approach, a social and emotional learning intervention, on changing the relations between mathematics teacher and classroom inputs (mathematical knowledge for teaching [MKT] and standards-based mathematics teaching practices) and student mathematics achievement. Work was…

  14. Response to Intervention, Family Involvement, and Student Achievement at Tier 2: A Mixed Methods Study of K-1 Students and Their Families

    ERIC Educational Resources Information Center

    Gerzel-Short, Lydia

    2013-01-01

    This dissertation examined the importance of family involvement in student learning and achievement within the Response to Intervention framework. This study built upon the premise that family involvement in a child's education is paramount if educational gaps are to be closed. Families included in this study were randomly assigned into a…

  15. The Assessment of Achievement Anxieties in Children: How Important is Response Set and Multidimensionality in the Test Anxiety Scale for Children?

    ERIC Educational Resources Information Center

    Feld, Sheila; Lewis, Judith

    This is a progress report on research conducted (1) to consider the methodological issues of response set and multidimensionality, which might lead to a refinement of the Test Anxiety Scale for Children (TASC) and the Defensiveness Scale for Children and (2) to investigate social background and school achievement correlates of test anxiety and…

  16. A Story within a Story: Culturally Responsive Schooling and American Indian and Alaska Native Achievement in the National Indian Education Study

    ERIC Educational Resources Information Center

    Lopez, Francesca A.; Vasquez Heilig, Julian; Schram, Jacqueline

    2013-01-01

    There have been numerous calls to increase quantitative studies examining the role of culturally responsive schooling (CRS) on American Indian and Alaska Native (AIAN) achievement. The National Indian Education Study (NIES) is the only large-scale study focused on (AIAN) students' cultural experiences within the context of schools. Given…

  17. Prediction of clinical and endoscopic responses to anti-tumor necrosis factor-α antibodies in ulcerative colitis.

    PubMed

    Morita, Yukihiro; Bamba, Shigeki; Takahashi, Kenichiro; Imaeda, Hirotsugu; Nishida, Atsushi; Inatomi, Osamu; Sasaki, Masaya; Tsujikawa, Tomoyuki; Sugimoto, Mitsushige; Andoh, Akira

    2016-08-01

    Objective In patients with ulcerative colitis (UC), the relationship between the initial endoscopic findings and the response to anti-tumor necrosis factor (TNF)-α antibodies remains unclear. We herein evaluated the potential of endoscopic assessment using the ulcerative colitis endoscopic index of severity (UCEIS) to predict the response to anti-TNF-α antibodies. Methods We enrolled 64 patients with UC undergoing anti-TNF-α maintenance therapy with infliximab (IFX) or adalimumab (ADA) between April 2010 and March 2015. Anti-TNF-α trough levels were determined by ELISA. Endoscopic disease activity was assessed using the UCEIS. Results The clinical response rate at 8 weeks was 77.4% for IFX and 66.7% for ADA. Serum albumin levels were significantly higher and the UCEIS bleeding descriptor before treatment was significantly lower in the responders than in the non-responders (p < 0.05 each). The CRP levels at 2 weeks were significantly lower in the responders (p < 0.001). The serum albumin levels before treatment were significantly higher and the UCEIS erosions and ulcers descriptor was significantly lower in the mucosal healing group than in the non-mucosal healing group (p < 0.05 each). A significant and negative correlation between the trough levels of anti-TNF-α antibodies and the UCEIS descriptors was observed. The trough levels of anti-TNF-α antibodies to achieve mucosal healing were 2.7 μg/mL for IFX and 10.3 μg/mL for ADA. Conclusions The UCEIS score, as well as some clinical markers (serum albumin and CRP levels), is useful for the prediction of the treatment outcome of UC patients in response to anti-TNF-α antibodies. PMID:26888161

  18. The effects of training and competition on achievement goals, motivational responses, and performance in a golf-putting task.

    PubMed

    van de Pol P, K C; Kavussanu, Maria; Ring, Christopher

    2012-12-01

    This study examined whether (a) training and competition influence achievement goals, effort, enjoyment, tension, and performance; (b) achievement goals mediate the effects of training and competition on effort, enjoyment, tension, and performance; and (c) the context influences the relationships between goals and effort, enjoyment, tension, and performance. Participants (32 males, 28 females; M age = 19.12 years) performed a golf-putting task in a training condition and a competition condition and completed measures of goal involvement, effort, enjoyment, and tension; putting performance was also measured. Both task and ego involvement varied across training and competition, and variation in ego involvement explained variation in effort and enjoyment between these conditions. Ego involvement positively predicted effort in training and performance in competition, and interacted positively with task involvement to predict effort and enjoyment in competition. Our findings suggest that the distinction between training and competition is a valuable one when examining individuals' achievement motivation. PMID:23204359

  19. Fetal Magnetoencephalography--Achievements and Challenges in the Study of Prenatal and Early Postnatal Brain Responses: A Review

    ERIC Educational Resources Information Center

    Sheridan, Carolin J.; Matuz, Tamara; Draganova, Rossitza; Eswaran, Hari; Preissl, Hubert

    2010-01-01

    Fetal magnetoencephalography (fMEG) is the only non-invasive method for investigating evoked brain responses and spontaneous brain activity generated by the fetus "in utero". Fetal auditory as well as visual-evoked fields have been successfully recorded in basic stimulus-response studies. Moreover, paradigms investigating precursors for cognitive…

  20. Effects On Achievement from Programmed Instruction of Experimentally Induced Familiarization of Content and Different Response Modes. Final Report.

    ERIC Educational Resources Information Center

    Abramson, Theodore; Kagen, Edward

    A study of programed instruction sought to establish an attribute by treatment interaction (ATI) between prior familiarity of material and response mode. Two experimental variables (familiarization and response mode) and two subject attributes (sex and I.Q.) were employed. Junior High (JH) and graduate student (GS) were assigned to familiarization…

  1. Predicting Ovarian Cancer Patients' Clinical Response to Platinum-Based Chemotherapy by Their Tumor Proteomic Signatures.

    PubMed

    Yu, Kun-Hsing; Levine, Douglas A; Zhang, Hui; Chan, Daniel W; Zhang, Zhen; Snyder, Michael

    2016-08-01

    Ovarian cancer is the deadliest gynecologic malignancy in the United States with most patients diagnosed in the advanced stage of the disease. Platinum-based antineoplastic therapeutics is indispensable to treating advanced ovarian serous carcinoma. However, patients have heterogeneous responses to platinum drugs, and it is difficult to predict these interindividual differences before administering medication. In this study, we investigated the tumor proteomic profiles and clinical characteristics of 130 ovarian serous carcinoma patients analyzed by the Clinical Proteomic Tumor Analysis Consortium (CPTAC), predicted the platinum drug response using supervised machine learning methods, and evaluated our prediction models through leave-one-out cross-validation. Our data-driven feature selection approach indicated that tumor proteomics profiles contain information for predicting binarized platinum response (P < 0.0001). We further built a least absolute shrinkage and selection operator (LASSO)-Cox proportional hazards model that stratified patients into early relapse and late relapse groups (P = 0.00013). The top proteomic features indicative of platinum response were involved in ATP synthesis pathways and Ran GTPase binding. Overall, we demonstrated that proteomic profiles of ovarian serous carcinoma patients predicted platinum drug responses as well as provided insights into the biological processes influencing the efficacy of platinum-based therapeutics. Our analytical approach is also extensible to predicting response to other antineoplastic agents or treatment modalities for both ovarian and other cancers. PMID:27312948

  2. Global clinical response in Cushing’s syndrome patients treated with mifepristone

    PubMed Central

    Katznelson, Laurence; Loriaux, D Lynn; Feldman, David; Braunstein, Glenn D; Schteingart, David E; Gross, Coleman

    2014-01-01

    Objective Mifepristone, a glucocorticoid receptor antagonist, improves clinical status in patients with Cushing’s syndrome (CS). We examined the pattern, reliability and correlates of global clinical response (GCR) assessments during a 6-month clinical trial of mifepristone in CS. Design Post hoc analysis of secondary end-point data from a 24-week multicentre, open-label trial of mifepristone (300–1200mg daily) in CS. Intraclass correlation coefficient (ICC) was used to examine rater concordance, and drivers of clinical improvement were determined by multivariate regression analysis. Patients Forty-six adult patients with refractory CS along with diabetes mellitus type 2 or impaired glucose tolerance, and/or a diagnosis of hypertension. Measurements Global clinical assessment made by three independent reviewers using a three-point ordinal scale (+1 = improvement; 0=no change; −1=worsening) based on eight broad clinical categories including glucose control, lipids, blood pressure, body composition, clinical appearance, strength, psychiatric/cognitive symptoms and quality of life at Weeks 6, 10, 16, and 24. Results Positive GCR increased progressively over time with 88% of patients having improved at Week 24 (P<0·001). The full concordance among reviewers occurred in 76·6% of evaluations resulting in an ICC of 0·652 (P<0·001). Changes in body weight (P<0·0001), diastolic blood pressure (P<0·0001), two-hour postoral glucose challenge glucose concentration (P = 0·0003), and Cushingoid appearance (P=0·022) were strong correlates of GCR. Conclusions Mifepristone treatment for CS results in progressive clinical improvement. Overall agreement among clinical reviewers was substantial and determinants of positive GCR included change in weight, blood pressure, glucose levels and appearance. PMID:24102404

  3. Association of Clinical Response and Long-term Outcome Among Patients With Biopsied Orbital Pseudotumor Receiving Modern Radiation Therapy

    SciTech Connect

    Prabhu, Roshan S.; Kandula, Shravan; Liebman, Lang; Wojno, Ted H.; Hayek, Brent; Hall, William A.; Shu, Hui-Kuo; Crocker, Ian

    2013-03-01

    Purpose: To retrospectively evaluate institutional outcomes for patients treated with modern radiation therapy (RT) for biopsied orbital pseudotumor (OP). Methods and Materials: Twenty patients (26 affected orbits) with OP were treated with RT between January 2002 and December 2011. All patients underwent biopsy with histopathologic exclusion of other disease processes. Sixteen patients (80%) were treated with intensity modulated RT, 3 (15%) with opposed lateral beams, and 1 (5%) with electrons. Median RT dose was 27 Gy (range 25.2-30.6 Gy). Response to RT was evaluated at 4 months post-RT. Partial response (PR) was defined as improvement in orbital symptoms without an increase in steroid dose. Complete response (CR) 1 and CR 2 were defined as complete resolution of orbital symptoms with reduction in steroid dose (CR 1) or complete tapering of steroids (CR 2). The median follow-up period was 18.6 months (range 4-81.6 months). Results: Seventeen patients (85%) demonstrated response to RT, with 7 (35%), 1 (5%), and 9 (45%) achieving a PR, CR 1, and CR 2, respectively. Of the 17 patients who had ≥PR at 4 months post-RT, 6 (35%) experienced recurrence of symptoms. Age (>46 years vs ≤46 years, P=.04) and clinical response to RT (CR 2 vs CR 1/PR, P=.05) were significantly associated with pseudotumor recurrence. Long-term complications were seen in 7 patients (35%), including 4 with cataract formation, 1 with chronic dry eye, 1 with enophthalmos, and 1 with keratopathy. Conclusions: RT is an effective treatment for improving symptoms and tapering steroids in patients with a biopsy supported diagnosis of OP. Older age and complete response to RT were associated with a significantly reduced probability of symptom recurrence. The observed late complications may be related to RT, chronic use of steroids/immunosuppressants, medical comorbidities, or combination of factors.

  4. The Relationship between Self Concept and Response towards Student's Academic Achievement among Students Leaders in University Putra Malaysia

    ERIC Educational Resources Information Center

    Ahmad, Jamaludin; Ghazali, Mazila; Hassan, Aminuddin

    2011-01-01

    This is a quantitative research using correlational method. The purpose of this research is to study the relationship between self concept and ability to handle stress on academic achievement of student leaders in University Putra Malaysia. The sample size consists of 106 respondents who are the Student Supreme Council and Student Representative…

  5. An Evaluation of Student Achievement before and after Training in Response to Instruction in a Rural School District

    ERIC Educational Resources Information Center

    Davis, Caroline

    2014-01-01

    The purpose of this quantitative study was to provide research in examining the difference in student achievement in reading and math through the quantitative data collection of North Carolina EOG scores for students in third through fifth grade from one high poverty and high performing North Carolina public school district before and after…

  6. Dopamine blockade and clinical response: Evidence for two biological subgroups of schizophrenia

    SciTech Connect

    Wolkin, A.; Barouche, F.; Wolf, A.P.; Rotrosen, J.; Fowler, J.S.; Shiue, C.Y.; Cooper, T.B.; Brodie, J.D. )

    1989-07-01

    Because CNS neuroleptic concentration cannot be directly measured in patients, the relation between clinical response and extent of dopamine receptor blockade is unknown. This relationship is critical in ascertaining whether nonresponse to neuroleptics is the result merely of inadequate CNS drug levels or of more basic biological differences in pathophysiology. Using ({sup 18}F)N-methylspiroperidol and positron emission tomography, the authors assessed dopamine receptor occupancy in 10 schizophrenic patients before and after treatment with haloperidol. Responders and nonresponders had virtually identical indices of ({sup 18}F)N-methylspiroperidol uptake after treatment, indicating that failure to respond clinically was not a function of neuroleptic uptake or binding in the CNS.

  7. Clinical Parameters Predicting Pathologic Tumor Response After Preoperative Chemoradiotherapy for Rectal Cancer

    SciTech Connect

    Yoon, Sang Min; Kim, Dae Yong Kim, Tae Hyun; Jung, Kyung Hae; Chang, Hee Jin; Koom, Woong Sub; Lim, Seok-Byung; Choi, Hyo Seong; Jeong, Seung-Yong; Park, Jae-Gahb

    2007-11-15

    Purpose: To identify pretreatment clinical parameters that could predict pathologic tumor response to preoperative chemoradiotherapy (CRT) for rectal cancer. Methods and Materials: The study involved 351 patients who underwent preoperative CRT followed by surgery between October 2001 and July 2006. Tumor responses to preoperative CRT were assessed in terms of tumor downstaging and tumor regression. Statistical analyses were performed to identify clinical factors associated with pathologic tumor response. Results: Tumor downstaging (defined as ypT2 or less) was observed in 167 patients (47.6%), whereas tumor regression (defined as Dworak's Regression Grades 3 or 4) was observed in 103 patients (29.3%) and complete regression in 51 patients (14.5%). Multivariate analysis found that predictors of downstaging were pretreatment hemoglobin level (p = 0.045), cN0 classification (p < 0.001), and serum carcinoembryonic antigen (CEA) level (p < 0.001), that predictors of tumor regression were cN0 classification (p = 0.044) and CEA level (p < 0.001), and that the predictor of complete regression was CEA level (p = 0.004). Conclusions: The data suggest that pretreatment CEA level is the most important clinical predictor of pathologic tumor response. It may be of benefit in the selection of treatment options as well as the assessment of individual prognosis.

  8. Appraisals and Responses to Experimental Symptom Analogues in Clinical and Nonclinical Individuals With Psychotic Experiences

    PubMed Central

    Ward, Thomas A.; Gaynor, Keith J.; Hunter, Mike D.; Woodruff, Peter W. R.; Garety, Philippa A.; Peters, Emmanuelle R.

    2014-01-01

    Objective: Cognitive models of psychosis suggest that anomalous experiences alone do not always lead to clinical psychosis, with appraisals and responses to experiences being central to understanding the transition to “need for care”. Methods: The appraisals and response styles of Clinical (C; n = 28) and Nonclinical (NC; n = 34) individuals with psychotic experiences were compared following experimental analogues of thought interference (Cards Task) and auditory hallucinations (Virtual Acoustic Space Paradigm). Results: The groups were matched in terms of their psychotic experiences. As predicted, the C group scored higher than the NC group on maladaptive appraisals following both tasks, rated the experience as more personally significant, and was more likely to incorporate the experimental setup into their ongoing experiences. The C group also appraised the Cards Task as more salient, distressing, and threatening; this group scored higher on maladaptive—and lower on adaptive—response styles, than the NC group on both tasks. Conclusions: The findings are consistent with cognitive models of psychosis, with maladaptive appraisals and response styles characterizing the C group only. Clinical applications of both tasks are suggested to facilitate the identification and modification of maladaptive appraisals. PMID:23858493

  9. Genetic knowledge and moral responsibility: ambiguity at the interface of genetic research and clinical practice.

    PubMed

    Pullman, D; Hodgkinson, K

    2006-03-01

    Despite a rapidly expanding literature on the issue of duty to warn at-risk relatives in the context of clinical genetic testing, little has been written on parallel issues with regard to the management of genetic research results. Some might view this lack as an indication that there is little to discuss in this regard. That is, standard practice is that data obtained through medical research should not be treated as though they are clinically relevant, and this standard should hold for genetic research as well. This paper challenges this conclusion and its underlying assumptions. We argue that the line between genetic research and clinical practice is often ambiguous. In some cases, research data gathered from a very small number of subjects could have immediate clinical implications. Hence, it is unethical for genetic researchers to absolve themselves of clinical responsibilities for research subjects and/or their families, on the grounds that the data were obtained for research purposes. Indeed, we argue that it could well be unethical to embark on some forms of genetic research unless advance arrangements have been made for genetic counseling and clinical follow-up. Furthermore, in some cases, it might be unethical to enroll subjects in studies if the subjects are unwilling to receive their individual results. PMID:16542381

  10. Genetic studies of DRD4 and clinical response to neuroleptic medications

    SciTech Connect

    Kennedy, J.L.; Petronis, A.; Gao, J.

    1994-09-01

    Clozapine is an atypical antipsychotic drug that, like most other medications, is effective for some people and not for others. This variable response across individuals is likely significantly determined by genetic factors. An important candidate gene to investigate in clozapine response is the dopamine D4 receptor gene (DRD4). The D4 receptor has a higher affinity for clozapine than any of the other dopamine receptors. Furthermore, recent work by our consortium has shown a remarkable level of variability in the part of the gene coding for the third cytoplasmic loop. We have also identified polymorphisms in the upstream 5{prime} putative regulatory region and at two other sites. These polymorphisms were typed in a group of treatment-resistant schizophrenia subjects who were subsequently placed on clozapine (n = 60). In a logistic regression analysis, we compared genotype at the DRD4 polymorphism to response versus non-response to clozapine. Neither the exon-III nor any of the 5{prime} polymorphisms alone significantly predicted response; however, when the information from these polymorphisms was combined, more predictive power was obtained. In a correspondence analysis of the four DRD4 polymorphisms vs. response, we were able to predict 76% of the variance in response. Refinement of the analyses will include assessment of subfactors involved in clinical response phenotype and incorporation of the debrisoquine metabolizing locus (CYP2D6) into the prediction algorithm.

  11. Bioengineered human myobundles mimic clinical responses of skeletal muscle to drugs.

    PubMed

    Madden, Lauran; Juhas, Mark; Kraus, William E; Truskey, George A; Bursac, Nenad

    2015-01-01

    Existing in vitro models of human skeletal muscle cannot recapitulate the organization and function of native muscle, limiting their use in physiological and pharmacological studies. Here, we demonstrate engineering of electrically and chemically responsive, contractile human muscle tissues ('myobundles') using primary myogenic cells. These biomimetic constructs exhibit aligned architecture, multinucleated and striated myofibers, and a Pax7(+) cell pool. They contract spontaneously and respond to electrical stimuli with twitch and tetanic contractions. Positive correlation between contractile force and GCaMP6-reported calcium responses enables non-invasive tracking of myobundle function and drug response. During culture, myobundles maintain functional acetylcholine receptors and structurally and functionally mature, evidenced by increased myofiber diameter and improved calcium handling and contractile strength. In response to diversely acting drugs, myobundles undergo dose-dependent hypertrophy or toxic myopathy similar to clinical outcomes. Human myobundles provide an enabling platform for predictive drug and toxicology screening and development of novel therapeutics for muscle-related disorders. PMID:25575180

  12. Adaptive Response, Evidence of Cross-Resistance and Its Potential Clinical Use

    PubMed Central

    Milisav, Irina; Poljsak, Borut; Šuput, Dušan

    2012-01-01

    Organisms and their cells are constantly exposed to environmental fluctuations. Among them are stressors, which can induce macromolecular damage that exceeds a set threshold, independent of the underlying cause. Stress responses are mechanisms used by organisms to adapt to and overcome stress stimuli. Different stressors or different intensities of stress trigger different cellular responses, namely induce cell repair mechanisms, induce cell responses that result in temporary adaptation to some stressors, induce autophagy or trigger cell death. Studies have reported life-prolonging effects of a wide variety of so-called stressors, such as oxidants, heat shock, some phytochemicals, ischemia, exercise and dietary energy restriction, hypergravity, etc. These stress responses, which result in enhanced defense and repair and even cross-resistance against multiple stressors, may have clinical use and will be discussed, while the emphasis will be on the effects/cross-effects of oxidants. PMID:23109822

  13. A systematic review on the effect of sweeteners on glycemic response and clinically relevant outcomes

    PubMed Central

    2011-01-01

    Background The major metabolic complications of obesity and type 2 diabetes may be prevented and managed with dietary modification. The use of sweeteners that provide little or no calories may help to achieve this objective. Methods We did a systematic review and network meta-analysis of the comparative effectiveness of sweetener additives using Bayesian techniques. MEDLINE, EMBASE, CENTRAL and CAB Global were searched to January 2011. Randomized trials comparing sweeteners in obese, diabetic, and healthy populations were selected. Outcomes of interest included weight change, energy intake, lipids, glycated hemoglobin, markers of insulin resistance and glycemic response. Evidence-based items potentially indicating risk of bias were assessed. Results Of 3,666 citations, we identified 53 eligible randomized controlled trials with 1,126 participants. In diabetic participants, fructose reduced 2-hour blood glucose concentrations by 4.81 mmol/L (95% CI 3.29, 6.34) compared to glucose. Two-hour blood glucose concentration data comparing hypocaloric sweeteners to sucrose or high fructose corn syrup were inconclusive. Based on two ≤10-week trials, we found that non-caloric sweeteners reduced energy intake compared to the sucrose groups by approximately 250-500 kcal/day (95% CI 153, 806). One trial found that participants in the non-caloric sweetener group had a decrease in body mass index compared to an increase in body mass index in the sucrose group (-0.40 vs 0.50 kg/m2, and -1.00 vs 1.60 kg/m2, respectively). No randomized controlled trials showed that high fructose corn syrup or fructose increased levels of cholesterol relative to other sweeteners. Conclusions Considering the public health importance of obesity and its consequences; the clearly relevant role of diet in the pathogenesis and maintenance of obesity; and the billions of dollars spent on non-caloric sweeteners, little high-quality clinical research has been done. Studies are needed to determine the role

  14. A Raman spectroscopic study of cell response to clinical doses of ionizing radiation.

    PubMed

    Harder, Samantha J; Matthews, Quinn; Isabelle, Martin; Brolo, Alexandre G; Lum, Julian J; Jirasek, Andrew

    2015-01-01

    The drive toward personalized radiation therapy (RT) has created significant interest in determining patient-specific tumor and normal tissue responses to radiation. Raman spectroscopy (RS) is a non-invasive and label-free technique that can detect radiation response through assessment of radiation-induced biochemical changes in tumor cells. In the current study, single-cell RS identified specific radiation-induced responses in four human epithelial tumor cell lines: lung (H460), breast (MCF-7, MDA-MB-231), and prostate (LNCaP), following exposure to clinical doses of radiation (2-10 Gy). At low radiation doses (2 Gy), H460 and MCF-7 cell lines showed an increase in glycogen-related spectral features, and the LNCaP cell line showed a membrane phospholipid-related radiation response. In these cell lines, only spectral information from populations receiving 10 Gy or less was required to identify radiation-related features using principal component analysis (PCA). In contrast, the MDA-MB-231 cell line showed a significant increase in protein relative to nucleic acid and lipid spectral features at doses of 6 Gy or higher, and high-dose information (30, 50 Gy) was required for PCA to identify this biological response. The biochemical nature of the radiation-related changes occurring in cells exposed to clinical doses was found to segregate by status of p53 and radiation sensitivity. Furthermore, the utility of RS to identify a biological response in human tumor cells exposed to therapeutic doses of radiation was found to be governed by the extent of the biochemical changes induced by a radiation response and is therefore cell line specific. The results of this study demonstrate the utility and effectiveness of single-cell RS to identify and measure biological responses in tumor cells exposed to standard radiotherapy doses. PMID:25588147

  15. The effectiveness of personal response systems at increasing the engagement and achievement of students in a science classroom

    NASA Astrophysics Data System (ADS)

    Gilson, Renee L.

    Student engagement and immediate assessment of learning is crucial for students to successfully master the rigorous chemistry curriculum set forth under the Michigan Merit Curriculum. It has been my observation that students who are actively engaged and involved in the classroom discussion achieve greater success than students who aren't. The use of iClickers to increase every student's engagement and achievement in a non college prep chemistry course was evaluated. Specifically, students were evaluated on pretests and posttests and their results compared using a paired t test in two sections of a unit in the ChemCom curriculum. During the first section students regularly used the iClickers and during the second section they did not use them at all. Both student engagement and achievement improved with the use of the iClickers as reported on student surveys and compared through pre- and posttest data. Students expressed that they liked using the iClickers and that the immediate feedback helped them better understand their mistakes. Student performance increased on all compared questions and the results of a paired t test showed significant p values for six out of the eight questions compared.

  16. AMERICAN CUTANEOUS LEISHMANIASIS WITH UNUSUAL CLINICAL PRESENTATION AND RESPONSE TO TREATMENT

    PubMed Central

    FERNANDES, Andrea Claudia Bekner Silva; PEDROSO, Raíssa Bocchi; VENAZZI, Eneide Aparecida Sabaini; ZANZARINI, Paulo Donizeti; ARISTIDES, Sandra Mara Alessi; LONARDONI, Maria Valdrinez Campana; SILVEIRA, Thaís Gomes Verzignassi

    2016-01-01

    The clinical manifestations and prognosis of cutaneous leishmaniasis (CL) can be influenced by the immune response of the patient and the species of the parasite. A case of atypical clinical presentation of CL, with development of non-characteristic lesions, poor response to therapy, and a long time to resolution is reported. Confirmatory laboratory tests included parasite detection, indirect immunofluorescence, Montenegro skin test, polymerase chain reaction, and parasite identification by multilocus enzyme electrophoresis. The parasite was identified as Leishmaniabraziliensis. The lesion was unresponsive to three complete courses of N-methylglucamine antimoniate intramuscular, and to treatment with pentamidine. The patient did not tolerate amphotericin B. The lesion finally receded after treatment with intravenous N-methylglucamine antimoniate. It is essential to ensure the accuracy of diagnosis and the appropriate treatment, which can include the use a second choice drug or a different route of administration. PMID:27007563

  17. AMERICAN CUTANEOUS LEISHMANIASIS WITH UNUSUAL CLINICAL PRESENTATION AND RESPONSE TO TREATMENT.

    PubMed

    Fernandes, Andrea Claudia Bekner Silva; Pedroso, Raíssa Bocchi; Venazzi, Eneide Aparecida Sabaini; Zanzarini, Paulo Donizeti; Aristides, Sandra Mara Alessi; Lonardoni, Maria Valdrinez Campana; Silveira, Thaís Gomes Verzignassi

    2016-01-01

    The clinical manifestations and prognosis of cutaneous leishmaniasis (CL) can be influenced by the immune response of the patient and the species of the parasite. A case of atypical clinical presentation of CL, with development of non-characteristic lesions, poor response to therapy, and a long time to resolution is reported. Confirmatory laboratory tests included parasite detection, indirect immunofluorescence, Montenegro skin test, polymerase chain reaction, and parasite identification by multilocus enzyme electrophoresis. The parasite was identified as Leishmaniabraziliensis. The lesion was unresponsive to three complete courses of N-methylglucamine antimoniate intramuscular, and to treatment with pentamidine. The patient did not tolerate amphotericin B. The lesion finally receded after treatment with intravenous N-methylglucamine antimoniate. It is essential to ensure the accuracy of diagnosis and the appropriate treatment, which can include the use a second choice drug or a different route of administration. PMID:27007563

  18. Drosophila Embryos as a Model for Wound-Induced Transcriptional Dynamics: Genetic Strategies to Achieve a Localized Wound Response

    PubMed Central

    Juarez, Michelle T.

    2016-01-01

    While many studies have established a paradigm for tissue repair at the level of cellular remodeling, it is not clear how an organism restricts a response only to the injured region of a damaged tissue. Skin, the largest organ in the human body, is prone to injury, and repair of epidermal tissue represents a medically relevant system to investigate. Significance: Studies in Drosophila melanogaster provide a robust genetic system to identify molecular components that will positively impact repair and healing. The Drosophila skin consists of a single-cell epidermal layer and relies on well-conserved cellular mechanisms to coordinate gene expression during development. Many studies have established that key developmental genes promote a response to epidermal injury, but the balance between activator and inhibitor signals to coordinate a localized response remains unknown. Recent Advances: Discovery of a genetic pathway that promotes the restriction of transcriptional response to damage only in effected regions. Interestingly, genome-wide microarray studies have identified an intersection between gene expression after aseptic injury and activation of the innate immune response. Critical Issues: The use of a transcriptional activation reporter provides an innovative approach to uncover well-conserved components that promote the localization of a response during epidermal injury and may influence other pathological conditions of tissue damage. Future Directions: The work reviewed in this critical review may lead to development of molecular strategies of repair and improved healing after injury or infection. The outcomes on the fundamental contribution of a transcriptional response to injury will be translatable to mammalian systems. PMID:27274436

  19. Clinical, haematological and biochemical responses of sheep undergoing autologous blood transfusion

    PubMed Central

    2012-01-01

    Background This study aimed to evaluate the clinical, haematological and biochemical responses to autologous blood transfusion and the feasibility of this practice in sheep. Thus, we used eight male, 8 months old sheep, weighing on average 30 kg, from which 15 mL/kg of whole blood was collected and stored in CPDA-1 bags. Blood samples were refrigerated for 8 days and subsequently re-infused. The clinical, haematological and biochemical parameters were evaluated before blood collection and reinfusion, after 10 minutes of collection and reinfusion, after 3, 6, 12, 24, 48, 96 and 192 hours after collection and reinfusion. Results With respect to clinical parameters, we observed a decrease in heart rate after 24, 48 and 196 hours from reinfusion compared to basal values (p < 0.05). Haematological variables including globular volume and erythrocyte counts showed a significant decrease (p < 0.01) at all time points after collection and increased (p < 0.01) at all time points after reinfusion. There was a significant increase in total protein and calcium at all time points after reinfusion (p < 0.05). Conclusion Autologous transfusion in sheep slightly altered the physiological, biochemical and haematological responses of sheep, indicating that the technique proposed is safe and can be applied in the clinical practice of this species. The 8 d period was not sufficient for complete recovery of the haematological parameters after blood collection. PMID:22607611

  20. Vessel calibre—a potential MRI biomarker of tumour response in clinical trials

    PubMed Central

    Emblem, Kyrre E.; Farrar, Christian T.; Gerstner, Elizabeth R.; Batchelor, Tracy T.; Borra, Ronald J. H.; Rosen, Bruce R.; Sorensen, A. Gregory; Jain, Rakesh K.

    2015-01-01

    Our understanding of the importance of blood vessels and angiogenesis in cancer has increased considerably over the past decades, and the assessment of tumour vessel calibre and structure has become increasingly important for in vivo monitoring of therapeutic response. The preferred method for in vivo imaging of most solid cancers is MRI, and the concept of vessel-calibre MRI has evolved since its initial inception in the early 1990s. Almost a quarter of a century later, unlike traditional contrast-enhanced MRI techniques, vessel-calibre MRI remains widely inaccessible to the general clinical community. The narrow availability of the technique is, in part, attributable to limited awareness and a lack of imaging standardization. Thus, the role of vessel-calibre MRI in early phase clinical trials remains to be determined. By contrast, regulatory approvals of antiangiogenic agents that are not directly cytotoxic have created an urgent need for clinical trials incorporating advanced imaging analyses, going beyond traditional assessments of tumour volume. To this end, we review the field of vessel-calibre MRI and summarize the emerging evidence supporting the use of this technique to monitor response to anticancer therapy. We also discuss the potential use of this biomarker assessment in clinical imaging trials and highlight relevant avenues for future research. PMID:25113840

  1. Chronic Periodontal Disease May Influence the Pulp Sensitivity Response: Clinical Evaluation in Consecutive Patients

    PubMed Central

    Zuza, Elizangela Partata; Vanzato Carrareto, Ana Luiza; Pontes, Ana Emília Farias; Brunozzi, Marcelo; Pires, Juliana Rico; Toledo, Benedicto Egbert Corrêa

    2012-01-01

    Purpose. The aim of the present study was to evaluate the clinical response of the pulp in teeth with chronic periodontitis. Methods. Consecutive patients who had been admitted to the Clinics of Periodontology and fulfilled the criteria of inclusion were enrolled from January to December 2007. Ninety-eight single-root teeth from 27 patients with chronic periodontitis were evaluated clinically with regard to clinical attachment level (CAL), probing depth (PD), and gingival recession (REC). After periodontal measurements, Pulpal Sensitivity (PS) was evaluated with the use of a cooling stimulus test. Data was analyzed with Student's t test and contingency C coefficient. Results. Teeth that responded positively to PS test presented lower values of CAL (7.8 ± 2.8 mm), PD (5.0 ± 2.3 mm), and REC (2.8 ± 1.8 mm) in comparison to those that responded negatively (CAL = 12.0 ± 2.2 mm; PD = 7.9 ± 1.6 mm; REC = 4.1 ± 2.4 mm) (P < 0.01, Student's t test). In addition, significant correlations were observed between PS and periodontal parameters. Conclusions. Within the limits of this study, it could be suggested that the progression of periodontitis may significantly influence the negative pulpal response. PMID:22577567

  2. Future clinical uses of neurophysiological biomarkers to predict and monitor treatment response for schizophrenia

    PubMed Central

    Light, Gregory A.; Swerdlow, Neal R.

    2015-01-01

    Advances in psychiatric neuroscience have transformed our understanding of impaired and spared brain functions in psychotic illnesses. Despite substantial progress, few if any laboratory tests have graduated to clinics to inform diagnoses, guide treatments, and monitor treatment response. Providers must rely on careful behavioral observation and interview techniques to make inferences about patients’ inner experiences and then secondary deductions about impacted neural systems. Development of more effective treatments has also been hindered by a lack of translational quantitative biomarkers that can span the brain–behavior–treatment knowledge gap. Here, we describe an example of a simple, low-cost, and translatable electroencephalography (EEG) measure that offers promise for improving our understanding and treatment of psychotic illnesses: mismatch negativity (MMN). MMN is sensitive to and/or predicts response to some pharmacologic and non-pharmacologic interventions and accounts for substantial portions of variance in clinical, cognitive, and psychosocial functioning in schizophrenia. This measure has recently been validated for use in large-scale multisite clinical studies of schizophrenia. Lastly, MMN greatly improves our ability to forecast which individuals at high clinical risk actually develop a psychotic illness. These attributes suggest that MMN can contribute to personalized biomarker-guided treatment strategies aimed at ameliorating or even preventing the onset of psychosis. PMID:25752648

  3. Effectiveness of Music Education for the Improvement of Reading Skills and Academic Achievement in Young Poor Readers: A Pragmatic Cluster-Randomized, Controlled Clinical Trial

    PubMed Central

    Cogo-Moreira, Hugo; de Ávila, Clara Regina Brandão; Ploubidis, George B.; Mari, Jair de Jesus

    2013-01-01

    Introduction Difficulties in word-level reading skills are prevalent in Brazilian schools and may deter children from gaining the knowledge obtained through reading and academic achievement. Music education has emerged as a potential method to improve reading skills because due to a common neurobiological substratum. Objective To evaluate the effectiveness of music education for the improvement of reading skills and academic achievement among children (eight to 10 years of age) with reading difficulties. Method 235 children with reading difficulties in 10 schools participated in a five-month, randomized clinical trial in cluster (RCT) in an impoverished zone within the city of São Paulo to test the effects of music education intervention while assessing reading skills and academic achievement during the school year. Five schools were chosen randomly to incorporate music classes (n = 114), and five served as controls (n = 121). Two different methods of analysis were used to evaluate the effectiveness of the intervention: The standard method was intention-to-treat (ITT), and the other was the Complier Average Causal Effect (CACE) estimation method, which took compliance status into account. Results The ITT analyses were not very promising; only one marginal effect existed for the rate of correct real words read per minute. Indeed, considering ITT, improvements were observed in the secondary outcomes (slope of Portuguese = 0.21 [p<0.001] and slope of math = 0.25 [p<0.001]). As for CACE estimation (i.e., complier children versus non-complier children), more promising effects were observed in terms of the rate of correct words read per minute [β = 13.98, p<0.001] and phonological awareness [β = 19.72, p<0.001] as well as secondary outcomes (academic achievement in Portuguese [β = 0.77, p<0.0001] and math [β = 0.49, p<0.001] throughout the school year). Conclusion The results may be seen as promising, but they are not, in themselves

  4. Clinical Consequences of Immune Response to CT Upper Genital Tract Infection in Women

    PubMed Central

    Askienazy-Elbhar, M.; Orfila, J.

    1996-01-01

    C. TRACHOMATIS (CT) infections of the upper genital tract in women are either acute, sub acute or chronic. CT infection has a tendency to be chronic, latent and persistent as a consequence of the host immune reaction to CT major outer membrane protein, 57 Kd heat shock protein and lipopolysaccharide. Chlamydial persistence can be induced as a result of inflammatory and/or immune regulated cytokines, Interferon γ depletion of tryptophan causes a stress response involving development of abnormal forms with increased levels of stress response proteins which maintain host immune responses with continuous fibrin exudate. The main clinical consequences are acute and chronic pelvic inflammatory disease, with infertility, ectopic pregnancy and, less frequently, chronic pelvic pain as late sequelae. PID, when acute, is marked by bilateral pelvic pain, plus other infectious signs in typical cases: fever, leucorrhea, red and purulent cervix. In 50% cases, infectious signs are slight or absent or there is an atypical clinical situation. Laparoscopy is the key for diagnosis. It allows the surgeon to have a direct look at the pelvic organs and perform microbiologic and histologic sampling. In severe cases, laparoscopy allows the surgeon to aspirate the purulent discharge and successfully treat pelvic abscesses. Chronic PID usually is clinically silent. It is in most cases discovered some years after the onset of CT infection, in women operated on for tubal infertility or ectopic pregnancy. Further studies, to evaluate treatments efficiency in chronic cases and factors leading to ectopic pregnancy or to recurrence, are indicated. PMID:18476090

  5. Cognitive intrusions in a non-clinical population. I. Response style, subjective experience, and appraisal.

    PubMed

    Freeston, M H; Ladouceur, R; Thibodeau, N; Gagnon, F

    1991-01-01

    The present study identified distinctive response styles to unpleasant cognitive intrusions to further understanding of intrusive phenomena similar to those observed in obsessive-compulsive disorder and other anxiety disorders. Response styles were studied among 125 university students who completed a questionnaire describing and evaluating seven cognitive intrusions and inventories of depressive, anxious, and compulsive symptoms. Almost all subjects (99%) reported intrusions and 92% included effortful strategies in response to intrusions in their repertoire. Large differences were observed in the dominant strategy used. Three distinctive dominant response styles were identified including no effortful response (26%) and two effortful styles, attentive thinking (34%), and escape/avoidance (40%). The two groups using effortful strategies were more anxious and reported more difficulty removing intrusions. The group using escape/avoidance strategies reported more sadness, worry, guilt, and disapproval than subjects reporting no effortful response. The attentive thinking group reported more varied forms and more frequently triggered intrusions then the no effortful response group. Within subject analyses support the group comparisons and showed that intrusions eliciting escape/avoidance strategies were evaluated more disapprovingly than thoughts eliciting attentive thinking. The results are discussed in terms of Salkovskis' (Behavior Research and Therapy, 27, 677-682, 1985) formulation of obsessive-compulsive disorder and Borkovec's (Journal of Consulting and Clinical Psychology, 23, 481-482, 1985) and Barlow's (Anxiety and its disorders: The nature and treatment of anxiety and panic, 1988) discussions of worry and generalized anxiety. PMID:1759957

  6. Evaluation of the tip-bending response in clinically used endoscopes

    PubMed Central

    Rozeboom, Esther D.; Reilink, Rob; Schwartz, Matthijs P.; Fockens, Paul; Broeders, Ivo A. M. J.

    2016-01-01

    Background and study aims: Endoscopic interventions require accurate and precise control of the endoscope tip. The endoscope tip response depends on a cable pulling system, which is known to deliver a significantly nonlinear response that eventually reduces control. It is unknown whether the current technique of endoscope tip control is adequate for a future of high precision procedures, steerable accessories, and add-on robotics. The aim of this study was to determine the status of the tip response of endoscopes used in clinical practice. Materials and methods: We evaluated 20 flexible colonoscopes and five gastroscopes, used in the endoscopy departments of a Dutch university hospital and two Dutch teaching hospitals, in a bench top setup. First, maximal tip bending was determined manually. Next, the endoscope navigation wheels were rotated individually in a motor setup. Tip angulation was recorded with a USB camera. Cable slackness was derived from the resulting hysteresis plot. Results: Only two of the 20 colonoscopes (10 %) and none of the five gastroscopes reached the maximal tip angulation specified by the manufacturer. Four colonoscopes (20 %) and none of the gastroscopes demonstrated the recommended cable tension. Eight colonoscopes (40 %) had undergone a maintenance check 1 month before the measurements were made. The tip responses of these eight colonoscopies did not differ significantly from the tip responses of the other colonoscopes. Conclusion: This study suggests that the majority of clinically used endoscopes are not optimally tuned to reach maximal bending angles and demonstrate adequate tip responses. We suggest a brief check before procedures to predict difficulties with bending angles and tip responses. PMID:27092330

  7. Lenalidomide Plus Prednisone Results in Durable Clinical, Histopathologic, and Molecular Responses in Patients With Myelofibrosis

    PubMed Central

    Quintás-Cardama, Alfonso; Kantarjian, Hagop M.; Manshouri, Taghi; Thomas, Deborah; Cortes, Jorge; Ravandi, Farhad; Garcia-Manero, Guillermo; Ferrajoli, Alessandra; Bueso-Ramos, Carlos; Verstovsek, Srdan

    2009-01-01

    Purpose To investigate the safety and efficacy of the combination of lenalidomide and prednisone in patients with myelofibrosis (MF). Patients and Methods Forty patients with MF were treated. Therapy consisted of lenalidomide 10 mg/d (5 mg/d if baseline platelet count < 100 × 109/L) on days 1 through 21 of a 28-day cycle for six cycles, in combination with prednisone 30 mg/d orally during cycle 1, 15 mg/d during cycle 2, and 15 mg/d every other day during cycle 3. Lenalidomide therapy was continued indefinitely in patients exhibiting clinical benefit. Results The median follow-up was 22 months (range, 6 to 27). Responses were recorded in 12 patients (30%) and are ongoing in 10 (25%). The median time to response was 12 weeks (range, 2 to 32). According to the International Working Group for Myelofibrosis Research and Treatment consensus criteria, three patients (7.5%) had partial response and nine patients (22.5%) had clinical improvement durable for a median of 18 months (range, 3.5 to 24+). Overall response rates were 30% for anemia and 42% for splenomegaly. Moreover, 10 of 11 assessable responders who started therapy with reticulin fibrosis grade 4 experienced reductions to at least a score of 2. All eight JAK2V617F–positive responders experienced a reduction of the baseline mutant allele burden, which was greater than 50% in four, including one of whom the mutation became undetectable. Grade 3 to 4 hematologic adverse events included neutropenia (58%), anemia (42%), and thrombocytopenia (13%). Conclusion The combination of lenalidomide and prednisone induces durable clinical, molecular, and pathologic responses in MF. PMID:19720904

  8. Accountability: Cognitive Development and Academic Achievement of Children in the Responsive Head Start and Follow Through Programs.

    ERIC Educational Resources Information Center

    Far West Lab. for Educational Research and Development, Berkeley, CA.

    This brief report is a compilation of academic test score data collected on children in the Responsive Educational Programs sponsored by the Far West Laboratory. In some cases sampling was done and statistical tests run. In other situations sampling was not possible and comparisons are made with national norms. Diagrams and figures are given for…

  9. The Contribution of the Responsive Classroom Approach on Children's Academic Achievement: Results from a Three Year Longitudinal Study

    ERIC Educational Resources Information Center

    Rimm-Kaufman, Sara E.; Fan, Xitao; Chiu, Yu-Jen; You, Wenyi

    2007-01-01

    This paper reports the results of a quasi-experimental study on the contribution of the Responsive Classroom ("RC") Approach to elementary school children's reading and math performance over one-, two-, and three-year periods. All children enrolled in six schools (3 intervention and 3 control schools in a single district) were the participants in…

  10. The Effects on Achievement of Using the Forced Inferential Response Mode in an Intermediate Grade Population-Geography Unit.

    ERIC Educational Resources Information Center

    Dale, John Richmond

    This study describes and evaluates an intermediate grade self-instructional unit in population geography organized according to the Forced Inferential Response Mode (FIRM) method of presentation. This mode of presentation is compared with a conventional narrative mode supplemented with graphics. The study indicates no statistically significant…

  11. Using Gradient Analysis to Determine and Compare Invertebrate Responses to Urbanization: Can We Achieve Understanding Without Defining Reference Conditions?

    NASA Astrophysics Data System (ADS)

    Cuffney, T. F.; Giddings, E. M.; Coles, J. F.; Zappia, H.

    2005-05-01

    The U.S. Geological Survey's National Water-Quality Assessment Program uses a gradient design to investigate the effects of urbanization across the U.S. This design has successfully defined invertebrate responses in metropolitan areas associated with Boston, MA, Birmingham, AL, Salt Lake City, UT, and Raleigh, NC. An urban intensity index (UII) based on population, land use, land cover, and infrastructure is used to define the gradient without explicitly identifying reference sites, although the low end of the urban gradient may include such sites. Many invertebrate metrics (e.g., tolerance, biotic integrity, richness) are significantly related to UII. Detection of responses is not dependent upon reference conditions and this design can detect responses even when many low intensity (UII < 20) sites are excluded. Reference conditions can be inferred from regressions of metrics and UII by creating a "dummy" site where the components of the UII are set to background values (e.g., population = 0, road density = 0) and then extrapolating metrics for this site (UII = 0). Unfortunately, these end members (reference site conditions) tend to be highly variable and it is more difficult to determine these values than to detect the existence, form, and rate of response across the urban gradient.

  12. To Achieve an Earlier IFN-γ Response Is Not Sufficient to Control Mycobacterium tuberculosis Infection in Mice

    PubMed Central

    Marzo, Elena; Barril, Carles; Vegué, Marina; Diaz, Jorge; Valls, Joaquim; López, Daniel; Cardona, Pere-Joan

    2014-01-01

    The temporo-spatial relationship between the three organs (lung, spleen and lymph node) involved during the initial stages of Mycobacterium tuberculosis infection has been poorly studied. As such, we performed an experimental study to evaluate the bacillary load in each organ after aerosol or intravenous infection and developed a mathematical approach using the data obtained in order to extract conclusions. The results showed that higher bacillary doses result in an earlier IFN-γ response, that a certain bacillary load (BL) needs to be reached to trigger the IFN-γ response, and that control of the BL is not immediate after onset of the IFN-γ response, which might be a consequence of the spatial dimension. This study may have an important impact when it comes to designing new vaccine candidates as it suggests that triggering an earlier IFN-γ response might not guarantee good infection control, and therefore that additional properties should be considered for these candidates. PMID:24959669

  13. An examination of factors contributing to a reduction in subgroup differences on a constructed-response paper-and-pencil test of scholastic achievement.

    PubMed

    Edwards, Bryan D; Arthur, Winfred

    2007-05-01

    The authors investigated subgroup differences on a multiple-choice and constructed-response test of scholastic achievement in a sample of 197 African American and 258 White test takers. Although both groups had lower mean scores on the constructed-response test, the results showed a 39% reduction in subgroup differences compared with the multiple-choice test. The results demonstrate that the lower subgroup differences were explained by more favorable test perceptions for African Americans on the constructed-response test. In addition, the two test formats displayed comparable levels of criterion-related validity. The results suggest that the constructed-response test format may be a viable alternative to the traditional multiple-choice test format in efforts to simultaneously use valid predictors of performance and minimize subgroup differences in high-stakes testing. PMID:17484558

  14. Current HER2 Testing Recommendations and Clinical Relevance as a Predictor of Response to Targeted Therapy.

    PubMed

    Ballinger, Tarah J; Sanders, Melinda E; Abramson, Vandana G

    2015-06-01

    Clinical decision-making in the treatment of breast cancer depends on an accurate determination and understanding of human epidermal growth factor receptor 2 (HER2) status. The guidelines for HER2 testing were recently updated in late 2013, but limitations continue to exist in the interpretation and clinical application of results when the tumor specimens do not fall neatly into positive or negative categories with immunohistochemistry and fluorescence in situ hybridization testing. The issues, including discordance between pathologists or laboratories, polysomy, and genetic heterogeneity, present challenging situations that are difficult to translate into clinical significance. The present review discussed the changes in the updated American Society of Clinical Oncology/College of American Pathologists guidelines, the clinical relevance of complex issues in HER2 testing, and the implications of the results on the response to HER2-targeted therapies. Great advances have been made in the treatment of HER2-positive breast cancer; however, the challenge remains to determine the best testing analysis that will identify patients who will benefit the most from these therapies. PMID:25516402

  15. Flexible designs for phase II comparative clinical trials involving two response variables.

    PubMed

    Bersimis, S; Sachlas, A; Papaioannou, T

    2015-01-30

    The aim of phase II clinical trials is to determine whether an experimental treatment is sufficiently promising and safe to justify further testing. The need for reduced sample size arises naturally in phase II clinical trials owing to both technical and ethical reasons, motivating a significant part of research in the field during recent years, while another significant part of the research effort is aimed at more complex therapeutic schemes that demand the consideration of multiple endpoints to make decisions. In this paper, our attention is restricted to phase II clinical trials in which two treatments are compared with respect to two dependent dichotomous responses proposing some flexible designs. These designs permit the researcher to terminate the clinical trial when high rates of favorable or unfavorable outcomes are observed early enough requiring in this way a small number of patients. From the mathematical point of view, the proposed designs are defined on bivariate sequences of multi-state trials, and the corresponding stopping rules are based on various distributions related to the waiting time until a certain number of events appear in these sequences. The exact distributions of interest, under a unified framework, are studied using the Markov chain embedding technique, which appears to be very useful in clinical trials for the sample size determination. Tables of expected sample size and power are presented. The numerical illustration showed a very good performance for these new designs. PMID:25274584

  16. Holographic polymer networks formed in liquid crystal phase modulators via a He-Ne laser to achieve ultra-fast optical response.

    PubMed

    Chien, Chun-Yu; Hsu, Che-Ju; Chen, Yu-Wen; Tseng, Sheng-Hao; Sheu, Chia-Rong

    2016-04-01

    The holographic polymer network formed in liquid crystal (LC) phase modulators via a He-Ne laser in this study demonstrates ultra-fast optically response and low light scattering. These advantages are mainly caused by the small LC domains and uniform polymer network when processing LC cells via holographic exposure to a He-Ne laser. The use of this method to fabricate LC cells as phase modulators results in a decay time of 49 μs under 2π phase modulation at room temperature. The predicted fast optical response can be achieved when operating devices at high temperatures. PMID:27137042

  17. Histone Deacetylase Inhibitor Romidepsin Induces HIV Expression in CD4 T Cells from Patients on Suppressive Antiretroviral Therapy at Concentrations Achieved by Clinical Dosing

    PubMed Central

    Wei, Datsen George; Chiang, Vicki; Fyne, Elizabeth; Balakrishnan, Mini; Barnes, Tiffany; Graupe, Michael; Hesselgesser, Joseph; Irrinki, Alivelu; Murry, Jeffrey P.; Stepan, George; Stray, Kirsten M.; Tsai, Angela; Yu, Helen; Spindler, Jonathan; Kearney, Mary; Spina, Celsa A.; McMahon, Deborah; Lalezari, Jacob; Sloan, Derek; Mellors, John; Geleziunas, Romas; Cihlar, Tomas

    2014-01-01

    Persistent latent reservoir of replication-competent proviruses in memory CD4 T cells is a major obstacle to curing HIV infection. Pharmacological activation of HIV expression in latently infected cells is being explored as one of the strategies to deplete the latent HIV reservoir. In this study, we characterized the ability of romidepsin (RMD), a histone deacetylase inhibitor approved for the treatment of T-cell lymphomas, to activate the expression of latent HIV. In an in vitro T-cell model of HIV latency, RMD was the most potent inducer of HIV (EC50 = 4.5 nM) compared with vorinostat (VOR; EC50 = 3,950 nM) and other histone deacetylase (HDAC) inhibitors in clinical development including panobinostat (PNB; EC50 = 10 nM). The HIV induction potencies of RMD, VOR, and PNB paralleled their inhibitory activities against multiple human HDAC isoenzymes. In both resting and memory CD4 T cells isolated from HIV-infected patients on suppressive combination antiretroviral therapy (cART), a 4-hour exposure to 40 nM RMD induced a mean 6-fold increase in intracellular HIV RNA levels, whereas a 24-hour treatment with 1 µM VOR resulted in 2- to 3-fold increases. RMD-induced intracellular HIV RNA expression persisted for 48 hours and correlated with sustained inhibition of cell-associated HDAC activity. By comparison, the induction of HIV RNA by VOR and PNB was transient and diminished after 24 hours. RMD also increased levels of extracellular HIV RNA and virions from both memory and resting CD4 T-cell cultures. The activation of HIV expression was observed at RMD concentrations below the drug plasma levels achieved by doses used in patients treated for T-cell lymphomas. In conclusion, RMD induces HIV expression ex vivo at concentrations that can be achieved clinically, indicating that the drug may reactivate latent HIV in patients on suppressive cART. PMID:24722454

  18. Amplitude modulation following response in children as a clinical audiometric tool.

    PubMed

    Mauer, G; Döring, W H; Hamacher, V; Bell, C

    1997-11-01

    The current study was designed to investigate the clinical application of amplitude modulation following response (AMFR) in cochlear implant candidates. A new digital signal processor (DSP)-assisted PC-based hardware and software was developed to perform both simultaneous generation of amplitude-modulated stimuli and the recording, and synchronized signal processing of the electrode signals. Our first results show that AMFR can be recorded in adults as well as in children without any contamination by response-like stimulus artifacts. Very high sound pressure levels can be applied, allowing frequency-specific assessment of residual hearing. Response threshold detection, using spectral analysis, proved to be superior compared to visual evaluation of average time waveforms. PMID:9391622

  19. Achieving Potent Autologous Neutralizing Antibody Responses against Tier 2 HIV-1 Viruses by Strategic Selection of Envelope Immunogens

    PubMed Central

    Hessell, Ann J.; Malherbe, Delphine C.; Pissani, Franco; McBurney, Sean; Krebs, Shelly J.; Gomes, Michelle; Pandey, Shilpi; Sutton, William F.; Burwitz, Benjamin J.; Gray, Matthew; Robins, Harlan; Park, Byung S.; Sacha, Jonah B.; LaBranche, Celia C.; Fuller, Deborah H.; Montefiori, David C.; Stamatatos, Leonidas; Sather, D. Noah

    2016-01-01

    Advancement in immunogen selection and vaccine design that will rapidly elicit a protective Ab response is considered critical for HIV vaccine protective efficacy. Vaccine-elicited Ab responses must therefore have the capacity to prevent infection by neutralization-resistant phenotypes of transmitted/founder (T/F) viruses that establish infection in humans. Most vaccine candidates to date have been ineffective at generating Abs that neutralize T/F or early variants. In this study, we report that coimmunizing rhesus macaques with HIV-1 gp160 DNA and gp140 trimeric protein selected from native envelope gene sequences (envs) induced neutralizing Abs against Tier 2 autologous viruses expressing cognate envelope (Env). The Env immunogens were selected from envs emerging during the earliest stages of neutralization breadth developing within the first 2 years of infection in two clade B–infected human subjects. Moreover, the IgG responses in macaques emulated the targeting to specific regions of Env known to be associated with autologous and heterologous neutralizing Abs developed within the human subjects. Furthermore, we measured increasing affinity of macaque polyclonal IgG responses over the course of the immunization regimen that correlated with Tier 1 neutralization. In addition, we report firm correlations between Tier 2 autologous neutralization and Tier 1 heterologous neutralization, as well as overall TZM-bl breadth scores. Additionally, the activation of Env-specific follicular helper CD4 T cells in lymphocytes isolated from inguinal lymph nodes of vaccinated macaques correlated with Tier 2 autologous neutralization. These results demonstrate the potential for native Env derived from subjects at the time of neutralization broadening as effective HIV vaccine elements. PMID:26944928

  20. Achieving Potent Autologous Neutralizing Antibody Responses against Tier 2 HIV-1 Viruses by Strategic Selection of Envelope Immunogens.

    PubMed

    Hessell, Ann J; Malherbe, Delphine C; Pissani, Franco; McBurney, Sean; Krebs, Shelly J; Gomes, Michelle; Pandey, Shilpi; Sutton, William F; Burwitz, Benjamin J; Gray, Matthew; Robins, Harlan; Park, Byung S; Sacha, Jonah B; LaBranche, Celia C; Fuller, Deborah H; Montefiori, David C; Stamatatos, Leonidas; Sather, D Noah; Haigwood, Nancy L

    2016-04-01

    Advancement in immunogen selection and vaccine design that will rapidly elicit a protective Ab response is considered critical for HIV vaccine protective efficacy. Vaccine-elicited Ab responses must therefore have the capacity to prevent infection by neutralization-resistant phenotypes of transmitted/founder (T/F) viruses that establish infection in humans. Most vaccine candidates to date have been ineffective at generating Abs that neutralize T/F or early variants. In this study, we report that coimmunizing rhesus macaques with HIV-1 gp160 DNA and gp140 trimeric protein selected from native envelope gene sequences (envs) induced neutralizing Abs against Tier 2 autologous viruses expressing cognate envelope (Env). The Env immunogens were selected from envs emerging during the earliest stages of neutralization breadth developing within the first 2 years of infection in two clade B-infected human subjects. Moreover, the IgG responses in macaques emulated the targeting to specific regions of Env known to be associated with autologous and heterologous neutralizing Abs developed within the human subjects. Furthermore, we measured increasing affinity of macaque polyclonal IgG responses over the course of the immunization regimen that correlated with Tier 1 neutralization. In addition, we report firm correlations between Tier 2 autologous neutralization and Tier 1 heterologous neutralization, as well as overall TZM-bl breadth scores. Additionally, the activation of Env-specific follicular helper CD4 T cells in lymphocytes isolated from inguinal lymph nodes of vaccinated macaques correlated with Tier 2 autologous neutralization. These results demonstrate the potential for native Env derived from subjects at the time of neutralization broadening as effective HIV vaccine elements. PMID:26944928

  1. Prominent Clinical Dimension, Duration of Illness and Treatment Response in Schizophrenia: A Naturalistic Study

    PubMed Central

    Caldiroli, Alice; Panza, Gabriele; Altamura, Alfredo Carlo

    2012-01-01

    Objective Preliminary data indicate that predominant positive symptoms are predictive of subsequent treatment response, while negative and cognitive symptoms are associated with poor outcome. Purpose of the present study was to investigate the relation between the predominant clinical dimension, duration of illness and acute antipsychotic response in a sample of schizophrenic inpatients. Methods Fifty-one schizophrenic inpatients, receiving an antipsychotic mono-therapy, were dimensionally assessed at the admission in the Acute Psychiatric Unit of the University of Milan. Treatment response was selected as parameter of outcome and defined as a reduction >50% of baseline total The Positive and Negative Syndrome Scale (PANSS) score. Demographic and clinical variables between responders and non-responders were compared using one-way analysis of variance for continuous variables and χ2 test for dichotomous ones. Binary logistic regression was performed to find if dimensional scores and duration of illness were associated with acute antipsychotic response. Results A longer duration of illness was found in non-responders respect to responders (15.61 years vs. 8.28 years)(F=4.98, p=0.03). Higher scores on PANSS positive sub-scale (OR=1.3, p=0.03), lower scores on cognitive PANSS scores (OR=0.75, p=0.05) and shorter duration of illness (OR=0.93, p=0.04) were found to be predictive of acute antipsychotic response. Conclusion These preliminary results show that a long duration of illness as well as a more severe cognitive impairment is predictive of treatment non-response, indicating a worse outcome for chronic patients with predominant cognitive symptoms. PMID:23251199

  2. Similar Clinical and Surgical Outcomes Achieved with Early Compared to Late Anti-TNF Induction in Mild-to-Moderate Ulcerative Colitis: A Retrospective Cohort Study

    PubMed Central

    Fedorak, Darryl K.; Dieleman, Levinus A.; Halloran, Brendan P.

    2016-01-01

    Background. Biologic agents targeting tumor necrosis factor alpha are effective in the management of ulcerative colitis (UC), but their use is often postponed until after failure of other treatment modalities. Objectives. We aim to determine if earlier treatment with infliximab or adalimumab alters clinical and surgical outcomes in UC patients. Methods. A retrospective cohort study was conducted evaluating UC outpatients treated with infliximab or adalimumab from 2003 to 2014. Patients were stratified by time to first anti-TNF exposure; early initiation was defined as starting treatment within three years of diagnosis. Primary outcomes were colectomy, UC-related hospitalization, and clinical secondary loss of response. Kaplan-Meier analysis was used to assess time to the primary outcomes. Results. 115 patients were included (78 infliximab, 37 adalimumab). Median follow-up was 175.6 weeks (IQR 72.4–228.4 weeks). Fifty-seven (49.6%) patients received early anti-TNF therapy; median time to treatment in this group was 38.1 (23.3–91.0) weeks compared to 414.0 (254.0–561.3) weeks in the late initiator cohort (p < 0.0001). Patients treated with early anti-TNF therapy had more severe endoscopic disease at induction (mean Mayo endoscopy subscore 2.46 (SD ± 0.66) versus 1.86 (±0.67), p < 0.001) and trended towards increased risk of colectomy (17.5% versus 8.6%, p = 0.16) and UC-related hospitalization (43.9% versus 27.6%, p = 0.07). In multivariate regression analysis, early anti-TNF induction was not associated with colectomy (HR 2.02 [95% CI: 0.57–7.20]), hospitalization (HR 1.66 [0.84–3.30]), or secondary loss of response (HR 0.86 [0.52–1.42]). Conclusions. Anti-TNF therapy is initiated earlier in patients with severe UC but earlier treatment does not prevent hospitalization, colectomy, or secondary loss of response. PMID:27478817

  3. Long lasting clinical response to chemotherapy for advanced uterine leiomyosarcoma: a case report

    PubMed Central

    2013-01-01

    Introduction Uterine leiomyosarcoma is one of the most frequent uterine sarcomas. In the metastatic setting it is sensitive to doxorubicin, ifosfamide, gemcitabine, docetaxel and a few other drugs, but time to progression is generally short. For this reason prognosis is often poor and there are few reports in the literature of long responders. Case presentation We report a case of a 40-year-old Caucasian woman with metastatic uterine leiomyosarcoma who began treatment six years before the presentation of this case report and for the following six years underwent ten lines of chemotherapy, achieving excellent results and a good quality of life. Among the treatments administered we observed a long response to temolozomide, an unconventional drug for this kind of disease. Conclusion Although there are few chemotherapeutic options for the management of metastatic uterine leiomyosarcoma, a small number of patients have an unexpected long lasting response to treatment. For this reason further research is needed to identify new therapeutic agents and the predictive factors for the achievement of response. PMID:23347560

  4. Immune response phenotype of allergic versus clinically tolerant pigs in a neonatal swine model of allergy.

    PubMed

    Schmied, Julie; Rupa, Prithy; Garvie, Sarah; Wilkie, Bruce

    2013-07-15

    The prevalence of childhood food allergy and the duration of these allergies, particularly those considered to be transient, like egg and milk allergy, are increasing. The identification of allergic individuals using minimally invasive, non-anaphylaxis-threatening methods is therefore of increasing importance. In this experiment, correlates were sought of an allergic immune response (IR) phenotype in pigs. Using pigs pre-treated with heat-killed bacteria or bacterial components before allergic sensitization with the egg white protein ovomucoid (Ovm), differences were determined in IR phenotype of pigs in the categories treated-allergic, treated-tolerant, control-allergic (CA) and control-tolerant. Phenotype was established by measuring immunoglobulin (Ig)-associated antibody activity (AbA), cytokine profiles and the proportion of blood T-regulatory cells (T-regs) and observing late-phase allergen-specific skin tests (ST). Although 100% of pigs became sensitized to Ovm, only 33% of pigs had clinical signs of allergy after oral challenge with egg white. Pigs without clinical signs were classified as clinically tolerant. Sixty-seven percent of allergic pigs had a positive, late-phase ST classified as very strong or strong, while 84% of clinically tolerant pigs did not have late-phase ST. Treated-allergic pigs and CA pigs had greater total antibody IgG (H+L), IgE and IgG1 AbA than clinically tolerant pigs. Cytokine profiles of allergic pigs and the proportion of circulating T-regs, did not differ significantly between allergic and clinically tolerant pigs. Therefore, measurement of allergen-specific IgG, IgG1 and/or IgE activity and evaluation of late-phase ID ST may be useful in identifying allergic IR phenotypes in swine models of food allergy, which may be extended toward human use. PMID:23664639

  5. Cronobacter sakazakii clinical isolates overcome host barriers and evade the immune response.

    PubMed

    Almajed, Faisal S; Forsythe, Stephen J

    2016-01-01

    Cronobacter sakazakii is the most frequently clinically isolated species of the Cronobacter genus. However the virulence factors of C. sakazakii including their ability to overcome host barriers remains poorly studied. In this study, ten clinical isolates of C. sakazakii were assessed for their ability to invade and translocate through human colonic carcinoma epithelial cells (Caco-2) and human brain microvascular endothelial cells (HBMEC). Their ability to avoid phagocytosis in human macrophages U937 and human brain microglial cells was investigated. Additionally, they were tested for serum sensitivity and the presence of the Cronobacter plasminogen activation gene (cpa) gene, which is reported to confer serum resistance. Our data showed that the clinical C. sakazakii strains invaded and translocated through Caco-2 and HBMEC cell lines and some strains showed significantly higher levels of invasion and translocation. Moreover, C. sakazakii was able to persist and even multiply in phagocytic macrophage and microglial cells. All strains, except one, were able to withstand human serum exposure, the single serum sensitive strain was also the only one which did not encode for the cpa gene. These results demonstrate that C. sakazakii clinical isolates are able to overcome host barriers and evade the host immune response indicating their capacity to cause diseases such as necrotizing enterocolitis (NEC) and meningitis. Our data showed for the first time the ability of C. sakazakii clinical isolates to survive and multiply within human microglial cells. Additionally, it was shown that C. sakazakii clinical strains have the capacity to translocate through the Caco-2 and HBMEC cell lines paracellularly. PMID:26616163

  6. Development of a provisional core set of response measures for clinical trials of systemic sclerosis

    PubMed Central

    Khanna, D; Lovell, D J; Giannini, E; Clements, P J; Merkel, P A; Seibold, J R; Matucci-Cerinic, M; Denton, C P; Mayes, M D; Steen, V D; Varga, J; Furst, D E

    2013-01-01

    Objective To develop a provisional core set of response measures for clinical trials of systemic sclerosis (SSc). Methods The Scleroderma Clinical Trials Consortium (SCTC) conducted a structured, 3-round Delphi exercise to reach consensus on a core set of measures for clinical trials of SSc. Round 1 asked the SCTC investigators to list items in 11 pre-defined domains (skin, musculoskeletal, cardiac, pulmonary, cardio-pulmonary, gastrointestinal, renal, Raynaud phenomenon and digital ulcers, health-related quality of life and function, global health, and biomarkers) for SSc clinical trials. Round 2 asked respondents to rate the importance of the chosen items and was followed by a meeting, during which the Steering Committee discussed the feasibility, reliability, redundancy and validity of the items. Round 3 sought to obtain broader consensus on the core set measures. Members also voted on items that had data on feasibility but lacked data on reliability and validity, but may still be useful research outcome measures for future trials. Results A total of 50 SCTC investigators participated in round 1, providing 212 unique items for the 11 domains. In all, 46 (92%) participants responded in round 2 and rated 177 items. The ratings of 177 items were reviewed by the Steering Committee and 31 items from the 11 domains were judged to be appropriate for inclusion in a 1-year multi-centre clinical trial. In total, 40 SCTC investigators completed round 3 and ranked 30 of 31 items as acceptable for inclusion in the core set. The Steering Committee also proposed 14 items for a research agenda. Conclusion Using a Delphi exercise, we have developed a provisional core set of measures for assessment of disease activity and severity in clinical trials of SSc. PMID:17893248

  7. Biomarkers for predicting clinical response to immunosuppressive therapy in aplastic anemia.

    PubMed

    Narita, Atsushi; Kojima, Seiji

    2016-08-01

    The decision to select hematopoietic stem cell transplantation (HSCT) or immunosuppressive therapy (IST) as initial therapy in acquired aplastic anemia (AA) is currently based on patient age and the availability of a human leukocyte antigen (HLA)-matched donor. Although IST is a promising treatment option, the ability to predict its long-term outcomes remains poor due to refractoriness, relapses, and the risk of clonal evolution. Several predictive biomarkers for response to IST have been posited, including age, gender, pre-treatment blood cell counts, cytokines, gene mutations, paroxysmal nocturnal hemoglobinuria (PNH), and telomere length (TL). While previous studies have provided substantial biological insights into the utility of IST, the prognostic power of the reported biomarkers is currently insufficient to contribute to clinical decision making. Recently, a large retrospective analysis proposed the combination of minor PNH clones and TL as an efficient predictor of IST response. Identification of a reliable predictor would provide a useful tool for determining the most appropriate treatment choice for AA patients, including up-front HSCT from HLA-matched unrelated donor. The present review summarizes studies evaluating the utility of biomarkers in predicting the clinical response to IST of patients with AA, and provides a baseline for prospective studies aimed at validating previously reported biomarkers. PMID:27091471

  8. Clinical application of fluctuation dissipation theory - Prediction of heart rate response to spontaneous breathing trial

    NASA Astrophysics Data System (ADS)

    Niestemski, Liang R.; Chen, Man; Prevost, Robert; McRae, Michael; Cholleti, Sharath; Najarro, Gabriel; Buchman, Timothy G.; Deem, Michael W.

    2013-03-01

    Contrary to the traditional view of the healthy physiological state as being a single static state, variation in physiologic variables has more recently been suggested to be a key component of the healthy state. Indeed, aging and disease are characterized by a loss of such variability. We apply the conceptual framework of fluctuation-dissipation theory (FDT) to predict the response to a common clinical intervention from historical fluctuations in physiologic time series data. The non-equilibrium FDT relates the response of a system to a perturbation to natural fluctuations in the stationary state of the system. We seek to understand with the FDT a common clinical perturbation, the spontaneous breathing trial (SBT), in which mechanical ventilation is briefly suspended while the patient breathes freely for a period of time. As a stress upon the heart of the patient, the SBT can be characterized as a perturbation of heart rate dynamics. A non-equilibrium, but steady-state FDT allows us to predict the heart rate recovery after the SBT stress. We show that the responses of groups of similar patients to the spontaneous breathing trial can be predicted by this approach. This mathematical framework may serve as part of the basis for personalized critical care.

  9. Clinical application of Chamomilla recutita in phlebitis: dose response curve study.

    PubMed

    Reis, Paula Elaine Diniz Dos; Carvalho, Emilia Campos de; Bueno, Paula Carolina Pires; Bastos, Jairo Kenupp

    2011-01-01

    This experimental and dose-response curve study aimed to carry out the quality control of the Chamomilla recutita sample, as well as to estimate the ideal dose, for anti-inflammatory effect, of the extract of its capitula, in patients with phlebitis due to peripheral intravenous infusion of antineoplastic chemotherapy and to evaluate the toxicity of this extract in human beings. The therapeutic efficacy, concerning the anti-inflammatory potential, of different doses of Chamomilla recutita extract were analyzed and compared in 25 patients. The time of regression of phlebitis was shorter for groups with 2.5% concentration (mean=29.2h, standard deviation = 8.98) and 5% concentration (mean = 38.8h, standard deviation = 17.47). Local toxicity was almost not observed. This research contributes to the innovation of the nursing clinical practice, since it suggests an alternative for the treatment of phlebitis through the clinical use of phytotherapeutic drugs. PMID:21412623

  10. The Brief Accessibility, Responsiveness, and Engagement Scale: A Tool for Measuring Attachment Behaviors in Clinical Couples.

    PubMed

    Sandberg, Jonathan G; Novak, Joshua R; Davis, Stephanie Y; Busby, Dean M

    2016-01-01

    Measuring attachment behaviors is relevant to creating secure couple relationships. This article seeks to test and examine the reliability and validity of the Brief Accessibility, Responsiveness, and Engagement (BARE) Scale-a practical measure of couple attachment-in a clinical sample. Couples took the BARE and other assessments measuring relationship functioning (self and partner reports of relationship satisfaction, relationship stability, positive and negative communication, and attachment styles). Results suggest that the BARE appears to be a reliable and valid tool for assessing couple attachment and can accurately predict and classify whether the couples belong in the clinical or nonclinical group, as well as their level of relationship satisfaction. Results also indicate attachment behaviors are related to relationship outcomes. PMID:26748730

  11. Challenges and responsibilities of clinical teachers in the workplace: an ethnographic approach.

    PubMed

    Magnier, Kirsty M; Wang, Ruolan; Dale, Vicki H M; Pead, Matthew J

    2014-01-01

    This study aimed to explore the complex role of the clinical teacher in the workplace, with a view to identifying effective teaching practices. An ethnographic case-study approach was taken, including participant observations and semi-structured interviews with three participants that were selected from two participating veterinary institutions. The clinical teacher has several responsibilities, such as establishing a rapport with learners and maximizing the use of case-based learning opportunities to provide instruction and support to individual learners in a safe but challenging environment. Associated difficulties include balancing the competing demands of students' learning needs and patients' welfare, as well as maximizing the learning opportunities within available case material. Participants in this study demonstrated a reflective approach, adjusting their teaching approach "in action" and "on action" as appropriate. PMID:24637357

  12. Peptide Decoration of Nanovehicles to Achieve Active Targeting and Pathology-Responsive Cellular Uptake for Bone Metastasis Chemotherapy

    PubMed Central

    Jia, Huizhen; Jia, Wanjian; Miller, Scott; Bowman, Beth; Feng, Jun; Zhan, Fenghuang

    2015-01-01

    To improve bone metastases chemotherapy, a peptide-conjugated diblock copolymer consisting of chimeric peptide, poly(ethylene glycol) and poly(trimethylene carbonate) (Pep-b-PEG-b-PTMC) is fabricated as a drug carrier capable of bone-seeking targeting as well as pathology-responsive charge reversal to ensure effective cellular uptake at the lesion sites. The chimeric peptide CKGHPGGPQAsp8 consists of an osteotropic anionic Asp8, a cathepsin K (CTSK)-cleavable substrate (HPGGPQ) and cationic residue tethered to polymer chain. Pep-b-PEG-b-PTMC can spontaneously self-assemble into negatively charged nanomicelles (~75 nm). As to the model drug of doxorubicin, Pep-b-PEG-b-PTM shows 30.0 ± 1 % and 90.1 ± 2 % for loading content and loading efficiency, respectively. High bone binding capability is demonstrated with that 66 % of Pep-b-PEG-b-PTMC micelles are able to bind to hydroxyl apatite, whereas less than 15 % is for Pep-free micelles. The nanomicelles exhibit a negative-to-positive charge conversion from −18.5 ± 1.9 mV to 15.2 ± 1.8 mV upon exposure to CTSK, an enzyme overexpressed in bone metastatic microenvironments. Such a pathology-responsive transition would lead to remarkably enhanced cellular uptake of the nanomicelles upon reaching lesion sites, thus improving the drug efficacy as verified by the in vitro cytotoxicity assay and the in vivo study in myeloma-bearing 5TGM1 mice model. PMID:26082834

  13. Role of opsonins in clinical response to granulocyte transfusion in granulocytopenic patients

    SciTech Connect

    Keusch, G.T.; Ambinder, E.P.; Kovacs, I.; Goldberg, J.D.; Phillips, D.M.; Holland, J.F.

    1982-10-01

    Fifty febrile severely granulocytopenic patients were given four daily transfusions of 2.2 X 10(10) normal donor granulocytes. Twenty-three responded clinically, although both responders and nonresponders were similar in clinical characteristics at the outset. This study examines the relation between serum opsonic activity before initiation of granulocyte administration and clinical response. Opsonic activity to three test organisms (Escherichia coli 286 and ON 2, and Staphylococcus aureus) and to 15 blood stream isolates from 14 patients was measured as serum-dependent uptake of heat-killed /sup 14/C-labeled bacteria by normal donor leukopheresis granulocytes in an in vitro assay and compared with results obtained with a standard normal serum in each assay. At a concentration of 8 percent serum, all patient groups were equivalent to standard for the three test organisms. When rate-limiting concentrations of serum were employed, opsonic activity remained similar to standard for S. aureus in all patient groups and for the two E. coli strains in responders. In contrast, opsonins for E. coli decreased to 41 to 50 percent of standard in nonresponders. When patients with proved infection were separately analyzed, opsonin activity for E. coli was significantly greater in responders than nonresponders. Eight of 10 patients with 75 percent or greater of standard for opsonic activity against their own blood stream isolates also responded, whereas zero of four with less than 75 percent of standard had a favorable outcome. These results indicate that serum opsonic activity may be a determinant of clinical response to granulocyte transfusion in infected granulocytopenic patients. We conclude that opsonic activity should be assessed in such patients before granulocyte administration and suggest a trial of plasma infusion in opsonin-deficient patients.

  14. B in TB: B Cells as Mediators of Clinically Relevant Immune Responses in Tuberculosis

    PubMed Central

    Rao, Martin; Valentini, Davide; Poiret, Thomas; Dodoo, Ernest; Parida, Shreemanta; Zumla, Alimuddin; Brighenti, Susanna; Maeurer, Markus

    2015-01-01

    The protective role of B cells and humoral immune responses in tuberculosis infection has been regarded as inferior to cellular immunity directed to the intracellular pathogen Mycobacterium tuberculosis. However, B-cell–mediated immune responses in tuberculosis have recently been revisited in the context of B-cell physiology and antigen presentation. We discuss in this review the diverse functions of B cells in tuberculosis, with a focus on their biological and clinical relevance to progression of active disease. We also present the peptide microarray platform as a promising strategy to discover unknown antigenic targets of M. tuberculosis that could contribute to the better understanding of epitope focus of the humoral immune system against M. tuberculosis. PMID:26409285

  15. Clinical Response of Metastatic Breast Cancer to Multi-targeted Therapeutic Approach: A Single Case Report

    PubMed Central

    Meiners, Christian

    2011-01-01

    The present article describes the ongoing (partial) remission of a female patient (41 years old) from estrogen receptor (ER)-positive/progesterone receptor (PR)-negative metastatic breast cancer in response to a combination treatment directed towards the revitalization of the mitochondrial respiratory chain (oxidative phosphorylation), the suppression of NF-kappaB as a factor triggering the inflammatory response, and chemotherapy with capecitabine. The reduction of tumor mass was evidenced by a continuing decline of CA15-3 and CEA tumor marker serum levels and 18FDG-PET-CT plus magnetic resonance (MR) imaging. It is concluded that such combination treatment might be a useful option for treating already formed metastases and for providing protection against the formation of metastases in ER positive breast cancer. The findings need to be corroborated by clinical trials. Whether similar results can be expected for other malignant tumor phenotypes relying on glycolysis as the main energy source remains to be elucidated. PMID:24212668

  16. Crisis averted: How consumers experienced a police and clinical early response (PACER) unit responding to a mental health crisis.

    PubMed

    Evangelista, Eloisa; Lee, Stuart; Gallagher, Angela; Peterson, Violeta; James, Jo; Warren, Narelle; Henderson, Kathryn; Keppich-Arnold, Sandra; Cornelius, Luke; Deveny, Elizabeth

    2016-08-01

    When mental health crisis situations in the community are poorly handled, it can result in physical and emotional injuries. The purpose of this study was to ascertain the experiences and opinions of consumers about the way police and mental health services worked together, specifically via the Alfred Police and Clinical Early Response (A-PACER) model, to assist people experiencing a mental health crisis. Semi-structured in-depth interviews were conducted with 12 mental health consumers who had direct contact with the A-PACER team between June 2013 and March 2015. The study highlighted that people who encountered the A-PACER team generally valued and saw the benefit of a joint police-mental health clinician team response to a mental health crisis situation in the community. In understanding what worked well in how the A-PACER team operated, consumers perspectives can be summarized into five themes: communication and de-escalation, persistence of the A-PACER team, providing a quick response and working well under pressure, handover of information, and A-PACER helped consumers achieve a preferred outcome. All consumers acknowledged the complementary roles of the police officer and mental health clinician, and described the A-PACER team's supportive approach as critical in gaining their trust, engagement and in de-escalating the crises. Further education and training for police officers on how to respond to people with a mental illness, increased provision of follow-up support to promote rehabilitation and prevent future crises, and measures to reduce public scrutiny for the consumer when police responded, were proposed opportunities for improvement. PMID:26931611

  17. Clinical test responses to different orthoptic exercise regimes in typical young adults

    PubMed Central

    Horwood, Anna; Toor, Sonia

    2014-01-01

    Purpose The relative efficiency of different eye exercise regimes is unclear, and in particular the influences of practice, placebo and the amount of effort required are rarely considered. This study measured conventional clinical measures following different regimes in typical young adults. Methods A total of 156 asymptomatic young adults were directed to carry out eye exercises three times daily for 2 weeks. Exercises were directed at improving blur responses (accommodation), disparity responses (convergence), both in a naturalistic relationship, convergence in excess of accommodation, accommodation in excess of convergence, and a placebo regime. They were compared to two control groups, neither of which were given exercises, but the second of which were asked to make maximum effort during the second testing. Results Instruction set and participant effort were more effective than many exercises. Convergence exercises independent of accommodation were the most effective treatment, followed by accommodation exercises, and both regimes resulted in changes in both vergence and accommodation test responses. Exercises targeting convergence and accommodation working together were less effective than those where they were separated. Accommodation measures were prone to large instruction/effort effects and monocular accommodation facility was subject to large practice effects. Conclusions Separating convergence and accommodation exercises seemed more effective than exercising both systems concurrently and suggests that stimulation of accommodation and convergence may act in an additive fashion to aid responses. Instruction/effort effects are large and should be carefully controlled if claims for the efficacy of any exercise regime are to be made. PMID:24471739

  18. Bioengineered human myobundles mimic clinical responses of skeletal muscle to drugs

    PubMed Central

    Madden, Lauran; Juhas, Mark; Kraus, William E; Truskey, George A; Bursac, Nenad

    2015-01-01

    Existing in vitro models of human skeletal muscle cannot recapitulate the organization and function of native muscle, limiting their use in physiological and pharmacological studies. Here, we demonstrate engineering of electrically and chemically responsive, contractile human muscle tissues (‘myobundles’) using primary myogenic cells. These biomimetic constructs exhibit aligned architecture, multinucleated and striated myofibers, and a Pax7+ cell pool. They contract spontaneously and respond to electrical stimuli with twitch and tetanic contractions. Positive correlation between contractile force and GCaMP6-reported calcium responses enables non-invasive tracking of myobundle function and drug response. During culture, myobundles maintain functional acetylcholine receptors and structurally and functionally mature, evidenced by increased myofiber diameter and improved calcium handling and contractile strength. In response to diversely acting drugs, myobundles undergo dose-dependent hypertrophy or toxic myopathy similar to clinical outcomes. Human myobundles provide an enabling platform for predictive drug and toxicology screening and development of novel therapeutics for muscle-related disorders. DOI: http://dx.doi.org/10.7554/eLife.04885.001 PMID:25575180

  19. Intra-articular corticosteroids are effective in osteoarthritis but there are no clinical predictors of response.

    PubMed Central

    Jones, A; Doherty, M

    1996-01-01

    OBJECTIVES: To show whether intra-articular steroid injections are effective in osteoarthritis; to determine factors that predict response; and to determine whether injection has a beneficial effect on muscle strength. METHODS: Double blind, placebo controlled, crossover study in 59 patients with symptomatic osteoarthritis of the knee. Outcome measure-Primary outcome measure: change in visual analogue score for pain at three weeks. Predictors of response analysed using logistic regression with a 15% decrease in pain score at three weeks defining response. RESULTS: Intra-articular methyl prednisolone acetate produced a significant reduction in visual analogue pain score at three weeks compared to both baseline (median change -2.0 mm, interquartile range -16.25 to 4.0) and placebo (median 0.0 mm, interquartile range -9.0 to 6.25). No clinical predictors of response could be identified. Muscle strength was not significantly improved in the short term by intra-articular injection. CONCLUSIONS: Intra-articular corticosteroids are effective for short term relief of pain in osteoarthritis but predicting responders is not possible. There may be a place for their more widespread use. PMID:8976640

  20. Clinical presentation and pharmacotherapy response in social anxiety disorder: The effect of etiological beliefs.

    PubMed

    Cohen, Jonah N; Potter, Carrie M; Drabick, Deborah A G; Blanco, Carlos; Schneier, Franklin R; Liebowitz, Michael R; Heimberg, Richard G

    2015-07-30

    Therapies for social anxiety disorder (SAD) leave many patients symptomatic at the end of treatment and little is known about predictors of treatment response. This study investigated the predictive relationship of patients' etiological attributions to initial clinical features and response to pharmacotherapy. One hundred thirty-seven individuals seeking treatment for SAD received 12 weeks of open treatment with paroxetine. Participants completed the Attributions for the Etiology of Social Anxiety Scale at baseline in addition to measures of social anxiety and depression at baseline and over the course of treatment. A latent class analysis suggested four profiles of etiological beliefs about one's SAD that may be characterized as: Familial Factors, Need to be Liked, Bad Social Experiences, and Diffuse Beliefs. Patients in the more psychosocially-driven classes, Need to be Liked and Bad Social Experiences, had the most severe social anxiety and depression at baseline. Patients in the Familial Factors class, who attributed their SAD to genetic, biological, and early life experiences, had the most rapid response to paroxetine.These results highlight the effect of biological and genetically-oriented etiological beliefs on pharmacological intervention, have implications for person-specific treatment selection, and identify potential points of intervention to augment treatment response. PMID:25920804

  1. Implant-supported overdenture manufactured using CAD/CAM techniques to achieve horizontal path insertion between the primary and secondary structure: A clinical case report

    PubMed Central

    Agustín-Panadero, Rubén; Peñarrocha-Oltra, David; Gomar-Vercher, Sonia; Ferreiroa, Alberto

    2015-01-01

    This report describes the case of an edentulous patient with an atrophic maxilla and severe class III malocclusion. Prosthetic rehabilitation was performed using CAD/CAM techniques for manufacturing an implant-supported overdenture with horizontal insertion. A vestibulo-lingual insertion overdenture is a precision prosthesis with a fixation system affording a good fit between the primary and secondary structure. Both structures exhibit passive horizontal adjustment. This treatment option requires the same number of implants as implant-supported fixed dentures. The horizontal assembly system prevents the prosthesis from loosening or moving in response to axial and non-axial forces. The technique was used to rehabilitate a patient presenting an atrophic upper maxilla, with the insertion of 8 implants. No complications were reported at follow-up 3, 6 and 12 months after fitting of the prosthesis. This system offers solutions to the clinical and laboratory complications associated with hybrid prostheses, concealing emergence of the chimneys and improving implant-prosthesis hygiene. PMID:26140179

  2. HIV-specific humoral responses benefit from stronger prime in phase Ib clinical trial

    PubMed Central

    Bart, Pierre-Alexandre; Huang, Yunda; Karuna, Shelly T.; Chappuis, Samuel; Gaillard, Julien; Kochar, Nidhi; Shen, Xiaoying; Allen, Mary A.; Ding, Song; Hural, John; Liao, Hua-Xin; Haynes, Barton F.; Graham, Barney S.; Gilbert, Peter B.; McElrath, M. Juliana; Montefiori, David C.; Tomaras, Georgia D.; Pantaleo, Giuseppe; Frahm, Nicole

    2014-01-01

    BACKGROUND. Vector prime-boost immunization strategies induce strong cellular and humoral immune responses. We examined the priming dose and administration order of heterologous vectors in HIV Vaccine Trials Network 078 (HVTN 078), a randomized, double-blind phase Ib clinical trial to evaluate the safety and immunogenicity of heterologous prime-boost regimens, with a New York vaccinia HIV clade B (NYVAC-B) vaccine and a recombinant adenovirus 5–vectored (rAd5-vectored) vaccine. METHODS. NYVAC-B included HIV-1 clade B Gag-Pol-Nef and gp120, while rAd5 included HIV-1 clade B Gag-Pol and clades A, B, and C gp140. Eighty Ad5-seronegative subjects were randomized to receive 2 × NYVAC-B followed by 1 × 1010 PFU rAd5 (NYVAC/Ad5hi); 1 × 108 PFU rAd5 followed by 2 × NYVAC-B (Ad5lo/NYVAC); 1 × 109 PFU rAd5 followed by 2 × NYVAC-B (Ad5med/NYVAC); 1 × 1010 PFU rAd5 followed by 2 × NYVAC-B (Ad5hi/NYVAC); or placebo. Immune responses were assessed 2 weeks after the final vaccination. Intracellular cytokine staining measured T cells producing IFN-γ and/or IL-2; cross-clade and epitope-specific binding antibodies were determined; and neutralizing antibodies (nAbs) were assessed with 6 tier 1 viruses. RESULTS. CD4+ T cell response rates ranged from 42.9% to 93.3%. NYVAC/Ad5hi response rates (P ≤ 0.01) and magnitudes (P ≤ 0.03) were significantly lower than those of other groups. CD8+ T cell response rates ranged from 65.5% to 85.7%. NYVAC/Ad5hi magnitudes were significantly lower than those of other groups (P ≤ 0.04). IgG response rates to the group M consensus gp140 were 89.7% for NYVAC/Ad5hi and 21.4%, 84.6%, and 100% for Ad5lo/NYVAC, Ad5med/NYVAC, and Ad5hi/NYVAC, respectively, and were similar for other vaccine proteins. Overall nAb responses were low, but aggregate responses appeared stronger for Ad5med/NYVAC and Ad5hi/NYVAC than for NYVAC/Ad5hi. CONCLUSIONS. rAd5 prime followed by NYVAC boost is superior to the reverse regimen for both vaccine

  3. Cryptococcal Genotype Influences Immunologic Response and Human Clinical Outcome after Meningitis

    PubMed Central

    Wiesner, Darin L.; Moskalenko, Oleksandr; Corcoran, Jennifer M.; McDonald, Tami; Rolfes, Melissa A.; Meya, David B.; Kajumbula, Henry; Kambugu, Andrew; Bohjanen, Paul R.; Knight, Joseph F.; Boulware, David R.; Nielsen, Kirsten

    2012-01-01

    ABSTRACT In sub-Saharan Africa, cryptococcal meningitis (CM) continues to be a predominant cause of AIDS-related mortality. Understanding virulence and improving clinical treatments remain important. To characterize the role of the fungal strain genotype in clinical disease, we analyzed 140 Cryptococcus isolates from 111 Ugandans with AIDS and CM. Isolates consisted of 107 nonredundant Cryptococcus neoformans var. grubii strains and 8 C. neoformans var. grubii/neoformans hybrid strains. Multilocus sequence typing (MLST) was used to characterize genotypes, yielding 15 sequence types and 4 clonal clusters. The largest clonal cluster consisted of 74 isolates. The results of Burst and phylogenetic analysis suggested that the C. neoformans var. grubii strains could be separated into three nonredundant evolutionary groups (Burst group 1 to group 3). Patient mortality was differentially associated with the different evolutionary groups (P = 0.04), with the highest mortality observed among Burst group 1, Burst group 2, and hybrid strains. Compared to Burst group 3 strains, Burst group 1 strains were associated with higher mortality (P = 0.02), exhibited increased capsule shedding (P = 0.02), and elicited a more pronounced Th2 response during ex vivo cytokine release assays with strain-specific capsule stimulation (P = 0.02). The results of these analyses suggest that cryptococcal strain variation can be an important determinant of human immune responses and mortality. PMID:23015735

  4. Inflammation and clinical response to treatment in depression: A meta-analysis.

    PubMed

    Strawbridge, R; Arnone, D; Danese, A; Papadopoulos, A; Herane Vives, A; Cleare, A J

    2015-10-01

    The depressive state has been characterised as one of elevated inflammation, which holds promise for better understanding treatment-resistance in affective disorders as well as for future developments in treatment stratification. Aiming to investigate alterations in the inflammatory profiles of individuals with depression as putative biomarkers for clinical response, we conducted meta-analyses examining data from 35 studies that investigated inflammation before and after treatment in depressed patients together with a measure of clinical response. There were sufficient data to analyse IL-6, TNFα and CRP. Levels of IL-6 decreased with antidepressant treatment regardless of outcome, whereas persistently elevated TNFα was associated with prospectively determined treatment resistance. Treatment non-responders tended to have higher baseline inflammation, using a composite measure of inflammatory markers. Our findings suggest that elevated levels of inflammation are contributory to treatment resistance. Combining inflammatory biomarkers might prove a useful tool to improve diagnosis and detection of treatment refractoriness, and targeting persistent inflammation in treatment-resistant depression may offer a potential target for the development of novel intervention strategies. PMID:26169573

  5. Threshold tracking pacing based on beat by beat evoked response detection: clinical benefits and potential problems.

    PubMed

    Duru, F; Bauersfeld, U; Schüller, H; Candinas, R

    2000-10-01

    Continuous monitoring of pacemaker stimulation thresholds and automatic adjustment of pacemaker outputs were among the longstanding goals of the pacing community. The first clinically successful implementation of threshold tracking pacing was the Autocapture feature which has accomplished automatic ventricular capture verification for every single stimulus by monitoring the Evoked Response (ER) signal resulting from myocardial depolarization. The Autocapture feature not only decreases energy consumption by keeping the stimulation output slightly above the actual threshold, but also increases patient safety by access to high-output back-up pulses if there is loss of capture. Furthermore, it provides valuable documentation of stimulation thresholds over time and serves as a valuable research tool. Current limitations for its widespread use include the requirements for implantation of bipolar low polarization leads and unipolar pacing in the ventricle. Fusion/pseudofusion beats with resultant insufficient or even non-existent ER signal amplitudes followed by unnecessary delivery of back-up pulses and a possible increase in pacemaker output is not an uncommon observation unique to the Autocapture feature. The recent incorporation of the Autocapture algorithm in dual chamber pacemakers has been challenging because of more frequent occurrence of fusion/pseudofusion beats in the presence of normal AV conduction. Along with a review of the previously published studies and our clinical experience, this article discusses the clinical advantages and potential problems of Autocapture. PMID:11046190

  6. Hypokalemic periodic paralysis; two different genes responsible for similar clinical manifestations.

    PubMed

    Kim, Hunmin; Hwang, Hee; Cheong, Hae Il; Park, Hye Won

    2011-11-01

    Primary hypokalemic periodic paralysis (HOKPP) is an autosomal dominant disorder manifesting as recurrent periodic flaccid paralysis and concomitant hypokalemia. HOKPP is divided into type 1 and type 2 based on the causative gene. Although 2 different ion channels have been identified as the molecular genetic cause of HOKPP, the clinical manifestations between the 2 groups are similar. We report the cases of 2 patients with HOKPP who both presented with typical clinical manifestations, but with mutations in 2 different genes (CACNA1Sp.Arg528His and SCN4A p.Arg672His). Despite the similar clinical manifestations, there were differences in the response to acetazolamide treatment between certain genotypes of SCN4A mutations and CACNA1S mutations. We identified p.Arg672His in the SCN4A gene of patient 2 immediately after the first attack through a molecular genetic testing strategy. Molecular genetic diagnosis is important for genetic counseling and selecting preventive treatment. PMID:22253645

  7. Sparse Multi-Response Tensor Regression for Alzheimer's Disease Study With Multivariate Clinical Assessments.

    PubMed

    Li, Zhou; Suk, Heung-Il; Shen, Dinggang; Li, Lexin

    2016-08-01

    Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disorder that has recently seen serious increase in the number of affected subjects. In the last decade, neuroimaging has been shown to be a useful tool to understand AD and its prodromal stage, amnestic mild cognitive impairment (MCI). The majority of AD/MCI studies have focused on disease diagnosis, by formulating the problem as classification with a binary outcome of AD/MCI or healthy controls. There have recently emerged studies that associate image scans with continuous clinical scores that are expected to contain richer information than a binary outcome. However, very few studies aim at modeling multiple clinical scores simultaneously, even though it is commonly conceived that multivariate outcomes provide correlated and complementary information about the disease pathology. In this article, we propose a sparse multi-response tensor regression method to model multiple outcomes jointly as well as to model multiple voxels of an image jointly. The proposed method is particularly useful to both infer clinical scores and thus disease diagnosis, and to identify brain subregions that are highly relevant to the disease outcomes. We conducted experiments on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, and showed that the proposed method enhances the performance and clearly outperforms the competing solutions. PMID:26960221

  8. Clinical Response and Transfusion Reactions of Sheep Subjected to Single Homologous Blood Transfusion

    PubMed Central

    Sousa, Rejane Santos; Minervino, Antonio Humberto Hamad; Araújo, Carolina Akiko Sato Cabral; Rodrigues, Frederico Augusto Mazzocca Lopes; Oliveira, Francisco Leonardo Costa; Zaminhan, Janaina Larissa Rodrigues; Moreira, Thiago Rocha; Sousa, Isadora Karolina Freitas; Ortolani, Enrico Lippi; Barrêto Júnior, Raimundo Alves

    2014-01-01

    Studies in relation to blood conservation and responses to transfusion are scarce for ruminants. We evaluated the clinical manifestations of sheep that received a single homologous transfusion of whole blood, focusing on transfusion reactions. Eighteen adult sheep were subjected to a single phlebotomy to withdraw 40% of the total blood volume, which was placed into CPDA-1 bags and then divided into G0, animals that received fresh blood, and G15 and G35, animals that received blood stored for 15 or 35 days, respectively. Clinical observations were recorded throughout the transfusion, whereas heart rate, respiratory rate, and rectal temperature were assessed at the following times: 24 hours after phlebotomy and before transfusion; 30 minutes, six, twelve, 24, 48, 72, and 96 hours and eight and 16 days after transfusion. All groups presented transfusion reactions, among which hyperthermia was the most frequent (50% of animals). Tachycardia occurred most frequently in the G35 animals (50% of them). During transfusion G35 animals presented more clinical manifestation (P < 0.05). Transfusion of fresh or stored total blood improved the blood volume, but transfusion reactions occurred, demonstrating that a single transfusion of fresh or stored blood can cause inflammatory and febrile nonhemolytic transfusion reactions in sheep. PMID:25544959

  9. Circulating Chromogranin A as A Marker for Monitoring Clinical Response in Advanced Gastroenteropancreatic Neuroendocrine Tumors

    PubMed Central

    Li, Na; Li, Yanyan; Lu, Ming; Li, Zhongwu; Lu, Zhihao; Li, Jie; Shen, Lin

    2016-01-01

    Chromogranin A (CgA), present in the chromaffin granules of neuroendocrine cells, is a useful biomarker for the diagnosis of patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs). This study was conducted to investigate the potential role of circulating CgA in monitoring clinical response in Chinese patients with advanced GEP-NETs. Eighty patients with advanced GEP-NETs treated in Peking University Cancer Hospital from September 2011 to May 2014 and 65 healthy individuals were included in this study. Serum CgA levels were analyzed for relationship with patient’s baseline characteristics and clinical outcome. Median CgA levels were significantly higher in patients with advanced GEP-NETs than in healthy individuals (93.8 ng/mL vs. 37.1 ng/mL; P<0.01), as well as significantly higher in patients with carcinoid syndrome or liver metastasis than in those without carcinoid syndrome (298.8 ng/mL vs. 82.9 ng/mL; P = 0.011) or liver metastasis (137.0 ng/mL vs. 64.4 ng/mL; P = 0.023). A CgA cutoff value of 46.2 ng/mL was used in this study with a sensitivity of 78.8% and specificity of 73.8%. Patients with CgA levels higher than 46.2 ng/mL had a worse prognosis than patients with CgA levels lower than 46.2 ng/mL (P = 0.045). Notably, a weak correlation was observed between changes in serum CgA levels and clinical response to the IP regimen as well as SSAs. Our data also indicate that serum CgA could be a useful indicator of patient prognosis though there is more research required in order to validate such claims. PMID:27159453

  10. Does contemporary vancomycin dosing achieve therapeutic targets in a heterogeneous clinical cohort of critically ill patients? Data from the multinational DALI study

    PubMed Central

    2014-01-01

    Introduction The objective of this study was to describe the pharmacokinetics of vancomycin in ICU patients and to examine whether contemporary antibiotic dosing results in concentrations that have been associated with favourable response. Methods The Defining Antibiotic Levels in Intensive Care (DALI) study was a prospective, multicentre pharmacokinetic point-prevalence study. Antibiotic dosing was as per the treating clinician either by intermittent bolus or continuous infusion. Target trough concentration was defined as ≥15 mg/L and target pharmacodynamic index was defined as an area under the concentration-time curve over a 24-hour period divided by the minimum inhibitory concentration of the suspected bacteria (AUC0–24/MIC ratio) >400 (assuming MIC ≤1 mg/L). Results Data of 42 patients from 26 ICUs were eligible for analysis. A total of 24 patients received vancomycin by continuous infusion (57%). Daily dosage of vancomycin was 27 mg/kg (interquartile range (IQR) 18 to 32), and not different between patients receiving intermittent or continuous infusion. Trough concentrations were highly variable (median 27, IQR 8 to 23 mg/L). Target trough concentrations were achieved in 57% of patients, but more frequently in patients receiving continuous infusion (71% versus 39%; P = 0.038). Also the target AUC0–24/MIC ratio was reached more frequently in patients receiving continuous infusion (88% versus 50%; P = 0.008). Multivariable logistic regression analysis with adjustment by the propensity score could not confirm continuous infusion as an independent predictor of an AUC0–24/MIC >400 (odds ratio (OR) 1.65, 95% confidence interval (CI) 0.2 to 12.0) or a Cmin ≥15 mg/L (OR 1.8, 95% CI 0.4 to 8.5). Conclusions This study demonstrated large interindividual variability in vancomycin pharmacokinetic and pharmacodynamic target attainment in ICU patients. These data suggests that a re-evaluation of current vancomycin dosing recommendations in

  11. Clinically Relevant Progestins Regulate Neurogenic and Neuroprotective Responses in Vitro and in Vivo

    PubMed Central

    Liu, Lifei; Zhao, Liqin; She, Hongyun; Chen, Shuhua; Wang, Jun Ming; Wong, Charisse; McClure, Kelsey; Sitruk-Ware, Regine; Brinton, Roberta Diaz

    2010-01-01

    Previously, we demonstrated that progesterone (P4) promoted adult rat neural progenitor cell (rNPC) proliferation with concomitant regulation of cell-cycle gene expression via the P4 receptor membrane component/ERK pathway. Here, we report the efficacy of seven clinically relevant progestins alone or in combination with 17β-estradiol (E2) on adult rNPC proliferation and hippocampal cell viability in vitro and in vivo. In vitro analyses indicated that P4, norgestimate, Nestorone, norethynodrel, norethindrone, and levonorgestrel (LNG) significantly increased in rNPC proliferation, whereas norethindrone acetate was without effect, and medroxyprogesterone acetate (MPA) inhibited rNPC proliferation. Proliferative progestins in vitro were also neuroprotective. Acute in vivo exposure to P4 and Nestorone significantly increased proliferating cell nuclear antigen and cell division cycle 2 expression and total number of hippocampal 5-bromo-2-deoxyuridine (BrdU)-positive cells, whereas LNG and MPA were without effect. Mechanistically, neurogenic progestins required activation of MAPK to promote proliferation. P4, Nestorone, and LNG significantly increased ATP synthase subunit α (complex V, subunit α) expression, whereas MPA was without effect. In combination with E2, P4, Nestorone, LNG, and MPA significantly increased BrdU incorporation. However, BrdU incorporation induced by E2 plus LNG or MPA was paralleled by a significant increase in apoptosis. A rise in Bax/Bcl-2 ratio paralleled apoptosis induced by LNG and MPA. With the exception of P4, clinical progestins antagonized E2-induced rise in complex V, subunit α. These preclinical translational findings indicate that the neurogenic response to clinical progestins varies dramatically. Progestin impact on the regenerative capacity of the brain has clinical implications for contraceptive and hormone therapy formulations prescribed for pre- and postmenopausal women. PMID:20943809

  12. Can a Clinical Test of Reaction Time Predict a Functional Head-Protective Response?

    PubMed Central

    ECKNER, JAMES T.; LIPPS, DAVID B.; KIM, HOGENE; RICHARDSON, JAMES K.; ASHTON-MILLER, JAMES A.

    2015-01-01

    Purpose Reaction time is commonly prolonged after a sport-related concussion. Besides being a marker for injury, a rapid reaction time is necessary for protective maneuvers that can reduce the frequency and severity of additional head impacts. The purpose of this study was to determine whether a clinical test of simple visuomotor reaction time predicted the time taken to raise the hands to protect the head from a rapidly approaching ball. Methods Twenty-six healthy adult participants recruited from campus and community recreation and exercise facilities completed two experimental protocols during a single session: a manual visuomotor simple reaction time test (RTclin) and a sport-related head-protective response (RTsprt). RTclin measured the time required to catch a thin vertically oriented device on its release by the tester and was calculated from the distance the device fell before being arrested. RTsprt measured the time required to raise the hands from waist level to block a foam tennis ball fired toward the subject’s face from an air cannon and was determined using an optoelectronic camera system. A correlation coefficient was calculated between RTclin and RTsprt, with linear regression used to assess for effect modification by other covariates. Results A strong positive correlation was found between RTclin and RTsprt (r = 0.725, P < 0.001) independent of age, gender, height, or weight. Conclusions RTclin is predictive of a functional sport-related head-protective response. To our knowledge, this is the first demonstration of a clinical test predicting the ability to protect the head in a simulated sport environment. This correlation with a functional head-protective response is a relevant consideration for the potential use of RTclin as part of a multifaceted concussion assessment program. PMID:20689458

  13. How Iranian Medical Trainees Approach their Responsibilities in Clinical Settings; A Grounded Theory Research

    PubMed Central

    Asemani, Omid; Iman, Mohammad Taghi; Moattari, Marzieh; Khayyer, Mohammad; Sharif, Farkhondeh; Tabei, Seyed Ziaaddin

    2015-01-01

    Background: It seems we are now experiencing “responsibility problems” among medical trainees (MTs) and some of those recently graduated from medical schools in Iran. Training responsible professionals have always been one of the main concerns of medical educators. Nevertheless, there is a dearth of research in the literature on “responsibility” especially from the medical education point of view. Therefore, the present study was carried out with the aim of presenting a theoretical based framework for understanding how MTs approach their responsibilities in educational settings. Method: This qualitative study was conducted at Shiraz University of Medical Sciences (SUMS) using the grounded theory methodology. 15 MTs and 10 clinical experts and professional nurses were purposefully chosen as participants. Data was analyzed using the methodology suggested by Corbin and Strauss, 1998. Results: “Try to find acceptance toward expectations”, “try to be committed to meet the expectations” and “try to cope with unacceptable expectations” were three main categories extracted based on the research data. Abstractly, the main objective for using these processes was “to preserve the integrity of student identity” which was the core category of this research too. Moreover, it was also found that practically, “responsibility” is considerably influenced by lots of positive and negative contextual and intervening conditions. Conclusion: “Acceptance” was the most decisive variable highly effective in MTs’ responsibility. Therefore, investigating the “process of acceptance” regarding the involved contextual and intervening conditions might help medical educators correctly identify and effectively control negative factors and reinforce the constructive ones that affect the concept of responsibility in MTs. PMID:26379351

  14. Triptan-induced contractile (5-HT1B receptor) responses in human cerebral and coronary arteries: relationship to clinical effect.

    PubMed

    Edvinsson, Lars; Uddman, Erik; Wackenfors, Angelica; Davenport, Anthony; Longmore, Jenny; Malmsjö, Malin

    2005-09-01

    Triptans are agonists at 5-HT1B and 5-HT1D (where 5-HT is 5-hydroxytryptamine; serotonin) receptors and cause vasoconstriction of isolated blood vessels. The aim of the present study was to determine vasoconstrictor potency (EC50) of triptans in human coronary and cerebral arteries and to examine whether there was any relationship with the maximal plasma concentrations (Cmax; nM) of the drugs achieved following oral administration of clinically relevant doses to man using values reported in the literature. We also examined the expression of 5-HT1B receptors in atherosclerotic and normal coronary arteries. The vasocontractile responses to sumatriptan, rizatriptan or eletriptan were characterized by in vitro pharmacology. The ratio of Cmax/EC50 was calculated. 5-HT1B and 5-HT1D receptors were visualized by immunohistochemical techniques in coronary arteries. Sumatriptan, rizatriptan and eletriptan were powerful vasoconstrictors in cerebral artery. The rank order of agonist potency was eletriptan=rizatriptan=sumatriptan. In the coronary artery, the triptans were weaker vasoconstrictors. The rank order of potency was similar. In cerebral artery the ratio of Cmax/EC50 was not significantly different from unity, indicating a relationship between these two parameters. In general for the coronary artery, the ratios were significantly less than unity, indicating no direct relationship. Immunohistochemistry showed expression of 5-HT1B receptors in the medial layer, but did not reveal any obvious difference in 5-HT1B receptor expression between normal and atherosclerotic coronary arteries. The results support the notion that triptans are selective vasoconstrictors of cerebral arteries over coronary arteries and that there is a relationship between vasoconstrictor potency in cerebral arteries and clinically relevant plasma levels. PMID:15853772

  15. Clinical utility of clocortolone pivalate for the treatment of corticosteroid-responsive skin disorders: a systematic review

    PubMed Central

    Singh, Sanjay; Mann, Baldeep Kaur

    2012-01-01

    Clocortolone pivalate 0.1% cream is a class IV mid-strength topical glucocorticoid. After topical application the glucocorticoid achieves higher concentration in inflamed skin compared with normal skin. Furthermore, pharmacologic studies have shown that there is little systemic absorption of clocortolone pivalate and hence no adrenal suppression. Systematic review was performed to evaluate the efficacy and safety of the glucocorticoid. PubMed, the Cochrane Library, and individual websites of the top 20 dermatology journals were searched using a defined strategy. Following the selection criteria, eight clinical trials were selected, of which five were randomized controlled trials. The trials mainly included patients with atopic dermatitis and eczemas. Quality appraisal of randomized controlled trials was done using the Delphi list, which showed that the trials had weaknesses in several items. The results of the systematic review tend to show that clocortolone pivalate cream is generally effective with early onset of action and has a good safety profile in the treatment of these conditions. Further studies comparing this glucocorticoid with other glucocorticoids and treatments in steroid-responsive dermatoses are desirable. PMID:22791998

  16. TNFRSF14 aberrations in follicular lymphoma increase clinically significant allogeneic T-cell responses

    PubMed Central

    Kotsiou, Eleni; Okosun, Jessica; Besley, Caroline; Iqbal, Sameena; Matthews, Janet; Fitzgibbon, Jude; Gribben, John G.

    2016-01-01

    Donor T-cell immune responses can eradicate lymphomas after allogeneic hematopoietic stem cell transplantation (AHSCT), but can also damage healthy tissues resulting in harmful graft-versus-host disease (GVHD). Next-generation sequencing has recently identified many new genetic lesions in follicular lymphoma (FL). One such gene, tumor necrosis factor receptor superfamily 14 (TNFRSF14), abnormal in 40% of FL patients, encodes the herpes virus entry mediator (HVEM) which limits T-cell activation via ligation of the B- and T-lymphocyte attenuator. As lymphoma B cells can act as antigen-presenting cells, we hypothesized that TNFRSF14 aberrations that reduce HVEM expression could alter the capacity of FL B cells to stimulate allogeneic T-cell responses and impact the outcome of AHSCT. In an in vitro model of alloreactivity, human lymphoma B cells with TNFRSF14 aberrations had reduced HVEM expression and greater alloantigen-presenting capacity than wild-type lymphoma B cells. The increased immune-stimulatory capacity of lymphoma B cells with TNFRSF14 aberrations had clinical relevance, associating with higher incidence of acute GVHD in patients undergoing AHSCT. FL patients with TNFRSF14 aberrations may benefit from more aggressive immunosuppression to reduce harmful GVHD after transplantation. Importantly, this study is the first to demonstrate the impact of an acquired genetic lesion on the capacity of tumor cells to stimulate allogeneic T-cell immune responses which may have wider consequences for adoptive immunotherapy strategies. PMID:27103745

  17. Respiratory responses to cold water immersion: neural pathways, interactions, and clinical consequences awake and asleep.

    PubMed

    Datta, Avijit; Tipton, Michael

    2006-06-01

    The ventilatory responses to immersion and changes in temperature are reviewed. A fall in skin temperature elicits a powerful cardiorespiratory response, termed "cold shock," comprising an initial gasp, hypertension, and hyperventilation despite a profound hypocapnia. The physiology and neural pathways of this are examined with data from original studies. The respiratory responses to skin cooling override both conscious and other autonomic respiratory controls and may act as a precursor to drowning. There is emerging evidence that the combination of the reestablishment of respiratory rhythm following apnea, hypoxemia, and coincident sympathetic nervous and cyclic vagal stimulation appears to be an arrhythmogenic trigger. The potential clinical implications of this during wakefulness and sleep are discussed in relation to sudden death during immersion, underwater birth, and sleep apnea. A drop in deep body temperature leads to a slowing of respiration, which is more profound than the reduced metabolic demand seen with hypothermia, leading to hypercapnia and hypoxia. The control of respiration is abnormal during hypothermia, and correction of the hypoxia by inhalation of oxygen may lead to a further depression of ventilation and even respiratory arrest. The immediate care of patients with hypothermia needs to take these factors into account to maximize the chances of a favorable outcome for the rescued casualty. PMID:16714416

  18. TNFRSF14 aberrations in follicular lymphoma increase clinically significant allogeneic T-cell responses.

    PubMed

    Kotsiou, Eleni; Okosun, Jessica; Besley, Caroline; Iqbal, Sameena; Matthews, Janet; Fitzgibbon, Jude; Gribben, John G; Davies, Jeffrey K

    2016-07-01

    Donor T-cell immune responses can eradicate lymphomas after allogeneic hematopoietic stem cell transplantation (AHSCT), but can also damage healthy tissues resulting in harmful graft-versus-host disease (GVHD). Next-generation sequencing has recently identified many new genetic lesions in follicular lymphoma (FL). One such gene, tumor necrosis factor receptor superfamily 14 (TNFRSF14), abnormal in 40% of FL patients, encodes the herpes virus entry mediator (HVEM) which limits T-cell activation via ligation of the B- and T-lymphocyte attenuator. As lymphoma B cells can act as antigen-presenting cells, we hypothesized that TNFRSF14 aberrations that reduce HVEM expression could alter the capacity of FL B cells to stimulate allogeneic T-cell responses and impact the outcome of AHSCT. In an in vitro model of alloreactivity, human lymphoma B cells with TNFRSF14 aberrations had reduced HVEM expression and greater alloantigen-presenting capacity than wild-type lymphoma B cells. The increased immune-stimulatory capacity of lymphoma B cells with TNFRSF14 aberrations had clinical relevance, associating with higher incidence of acute GVHD in patients undergoing AHSCT. FL patients with TNFRSF14 aberrations may benefit from more aggressive immunosuppression to reduce harmful GVHD after transplantation. Importantly, this study is the first to demonstrate the impact of an acquired genetic lesion on the capacity of tumor cells to stimulate allogeneic T-cell immune responses which may have wider consequences for adoptive immunotherapy strategies. PMID:27103745

  19. Immunotherapy in non-small cell lung cancer: the clinical impact of immune response and targeting

    PubMed Central

    Linardou, Helena; Kosmidis, Paris

    2016-01-01

    Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related death worldwide. In recent years, through a better understanding of the interactions between the immune system and tumor cells (TC), immunotherapy has emerged as a promising therapeutic strategy. Chemotherapy has long been reported to interfere with the immune response to the tumor and conversely, anti-tumor immunity may add to those effects. Anti-tumor vaccines, such as MAGE-A3, Tecetomide, TG4010, CIMAvax, tumor cell vaccines and dendritic cell (DC) vaccines emerged as potent inducers of the immune response against the tumor. More recently the approval of the anti-programmed cell death 1 (anti-PD-1) monoclonal antibodies nivolumab and pembrolizumab for previously treated advanced squamous and non-squamous NSCLC, as well as other immune checkpoint inhibitors delivering promising results, has radically transformed the therapeutic landscape of NSCLC. Combination strategies now appear as the next step. Notwithstanding these successes, immunotherapy still holds significant drawbacks and currently several improvements are needed before routine use in clinical practice, including identification of robust biomarkers for optimal patient selection, as well as defining the best way to evaluate response. PMID:27563655

  20. Immunotherapy in non-small cell lung cancer: the clinical impact of immune response and targeting.

    PubMed

    Mountzios, Giannis; Linardou, Helena; Kosmidis, Paris

    2016-07-01

    Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related death worldwide. In recent years, through a better understanding of the interactions between the immune system and tumor cells (TC), immunotherapy has emerged as a promising therapeutic strategy. Chemotherapy has long been reported to interfere with the immune response to the tumor and conversely, anti-tumor immunity may add to those effects. Anti-tumor vaccines, such as MAGE-A3, Tecetomide, TG4010, CIMAvax, tumor cell vaccines and dendritic cell (DC) vaccines emerged as potent inducers of the immune response against the tumor. More recently the approval of the anti-programmed cell death 1 (anti-PD-1) monoclonal antibodies nivolumab and pembrolizumab for previously treated advanced squamous and non-squamous NSCLC, as well as other immune checkpoint inhibitors delivering promising results, has radically transformed the therapeutic landscape of NSCLC. Combination strategies now appear as the next step. Notwithstanding these successes, immunotherapy still holds significant drawbacks and currently several improvements are needed before routine use in clinical practice, including identification of robust biomarkers for optimal patient selection, as well as defining the best way to evaluate response. PMID:27563655

  1. Development and validation of a questionnaire to evaluate medical students’ and residents’ responsibility in clinical settings

    PubMed Central

    Asemani, Omid; Iman, Mohammad Taghi; Khayyer, Mohammad; Tabei, Seyed Ziaaddin; Sharif, Farkhondeh; Moattari, Marzieh

    2014-01-01

    There is a shortage of quantitative measures for assessing the concept of responsibility as a fundamental construct in medical education, ethics and professionalism in existing literature. This study aimed to develop an instrument for measuring responsibility in both undergraduate and graduate medical students during clinical training. Instrument content was based on literature review and mainly qualitative data obtained from a published grounded theory research. The draft questionnaire (Persian version) was then validated and revised with regard to face and content validity. The finalized 41-item questionnaire consists of four domains that were identified using factor analysis. Test-retest reliability and internal consistency were also assessed. Test-retest reliability was rather high, ranging between 0.70 and 0.75 for all domains. Cronbach’s alpha coefficients were 0.75 – 0.76 for all domains and 0.90 for the composite scale of the whole questionnaire. Correlations between the four domains of the instrument were also satisfactory (r ≤ 0.47 for most domains). The correlation between each domain and the composite scale was higher than its correlation with other domains (r ≥ 0.79 for most domains). The instrument demonstrated good construct and internal validity, and can be suitable for measuring the concept of responsibility in practice in different groups of undergraduate and graduate medical trainees (MTs). PMID:25512836

  2. Integrating in vitro sensitivity and dose-response slope is predictive of clinical response to ABL kinase inhibitors in chronic myeloid leukemia.

    PubMed

    Vainstein, Vladimir; Eide, Christopher A; O'Hare, Thomas; Shukron, Ofir; Druker, Brian J

    2013-11-01

    BCR-ABL mutations result in clinical resistance to ABL tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML). Although in vitro 50% inhibitory concentration (IC(50)) values for specific mutations have been suggested to guide TKI choice in the clinic, the quantitative relationship between IC(50) and clinical response has never been demonstrated. We used Hill's equation for in vitro response of Ba/F3 cells transduced with various BCR-ABL mutants to determine IC(50) and the slope of the dose-response curve. We found that slope variability between mutants tracked with in vitro TKI resistance, provides particular additional interpretive value in cases where in vitro IC(50) and clinical response are disparate. Moreover, unlike IC(50) alone, higher inhibitory potential at peak concentration (IPP), which integrates IC(50), slope, and peak concentration (Cmax), correlated with improved complete cytogenetic response (CCyR) rates in CML patients treated with dasatinib. Our findings suggest a metric integrating in vitro and clinical data may provide an improved tool for BCR-ABL mutation-guided TKI selection. PMID:24062017

  3. Patterns of Clinical Response to PSA Elevation in American Indian/Alaska Native Men: A Multi-center Pilot Study

    PubMed Central

    Tilburt, Jon C.; Koller, Kathryn; Tiesinga, James J.; Wilson, Robin T.; Trinh, Anne C.; Hill, Kristin; Hall, Ingrid J.; Smith, Judith Lee; Ekwueme, Donatus U.; Petersen, Wesley O.

    2016-01-01

    Objective To assess clinical treatment patterns and response times among American Indian/Alaska Native men with a newly elevated PSA. Methods We retrospectively identified men ages 50–80 receiving care in one of three tribally-operated clinics in Northern Minnesota, one medical center in Alaska, and who had an incident PSA elevation (≥ 4 ng/ml) in a specified time period. A clinical response was considered timely if it was documented as occurring within 90 days of the incident PSA elevation. Results Among 82 AI/AN men identified from medical records with an incident PSA elevation, 49 (60%) received a timely clinical response, while 18 (22%) had no documented clinical response. Conclusions One in five AI/AN men in our study had no documented clinical action following an incident PSA elevation. Although a pilot study, these findings suggest the need to improve the documentation, notification, and care following an elevated PSA at clinics serving AI/AN men. PMID:24185163

  4. Clinical Responses to Atomoxetine in Attention-Deficit/Hyperactivity Disorder: The Integrated Data Exploratory Analysis (IDEA) Study

    ERIC Educational Resources Information Center

    Newcorn, Jeffrey H.; Sutton, Virginia K.; Weiss, Margaret D.; Sumner, Calvin R.

    2009-01-01

    Data from six randomized controlled trials in the U.S. reveal that 47 percent of patients aged six to 18 years showed a much improved clinical response to atomoxetine as a treatment for attention deficit hyperactivity disorder while 40 percent did not have a response. Augmenting or switching treatment in non-responders by week 4 is suggested.

  5. Clinical and pathological responses of pigs from two genetically diverse commercial lines to porcine respiratory and reproductive syndrome virus infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The response to infection from porcine reproductive and respiratory syndrome virus (PRRSV) for two genetically diverse commercial pig lines was investigated. Seventy two pigs from each line, aged 6 weeks, were challenged with PRRSV VR-2385, and 66 littermates served as control. The clinical response...

  6. Systolic pressure response to voluntary apnea predicts sympathetic tone in obstructive sleep apnea as a clinically useful index.

    PubMed

    Jouett, Noah P; Hardisty, Janelle M; Mason, J Ryan; Niv, Dorene; Romano, James J; Watenpaugh, Donald E; Burk, John R; Smith, Michael L

    2016-01-01

    The present investigation tested the hypotheses that systolic arterial pressure (SAP) responses to voluntary apnea (a) serve as a surrogate of sympathetic nerve activity (SNA), (b) can distinguish Obstructive Sleep Apnea (OSA) patients from control subjects and (c) can document autonomic effects of treatment. 9 OSA and 10 control subjects were recruited in a laboratory study; 44 OSA subjects and 78 control subjects were recruited in a clinical study; and 21 untreated OSA subjects and 14 well-treated OSA subjects were recruited into a treatment study. Each subject performed hypoxic and room air voluntary apneas in triplicate. Muscle SNA (MSNA) and continuous AP were measured during each apnea in the laboratory study, while systolic arterial pressure (SAP) responses were measured continuously and by standard auscultation in the clinical and treatment studies. OSA subjects exhibited increased mean arterial pressure (MAP), SAP and MSNA responses to hypoxic apnea (all P<0.01) and the SAP response highly correlated with the MSNA response (R(2)=0.72, P<0.001). Clinical assessment confirmed that OSA subjects exhibited markedly elevated SAP responses (P<0.01), while treated OSA subjects had a decreased SAP response to apnea (P<0.04) compared to poorly treated subjects. These data indicate that (a) OSA subjects exhibit increased pressor and MSNA responses to apnea, and that (b) voluntary apnea may be a clinically useful assessment tool of autonomic dysregulation and treatment efficacy in OSA. PMID:26774324

  7. The Pharmacogenetics Research Network: From SNP Discovery to Clinical Drug Response

    PubMed Central

    Giacomini, KM; Brett, CM; Altman, RB; Benowitz, NL; Dolan, ME; Flockhart, DA; Johnson, JA; Hayes, DF; Klein, T; Krauss, RM; Kroetz, DL; McLeod, HL; Nguyen, AT; Ratain, MJ; Relling, MV; Reus, V; Roden, DM; Schaefer, CA; Shuldiner, AR; Skaar, T; Tantisira, K; Tyndale, RF; Wang, L; Weinshilboum, RM; Weiss, ST; Zineh, I

    2016-01-01

    The NIH Pharmacogenetics Research Network (PGRN) is a collaborative group of investigators with a wide range of research interests, but all attempting to correlate drug response with genetic variation. Several research groups concentrate on drugs used to treat specific medical disorders (asthma, depression, cardiovascular disease, addiction of nicotine, and cancer), whereas others are focused on specific groups of proteins that interact with drugs (membrane transporters and phase II drug-metabolizing enzymes). The diverse scientific information is stored and annotated in a publicly accessible knowledge base, the Pharmacogenetics and Pharmacogenomics Knowledge base (PharmGKB). This report highlights selected achievements and scientific approaches as well as hypotheses about future directions of each of the groups within the PGRN. Seven major topics are included: informatics (PharmGKB), cardiovascular, pulmonary, addiction, cancer, transport, and metabolism. PMID:17339863

  8. Modeling Pathologic Response of Esophageal Cancer to Chemoradiation Therapy Using Spatial-Temporal {sup 18}F-FDG PET Features, Clinical Parameters, and Demographics

    SciTech Connect

    Zhang, Hao; Tan, Shan; Chen, Wengen; Kligerman, Seth; Kim, Grace; D'Souza, Warren D.; Suntharalingam, Mohan; Lu, Wei

    2014-01-01

    Purpose: To construct predictive models using comprehensive tumor features for the evaluation of tumor response to neoadjuvant chemoradiation therapy (CRT) in patients with esophageal cancer. Methods and Materials: This study included 20 patients who underwent trimodality therapy (CRT + surgery) and underwent {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) both before and after CRT. Four groups of tumor features were examined: (1) conventional PET/CT response measures (eg, standardized uptake value [SUV]{sub max}, tumor diameter); (2) clinical parameters (eg, TNM stage, histology) and demographics; (3) spatial-temporal PET features, which characterize tumor SUV intensity distribution, spatial patterns, geometry, and associated changes resulting from CRT; and (4) all features combined. An optimal feature set was identified with recursive feature selection and cross-validations. Support vector machine (SVM) and logistic regression (LR) models were constructed for prediction of pathologic tumor response to CRT, cross-validations being used to avoid model overfitting. Prediction accuracy was assessed by area under the receiver operating characteristic curve (AUC), and precision was evaluated by confidence intervals (CIs) of AUC. Results: When applied to the 4 groups of tumor features, the LR model achieved AUCs (95% CI) of 0.57 (0.10), 0.73 (0.07), 0.90 (0.06), and 0.90 (0.06). The SVM model achieved AUCs (95% CI) of 0.56 (0.07), 0.60 (0.06), 0.94 (0.02), and 1.00 (no misclassifications). With the use of spatial-temporal PET features combined with conventional PET/CT measures and clinical parameters, the SVM model achieved very high accuracy (AUC 1.00) and precision (no misclassifications)—results that were significantly better than when conventional PET/CT measures or clinical parameters and demographics alone were used. For groups with many tumor features (groups 3 and 4), the SVM model achieved significantly higher

  9. TU-C-12A-09: Modeling Pathologic Response of Locally Advanced Esophageal Cancer to Chemo-Radiotherapy Using Quantitative PET/CT Features, Clinical Parameters and Demographics

    SciTech Connect

    Zhang, H; Chen, W; Kligerman, S; D’Souza, W; Suntharalingam, M; Lu, W; Tan, S; Kim, G

    2014-06-15

    Purpose: To develop predictive models using quantitative PET/CT features for the evaluation of tumor response to neoadjuvant chemo-radiotherapy (CRT) in patients with locally advanced esophageal cancer. Methods: This study included 20 patients who underwent tri-modality therapy (CRT + surgery) and had {sup 18}F-FDG PET/CT scans before initiation of CRT and 4-6 weeks after completion of CRT but prior to surgery. Four groups of tumor features were examined: (1) conventional PET/CT response measures (SUVmax, tumor diameter, etc.); (2) clinical parameters (TNM stage, histology, etc.) and demographics; (3) spatial-temporal PET features, which characterize tumor SUV intensity distribution, spatial patterns, geometry, and associated changes resulting from CRT; and (4) all features combined. An optimal feature set was identified with recursive feature selection and cross-validations. Support vector machine (SVM) and logistic regression (LR) models were constructed for prediction of pathologic tumor response to CRT, using cross-validations to avoid model over-fitting. Prediction accuracy was assessed via area under the receiver operating characteristic curve (AUC), and precision was evaluated via confidence intervals (CIs) of AUC. Results: When applied to the 4 groups of tumor features, the LR model achieved AUCs (95% CI) of 0.57 (0.10), 0.73 (0.07), 0.90 (0.06), and 0.90 (0.06). The SVM model achieved AUCs (95% CI) of 0.56 (0.07), 0.60 (0.06), 0.94 (0.02), and 1.00 (no misclassifications). Using spatial-temporal PET features combined with conventional PET/CT measures and clinical parameters, the SVM model achieved very high accuracy (AUC 1.00) and precision (no misclassifications), significantly better than using conventional PET/CT measures or clinical parameters and demographics alone. For groups with a large number of tumor features (groups 3 and 4), the SVM model achieved significantly higher accuracy than the LR model. Conclusion: The SVM model using all features

  10. Comparing Science Achievement Constructs: Targeted and Achieved

    ERIC Educational Resources Information Center

    Ferrara, Steve; Duncan, Teresa

    2011-01-01

    This article illustrates how test specifications based solely on academic content standards, without attention to other cognitive skills and item response demands, can fall short of their targeted constructs. First, the authors inductively describe the science achievement construct represented by a statewide sixth-grade science proficiency test.…

  11. A Study of the Pre-Licensure Nursing Students' Perception of the Simulation Learning Environment as Helpful in Achieving Clinical Competencies and Their Perception of the Impact of the Level of Fidelity

    ERIC Educational Resources Information Center

    Crary, Wendy M.

    2012-01-01

    The research question of this study was: to what degree do nursing students perceive using the High Fidelity Simulation (HFS) learning environment to be helpful in their ability to achieve clinical competency. The research sub-questions (7) explored the students' demographics as an influence on rating of reality and helpfulness and the…

  12. The use of tumour volumetrics to assess response to therapy in anticancer clinical trials

    PubMed Central

    Goldmacher, Gregory V; Conklin, James

    2012-01-01

    Serial evaluations of tumour burden using imaging, mainly computed tomography and magnetic resonance imaging, form the basis for assessing treatment response in many clinical trials of anticancer therapeutics. Traditionally, these evaluations have been based on linear measurements of tumour size. Such measurements have limitations related to variability in technical factors, tumour morphology and reader decisions. Measurements of entire tumour volumes may overcome some of the limitations of linear tumour measurements, improving our ability to detect small changes reliably and increasing statistical power per subject in a trial. Certain technical factors are known to affect the accuracy and precision of volume measurements, and work is in progress to define these factors more thoroughly and to qualify tumour volume as a biomarker for the purposes of drug development. PMID:22242836

  13. Clinical characteristics and treatment response to SSRI in a female pedophile.

    PubMed

    Chow, Eva W C; Choy, Alberto L

    2002-04-01

    Although much investigation has been done with male sex offenders, there have been few studies on female sex offenders. Female sex offenders have been reported as having a high incidence of psychiatric disorders, but female paraphilics were rarely described. The literature on the treatment of female sex offenders is also limited and treatment with a selective serotonin reuptake inhibitor (SSRI) has not been reported. This paper presents the case of a woman with DSM-IV pedophilia. Her clinical characteristics, her offense history, and her positive response to treatment with sertraline (a SSRI) are described. This case adds to the limited literature on female pedophiles and suggests that SSRIs may be an effective treatment for paraphilic disorders in female sex offenders. PMID:11974646

  14. Quick Detection of FKS1 Mutations Responsible for Clinical Echinocandin Resistance in Candida albicans.

    PubMed

    Dudiuk, Catiana; Gamarra, Soledad; Jimenez-Ortigosa, Cristina; Leonardelli, Florencia; Macedo, Daiana; Perlin, David S; Garcia-Effron, Guillermo

    2015-07-01

    A rapid molecular-based assay for the detection of the Candida albicans FKS1 gene mutations responsible for resistance to echinocandin drugs was designed and evaluated. The assay consisted of a multiplexed PCR set of 5 tubes able to detect the most commonly described resistance mechanism, including FKS1 hot spot 1 and hot spot 2 mutations. The performance and specificity of the assay was evaluated using a double-blinded panel of 50 C. albicans strains. The assay showed a sensitivity of 96% and was able to detect all homozygous mutants included in the collection of strains, demonstrating that it is a robust, quick, and labor-saving method that is suitable for a routine clinical diagnostic laboratory. PMID:25878347

  15. Structure and Measurement of Depression in Youth: Applying Item Response Theory to Clinical Data

    PubMed Central

    Cole, David A.; Cai, Li; Martin, Nina C.; Findling, Robert L; Youngstrom, Eric A.; Garber, Judy; Curry, John F.; Hyde, Janet S.; Essex, Marilyn J.; Compas, Bruce E.; Goodyer, Ian M.; Rohde, Paul; Stark, Kevin D.; Slattery, Marcia J.; Forehand, Rex

    2013-01-01

    Goals of the paper were to use item response theory (IRT) to assess the relation of depressive symptoms to the underlying dimension of depression and to demonstrate how IRT-based measurement strategies can yield more reliable data about depression severity than conventional symptom counts. Participants were 3403 clinic and nonclinic children and adolescents from 12 contributing samples, all of whom received the Kiddie Schedule of Affective Disorders and Schizophrenia for school-aged children. Results revealed that some symptoms reflected higher levels of depression and were more discriminating than others. Results further demonstrated that utilization of IRT-based information about symptom severity and discriminability in the measurement of depression severity can reduce measurement error and increase measurement fidelity. PMID:21534696

  16. A periodic analysis of longitudinal binary responses: a case study of clinical mastitis in Norwegian Red cows

    PubMed Central

    Chang, Yu-mei; Gianola, Daniel; Heringstad, Bjørg; Klemetsdal, Gunnar

    2007-01-01

    A Bayesian procedure for analyzing longitudinal binary responses using a periodic cosine function was developed. It was assumed that, after adjustment for "seasonal" effects, the oscillation of the underlying latent variables for longitudinal binary responses was a stationary series. Based on this assumption, a single dimension sinusoidal analysis of longitudinal binary responses using the Gibbs sampling and Metropolis algorithms was implemented in a study of clinical mastitis records of Norwegian Red cows taken over five lactations. PMID:17433240

  17. ASAS40 and ASDAS clinical responses in the ABILITY-1 clinical trial translate to meaningful improvements in physical function, health-related quality of life and work productivity in patients with non-radiographic axial spondyloarthritis

    PubMed Central

    Joshi, Avani; Pangan, Aileen L.; Chen, Naijun; Betts, Keith; Mittal, Manish; Bao, Yanjun

    2016-01-01

    Objective. To assess the impact of achieving Assessment in SpondyloArthritis international Society 40% (ASAS40) response or an Ankylosing Spondylitis Disease Activity Score inactive disease (ASDAS-ID) state on patient-reported outcomes (PROs) among patients with non-radiographic axial SpA (nr-axSpA). Methods. Data are from ABILITY-1, a phase 3 trial of adalimumab vs placebo in nr-axSpA patients. PROs included the HAQ for Spondyloarthropathies (HAQ-S), 36-item Short Form Health Survey (SF-36) physical component summary (PCS) score and Work Productivity and Activity Impairment Questionnaire. Patients were grouped by clinical response using ASAS40 response and ASDAS disease states at week 12. Changes in PROs from baseline to week 12 were compared between groups using analysis of covariance with adjustment for baseline scores. Results. At week 12, 47 of 179 patients were ASAS40 responders and 26 of 176 patients achieved ASDAS-ID (ASDAS <1.3). Compared with non-responders (n = 132), ASAS40 responders (n = 47) had a significantly greater improvement in mean HAQ-S (–0.65 vs -0.05, P < 0.0001), SF-36 PCS (12.4 vs 0.7, P < 0.0001), presenteeism (–24.7 vs -2.2, P < 0.0001), overall work impairment (–23.9 vs -2.5, P < 0.0001) and activity impairment (–33.5 vs -0.9, P < 0.0001) at week 12. Similarly, ASDAS-ID, ASDAS clinically important improvement (ASDAS-CII; improvement >1.1) and major improvement (ASDAS-MI; improvement >2.0) were associated with significantly greater improvements from baseline in the majority of the PROs. Conclusion. Among nr-axSpA patients, ASAS40, ASDAS-CII and ASDAS-MI response and achievement of ASDAS-ID were associated with statistically significant and clinically meaningful improvements in physical function, health-related quality of life and work productivity in a higher percentage of patients. PMID:26316575

  18. Tocilizumab in patients with active rheumatoid arthritis and inadequate responses to DMARDs and/or TNF inhibitors: a large, open-label study close to clinical practice

    PubMed Central

    Bykerk, Vivian P; Östör, Andrew J K; Alvaro-Gracia, José; Pavelka, Karel; Ivorra, José Andrés Román; Graninger, Winfried; Bensen, William; Nurmohamed, Michael T; Krause, Andreas; Bernasconi, Corrado; Stancati, Andrea; Sibilia, Jean

    2012-01-01

    Objective To evaluate the safety and efficacy of tocilizumab in clinical practice in patients with rheumatoid arthritis (RA) with inadequate responses (IR) to disease-modifying antirheumatic drugs (DMARDs) or both DMARDs and tumour necrosis factor α inhibitors (TNFis). Methods Patients—categorised as TNFi-naive, TNFi-previous (washout) or TNFi-recent (no washout) —received open-label tocilizumab (8 mg/kg) every 4 weeks ± DMARDs for 24 weeks. Adverse events (AEs) and treatment discontinuations were monitored. Efficacy end points included American College of Rheumatology (ACR) responses, 28-joint disease activity score (DAS28) and European League Against Rheumatism responses. Results Overall, 1681 (976 TNF-naive, 298 TNFi-previous and 407 TNFi-recent) patients were treated; 5.1% discontinued treatment because of AEs. The AE rate was numerically higher in TNFi-recent (652.6/100 patient-years (PY)) and TNFi-previous (653.6/100PY) than in TNFi-naive (551.1/100PY) patients. Serious AE rates were 18.0/100PY, 28.0/100PY and 18.6/100PY; serious infection rates were 6.0/100PY, 6.8/100PY and 4.2/100PY, respectively. At week 4, 36.5% of patients achieved ACR20 response and 14.9% DAS28 remission (<2.6); at week 24, 66.9%, 46.6%, 26.4% and 56.8% achieved ACR20/ACR50/ACR70 responses and DAS28 remission, respectively. Overall, 61.6% (TNFi-naive), 48.5% (TNFi-previous) and 50.4% (TNFi-recent) patients achieved DAS28 remission. Conclusions In patients with RA who were DMARD-IR/TNFi-IR, tocilizumab ± DMARDs provided rapid and sustained efficacy without unexpected safety concerns. PMID:22615456

  19. Clinical Laboratory Response to a Mock Outbreak of Invasive Bacterial Infections: a Preparedness Study

    PubMed Central

    Fittipaldi, Nahuel; Kachroo, Priyanka; Sanson, Misu A.; Long, S. Wesley; Como-Sabetti, Kathryn J.; Valson, Chandni; Cantu, Concepcion; Lynfield, Ruth; Van Beneden, Chris; Beres, Stephen B.; Musser, James M.

    2014-01-01

    Large hospital-based clinical laboratories must be prepared to rapidly investigate potential infectious disease outbreaks. To challenge the ability of our molecular diagnostics laboratory to use whole-genome sequencing in a potential outbreak scenario and identify impediments to these efforts, we studied 84 invasive serotype emm59 group A streptococcus (GAS) strains collected in the United States. We performed a rapid-response exercise to the mock outbreak scenario using whole-genome sequencing, genome-wide transcript analysis, and mouse virulence studies. The protocol changes installed in response to the lessons learned were tested in a second iteration. The initial investigation was completed in 9 days. Whole-genome sequencing showed that the invasive infections were caused by multiple subclones of epidemic emm59 GAS strains likely spread to the United States from Canada. The phylogenetic tree showed a strong temporal-spatial structure with diversity in mobile genetic element content, features that are useful for identifying closely related strains and possible transmission events. The genome data informed the epidemiology, identifying multiple patients who likely acquired the organisms through direct person-to-person transmission. Transcriptome analysis unexpectedly revealed significantly altered expression of genes encoding a two-component regulator and the hyaluronic acid capsule virulence factor. Mouse infection studies confirmed a high-virulence capacity of these emm59 organisms. Whole-genome sequencing, coupled with transcriptome analysis and animal virulence studies, can be rapidly performed in a clinical environment to effectively contribute to patient care decisions and public health maneuvers. PMID:25253790

  20. Bronchodilator response in adults with bronchiectasis: correlation with clinical parameters and prognostic implications

    PubMed Central

    Guan, Wei-Jie; Gao, Yong-Hua; Xu, Gang; Li, Hui-Min; Yuan, Jing-Jing; Zheng, Jin-Ping

    2016-01-01

    Background Bronchial dilation testing is an important tool to assess airway reversibility in adults with bronchiectasis. This study aims to investigate the association of bronchodilator response (BDR) and clinical parameters in bronchiectasis, and the utility of BDR to indicate lung function decline and risks of bronchiectasis exacerbations (BEs). Methods We recruited 129 patients with clinically stable bronchiectasis. Baseline measurements included assessment of sputum inflammation and matrix metalloproteinase-8 and -9, sputum bacterial culture, spirometry, bronchial dilation test (for baseline FEV1 less than 80% predicted only) and chest high-resolution computed tomography (HRCT). Bronchiectasis patients were followed-up for 1 year to determine the incidence of BEs and lung function trajectories. Significant BDR was defined as FEV1 improvement from pre-dose value by at least 200 mL and 12%. Clinical trial registry No.: NCT01761214; URL: www.clinicaltrials.gov. Results BDR was negatively correlated with baseline FEV1 percentage predicted, but not blood or sputum eosinophil count. Significant BDR was not associated with greater proportion of never-smokers, poorer past history, greater HRCT scores, poorer diffusing capacity or increased sputum matrix metalloproteinases (all P>0.05). There was a trend towards higher bronchiectasis severity index (BSI) and greater proportion of patients with Pseudomonas aeruginosa isolation or infection. Significant BDR at baseline was linked to poorer spirometry, but not more rapid lung function decline, throughout follow-up. Patients with significant BDR demonstrated non-significantly lower risks of experiencing the first BEs than those without (P=0.09 for log-rank test). Conclusions Significant BDR is associated with poorer lung function compared with non-significant BDR. Whether BDR predicts future risks of BEs needs to be tested in a larger cohort. PMID:26904207

  1. Effectiveness and clinical response rates of a residential eating disorders facility.

    PubMed

    Twohig, Michael P; Bluett, Ellen J; Cullum, Jodi L; Mitchell, P R; Powers, Pauline S; Lensegrav-Benson, Tera; Quakenbush-Roberts, Benita

    2016-01-01

    The purpose of this study was to determine the effectiveness of a residential treatment program for adults and adolescents with eating disorders across a wide spectrum of measures. Data on body mass, eating disorder severity, depression, anxiety, and two measures of quality of life were collected on 139 consecutively admitted adolescents and 111 adults at a residential treatment program (N = 250). The same measures were completed at post-treatment. Group level analyses showed that adults and adolescents improved on all measures analyzed. Only 1.7% of adolescents and 2.3% of adults were below a Body Mass Index of 18.5 at discharge. Positive results across diagnoses and ages are reported for three subscales of the Eating Disorder Inventory-3, with clinical response rates reported. Using clinical responder analyses, it was found that for all individuals struggling with secondary issues, 74.7% were responders on the Beck Depression Inventory-II, 41.0% on the Beck Anxiety Inventory, 63.5% on a measure of quality of life, and 95.8% were responders on the physical subscale and 72.6% on the mental subscale of the SF-36-v2. This study suggests that residential treatment for eating disorders is effective at the group level, and it was effective for the majority of individuals within the group. PMID:26214231

  2. Determinants of clinical response and survival in patients with congestive heart failure treated with captopril.

    PubMed

    Creager, M A; Faxon, D P; Halperin, J L; Melidossian, C D; McCabe, C H; Schick, E C; Ryan, T J

    1982-11-01

    The efficacy of chronic ambulatory captopril (CPT) therapy was evaluated over an 18-month period in 36 patients with refractory chronic congestive heart failure (CHF) by cardiac catheterization, treadmill exercise, nuclear scintigraphy, echocardiography, and symptomatology. Clinical improvement to New York Heart Association functional class I or class II was observed in 63% of the patients (20 of 32) after 2 months of treatment; this amelioration of CHF symptoms was sustained in 63% of the patients (10 of 16) at 18 months. Exercise tolerance increased in 64% of the patients (16 of 25) at early follow-up and in 79% (11 of 14) at late follow-up. Univariate analysis revealed that the pre- and post-CPT stroke work indices (SWI) and the post-CPT cardiac index related to favorable long-term clinical response. Fourteen CHF patients (39%) died during the 18-month follow-up. Univariate analysis revealed that the pretreatment SWI, right atrial pressure, plasma norepinephrine concentration, and echocardiographic shortening fraction were significant predictors of mortality. Multivariate analysis indicated that the SWI was the principal determinant of survival: the 18-month cumulative survival rate for CHF patients with a SWI less than 32 gm . m/m2 was 44% compared to 88% when the SWI was greater than 32 gm . m/m2. Thus, CPT results in sustained symptomatic and functional improvements in patients with advanced CHF, but the mortality remains high and is primarily related to the severity of cardiac dysfunction. PMID:6291360

  3. The Physiological Basis and Clinical Use of the Binaural Interaction Component of the Auditory Brainstem Response.

    PubMed

    Laumen, Geneviève; Ferber, Alexander T; Klump, Georg M; Tollin, Daniel J

    2016-01-01

    The auditory brainstem response (ABR) is a sound-evoked noninvasively measured electrical potential representing the sum of neuronal activity in the auditory brainstem and midbrain. ABR peak amplitudes and latencies are widely used in human and animal auditory research and for clinical screening. The binaural interaction component (BIC) of the ABR stands for the difference between the sum of the monaural ABRs and the ABR obtained with binaural stimulation. The BIC comprises a series of distinct waves, the largest of which (DN1) has been used for evaluating binaural hearing in both normal hearing and hearing-impaired listeners. Based on data from animal and human studies, the authors discuss the possible anatomical and physiological bases of the BIC (DN1 in particular). The effects of electrode placement and stimulus characteristics on the binaurally evoked ABR are evaluated. The authors review how interaural time and intensity differences affect the BIC and, analyzing these dependencies, draw conclusion about the mechanism underlying the generation of the BIC. Finally, the utility of the BIC for clinical diagnoses are summarized. PMID:27232077

  4. Veteran satisfaction and treatment preferences in response to a posttraumatic stress disorder specialty clinic orientation group.

    PubMed

    Schumm, Jeremiah A; Walter, Kristen H; Bartone, Anne S; Chard, Kathleen M

    2015-06-01

    To maximize accessibility to evidence-based treatments for posttraumatic stress disorder (PTSD), the United States Department of Veterans Affairs (VA) has widely disseminated cognitive processing therapy (CPT) and prolonged exposure (PE) therapy to VA clinicians. However, there is a lack of research on veteran preferences when presented with a range of psychotherapy and medication options. This study uses a mixed-method approach to explore veteran satisfaction with a VA PTSD specialty clinic pre-treatment orientation group, which provides education about available PTSD treatment options. This study also tested differences in treatment preference in response to the group. Participants were 183 US veterans. Most were White, male, and referred to the clinic by a VA provider. Results indicated high satisfaction with the group in providing an overview of services and helping to inform treatment choice. Most preferred psychotherapy plus medications (63.4%) or psychotherapy only (30.1%). Participants endorsed a significantly stronger preference for CPT versus other psychotherapies. PE was significantly preferred over nightmare resolution therapy and present-centered therapy, and both PE and cognitive-behavioral conjoint therapy were preferred over virtual reality exposure therapy. Results suggest that by informing consumers about evidence-based treatments for PTSD, pre-treatment educational approaches may increase consumer demand for these treatment options. PMID:25898342

  5. Investigating the Clinical Usefulness of the Social Responsiveness Scale (SRS) in a Tertiary Level, Autism Spectrum Disorder Specific Assessment Clinic

    ERIC Educational Resources Information Center

    Aldridge, Fiona J.; Gibbs, Vicki M.; Schmidhofer, Katherine; Williams, Megan

    2012-01-01

    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…

  6. Better short-term clinical response to etanercept in Chinese than Caucasian patients with active ankylosing spondylitis.

    PubMed

    Chou, Chung-Tei; Tsai, Chang-Youh; Liang, Tung-Hua; Chang, Te-Ming; Lai, Chen-Hung; Wei, Cheng-Chung; Chen, Kun-Hung; Lin, Shih-Chang; Yu, Chia-Li; Liou, Lieh-Bang; Luo, Shue-Fen; Lee, Chyou-Shen; Hsue, Yin-Tzu; Huang, Chung-Ming; Chen, Jiunn-Hong; Lai, Ning-Sheng; Cheng, He-Hsiung; Cheng, Tien-Tsai; Lai, Han-Ming; Tsai, Wen-Chan; Yen, Jeng-Hsien; Lu, Ling-Ying; Chang, Chung-Pei

    2010-12-01

    Tumor necrosis factor-alpha (TNF-α) inhibitors including etanercept have been demonstrated to be very effective in severe ankylosing spondylitis (AS) in Caucasian patients. However, clinical efficacy of etanercept to treat active AS in Chinese patients has not been reported. In this study, a prospective, open-label trial of etanercept (25 mg BIW), involving 46 AS patients from 16 medical centers of Taiwan, was conducted. Questionnaire was utilized to record demographic data and clinical parameters, including Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), Bath AS Global Index (BASGI), Assessment in Ankylosing Spondylitis (ASAS) 20, 50, and 70, and others, before and at different time intervals after etanercept treatment. Laboratory tests including blood chemistry, hematology, urine analysis, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were done at baseline and at weeks 4, 8, and 12. In this 12-week study, etanercept demonstrated rapid and significant improvement in the ASAS20 response criteria (91.3%), at as early as 2 weeks of therapy (71.3%). Partial remission of AS was achieved in 49.3% of patients after 12 weeks of treatment. Disease activity (BASDAI) and function (BASFI) were also significantly improved after 12 weeks etanercept treatment (p < 0.0001 and p < 0.0001, respectively). In addition, significant increase of chest expansion (2.77 ± 1.69 cm versus 3.56 ± 1.82 cm, p = 0.0004) and lumbar flexion (2.11 ± 2.76 cm versus 2.58 ± 3.42 cm, p = 0.0075) and significant reduction of occiput-to-wall distance (6.59 ± 7.14 cm versus 5.32 ± 6.65 cm, p = 0.0006) were also demonstrated. Both ESR and CRP declined significantly after patients were treated with etanercept. There were no severe adverse effects during the treatment period. Etanercept is generally safe, well tolerated, and effective in Chinese patients with severe AS. Clinical efficacy, including partial remission and BASDAI, is even better in Chinese

  7. Population pharmacokinetic–pharmacodynamic modelling in oncology: a tool for predicting clinical response

    PubMed Central

    Bender, Brendan C; Schindler, Emilie; Friberg, Lena E

    2015-01-01

    In oncology trials, overall survival (OS) is considered the most reliable and preferred endpoint to evaluate the benefit of drug treatment. Other relevant variables are also collected from patients for a given drug and its indication, and it is important to characterize the dynamic effects and links between these variables in order to improve the speed and efficiency of clinical oncology drug development. However, the drug-induced effects and causal relationships are often difficult to interpret because of temporal differences. To address this, population pharmacokinetic–pharmacodynamic (PKPD) modelling and parametric time-to-event (TTE) models are becoming more frequently applied. Population PKPD and TTE models allow for exploration towards describing the data, understanding the disease and drug action over time, investigating relevance of biomarkers, quantifying patient variability and in designing successful trials. In addition, development of models characterizing both desired and adverse effects in a modelling framework support exploration of risk-benefit of different dosing schedules. In this review, we have summarized population PKPD modelling analyses describing tumour, tumour marker and biomarker responses, as well as adverse effects, from anticancer drug treatment data. Various model-based metrics used to drive PD response and predict OS for oncology drugs and their indications are also discussed. PMID:24134068

  8. Hoarding in Youth with Autism Spectrum Disorders and Anxiety: Incidence, Clinical Correlates, and Behavioral Treatment Response.

    PubMed

    Storch, Eric A; Nadeau, Joshua M; Johnco, Carly; Timpano, Kiara; McBride, Nicole; Jane Mutch, P; Lewin, Adam B; Murphy, Tanya K

    2016-05-01

    This study examined the nature and correlates of hoarding among youth with autism spectrum disorders (ASD). Forty children with ASD and a comorbid anxiety disorder were administered a battery of clinician-administered measures assessing presence of psychiatric disorders and anxiety severity. Parents completed questionnaires related to child hoarding behaviors, social responsiveness, internalizing and externalizing behaviors, and functional impairment. We examined the impact of hoarding behaviors on treatment response in a subsample of twenty-six youth who completed a course of personalized cognitive-behavioral therapy targeting anxiety symptoms. Hoarding symptoms were common and occurred in a clinically significant manner in approximately 25 % of cases. Overall hoarding severity was associated with increased internalizing and anxiety/depressive symptoms, externalizing behavior, and attention problems. Discarding items was associated with internalizing and anxious/depressive symptoms, but acquisition was not. Hoarding decreased following cognitive-behavioral therapy but did not differ between treatment responders and non-responders. These data are among the first to examine hoarding among youth with ASD; implications of study findings and future directions are highlighted. PMID:26749256

  9. Plasma genetic and genomic abnormalities predict treatment response and clinical outcome in advanced prostate cancer.

    PubMed

    Xia, Shu; Kohli, Manish; Du, Meijun; Dittmar, Rachel L; Lee, Adam; Nandy, Debashis; Yuan, Tiezheng; Guo, Yongchen; Wang, Yuan; Tschannen, Michael R; Worthey, Elizabeth; Jacob, Howard; See, William; Kilari, Deepak; Wang, Xuexia; Hovey, Raymond L; Huang, Chiang-Ching; Wang, Liang

    2015-06-30

    Liquid biopsies, examinations of tumor components in body fluids, have shown promise for predicting clinical outcomes. To evaluate tumor-associated genomic and genetic variations in plasma cell-free DNA (cfDNA) and their associations with treatment response and overall survival, we applied whole genome and targeted sequencing to examine the plasma cfDNAs derived from 20 patients with advanced prostate cancer. Sequencing-based genomic abnormality analysis revealed locus-specific gains or losses that were common in prostate cancer, such as 8q gains, AR amplifications, PTEN losses and TMPRSS2-ERG fusions. To estimate tumor burden in cfDNA, we developed a Plasma Genomic Abnormality (PGA) score by summing the most significant copy number variations. Cox regression analysis showed that PGA scores were significantly associated with overall survival (p < 0.04). After androgen deprivation therapy or chemotherapy, targeted sequencing showed significant mutational profile changes in genes involved in androgen biosynthesis, AR activation, DNA repair, and chemotherapy resistance. These changes may reflect the dynamic evolution of heterozygous tumor populations in response to these treatments. These results strongly support the feasibility of using non-invasive liquid biopsies as potential tools to study biological mechanisms underlying therapy-specific resistance and to predict disease progression in advanced prostate cancer. PMID:25915538

  10. Cryptosporidiosis in HIV/AIDS Patients in Kenya: Clinical Features, Epidemiology, Molecular Characterization and Antibody Responses

    PubMed Central

    Wanyiri, Jane W.; Kanyi, Henry; Maina, Samuel; Wang, David E.; Steen, Aaron; Ngugi, Paul; Kamau, Timothy; Waithera, Tabitha; O'Connor, Roberta; Gachuhi, Kimani; Wamae, Claire N.; Mwamburi, Mkaya; Ward, Honorine D.

    2014-01-01

    We investigated the epidemiological and clinical features of cryptosporidiosis, the molecular characteristics of infecting species and serum antibody responses to three Cryptosporidium-specific antigens in human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients in Kenya. Cryptosporidium was the most prevalent enteric pathogen and was identified in 56 of 164 (34%) of HIV/AIDS patients, including 25 of 70 (36%) with diarrhea and 31 of 94 (33%) without diarrhea. Diarrhea in patients exclusively infected with Cryptosporidium was significantly associated with the number of children per household, contact with animals, and water treatment. Cryptosporidium hominis was the most prevalent species and the most prevalent subtype family was Ib. Patients without diarrhea had significantly higher serum IgG levels to Chgp15, Chgp40 and Cp23, and higher fecal IgA levels to Chgp15 and Chgp40 than those with diarrhea suggesting that antibody responses to these antigens may be associated with protection from diarrhea and supporting further investigation of these antigens as vaccine candidates. PMID:24865675

  11. Radiation Induced Non-targeted Response: Mechanism and Potential Clinical Implications

    PubMed Central

    Hei, Tom K.; Zhou, Hongning; Chai, Yunfei; Ponnaiya, Brian; Ivanov, Vladimir N.

    2012-01-01

    Generations of students in radiation biology have been taught that heritable biological effects require direct damage to DNA. Radiation-induced non-targeted/bystander effects represent a paradigm shift in our understanding of the radiobiological effects of ionizing radiation in that extranuclear and extracellular effects may also contribute to the biological consequences of exposure to low doses of radiation. Although radiation induced bystander effects have been well documented in a variety of biological systems, including 3D human tissue samples and whole organisms, the mechanism is not known. There is recent evidence that the NF-κB-dependent gene expression of interleukin 8, interleukin 6, cyclooxygenase-2, tumor necrosis factor and interleukin 33 in directly irradiated cells produced the cytokines and prostaglandin E2 with autocrine/paracrine functions, which further activated signaling pathways and induced NF-κB-dependent gene expression in bystander cells. The observations that heritable DNA alterations can be propagated to cells many generations after radiation exposure and that bystander cells exhibit genomic instability in ways similar to directly hit cells indicate that the low dose radiation response is a complex interplay of various modulating factors. The potential implication of the non-targeted response in radiation induced secondary cancer is discussed. A better understanding of the mechanism of the non-targeted effects will be invaluable to assess its clinical relevance and ways in which the bystander phenomenon can be manipulated to increase therapeutic gain in radiotherapy. PMID:21143185

  12. Plasma genetic and genomic abnormalities predict treatment response and clinical outcome in advanced prostate cancer

    PubMed Central

    Du, Meijun; Dittmar, Rachel L.; Lee, Adam; Nandy, Debashis; Yuan, Tiezheng; Guo, Yongchen; Wang, Yuan; Tschannen, Michael R.; Worthey, Elizabeth; Jacob, Howard; See, William; Kilari, Deepak; Wang, Xuexia; Hovey, Raymond L.; Huang, Chiang-Ching; Wang, Liang

    2015-01-01

    Liquid biopsies, examinations of tumor components in body fluids, have shown promise for predicting clinical outcomes. To evaluate tumor-associated genomic and genetic variations in plasma cell-free DNA (cfDNA) and their associations with treatment response and overall survival, we applied whole genome and targeted sequencing to examine the plasma cfDNAs derived from 20 patients with advanced prostate cancer. Sequencing-based genomic abnormality analysis revealed locus-specific gains or losses that were common in prostate cancer, such as 8q gains, AR amplifications, PTEN losses and TMPRSS2-ERG fusions. To estimate tumor burden in cfDNA, we developed a Plasma Genomic Abnormality (PGA) score by summing the most significant copy number variations. Cox regression analysis showed that PGA scores were significantly associated with overall survival (p < 0.04). After androgen deprivation therapy or chemotherapy, targeted sequencing showed significant mutational profile changes in genes involved in androgen biosynthesis, AR activation, DNA repair, and chemotherapy resistance. These changes may reflect the dynamic evolution of heterozygous tumor populations in response to these treatments. These results strongly support the feasibility of using non-invasive liquid biopsies as potential tools to study biological mechanisms underlying therapy-specific resistance and to predict disease progression in advanced prostate cancer. PMID:25915538

  13. [Achievement of therapeutic objectives].

    PubMed

    Mantilla, Teresa

    2014-07-01

    Therapeutic objectives for patients with atherogenic dyslipidemia are achieved by improving patient compliance and adherence. Clinical practice guidelines address the importance of treatment compliance for achieving objectives. The combination of a fixed dose of pravastatin and fenofibrate increases the adherence by simplifying the drug regimen and reducing the number of daily doses. The good tolerance, the cost of the combination and the possibility of adjusting the administration to the patient's lifestyle helps achieve the objectives for these patients with high cardiovascular risk. PMID:25043543

  14. Mucosal Immune Responses Predict Clinical Outcomes during Influenza Infection Independently of Age and Viral Load

    PubMed Central

    Oshansky, Christine M.; Gartland, Andrew J.; Wong, Sook-San; Jeevan, Trushar; Wang, David; Roddam, Philippa L.; Caniza, Miguela A.; Hertz, Tomer; DeVincenzo, John P.; Webby, Richard J.

    2014-01-01

    Rationale: Children are an at-risk population for developing complications following influenza infection, but immunologic correlates of disease severity are not understood. We hypothesized that innate cellular immune responses at the site of infection would correlate with disease outcome. Objectives: To test the immunologic basis of severe illness during natural influenza virus infection of children and adults at the site of infection. Methods: An observational cohort study with longitudinal sampling of peripheral and mucosal sites in 84 naturally influenza-infected individuals, including infants. Cellular responses, viral loads, and cytokines were quantified from nasal lavages and blood, and correlated to clinical severity. Measurements and Main Results: We show for the first time that although viral loads in children and adults were similar, innate responses in the airways were stronger in children and varied considerably between plasma and site of infection. Adjusting for age and viral load, an innate immune profile characterized by increased nasal lavage monocyte chemotactic protein-3, IFN-α2, and plasma IL-10 levels at enrollment predicted progression to severe disease. Increased plasma IL-10, monocyte chemotactic protein-3, and IL-6 levels predicted hospitalization. This inflammatory cytokine production correlated significantly with monocyte localization from the blood to the site of infection, with conventional monocytes positively correlating with inflammation. Increased frequencies of CD14lo monocytes were in the airways of participants with lower inflammatory cytokine levels. Conclusions: An innate profile was identified that correlated with disease progression independent of viral dynamics and age. The airways and blood displayed dramatically different immune profiles emphasizing the importance of cellular migration and localized immune phenotypes. PMID:24308446

  15. Acute radiation-induced pulmonary damage: a clinical study on the response to fractionated radiation therapy.

    PubMed

    Mah, K; Van Dyk, J; Keane, T; Poon, P Y

    1987-02-01

    Acute radiation-induced pulmonary damage can be a significant cause of morbidity in radiation therapy of the thorax. A prospective, clinical study was conducted to obtain dose-response data on acute pulmonary damage caused by fractionated radiation therapy. The endpoint was a visible increase in lung density within the irradiated volume on a computed tomographic (CT) examination as observed independently by three diagnostic radiologists. Fifty-four patients with various malignancies of the thorax completed the study. CT chest scans were taken before and at preselected times following radiotherapy. To represent different fractionation schedules of equivalent biological effect, the estimated single dose (ED) model, ED = D X N-0.377 X T-0.058 was used in which D was the average lung dose within the high dose region in cGy, N was the number of fractions, and T was the overall treatment time in days. Patients were grouped according to ED and the percent incidence of pulmonary damage for each group was determined. Total average lung doses ranged from 29.8 Gy to 53.6 Gy given in 10 to 30 fractions over a range of 12 to 60 days. Five patient groups with incidence ranging from 30% (ED of 930) to 90% (ED of 1150) were obtained. The resulting dose-response curve predicted a 50% incidence level at an ED value (ED50) of 1000 +/- 40 ED units. This value represents fractionation schedules equivalent to a total average lung dose of 32.9 Gy given in 15 fractions over 19 days. Over the linear portion of the dose-response curve, a 5% increase in ED (or total dose if N and T remain constant), predicts a 12% increase in the incidence of acute radiation-induced pulmonary damage. PMID:3818385

  16. Clinical efficacy and determinants of response to treatment with desmopressin in mild hemophilia a.

    PubMed

    Di Perna, Caterina; Riccardi, Federica; Franchini, Massimo; Rivolta, Gianna Franca; Pattacini, Corrado; Tagliaferri, Annarita

    2013-10-01

    Although desmopressin (DDAVP) is considered as the treatment of choice for many patients with mild hemophilia A, several aspects of DDAVP therapy remain unclear, including the rate and type of response and the molecular determinants of its clinical efficacy. To investigate these issues, we retrospectively studied all patients with mild hemophilia A followed up at the Parma Hemophilia Center. A total of 75 patients were enrolled who underwent a DDAVP test, and out of whom, 76% (57/75) had a complete or partial response. Response to DDAVP was significantly correlated to the patients' age (median age of responders and nonresponders: 24 and 18 y, respectively; p = 0.04) and type of mutation (all the 10 patients with mutations in the promoter region were nonresponders). The median basal factor VIII (FVIII):C level was significantly lower in responders than in nonresponders (0.14 vs. 0.19 IU/mL, respectively; p = 0.01); this was mainly due to nonresponders with promoter region mutations who had higher basal FVIII:C levels. During the 12-year follow-up, 82 of 237 (35%) bleeding episodes occurring in 27 responder patients were treated with 246 DDAVP infusions with complete or partial efficacy in 92% (75/82). Overall, 142 events were managed with 253 prophylactic DDAVP infusions, which were hemostatically effective in 96% of cases. No severe adverse reactions to DDAVP administration were recorded during the study period. These results document the safety and efficacy of DDAVP as a treatment or prevention of bleeding in patients with mild hemophilia A, also in the context of home treatment, and encourage the more widespread use of this product. PMID:24030345

  17. Influence of Study Design on Treatment Response in Anxiety Disorder Clinical Trials

    PubMed Central

    Rutherford, Bret R; Bailey, Veronika S.; Schneier, Franklin R.; Pott, Emily; Brown, Patrick J.; Roose, Steven P.

    2016-01-01

    Objective The influence of study design variables and publication year on response to medication and placebo was investigated in clinical trials for social anxiety disorder (SAD), generalized anxiety disorder (GAD), and panic disorder (PD). Method Hierarchical linear modeling determined whether publication year, treatment assignment (medication vs. placebo), study type (placebo-controlled or active comparator), study duration, and the number of study visits affected the mean change associated with medication and placebo. Results In the 66 trials examined, the change associated with both medication and placebo increased over time (t = 4.23, df = 39, P < .001), but average drug–placebo differences decreased over time (t = −2.04, df = 46, P = .047). More severe baseline illness was associated with greater drug–placebo differences for serotonin norepinephrine reuptake inhibitors (SNRIs, t = 3.46, df = 106, P = .001) and selective serotonin reuptake inhibitors (SSRI, t = 10.37, df = 106, P < .001). Improvement with medication was significantly greater in active-comparator studies compared to placebo-controlled trials (t = 3.41, df = 39, P = .002). A greater number of study visits was associated with greater symptom improvement in PD trials relative to SAD (t = 2.83, df = 39, P = .008) and GAD (t = 2.16, df = 39, P= .037). Conclusions Placebo response is substantial in SAD, GAD, and PD trials, and its rise over time has been associated with diminished drug–placebo differences. Study design features that influence treatment response in anxiety disorder trials include patient expectancy, frequency of follow-up visits, and baseline illness severity. PMID:26437267

  18. Paradoxical Lung Function Response to Beta2-agonists: Radiologic Correlates and Clinical Implications

    PubMed Central

    Bhatt, Surya P.; Wells, James M.; Kim, Victor; Criner, Gerard J.; Hersh, Craig P.; Hardin, Megan; Bailey, William C.; Nath, Hrudaya; il-Kim, Young; Foreman, Marilyn G.; Stinson, Douglas S.; Wilson, Carla G.; Rennard, Stephen I.; Silverman, Edwin K.; Make, Barry J.; Dransfield, Mark T.

    2014-01-01

    Background Bronchodilator response is seen in a significant proportion of patients with chronic obstructive pulmonary disease (COPD). However, there are also reports of a paradoxical response (PR) to beta2-agonists, resulting in bronchoconstriction. Asymptomatic bronchoconstriction is likely far more common but there has been no systematic study of this phenomenon.We assessed theprevalence of PR in current and former smokers with and without COPD, and its radiologic correlates and clinical implications. Methods Subjects from a large multicenter study (COPDGene) were categorized into two groups based on PR defined as at least a 12% and 200mLreduction in FEV1 and/or FVC after administration of a short-acting beta2-agonist (180ucg albuterol). Predictors of PR and associations with respiratory morbidity and computed tomographic measures of emphysema and airway disease were assessed. Findings 9986 subjects were included. PR was seen in 4.54% and the frequency was similar in those with COPD and smokers without airflow obstruction. Compared to Caucasians, PR was twice as common in African-Americans (6.9% vs. 3.4%;p <0.001). On multivariate analyses, African- American race (adjusted OR 1.89, 95%CI 1.50 to 2.39), lesspercent emphysema (OR 0.96, 95%CI 0.92 to 0.99) and increased wall-area% of segmental airways (OR 1.04,95%CI 1.01 to 1.08) were independently associated with PR.PR was independently associated with worse dyspnea, lower six-minute-walk distance, higher BODE index, and a greater frequency of exacerbations(increased by a factor of 1.35, 95%CI 1.003 to 1.81). Interpretation Paradoxical response to beta2-agonists is associated with respiratory morbidity and is more common in African Americans. PMID:25217076

  19. Oxygen sensors and energy sensors act synergistically to achieve a graded alteration in gene expression: consequences for assessing the level of neuroprotection in response to stressors.

    PubMed

    Renshaw, Gillian M C; Warburton, Joshua; Girjes, Adeeb

    2004-01-01

    Changes in gene expression are associated with switching to an autoprotected phenotype in response to environmental and physiological stress. Ubiquitous molecular chaperones from the heat shock protein (HSP) superfamily confer neuronal protection that can be blocked by antibodies. Recent research has focused on the interactions between the molecular sensors that affect the increased expression of neuroprotective HSPs above constitutive levels. An examination of the conditions under which the expression of heat shock protein 70 (Hsp70) was up regulated in a hypoxia and anoxia tolerant tropical species, the epaulette shark (Hemiscyllium ocellatum), revealed that up-regulation was dependent on exceeding a stimulus threshold for an oxidative stressor. While hypoxic-preconditioning confers neuroprotective changes, there was no increase in the level of Hsp70 indicating that its increased expression was not associated with achieving a neuroprotected state in response to hypoxia in the epaulette shark. Conversely, there was a significant increase in Hsp70 in response to anoxic-preconditioning, highlighting the presence of a stimulus threshold barrier and raising the possibility that, in this species, Hsp70 contributes to the neuroprotective response to extreme crises, such as oxidative stress. Interestingly, there was a synergistic effect of coincident stressors on Hsp70 expression, which was revealed when metabolic stress was superimposed upon oxidative stress. Brain energy charge was significantly lower when adenosine receptor blockade, provided by treatment with aminophylline, was present prior to the final anoxic episode, under these circumstances, the level of Hsp70 induced was significantly higher than in the pair-matched saline treated controls. An understanding of the molecular and metabolic basis for neuroprotective switches, which result in an up-regulation of neuroprotective Hsp70 expression in the brain, is needed so that intervention strategies can be devised

  20. Achieving sustained virologic response after interferon-free hepatitis C virus treatment correlates with hepatic interferon gene expression changes independent of cirrhosis.

    PubMed

    Meissner, E G; Kohli, A; Virtaneva, K; Sturdevant, D; Martens, C; Porcella, S F; McHutchison, J G; Masur, H; Kottilil, S

    2016-07-01

    Chronic hepatitis C virus (HCV) infection can now be treated with oral directly acting antiviral agents, either with or without ribavirin (RBV). Virologic relapse after treatment can occur, and in some studies was more common in cirrhotic subjects. We previously observed changes in hepatic immunity during interferon (IFN)-free therapy that correlated with favourable outcome in subjects with early liver disease. Here, we compared changes in endogenous IFN pathways during IFN-free, RBV-free therapy between cirrhotic and noncirrhotic subjects. mRNA and microRNA (miRNA) expression analyses were performed on paired pre- and post-treatment liver biopsies from genotype-1 HCV subjects treated with sofosbuvir/ledipasvir (SOF/LDV) for 12 weeks (n = 4, 3 cirrhotics) or SOF/LDV combined with GS-9669 or GS-9451 for 6 weeks (n = 6, 0 cirrhotics). Nine of ten subjects achieved a sustained virologic response (SVR), while one noncirrhotic subject relapsed. Hepatic IFN-stimulated gene expression decreased with treatment in the liver of all subjects, with no observable impact of cirrhosis. Hepatic gene expression of type III IFNs (IFNL1, IFNL3, IFNL4-ΔG) similarly decreased with treatment, while IFNA2 expression, undetectable in all subjects pretreatment, was detected post-treatment in three subjects who achieved a SVR. Only the subject who relapsed had detectable IFNL4-ΔG expression in post-treatment liver. Other IFNs had no change in gene expression (IFNG, IFNB1, IFNA5) or could not be detected. Although expression of multiple hepatic miRNAs changed with treatment, many miRNAs previously implicated in HCV replication and IFN signalling had unchanged expression. In conclusion, favourable treatment outcome during IFN-free HCV therapy is associated with changes in the host IFN response regardless of cirrhosis. PMID:26840694

  1. 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

  2. Discordant Immune Response with Antiretroviral Therapy in HIV-1: A Systematic Review of Clinical Outcomes

    PubMed Central

    Kelly, Christine; Gaskell, Katherine M.; Richardson, Marty; Klein, Nigel; Garner, Paul; MacPherson, Peter

    2016-01-01

    Background A discordant immune response (DIR) is a failure to satisfactorily increase CD4 counts on ART despite successful virological control. Literature on the clinical effects of DIR has not been systematically evaluated. We aimed to summarise the risk of mortality, AIDS and serious non-AIDS events associated with DIR with a systematic review. Methods The protocol is registered with the Centre for Review Dissemination, University of York (registration number CRD42014010821). Included studies investigated the effect of DIR on mortality, AIDS, or serious non-AIDS events in cohort studies or cohorts contained in arms of randomised controlled trials for adults aged 16 years or older. DIR was classified as a suboptimal CD4 count (as defined by the study) despite virological suppression following at least 6 months of ART. We systematically searched PubMed, Embase, and the Cochrane Library to December 2015. Risk of bias was assessed using the Cochrane tool for assessing risk of bias in cohort studies. Two authors applied inclusion criteria and one author extracted data. Risk ratios were calculated for each clinical outcome reported. Results Of 20 studies that met the inclusion criteria, 14 different definitions of DIR were used. Risk ratios for mortality in patients with and without DIR ranged between 1.00 (95% CI 0.26 to 3.92) and 4.29 (95% CI 1.96 to 9.38) with the majority of studies reporting a 2 to 3 fold increase in risk. Conclusions DIR is associated with a marked increase in mortality in most studies but definitions vary widely. We propose a standardised definition to aid the development of management options for DIR. PMID:27284683

  3. Ethical responsibilities toward indirect and collateral participants in pragmatic clinical trials

    PubMed Central

    Smalley, Jaye Bea; Merritt, Maria W.; Al-Khatib, Sana M.; McCall, Debbe; Staman, Karen L.; Stepnowsky, Carl

    2016-01-01

    Pragmatic Clinical Trials (PCTs) are designed to inform decision makers about the benefits, burdens, and risks of health interventions in real-world settings. PCTs often use for research purposes data collected in the course of clinical practice. The distinctive features of PCTs demand fresh thinking about what is required to act properly toward people affected by their conduct, in ways that go beyond ensuring the protection of rights and welfare for “human research subjects” under conventional research ethics regulations. To stimulate such work, we propose to distinguish among categories of research participants in PCTs as follows: Direct participants: (1) Individuals being directly intervened upon and/or (2) individuals from whom personal identifiable data are being collected for the purposes of the PCT. Indirect participants: Individuals who are (1) not identified as direct participants and (2) whose rights and welfare may be affected by the intervention through their routine exposure to the environment in which the intervention is being deployed. Collateral Participants: Patient groups and other stakeholder communities who may be otherwise affected by the occurrence and findings of the PCT. We illustrate these distinctions with case examples and discuss the distinctive responsibilities of researchers and PCT leadership toward each type of participant. We suggest that PCT investigators, Institutional Review Boards (IRBs), health systems leaders, and others engaged in the research enterprise work together to identify these participants. For indirect participants, risks and benefits to which they are exposed should be weighed to ensure that their rights and welfare are protected accordingly, and communication strategies should be considered to help them make well-informed decisions. Collateral participants could provide input on the design, planning and conduct of a PCT, and offer insights regarding the best way to communicate the trial’s results to their

  4. Virologic response and haematologic toxicity of boceprevir- and telaprevir-containing regimens in actual clinical settings

    PubMed Central

    Butt, A. A.; Yan, P.; Shaikh, O. S.; Freiberg, M. S.; Re, V. Lo; Justice, A. C.; Sherman, K. E.

    2016-01-01

    SUMMARY Effectiveness, safety and tolerability of boceprevir (BOC) and telaprevir (TPV) in actual clinical settings remain unknown. We determined rates of sustained virologic response (SVR) and haematologic adverse effects among persons treated with BOC- or TPV-containing regimens, compared with pegylated interferon/ribavirin (PEG/RBV). Using an established cohort of hepatitis C virus (HCV)-infected persons, Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES), we identified those treated with a BOC- or TPV-containing regimen and HCV genotype 1-infected controls treated with PEG/RBV. We excluded those with HIV co-infection and missing HCV RNA values to determine SVR. Primary endpoints were SVR (undetectable HCV RNA ≥12 weeks after treatment completion) and haematologic toxicity (grade 3/4 anaemia, neutropenia and thrombocytopenia). We evaluated 2288 persons on BOC-, 409 on TPV-containing regimen and 6308 on PEG/RBV. Among these groups, respectively, 31%, 43% and 9% were treatment-experienced; 17%, 37% and 14% had baseline cirrhosis; 63%, 54% and 48% were genotype 1a. SVR rates among noncirrhotics were as follows: treatment naïve: 65% (BOC), 67% (TPV) and 31% (PEG/RBV); treatment experienced: 57% (BOC), 54% (TPV) and 13% (PEG/RBV); (P-value not significant for BOC vs TPV; P < 0.0001 for BOC or TPV vs PEG/RBV). Haematologic toxicities among BOC-, TPV- and PEG/RBV-treated groups were as follows: grade 3/4 anaemia 7%, 11% and 3%; grade 4 thrombocytopenia 2.2%, 5.4% and 1.7%; grade 4 neutropenia 8.2%, 5.6% and 3.4%. SVR rates are higher and closer to those reported in pivotal clinical trials among BOC- and TPV-treated persons compared with PEG/RBV-treated persons. Haematologic adverse events are frequent, but severe toxicity is uncommon. PMID:25524834

  5. Neuroinflammatory responses to traumatic brain injury: etiology, clinical consequences, and therapeutic opportunities

    PubMed Central

    Lozano, Diego; Gonzales-Portillo, Gabriel S; Acosta, Sandra; de la Pena, Ike; Tajiri, Naoki; Kaneko, Yuji; Borlongan, Cesar V

    2015-01-01

    Traumatic brain injury (TBI) is a serious public health problem accounting for 1.4 million emergency room visits by US citizens each year. Although TBI has been traditionally considered an acute injury, chronic symptoms reminiscent of neurodegenerative disorders have now been recognized. These progressive neurodegenerative-like symptoms manifest as impaired motor and cognitive skills, as well as stress, anxiety, and mood affective behavioral alterations. TBI, characterized by external bumps or blows to the head exceeding the brain’s protective capacity, causes physical damage to the central nervous system with accompanying neurological dysfunctions. The primary impact results in direct neural cell loss predominantly exhibiting necrotic death, which is then followed by a wave of secondary injury cascades including excitotoxicity, oxidative stress, mitochondrial dysfunction, blood–brain barrier disruption, and inflammation. All these processes exacerbate the damage, worsen the clinical outcomes, and persist as an evolving pathological hallmark of what we now describe as chronic TBI. Neuroinflammation in the acute stage of TBI mobilizes immune cells, astrocytes, cytokines, and chemokines toward the site of injury to mount an antiinflammatory response against brain damage; however, in the chronic stage, excess activation of these inflammatory elements contributes to an “inflamed” brain microenvironment that principally contributes to secondary cell death in TBI. Modulating these inflammatory cells by changing their phenotype from proinflammatory to antiinflammatory would likely promote therapeutic effects on TBI. Because neuroinflammation occurs at acute and chronic stages after the primary insult in TBI, a treatment targeting neuroinflammation may have a wider therapeutic window for TBI. To this end, a better understanding of TBI etiology and clinical manifestations, especially the pathological presentation of chronic TBI with neuroinflammation as a major

  6. The genetic and genomic background of multiple myeloma patients achieving complete response after induction therapy with bortezomib, thalidomide and dexamethasone (VTD).

    PubMed

    Terragna, Carolina; Remondini, Daniel; Martello, Marina; Zamagni, Elena; Pantani, Lucia; Patriarca, Francesca; Pezzi, Annalisa; Levi, Giuseppe; Offidani, Massimo; Proserpio, Ilaria; De Sabbata, Giovanni; Tacchetti, Paola; Cangialosi, Clotilde; Ciambelli, Fabrizio; Viganò, Clara Virginia; Dico, Flores Angela; Santacroce, Barbara; Borsi, Enrica; Brioli, Annamaria; Marzocchi, Giulia; Castellani, Gastone; Martinelli, Giovanni; Palumbo, Antonio; Cavo, Michele

    2016-03-01

    The prime focus of the current therapeutic strategy for Multiple Myeloma (MM) is to obtain an early and deep tumour burden reduction, up to the level of complete response (CR). To date, no description of the characteristics of the plasma cells (PC) prone to achieve CR has been reported. This study aimed at the molecular characterization of PC obtained at baseline from MM patients in CR after bortezomib-thalidomide-dexamethasone (VTD) first line therapy.One hundred and eighteen MM primary tumours obtained from homogeneously treated patients were profiled both for gene expression and for single nucleotide polymorphism genotype. Genomic results were used to obtain a predictor of sensitivity to VTD induction therapy, as well as to describe both the transcription and the genomic profile of PC derived from MM with subsequent optimal response to primary induction therapy.By analysing the gene profiles of CR patients, we identified a 5-gene signature predicting CR with an overall median accuracy of 75% (range: 72%-85%). In addition, we highlighted the differential expression of a series of genes, whose deregulation might explain patients' sensitivity to VTD therapy. We also showed that a small copy number loss, covering 606Kb on chromosome 1p22.1 was the most significantly associated with CR patients. PMID:26575327

  7. The genetic and genomic background of multiple myeloma patients achieving complete response after induction therapy with bortezomib, thalidomide and dexamethasone (VTD)

    PubMed Central

    Terragna, Carolina; Remondini, Daniel; Martello, Marina; Zamagni, Elena; Pantani, Lucia; Patriarca, Francesca; Pezzi, Annalisa; Levi, Giuseppe; Offidani, Massimo; Proserpio, Ilaria; De Sabbata, Giovanni; Tacchetti, Paola; Cangialosi, Clotilde; Ciambelli, Fabrizio; Viganò, Clara Virginia; Dico, Flores Angela; Santacroce, Barbara; Borsi, Enrica; Brioli, Annamaria; Marzocchi, Giulia; Castellani, Gastone; Martinelli, Giovanni; Palumbo, Antonio; Cavo, Michele

    2016-01-01

    The prime focus of the current therapeutic strategy for Multiple Myeloma (MM) is to obtain an early and deep tumour burden reduction, up to the level of complete response (CR). To date, no description of the characteristics of the plasma cells (PC) prone to achieve CR has been reported. This study aimed at the molecular characterization of PC obtained at baseline from MM patients in CR after bortezomib-thalidomide-dexamethasone (VTD) first line therapy. One hundred and eighteen MM primary tumours obtained from homogeneously treated patients were profiled both for gene expression and for single nucleotide polymorphism genotype. Genomic results were used to obtain a predictor of sensitivity to VTD induction therapy, as well as to describe both the transcription and the genomic profile of PC derived from MM with subsequent optimal response to primary induction therapy. By analysing the gene profiles of CR patients, we identified a 5-gene signature predicting CR with an overall median accuracy of 75% (range: 72%–85%). In addition, we highlighted the differential expression of a series of genes, whose deregulation might explain patients' sensitivity to VTD therapy. We also showed that a small copy number loss, covering 606Kb on chromosome 1p22.1 was the most significantly associated with CR patients. PMID:26575327

  8. Classification of childhood asthma phenotypes and long-term clinical responses to inhaled anti-inflammatory medications

    PubMed Central

    Howrylak, Judie A.; Fuhlbrigge, Anne L.; Strunk, Robert C.; Zeiger, Robert S.; Weiss, Scott T.; Raby, Benjamin A.

    2014-01-01

    Background Although recent studies have identified the presence of phenotypic clusters in asthmatic patients, the clinical significance and temporal stability of these clusters have not been explored. Objective Our aim was to examine the clinical relevance and temporal stability of phenotypic clusters in children with asthma. Methods We applied spectral clustering to clinical data from 1041 children with asthma participating in the Childhood Asthma Management Program. Posttreatment randomization follow-up data collected over 48 months were used to determine the effect of these clusters on pulmonary function and treatment response to inhaled anti-inflammatory medication. Results We found 5 reproducible patient clusters that could be differentiated on the basis of 3 groups of features: atopic burden, degree of airway obstruction, and history of exacerbation. Cluster grouping predicted long-term asthma control, as measured by the need for oral prednisone (P < .0001) or additional controller medications (P = .001), as well as longitudinal differences in pulmonary function (P < .0001). We also found that the 2 clusters with the highest rates of exacerbation had different responses to inhaled corticosteroids when compared with the other clusters. One cluster demonstrated a positive response to both budesonide (P = .02) and nedocromil (P = .01) compared with placebo, whereas the other cluster demonstrated minimal responses to both budesonide (P = .12) and nedocromil (P = .56) compared with placebo. Conclusion Phenotypic clustering can be used to identify longitudinally consistent and clinically relevant patient subgroups, with implications for targeted therapeutic strategies and clinical trials design. PMID:24892144

  9. Effect of statins on clinical and molecular responses to intramuscular interferon beta-1a

    PubMed Central

    Rudick, R A.; Pace, A; Rani, M R.S.; Hyde, R; Panzara, M; Appachi, S; Shrock, J; Maurer, S L.; Calabresi, P A.; Confavreux, C; Galetta, S L.; Lublin, F D.; Radue, E -W.; Ransohoff, R M.

    2009-01-01

    Background: Findings from a small clinical study suggested that statins may counteract the therapeutic effects of interferon beta (IFNβ) in patients with relapsing-remitting multiple sclerosis (RRMS). Methods: We conducted a post hoc analysis of data from the Safety and Efficacy of Natalizumab in Combination With IFNβ-1a in Patients With Relapsing-Remitting Multiple Sclerosis (SENTINEL) study to determine the effects of statins on efficacy of IFNβ. SENTINEL was a prospective trial of patients with RRMS treated with natalizumab (Tysabri®, Biogen Idec, Inc., Cambridge, MA) plus IM IFNβ-1a (Avonex®, Biogen Idec, Inc.) 30 μg compared with placebo plus IM IFNβ-1a 30 μg. Clinical and MRI outcomes in patients treated with IM IFNβ-1a only (no-statins group, n = 542) were compared with those of patients taking IM IFNβ-1a and statins at doses used to treat hyperlipidemia (statins group, n = 40). Results: No significant differences were observed between treatment groups in adjusted annualized relapse rate (p = 0.937), disability progression (p = 0.438), number of gadolinium-enhancing lesions (p = 0.604), or number of new or enlarging T2-hyperintense lesions (p = 0.802) at 2 years. More patients in the statins group reported fatigue, extremity pain, muscle aches, and increases in hepatic transaminases compared with patients in the no-statins group. Statin treatment had no ex vivo or in vitro effect on induction of IFN-stimulated genes. Conclusions: Statin therapy does not appear to affect clinical effects of IM interferon beta-1a in patients with relapsing-remitting multiple sclerosis or the primary molecular response to interferon beta treatment. GLOSSARY ANCOVA = analysis of covariance; CI = confidence interval; EDSS = Expanded Disability Status Scale; GAPDH = glyceraldehyde-3-phosphate dehydrogenase; Gd+ = gadolinium-enhancing; IFNβ = interferon beta; ISG = IFN-stimulated gene; RRMS = relapsing-remitting multiple sclerosis; SENTINEL = Safety and Efficacy of

  10. Long-term survival and T-cell kinetics in relapsed/refractory ALL patients who achieved MRD response after blinatumomab treatment.

    PubMed

    Zugmaier, Gerhard; Gökbuget, Nicola; Klinger, Matthias; Viardot, Andreas; Stelljes, Matthias; Neumann, Svenja; Horst, Heinz-A; Marks, Reinhard; Faul, Christoph; Diedrich, Helmut; Reichle, Albrecht; Brüggemann, Monika; Holland, Chris; Schmidt, Margit; Einsele, Hermann; Bargou, Ralf C; Topp, Max S

    2015-12-10

    This long-term follow-up analysis evaluated overall survival (OS) and relapse-free survival (RFS) in a phase 2 study of the bispecific T-cell engager antibody construct blinatumomab in 36 adults with relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL). In the primary analysis, 25 (69%) patients with relapsed/refractory ALL achieved complete remission with full (CR) or partial (CRh) hematologic recovery of peripheral blood counts within the first 2 cycles. Twenty-five patients (69%) had a minimal residual disease (MRD) response (<10(-4) blasts), including 22 CR/CRh responders, 2 patients with hypocellular bone marrow, and 1 patient with normocellular bone marrow but low peripheral counts. Ten of the 36 patients (28%) were long-term survivors (OS ≥30 months). Median OS was 13.0 months (median follow-up, 32.6 months). MRD response was associated with significantly longer OS (Mantel-Byar P = .009). All 10 long-term survivors had an MRD response. Median RFS was 8.8 months (median follow-up, 28.9 months). A plateau for RFS was reached after ∼18 months. Six of the 10 long-term survivors remained relapse-free, including 4 who received allogeneic stem cell transplantation (allo-SCT) as consolidation for blinatumomab and 2 who received 3 additional cycles of blinatumomab instead of allo-SCT. Three long-term survivors had neurologic events or cytokine release syndrome, resulting in temporary blinatumomab discontinuation; all restarted blinatumomab successfully. Long-term survivors had more pronounced T-cell expansion than patients with OS <30 months. PMID:26480933

  11. Long-term survival and T-cell kinetics in relapsed/refractory ALL patients who achieved MRD response after blinatumomab treatment

    PubMed Central

    Gökbuget, Nicola; Klinger, Matthias; Viardot, Andreas; Stelljes, Matthias; Neumann, Svenja; Horst, Heinz-A.; Marks, Reinhard; Faul, Christoph; Diedrich, Helmut; Reichle, Albrecht; Brüggemann, Monika; Holland, Chris; Schmidt, Margit; Einsele, Hermann; Bargou, Ralf C.; Topp, Max S.

    2015-01-01

    This long-term follow-up analysis evaluated overall survival (OS) and relapse-free survival (RFS) in a phase 2 study of the bispecific T-cell engager antibody construct blinatumomab in 36 adults with relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL). In the primary analysis, 25 (69%) patients with relapsed/refractory ALL achieved complete remission with full (CR) or partial (CRh) hematologic recovery of peripheral blood counts within the first 2 cycles. Twenty-five patients (69%) had a minimal residual disease (MRD) response (<10−4 blasts), including 22 CR/CRh responders, 2 patients with hypocellular bone marrow, and 1 patient with normocellular bone marrow but low peripheral counts. Ten of the 36 patients (28%) were long-term survivors (OS ≥30 months). Median OS was 13.0 months (median follow-up, 32.6 months). MRD response was associated with significantly longer OS (Mantel-Byar P = .009). All 10 long-term survivors had an MRD response. Median RFS was 8.8 months (median follow-up, 28.9 months). A plateau for RFS was reached after ∼18 months. Six of the 10 long-term survivors remained relapse-free, including 4 who received allogeneic stem cell transplantation (allo-SCT) as consolidation for blinatumomab and 2 who received 3 additional cycles of blinatumomab instead of allo-SCT. Three long-term survivors had neurologic events or cytokine release syndrome, resulting in temporary blinatumomab discontinuation; all restarted blinatumomab successfully. Long-term survivors had more pronounced T-cell expansion than patients with OS <30 months. PMID:26480933

  12. Maternal Antibodies: Clinical Significance, Mechanism of Interference with Immune Responses, and Possible Vaccination Strategies

    PubMed Central

    Niewiesk, Stefan

    2014-01-01

    Neonates have an immature immune system, which cannot adequately protect against infectious diseases. Early in life, immune protection is accomplished by maternal antibodies transferred from mother to offspring. However, decaying maternal antibodies inhibit vaccination as is exemplified by the inhibition of seroconversion after measles vaccination. This phenomenon has been described in both human and veterinary medicine and is independent of the type of vaccine being used. This review will discuss the use of animal models for vaccine research. I will review clinical solutions for inhibition of vaccination by maternal antibodies, and the testing and development of potentially effective vaccines. These are based on new mechanistic insight about the inhibitory mechanism of maternal antibodies. Maternal antibodies inhibit the generation of antibodies whereas the T cell response is usually unaffected. B cell inhibition is mediated through a cross-link between B cell receptor (BCR) with the Fcγ-receptor IIB by a vaccine–antibody complex. In animal experiments, this inhibition can be partially overcome by injection of a vaccine-specific monoclonal IgM antibody. IgM stimulates the B cell directly through cross-linking the BCR via complement protein C3d and antigen to the complement receptor 2 (CR2) signaling complex. In addition, it was shown that interferon alpha binds to the CD21 chain of CR2 as well as the interferon receptor and that this dual receptor usage drives B cell responses in the presence of maternal antibodies. In lieu of immunizing the infant, the concept of maternal immunization as a strategy to protect neonates has been proposed. This approach would still not solve the question of how to immunize in the presence of maternal antibodies but would defer the time of infection to an age where infection might not have such a detrimental outcome as in neonates. I will review successful examples and potential challenges of implementing this concept. PMID

  13. Durable Clinical Response to Entrectinib in NTRK1-Rearranged Non-Small Cell Lung Cancer

    PubMed Central

    Le, Long P.; Zheng, Zongli; Muzikansky, Alona; Drilon, Alexander; Patel, Manish; Bauer, Todd M.; Liu, Stephen V.; Ou, Sai-Hong I.; Jackman, David; Costa, Daniel B.; Multani, Pratik S.; Li, Gary G.; Hornby, Zachary; Chow-Maneval, Edna; Luo, David; Lim, Jonathan E.; Iafrate, Anthony J.; Shaw, Alice T.

    2015-01-01

    Introduction: Chromosomal rearrangements involving neurotrophic tyrosine kinase 1 (NTRK1) occur in a subset of non-small cell lung cancers (NSCLCs) and other solid tumor malignancies, leading to expression of an oncogenic TrkA fusion protein. Entrectinib (RXDX-101) is an orally available tyrosine kinase inhibitor, including TrkA. We sought to determine the frequency of NTRK1 rearrangements in NSCLC and to assess the clinical activity of entrectinib. Methods: We screened 1378 cases of NSCLC using anchored multiplex polymerase chain reaction (AMP). A patient with an NTRK1 gene rearrangement was enrolled onto a Phase 1 dose escalation study of entrectinib in adult patients with locally advanced or metastatic tumors (NCT02097810). We assessed safety and response to treatment. Results: We identified NTRK1 gene rearrangements at a frequency of 0.1% in this cohort. A patient with stage IV lung adenocrcinoma with an SQSTM1-NTRK1 fusion transcript expression was treated with entrectinib. Entrectinib was well tolerated, with no grade 3–4 adverse events. Within three weeks of starting on treatment, the patient reported resolution of prior dyspnea and pain. Restaging CT scans demonstrated a RECIST partial response (PR) and complete resolution of all brain metastases. This patient has continued on treatment for over 6 months with an ongoing PR. Conclusions: Entrectinib demonstrated significant anti-tumor activity in a patient with NSCLC harboring an SQSTM1-NTRK1 gene rearrangement, indicating that entrectinib may be an effective therapy for tumors with NTRK gene rearrangements, including those with central nervous system metastases. PMID:26565381

  14. Group differences in physician responses to handheld presentation of clinical evidence: a verbal protocol analysis

    PubMed Central

    Lottridge, Danielle M; Chignell, Mark; Danicic-Mizdrak, Romana; Pavlovic, Nada J; Kushniruk, Andre; Straus, Sharon E

    2007-01-01

    Background To identify individual differences in physicians' needs for the presentation of evidence resources and preferences for mobile devices. Methods Within-groups analysis of responses to semi-structured interviews. Interviews consisted of using prototypes in response to task-based scenarios. The prototypes were implemented on two different form factors: a tablet style PC and a pocketPC. Participants were from three user groups: general internists, family physicians and medicine residents, and from two different settings: urban and semi-urban. Verbal protocol analysis, which consists of coding utterances, was conducted on the transcripts of the testing sessions. Statistical relationships were investigated between staff physicians' and residents' background variables, self-reported experiences with the interfaces, and verbal code frequencies. Results 47 physicians were recruited from general internal medicine, family practice clinics and a residency training program. The mean age of participants was 42.6 years. Physician specialty had a greater effect on device and information-presentation preferences than gender, age, setting or previous technical experience. Family physicians preferred the screen size of the tablet computer and were less concerned about its portability. Residents liked the screen size of the tablet, but preferred the portability of the pocketPC. Internists liked the portability of the pocketPC, but saw less advantage to the large screen of the tablet computer (F[2,44] = 4.94, p = .012). Conclusion Different types of physicians have different needs and preferences for evidence-based resources and handheld devices. This study shows how user testing can be incorporated into the process of design to inform group-based customization. PMID:17655759

  15. High-level plasmid-mediated gentamicin resistance and pheromone response of plasmids present in clinical isolates of Enterococcus faecalis.

    PubMed Central

    Shiojima, M; Tomita, H; Tanimoto, K; Fujimoto, S; Ike, Y

    1997-01-01

    Eleven pheromone-responding plasmids encoding erythromycin or gentamicin resistance were isolated from multiresistant clinical Enterococcus faecalis isolates. The plasmids were classified into six types with respect to their pheromone responses. The three erythromycin resistance plasmids responded to different pheromones. Of the eight gentamicin resistance plasmids, four plasmids responded to same pheromone. Southern hybridization studies showed that the genes involved in regulation of the pheromone response were conserved in the drug resistance plasmids. PMID:9056018

  16. 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. PMID:21516433

  17. Research misconduct in clinical research--the American experience and response.

    PubMed

    Ryan, K J

    1999-01-01

    Research misconduct in the United States has occurred sporadically since 1961 in the laboratories of some of our most distinguished scientists. In view of the enormous number of research grants funded, cases of this kind are relatively uncommon, but have none the less attracted governmental supervision and calls for reform. The scientific community, universities and government have addressed the issue in various ways and changes have been proposed and some actually instituted. In view of human nature, no one seriously believes that dishonesty in research can be prevented to any greater extent than in any other human activity. However, some practices may discourage and mitigate such occurrences. These include: education in sound laboratory research practices, a fair distribution of authorship assignment, and adequate supervision of research personnel including appropriate reviewing of primary data. Other measures which might be considered include: an adequate check of the credentials of all new personnel, audits for clinical research, especially for those involving significant numbers of patients and multiple institutions, and the introduction of quality control concepts into research procedures. The hope is that the senior individual scientist responsible for the quality and integrity of the research will institute such measures as needed, and that institutional and government supervision will not interfere with the creative process. PMID:10090695

  18. Borrelia burgdorferi clinical isolates induce human innate immune responses that are not dependent on genotype.

    PubMed

    Mason, Lauren M K; Herkes, Eduard A; Krupna-Gaylord, Michelle A; Oei, Anneke; van der Poll, Tom; Wormser, Gary P; Schwartz, Ira; Petzke, Mary M; Hovius, Joppe W R

    2015-10-01

    Borrelia burgdorferi can be categorized based on restriction fragment length polymorphism analysis into ribosomal spacer type (RST) 1, 2 and 3. A correlation between RST type and invasiveness of Borrelia isolates has been demonstrated in clinical studies and experimental models, and RST 1 isolates are more likely to cause disseminated disease than RST 3 isolates. We hypothesized that this could partially be due to increased susceptibility of RST 3 isolates to killing by the innate immune system early in infection. Thus, we investigated the interaction of five RST 1 and five RST 3 isolates with various components of the human innate immune system in vitro. RST 3 isolates induced significantly greater upregulation of activation markers in monocyte-derived dendritic cells compared to RST 1 isolates at a low multiplicity of infection. However, RST 1 isolates stimulated greater interleukin-6 production. At a high multiplicity of infection no differences in dendritic cell activation or cytokine production were observed. In addition, we observed no differences in the ability of RST 1 and RST 3 isolates to activate monocytes or neutrophils and all strains were phagocytosed at a comparable rate. Finally, all isolates tested were equally resistant to complement-mediated killing, as determined by dark-field microscopy and a growth inhibition assay. In conclusion, we demonstrate that the RST 1 and 3 isolates showed no distinction in their susceptibility to the various components of the human immune system studied here, suggesting that other factors are responsible for their differential invasiveness. PMID:26093919

  19. Tractography Activation Patterns in Dorsolateral Prefrontal Cortex Suggest Better Clinical Responses in OCD DBS

    PubMed Central

    Hartmann, Christian J.; Lujan, J. Luis; Chaturvedi, Ashutosh; Goodman, Wayne K.; Okun, Michael S.; McIntyre, Cameron C.; Haq, Ihtsham U.

    2016-01-01

    Background: Medication resistant obsessive-compulsive disorder (OCD) patients can be successfully treated with Deep Brain Stimulation (DBS) which targets the anterior limb of the internal capsule (ALIC) and the nucleus accumbens (NA). Growing evidence suggests that in patients who respond to DBS, axonal fiber bundles surrounding the electrode are activated, but it is currently unknown which discrete pathways are critical for optimal benefit. Our aim was to identify axonal pathways mediating clinical effects of ALIC-NA DBS. Methods: We created computational models of ALIC-NA DBS to simulate the activation of fiber tracts and to identify connected cerebral regions. The pattern of activated axons and their cortical targets was investigated in six OCD patients who underwent ALIC-NA DBS. Results: Modulation of the right anterior middle frontal gyrus (dorsolateral prefrontal cortex) was associated with an excellent response. In contrast, non-responders showed high activation in the orbital part of the right inferior frontal gyrus (lateral orbitofrontal cortex/anterior ventrolateral prefrontal cortex). Factor analysis followed by step-wise linear regression indicated that YBOCS improvement was inversely associated with factors that were predominantly determined by gray matter activation results. Discussion: Our findings support the hypothesis that optimal therapeutic results are associated with the activation of distinct fiber pathways. This suggests that in DBS for OCD, focused stimulation of specific fiber pathways, which would allow for stimulation with lower amplitudes, may be superior to activation of a wide array of pathways, typically associated with higher stimulation amplitudes. PMID:26834544

  20. Strategic response by providers to specialty hospitals, ambulatory surgery centers, and retail clinics.

    PubMed

    Burns, Lawton R; David, Guy; Helmchen, Lorens A

    2011-04-01

    Radical innovation and disruptive technologies are frequently heralded as a solution to delivering higher quality, lower cost health care. According to the literature on disruption, local hospitals and physicians (incumbent providers) may be unable to competitively respond to such "creative destruction" and alter their business models for a host of reasons, thus threatening their future survival. However, strategic management theory and research suggest that, under certain conditions, incumbent providers may be able to weather the discontinuities posed by the disrupters. This article analyzes 3 disruptive innovations in service delivery: single-specialty hospitals, ambulatory surgical centers, and retail clinics. We first discuss the features of these innovations to assess how disruptive they are. We then draw on the literature on strategic adaptation to suggest how incumbents develop competitive responses to these disruptive innovations that assure their continued survival. These arguments are then evaluated in a field study of several urban markets based on interviews with both incumbents and entrants. The interviews indicate that entrants have failed to disrupt incumbent providers primarily as a result of strategies pursued by the incumbents. The findings cast doubt on the prospects for these disruptive innovations to transform health care. PMID:21091376

  1. A Mixed-methods Investigation of Sensory Response Patterns in Barth Syndrome: A Clinical Phenotype?

    PubMed Central

    Reynolds, Stacey; Kreider, Consuelo; Bendixen, Roxanna

    2012-01-01

    Barth syndrome is a genetic disorder that affects approximately 1/500,000 boys each year. While treatment of medical complications associated with Barth is of primary importance, there is a concomitant need to look at behavioral and clinical features of the disorder. The purpose of this study was to examine the prevalence of atypical sensory processing in 21 boys with Barth syndrome and to explore if phenotypic patterns of sensory responsiveness may be useful in early diagnosis. Using a mixed methods approach, we found that sensory issues related to feeding and eating were ubiquitous in our sample, with some behaviors such as strong gag reflex identifiable early in development. Specifically, boys with Barth had a strong preference for salty, cheesy, and spicy foods while having an overall restricted repertoire of foods they would eat (e.g. picky eaters). In boys with Barth as they age, auditory sensitivity and auditory filtering issues also emerged as potential sensory-related behaviors affecting academic performance and participation. Overall, this study suggests that early identification of sensory patterns in Barth may assist in differential diagnosis and create opportunities for early interventions that may minimize the impact of these behaviors on function and participation. PMID:22711649

  2. RESPONSES OF OYSTER (CRASSOSTREA VIRGINICA) HEMOCYTES TO NONPATHOGENIC AND CLINICAL ISOLATES OF VIBRIO PARAHAEMOLYTICUS

    EPA Science Inventory

    Bacterial uptake by oysters (Crassostrea virginica) and bactericidal activity of oyster hemocytes were studied using four environmental isolates and three clinical isolates of Vibrio parahaemolyticus. Clinical isolates (2030, 2062, 2107) were obtained from gastroenteritis patien...

  3. Relation between humoral responses to HIV gag and env proteins at seroconversion and clinical outcome of HIV infection.

    PubMed Central

    Cheingsong-Popov, R; Panagiotidi, C; Bowcock, S; Aronstam, A; Wadsworth, J; Weber, J

    1991-01-01

    OBJECTIVE--To study the contribution of the humoral response to HIV-I at seroconversion to disease outcome after 84 months. DESIGN--A retrospective longitudinal study. SETTING--Two haemophilia centres in the United Kingdom. PATIENTS--88 Haemophiliac patients infected with HIV-I for whom sera were available from before seroconversion and in whom clinical follow up data were available. RESULTS--Kaplan-Meier survival analysis showed a significant difference between a high titre (greater than 1600) p24 antibody response at seroconversion and prolonged time before the development of HIV related disease (p = 0.0008). In contrast, higher titres of antibody to gp120 at seroconversion (greater than 25,600) correlated with more rapid clinical deterioration (p = 0.025). CONCLUSIONS--The first humoral response to HIV proteins at seroconversion is associated with clinical outcome; patients with an initial low titre antibody response to the gagp24 protein have a significantly faster rate of progression to CDC stage IV disease. Patients with a high titre p24 antibody response progress to AIDS more slowly, and these data provide an explanation why p24 antigenaemia is not universally detected in patients with AIDS. It is unclear whether the association between a strong initial p24 antibody response and slower progression of HIV disease is causal and if so whether it is due to viral or host factors. PMID:1899349

  4. Emotional responses to images of food in adults with an eating disorder: a comparative study with healthy and clinical controls.

    PubMed

    Hay, Phillipa; Katsikitis, Mary

    2014-08-01

    Emotive responses to foods in people with eating disorders are incompletely understood in relation to whether the extent of emotional response is due to the eating disorder or non-specific emotional states. The aims of the present study were to investigate negative and positive emotive responses to food images in adults with an eating disorder, and to compare responses to a (i) healthy and a (ii) clinic (psychiatry) control group. Participants viewed 20 images (16 of foods previously found to evoke fear, disgust and happiness and 4 neutral images) at half-minute intervals and rated emotive responses on 3 visual analogue scales for each image. Participants with an eating disorder (n=26) were found to have significantly increased negative emotive (disgust and fear) responses and reduced positive (happiness) responses to the images compared to the 20 clinic and 61 healthy participants. Differences between groups remained significant when controlling for baseline levels of fear, disgust and happiness. Thus, the emotive responses to foods did not appear due to non-specific increases in anxiety or depression but rather was due to the presence of an eating disorder. PMID:25064283

  5. Early predictors of a clinical response at 8 weeks in patients with first-episode psychosis treated with paliperidone ER.

    PubMed

    Chung, Young-Chul; Cui, Yin; Kim, Min-Gul; Kim, Yun-Jeong; Lee, Keon-Hak; Chae, Soo-Wan

    2016-08-01

    Identification of early clinical markers that predict later treatment outcomes in first-episode psychosis is highly valuable. The present study was conducted to determine the best time at which to predict the late treatment response in first-episode psychosis patients treated with paliperidone extended release (ER), the factors predicting early treatment responses (at Week 2 and Week 3) and the relationships between the paliperidone ER plasma concentrations at Week 2 and Week 3, and the treatment responses at Week 2, Week 3 and Week 8. Various criteria for assessing treatment response were employed. We determined the plasma paliperidone concentrations at Week 2 and Week 3, using validated high-performance liquid chromatography/tandem mass spectrometry (HPLC-MS/MS). The treatment response at Week 3 optimally predicted the later (Week 8) response, in terms of negative predictive value (NPV). Independent predictors for good treatment responses at Week 2 and Week 3 were: Female gender, a higher educational level, a higher Positive and Negative Syndrome Scale (PANSS) excited score, and/or a shorter duration of untreated psychosis (DUP). The plasma paliperidone concentration at Week 3, but not Week 2, was a significant predictor of the late treatment response at Week 8. These results may help appropriate clinical decision-making for early non-responders after having their first episode of psychosis. PMID:27334812

  6. Meta-Evaluation in Clinical Anatomy: A Practical Application of Item Response Theory in Multiple Choice Examinations

    ERIC Educational Resources Information Center

    Severo, Milton; Tavares, Maria A. Ferreira

    2010-01-01

    The nature of anatomy education has changed substantially in recent decades, though the traditional multiple-choice written examination remains the cornerstone of assessing students' knowledge. This study sought to measure the quality of a clinical anatomy multiple-choice final examination using item response theory (IRT) models. One hundred…

  7. Preexisting Neutralizing Antibody Responses Distinguish Clinically Inapparent and Apparent Dengue Virus Infections in a Sri Lankan Pediatric Cohort

    PubMed Central

    Corbett, Kizzmekia S.; Katzelnick, Leah; Tissera, Hasitha; Amerasinghe, Ananda; de Silva, Aruna Dharshan; de Silva, Aravinda M.

    2015-01-01

    Dengue viruses (DENVs) are mosquito-borne flaviviruses that infect humans. The clinical presentation of DENV infection ranges from inapparent infection to dengue hemorrhagic fever and dengue shock syndrome. We analyzed samples from a pediatric dengue cohort study in Sri Lanka to explore whether antibody responses differentiated clinically apparent infections from clinically inapparent infections. In DENV-naive individuals exposed to primary DENV infections, we observed no difference in the quantity or quality of acquired antibodies between inapparent and apparent infections. Children who experienced primary infections had broad, serotype–cross-neutralizing antibody responses that narrowed in breadth to a single serotype over a 12-month period after infection. In DENV immune children who were experiencing a repeat infection, we observed a strong association between preexisting neutralizing antibodies and clinical outcome. Notably, children with preexisting monospecific neutralizing antibody responses were more likely to develop fever than children with cross-neutralizing responses. Preexisting DENV neutralizing antibodies are correlated with protection from dengue disease. PMID:25336728

  8. Clinical aspects and cytokine response in severe H1N1 influenza A virus infection

    PubMed Central

    2010-01-01

    Introduction The immune responses in patients with novel A(H1N1) virus infection (nvA(H1N1)) are incompletely characterized. We investigated the profile of Th1 and Th17 mediators and interferon-inducible protein-10 (IP-10) in groups with severe and mild nvA(H1N1) disease and correlated them with clinical aspects. Methods Thirty-two patients hospitalized with confirmed nvA(H1N1) infection were enrolled in the study: 21 patients with nvA(H1N1)-acute respiratory distress syndrome (ARDS) and 11 patients with mild disease. One group of 20 patients with bacterial sepsis-ARDS and another group of 15 healthy volunteers were added to compare their cytokine levels with pandemic influenza groups. In the nvA(H1N1)-ARDS group, the serum cytokine samples were obtained on admission and 3 days later. The clinical aspects were recorded prospectively. Results In the nvA(H1N1)-ARDS group, obesity and lymphocytopenia were more common and IP-10, interleukin (IL)-12, IL-15, tumor necrosis factor (TNF)α, IL-6, IL-8 and IL-9 were significantly increased versus control. When comparing mild with severe nvA(H1N1) groups, IL-6, IL-8, IL-15 and TNFα were significantly higher in the severe group. In nonsurvivors versus survivors, IL-6 and IL-15 were increased on admission and remained higher 3 days later. A positive correlation of IL-6, IL-8 and IL-15 levels with C-reactive protein and with > 5-day interval between symptom onset and admission, and a negative correlation with the PaO2:FiO2 ratio, were found in nvA(H1N1) groups. In obese patients with influenza disease, a significant increased level of IL-8 was found. When comparing viral ARDS with bacterial ARDS, the level of IL-8, IL-17 and TNFα was significantly higher in bacterial ARDS and IL-12 was increased only in viral ARDS. Conclusions In our critically ill patients with novel influenza A(H1N1) virus infection, the hallmarks of the severity of disease were IL-6, IL-15, IL-8 and TNFα. These cytokines, except TNFα, had a positive

  9. Clinical Response, Outbreak Investigation, and Epidemiology of the Fungal Meningitis Epidemic in the United States: Systematic Review

    PubMed Central

    Abbas, Kaja M.; Dorratoltaj, Nargesalsadat; O'Dell, Margaret L.; Bordwine, Paige; Kerkering, Thomas M.; Redican, Kerry J.

    2016-01-01

    We conducted a systematic review of the 2012-2013 multistate fungal meningitis epidemic in the United States from the perspectives of clinical response, outbreak investigation, and epidemiology. Articles focused on clinical response, outbreak investigation, and epidemiology were included, whereas articles focused on compounding pharmacies, legislation and litigation, diagnostics, microbiology, and pathogenesis were excluded. We reviewed 19 articles by use of the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) framework. The source of the fungal meningitis outbreak was traced to the New England Compounding Center in Massachusetts, where injectable methylprednisolone acetate products were contaminated with the predominant pathogen, Exserohilum rostratum. As of October 23, 2013, the final case count stood at 751 patients and 64 deaths, and no additional cases are anticipated. The multisectoral public health response to the fungal meningitis epidemic from the hospitals, clinics, pharmacies, and the public health system at the local, state, and federal levels led to an efficient epidemiological investigation to trace the outbreak source and rapid implementation of multiple response plans. This systematic review reaffirms the effective execution of a multisectoral public health response and efficient delivery of the core functions of public health assessment, policy development, and service assurances to improve population health. PMID:26681583

  10. No Clinically Significant Association Between CFH and ARMS2 Genotypes and Response to Nutritional Supplements

    PubMed Central

    Chew, Emily Y.; Klein, Michael L.; Clemons, Traci E.; Agrón, Elvira; Ratnapriya, Rinki; Edwards, Albert O.; Fritsche, Lars G.; Swaroop, Anand; Abecasis, Gonçalo R.

    2014-01-01

    Objective To determine whether genotypes at two major loci associated with late age-related macular degeneration (AMD), complement factor H (CFH) and Age-Related Maculopathy Susceptibility 2 (ARMS2), influenced the relative benefits of Age-Related Eye Disease Study (AREDS) supplements. Design Unplanned retrospective evaluation of a prospective, randomized, placebo-controlled clinical trial of vitamins and minerals for the treatment of AMD. Subjects AREDS participants (mean age of 69 years) who were at risk for developing late AMD and who were randomized to the 4 arms of the AREDS supplements. Methods Analyses were performed using the Cox proportional hazards model to predict progression to late AMD (neovascular or central geographic atrophy). Statistical models, adjusted for age, gender, smoking status and baseline AMD severity, were used to examine the influence of genotypes on the response to therapy with 4 randomly assigned arms of AREDS supplement components: placebo, antioxidants (vitamins C, E, beta-carotene), zinc with copper, or the combination. Main Outcome Measures The influence of the genotype on the relative treatment response to the randomized components of the AREDS supplement, measured as progression to late AMD. Results Of the 1237 genotyped AREDS participants of Caucasian ethnicity, 385 (31.1%) developed late AMD during the mean follow-up period of 6.6 years. As previously demonstrated, both CFH genotype (p=0.005), ARMS2 (<0.0001) and supplement were each individually associated with progression to late AMD. An interaction analysis found no evidence that the relative benefits of AREDS supplementation varied by genotype. Analysis of (1) CFH rs1061170 and rs1410996 combined with ARMS2 rs10490924, with the 4 randomly assigned arms of AREDS supplement and (2) analysis of the combination of CFH rs412852 and rs3766405 with ARMS2 c.372_815del443ins54 with the AREDS components resulted in no interaction (p=0.06 and p=0.45, respectively, before multiplicity

  11. Prothymosin Alpha and Immune Responses: Are We Close to Potential Clinical Applications?

    PubMed

    Samara, P; Ioannou, K; Tsitsilonis, O E

    2016-01-01

    The thymus gland produces soluble molecules, which mediate significant immune functions. The first biologically active thymic extract was thymosin fraction V, the fractionation of which led to the isolation of a series of immunoactive polypeptides, including prothymosin alpha (proTα). ProTα displays a dual role, intracellularly as a survival and proliferation mediator and extracellularly as a biological response modifier. Accordingly, inside the cell, proTα is implicated in crucial intracellular circuits and may serve as a surrogate tumor biomarker, but when found outside the cell, it could be used as a therapeutic agent for treating immune system deficiencies. In fact, proTα possesses pleiotropic adjuvant activity and a series of immunomodulatory effects (eg, anticancer, antiviral, neuroprotective, cardioprotective). Moreover, several reports suggest that the variable activity of proTα might be exerted through different parts of the molecule. We first reported that the main immunoactive region of proTα is the carboxy-terminal decapeptide proTα(100-109). In conjunction with data from others, we also revealed that proTα and proTα(100-109) signal through Toll-like receptor 4. Although their precise molecular mechanism of action is yet not fully elucidated, proTα and proTα(100-109) are viewed as candidate adjuvants for cancer immunotherapy. Here, we present a historical overview on the discovery and isolation of thymosins with emphasis on proTα and data on some immune-related new activities of the polypeptide and smaller immunostimulatory peptides thereof. Finally, we propose a compiled scenario on proTα's mode of action, which could eventually contribute to its clinical application. PMID:27450735

  12. Early practical experience and the social responsiveness of clinical education: systematic review

    PubMed Central

    Littlewood, Sonia; Ypinazar, Valmae; Margolis, Stephen A; Scherpbier, Albert; Spencer, John; Dornan, Tim

    2005-01-01

    Objectives To find how early experience in clinical and community settings (“early experience”) affects medical education, and identify strengths and limitations of the available evidence. Design A systematic review rating, by consensus, the strength and importance of outcomes reported in the decade 1992-2001. Data sources Bibliographical databases and journals were searched for publications on the topic, reviewed under the auspices of the recently formed Best Evidence Medical Education (BEME) collaboration. Selection of studies All empirical studies (verifiable, observational data) were included, whatever their design, method, or language of publication. Results Early experience was most commonly provided in community settings, aiming to recruit primary care practitioners for underserved populations. It increased the popularity of primary care residencies, albeit among self selected students. It fostered self awareness and empathic attitudes towards ill people, boosted students' confidence, motivated them, gave them satisfaction, and helped them develop a professional identity. By helping develop interpersonal skills, it made entering clerkships a less stressful experience. Early experience helped students learn about professional roles and responsibilities, healthcare systems, and health needs of a population. It made biomedical, behavioural, and social sciences more relevant and easier to learn. It motivated and rewarded teachers and patients and enriched curriculums. In some countries, junior students provided preventive health care directly to underserved populations. Conclusion Early experience helps medical students learn, helps them develop appropriate attitudes towards their studies and future practice, and orientates medical curriculums towards society's needs. Experimental evidence of its benefit is unlikely to be forthcoming and yet more medical schools are likely to provide it. Effort could usefully be concentrated on evaluating the methods and

  13. Social Responsiveness Scale-aided analysis of the clinical impact of copy number variations in autism.

    PubMed

    van Daalen, Emma; Kemner, Chantal; Verbeek, Nienke E; van der Zwaag, Bert; Dijkhuizen, Trijnie; Rump, Patrick; Houben, Renske; van 't Slot, Ruben; de Jonge, Maretha V; Staal, Wouter G; Beemer, Frits A; Vorstman, Jacob A S; Burbach, J Peter H; van Amstel, Hans Kristian Ploos; Hochstenbach, Ron; Brilstra, Eva H; Poot, Martin

    2011-11-01

    Recent array-based studies have detected a wealth of copy number variations (CNVs) in patients with autism spectrum disorders (ASD). Since CNVs also occur in healthy individuals, their contributions to the patient's phenotype remain largely unclear. In a cohort of children with symptoms of ASD, diagnosis of the index patient using ADOS-G and ADI-R was performed, and the Social Responsiveness Scale (SRS) was administered to the index patients, both parents, and all available siblings. CNVs were identified using SNP arrays and confirmed by FISH or array CGH. To evaluate the clinical significance of CNVs, we analyzed three families with multiple affected children (multiplex) and six families with a single affected child (simplex) in which at least one child carried a CNV with a brain-transcribed gene. CNVs containing genes that participate in pathways previously implicated in ASD, such as the phosphoinositol signaling pathway (PIK3CA, GIRDIN), contactin-based networks of cell communication (CNTN6), and microcephalin (MCPH1) were found not to co-segregate with ASD phenotypes. In one family, a loss of CNTN5 co-segregated with disease. This indicates that most CNVs may by themselves not be sufficient to cause ASD, but still may contribute to the phenotype by additive or epistatic interactions with inherited (transmitted) mutations or non-genetic factors. Our study extends the scope of genome-wide CNV profiling beyond de novo CNVs in sporadic patients and may aid in uncovering missing heritability in genome-wide screening studies of complex psychiatric disorders. PMID:21837366

  14. Canine brainstem auditory evoked responses are not clinically impacted by head size or breed.

    PubMed

    Kemper, Debra L; Scheifele, Peter M; Clark, John Greer

    2013-02-17

    Accurate assessment of canine hearing is essential to decrease the incidence of hereditary deafness in predisposed breeds and to substantiate hearing acuity. The Brainstem Auditory Evoked Response (BAER) is a widely accepted, objective test used in humans and animals for estimation of hearing thresholds and deafness diagnosis. In contrast to humans, testing and recording parameters for determination of normal values for canine hearing are not available. Conflicting information concerning breed and head size effects on canine BAER tests are major contributors preventing this normalization. The present study utilized standard head measurement techniques coupled with BAER testing and recording parameters modeled from humans to examine the effect canine head size and breed have on BAER results. Forty-three adult dogs from fourteen different breeds had head size measurements and BAER tests performed. The mean latencies compared by breed for waves I, II, III, IV, and V were as follows: 1.46±0.49 ms, 2.52±0.54 ms, 3.45±0.41 ms, 4.53±0.83 ms and 5.53±0.43 ms, respectively. The mean wave I-V latency interval for all breeds was 3.69 ms. All dogs showed similar waveform morphology, structures, including the presence of five waves occurring within 11 ms after stimulus presentation and a significant trough occurring after Wave V. All of the waveform morphology for our subjects occurred with consistent interpeak latencies as shown by statistical testing. All animals had diagnostic results within the expected ranges for each wave latency and interwave interval allowing diagnostic evaluation. Our results establish that neither differences in head size nor breed impact determination of canine BAER waveform morphology, latency, or hearing sensitivity for diagnostic purposes. The differences in canine head size do not have a relevant impact on canine BAERs and are not clinically pertinent to management or diagnostic decisions. PMID:23262145

  15. Apolipoprotein E epsilon4 allele differentiates the clinical response to donepezil in Alzheimer's disease.

    PubMed

    Bizzarro, A; Marra, C; Acciarri, A; Valenza, A; Tiziano, F D; Brahe, C; Masullo, C

    2005-01-01

    The existence of an association between apolipoprotein E (APOE) and Alzheimer's disease (AD) has been reported in several studies. The possession of an ApoE epsilon4 allele is now considered a genetic risk factor for sporadic AD. There has been a growing agreement about the role exerted by the ApoE epsilon4 allele on the neuropsychological profile and the rate of cognitive decline in AD patients. However, a more controversial issue remains about a possible influence of the APOE genotype on acetylcholinesterase inhibitor therapy response in AD patients. In order to address this issue, 81 patients diagnosed as having probable AD were evaluated by a complete neuropsychological test battery at the time of diagnosis (baseline) and after 12-16 months (retest). Patients were divided into two subgroups: (1) treated with donepezil at a dose of 5 mg once a day (n = 41) and (2) untreated (n = 40). Donepezil therapy was started after baseline evaluation. The APOE genotype was determined according to standardized procedures. We evaluated the possible effect of the APOE genotype on the neuropsychological tasks in relation to donepezil therapy. The statistical analysis of the results showed a global worsening of cognitive performances for all AD patients at the retest. Differences in the clinical outcome were analysed in the four subgroups of AD patients for each neuropsychological task. ApoE epsilon4 carriers/treated patients had improved or unchanged scores at retest evaluation for the following tasks: visual and verbal memory, visual attention and inductive reasoning and Mini Mental State Examination. These results indicate an effect of donepezil on specific cognitive domains (attention and memory) in the ApoE epsilon4 carriers with AD. This might suggest an early identification of AD patients carrying at least one epsilon4 allele as responders to donepezil therapy. PMID:16103669

  16. Mid-stage intervention achieves similar efficacy as conventional early-stage treatment using gene therapy in a pre-clinical model of retinitis pigmentosa

    PubMed Central

    Wert, Katherine J.; Sancho-Pelluz, Javier; Tsang, Stephen H.

    2014-01-01

    Deficiencies in rod-specific cyclic guanosine monophosphate (cGMP) phosphodiesterase-6 (PDE6) are the third most common cause of autosomal recessive retinitis pigmentosa (RP). Previously, viral gene therapy approaches on pre-clinical models with mutations in PDE6 have demonstrated that the photoreceptor cell survival and visual function can be rescued when the gene therapy virus is delivered into the subretinal space before the onset of disease. However, no studies have currently been published that analyze rescue effects after disease onset, a time when human RP patients are diagnosed by a clinician and would receive the treatment. We utilized the AAV2/8(Y733F)-Rho-Pde6α gene therapy virus and injected it into a pre-clinical model of RP with a mutation within the alpha subunit of PDE6: Pde6αD670G. These mice were previously shown to have long-term photoreceptor cell rescue when this gene therapy virus was delivered before the onset of disease. Now, we have determined that subretinal transduction of this rod-specific transgene at post-natal day (P) 21, when approximately half of the photoreceptor cells have undergone degeneration, is more efficient in rescuing cone than rod photoreceptor function long term. Therefore, AAV2/8(Y733F)-Rho-Pde6α is an effective gene therapy treatment that can be utilized in the clinical setting, in human patients who have lost portions of their peripheral visual field and are in the mid-stage of disease when they first present to an eye-care professional. PMID:24101599

  17. Mid-stage intervention achieves similar efficacy as conventional early-stage treatment using gene therapy in a pre-clinical model of retinitis pigmentosa.

    PubMed

    Wert, Katherine J; Sancho-Pelluz, Javier; Tsang, Stephen H

    2014-01-15

    Deficiencies in rod-specific cyclic guanosine monophosphate (cGMP) phosphodiesterase-6 (PDE6) are the third most common cause of autosomal recessive retinitis pigmentosa (RP). Previously, viral gene therapy approaches on pre-clinical models with mutations in PDE6 have demonstrated that the photoreceptor cell survival and visual function can be rescued when the gene therapy virus is delivered into the subretinal space before the onset of disease. However, no studies have currently been published that analyze rescue effects after disease onset, a time when human RP patients are diagnosed by a clinician and would receive the treatment. We utilized the AAV2/8(Y733F)-Rho-Pde6α gene therapy virus and injected it into a pre-clinical model of RP with a mutation within the alpha subunit of PDE6: Pde6α(D670G). These mice were previously shown to have long-term photoreceptor cell rescue when this gene therapy virus was delivered before the onset of disease. Now, we have determined that subretinal transduction of this rod-specific transgene at post-natal day (P) 21, when approximately half of the photoreceptor cells have undergone degeneration, is more efficient in rescuing cone than rod photoreceptor function long term. Therefore, AAV2/8(Y733F)-Rho-Pde6α is an effective gene therapy treatment that can be utilized in the clinical setting, in human patients who have lost portions of their peripheral visual field and are in the mid-stage of disease when they first present to an eye-care professional. PMID:24101599

  18. Long-Term (Six Years) Clinical Outcome Discrimination of Patients in the Vegetative State Could be Achieved Based on the Operational Architectonics EEG Analysis: A Pilot Feasibility Study

    PubMed Central

    Fingelkurts, Andrew A.; Fingelkurts, Alexander A.; Bagnato, Sergio; Boccagni, Cristina; Galardi, Giuseppe

    2016-01-01

    Electroencephalogram (EEG) recordings are increasingly used to evaluate patients with disorders of consciousness (DOC) or assess their prognosis outcome in the short-term perspective. However, there is a lack of information concerning the effectiveness of EEG in classifying long-term (many years) outcome in chronic DOC patients. Here we tested whether EEG operational architectonics parameters (geared towards consciousness phenomenon detection rather than neurophysiological processes) could be useful for distinguishing a very long-term (6 years) clinical outcome of DOC patients whose EEGs were registered within 3 months post-injury. The obtained results suggest that EEG recorded at third month after sustaining brain damage, may contain useful information on the long-term outcome of patients in vegetative state: it could discriminate patients who remain in a persistent vegetative state from patients who reach a minimally conscious state or even recover a full consciousness in a long-term perspective (6 years) post-injury. These findings, if confirmed in further studies, may be pivotal for long-term planning of clinical care, rehabilitative programs, medical-legal decisions concerning the patients, and policy makers. PMID:27347266

  19. American Academy of Clinical Neuropsychology Consensus Conference Statement on the neuropsychological assessment of effort, response bias, and malingering.

    PubMed

    Heilbronner, Robert L; Sweet, Jerry J; Morgan, Joel E; Larrabee, Glenn J; Millis, Scott R

    2009-09-01

    During the past two decades clinical and research efforts have led to increasingly sophisticated and effective methods and instruments designed to detect exaggeration or fabrication of neuropsychological dysfunction, as well as somatic and psychological symptom complaints. A vast literature based on relevant research has emerged and substantial portions of professional meetings attended by clinical neuropsychologists have addressed topics related to malingering (Sweet, King, Malina, Bergman, & Simmons, 2002). Yet, despite these extensive activities, understanding the need for methods of detecting problematic effort and response bias and addressing the presence or absence of malingering has proven challenging for practitioners. A consensus conference, comprised of national and international experts in clinical neuropsychology, was held at the 2008 Annual Meeting of the American Academy of Clinical Neuropsychology (AACN) for the purposes of refinement of critical issues in this area. This consensus statement documents the current state of knowledge and recommendations of expert clinical neuropsychologists and is intended to assist clinicians and researchers with regard to the neuropsychological assessment of effort, response bias, and malingering. PMID:19735055

  20. Recombinant interferon-α in myelofibrosis reduces bone marrow fibrosis, improves its morphology and is associated with clinical response.

    PubMed

    Pizzi, Marco; Silver, Richard T; Barel, Ariella; Orazi, Attilio

    2015-10-01

    Recombinant interferon-α represents a well-established therapeutic option for the treatment of polycythemia vera and essential thrombocythemia. Recent studies also suggest a role for recombinant interferon-α in the treatment of 'early stage' primary myelofibrosis, but few studies have reported the bone marrow changes after clinically successful interferon therapy. The aim of the present study is to detail the histological responses to recombinant interferon-α in primary myelofibrosis and post-polycythemia vera/post-essential thrombocythemia myelofibrosis and to correlate these with clinical findings. We retrospectively studied 12 patients with primary myelofibrosis or post-polycythemia vera/post-essential thrombocythemia myelofibrosis, who had been treated with recombinant interferon-α. Six patients had received other prior cytoreductive therapies. Bone marrow biopsy was assessed for the following histological parameters: (i) cellularity; (ii) myeloid-to-erythroid ratio; (iii) megakaryocyte tight clusters; (iv) megakaryocyte and naked nuclei density; (v) megakaryocytic atypia; (vi) fibrosis; and (vii) the percentage of blasts. Clinical and laboratory data were included: (i) constitutional symptoms; (ii) splenomegaly, if present; and (iii) complete cell blood count. The clinical response to therapy was evaluated using the International Working Group for Myelofibrosis Research and Treatment/European LeukemiaNet response criteria. The Dynamic International Prognostic Scoring System (DIPSS) score was calculated before and after recombinant interferon-α administration. Successful interferon therapy for myelofibrosis was associated with a significant reduction of marrow fibrosis, cellularity, megakaryocyte density and naked nuclei density. The presence of JAK2(V617F) mutation correlated with improved DIPSS score. JAK2(V617F)-negative cases showed worsening of such score or evolution to acute myeloid leukemia. Cytogenetic analysis documented a normal karyotype in all

  1. Predicting beneficial effects of atomoxetine and citalopram on response inhibition in Parkinson's disease with clinical and neuroimaging measures.

    PubMed

    Ye, Zheng; Rae, Charlotte L; Nombela, Cristina; Ham, Timothy; Rittman, Timothy; Jones, Peter Simon; Rodríguez, Patricia Vázquez; Coyle-Gilchrist, Ian; Regenthal, Ralf; Altena, Ellemarije; Housden, Charlotte R; Maxwell, Helen; Sahakian, Barbara J; Barker, Roger A; Robbins, Trevor W; Rowe, James B

    2016-03-01

    Recent studies indicate that selective noradrenergic (atomoxetine) and serotonergic (citalopram) reuptake inhibitors may improve response inhibition in selected patients with Parkinson's disease, restoring behavioral performance and brain activity. We reassessed the behavioral efficacy of these drugs in a larger cohort and developed predictive models to identify patient responders. We used a double-blind randomized three-way crossover design to investigate stopping efficiency in 34 patients with idiopathic Parkinson's disease after 40 mg atomoxetine, 30 mg citalopram, or placebo. Diffusion-weighted and functional imaging measured microstructural properties and regional brain activations, respectively. We confirmed that Parkinson's disease impairs response inhibition. Overall, drug effects on response inhibition varied substantially across patients at both behavioral and brain activity levels. We therefore built binary classifiers with leave-one-out cross-validation (LOOCV) to predict patients' responses in terms of improved stopping efficiency. We identified two optimal models: (1) a "clinical" model that predicted the response of an individual patient with 77-79% accuracy for atomoxetine and citalopram, using clinically available information including age, cognitive status, and levodopa equivalent dose, and a simple diffusion-weighted imaging scan; and (2) a "mechanistic" model that explained the behavioral response with 85% accuracy for each drug, using drug-induced changes of brain activations in the striatum and presupplementary motor area from functional imaging. These data support growing evidence for the role of noradrenaline and serotonin in inhibitory control. Although noradrenergic and serotonergic drugs have highly variable effects in patients with Parkinson's disease, the individual patient's response to each drug can be predicted using a pattern of clinical and neuroimaging features. PMID:26757216

  2. Effects of the Clinical Environment on Physicians' Response to Postgraduate Medical Education.

    ERIC Educational Resources Information Center

    Mazzuca, Steven A.; And Others

    1990-01-01

    Effects of a medical education program about diabetes mellitus were studied as a function of the extent to which participants' clinical environments were made to facilitate recommended practices. Subjects were 99 internal medicine residents and 15 internists staffing a general medicine clinic who attended a 3.5-hour diabetes seminar. (SLD)

  3. RESPONSES OF OYSTERS AND THEIR HEMOCYTES TO CLINICAL AND ENVIRONMENTAL ISOLATES OF VIBRIO PARAHAEMOLYTICUS

    EPA Science Inventory

    Interactions of Vibrio parahaemolyticus with oysters and oyster hemocytes were studied using three environmental isolates (1094, 1163 and ATCC 17802) and three clinical isolates (2030, 2062, 2107). Clinical isolates were from patients who became ill during the June 1998 food pois...

  4. The OnyCOE-t™ questionnaire: responsiveness and clinical meaningfulness of a patient-reported outcomes questionnaire for toenail onychomycosis

    PubMed Central

    Potter, Lori P; Mathias, Susan D; Raut, Monika; Kianifard, Farid; Tavakkol, Amir

    2006-01-01

    Background This research was conducted to confirm the validity and reliability and to assess the responsiveness and clinical meaningfulness of the OnyCOE-t™, a questionnaire specifically designed to measure patient-reported outcomes (PRO) associated with toenail onychomycosis. Methods 504 patients with toenail onychomycosis randomized to receive 12 weeks of terbinafine 250 mg/day with or without target toenail debridement in the IRON-CLAD® trial completed the OnyCOE-t™ at baseline, weeks 6, 12, 24, and 48. The OnyCOE-t™ is composed of 6 multi-item scales and 1 single-item scale. These include a 7-item Toenail Symptom assessment, which comprises both Symptom Frequency and Symptom Bothersomeness scales; an 8-item Appearance Problems scale; a 7-item Physical Activities Problems scale; a 1-item Overall Problem scale; a 7-item Stigma scale; and a 3-item Treatment Satisfaction scale. In total, 33 toenail onychomycosis-specific items are included in the OnyCOE-t™. Clinical data, in particular the percent clearing of mycotic involvement in the target toenail, and OnyCOE-t™ responses were used to evaluate the questionnaire's reliability, validity, responsiveness, and the minimally clinical important difference (MCID). Results The OnyCOE-t™ was shown to be reliable and valid. Construct validity and known groups validity were acceptable. Internal consistency reliability of multi-item scales was demonstrated by Cronbach's alpha > .84. Responsiveness was good, with the Treatment Satisfaction, Symptom Frequency, Overall Problem, and Appearance Problem scales demonstrating the most responsiveness (Guyatt's statistic of 1.72, 1.31, 1.13, and 1.11, respectively). MCID was evaluated for three different clinical measures, and indicated that approximately an 8.5-point change (on a 0 to 100 scale) was clinically meaningful based on a 25% improvement in target nail clearing. Conclusion The OnyCOE-t™ questionnaire is a unique, toenail-specific PRO questionnaire that can be

  5. Factors affecting the response to the specific treatment of several forms of clinical anestrus in high producing dairy cows.

    PubMed

    López-Gatius, F; Mirzaei, A; Santolaria, P; Bech-Sàbat, G; Nogareda, C; García-Ispierto, I; Hanzen, Ch; Yániz, J L

    2008-06-01

    This study was designed to examine estrous response rates to the therapeutic treatment of clinical anestrus in high producing dairy cows and to identify the factors that could affect these rates. Cows with silent ovulation (Subestrus group), cystic ovarian disease (Cyst group) or ovarian hypofunction (OH group) were given specific treatment for their disorder. Data were derived from 1764 treatments in cows producing a mean of 45.4 kg of milk upon treatment including: 889 subestrous cows, 367 cystic cows and 508 cows with ovarian hypofunction. Cows showing estrus following treatment exhibited a similar pregnancy rate to cows attaining natural estrus used as reference: 33% (337/1006) and 35% (626/1796), respectively. No significant differences in pregnancy rates were observed among the Subestrus, Cyst and OH groups (34% (196/571), 34% (44/130), 32% (97/305), respectively. Based on the odds ratio, an estrous response for all groups was less likely to occur in cows that had suffered previous anestrus, compared to cows that were anestrous for the first time, whereas the likelihood of an estrous response increased in cows treated after 90 days in milk. Our results indicate that previous anestrus and a late stage of lactation can have a negative and positive effect, respectively, on the estrous response to the specific treatment of clinical anestrus shown by high producing dairy cows. Treatment targeted at each type of clinical anestrus can render similar pregnancy rates to those shown by cows in natural estrus. PMID:18359070

  6. Ethnic minority under-representation in clinical trials. Whose responsibility is it anyway?

    PubMed

    Hussain-Gambles, Mahvash

    2003-01-01

    Ethnic minority people are frequently under-represented in clinical trials. This potentially affects the generalisability/external validity of the trial findings. This not only has important repercussions regarding the safety and the efficacy of new drug use in ethnic minority groups, but also reduces opportunities for subgroup analysis. There can be no scientific basis for excluding this group of people from clinical trials. Aims to provide a mix of theoretical and empirical debates, in order to make sense of ethnic minority exclusion from clinical trials, and suggest possibility of change. Recommends that educational programmes should be directed at clinical trial investigators and funding bodies, to increase their awareness of under-representation of ethnic minority people in clinical trials. Ethics committees could also redress this inequality by providing guidance for investigators, and by being more rigorous about reviewing clinical trial protocols. Provides a set of guidelines to "enlighten" and aid health professionals in working with ethnic, linguistic and culturally diverse populations. The guidelines require additional work and have cost implications. Argues that cost should not be allowed as an acceptable excuse for excluding ethnic minority people from clinical trials. PMID:12916177

  7. Clinical Utility of a New Automated Hepatitis C Virus Core Antigen Assay for Prediction of Treatment Response in Patients with Chronic Hepatitis C.

    PubMed

    Kim, Mi Na; Kim, Hyon Suk; Kim, Ja Kyung; Kim, Beom Kyung; Kim, Seung Up; Park, Jun Yong; Kim, Do Young; Ahn, Sang Hoon; Han, Kwang Hyub

    2016-09-01

    Hepatitis C virus core antigen (HCV Ag) is a recently developed marker of hepatitis C virus (HCV) infection. We investigated the clinical utility of the new HCV Ag assay for prediction of treatment response in HCV infection. We analyzed serum from 92 patients with HCV infection who had been treated with pegylated interferon and ribavirin. HCV Ag levels were determined at baseline in all enrolled patients and at week 4 in 15 patients. Baseline HCV Ag levels showed good correlations with HCV RNA (r = 0.79, P < 0.001). Mean HCV Ag levels at baseline were significantly lower in patients with a sustained virologic response (SVR) than in those with a non SVR (relapse plus non responder) based on HCV RNA analysis (2.8 log₁₀fmol/L vs. 3.27 log₁₀fmol/L, P = 0.023). Monitoring of the viral kinetics by determination of HCV RNA and HCV Ag levels resulted in similarly shaped curves. Patients with undetectable HCV Ag levels at week 4 had a 92.3% probability of achieving SVR based on HCV RNA assay results. The HCV Ag assay may be used as a supplement for predicting treatment response in HCV infection, but not as an alternative to the HCV RNA assay. PMID:27510387

  8. Clinical Utility of a New Automated Hepatitis C Virus Core Antigen Assay for Prediction of Treatment Response in Patients with Chronic Hepatitis C

    PubMed Central

    2016-01-01

    Hepatitis C virus core antigen (HCV Ag) is a recently developed marker of hepatitis C virus (HCV) infection. We investigated the clinical utility of the new HCV Ag assay for prediction of treatment response in HCV infection. We analyzed serum from 92 patients with HCV infection who had been treated with pegylated interferon and ribavirin. HCV Ag levels were determined at baseline in all enrolled patients and at week 4 in 15 patients. Baseline HCV Ag levels showed good correlations with HCV RNA (r = 0.79, P < 0.001). Mean HCV Ag levels at baseline were significantly lower in patients with a sustained virologic response (SVR) than in those with a non SVR (relapse plus non responder) based on HCV RNA analysis (2.8 log10fmol/L vs. 3.27 log10fmol/L, P = 0.023). Monitoring of the viral kinetics by determination of HCV RNA and HCV Ag levels resulted in similarly shaped curves. Patients with undetectable HCV Ag levels at week 4 had a 92.3% probability of achieving SVR based on HCV RNA assay results. The HCV Ag assay may be used as a supplement for predicting treatment response in HCV infection, but not as an alternative to the HCV RNA assay. PMID:27510387

  9. Association between dynamic features of breast DCE-MR imaging and clinical response of neoadjuvant chemotherapy: a preliminary analysis

    NASA Astrophysics Data System (ADS)

    Huang, Lijuan; Fan, Ming; Li, Lihua; Zhang, Juan; Shao, Guoliang; Zheng, Bin

    2016-03-01

    Neoadjuvant chemotherapy (NACT) is being used increasingly in the management of patients with breast cancer for systemically reducing the size of primary tumor before surgery in order to improve survival. The clinical response of patients to NACT is correlated with reduced or abolished of their primary tumor, which is important for treatment in the next stage. Recently, the dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is used for evaluation of the response of patients to NACT. To measure this correlation, we extracted the dynamic features from the DCE- MRI and performed association analysis between these features and the clinical response to NACT. In this study, 59 patients are screened before NATC, of which 47 are complete or partial response, and 12 are no response. We segmented the breast areas depicted on each MR image by a computer-aided diagnosis (CAD) scheme, registered images acquired from the sequential MR image scan series, and calculated eighteen features extracted from DCE-MRI. We performed SVM with the 18 features for classification between patients of response and no response. Furthermore, 6 of the 18 features are selected to refine the classification by using Genetic Algorithm. The accuracy, sensitivity and specificity are 87%, 95.74% and 50%, respectively. The calculated area under a receiver operating characteristic (ROC) curve is 0.79+/-0.04. This study indicates that the features of DCE-MRI of breast cancer are associated with the response of NACT. Therefore, our method could be helpful for evaluation of NACT in treatment of breast cancer.

  10. Diuretic response in patients with acute decompensated heart failure: characteristics and clinical outcome—an analysis from RELAX-AHF

    PubMed Central

    Voors, Adriaan A; Davison, Beth A; Teerlink, John R; Felker, G Michael; Cotter, Gad; Filippatos, Gerasimos; Greenberg, Barry H; Pang, Peter S; Levin, Bruce; Hua, Tsushung A; Severin, Thomas; Ponikowski, Piotr; Metra, Marco

    2014-01-01

    Aims We studied the characteristics and clinical outcome related to diuretic response and the effects of serelaxin in patients hospitalized for acute heart failure (AHF). Methods and results RELAX-AHF was a double-blind, placebo-controlled trial, enrolling 1161 patients admitted to hospital for AHF who were randomized to 48 h i.v infusions of placebo or serelaxin (30 µg/kg per day) within 16 h from presentation. Diuretic response was defined as Δ weight kg/[(total i.v. dose)/40 mg] + [(total oral dose)/80 mg)] furosemide (or equivalent loop diuretic dose) up to day 5. Median diuretic response was −0.42 (−1.00, −0.14) kg/40 mg. A poor diuretic response was independently associated with Western-like region (Western Europe, North America, Israel, and Poland), lower diastolic blood pressure, the absence of oedema, higher blood urea nitrogen, and lower levels of aspartate aminotransferase and potassium (all P < 0.01). Randomization to serelaxin was associated with lower doses of i.v. loop diuretics and slightly less weight loss, resulting in a neutral effect on diuretic response. Worse diuretic response was independently associated both with less relief of dyspnoea, measured with a visual analogue scale (VAS) at day 5 (primary endpoint; P = 0.0002), and with a higher risk of cardiovascular death or rehospitalization for heart failure or renal failure through day 60 (secondary endpoint, P < 0.0001), but not with increased 180-day cardiovascular mortality (P = 0.507). Conclusions In patients hospitalized for AHF, a poor diuretic response was associated with a poor in-hospital and early post-discharge clinical outcome. Serelaxin had a neutral effect on diuretic response. Trial registration: NCT00520806 PMID:25287144

  11. Somatosensory evoked potentials in cervical spondylosis. Correlation of median, ulnar and posterior tibial nerve responses with clinical and radiological findings.

    PubMed

    Yu, Y L; Jones, S J

    1985-06-01

    Somatosensory evoked potentials (SEPs) following median, ulnar and tibial nerve stimulation were recorded from sites over the shoulders, neck and scalp in 34 patients with cervical spondylosis. Twenty control subjects were matched for sex and age. Detailed clinical and radiological data were assembled, with particular attention to the sensory modalities impaired and the locus and severity of cord compression. The patients were divided clinically into 4 groups: combined myelopathy and radiculopathy (6 cases), myelopathy alone (15), radiculopathy (6) and neck pain (7). Four cases are described in detail. SEP abnormalities were strongly correlated with clinical myelopathy, but not with radiculopathy. Median and ulnar nerve responses were less often affected than tibial, even with myelopathy above C6 level. Tibial nerve SEP abnormalities were strongly correlated with posterior column signs on the same side of the body, but not with anterolateral column sensory signs. In myelopathy cases, the SEP examination appeared to be more sensitive to sensory pathway involvement than clinical sensory testing. SEP abnormalities were infrequent in cases of radiculopathy and neck pain, bearing no relation to the clinical locus of root lesions. Abnormal SEPs consistent with subclinical posterior column involvement, however, were recorded in 1 patient with radiculopathy and 2 with neck pain. Follow-up recordings made postoperatively in 7 myelopathy cases reflected the clinical course (improvement, deterioration or no change) in 4, but failed to reflect improvement in 3. The correlation of SEP findings with radiological data was generally poor. SEP abnormalities were detected in 6 out of 8 patients with clinical myelopathy but no radiological evidence of posterior cord compression, suggesting that impairment of the blood supply may be an important factor contributing to cord damage. An application for SEPs in the clinical management of cervical spondylosis may lie in the detection of

  12. A Genomic Signature of Influenza Infection Shows Potential for Presymptomatic Detection, Guiding Early Therapy, and Monitoring Clinical Responses

    PubMed Central

    McClain, Micah T.; Nicholson, Bradly P.; Park, Lawrence P.; Liu, Tzu-Yu; Hero, Alfred O.; Tsalik, Ephraim L.; Zaas, Aimee K.; Veldman, Timothy; Hudson, Lori L.; Lambkin-Williams, Robert; Gilbert, Anthony; Burke, Thomas; Nichols, Marshall; Ginsburg, Geoffrey S.; Woods, Christopher W.

    2016-01-01

    Early, presymptomatic intervention with oseltamivir (corresponding to the onset of a published host-based genomic signature of influenza infection) resulted in decreased overall influenza symptoms (aggregate symptom scores of 23.5 vs 46.3), more rapid resolution of clinical disease (20 hours earlier), reduced viral shedding (total median tissue culture infectious dose [TCID50] 7.4 vs 9.7), and significantly reduced expression of several inflammatory cytokines (interferon-γ, tumor necrosis factor-α, interleukin-6, and others). The host genomic response to influenza infection is robust and may provide the means for early detection, more timely therapeutic interventions, a meaningful reduction in clinical disease, and an effective molecular means to track response to therapy. PMID:26933666

  13. Netherton Syndrome Mimicking Pustular Psoriasis: Clinical Implications and Response to Intravenous Immunoglobulin.

    PubMed

    Small, Alison M; Cordoro, Kelly M

    2016-05-01

    We present two cases of Netherton syndrome mimicking pustular psoriasis and discuss potential pathomechanisms of clinical and histologic similarities between Netherton syndrome and pustular psoriasis and implications for management. PMID:27086664

  14. Yin and yang of cytidine deaminase roles in clinical response to azacitidine in the elderly: a pharmacogenetics tale.

    PubMed

    Fanciullino, Raphaelle; Mercier, Cédric; Serdjebi, Cindy; Venton, Geoffroy; Colle, Julien; Fina, Frédéric; Ouafik, L'Houcine; Lacarelle, Bruno; Ciccolini, Joseph; Costello, Régis

    2015-11-01

    Azacitidine is a mainstay for treating hematological disorders. Azacitidine is metabolized by cytidine deaminase, coded by a highly polymorphic gene. Here, we present two elderly patients with opposite clinical outcomes after azacitidine treatment. First, an acute myeloid leukemia patient showed life-threatening toxicities, but outstanding complete remission, after a single round of azacitidine. Further investigations showed that this patient was cytidine deaminase 79A>C (rs2072671) homozygous with a marked deficient phenotype. Next, a chronic myelomonocytic leukemia patient displayed complete lack of response despite several cycles of azacitidine. This patient had a rapid-deaminator phenotype linked to the -31delC deletion (rs3215400). These polymorphisms lead to opposite clinical outcomes in patients with myelodysplastic syndromes treated with azacitidine, thus suggesting that determining cytidine deaminase status could help to forecast clinical outcome. PMID:26556583

  15. The Relationship between Reading Response Journals as an Intervention and Reading Achievement of Fourth and Fifth Graders in a Suburban School District

    ERIC Educational Resources Information Center

    Hume, Julie M.

    2013-01-01

    Many of today's students are reading below grade level and schools are investigating methods for increasing student achievement in the area of reading. This mixed method research study investigated the achievement of students who were reading below grade level. The purpose of this study was to investigate the relationship between reading response…

  16. Developing new student clinical sites: a response to downsizing of hospitals.

    PubMed

    McNamee, M

    1997-01-01

    The settings for nursing practice are changing rapidly. Dwindling in-patient numbers and increasing out-patient care have compelled nursing programs to find student "clinical" learning experiences that reflect the changing health care delivery system. This article presents specific strategies for changing the clinical learning practicum experiences in nursing programs to respond to the changes in the health care delivery system. PMID:9348974

  17. [Achievement of therapeutic target in subjects on statin treatment in clinical practice. Results of the STAR (Statins Target Assessment in Real practice) study].

    PubMed

    Degli Esposti, Luca; Sangiorgi, Diego; Arca, Marcello; Vigna, Giovanni B; Budal, Stefano; Degli Esposti, Ezio

    2011-12-01

    The primary aim of the STAR Study (Statins Target Assessment in Real practice) was to determine the LDL-cholesterol reduction and to analyse patient's and therapeutic factors associated to LDL-cholesterol target attainment in newly treated subjects with statins in an unselected population in clinical practice setting. Administrative databases (including pharmaceutical prescriptions and hospital admissions) and laboratory test databases (including LDL-cholesterol values) of five local health units, distributed in Emilia Romagna, Toscana and Umbria, were linked. A retrospective cohort study was conducted and all subjects aged > or =18 years with a first prescription for statins (newly treated subjects) between January 1st, 2007 and June 30th, 2008 were included. All statin prescriptions over a 12 months follow-up period were considered and used to calculate adherence to treatment. Baseline and follow-up LDL-cholesterol, respectively, were defined according to the nearest determination to the first prescription for statins and to the end of the follow-up period. A total of 3.232 subjects was included, 1.516 males (47%) and 1.716 females (53%), with an average age equal to 65.9 +/- 11.3 years. Among included subjects, 22.,6% had a gap to LDL-cholesterol target <10%, 30.0% between 10 and 29%, 20.7% between 30 and 49%, and 26.7% . or =50%. Among those with a gap to target > or =50%, 30-49%, and 10-29%, respectively, LDL-cholesterol target was attained by 7.1%, 41.8%, and 62.% of subjects. LDL-cholesterol target attainment was associated to gap to target, adherence with treatment, and type of statin. PMID:22567731

  18. Socio-demographic and clinical predictors of non-response/non-remission in treatment resistant depressed patients: A systematic review.

    PubMed

    De Carlo, Vera; Calati, Raffaella; Serretti, Alessandro

    2016-06-30

    Up to one third of patients adequately treated for Major Depressive Disorder (MDD) do not respond to multiple interventions. Many studies investigated predictors in MDD outcome, but no study focused on predictors of non-response or non-remission to antidepressants in subjects with treatment resistant depression (TRD). The present study aimed to evaluate possible socio-demographic and clinical predictors of non-response and non-remission in MDD patients who failed to benefit from at least one antidepressant trial. A total of 51 papers were included. A number of severity indicators, such as longer duration of depressive episode, moderate-high suicidal risk, anxious comorbidity, higher number of hospitalizations and higher dosage of antidepressants, were associated with non-response as well as age. Interestingly, severity of illness, as well as comorbid personality disorders and anxiety symptoms, had also a predictive value in non-remission with the addition of marital status. Considering limitations, selected studies were observational or randomized non controlled/controlled trials and different TRD definitions and outcome measures were used. Overall, predictors of outcome were similar to MDD, but specific socio-demographic and clinical factors should be considered in clinical practice to formulate a more focused treatment in TRD patients. PMID:27155594

  19. New Perspectives on Predictive Biomarkers of Tumor Response and Their Clinical Application in Preoperative Chemoradiation Therapy for Rectal Cancer.

    PubMed

    Kim, Nam Kyu; Hur, Hyuk

    2015-11-01

    Preoperative chemoradiation therapy (CRT) is the standard treatment for patients with locally advanced rectal cancer (LARC) and can improve local control and survival outcomes. However, the responses of individual tumors to CRT are not uniform and vary widely, from complete response to disease progression. Patients with resistant tumors can be exposed to irradiation and chemotherapy that are both expensive and at times toxic without benefit. In contrast, about 60% of tumors show tumor regression and T and N down-staging. Furthermore, a pathologic complete response (pCR), which is characterized by sterilization of all tumor cells, leads to an excellent prognosis and is observed in approximately 10-30% of cases. This variety in tumor response has lead to an increased need to develop a model predictive of responses to CRT in order to identify patients who will benefit from this multimodal treatment. Endoscopy, magnetic resonance imaging, positron emission tomography, serum carcinoembryonic antigen, and molecular biomarkers analyzed using immunohistochemistry and gene expression profiling are the most commonly used predictive models in preoperative CRT. Such modalities guide clinicians in choosing the best possible treatment options and the extent of surgery for each individual patient. However, there are still controversies regarding study outcomes, and a nomogram of combined models of future trends is needed to better predict patient response. The aim of this article was to review currently available tools for predicting tumor response after preoperative CRT in rectal cancer and to explore their applicability in clinical practice for tailored treatment. PMID:26446626

  20. New Perspectives on Predictive Biomarkers of Tumor Response and Their Clinical Application in Preoperative Chemoradiation Therapy for Rectal Cancer

    PubMed Central

    Hur, Hyuk

    2015-01-01

    Preoperative chemoradiation therapy (CRT) is the standard treatment for patients with locally advanced rectal cancer (LARC) and can improve local control and survival outcomes. However, the responses of individual tumors to CRT are not uniform and vary widely, from complete response to disease progression. Patients with resistant tumors can be exposed to irradiation and chemotherapy that are both expensive and at times toxic without benefit. In contrast, about 60% of tumors show tumor regression and T and N down-staging. Furthermore, a pathologic complete response (pCR), which is characterized by sterilization of all tumor cells, leads to an excellent prognosis and is observed in approximately 10-30% of cases. This variety in tumor response has lead to an increased need to develop a model predictive of responses to CRT in order to identify patients who will benefit from this multimodal treatment. Endoscopy, magnetic resonance imaging, positron emission tomography, serum carcinoembryonic antigen, and molecular biomarkers analyzed using immunohistochemistry and gene expression profiling are the most commonly used predictive models in preoperative CRT. Such modalities guide clinicians in choosing the best possible treatment options and the extent of surgery for each individual patient. However, there are still controversies regarding study outcomes, and a nomogram of combined models of future trends is needed to better predict patient response. The aim of this article was to review currently available tools for predicting tumor response after preoperative CRT in rectal cancer and to explore their applicability in clinical practice for tailored treatment. PMID:26446626

  1. From the Consulting Room to the Court Room? Taking the Clinical Model of Responsibility Without Blame into the Legal Realm

    PubMed Central

    Lacey, Nicola; Pickard, Hanna

    2013-01-01

    Within contemporary penal philosophy, the view that punishment can only be justified if the offender is a moral agent who is responsible and hence blameworthy for their offence is one of the few areas on which a consensus prevails. In recent literature, this precept is associated with the retributive tradition, in the modern form of ‘just deserts’. Turning its back on the rehabilitative ideal, this tradition forges a strong association between the justification of punishment, the attribution of responsible agency in relation to the offence, and the appropriateness of blame. By contrast, effective clinical treatment of disorders of agency employs a conceptual framework in which ideas of responsibility and blameworthiness are clearly separated from what we call ‘affective blame’: the range of hostile, negative attitudes and emotions that are typical human responses to criminal or immoral conduct. We argue that taking this clinical model of ‘responsibility without blame’ into the legal realm offers new possibilities. Theoretically, it allows for the reconciliation of the idea of ‘just deserts’ with a rehabilitative ideal in penal philosophy. Punishment can be reconceived as consequences—typically negative but occasionally not, so long as they are serious and appropriate to the crime and the context—imposed in response to, by reason of, and in proportion to responsibility and blameworthiness, but without the hard treatment and stigma typical of affective blame. Practically, it suggests how sentencing and punishment can better avoid affective blame and instead further rehabilitative and related ends, while yet serving the demands of justice. PMID:24771953

  2. Predicting beneficial effects of atomoxetine and citalopram on response inhibition in Parkinson's disease with clinical and neuroimaging measures

    PubMed Central

    Ye, Zheng; Rae, Charlotte L.; Nombela, Cristina; Ham, Timothy; Rittman, Timothy; Jones, Peter Simon; Rodríguez, Patricia Vázquez; Coyle‐Gilchrist, Ian; Regenthal, Ralf; Altena, Ellemarije; Housden, Charlotte R.; Maxwell, Helen; Sahakian, Barbara J.; Barker, Roger A.; Robbins, Trevor W.

    2016-01-01

    Abstract Recent studies indicate that selective noradrenergic (atomoxetine) and serotonergic (citalopram) reuptake inhibitors may improve response inhibition in selected patients with Parkinson's disease, restoring behavioral performance and brain activity. We reassessed the behavioral efficacy of these drugs in a larger cohort and developed predictive models to identify patient responders. We used a double‐blind randomized three‐way crossover design to investigate stopping efficiency in 34 patients with idiopathic Parkinson's disease after 40 mg atomoxetine, 30 mg citalopram, or placebo. Diffusion‐weighted and functional imaging measured microstructural properties and regional brain activations, respectively. We confirmed that Parkinson's disease impairs response inhibition. Overall, drug effects on response inhibition varied substantially across patients at both behavioral and brain activity levels. We therefore built binary classifiers with leave‐one‐out cross‐validation (LOOCV) to predict patients’ responses in terms of improved stopping efficiency. We identified two optimal models: (1) a “clinical” model that predicted the response of an individual patient with 77–79% accuracy for atomoxetine and citalopram, using clinically available information including age, cognitive status, and levodopa equivalent dose, and a simple diffusion‐weighted imaging scan; and (2) a “mechanistic” model that explained the behavioral response with 85% accuracy for each drug, using drug‐induced changes of brain activations in the striatum and presupplementary motor area from functional imaging. These data support growing evidence for the role of noradrenaline and serotonin in inhibitory control. Although noradrenergic and serotonergic drugs have highly variable effects in patients with Parkinson's disease, the individual patient's response to each drug can be predicted using a pattern of clinical and neuroimaging features. Hum Brain Mapp 37:1026–1037

  3. Rosuvastatin versus atorvastatin in achieving lipid goals in patients at high risk for cardiovascular disease in clinical practice: A randomized, open-label, parallel-group, multicenter study (DISCOVERY Alpha study)

    PubMed Central

    Binbrek, Azan S.; Elis, Avishay; Al-Zaibag, Muayed; Eha, Jaan; Keber, Irena; Cuevas, Ada M.; Mukherjee, Swati; Miller, Thomas R.

    2006-01-01

    Background: The majority of clinical trials investigating the clinical benefits of lipid-lowering therapies (LLTs) have focused on North American or western and nothern European populations. Therefore, it is timely to confirm the efficacy of these agents in other patient populations in routine clinical practice. Objective: The aim of the Direct Statin COmparison of low-density lipoprotein cholesterol (LDL-C) Values: an Evaluation of Rosuvastatin therapY (DISCOVERY) Alpha study was to compare the effects of rosuvastatin 10 mg with those of atorvastatin 10 mg in achieving LDL-C goals in the Third Joint Task Force of European and Other Societies on Cardiovascular Disease Prevention in Clinical Practice guidelines. Methods: This randomized, open-label, parallel-group study was conducted at 93 centers in eastern Europe (Estonia, Latvia, Romania, Russia, Slovenia), Central and South America (Chile, Dominican Republic, El Salvador, Guatemala, Honduras, Nicaragua, Panama), and the Middle East (Israel, Kuwait, Saudi Arabia, United Arab Emirates). Male and female patients aged ≥18 years with primary hypercholesterolemia (LDL-C level, >135 mg/dL if LLT-naive or ≥120 mg/dL if switching statins; triglyceride [TG] level, <400 mg/dL) and a 10-year coronary heart disease (CHD) risk >20% or a history of CHD or other established atherosclerotic disease were eligible for inclusion in the study. Patients were randomly assigned to receive rosuvastatin 10-mg or atorvastatin 10-mg tablets QD for 12 weeks. No formal statistical analyses or comparisons were performed on lipid changes between switched and LLT-naive patients because of the different lipid inclusion criteria for these patients. The primary end point was the proportion of patients achieving 1998 European LDL-C goals after 12 weeks of treatment. A subanalysis was performed to assess the effects of statins in patients who had received previous statin treatment versus those who were LLT-naive. Tolerability was assessed using

  4. Can a physician predict the clinical response to first-line immunomodulatory treatment in relapsing–remitting multiple sclerosis?

    PubMed Central

    Mezei, Zsolt; Bereczki, Daniel; Racz, Lilla; Csiba, Laszlo; Csepany, Tünde

    2012-01-01

    Background Decreased relapse rate and slower disease progression have been reported with long-term use of immunomodulatory treatments (IMTs, interferon beta or glatiramer acetate) in relapsing–remitting multiple sclerosis. There are, however, patients who do not respond to such treatments, and they can be potential candidates for alternative therapeutic approaches. Objective To identify clinical factors as possible predictors of poor long-term response. Methods A 9-year prospective, continuous follow-up at a single center in Hungary to assess clinical efficacy of IMT. Results In a patient group of 81 subjects with mean IMT duration of 54 ± 33 months, treatment efficacy expressed as annual relapse rate and change in clinical severity from baseline did not depend on the specific IMT (any of the interferon betas or glatiramer acetate), and on mono- or multifocal features of the initial appearance of the disease. Responders had shorter disease duration and milder clinical signs at the initiation of treatment. Relapse-rate reduction in the initial 2 years of treatment predicted clinical efficacy in subsequent years. Conclusion Based on these observations, we suggest that a 2-year trial period is sufficient to decide on the efficacy of a specific IMT. For those with insufficient relapse reduction in the first 2 years of treatment, a different IMT or other therapeutic approaches should be recommended. PMID:23118540

  5. Early Clinical Response after 2 Weeks of Sorafenib Therapy Predicts Outcomes and Anti-Tumor Response in Patients with Advanced Hepatocellular Carcinoma

    PubMed Central

    Kuzuya, Teiji; Ishigami, Masatoshi; Ishizu, Yoji; Honda, Takashi; Hayashi, Kazuhiko; Katano, Yoshiaki; Hirooka, Yoshiki; Ishikawa, Tetsuya; Nakano, Isao; Goto, Hidemi

    2015-01-01

    Background & Aims We evaluated the relationship between the early clinical response after 2 weeks of sorafenib therapy and the outcomes and anti-tumor response in patients with advanced hepatocellular carcinoma. Methods Fifty-seven patients who had intrahepatic hypervascular hepatocellular carcinoma and Child-Pugh (CP) class A disease at baseline were enrolled in this prospective, multicenter, observational, non-interventional study. As an early clinical response after 2 weeks of sorafenib therapy, changes in intra-tumor blood flow on contrast-enhanced computed tomography (CE-CT), alpha-fetoprotein (AFP) levels, and remnant liver function were investigated. Results After 2 weeks of sorafenib therapy, there were 26 patients (45.6%) without disappearance of arterial tumor enhancement on CE-CT, 15 patients (26.3%) with an AFP ratio of >1.2, and seven patients (12.3%) with two or more increments in the CP score. Multivariate analysis showed that the absence of disappearance of arterial tumor enhancement on CE-CT, AFP ratio of >1.2, and two or more increments in the CP score after 2 weeks of sorafenib therapy were significant and independent predictors of worse survival. Upon scoring these three variables as "poor prognostic factors", patients with poor prognostic score 4, 3 or 2 (n = 17) had significantly worse outcomes and a significantly higher progressive disease (PD) rate based on modified Response Evaluation Criteria in Solid Tumors at 6 weeks after sorafenib therapy than those with poor prognostic score 1 or 0 (n = 40) (median overall survival: 194 days vs. 378 days; p = 0.0010, PD rate: 70.6% vs. 20.0%; p = 0.0003, respectively). Conclusions Changes in intra-tumor blood flow on CE-CT, AFP levels, and remnant liver function after 2 weeks of sorafenib therapy may be useful for predicting the outcomes and anti-tumor response to sorafenib in patients with advanced hepatocellular carcinoma. PMID:26421430

  6. Magnitude of placebo response and response variance in antidepressant clinical trials using structured, taped and appraised rater interviews compared to traditional rating interviews.

    PubMed

    Khan, Arif; Faucett, James; Brown, Walter A

    2014-04-01

    The high failure rate of antidepressant clinical trials is due in part to a high magnitude of placebo response and considerable variance in placebo response. In some recent trials enhanced patient interview techniques consisting of Structured Interview Guide for the Montgomery-Asberg Depression Rating Scale (SIGMA) interviews, audiotaping of patient interviews and 'central' appraisal with Rater Applied Performance Scale (RAPS) criteria have been implemented in the hope of increasing reliability and thus reducing the placebo response. However, the data supporting this rationale for a change in patient interview technique are sparse. We analyzed data from depressed patients assigned to placebo in antidepressant clinical trials conducted at a single research site between 2008 and 2012. Three trials included 34 depressed patients undergoing SIGMA depression interviews with taping and RAPS appraisal and 4 trials included 128 depressed patients using traditional interview methods. Using patient level data we assessed the mean decrease in total MADRS scores and the variability of the decrease in MADRS scores in trials using SIGMA interviews versus trials using traditional interviews. Mean decrease in total MADRS score was significantly higher in the 3 trials that used SIGMA interviews compared to the 4 trials using traditional interviews (M = 13.0 versus 8.3, t(df = 160) = 2.04, p = 0.047). Furthermore, trials using SIGMA had a larger magnitude of response variance based on Levene's test for equality of variance (SD = 12.3 versus 9.4, F = 7.3, p = 0.008). The results of our study suggest that enhanced patient interview techniques such as SIGMA interviews, audiotaping and RAPS appraisal may not result in the intended effect of reducing the magnitude of placebo response and placebo variance. PMID:24477068

  7. Clinical decision making in response to performance validity test failure in a psychiatric setting.

    PubMed

    Marcopulos, Bernice A; Caillouet, Beth A; Bailey, Christopher M; Tussey, Chriscelyn; Kent, Julie-Ann; Frederick, Richard

    2014-01-01

    This study examined the clinical utility of a performance validity test (PVT) for screening consecutive referrals (N = 436) to a neuropsychology service at a state psychiatric hospital treating both civilly committed and forensic patients. We created a contingency table with Test of Memory Malingering (TOMM) pass/fail (355/81) and secondary gain present/absent (181/255) to examine pass rates associated with patient demographic, clinical and forensic status characteristics. Of the 81 failed PVTs, 48 had secondary gain defined as active criminal legal charges; 33 failed PVTs with no secondary gain. These individuals tended to be older, female, Caucasian, and civilly committed compared with the group with secondary gain who failed. From estimations of TOMM False Positive Rate and True Positive Rate we estimated base rates of neurocognitive malingering for our clinical population using the Test Validation Summary (TVS; Frederick & Bowden, 2009 ). Although PVT failure is clearly more common in a group with secondary gain (31%), there were a number of false positives (11%). Clinical ratings of patients without gain who failed suggested cognitive deficits, behavioral issues, and inattention. Low scores on PVTs in the absence of secondary gain provide useful information on test engagement and can inform clinical decisions about testing. PMID:24678658

  8. Induction of clinical response and remission of inflammatory bowel disease by use of herbal medicines: A meta-analysis

    PubMed Central

    Rahimi, Roja; Nikfar, Shekoufeh; Abdollahi, Mohammad

    2013-01-01

    AIM: To evaluate the efficacy and tolerability of herbal medicines in inflammatory bowel disease (IBD) by conducting a meta-analysis. METHODS: Electronic databases were searched for studies investigating efficacy and/or tolerability of herbal medicines in the management of different types of IBD. The search terms were: “herb” or “plant” or “herbal” and “inflammatory bowel disease”. Data were collected from 1966 to 2013 (up to Feb). The “clinical response”, “clinical remission”, “endoscopic response”, “endoscopic remission”, “histological response”, “histological remission”, “relapse”, “any adverse events”, and “serious adverse events” were the key outcomes of interest. We used the Mantel-Haenszel, Rothman-Boice method for fixed effects and DerSimonian-Laird method for random-effects. For subgroup analyses, we separated the studies by type of IBD and type of herbal medicine to determine confounding factors and reliability. RESULTS: Seven placebo controlled clinical trials met our criteria and were included (474 patients). Comparison of herbal medicine with placebo yielded a significant RR of 2.07 (95%CI: 1.41-3.03, P = 0.0002) for clinical remission; a significant RR of 2.59 (95%CI: 1.24-5.42, P = 0.01) for clinical response; a non-significant RR of 1.33 (95%CI: 0.93-1.9, P = 0.12) for endoscopic remission; a non-significant RR of 1.69 (95%CI: 0.69-5.04) for endoscopic response; a non-significant RR of 0.64 (95%CI: 0.25-1.81) for histological remission; a non-significant RR of 0.86 (95%CI: 0.55-1.55) for histological response; a non-significant RR of 0.95 (95%CI: 0.52-1.73) for relapse; a non-significant RR of 0.89 (95%CI: 0.75-1.06, P = 0.2) for any adverse events; and a non-significant RR of 0.97 (95%CI: 0.37-2.56, P = 0.96) for serious adverse events. CONCLUSION: The results showed that herbal medicines may safely induce clinical response and remission in patients with IBD without significant effects on

  9. Stratification of pediatric ALL by in vitro cellular responses to DNA double-strand breaks provides insight into the molecular mechanisms underlying clinical response.

    PubMed

    Marston, Eliot; Weston, Victoria; Jesson, Jennifer; Maina, Esther; McConville, Carmel; Agathanggelou, Angelo; Skowronska, Anna; Mapp, Katie; Sameith, Katrin; Powell, Judith E; Lawson, Sarah; Kearns, Pamela; Falciani, Francesco; Taylor, Malcolm; Stankovic, Tatjana

    2009-01-01

    The molecular basis of different outcomes in pediatric acute lymphoblastic leukemia (ALL) remains poorly understood. We addressed the clinical significance and mechanisms behind in vitro cellular responses to ionizing radiation (IR)-induced DNA double-strand breaks in 74 pediatric patients with ALL. We found an apoptosis-resistant response in 36% of patients characterized by failure to cleave caspase-3, -7, -9, and PARP1 by 24 hours after IR and an apoptosis-sensitive response with the cleavage of the same substrates in the remaining 64% of leukemias. Resistance to IR in vitro was associated with poor early blast clearance at day 7 or 15 and persistent minimal residual disease (MRD) at day 28 of induction treatment. Global gene expression profiling revealed abnormal up-regulation of multiple prosurvival pathways in response to IR in apoptosis-resistant leukemias and differential posttranscriptional activation of the PI3-Akt pathway was observed in representative resistant cases. Importantly, pharmacologic inhibition of selected prosurvival pathways sensitized apoptosis-resistant ALL cells to IR in vitro. We suggest that abnormal prosurvival responses to DNA damage provide one of the mechanisms of primary resistance in ALL, and that they should be considered as therapeutic targets in children with aggressive disease. PMID:18941120

  10. Phenotype of subjects with type 2 diabetes mellitus may determine clinical response to chromium suppplementation.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The goal of this study was to assess which patient characteristics best determine response to supplemental chromium (Cr). We assessed response to Cr using hyperinsulinemic-euglycemic clamps before and after Cr supplementation in 38 subjects with Type 2 diabetes. The evaluations were double-blinded,...

  11. 77 FR 69631 - Draft Guidance for IRBs, Clinical Investigators, and Sponsors: IRB Responsibilities for Reviewing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-20

    ... Persons with access to the Internet may obtain the document at http://www.fda.gov/ScienceResearch/Special... Sponsors: IRB Responsibilities for Reviewing the Qualifications of Investigators, Adequacy of Research... Responsibilities for Reviewing the Qualifications of Investigators, Adequacy of Research Sites, and...

  12. Legislating Clinical Practice: Counselor Responses to an Evidence-Based Practice Mandate

    PubMed Central

    Rieckmann, Traci; Bergmann, Luke; Rasplica, Caitlin

    2013-01-01

    The demand to connect research findings with clinical practice for patients with substance use disorders has accelerated state and federal efforts focused on implementation of evidence-based practices (EBPs). One unique state driven strategy is Oregon’s Evidence-Based Practice mandate, which ties state funds to specific treatment practices. Clinicians play an essential role in implementation of shifts in practice patterns and use of EBPs, but little is understood about how legislative efforts impact clinicians’ sentiments and decision-making. This study presents longitudinal data from focus groups and interviews completed during the planning phase (n = 66) and early implementation of the mandate (n = 73) to investigate provider attitudes toward this policy change. Results reflect three emergent themes: (1) concern about retaining individualized treatment and clinical latitude, (2) distrust of government involvement in clinical care, and (3) the need for accountability and credibility for the field. We conclude with recommendations for state agencies considering EBP mandates. PMID:22185037

  13. Legislating clinical practice: counselor responses to an evidence-based practice mandate.

    PubMed

    Rieckmann, Traci; Bergmann, Luke; Rasplica, Caitlin

    2011-09-01

    The demand to connect research findings with clinical practice for patients with substance use disorders has accelerated state and federal efforts focused on implementation of evidence-based practices (EBPs). One unique state driven strategy is Oregon's Evidence-Based Practice mandate, which ties state funds to specific treatment practices. Clinicians play an essential role in implementation of shifts in practice patterns and use of EBPs, but little is understood about how legislative efforts impact clinicians' sentiments and decision-making. This study presents longitudinal data from focus groups and interviews completed during the planning phase (n = 66) and early implementation of the mandate (n = 73) to investigate provider attitudes toward this policy change. Results reflect three emergent themes: (1) concern about retaining individualized treatment and clinical latitude, (2) distrust of government involvement in clinical care, and (3) the need for accountability and credibility for the field. We conclude with recommendations for state agencies considering EBP mandates. PMID:22185037

  14. Effect of Anti-TNF Antibodies on Clinical Response in Rheumatoid Arthritis Patients: A Meta-Analysis

    PubMed Central

    Wang, Shengxu; Xian, Peifeng; Mo, Xianjie

    2016-01-01

    Background. Antitumor necrosis factor (anti-TNF) drugs have been applied for rheumatoid arthritis (RA) treatment; however, patients having anti-drug antibodies (ADAbs) do not benefit from these drugs. The meta-analysis aims to comprehensively assess the relationship between ADAb positive (ADAb+) and anti-TNF response in RA patients. Methods. Observational studies comparing different clinical response between ADAb+ and ADAb negative groups were included. Odds ratio (OR) with its corresponding 95% confidence interval (CI) was used as effect size. Subgroup analyses stratified by TNF inhibitor types and assay methods for ADAb detection were performed. Results. Totally, 10 eligible studies containing 1806 subjects were included. ADAb+ was significantly associated with reduced anti-TNF response to RA at all the time points after follow-up (P < 0.001). Subgroup analysis also supported this significant association (P < 0.05), except for enzyme-linked immunosorbent assay (ELISA) group at 3 months, infliximab (INF) and enzyme-linked immunosorbent assay (ELISA) groups at 6 months, and Immunological Multi-Parameter Chip Technology (IMPACT) group at 12 months. Conclusion. ADAb+ was significantly associated with reduced clinical response in RA patients, and other alternatives should be considered in RA patients presenting ADAb+. PMID:27556040

  15. Response to Bodin and Grote regarding postdoctoral recruitment in clinical neuropsychology.

    PubMed

    Nelson, Aaron; Bilder, Robert M; O'Connor, Margaret; Brandt, Jason; Weintraub, Sandra; Bauer, Russell M

    2016-07-01

    Bodin and Grote convey their opinion that the field of clinical neuropsychology would be best served by a match system for recruitment into postdoctoral training. We critically review their arguments and offer an alternative point of view. Our view considers the current state of the match system in neuropsychology, incorporates comparisons with other disciplines that rely on a match system, and addresses the role of postdoctoral training and the specialization that takes shape at this level. We make recommendations aimed at promoting greater unity among postdoctoral training programs with the goal of focusing leadership efforts on advancing our shared mission of providing the highest quality training in clinical neuropsychology. PMID:27240699

  16. A genome-wide association analysis of temozolomide response using lymphoblastoid cell lines reveals a clinically relevant association with MGMT

    PubMed Central

    Brown, Chad C.; Havener, Tammy M.; Medina, Marisa Wong; Auman, J. Todd; Mangravite, Lara M.; Krauss, Ronald M.; McLeod, Howard L.; Motsinger-Reif, Alison A.

    2013-01-01

    Recently, lymphoblastoid cell lines (LCLs) have emerged as an innovative model system for mapping gene variants that predict dose response to chemotherapy drugs. In the current study, this strategy was expanded to the in vitro genome-wide association approach, using 516 LCLs derived from a Caucasian cohort to assess cytotoxic response to temozolomide. Genome-wide association analysis using approximately 2.1 million quality controlled single-nucleotide polymorphisms (SNPs) identified a statistically significant association (p < 10−8) with SNPs in the O6-methylguanine–DNA methyltransferase (MGMT) gene. We also demonstrate that the primary SNP in this region is significantly associated with differential gene expression of MGMT (p< 10−26) in LCLs, and differential methylation in glioblastoma samples from The Cancer Genome Atlas. The previously documented clinical and functional relationships between MGMT and temozolomide response highlight the potential of well-powered GWAS of the LCL model system to identify meaningful genetic associations. PMID:23047291

  17. Integrative genomics identifies 7p11.2 as a novel locus for fever and clinical stress response in humans

    PubMed Central

    Ferguson, Jane F.; Meyer, Nuala J.; Qu, Liming; Xue, Chenyi; Liu, Yichuan; DerOhannessian, Stephanie L.; Rushefski, Melanie; Paschos, Georgios K.; Tang, Soonyew; Schadt, Eric E.; Li, Mingyao; Christie, Jason D.; Reilly, Muredach P.

    2015-01-01

    Fever predicts clinical outcomes in sepsis, trauma and during cardiovascular stress, yet the genetic determinants are poorly understood. We used an integrative genomics approach to identify novel genomic determinants of the febrile response to experimental endotoxemia. We highlight multiple integrated lines of evidence establishing the clinical relevance of this novel fever locus. Through genome-wide association study (GWAS) of evoked endotoxemia (lipopolysaccharide (LPS) 1 ng/kg IV) in healthy subjects of European ancestry we discovered a locus on chr7p11.2 significantly associated with the peak febrile response to LPS (top single nucleotide polymorphism (SNP) rs7805622, P = 2.4 × 10−12), as well as with temperature fluctuation over time. We replicated this association in a smaller independent LPS study (rs7805622, P = 0.03). In clinical translation, this locus was also associated with temperature and mortality in critically ill patients with trauma or severe sepsis. The top GWAS SNPs are not located within protein-coding genes, but have significant cis-expression quantitative trait loci (eQTL) associations with expression of a cluster of genes ∼400 kb upstream, several of which (SUMF2, CCT6A, GBAS) are regulated by LPS in vivo in blood cells. LPS- and cold-treatment of adipose stromal cells in vitro suggest genotype-specific modulation of eQTL candidate genes (PSPH). Several eQTL genes were up-regulated in brown and white adipose following cold exposure in mice, highlighting a potential role in thermogenesis. Thus, through genomic interrogation of experimental endotoxemia, we identified and replicated a novel fever locus on chr7p11.2 that modulates clinical responses in trauma and sepsis, and highlight integrated in vivo and in vitro evidence for possible novel cis candidate genes conserved across human and mouse. PMID:25416278

  18. Integrative genomics identifies 7p11.2 as a novel locus for fever and clinical stress response in humans.

    PubMed

    Ferguson, Jane F; Meyer, Nuala J; Qu, Liming; Xue, Chenyi; Liu, Yichuan; DerOhannessian, Stephanie L; Rushefski, Melanie; Paschos, Georgios K; Tang, Soonyew; Schadt, Eric E; Li, Mingyao; Christie, Jason D; Reilly, Muredach P

    2015-03-15

    Fever predicts clinical outcomes in sepsis, trauma and during cardiovascular stress, yet the genetic determinants are poorly understood. We used an integrative genomics approach to identify novel genomic determinants of the febrile response to experimental endotoxemia. We highlight multiple integrated lines of evidence establishing the clinical relevance of this novel fever locus. Through genome-wide association study (GWAS) of evoked endotoxemia (lipopolysaccharide (LPS) 1 ng/kg IV) in healthy subjects of European ancestry we discovered a locus on chr7p11.2 significantly associated with the peak febrile response to LPS (top single nucleotide polymorphism (SNP) rs7805622, P = 2.4 × 10(-12)), as well as with temperature fluctuation over time. We replicated this association in a smaller independent LPS study (rs7805622, P = 0.03). In clinical translation, this locus was also associated with temperature and mortality in critically ill patients with trauma or severe sepsis. The top GWAS SNPs are not located within protein-coding genes, but have significant cis-expression quantitative trait loci (eQTL) associations with expression of a cluster of genes ∼400 kb upstream, several of which (SUMF2, CCT6A, GBAS) are regulated by LPS in vivo in blood cells. LPS- and cold-treatment of adipose stromal cells in vitro suggest genotype-specific modulation of eQTL candidate genes (PSPH). Several eQTL genes were up-regulated in brown and white adipose following cold exposure in mice, highlighting a potential role in thermogenesis. Thus, through genomic interrogation of experimental endotoxemia, we identified and replicated a novel fever locus on chr7p11.2 that modulates clinical responses in trauma and sepsis, and highlight integrated in vivo and in vitro evidence for possible novel cis candidate genes conserved across human and mouse. PMID:25416278

  19. Roles and Responsibilities of Clinical Faculty in Selected Educational Leadership Programs

    ERIC Educational Resources Information Center

    Hackmann, Donald G.

    2007-01-01

    This article explores the full-time clinical faculty position in selected educational leadership programs. Due to a gap in the literature, the need exists to engage in research studies to gain a greater understanding of this position. Questions guiding this study included: What is the experiential background of individuals who assume full-time…

  20. Methodology to Determinate Pupillary Responses Based in High Speed Videoculography in Clinical Eye Applications

    NASA Astrophysics Data System (ADS)

    Villamar, Luis A.; Sánchez, Anabel S.; Suaste, Ernesto

    2010-12-01

    The aim of this article is to present the application of high speed videoculography as a tool during the development of a methodology to employ in the ocular clinic diagnostic. It shows exist a significant statistically difference between groups in the time to maximum contraction velocity. And it does not exit a significant statistically difference in the latency and the maximum contraction velocity.

  1. Cultural Responsivity in Clinical Psychology Graduate Students: A Developmental Approach to the Prediction of Learning

    ERIC Educational Resources Information Center

    Berrin, Sebastian Everett

    2010-01-01

    This study used a mixed-method approach to examine students' experiences in multicultural training and their opinions about various aspects of their course(s). A developmental model of learning was employed to analyze results. More specifically, this study explored the relationship between clinical psychology doctoral students' self-reported…

  2. Immunological and Clinical Responses following the Use of Antiretroviral Therapy among Elderly HIV-Infected Individuals Attending Care and Treatment Clinic in Northwestern Tanzania: A Retrospective Cohort Study

    PubMed Central

    Mpondo, Bonaventura C. T.; Gunda, Daniel W.; Kilonzo, Semvua B.; Mgina, Erick

    2016-01-01

    Background. Limited information exists on adults ≥50 years receiving HIV care in sub-Saharan Africa despite their increasing number. We aimed at studying immunologic and clinical responses to ART in this population. Methods. Data of patients who initiated HAART between 30th of June 2004 and 1st of May 2008 at Sekou Toure Care and Treatment Clinic were retrospectively analyzed. Date of ART initiation was used as a baseline and 48 months as a follow-up date. Immune recovery was defined as a CD4 count of ≥350 cells/mm3 at 48 months and late presentation as presentation with WHO stage 3 or 4 at clinic enrollment. Proportions of patients reaching this endpoint were compared between the two groups. Results. A total of 728 patients were included in our study; of these 73 (10.0%) were aged 50 years and above. Late presentation was more common in elderly patients than young patients (65.7% versus 56.1%, P = 0.12). Proportion of patients with CD4 count ≥350 (immune recovery) was higher in younger patients than in elderly patients, although this was not statistically significant (54.5% versus 44.9%, P = 0.2). Median absolute increase in CD4 at 48 months was higher in younger patients than in elderly patients (+241.5 cells/mm3 versus +146 cells/mm3, P = 0.007). Conclusion. Elderly HIV patients have higher rates of late presentation, with lower immune recovery. Strategies to increase HIV testing in this group are required for early diagnosis and treatment to improve outcomes. PMID:27042375

  3. Multifactorial analysis of human blood cell responses to clinical total body irradiation

    NASA Technical Reports Server (NTRS)

    Yuhas, J. M.; Stokes, T. R.; Lushbaugh, C. C.

    1972-01-01

    Multiple regression analysis techniques are used to study the effects of therapeutic radiation exposure, number of fractions, and time on such quantal responses as tumor control and skin injury. The potential of these methods for the analysis of human blood cell responses is demonstrated and estimates are given of the effects of total amount of exposure and time of protraction in determining the minimum white blood cell concentration observed after exposure of patients from four disease groups.

  4. Assessment of clinical and radiological response to sorafenib in hepatocellular carcinoma patients

    PubMed Central

    Sacco, Rodolfo; Mismas, Valeria; Romano, Antonio; Bertini, Marco; Bertoni, Michele; Federici, Graziana; Metrangolo, Salvatore; Parisi, Giuseppe; Tumino, Emanuele; Bresci, Giampaolo; Giacomelli, Luca; Marceglia, Sara; Bargellini, Irene

    2015-01-01

    Sorafenib is an effective anti-angiogenic treatment for hepatocellular carcinoma (HCC). The assessment of tumor progression in patients treated with sorafenib is crucial to help identify potentially-resistant patients, avoiding unnecessary toxicities. Traditional methods to assess tumor progression are based on variations in tumor size and provide unreliable results in patients treated with sorafenib. New methods to assess tumor progression such as the modified Response Evaluation Criteria in Solid Tumors or European Association for the Study of Liver criteria are based on imaging to measure the vascularization and tumor volume (viable or necrotic). These however fail especially when the tumor response results in irregular development of necrotic tissue. Newer assessment techniques focus on the evaluation of tumor volume, density or perfusion. Perfusion computed tomography and Dynamic Contrast-Enhanced-UltraSound can measure the vascularization of HCC lesions and help predict tumor response to anti-angiogenic therapies. Mean Transit Time is a possible predictive biomarker to measure tumor response. Volumetric techniques are reliable, reproducible and time-efficient and can help measure minimal changes in viable tumor or necrotic tissue, allowing the prompt identification of non-responders. Volume ratio may be a reproducible biomarker for tumor response. Larger trials are needed to confirm the use of these techniques in the prediction of response to sorafenib. PMID:25624994

  5. Achieving Goal Blood Pressure.

    PubMed

    Laurent, Stéphane

    2015-07-01

    Both monotherapy and combination therapy options are appropriate for antihypertensive therapy according to the 2013 European Society of Hypertension (ESH)/European Society of Cardiology (ESC) guidelines. Most patients require more than one agent to achieve blood pressure (BP) control, and adding a second agent is more effective than doubling the dose of existing therapy. The addition of a third agent may be required to achieve adequate BP reductions in some patients. Single-pill fixed-dose combinations (FDCs) allow multiple-drug regimens to be delivered without any negative impact on patient compliance or persistence with therapy. FDCs also have documented beneficial clinical effects and use of FDCs containing two or three agents is recommended by the 2013 ESH/ESC guidelines. PMID:26002423

  6. Relationship between pharmacokinetic profile of subcutaneously administered alemtuzumab and clinical response in patients with chronic lymphocytic leukemia

    PubMed Central

    Montagna, Michela; Montillo, Marco; Avanzini, Maria A.; Tinelli, Carmine; Tedeschi, Alessandra; Visai, Livia; Ricci, Francesca; Vismara, Eleonora; Morra, Enrica; Regazzi, Mario

    2011-01-01

    Alemtuzumab serum levels and clinical response after subcutaneous administration (10 mg 3 times/week for six weeks) have been explored in 29 chronic lymphocytic leukemia patients receiving the monoclonal antibody as consolidation. Serum concentrations after each administration gradually increased during the first week and more markedly during weeks 2 and 3, approaching the steady-state at week 6. Absorption continued slowly through the tissues for about 2–3 weeks after the last administration, starting to decrease thereafter. Difference between Responders and Non-responders was statistically significant: maximal concentration (Cmax) was 1.69 μg/mL vs. 0.44 μg/mL; concentration before subcutaneous administration (Cpre-dose) on day 15 was 0.7 vs. 0.21 μg/mL, area under curve (AUC0−12h) was 11.09 vs. 2.26 μg x h/mL for Responders and Non-responders, respectively. Higher systemic exposure to alemtuzumab correlated with a better clinical response and minimal residual disease. Results suggest that an adjusted schedule according to serum level could improve clinical outcome of patients receiving subcutaneous alemtuzumab. PMID:21330330

  7. A Training Program Using an Audience Response System to Calibrate Dental Faculty Members Assessing Student Clinical Competence.

    PubMed

    Metz, Michael J; Metz, Cynthia J; Durski, Marcelo T; Aiken, Sean A; Mayfield, Theresa G; Lin, Wei-Shao

    2016-09-01

    The aim of this study was to assess the effectiveness of calibration training of departmental faculty and competency graders using an audience response system on operative dentistry concepts across 12 months. The training sessions were designed to further solidify the process and equilibration of clinical opinions among faculty members and provide a more calibrated grading assessment during patient care for student performance feedback. Four (quarterly) calibration sessions occurred over 12 months in 2015. The first session was considered the baseline (control value) for this study. Pre- and post-calibration interrater agreement was assessed. Additionally, a pre and post assessment with ten Likert-scale questions was used to measure students' perceptions of instructional consistency. The results showed that a statistically significant increase in conceptual knowledge scores occurred for both departmental faculty members and competency graders across each of the four sessions (one-factor ANOVA; p<0.05). Interrater reliability agreement also significantly improved for both department faculty members and competency graders' clinical assessments over 12 months of implementation (Cohen's Kappa; p<0.05). There was a statistically significant increase in positive student perceptions on all ten questions (dependent t-test; p<0.05). Implementation of an audience response system for departmental and competency graders was found to be effective in facilitating a discussion forum, calibrating clinical assessments, and improving student perceptions. The positive results from this study support the value of dental schools' introducing faculty development programs to ensure consistent instruction for assessing dental student competence. PMID:27587578

  8. Teacher Attitudes on Personal Teaching Efficacy and Responsive Teaching, and Principal Leadership Behaviors in the Areas of Leader Social Relationships, Leadership/Goal Setting, and Collaboration for Learning in Low Wealth, Low and High Achieving Middle Schools

    ERIC Educational Resources Information Center

    Levey, Eliana K.

    2014-01-01

    The purpose of this study was to investigate whether middle school teacher attitudes on personal teaching efficacy and responsive teaching and their descriptions of their principal's leadership behaviors in the areas of leader social relationships, leadership/goal setting, and collaboration for learning differ for high- and low-achieving Grade 8…

  9. Development of criteria for evaluating clinical response in thyroid eye disease (CRI-TED) using a modified Delphi technique

    PubMed Central

    Douglas, Raymond S.; Tsirbas, Angelo; Gordon, Mark; Lee, Diana; Khadavi, Nicole; Garneau, Helene Chokron; Goldberg, Robert A.; Cahill, Kenneth; Dolman, Peter J.; Elner, Victor; Feldon, Steve; Lucarelli, Mark; Uddin, Jimmy; Kazim, Michael; Smith, Terry J.; Khanna, Dinesh

    2014-01-01

    To identify components of a provisional clinical response index for thyroid eye disease (CRI-TED) using a modified Delphi technique. The International Thyroid Eye Disease Society (ITEDS) conducted a structured, 3-round Delphi exercise establishing consensus for a core set of measures for clinical trials in TED. The steering committee discussed the results in a face-to-face meeting (nominal group technique) and evaluated each criterion with respect to its feasibility, reliability, redundancy, and validity. Redundant measures were consolidated or excluded. Criteria were parsed into 11 domains for the Delphi surveys. Eighty four respondents participated in the Delphi-1 survey, providing 220 unique items. Ninety- two members (100% of the respondents from Delphi 1 plus eight new participants) responded in Delphi-2 and rated the same 220 items. Sixty-four members (76% of participants) rated 153 criteria in Delphi-3 (67 criteria were excluded due to redundancy). Criteria with a mean greater than 6 (1 least appropriate to 9 most appropriate) were further evaluated by the nominal group technique and provisional core measures were chosen. Using a Delphi exercise, we developed provisional core measures for assessing disease activity and severity in clinical trials of therapies for TED. These measures will be iteratively refined for use in multicenter clinical trials. PMID:19752424

  10. Subclinical hypothyroidism is a risk factor for delayed clinical complete response in patients with systemic lupus erythematosus (SLE)

    PubMed Central

    Dong, Lin; Jia, Liu; Hong, Xuezhi; Chen, Guangliang; Mo, Hanyou

    2014-01-01

    The objective of the study was to investigate whether subclinical hypothyroidism is a risk factor for a delayed clinical complete response in patients with SLE. This study included 363 patients with SLE classified according to the ACR classification criteria. These patients were divided into three groups: those who had subclinical hypothyroidism, a euthyroid state, and clinical hypothyroidism. The first group contained 41 cases with SLE and subclinical hypothyroidism, the second group contained 7 cases with SLE and clinical hypothyroidism, and the third group contained 315 positive control cases with SLE and a euthyroid state. Patients were observed for general observational parameters, and an efficacy assessment was performed using SLEDAI, PGA, and SLICC. Results: Patients in the subclinical hypothyroidism group without supplementary treatment had no higher immune activity indicators, SLE activity, and organ damage than those SLE with euthyroid state. These parameters were also no higher than in those who were given treatment in the SLE with clinical hypothyroidism group at 6 months; Immune activity indicators, SLE activity, organ damage, and remission rate were improved after 3 months’ supplementary treatment in 14 subclinical hypothyroidism cases that did not display remission non-remission cases at 6 months. Additionally, no significant difference in remission rate was observed in comparison with the group of SLE patients with a euthyroid state after 6 months’ supplementary treatment. Conclusion: Subclinical hypothyroidism can the slow remission rate of SLE. Supplementary treatment should be performed earlier to improve the remission rate. PMID:25356146

  11. The pharmaceutical industry's responsibility for protecting human subjects of clinical trials in developing nations.

    PubMed

    Kelleher, Finnuala

    2004-01-01

    Pharmaceutical companies increasingly perform clinical trials in developing nations. Governments of host nations see the trials as a way to provide otherwise unaffordable medical care, while trial sponsors are drawn to those countries by lower costs, the prevalence of diseases rare in developed nations, and large numbers of impoverished patients. Local governments, however, fail to police trials, and the FDA does not monitor trials in foreign countries, resulting in the routine violation of international standards for the protection of human subjects. This Note proposes independent accreditation of those institutions involved in clinical trials--the institutional review boards which oversee trial protocol; the organizations, such as pharmaceutical companies, which sponsor the trials; and the research organizations that conduct the trials. Accreditation, similar to that used in the footwear and apparel industries, would increase the transparency of pharmaceutical trials and would enable the United States government and consumers to hold trial sponsors accountable for their actions. PMID:16755695

  12. Contralateral Clinically Unaffected Eyes of Patients With Unilateral Infectious Keratitis Demonstrate a Sympathetic Immune Response

    PubMed Central

    Cruzat, Andrea; Schrems, Wolfgang A.; Schrems-Hoesl, Laura M.; Cavalcanti, Bernardo M.; Baniasadi, Neda; Witkin, Deborah; Pavan-Langston, Deborah; Dana, Reza; Hamrah, Pedram

    2015-01-01

    Purpose To analyze the contralateral unaffected eyes of patients with microbial keratitis (MK) for any immune cell or nerve changes by laser in vivo confocal microscopy (IVCM). Methods A prospective study was performed on 28 patients with MK, including acute bacterial, fungal, and Acanthamoeba keratitis, as well as on their contralateral clinically unaffected eyes and on control groups, which consisted of 28 age-matched normal controls and 15 control contact lens (CL) wearers. Laser IVCM with the Heidelberg Retinal Tomograph 3/Rostock Cornea Module and Cochet-Bonnet esthesiometry of the central cornea were performed. Two masked observers assessed central corneal dendritiform cell density and subbasal corneal nerve parameters. Results The contralateral clinically unaffected eyes of patients with MK demonstrated significant diminishment in nerve density (15,603.8 ± 1265.2 vs. 24,102.1 ± 735.6 μm/mm2), total number of nerves (11.9 ± 1.0 vs. 24.9 ± 1.2/frame), number of branches (1.7 ± 0.2 vs. 19.9 ± 1.3/frame), and branch nerve length (5775.2 ± 757.1 vs. 12,715.4 ± 648.4 μm/mm2) (P < 0.001 for all parameters) compared to normal controls and CL wearers. Further, dendritiform cell density in the contralateral unaffected eyes was significantly increased as compared to that in controls (117.5 ± 19.9 vs. 24.2 ± 3.5 cells/mm2, P < 0.001). Conclusions We demonstrate a subclinical involvement in the contralateral clinically unaffected eyes in patients with unilateral acute MK. In vivo confocal microscopy reveals not only a diminishment of the subbasal corneal nerves and sensation, but also an increase in dendritiform cell density in the contralateral unaffected eyes of MK patients. These findings show bilateral immune alterations in a clinically unilateral disease. PMID:26465889

  13. Cytokines as a predictor of clinical response following hip arthroscopy: minimum 2-year follow-up.

    PubMed

    Shapiro, Lauren M; Safran, Marc R; Maloney, William J; Goodman, Stuart B; Huddleston, James I; Bellino, Michael J; Scuderi, Gaetano J; Abrams, Geoffrey D

    2016-08-01

    Hip arthroscopy in patients with osteoarthritis has been shown to have suboptimal outcomes. Elevated cytokine concentrations in hip synovial fluid have previously been shown to be associated with cartilage pathology. The purpose of this study was to determine whether a relationship exists between hip synovial fluid cytokine concentration and clinical outcomes at a minimum of 2 years following hip arthroscopy. Seventeen patients without radiographic evidence of osteoarthritis had synovial fluid aspirated at time of portal establishment during hip arthroscopy. Analytes included fibronectin-aggrecan complex as well as a multiplex cytokine array. Patients completed the modified Harris Hip Score, Western Ontario and McMaster Universities Arthritis Index and the International Hip Outcomes Tool pre-operatively and at a minimum of 2 years following surgery. Pre and post-operative scores were compared with a paired t-test, and the association between cytokine values and clinical outcome scores was performed with Pearson's correlation coefficient with an alpha value of 0.05 set as significant. Sixteen of seventeen patients completed 2-year follow-up questionnaires (94%). There was a significant increase in pre-operative to post-operative score for each clinical outcome measure. No statistically significant correlation was seen between any of the intra-operative cytokine values and either the 2-year follow-up scores or the change from pre-operative to final follow-up outcome values. No statistically significant associations were seen between hip synovial fluid cytokine concentrations and 2-year follow-up clinical outcome assessment scores for those undergoing hip arthroscopy. PMID:27583163

  14. Clinical and laboratory characteristics of ocular syphilis, co-infection, and therapy response

    PubMed Central

    Sahin, Ozlem; Ziaei, Alireza

    2016-01-01

    Purpose To describe the clinical presentation of patients diagnosed with presumed latent ocular syphilis and congenital ocular syphilis at tertiary referral center in Turkey, and to compare the clinical findings with patients described in other studies, specifically focusing on demographics and co-infections. Methods This is a retrospective study reviewing the medical records of patients diagnosed with ocular inflammation between January 2012 and June 2014 at a tertiary referral center in Turkey. Ocular syphilis was diagnosed on the basis of non-treponemal and treponemal antibody tests, and cerebrospinal fluid analysis. All the patients diagnosed with ocular syphilis were tested for human immunodeficiency virus (HIV), Toxoplasma gondii, rubella, cytomegalovirus, and herpes. Results A total of 1,115 patients were evaluated between January 2012 and June 2014, and 12 patients (1.07%) were diagnosed with ocular syphilis based on the inclusion criteria. None of the patients were seropositive for HIV. Two patients were seropositive for T. gondii-specific IgG. Clinical presentations include non-necrotizing anterior scleritis, non-necrotizing sclerokeratitis, anterior uveitis, intermediate uveitis, posterior uveitis, panuveitis, and optic neuritis. All of the patients showed clinical improvement in the level of ocular inflammation with intravenous penicillin 24 million U/day for 10 days. Three patients received additional oral methotrexate as an adjunctive therapy. Two cases received low-dose trimethoprim–sulfamethoxazole. Conclusion Ocular syphilis is an uncommon cause of ocular inflammation in HIV-negative patients. Central retinochoroiditis is the most common ocular manifestation, and it is the most common cause of visual impairment. Ocular syphilis might present associated with co-infections such as T. gondii in developing countries. Oral methotrexate might be beneficial as an adjunctive therapy for ocular syphilis in resolving the residual intraocular inflammation

  15. Cytokines as a predictor of clinical response following hip arthroscopy: minimum 2-year follow-up

    PubMed Central

    Shapiro, Lauren M.; Safran, Marc R.; Maloney, William J.; Goodman, Stuart B.; Huddleston, James I.; Bellino, Michael J.; Scuderi, Gaetano J.; Abrams, Geoffrey D.

    2016-01-01

    Hip arthroscopy in patients with osteoarthritis has been shown to have suboptimal outcomes. Elevated cytokine concentrations in hip synovial fluid have previously been shown to be associated with cartilage pathology. The purpose of this study was to determine whether a relationship exists between hip synovial fluid cytokine concentration and clinical outcomes at a minimum of 2 years following hip arthroscopy. Seventeen patients without radiographic evidence of osteoarthritis had synovial fluid aspirated at time of portal establishment during hip arthroscopy. Analytes included fibronectin–aggrecan complex as well as a multiplex cytokine array. Patients completed the modified Harris Hip Score, Western Ontario and McMaster Universities Arthritis Index and the International Hip Outcomes Tool pre-operatively and at a minimum of 2 years following surgery. Pre and post-operative scores were compared with a paired t-test, and the association between cytokine values and clinical outcome scores was performed with Pearson’s correlation coefficient with an alpha value of 0.05 set as significant. Sixteen of seventeen patients completed 2-year follow-up questionnaires (94%). There was a significant increase in pre-operative to post-operative score for each clinical outcome measure. No statistically significant correlation was seen between any of the intra-operative cytokine values and either the 2-year follow-up scores or the change from pre-operative to final follow-up outcome values. No statistically significant associations were seen between hip synovial fluid cytokine concentrations and 2-year follow-up clinical outcome assessment scores for those undergoing hip arthroscopy. PMID:27583163

  16. In vitro sensitivity to methyl-prednisolone is associated with clinical response in pediatric idiopathic nephrotic syndrome.

    PubMed

    Cuzzoni, E; De Iudicibus, S; Stocco, G; Favretto, D; Pelin, M; Messina, G; Ghio, L; Monti, E; Pasini, A; Montini, G; Decorti, G

    2016-09-01

    The aim of this study was to evaluate the in vitro steroid sensitivity as a predictor of clinical response to glucocorticoids in childhood idiopathic nephrotic syndrome (INS). Seventy-four patients (median age 4.33, interquartile range [IQR] 2.82-7.23; 63.5% male) were enrolled in a prospective multicenter study: in vitro steroid inhibition of patients' peripheral blood mononuclear cell proliferation was evaluated by [methyl-(3) H] thymidine incorporation assay at disease onset (T0) and after 4 weeks (T4) of treatment. Steroid dependence was associated with increased in vitro sensitivity at T4 assessed both as drug concentration inducing 50% of inhibition (IC50 ; odds ratio [OR] = 0.48, 95% confidence interval [CI] = 0.24-0.85; P = 0.0094) and maximum inhibition at the highest drug concentration (Imax ; OR = 1.13, 95% CI = 1.02-1.31; P = 0.017). IC50 > 4.4 nM and Imax < 92% at T4 were good predictors for optimal clinical response. These results suggest that this test may be useful for predicting the response to glucocorticoid therapy in pediatric INS. PMID:27007551

  17. The Reflux Disease Questionnaire: a measure for assessment of treatment response in clinical trials

    PubMed Central

    Shaw, Michael; Dent, John; Beebe, Timothy; Junghard, Ola; Wiklund, Ingela; Lind, Tore; Johnsson, Folke

    2008-01-01

    Background Critical needs for treatment trials in gastroesophageal reflux disease (GERD) include assessing response to treatment, evaluating symptom severity, and translation of symptom questionnaires into multiple languages. We evaluated the previously validated Reflux Disease Questionnaire (RDQ) for internal consistency, reliability, responsiveness to change during treatment and the concordance between RDQ and specialty physician assessment of symptom severity, after translation into Swedish and Norwegian. Methods Performance of the RDQ after translation into Swedish and Norwegian was evaluated in 439 patients with presumed GERD in a randomized, double-blind trial of active treatment with a proton pump inhibitor. Results The responsiveness was excellent across three RDQ indicators. Mean change scores in patients on active treatment were large, also reflected in effect sizes that ranged from a low of 1.05 (dyspepsia) to a high of 2.05 (heartburn) and standardized response means 0.99 (dyspepsia) and 1.52 (heartburn). A good positive correlation between physician severity ratings and RDQ scale scores was seen. The internal consistency reliability using alpha coefficients of the scales, regardless of language, ranged from 0.67 to 0.89. Conclusion The results provide strong evidence that the RDQ is amenable to translation and represents a viable instrument for assessing response to treatment, and symptom severity. PMID:18447946

  18. Improved growth and clinical, nutritional, and respiratory changes in response to nutritional therapy in cystic fibrosis.

    PubMed

    Shepherd, R; Cooksley, W G; Cooke, W D

    1980-09-01

    To investigate the role of nutritional factors in growth and in the clinical, nurtitional, and respiratory status in cystic fibrosis, we studied 12 problem CF patients from six months before to six months after a period of supplemental parenteral nutrition. During the initial six months' observation period on appropriate conventional therapy, the patients (aged 0.5 to 11 years) had inadequate growth and weight gain, a total of 21 active pulmonary infections, and, despite dietary supplements, inadequate ad libitum nutrient intakes. After nutritional therapy, providing a balanced consistent hypercaloric intake for 21 days, catch-up weight gain occurred by one month and continued at six months; catch-up in linear growth was observed by three months and continued at six months. In addition, significantly fewer pulmonary infections were observed in the six months' post-therapy (n = 3), sustained and significant improvements were noted in clinical score and plumonary function, and there was a marked improvement in well-being and ad libitum nutrient intake. We conclude that adequate nutritional support can favorably affect growth, clinical status, and the course of chronic pulmonary disease in problem cases of CF. PMID:6774070

  19. Evaluation of Factors Contributing to the Achievement of Students Participating in a Culturally Responsive Curriculum in Hawai`i Public Schools

    ERIC Educational Resources Information Center

    Bowditch, Scott A.

    2013-01-01

    This research explored the effectiveness of "Ka Hana 'Imi Na 'auao," a culturally responsive science curriculum developed for Hawaiian and other students in Hawai'i high schools. An instrument, The Culturally Responsive Science Perception (CRSP) inventory was developed to measure students' (a) perceptions of their…

  20. Risk Factor Analysis for the Immunogenicity of Adalimumab Associated with Decreased Clinical Response in Chinese Patients with Psoriasis.

    PubMed

    Chiu, Hsien-Yi; Wang, Ting-Shun; Chan, Chih-Chieh; Lin, Sung-Jan; Tsai, Tsen-Fang

    2015-07-01

    Although anti-drug antibodies against biologics have been associated with decreased clinical efficacy, the immunogenicity of biologics seems to vary between drugs, diseases and ethnicities. This study aims to investigate the predictors for the formation of anti-adalimumab antibodies (AAA) and the clinical consequences of AAA formation. In 53 Chinese psoriatic patients treated with adalimumab, AAA was detected in 50.9%. Differences in Psoriasis Area and Severity Index 75 (PASI75) response rates among patients with and without AAA were significant (44.4% vs. 88.5%; p = 0.001). Patients with AAA had significantly lower trough concentrations of adalimumab than those without AAA. Risk factor analysis showed that treatment interruption, low trough adalimumab concentration, absence of concomitant methotrexate use and biologics switching were associated with a higher AAA titre. The treatment pattern of biologics influences the risk of AAA formation, thereby leading to reduced efficacy of adalimumab. PMID:25673333

  1. Prospective Evaluation to Establish a Dose Response for Clinical Oral Mucositis in Patients Undergoing Head-and-Neck Conformal Radiotherapy

    SciTech Connect

    Narayan, Samir Lehmann, Joerg; Coleman, Matthew A.; Vaughan, Andrew; Yang, Claus Chunli; Enepekides, Danny; Farwell, Gregory; Purdy, James A.; Laredo, Grace; Nolan, Kerry A.S.; Pearson, Francesca S.; Vijayakumar, Srinivasan

    2008-11-01

    Purpose: We conducted a clinical study to correlate oral cavity dose with clinical mucositis, perform in vivo dosimetry, and determine the feasibility of obtaining buccal mucosal cell samples in patients undergoing head-and-neck radiation therapy. The main objective is to establish a quantitative dose response for clinical oral mucositis. Methods and Materials: Twelve patients undergoing radiation therapy for head-and-neck cancer were prospectively studied. Four points were chosen in separate quadrants of the oral cavity. Calculated dose distributions were generated by using AcQPlan and Eclipse treatment planning systems. MOSFET dosimeters were used to measure dose at each sampled point. Each patient underwent buccal sampling for future RNA analysis before and after the first radiation treatment at the four selected points. Clinical and functional mucositis were assessed weekly according to National Cancer Institute Common Toxicity Criteria, Version 3. Results: Maximum and average doses for sampled sites ranged from 7.4-62.3 and 3.0-54.3 Gy, respectively. A cumulative point dose of 39.1 Gy resulted in mucositis for 3 weeks or longer. Mild severity (Grade {<=} 1) and short duration ({<=}1 week) of mucositis were found at cumulative point doses less than 32 Gy. Polymerase chain reaction consistently was able to detect basal levels of two known radiation responsive genes. Conclusions: In our sample, cumulative doses to the oral cavity of less than 32 Gy were associated with minimal acute mucositis. A dose greater than 39 Gy was associated with longer duration of mucositis. Our technique for sampling buccal mucosa yielded sufficient cells for RNA analysis using polymerase chain reaction.

  2. Effects of Computer-Based Early-Reading Academic Learning Time on Early-Reading Achievement: A Dose-Response Approach

    ERIC Educational Resources Information Center

    Heuston, Edward Benjamin Hull

    2010-01-01

    Academic learning time (ALT) has long had the theoretical underpinnings sufficient to claim a causal relationship with academic achievement, but to this point empirical evidence has been lacking. This dearth of evidence has existed primarily due to difficulties associated with operationalizing ALT in traditional educational settings. Recent…

  3. Serological response to syphilis treatment in HIV‐positive and HIV‐negative patients attending sexually transmitted diseases clinics

    PubMed Central

    Ghanem, K G; Erbelding, E J; Wiener, Z S; Rompalo, A M

    2007-01-01

    Background HIV‐positive patients treated for syphilis may be at increased risk for serological failure. Objective To compare follow‐up serologies and serological responses to treatment between HIV‐positive and HIV‐negative patients attending two sexually transmitted disease (STD) clinics. Study design Existing records were reviewed from HIV‐positive patients who were diagnosed and treated for syphilis at the public STD clinics in Baltimore, Maryland, USA, between 1992 and 2000. Results of their serological follow‐up were compared with those of HIV‐negative clinic patients at the time of syphilis treatment. Failure was defined as lack of a fourfold drop in rapid plasma reagin (RPR) titre by 400 days after treatment or a fourfold increased titre between 30 and 400 days. Results Of the 450 HIV‐positive patients with syphilis, 288 (64%) did not have documented follow‐up serologies and 129 (28.5%) met the inclusion criteria; 168 (17%) of 1000 known HIV‐negative patients were similarly eligible. There were 22 failures in the HIV‐positive group and 5 in the HIV‐negative group (p<0.001). The median times to successful serological responses in both groups were 278 (95% confidence interval (CI) 209 to 350) and 126 (95% CI 108 to 157) days, respectively (p<0.001). A multivariate Cox's proportional hazards model showed an increased risk of serological failure among the HIV‐positive patients (hazards ratio 6.0, 95% CI 1.5 to 23.9; p = 0.01). Conclusion HIV‐positive patients treated for syphilis may be at higher risk of serological failure. Despite recommendations for more frequent serological follow‐up, most patients did not have documentation of serological response after standard treatment for syphilis. PMID:16943224

  4. Bioprinted 3D Primary Liver Tissues Allow Assessment of Organ-Level Response to Clinical Drug Induced Toxicity In Vitro

    PubMed Central

    Funk, Juergen; Robbins, Justin B.; Crogan-Grundy, Candace; Presnell, Sharon C.; Singer, Thomas; Roth, Adrian B.

    2016-01-01

    Modeling clinically relevant tissue responses using cell models poses a significant challenge for drug development, in particular for drug induced liver injury (DILI). This is mainly because existing liver models lack longevity and tissue-level complexity which limits their utility in predictive toxicology. In this study, we established and characterized novel bioprinted human liver tissue mimetics comprised of patient-derived hepatocytes and non-parenchymal cells in a defined architecture. Scaffold-free assembly of different cell types in an in vivo-relevant architecture allowed for histologic analysis that revealed distinct intercellular hepatocyte junctions, CD31+ endothelial networks, and desmin positive, smooth muscle actin negative quiescent stellates. Unlike what was seen in 2D hepatocyte cultures, the tissues maintained levels of ATP, Albumin as well as expression and drug-induced enzyme activity of Cytochrome P450s over 4 weeks in culture. To assess the ability of the 3D liver cultures to model tissue-level DILI, dose responses of Trovafloxacin, a drug whose hepatotoxic potential could not be assessed by standard pre-clinical models, were compared to the structurally related non-toxic drug Levofloxacin. Trovafloxacin induced significant, dose-dependent toxicity at clinically relevant doses (≤ 4uM). Interestingly, Trovafloxacin toxicity was observed without lipopolysaccharide stimulation and in the absence of resident macrophages in contrast to earlier reports. Together, these results demonstrate that 3D bioprinted liver tissues can both effectively model DILI and distinguish between highly related compounds with differential profile. Thus, the combination of patient-derived primary cells with bioprinting technology here for the first time demonstrates superior performance in terms of mimicking human drug response in a known target organ at the tissue level. PMID:27387377

  5. A Personalized BEST: Characterization of Latent Clinical Classes of Nonischemic Heart Failure That Predict Outcomes and Response to Bucindolol

    PubMed Central

    Kao, David P.; Wagner, Brandie D.; Robertson, Alastair D.; Bristow, Michael R.; Lowes, Brian D.

    2012-01-01

    Background Heart failure patients with reduced ejection fraction (HFREF) are heterogenous, and our ability to identify patients likely to respond to therapy is limited. We present a method of identifying disease subtypes using high-dimensional clinical phenotyping and latent class analysis that may be useful in personalizing prognosis and treatment in HFREF. Methods A total of 1121 patients with nonischemic HFREF from the β-blocker Evaluation of Survival Trial were categorized according to 27 clinical features. Latent class analysis was used to generate two latent class models, LCM A and B, to identify HFREF subtypes. LCM A consisted of features associated with HF pathogenesis, whereas LCM B consisted of markers of HF progression and severity. The Seattle Heart Failure Model (SHFM) Score was also calculated for all patients. Mortality, improvement in left ventricular ejection fraction (LVEF) defined as an increase in LVEF ≥5% and a final LVEF of 35% after 12 months, and effect of bucindolol on both outcomes were compared across HFREF subtypes. Performance of models that included a combination of LCM subtypes and SHFM scores towards predicting mortality and LVEF response was estimated and subsequently validated using leave-one-out cross-validation and data from the Multicenter Oral Carvedilol Heart Failure Assessment Trial. Results A total of 6 subtypes were identified using LCM A and 5 subtypes using LCM B. Several subtypes resembled familiar clinical phenotypes. Prognosis, improvement in LVEF, and the effect of bucindolol treatment differed significantly between subtypes. Prediction improved with addition of both latent class models to SHFM for both 1-year mortality and LVEF response outcomes. Conclusions The combination of high-dimensional phenotyping and latent class analysis identifies subtypes of HFREF with implications for prognosis and response to specific therapies that may provide insight into mechanisms of disease. These subtypes may facilitate

  6. Outcomes of patients with myelodysplastic syndromes who achieve stable disease after treatment with hypomethylating agents.

    PubMed

    Nazha, Aziz; Sekeres, Mikkael A; Garcia-Manero, Guillermo; Barnard, John; Al Ali, Najla H; Roboz, Gail J; Steensma, David P; DeZern, Amy E; Zimmerman, Cassie; Jabbour, Elias J; Zell, Katrina; List, Alan F; Kantarjian, Hagop M; Maciejewski, Jaroslaw P; Komrokji, Rami S

    2016-02-01

    Treatment with hypomethylating agents (HMAs) improves overall survival (OS) in patients who achieve a response of stable disease (SD) or better (complete remission [CR], partial remission [PR], or hematologic improvement [HI]). It is not well established if patients who achieve SD at 4-6 months of therapy should be offered different therapies to optimize their response or continue with the same regimen. Clinical data were obtained from the MDS Clinical Research Consortium database. SD was defined as no evidence of progression and without achievement of any other responses. Of 291 patients treated with AZA or DAC, 55% achieved their best response (BR) at 4-6 months. Among patients with SD at 4-6 months, 29 (20%) achieved a better response at a later treatment time point. Younger patients with lower bone marrow blast percentages, and intermediate risk per IPSS-R were more likely to achieve a better response (CR, PR, or HI) after SD at 4-6 months. Patients with SD who subsequently achieved CR had superior OS compared to patients who remained with SD (28.1 vs. 14.4 months, respectively, p=.04). In conclusion, patients treated with HMAs who achieves CR after a SD status had longer survival with continuous treatment after 6 months. PMID:26777537

  7. Outcomes of patients with myelodysplastic syndromes who achieve stable disease after treatment with hypomethylating agents

    PubMed Central

    Nazha, Aziz; Sekeres, Mikkael A.; Garcia-Manero, Guillermo; Barnard, John; Al Ali, Najla H.; Roboz, Gail J.; Steensma, David P.; DeZern, Amy E.; Zimmerman, Cassie; Jabbour, Elias J.; Zell, Katrina; List, Alan F.; Kantarjian, Hagop M.; Maciejewski, Jaroslaw P.; Komrokji, Rami S.

    2016-01-01

    Treatment with hypomethylating agents (HMAs) improves overall survival (OS) in patients who achieve a response of stable disease (SD) or better (complete remission [CR], partial remission [PR], or hematologic improvement [HI]). It is not well established if patients who achieve SD at 4–6 months of therapy should be offered different therapies to optimize their response or continue with the same regimen. Clinical data were obtained from the MDS Clinical Research Consortium database. SD was defined as no evidence of progression and without achievement of any other responses. Of 291 patients treated with AZA or DAC, 55% achieved their best response (BR) at 4–6 months. Among patients with SD at 4–6 months, 29 (20%) achieved a better response at a later treatment time point. Younger patients with lower bone marrow blast percentages, and intermediate risk per IPSS-R were more likely to achieve a better response (CR, PR, or HI) after SD at 4–6 months. Patients with SD who subsequently achieved CR had superior OS compared to patients who remained with SD (28.1 vs. 14.4 months, respectively, p =.04). In conclusion, patients treated with HMAs who achieves CR after a SD status had longer survival with continuous treatment after 6 months. PMID:26777537

  8. Using Design To Achieve Sustainability

    EPA Science Inventory

    Sustainability is defined as meeting the needs of this generation without compromising the ability of future generations to meet their needs. This is a conditional statement that places the responsibility for achieving sustainability squarely in hands of designers and planners....

  9. Structure and Measurement of Depression in Youths: Applying Item Response Theory to Clinical Data

    ERIC Educational Resources Information Center

    Cole, David A.; Cai, Li; Martin, Nina C.; Findling, Robert L.; Youngstrom, Eric A.; Garber, Judy; Curry, John F.; Hyde, Janet S.; Essex, Marilyn J.; Compas, Bruce E.; Goodyer, Ian M.; Rohde, Paul; Stark, Kevin D.; Slattery, Marcia J.; Forehand, Rex

    2011-01-01

    Our goals in this article were to use item response theory (IRT) to assess the relation of depressive symptoms to the underlying dimension of depression and to demonstrate how IRT-based measurement strategies can yield more reliable data about depression severity than conventional symptom counts. Participants were 3,403 children and adolescents…

  10. Pattern of humoral immune response to Plasmodium falciparum blood stages in individuals presenting different clinical expressions of malaria

    PubMed Central

    Leoratti, Fabiana MS; Durlacher, Rui R; Lacerda, Marcus VG; Alecrim, Maria G; Ferreira, Antonio W; Sanchez, Maria CA; Moraes, Sandra L

    2008-01-01

    Background The development of protective immunity against malaria is slow and to be maintained, it requires exposure to multiple antigenic variants of malaria parasites and age-associated maturation of the immune system. Evidence that the protective immunity is associated with different classes and subclasses of antibodies reveals the importance of considering the quality of the response. In this study, we have evaluated the humoral immune response against Plasmodium falciparum blood stages of individuals naturally exposed to malaria who live in endemic areas of Brazil in order to assess the prevalence of different specific isotypes and their association with different malaria clinical expressions. Methods Different isotypes against P. falciparum blood stages, IgG, IgG1, IgG2, IgG3, IgG4, IgM, IgE and IgA, were determined by ELISA. The results were based on the analysis of different clinical expressions of malaria (complicated, uncomplicated and asymptomatic) and factors related to prior malaria exposure such as age and the number of previous clinical malaria attacks. The occurrence of the H131 polymorphism of the FcγIIA receptor was also investigated in part of the studied population. Results The highest levels of IgG, IgG1, IgG2 and IgG3 antibodies were observed in individuals with asymptomatic and uncomplicated malaria, while highest levels of IgG4, IgE and IgM antibodies were predominant among individuals with complicated malaria. Individuals reporting more than five previous clinical malaria attacks presented a predominance of IgG1, IgG2 and IgG3 antibodies, while IgM, IgA and IgE antibodies predominated among individuals reporting five or less previous clinical malaria attacks. Among individuals with uncomplicated and asymptomatic malaria, there was a predominance of high-avidity IgG, IgG1, IgG2 antibodies and low-avidity IgG3 antibodies. The H131 polymorphism was found in 44.4% of the individuals, and the highest IgG2 levels were observed among asymptomatic

  11. Amebiasis in HIV-1-infected Japanese men: clinical features and response to therapy.

    PubMed

    Watanabe, Koji; Gatanaga, Hiroyuki; Escueta-de Cadiz, Aleyla; Tanuma, Junko; Nozaki, Tomoyoshi; Oka, Shinichi

    2011-09-01

    Invasive amebic diseases caused by Entamoeba histolytica are increasing among men who have sex with men and co-infection of ameba and HIV-1 is an emerging problem in developed East Asian countries. To characterize the clinical and epidemiological features of invasive amebiasis in HIV-1 patients, the medical records of 170 co-infected cases were analyzed retrospectively, and E. histolytica genotype was assayed in 14 cases. In this series of HIV-1-infected patients, clinical presentation of invasive amebiasis was similar to that described in the normal host. High fever, leukocytosis and high CRP were associated with extraluminal amebic diseases. Two cases died from amebic colitis (resulting in intestinal perforation in one and gastrointestinal bleeding in one), and three cases died from causes unrelated to amebiasis. Treatment with metronidazole or tinidazole was successful in the other 165 cases. Luminal treatment was provided to 83 patients following metronidazole or tinidazole treatment. However, amebiasis recurred in 6 of these, a frequency similar to that seen in patients who did not receive luminal treatment. Recurrence was more frequent in HCV-antibody positive individuals and those who acquired syphilis during the follow-up period. Various genotypes of E. histolytica were identified in 14 patients but there was no correlation between genotype and clinical features. The outcome of metronidazole and tinidazole treatment of uncomplicated amebiasis was excellent even in HIV-1-infected individuals. Luminal treatment following metronidazole or tinidazole treatment does not reduce recurrence of amebiasis in high risk populations probably due to amebic re-infection. PMID:21931875

  12. Compensating and providing incentives for academic physicians: balancing earning, clinical, research, teaching, and administrative responsibilities.

    PubMed

    Ceriani, P J

    1992-04-01

    Providing a comprehensive compensation and incentive plan for a group of faculty members in a department with multiple goals provides a challenge that few administrators may take. Many academic departments have given up on implementing a comprehensive compensation and incentive plan since department goals generate competing uses of a faculty member's time. Whatever the plan design your department adopts, you can be sure that it will generate controversy. The JPN department has attempted to reward and encourage faculty members to pursue scholarly activities balanced with clinical activities. As a result, this strategy has only considered physicians who can generate both clinical income and research funding. Thus far, the JPN department faculty have embraced the plan. Long-term effects are not known as this is the first year of the plan. The measure of a successful total compensation program is one that develops a sense of entrepreneurship among its members to develop new clinical programs, to pursue new research collaborations, and to devise innovative methods of training. The program described in this article is not intended to serve as the ideal model for all departments, even in academic institutions, but rather to provide a strategy that may have applicability to many other departments where the goals induce inherent conflict for faculty members attempting to decide where to place their time commitments. In addition, this strategy does not work well on an individual basis for young, beginning faculty members but does work well in the collective--to promote the goals of the department. Be prepared, however, to modify your plan after a trial period of perhaps two years. You must allow time to monitor the effects of your compensation plan and its impact on the goals and direction of the department. PMID:10118362

  13. Clinical Predictors of Ketamine Response in Treatment-Resistant Major Depression

    PubMed Central

    Niciu, Mark J.; Luckenbaugh, David A.; Ionescu, Dawn F.; Guevara, Sara; Machado-Vieira, Rodrigo; Richards, Erica M.; Brutsche, Nancy E.; Nolan, Neal M.; Zarate, Carlos A.

    2015-01-01

    Objective The N-methyl-D-aspartate receptor antagonist ketamine has rapid antidepressant effects in treatment-resistant major depressive disorder (MDD) and bipolar depression. Clinical predictors may identify those more likely to benefit from ketamine within clinically-heterogeneous populations. Method Treatment-resistant inpatients with DSM-IV-TR-diagnosed MDD or bipolar I/II depression currently experiencing a moderate-to-severe major depressive episode were enrolled between November 2004 and March 2013. All subjects received a single subanesthetic (0.5mg/kg) ketamine infusion over 40 minutes. Patients were analyzed at the 230-minute post-infusion time point (N=108), at Day 1 (N=82), and at Day 7 (N=71). Univariate Pearson correlations were performed for each variable with change-from-baseline in the 17-item Hamilton Depression Rating Scale (HDRS). Multivariate linear regression was then conducted for statistically significant predictors (p<0.05, two-tailed). Results Higher body mass index (BMI) correlated with greater HDRS improvement at 230 minutes and at Day 1 (standardized β=−0.30, p=0.004), but not at Day 7 (standardized β=−0.18, p=0.10). Family history of an alcohol use disorder in a first-degree relative was associated with greater HDRS improvement at Day 1 (standardized β=−0.37, p=0.001) and Day 7 (standardized β=−0.41, p<0.001). No prior history of suicide attempt(s) was associated with greater improvement only at Day 7 (standardized β=0.28, p=0.01). The overall statistical model explained 13, 23, and 36 percent of HDRS percent change variance at 230 minutes, Day 1, and Day 7, respectively. Conclusion Despite its post-hoc nature, the study identified several clinical correlates of ketamine's rapid and durable antidepressant effects. Further investigation of these relationships is critical for individualized treatment of depression. PMID:24922494

  14. Clinical validity: Combinatorial pharmacogenomics predicts antidepressant responses and healthcare utilizations better than single gene phenotypes.

    PubMed

    Altar, C A; Carhart, J M; Allen, J D; Hall-Flavin, D K; Dechairo, B M; Winner, J G

    2015-10-01

    In four previous studies, a combinatorial multigene pharmacogenomic test (GeneSight) predicted those patients whose antidepressant treatment for major depressive disorder resulted in poorer efficacy and increased health-care resource utilizations. Here, we extended the analysis of clinical validity to the combined data from these studies. We also compared the outcome predictions of the combinatorial use of allelic variations in genes for four cytochrome P450 (CYP) enzymes (CYP2D6, CYP2C19, CYP2C9 and CYP1A2), the serotonin transporter (SLC6A4) and serotonin 2A receptor (HTR2A) with the outcome predictions for the very same subjects using traditional, single-gene analysis. Depression scores were measured at baseline and 8-10 weeks later for the 119 fully blinded subjects who received treatment as usual (TAU) with antidepressant standard of care, without the benefit of pharmacogenomic medication guidance. For another 96 TAU subjects, health-care utilizations were recorded in a 1-year, retrospective chart review. All subjects were genotyped after the clinical study period, and phenotype subgroups were created among those who had been prescribed a GeneSight panel medication that is a substrate for either CYP enzyme or serotonin effector protein. On the basis of medications prescribed for each subject at baseline, the combinatorial pharmacogenomic (CPGx™) GeneSight method categorized each subject into either a green ('use as directed'), yellow ('use with caution') or red category ('use with increased caution and with more frequent monitoring') phenotype, whereas the single-gene method categorized the same subjects with the traditional phenotype (for example, poor, intermediate, extensive or ultrarapid CYP metabolizer). The GeneSight combinatorial categorization approach discriminated and predicted poorer outcomes for red category patients prescribed medications metabolized by CYP2D6, CYP2C19 and CYP1A2 (P=0.0034, P=0.04 and P=0.03, respectively), whereas the single

  15. Clinical characteristics and response to therapy of autoimmune hepatitis in an urban Latino population

    PubMed Central

    Zahiruddin, Ayesha; Farahmand, Abtin; Gaglio, Paul; Massoumi, Hatef

    2016-01-01

    Aim: We hypothesized that AIH outcomes might be different in our patient population that consists of a large number of Latinos. Background: Literature has suggested that the presentation and outcome of autoimmune hepatitis can be different among different ethnicity and communities. Patients and methods: We performed a retrospective chart review of Latino patients with AIH diagnosed between 2002-2012. Complete and partial remissions were defined as normalization of liver enzyme values, or achieving less than twice the upper limit normal (ULN), respectively. Results: A total of 28 patients were identified. 26 (93%) were female. 13 (46%) had an acute presentation, one with type 2 AIH and 3 with ANA seronegative disease. The average pathologic stage (Ishak score) was 3.44±1.67 (range: 0-6). Complete and partial remission was achieved in 20 (71%) and 5 (18%) patients respectively. Ten patients (38%) required maintenance prednisone either alone (2), or in combination with Azathioprine (6) or Mycophenolate Mofetil (2). Remission in the majority of patients, including 14 (50%) who were cirrhotic. Six of 14 (43%) cirrhotic patients were asymptomatic at the time of diagnosis. Conclusion: In an urban Latino population, cirrhosis was the initial presentation of AIH in a significant percentage of patients raising concerns regarding insufficient screening for AIH in this patient population. A large number of patients required continuous prednisone to avoid relapse. PMID:27458516

  16. Blood Group O-Dependent Cellular Responses to Cholera Toxin: Parallel Clinical and Epidemiological Links to Severe Cholera.

    PubMed

    Kuhlmann, F Matthew; Santhanam, Srikanth; Kumar, Pardeep; Luo, Qingwei; Ciorba, Matthew A; Fleckenstein, James M

    2016-08-01

    Because O blood group has been associated with more severe cholera infections, it has been hypothesized that cholera toxin (CT) may bind non-O blood group antigens of the intestinal mucosae, thereby preventing efficient interaction with target GM1 gangliosides required for uptake of the toxin and activation of cyclic adenosine monophosphate (cAMP) signaling in target epithelia. Herein, we show that after exposure to CT, human enteroids expressing O blood group exhibited marked increase in cAMP relative to cells derived from blood group A individuals. Likewise, using CRISPR/Cas9 engineering, a functional group O line (HT-29-A(-/-)) was generated from a parent group A HT-29 line. CT stimulated robust cAMP responses in HT-29-A(-/-) cells relative to HT-29 cells. These findings provide a direct molecular link between blood group O expression and differential cellular responses to CT, recapitulating clinical and epidemiologic observations. PMID:27162272

  17. The study of responses to 'model' DNA breaks induced by restriction endonucleases in cells and cell-free systems: achievements and difficulties.

    PubMed

    Thacker, J

    1994-11-01

    The use of restriction endonucleases (RE) as a means of implicating DNA double-strand breaks (dsb) in cellular responses is reviewed. The introduction of RE into cells leads to many of the responses known to be characteristic of radiation damage--cell killing, chromosomal aberration, oncogenic transformation, gene mutation and amplification. Additionally, radiosensitive cell lines are hypersensitive to RE, including those from the human disorder ataxia-telangiectasia. However, quantitation of response and comparisons of the effectiveness of different RE are difficult, partly because of unknown activity and lifetime of RE in the cell. RE-induced dsb have also been used to reveal molecular mechanisms of repair and misrepair at specific sites in DNA. Dsb have been implicated in recombination processes including those leading to illegitimate rejoining (formation of deletions and rearrangements) at short sequence features in DNA. Also model dsb act as a signal to activate other cellular processes, which may influence or indirectly cause some responses, including cell death. In these signalling responses the detailed chemistry at the break site may not be very important, perhaps explaining why there is considerable overlap in responses to RE and to ionizing radiations. PMID:7983451

  18. Humoral Immune Response against Nontargeted Tumor Antigens after Treatment with Sipuleucel-T and Its Association with Improved Clinical Outcome

    PubMed Central

    GuhaThakurta, Debraj; Sheikh, Nadeem A.; Fan, Li-Qun; Kandadi, Harini; Meagher, T. Craig; Hall, Simon J.; Kantoff, Philip W.; Higano, Celestia S.; Small, Eric J.; Gardner, Thomas A.; Bailey, Kate; Vu, Tuyen; DeVries, Todd; Whitmore, James B.; Frohlich, Mark W.; Trager, James B.; Drake, Charles G.

    2016-01-01

    Purpose Antitumor activity of cancer immunotherapies may elicit immune responses to nontargeted (secondary) tumor antigens, or antigen spread. We evaluated humoral antigen spread after treatment with sipuleucel-T, an immunotherapy for asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC), designed to target prostatic acid phosphatase (PAP; primary antigen). Experimental Design Serum samples from patients with mCRPC enrolled in the placebo-controlled phase III IMPACT study (evaluable n = 142) were used to assess humoral antigen spread after treatment with sipuleucel-T. Immunoglobulin G (IgG) responses to self-antigens (including tumor antigens) were surveyed using protein microarrays and confirmed using Luminex xMAP. IgG responses were subsequently validated in ProACT (n = 33), an independent phase II study of sipuleucel-T. Association of IgG responses with overall survival (OS) was assessed using multivariate Cox models adjusted for baseline prostate-specific antigen (PSA) and lactate dehydrogenase levels. Results In patients from IMPACT and ProACT, levels of IgG against multiple secondary antigens, including PSA, KLK2/hK2, K-Ras, E-Ras, LGALS8/PCTA-1/galectin-8, and LGALS3/galectin-3, were elevated after treatment with sipuleucel-T (P < 0.01), but not control. IgG responses (≥2-fold elevation post-treatment) occurred in ≥25% of patients, appeared by 2 weeks after sipuleucel-T treatment, and persisted for up to 6 months. IgG responses to PSA and LGALS3 were associated with improved OS in sipuleucel-T–treated patients from IMPACT (P ≤ 0.05). Conclusions Sipuleucel-T induced humoral antigen spread in patients with mCRPC. IgG responses were associated with improved OS in IMPACT. The methods and results reported may identify pharmacodynamic biomarkers of clinical outcome after sipuleucel-T treatment, and help in clinical assessments of other cancer immunotherapies. PMID:25649018

  19. Analysis of factors in response to rotavirus vaccination counselling in a private paediatric clinic.

    PubMed

    Kannan Kutty, P; Pathmanathan, G; Salleh, N M

    2010-06-01

    Rotavirus vaccine is available as an optional vaccine in Malaysia. The counselling of optional vaccines is considered an integral part of the health services offered in a private paediatric clinic. While ensuring that all babies are up-todate with their compulsory immunization, counselling of optional vaccines like the rotavirus vaccine could give parents the choice to make an informed decision on the acceptance of this vaccine. Over a period of two years, we counselled the parents regarding diarrhoea caused by rotavirus disease and the rotavirus vaccine. In this study, the factors that were significantly associated with the acceptance of the rotavirus vaccine were the gender of the baby, the mother's age, the mother's occupation, the mode of payment for the vaccine, the number of previous visits to the clinic by the parents, the number of counselling sessions given to the parents and the pre-counselling awareness or knowledge of rotavirus disease and rotavirus vaccine. It is hoped that these findings may assist busy clinicians in their continuous efforts to provide health education and vaccination counselling to the parents of their patients. PMID:23756797

  20. Clinical Relevance of CYP2D6 Genetics for Tamoxifen Response in Breast Cancer

    PubMed Central

    Brauch, Hiltrud; Schroth, Werner; Eichelbaum, Michel; Schwab, Matthias; Harbeck, Nadia

    2008-01-01

    Summary Tamoxifen is a standard endocrine therapy for the prevention and treatment of steroid hormone receptor-positive breast cancer. Tamoxifen requires enzymatic activation by CYP 450 enzymes for the formation of clinically relevant metabolites, 4-OH-tamoxifen and endoxifen, which both have a greater affinity to the estrogen receptor and ability to inhibit cell proliferation when compared to the parent drug. CYP2D6 is the key enzyme in this biotransformation, and recent mechanistic, pharmacologic, and clinical pharmacogenetic evidence suggests that genetic variants and drug interaction by CYP2D6 inhibitors influence plasma concentrations of active tamoxifen metabolites and outcome of patients treated with adjuvant tamoxifen. Particularly, non-functional (poor metabolizer) and severely impaired (intermediate metabolizer) CYP2D6 variants are associated with higher recurrence rates. Accordingly, CYP2D6 genotyping prior to treatment for prediction of metabolizer status and outcome may open new avenues for the individualization of endocrine treatment choice and benefit. Moreover, strong CYP2D6 inhibitors such as the selective serotonin reuptake inhibitor paroxetine should be avoided as co-medication. PMID:20824020

  1. Idiopathic bile acid malabsorption--a review of clinical presentation, diagnosis, and response to treatment.

    PubMed Central

    Williams, A J; Merrick, M V; Eastwood, M A

    1991-01-01

    Between 1982 and 1989, the seven day retention of 75SeHCAT was measured in 181 patients with chronic diarrhoea that remained unexplained after full investigation. Altogether 121 of the 181 had a seven day 75SeHCAT retention greater than or equal to 15% and thus had no evidence of abnormal bile acid turnover. Twenty one had a seven day 75SeHCAT retention greater than or equal to 10% but less than 15%. Their clinical features were typical of the irritable bowel syndrome, and none of eight treated with cholestyramine showed symptomatic improvement. Sixteen patients had a seven day retention greater than or equal to 5% and less than 10%, six of whom had improved symptoms after treatment with bile acid chelating agents. The remaining 23 patients had a 75SeHCAT retention of less than 5% at seven days and responded to bile acid chelators. This group had a characteristic illness with intermittent watery diarrhoea, but no constitutional upset. It was not possible to distinguish the patients with bile acid malabsorption exclusively on the basis of the clinical symptoms and investigations, other than 75SeHCAT retention. We conclude that the measurement of 75SeHCAT retention is useful, appropriate, and necessary in patients with unexplained chronic diarrhoea. PMID:1916479

  2. Verbal conditioning of affect responses of process and reactive schizophrenics in a clinical interview situation.

    PubMed

    Pansa, M

    1979-06-01

    Sixteen process and 16 reactive schizoprenics out-patients were compared on a verbal conditioning task in an alternating conditioning-extinction design, using verbal and non-verbal positive social reinforcement to influence the emission of self-referred affect statements. It was found that process subjects failed to condition during the time periods used, while reactives demonstrated a significant trials effect showing trends consistent with those hypothesized from the type of design used. This differential conditionability between groups was shown not to be a function of diagnosis, sex, motivation, severity of illness, medication, hospitalization history, or general speech output. It was concluded that the degree of social responsiveness manifested in the premorbid history of the two groups is also operative in behaviour during the psychotic period, specifically, in responsiveness to positive social reinforcers in a verbal conditioning task. PMID:486358

  3. Different Candida parapsilosis clinical isolates and lipase deficient strain trigger an altered cellular immune response

    PubMed Central

    Tóth, Renáta; Alonso, Maria F.; Bain, Judith M.; Vágvölgyi, Csaba; Erwig, Lars-Peter; Gácser, Attila

    2015-01-01

    Numerous human diseases can be associated with fungal infections either as potential causative agents or as a result of changed immune status due to a primary disease. Fungal infections caused by Candida species can vary from mild to severe dependent upon the site of infection, length of exposure, and past medical history. Patients with impaired immune status are at increased risk for chronic fungal infections. Recent epidemiologic studies have revealed the increasing incidence of candidiasis caused by non-albicans species such as Candida parapsilosis. Due to its increasing relevance we chose two distinct C. parapsilosis strains, to describe the cellular innate immune response toward this species. In the first section of our study we compared the interaction of CLIB 214 and GA1 cells with murine and human macrophages. Both strains are commonly used to investigate C. parapsilosis virulence properties. CLIB 214 is a rapidly pseudohyphae-forming strain and GA1 is an isolate that mainly exists in a yeast form. Our results showed, that the phagocyte response was similar in terms of overall uptake, however differences were observed in macrophage migration and engulfment of fungal cells. As C. parapsilosis releases extracellular lipases in order to promote host invasion we further investigated the role of these secreted components during the distinct stages of the phagocytic process. Using a secreted lipase deficient mutant strain and the parental strain GA1 individually and simultaneously, we confirmed that fungal secreted lipases influence the fungi's virulence by detecting altered innate cellular responses. In this study we report that two isolates of a single species can trigger markedly distinct host responses and that lipase secretion plays a role on the cellular level of host–pathogen interactions. PMID:26528256

  4. Affective Neural Responses Modulated by Serotonin Transporter Genotype in Clinical Anxiety and Depression

    PubMed Central

    Oathes, Desmond J.; Hilt, Lori M.; Nitschke, Jack B.

    2015-01-01

    Serotonin transporter gene variants are known to interact with stressful life experiences to increase chances of developing affective symptoms, and these same variants have been shown to influence amygdala reactivity to affective stimuli in non-psychiatric populations. The impact of these gene variants on affective neurocircuitry in anxiety and mood disorders has been studied less extensively. Utilizing a triallelic assay (5-HTTLPR and rs25531) to assess genetic variation linked with altered serotonin signaling, this fMRI study investigated genetic influences on amygdala and anterior insula activity in 50 generalized anxiety disorder patients, 26 of whom also met DSM-IV criteria for social anxiety disorder and/or major depressive disorder, and 39 healthy comparison subjects. A Group x Genotype interaction was observed for both the amygdala and anterior insula in a paradigm designed to elicit responses in these brain areas during the anticipation of and response to aversive pictures. Patients who are S/LG carriers showed less activity than their LA/LA counterparts in both regions and less activity than S/LG healthy comparison subjects in the amygdala. Moreover, patients with greater insula responses reported higher levels of intolerance of uncertainty, an association that was particularly pronounced for patients with two LA alleles. A genotype effect was not established in healthy controls. These findings link the serotonin transporter gene to affective circuitry findings in anxiety and depression psychopathology and further suggest that its impact on patients may be different from effects typically observed in healthy populations. PMID:25675343

  5. Neurobiological markers predicting treatment response in anxiety disorders: A systematic review and implications for clinical application.

    PubMed

    Lueken, Ulrike; Zierhut, Kathrin C; Hahn, Tim; Straube, Benjamin; Kircher, Tilo; Reif, Andreas; Richter, Jan; Hamm, Alfons; Wittchen, Hans-Ulrich; Domschke, Katharina

    2016-07-01

    Anxiety disorders constitute the largest group of mental disorders with a high individual and societal burden. Neurobiological markers of treatment response bear potential to improve response rates by informing stratified medicine approaches. A systematic review was performed on the current evidence of the predictive value of genetic, neuroimaging and other physiological markers for treatment response (pharmacological and/or psychotherapeutic treatment) in anxiety disorders. Studies published until March 2015 were selected through search in PubMed, Web of Science, PsycINFO, Embase, and CENTRAL. Sixty studies were included, among them 27 on genetic, 17 on neuroimaging and 16 on other markers. Preliminary evidence was found for the functional 5-HTTLPR/rs25531 genotypes, anterior cingulate cortex function and cardiovascular flexibility to modulate treatment outcome. Studies varied considerably in methodological quality. Application of more stringent study methodology, predictions on the individual patient level and cross-validation in independent samples are recommended to set the next stage of biomarker research and to avoid flawed conclusions in the emerging field of "Mental Health Predictomics". PMID:27168345

  6. Ex Vivo Treatment Response of Primary Tumors and/or Associated Metastases for Preclinical and Clinical Development of Therapeutics

    PubMed Central

    Corben, Adriana D.; Uddin, Mohammad M.; Crawford, Brooke; Farooq, Mohammad; Modi, Shanu; Gerecitano, John; Chiosis, Gabriela; Alpaugh, Mary L.

    2015-01-01

    The molecular analysis of established cancer cell lines has been the mainstay of cancer research for the past several decades. Cell culture provides both direct and rapid analysis of therapeutic sensitivity and resistance. However, recent evidence suggests that therapeutic response is not exclusive to the inherent molecular composition of cancer cells but rather is greatly influenced by the tumor cell microenvironment, a feature that cannot be recapitulated by traditional culturing methods. Even implementation of tumor xenografts, though providing a wealth of information on drug delivery/efficacy, cannot capture the tumor cell/microenvironment crosstalk (i.e., soluble factors) that occurs within human tumors and greatly impacts tumor response. To this extent, we have developed an ex vivo (fresh tissue sectioning) technique which allows for the direct assessment of treatment response for preclinical and clinical therapeutics development. This technique maintains tissue integrity and cellular architecture within the tumor cell/microenvironment context throughout treatment response providing a more precise means to assess drug efficacy. PMID:25350385

  7. Cardiovascular Safety Assessment in Early-Phase Clinical Studies: A Meta-Analytical Comparison of Exposure-Response Models.

    PubMed

    Conrado, D J; Chen, D; Denney, W S

    2016-06-01

    Exposure-response analysis of QT interval in clinical studies has been proposed as a thorough QT study alternative. Many exposure-response model structures have been proposed for cardiovascular (CV) safety markers, but few studies have compared models across multiple drugs. To recommend preferred drug-effect exposure-response models on vital signs and electrocardiogram (ECG) intervals, an individual-level model-based meta-analysis (39 studies and 1,291 subjects) compared 90 model structures. Models were selected to describe the data and cross-validate studies on the same drug. The most commonly selected baseline model was an unstructured model (estimation of a value at each study nominal time) for all measures but blood pressure. The unstructured model estimated a better cross-validated drug-effect when considering all markers. A linear model was the most commonly selected to characterize drug-effect on all markers. We propose these models as a starting point assisting with CV safety exposure-response assessment in nondedicated small studies with healthy subjects. PMID:27318037

  8. Diagnostic Clinical and Laboratory Findings in Response to Predetermining Bacterial Pathogen: Data from the Meningitis Registry

    PubMed Central

    Karanika, Maria; Vasilopoulou, Vasiliki A.; Katsioulis, Antonios T.; Papastergiou, Panagiotis; Theodoridou, Maria N.; Hadjichristodoulou, Christos S.

    2009-01-01

    Background Childhood Meningitis continues to be an important cause of mortality in many countries. The search for rapid diagnosis of acute bacterial meningitis has lead to the further exploration of prognostic factors. This study was scheduled in an attempt to analyze various clinical symptoms as well as rapid laboratory results and provide an algorithm for the prediction of specific bacterial aetiology of childhood bacterial meningitis. Methodology and Principal Findings During the 32 year period, 2477 cases of probable bacterial meningitis (BM) were collected from the Meningitis Registry (MR). Analysis was performed on a total of 1331 confirmed bacterial meningitis cases of patients aged 1 month to 14 years. Data was analysed using EPI INFO (version 3.4.3-CDC-Atlanta) and SPSS (version 15.0 - Chicago) software. Statistically significant (p<0.05) variables were included in a conditional backward logistic regression model. A total of 838 (63.0%) attributed to Neisseria meningitidis, 252 (18.9%) to Haemophilus influenzae, 186 (14.0%) to Streptococcus pneumoniae and 55 (4.1%) due to other bacteria. For the diagnosis of Meningococcal Meningitis, the most significant group of diagnostic criteria identified included haemorrhagic rash (OR 22.36), absence of seizures (OR 2.51), headache (OR 1.83) and negative gram stain result (OR 1.55) with a Positive Predictive Value (PPV) of 96.4% (95%CI 87.7–99.6). For the diagnosis of Streptococcus pneumoniae, the most significant group of diagnostic criteria identified included absence of haemorrhagic rash (OR 13.62), positive gram stain (OR 2.10), coma (OR 3.11), seizures (OR 3.81) and peripheral WBC≥15000/µL (OR 2.19) with a PPV of 77.8% (95%CI 40.0–97.2). For the diagnosis of Haemophilus influenzae, the most significant group of diagnostic criteria included, absence of haemorrhagic rash (OR 13.61), age≥1year (OR 2.04), absence of headache (OR 3.01), CSF Glu<40 mg/dL (OR 3.62) and peripheral WBC<15000/µL (OR 1.74) with a

  9. Role of pill-taking, expectation and therapeutic alliance in the placebo response in clinical trials for major depression

    PubMed Central

    Leuchter, Andrew F.; Hunter, Aimee M.; Tartter, Molly; Cook, Ian A.

    2014-01-01

    Background Pill-taking, expectations and therapeutic alliance may account for much of the benefit of medication and placebo treatment for major depressive disorder (MDD). Aims To examine the effects of medication, placebo and supportive care on treatment outcome, and the relationships of expectations and therapeutic alliance to improvement. Method A total of 88 participants were randomised to 8 weeks of treatment with supportive care alone or combined with double-blind treatment with placebo or antidepressant medication. Expectations of medication effectiveness, general treatment effectiveness and therapeutic alliance were measured (trial registration at ClinicalTrials.gov: NCT00200902). Results Medication or placebo plus supportive care were not significantly different but had significantly better outcome than supportive care alone. Therapeutic alliance predicted response to medication and placebo; expectations of medication effectiveness at enrolment predicted only placebo response. Conclusions Pill treatment yielded better outcome than supportive care alone. Medication expectations uniquely predicted placebo treatment outcome and were formed by time of enrolment, suggesting that they were shaped by prior experiences outside the clinical trial. PMID:25213159

  10. Clinical and cellular roles for TDP1 and TOP1 in modulating colorectal cancer response to irinotecan

    PubMed Central

    Meisenberg, Cornelia; Gilbert, Duncan C; Chalmers, Anthony; Haley, Vikki; Gollins, Simon; Ward, Simon E.; El-Khamisy, Sherif F.

    2014-01-01

    Colorectal cancer (CRC) is the third most common cancer in the world. Despite surgery, up to 50% of patients relapse with incurable disease. First line chemotherapy utilises the topoisomerase 1 (TOP1) poison irinotecan, which triggers cell death by trapping TOP1 on DNA. The removal of TOP1 peptide from TOP1-DNA breaks is conducted by tyrosyl DNA phosphodiesterase 1 (TDP1). Despite putative roles for TDP1 and TOP1 in CRC, their role in cellular and clinical responses to TOP1 targeting therapies remains unclear. Here, we show varying expression levels of TOP1 and TDP1 polypeptides in multiple CRC cell lines and in clinical CRC samples. TDP1 overexpression or TOP1 depletion is protective. Conversely, TDP1 depletion increases DNA strand breakage and hypersensitivity to irinotecan in a TOP1 dependent manner, presenting a potential therapeutic opportunity in CRC. TDP1 protein levels correlate well with mRNA and with TDP1 catalytic activity. However, no correlation is observed between inherent TDP1 or TOP1 levels alone and irinotecan sensitivity, pointing at their limited utility as predictive biomarkers in CRC. These findings establish TDP1 as a potential therapeutic target for the treatment of CRC and question the validity of TOP1 or TDP1 on their own as predictive biomarkers for irinotecan response. PMID:25522766

  11. The Comparison of Inflammatory Responses and Clinical Results After Groin Hernia Repair Using Polypropylene or Polyester Meshes.

    PubMed

    Bulbuller, N; Kirkil, C; Godekmerdan, A; Aygen, E; Ilhan, Y S

    2015-12-01

    The aim of this study was to compare the clinical results and the inflammatory responses against polypropylene and polyester meshes after groin hernia repair. Ninety patients with unilateral inguinal hernia randomly underwent Shouldice herniorrhaphy or Lichtenstein hernioplasty using polypropylene or polyester meshes. Venous blood samples were collected to evaluate serum interleukin-6 (IL-6) and C-reactive protein (CRP) levels. Postoperative acute and chronic pain and time to attain to normal activities were evaluated. IL-6 levels decreased to preoperative levels in all groups at 48th hour. CRP levels of mesh-implanted groups are significantly higher than preoperative level at 48th hour, while it reduced to preoperative level in Shouldice herniorrhaphy group. Patients treated with mesh repair had less postoperative acute pain and recovered more rapidly than those who underwent Shouldice herniorrhaphy. It was concluded that polypropylene and polyester meshes used in hernia repair caused similar inflammatory responses and that clinical results after groin hernia repair with these prostheses were not significantly different. PMID:26730010

  12. [Dermatology - the key to ensure a good long term clinical response].

    PubMed

    Sahil, Maral; Boehncke, Wolf-Henning

    2016-01-13

    After efficacy and safety have been used for many years to evaluate therapies and treatment success in medicine, patient reported outcomes are now increasingly being incorported in this process. This trend acknowledges that patient adherence is a prerequisit for the good long-term outcome of a treatment. In the field of dermatology, namely for psoriasis, current guidelines already recommend to base clinical decision-making on a combination of objective as well as patient-reported outcomes. These parameters provide the basis for the concept of happy drug survival, building on the belief that a good quality of life reflects meaningful treatment success from the patient's point of view, motivating him to carry on with the therapy. PMID:26946698

  13. Design, clinical translation and immunological response of biomaterials in regenerative medicine

    NASA Astrophysics Data System (ADS)

    Sadtler, Kaitlyn; Singh, Anirudha; Wolf, Matthew T.; Wang, Xiaokun; Pardoll, Drew M.; Elisseeff, Jennifer H.

    2016-07-01

    The field of regenerative medicine aims to replace tissues lost as a consequence of disease, trauma or congenital abnormalities. Biomaterials serve as scaffolds for regenerative medicine to deliver cells, provide biological signals and physical support, and mobilize endogenous cells to repair tissues. Sophisticated chemistries are used to synthesize materials that mimic and modulate native tissue microenvironments, to replace form and to elucidate structure–function relationships of cell–material interactions. The therapeutic relevance of these biomaterial properties can only be studied after clinical translation, whereby key parameters for efficacy can be defined and then used for future design. In this Review, we present the development and translation of biomaterials for two tissue engineering targets, cartilage and cornea, both of which lack the ability to self-repair. Finally, looking to the future, we discuss the role of the immune system in regeneration and the potential for biomaterial scaffolds to modulate immune signalling to create a pro-regenerative environment.

  14. Clinical responses to rituximab in a case of neuroblastoma with refractory opsoclonus myoclonus ataxia syndrome.

    PubMed

    Alavi, Samin; Kord Valeshabad, Ali; Moradveisi, Borhan; Aminasnafi, Ali; Arzanian, Mohammad Taghi

    2012-01-01

    Opsoclonus myoclonus ataxia syndrome (OMS) is a rare neurologic syndrome. In a high proportion of children, it is associated with neuroblastoma. The etiology of this condition is thought to be immune mediated. In children, immunotherapy with conventional treatments such as corticosteroids, intravenous immunoglobulin, adrenocorticotropic hormone, and even antiepileptic drugs has been tried. Recently rituximab has been used safely for refractory OMS in children with neuroblastoma. Our patient was a 3.5-year-old girl referred for ataxia and dancing eye movements starting since 1.5 years ago. She was diagnosed with neuroblastoma on imaging studies on admission. The OMS was refractory to surgical resection, chemotherapy, corticosteroids, and intravenous immunoglobulin. Patient received rituximab simultaneously with chemotherapy. The total severity score decreased by 61.1% after rituximab. Patient's ataxia markedly improved that she was able to walk independently after 6 months. Our case confirmed the clinical efficacy and safety of rituximab in a refractory case of OMS. PMID:23198199

  15. fMRI investigation of response inhibition, emotion, impulsivity, and clinical high-risk behavior in adolescents

    PubMed Central

    Brown, Matthew R. G.; Benoit, James R. A.; Juhás, Michal; Dametto, Ericson; Tse, Tiffanie T.; MacKay, Marnie; Sen, Bhaskar; Carroll, Alan M.; Hodlevskyy, Oleksandr; Silverstone, Peter H.; Dolcos, Florin; Dursun, Serdar M.; Greenshaw, Andrew J.

    2015-01-01

    High-risk behavior in adolescents is associated with injury, mental health problems, and poor outcomes in later life. Improved understanding of the neurobiology of high-risk behavior and impulsivity shows promise for informing clinical treatment and prevention as well as policy to better address high-risk behavior. We recruited 21 adolescents (age 14–17) with a wide range of high-risk behavior tendencies, including medically high-risk participants recruited from psychiatric clinics. Risk tendencies were assessed using the Adolescent Risk Behavior Screen (ARBS). ARBS risk scores correlated highly (0.78) with impulsivity scores from the Barratt Impulsivity scale (BIS). Participants underwent 4.7 Tesla functional magnetic resonance imaging (fMRI) while performing an emotional Go/NoGo task. This task presented an aversive or neutral distractor image simultaneously with each Go or NoGo stimulus. Risk behavior and impulsivity tendencies exhibited similar but not identical associations with fMRI activation patterns in prefrontal brain regions. We interpret these results as reflecting differences in response inhibition, emotional stimulus processing, and emotion regulation in relation to participant risk behavior tendencies and impulsivity levels. The results are consistent with high impulsivity playing an important role in determining high risk tendencies in this sample containing clinically high-risk adolescents. PMID:26483645

  16. MicroRNAs are involved in cervical cancer development, progression, clinical outcome and improvement treatment response (Review).

    PubMed

    González-Quintana, Víctor; Palma-Berré, Lizbeth; Campos-Parra, Alma D; López-Urrutia, Eduardo; Peralta-Zaragoza, Oscar; Vazquez-Romo, Rafael; Pérez-Plasencia, Carlos

    2016-01-01

    Cervical cancer (CC) is the third most diagnosed cancer among females worldwide and the fourth cause of cancer-related mortality. Prophylactic HPV vaccines and traditional pap-smear screening are undoubtedly capable of decreasing the incidence and mortality of CC. However, a large number of females succumb to the disease each year due to late diagnosis and resistance to conventional treatments. Thus, it is necessary to identify new molecular markers to predict the clinical outcome and to design powerful treatments. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and are involved in the modulation of several cell pathways associated with progression from pre-malignant to invasive and metastatic disease, increasing tumor malignancy. The aim of this review was to summarize the recent data that describe the important role of miRNAS involved in CC in order to determine their potential as prognostic biomarkers and as therapy targets. Studies of >40 miRNAs with roles in cancer regulation were identified. We also identified 17 miRNAs associated with progression, 12 involved with clinical outcome and 7 that improved CC treatment response. The present review is expected to broaden understanding of the functional role and potential clinical uses of miRNAs in CC. PMID:26530778

  17. Psychoneurometric operationalization of threat sensitivity: Relations with clinical symptom and physiological response criteria.

    PubMed

    Yancey, James R; Venables, Noah C; Patrick, Christopher J

    2016-03-01

    The National Institute of Mental Health's Research Domain Criteria (RDoC) initiative calls for the incorporation of neurobiological approaches and findings into conceptions of mental health problems through a focus on biobehavioral constructs investigated across multiple domains of measurement (units of analysis). Although the constructs in the RDoC system are characterized in "process terms" (i.e., as functional concepts with brain and behavioral referents), these constructs can also be framed as dispositions (i.e., as dimensions of variation in biobehavioral functioning across individuals). Focusing on one key RDoC construct, acute threat or "fear," the current article illustrates a construct-oriented psychoneurometric strategy for operationalizing this construct in individual difference terms-as threat sensitivity (THT+). Utilizing data from 454 adult participants, we demonstrate empirically that (a) a scale measure of THT+ designed to tap general fear/fearlessness predicts effectively to relevant clinical problems (i.e., fear disorder symptoms), (b) this scale measure shows reliable associations with physiological indices of acute reactivity to aversive visual stimuli, and (c) a cross-domain factor reflecting the intersection of scale and physiological indicators of THT+ predicts effectively to both clinical and neurophysiological criterion measures. Results illustrate how the psychoneurometric approach can be used to create a dimensional index of a biobehavioral trait construct, in this case THT+, which can serve as a bridge between phenomena in domains of psychopathology and neurobiology. Implications and future directions are discussed with reference to the RDoC initiative and existing report-based conceptions of psychological traits. PMID:26877132

  18. Validity and responsiveness to change of clinically derived MDS scales in Alzheimer disease outcomes research.

    PubMed

    Smart, Kelly A; Herrmann, Nathan; Lanctôt, Krista L

    2011-06-01

    This analysis assessed 3 subscales derived from the nursing home Minimum Data Set (MDS), the Cognitive Performance Scale (CPS), Depression Rating Scale (DRS), and Aggressive Behavior Scale (ABS), as outcome measures in clinical trials of long-term care residents with Alzheimer disease (AD). A total of 26 patients with moderate-to-severe AD and agitation/aggression enrolled in a trial of memantine were assessed using the Mini-Mental State Examination (MMSE), Neuropsychiatric Inventory Nursing Home Version (NPI-NH), and the Cohen-Mansfield Agitation Inventory (CMAI) administered by trained researchers. MDS data were collected as part of their standard clinical care. The MDS subscales correlated significantly with their corresponding research scales: CPS and MMSE (r = -0.57, P = .003); DRS and NPI-NH total (r = 0.42, P = .038); DRS and NPI-NH depression (r = 0.41, P = .04), and ABS and CMAI (r = 0.54, P = .004). DRS and ABS scores did not change significantly from baseline to 3 months though the NPI-NH and CMAI did, indicating limited sensitivity to change. This suggests that the MDS subscales measure comparable aspects of cognitive function and depressive and agitated/aggressive behavior as the MMSE, NPI-NH, and CMAI. However, this analysis also suggests that sensitivity to change of the DRS and ABS may be limited compared to the NPI-NH and CMAI. As these findings are preliminary, further research is needed to determine the utility of MDS scales in outcomes research. PMID:21460341

  19. Near-Infrared Spectroscopy in Schizophrenia: A Possible Biomarker for Predicting Clinical Outcome and Treatment Response

    PubMed Central

    Koike, Shinsuke; Nishimura, Yukika; Takizawa, Ryu; Yahata, Noriaki; Kasai, Kiyoto

    2013-01-01

    Functional near-infrared spectroscopy (fNIRS) is a relatively new technique that can measure hemoglobin changes in brain tissues, and its use in psychiatry has been progressing rapidly. Although it has several disadvantages (e.g., relatively low spatial resolution and the possibility of shallow coverage in the depth of brain regions) compared with other functional neuroimaging techniques (e.g., functional magnetic resonance imaging and positron emission tomography), fNIRS may be a candidate instrument for clinical use in psychiatry, as it can measure brain activity in naturalistic position easily and non-invasively. fNIRS instruments are also small and work silently, and can be moved almost everywhere including schools and care units. Previous fNIRS studies have shown that patients with schizophrenia have impaired activity and characteristic waveform patterns in the prefrontal cortex during the letter version of the verbal fluency task, and part of these results have been approved as one of the Advanced Medical Technologies as an aid for the differential diagnosis of depressive symptoms by the Ministry of Health, Labor and Welfare of Japan in 2009, which was the first such approval in the field of psychiatry. Moreover, previous studies suggest that the activity in the frontopolar prefrontal cortex is associated with their functions in chronic schizophrenia and is its next candidate biomarker. Future studies aimed at exploring fNIRS differences in various clinical stages, longitudinal changes, drug effects, and variations during different task paradigms will be needed to develop more accurate biomarkers that can be used to aid differential diagnosis, the comprehension of the present condition, the prediction of outcome, and the decision regarding treatment options in schizophrenia. Future fNIRS researches will require standardized measurement procedures, probe settings, analytical methods and tools, manuscript description, and database systems in an fNIRS community

  20. Variations in myo-inositol in fronto-limbic regions and clinical response to electroconvulsive therapy in major depression.

    PubMed

    Njau, Stephanie; Joshi, Shantanu H; Leaver, Amber M; Vasavada, Megha; Van Fleet, Jessica; Espinoza, Randall; Narr, Katherine L

    2016-09-01

    Though electroconvulsive therapy (ECT) is an established treatment for severe depression, the neurobiological factors accounting for the clinical effects of ECT are largely unknown. Myo-inositol, a neurometabolite linked with glial activity, is reported as reduced in fronto-limbic regions in patients with depression. Whether changes in myo-inositol relate to the antidepressant effects of ECT is unknown. Using magnetic resonance spectroscopy ((1)H-MRS), we measured dorsomedial anterior cingulate cortex (dmACC) and left and right hippocampal myo-inositol in 50 ECT patients (mean age: 43.78, 14 SD) and 33 controls (mean age: 39.33, 12 SD) to determine cross sectional effects of diagnosis and longitudinal effects of ECT. Patients were scanned prior to treatment, after the second ECT and at completion of the ECT index series. Controls were scanned twice at intervals corresponding to patients' baseline and end of treatment scans. Myo-inositol increased over the course of ECT in the dmACC (p = 0.042). A significant hemisphere by clinical response effect was observed for the hippocampus (p = 0.003) where decreased myo-inositol related to symptom improvement in the left hippocampus. Cross-sectional differences between patients and controls at baseline were not detected. Changes in myo-inositol observed in the dmACC in association with ECT and in the hippocampus in association with ECT-related clinical response suggest the mechanisms of ECT could include gliogenesis or a reversal of gliosis that differentially affect dorsal and ventral limbic regions. Change in dmACC myo-inositol diverged from control values with ECT suggesting compensation, while hippocampal change suggested normalization. PMID:27285661

  1. Non-Esterified Fatty Acids Profiling in Rheumatoid Arthritis: Associations with Clinical Features and Th1 Response

    PubMed Central

    Rodríguez-Carrio, Javier; Alperi-López, Mercedes; López, Patricia; Ballina-García, Francisco Javier; Suárez, Ana

    2016-01-01

    Objectives Since lipid compounds are known to modulate the function of CD4+ T-cells and macrophages, we hypothesize that altered levels of serum non-esterified fatty acids (NEFA) may underlie rheumatoid arthritis (RA) pathogenesis. Methods Serum levels of NEFA (palmitic, stearic, palmitoleic, oleic, linoleic, γ-linoleic, arachidonic –AA–, linolenic, eicosapentaenoic –EPA– and docosahexaenoic –DHA–) were quantified by LC-MS/MS after methyl-tert-butylether (MTBE)-extraction in 124 RA patients and 56 healthy controls (HC). CD4+ phenotype was studied by flow cytometry. TNFα, IL-8, VEGF, GM-CSF, IFNγ, IL-17, CCL2, CXCL10, leptin and resistin serum levels were quantified by immunoassays. The effect of FA on IFNγ production by PBMC was evaluated in vitro. Results Lower levels of palmitic (p<0.0001), palmitoleic (p = 0.002), oleic (p = 0.010), arachidonic (p = 0.027), EPA (p<0.0001) and DHA (p<0.0001) were found in RA patients, some NEFA being altered at onset. Cluster analysis identified a NEFA profile (hallmarked by increased stearic and decreased EPA and DHA) overrepresented in RA patients compared to HC (p = 0.002), being associated with clinical features (RF, shared epitope and erosions), increased IFNγ expression in CD4+ T-cells (p = 0.002) and a Th1-enriched serum milieu (IFNγ, CCL2 and CXCL10, all p<0.005). In vitro assays demonstrated that imbalanced FA could underlie IFNγ production by CD4+ T-cells. Finally, changes on NEFA levels were associated with clinical response upon TNFα-blockade. Conclusion An altered NEFA profile can be found in RA patients associated with clinical characteristics of aggressive disease and enhanced Th1 response. These results support the relevance of lipidomic studies in RA and provide a rationale for new therapeutic targets. PMID:27487156

  2. Affective neural responses modulated by serotonin transporter genotype in clinical anxiety and depression.

    PubMed

    Oathes, Desmond J; Hilt, Lori M; Nitschke, Jack B

    2015-01-01

    Serotonin transporter gene variants are known to interact with stressful life experiences to increase chances of developing affective symptoms, and these same variants have been shown to influence amygdala reactivity to affective stimuli in non-psychiatric populations. The impact of these gene variants on affective neurocircuitry in anxiety and mood disorders has been studied less extensively. Utilizing a triallelic assay (5-HTTLPR and rs25531) to assess genetic variation linked with altered serotonin signaling, this fMRI study investigated genetic influences on amygdala and anterior insula activity in 50 generalized anxiety disorder patients, 26 of whom also met DSM-IV criteria for social anxiety disorder and/or major depressive disorder, and 39 healthy comparison subjects. A Group x Genotype interaction was observed for both the amygdala and anterior insula in a paradigm designed to elicit responses in these brain areas during the anticipation of and response to aversive pictures. Patients who are S/L(G) carriers showed less activity than their L(A)/L(A) counterparts in both regions and less activity than S/L(G) healthy comparison subjects in the amygdala. Moreover, patients with greater insula responses reported higher levels of intolerance of uncertainty, an association that was particularly pronounced for patients with two LA alleles. A genotype effect was not established in healthy controls. These findings link the serotonin transporter gene to affective circuitry findings in anxiety and depression psychopathology and further suggest that its impact on patients may be different from effects typically observed in healthy populations. PMID:25675343

  3. Clinical decision-making: midwifery students' recognition of, and response to, post partum haemorrhage in the simulation environment

    PubMed Central

    2012-01-01

    Background This paper reports the findings of a study of how midwifery students responded to a simulated post partum haemorrhage (PPH). Internationally, 25% of maternal deaths are attributed to severe haemorrhage. Although this figure is far higher in developing countries, the risk to maternal wellbeing and child health problem means that all midwives need to remain vigilant and respond appropriately to early signs of maternal deterioration. Methods Simulation using a patient actress enabled the research team to investigate the way in which 35 midwifery students made decisions in a dynamic high fidelity PPH scenario. The actress wore a birthing suit that simulated blood loss and a flaccid uterus on palpation. The scenario provided low levels of uncertainty and high levels of relevant information. The student's response to the scenario was videoed. Immediately after, they were invited to review the video, reflect on their performance and give a commentary as to what affected their decisions. The data were analysed using Dimensional Analysis. Results The students' clinical management of the situation varied considerably. Students struggled to prioritise their actions where more than one response was required to a clinical cue and did not necessarily use mnemonics as heuristic devices to guide their actions. Driven by a response to single cues they also showed a reluctance to formulate a diagnosis based on inductive and deductive reasoning cycles. This meant they did not necessarily introduce new hypothetical ideas against which they might refute or confirm a diagnosis and thereby eliminate fixation error. Conclusions The students response demonstrated that a number of clinical skills require updating on a regular basis including: fundal massage technique, the use of emergency standing order drugs, communication and delegation of tasks to others in an emergency and working independently until help arrives. Heuristic devices helped the students to evaluate their

  4. Etomidate Anesthesia during ERCP Caused More Stable Haemodynamic Responses Compared with Propofol: A Randomized Clinical Trial

    PubMed Central

    Song, Jin-Chao; Lu, Zhi-Jie; Jiao, Ying-Fu; Yang, Bin; Gao, Hao; Zhang, Jinmin; Yu, Wei-Feng

    2015-01-01

    Background: Propofol may result in hypotension and respiratory depression, while etomidate is considered to be a safe induction agent for haemodynamically unstable patients because of its low risk of hypotension. We hypothesized that etomidate anesthesia during ERCP caused more stable haemodynamic responses compared with propofol. The primary endpoint was to compare the haemodynamic effects of etomidate vs. propofol in ERCP cases. The secondary endpoint was overall survival. Methods: A total of 80 patients undergoing ERCP were randomly assigned to an etomidate or propofol group. Patients in the etomidate group received etomidate induction and maintenance during ERCP, and patients in the propofol group received propofol induction and maintenance. Cardiovascular parameters and procedure-related time were measured and recorded during ERCP. Results: The average percent change to baseline in MBP was -8.4±7.8 and -14.4±9.4 with P = 0.002, and in HR was 1.8±16.6 and 2.4±16.3 with P = 0.874 in the etomidate group and the propofol group, respectively. MBP values in the etomidate group decreased significantly less than those in the propofol group (P<0.05). The ERCP duration and recovery time in both groups was similar. There was no significant difference in the survival rates between groups ( p = 0.942). Conclusions: Etomidate anesthesia during ERCP caused more stable haemodynamic responses compared with propofol. PMID:26180512

  5. Contributions of GABA to alcohol responsivity during adolescence: Insights from preclinical and clinical studies

    PubMed Central

    Silveri, Marisa M.

    2015-01-01

    There is a considerable body of literature demonstrating that adolescence is a unique age period, which includes rapid and dramatic maturation of behavioral, cognitive, hormonal and neurobiological systems. Most notably, adolescence is also a period of unique responsiveness to alcohol effects, with both hyposensitivity and hypersensitivity observed to the various effects of alcohol. Multiple neurotransmitter systems are undergoing fine-tuning during this critical period of brain development, including those that contribute to the rewarding effects of drugs of abuse. The role of developmental maturation of the γ-amino-butyric acid (GABA) system, however, has received less attention in contributing to age-specific alcohol sensitivities. This review integrates GABA findings from human magnetic resonance spectroscopy studies as they may translate to understanding adolescent-specific responsiveness to alcohol effects. Better understanding of the vulnerability of the GABA system both during adolescent development, and in psychiatric conditions that include alcohol dependence, could point to a putative mechanism, boosting brain GABA, that may have increased effectiveness for treating alcohol abuse disorders. PMID:24631274

  6. Clinical and MRI responses to etanercept in early non-radiographic axial spondyloarthritis: 48-week results from the EMBARK study

    PubMed Central

    Maksymowych, Walter P; Dougados, Maxime; Sieper, Joachim; Braun, Jürgen; Citera, Gustavo; Van den Bosch, Filip; Logeart, Isabelle; Wajdula, Joseph; Jones, Heather; Marshall, Lisa; Bonin, Randi; Pedersen, Ron; Vlahos, Bonnie; Kotak, Sameer; Bukowski, Jack F

    2016-01-01

    Objective To evaluate the efficacy and safety of etanercept (ETN) after 48 weeks in patients with early active non-radiographic axial spondyloarthritis (nr-axSpA). Methods Patients meeting Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axSpA, but not modified New York radiographic criteria, received double-blind ETN 50 mg/week or placebo (PBO) for 12 weeks, then open-label ETN (ETN/ETN or PBO/ETN). Clinical, health, productivity, MRI and safety outcomes were assessed and the 48-week data are presented here. Results 208/225 patients (92%) entered the open-label phase at week 12 (ETN, n=102; PBO, n=106). The percentage of patients achieving ASAS40 increased from 33% to 52% between weeks 12 and 48 for ETN/ETN and from 15% to 53% for PBO/ETN (within-group p value <0.001 for both). For ETN/ETN and PBO/ETN, the EuroQol 5 Dimensions utility score improved by 0.14 and 0.08, respectively, between baseline and week 12 and by 0.23 and 0.22 between baseline and week 48. Between weeks 12 and 48, MRI Spondyloarthritis Research Consortium of Canada sacroiliac joint (SIJ) scores decreased by −1.1 for ETN/ETN and by −3.0 for PBO/ETN, p<0.001 for both. Decreases in MRI SIJ inflammation and C-reactive protein correlated with several clinical outcomes at weeks 12 and 48. Conclusions Patients with early active nr-axSpA demonstrated improvement from week 12 in clinical, health, productivity and MRI outcomes that was sustained to 48 weeks. Trial registration number NCT01258738. PMID:26269397

  7. Optimizing supercritical carbon dioxide in the inactivation of bacteria in clinical solid waste by using response surface methodology

    SciTech Connect

    Hossain, Md. Sohrab; Nik Ab Rahman, Nik Norulaini; Balakrishnan, Venugopal; Alkarkhi, Abbas F.M.; Ahmad Rajion, Zainul; Ab Kadir, Mohd Omar

    2015-04-15

    Highlights: • Supercritical carbon dioxide sterilization of clinical solid waste. • Inactivation of bacteria in clinical solid waste using supercritical carbon dioxide. • Reduction of the hazardous exposure of clinical solid waste. • Optimization of the supercritical carbon dioxide experimental conditions. - Abstract: Clinical solid waste (CSW) poses a challenge to health care facilities because of the presence of pathogenic microorganisms, leading to concerns in the effective sterilization of the CSW for safe handling and elimination of infectious disease transmission. In the present study, supercritical carbon dioxide (SC-CO{sub 2}) was applied to inactivate gram-positive Staphylococcus aureus, Enterococcus faecalis, Bacillus subtilis, and gram-negative Escherichia coli in CSW. The effects of SC-CO{sub 2} sterilizatio