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Sample records for achieved clinical response

  1. 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

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

    PubMed

    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.

  3. Achieving deeper molecular response is associated with a better clinical outcome in chronic myeloid leukemia patients on imatinib front-line therapy

    PubMed Central

    Etienne, Gabriel; Dulucq, Stéphanie; Nicolini, Franck-Emmanuel; Morisset, Stéphane; Fort, Marie-Pierre; Schmitt, Anna; Etienne, Madeleine; Hayette, Sandrine; Lippert, Eric; Bureau, Caroline; Tigaud, Isabelle; Adiko, Didier; Marit, Gérald; Reiffers, Josy; Mahon, François-Xavier

    2014-01-01

    Sustained imatinib treatment in chronic myeloid leukemia patients can result in complete molecular response allowing discontinuation without relapse. We set out to evaluate the frequency of complete molecular response in imatinib de novo chronic phase chronic myeloid leukemia patients, to identify base-line and under-treatment predictive factors of complete molecular response in patients achieving complete cytogenetic response, and to assess if complete molecular response is associated with a better outcome. A random selection of patients on front-line imatinib therapy (n=266) were considered for inclusion. Complete molecular response was confirmed and defined as MR 4.5 with undetectable BCR-ABL transcript levels. Median follow up was 4.43 years (range 0.79–10.8 years). Sixty-five patients (24%) achieved complete molecular response within a median time of 32.7 months. Absence of spleen enlargement at diagnosis, achieving complete cytogenetic response before 12 months of therapy, and major molecular response during the year following complete cytogenetic response was predictive of achieving further complete molecular response. Patients who achieved complete molecular response had better event-free and failure-free survivals than those with complete cytogenetic response irrespective of major molecular response status (95.2% vs. 64.7% vs. 27.7%, P=0.00124; 98.4% vs. 82.3% vs. 56%, P=0.0335), respectively. Overall survival was identical in the 3 groups. In addition to complete cytogenetic response and major molecular response, further deeper molecular response is associated with better event-free and failure-free survivals, and complete molecular response confers the best outcome. PMID:24362549

  4. 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.

  5. Achievement motivation and competition: perceptions and responses.

    PubMed

    Scanlan, T K; Ragan, J T

    1978-01-01

    This study investigated the influence of achievement motivation (Nach) on how individuals perceive an evaluative competition situation, whether they prefer to perform in this type of setting, and whether they seek the inherent appraisal information regarding their motoric competence. Specifically, perceived threat to self esteem was examined as indicated by state anxiety responses and measured by the Competitive Short Form of the Spielberger State Anxiety Inventory. State anxiety was assessed at rest, while performing a motor task alone in a nonevaluative setting, and during competition against an equal ability opponent. Situation perference and information seeking behavior were assessed at the conclusion of the closely paced competition. Subjects were asked whether they had perferred performing in the noncompetition or competition situation and were given the opportunity to select the relative ability level of a future opponent. As predicted, the major findings indicated that high Nach males experienced less threat during competition than low Nach males. Further, more high than low Nach individuals perferred the competition situation to the noncompetition situation and sought the evaluative ability information to a greater extent by choosing opponents of equal or greater relative ability for a future hypothetical competition.

  6. 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.…

  7. Maternal Employment and Adolescent Achievement: Effects of Demandingness, Responsiveness, and Commitment to Achievement.

    ERIC Educational Resources Information Center

    Paulson, Sharon E.; Slavin, Lesley A.

    This study examined the influences of three parenting variables on children's school achievement: commitment to children's school achievement, demandingness, and responsiveness. The study also examined the influence of maternal employment and satisfaction with employment on the three parenting variables and on children's achievement.…

  8. 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…

  9. 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

  10. 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)

  11. 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

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

    PubMed

    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

  13. 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)…

  14. 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…

  15. 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…

  16. Contextual Determinants of Achievement Responses in Men and Women.

    ERIC Educational Resources Information Center

    Albino, Judith E.; Shuell, Thomas J.

    Picture stimuli depicting females and males working together were shown to college students by either a male or a female experimenter. Subjects' responses to the pictures were assessed using standard need achievement scoring. A significant interaction was obtained between sex of subject and sex of experimenter, such that higher need achievement…

  17. Maternal responsiveness and children's achievement of language milestones.

    PubMed

    Tamis-LeMonda, C S; Bornstein, M H; Baumwell, L

    2001-01-01

    This prospective longitudinal study examined the contribution of dimensions of maternal responsiveness (descriptions, play, imitations) to the timing of five milestones in children's (N = 40) early expressive language: first imitations, first words, 50 words in expressive language, combinatorial speech, and the use of language to talk about the past. Events-History Analysis, a statistical technique that estimates the extent to which predictors influence the timing of events, was used. At 9 and 13 months, maternal responsiveness and children's activities (e.g., vocalizations, play) were coded from videotaped interactions of mother-child free play; information about children's language acquisition was obtained through biweekly interviews with mothers from 9 through 21 months. Maternal responsiveness at both ages predicted the timing of children's achieving language milestones over and above children's observed behaviors. Responsiveness at 13 months was a stronger predictor of the timing of language milestones than was responsiveness at 9 months, and certain dimensions of responsiveness were more predictive than others. The multidimensional nature of maternal responsiveness and specificity in mother-child language relations are discussed.

  18. Longitudinal study of young children's responses to challenging achievement situations.

    PubMed

    Ziegert, D I; Kistner, J A; Castro, R; Robertson, B

    2001-01-01

    Three studies were conducted to replicate and extend Dweck's findings regarding young children's responses to challenging achievement situations. Dweck's dichotomous helplessness classification system (i.e., task choice, task choice reason) was replicated with kindergartners, n = 235 (50% male), and first graders, n = 70 (46% male). To test whether individual differences in young children's responses to challenging situations are stable over time, 1- and 5-year follow-ups of the kindergartners were conducted. On the basis of children's responses on age-appropriate behavioral tasks, a composite of cognitive, behavioral, and affective helplessness indices predicted helplessness at 1 and 5 years later, n = 114 (50% male), above and beyond kindergarten task ability and gender, p<.05. Kindergarten helplessness predicted teacher ratings of children's helplessness 5 years later as well, p<.05. The implications of these findings for early intervention are discussed. PMID:11333088

  19. Soft commitment: self-control achieved by response persistence.

    PubMed Central

    Siegel, E; Rachlin, H

    1995-01-01

    With reinforcement contingent on a single peck on either of two available keys (concurrent continuous reinforcement schedules) 4 pigeons, at 80% of free-feeding weights, preferred a smaller-sooner reinforcer (2.5 s of mixed grain preceded by a 0.5-s delay) to a larger-later reinforcer (4.5 s of mixed grain preceded by a 3.5-s delay). However, when the smaller-sooner and larger-later reinforcers were contingent on a concurrent fixed-ratio 31 schedule (the first 30 pecks distributed in any way on the two keys), all pigeons obtained the larger-later reinforcer much more often than they did when only a single peck was required. This "self-control" was achieved by beginning to peck the key leading to the larger-later reinforcer and persisting on that key until reinforcement occurred. We call this persistence "soft commitment" to distinguish it from strict commitment, in which self-control is achieved by preventing changeovers. Soft commitment also effectively achieved self-control when a brief (1-s) signal was inserted between the 30th and 31st response of the ratio and with concurrent fixed-interval 30-s schedules (rather than ratio schedules) of reinforcement. In a second experiment with the same subjects, the fixed ratio was interrupted by darkening both keys and lighting a third (center) key on which pecking was required for various fractions of the fixed-ratio count. The interruption significantly reduced self-control. When interruption was complete (30 responses on the center key followed by a single choice response), pigeons chose the smaller-sooner reinforcer as frequently as they did when only a single choice response was required. PMID:7561671

  20. 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

  1. Intelligence and Academic Achievement in a Clinical Adolescent Population

    ERIC Educational Resources Information Center

    Stewart, David W.; Morris, Linda

    1977-01-01

    The present study was undertaken with two related goals: (a) to examine the relationships between the WRAT and CAT, and (b) to examine the relationships which may exist between these academic achievement tests -nd a standard intelligence battery such as the Wechsler Scale. (Author)

  2. 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.

  3. 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

  4. Facilitating cells: Translation of hematopoietic chimerism to achieve clinical tolerance.

    PubMed

    Ildstad, Suzanne T; Leventhal, Joseph; Wen, Yujie; Yolcu, Esma

    2015-04-01

    For over 50 y the association between hematopoietic chimerism and tolerance has been recognized. This originated with the brilliant observation by Dr. Ray Owen that freemartin cattle twins that shared a common placental blood supply were red blood cell chimeras, which led to the discovery that hematopoietic chimerism resulted in actively acquired tolerance. This was first confirmed in neonatal mice by Medawar et al. and subsequently in adult rodents. Fifty years later this concept has been successfully translated to solid organ transplant recipients in the clinic. The field is new, but cell-based therapies are being used with increasing frequency to induce tolerance and immunomodulation. The future is bright. This review focuses on chimerism and tolerance: past, present and prospects for the future.

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

    PubMed

    Lorenz, Laura S; Chilingerian, Jon A

    2011-02-16

    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

  6. 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

  7. 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…

  8. [Personnel reduction in clinics and legal responsibility].

    PubMed

    Schelling, P

    2011-06-01

    Executive clinical physicians are increasingly being made jointly responsible for the economic success of clinics and it is to be expected that this joint responsibility will result in measures to reduce personnel. In this article it will be explained to which limits a reduction in medical personnel can be justified with respect to liability and from what level a reduction in staff can result in forensic risks. Furthermore, it will be discussed which liability or even penal responsibility in this connection affects the physicians, the hospital and especially the senior medical personnel.

  9. Increased Student Achievement through Parental Involvement and Increased Student Responsibility.

    ERIC Educational Resources Information Center

    Boberg, Tim; Carpenter, Kerry; Haiges, Shelley; Lundsgaard, Barb

    This action research project addressed the problem of missing assignments among fourth- and fifth-graders at a school in northern Illinois. In order to document the extent to which students lacked responsibility for turning in daily assignments, the teacher-researchers kept track of missing assignments for each student and grade book records for 6…

  10. 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…

  11. Surface plasmon resonance microscopy: Achieving a quantitative optical response

    NASA Astrophysics Data System (ADS)

    Peterson, Alexander W.; Halter, Michael; Plant, Anne L.; Elliott, John T.

    2016-09-01

    Surface plasmon resonance (SPR) imaging allows real-time label-free imaging based on index of refraction and changes in index of refraction at an interface. Optical parameter analysis is achieved by application of the Fresnel model to SPR data typically taken by an instrument in a prism based figuration. We carry out SPR imaging on a microscope by launching light into a sample and collecting reflected light through a high numerical aperture microscope objective. The SPR microscope enables spatial resolution that approaches the diffraction limit and has a dynamic range that allows detection of subnanometer to submicrometer changes in thickness of biological material at a surface. However, unambiguous quantitative interpretation of SPR changes using the microscope system could not be achieved using the Fresnel model because of polarization dependent attenuation and optical aberration that occurs in the high numerical aperture objective. To overcome this problem, we demonstrate a model to correct for polarization diattenuation and optical aberrations in the SPR data and develop a procedure to calibrate reflectivity to index of refraction values. The calibration and correction strategy for quantitative analysis was validated by comparing the known indices of refraction of bulk materials with corrected SPR data interpreted with the Fresnel model. Subsequently, we applied our SPR microscopy method to evaluate the index of refraction for a series of polymer microspheres in aqueous media and validated the quality of the measurement with quantitative phase microscopy.

  12. Responsive Assessment: Assessing Student Nurses' Clinical Competence.

    ERIC Educational Resources Information Center

    Neary, Mary

    2001-01-01

    A study involving 300 nursing students, 155 nurse practitioners, and 80 assessors tested a model of responsive assessment that includes identification of learning needs and potential, assignment to suitable placements, continuous assessment of clinical practice and patient care, and alignment of teaching and assessment with patient needs and…

  13. [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,…

  14. 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

  15. RECIST for Response (Clinical and Imaging) in Neoadjuvant Clinical Trials in Operable Breast Cancer.

    PubMed

    Semiglazov, Vladimir

    2015-05-01

    Although approximately 70% of breast cancer patients demonstrate a clinical response on neoadjuvant systemic therapy on physical examination or on anatomic radiographic imaging, only 3%-40% achieve a pathologic complete response (pCR). Magnetic resonance imaging (MRI) is superior to physical examination, ultrasound, and mammography in response evaluation during neoadjuvant systemic therapy. The accuracy of breast MRI to predict pCR has a moderate sensitivity, but high specificity. The accuracy of anatomic imaging to assess residual disease and predict pCR depended on anatomic radiographic imaging cancer subtypes. Response monitoring using breast is accurate in triple-negative or HER2-positive tumors. It was inaccurate in estrogen receptor-positive/HER2-negative subtype. Another approach currently under investigation is dynamic contrast-enhanced MRI and diffusion weighted-imaging, (18)F-fluorodeoxyglucose positron emission tomography, fluorodeoxyglucose positron emission tomography/computed tomography. PMID:26063880

  16. 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…

  17. 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.

  18. Meta-Analysis of the Research on Response Cards: Effects on Test Achievement, Quiz Achievement, Participation, and Off-Task Behavior

    ERIC Educational Resources Information Center

    Randolph, Justus J.

    2007-01-01

    In this meta-analysis, the author analyzed 18 response card articles, theses, or dissertations to determine the magnitude of effect that response card strategies have on test achievement, quiz achievement, class participation, and intervals of off-task behavior. The author also determined whether the type of response cards used or the presence or…

  19. Adjuvant therapy sparing in rectal cancer achieving complete response after chemoradiation

    PubMed Central

    García-Albéniz, Xabier; Gallego, Rosa; Hofheinz, Ralf Dieter; Fernández-Esparrach, Gloria; Ayuso-Colella, Juan Ramón; Bombí, Josep Antoni; Conill, Carles; Cuatrecasas, Miriam; Delgado, Salvadora; Ginés, Angels; Miquel, Rosa; Pagés, Mario; Pineda, Estela; Pereira, Verónica; Sosa, Aarón; Reig, Oscar; Victoria, Iván; Feliz, Luis; María de Lacy, Antonio; Castells, Antoni; Burkholder, Iris; Hochhaus, Andreas; Maurel, Joan

    2014-01-01

    AIM: To evaluate the long-term results of conventional chemoradiotherapy and laparoscopic mesorectal excision in rectal adenocarcinoma patients without adjuvant therapy. METHODS: Patients with biopsy-proven adenocarcinoma of the rectum staged cT3-T4 by endoscopic ultrasound or magnetic resonance imaging received neoadjuvant continuous infusion of 5-fluorouracil for five weeks and concomitant radiotherapy. Laparoscopic surgery was planned after 5-8 wk. Patients diagnosed with ypT0N0 stage cancer were not treated with adjuvant therapy according to the protocol. Patients with ypT1-2N0 or ypT3-4 or N+ were offered 5-fluorouracil-based adjuvant treatment on an individual basis. An external cohort was used as a reference for the findings. RESULTS: One hundred and seventy six patients were treated with induction chemoradiotherapy and 170 underwent total mesorectal excision. Cancer staging of ypT0N0 was achieved in 26/170 (15.3%) patients. After a median follow-up of 58.3 mo, patients with ypT0N0 had five-year disease-free and overall survival rates of 96% (95%CI: 77-99) and 100%, respectively. We provide evidence about the natural history of patients with localized rectal cancer achieving a complete response after preoperative chemoradiation. The inherent good prognosis of these patients will have implications for clinical trial design and care of patients. CONCLUSION: Withholding adjuvant chemotherapy after complete response following standard neoadjuvant chemoradiotherapy and laparoscopic mesorectal excision might be safe within an experienced multidisciplinary team. PMID:25400468

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

    PubMed

    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

  1. 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

  2. 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

  3. Importance of Achieving Stringent Complete Response After Autologous Stem-Cell Transplantation in Multiple Myeloma

    PubMed Central

    Kapoor, Prashant; Kumar, Shaji K.; Dispenzieri, Angela; Lacy, Martha Q.; Buadi, Francis; Dingli, David; Russell, Stephen J.; Hayman, Suzanne R.; Witzig, Thomas E.; Lust, John A.; Leung, Nelson; Lin, Yi; Zeldenrust, Steven R.; McCurdy, Arleigh; Greipp, Philip R.; Kyle, Robert A.; Rajkumar, S. Vincent; Gertz, Morie A.

    2013-01-01

    Purpose To study the impact of achieving stringent complete response (sCR), an increasingly attainable goal, after autologous stem-cell transplantation (ASCT) in patients with multiple myeloma (MM). Patients and Methods Maximal response rates were determined in 445 consecutive patients who underwent ASCT within 12 months of diagnosis of MM. The patients achieving varying degrees of complete response (CR) are the focus of our study. Results One hundred and nine patients (25%) achieved sCR after ASCT. The median overall survival (OS) rate from the time of transplantation for patients attaining sCR was not reached (NR), in contrast to those patients achieving conventional complete response (CR; n = 37; OS, 81 months) or near CR (nCR; n = 91; OS, 60 months; P < .001). Five-year OS rates were 80%, 53%, and 47% for sCR, CR, and nCR, respectively. The median time to progression (TTP) from ASCT of patients achieving sCR was significantly longer (50 months) than TTP of patients achieving CR or nCR (20 months and 19 months, respectively). On multivariable analysis, post-ASCT response of sCR was an independent prognostic factor for survival (hazard ratio, 0.44; 95% CI, 0.25 to 0.80; versus CR; P = .008), in addition to proliferation rate, pre-ASCT cytogenetics, and performance status. OS rates of patients attaining sCR continued to remain superior at 2-year landmark (median, NR v 70 months for conventional CR group; P = .007). Conclusion Improved long-term outcome is seen after ASCT with achievement of sCR when compared with lesser degrees of responses. Myeloma trials reporting the response rates should identify patients achieving sCR and CR separately, owing to markedly disparate outcomes of the two categories. PMID:24248686

  4. 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…

  5. The Impact of Response to Intervention on Student Reading Achievement in Urban Elementary Schools

    ERIC Educational Resources Information Center

    Weaver, Wendy Smyth

    2011-01-01

    The purpose of this study was to determine if the implementation of a Response to Intervention framework had a positive impact on student reading achievement in urban elementary schools. This was a causal-comparative study that examined the reading performance of a sample of kindergarten through grade three students who experienced the Response to…

  6. 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.…

  7. 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

  8. 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

  9. 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

  10. 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.

  11. 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

  12. Multimodal treatment of unresectable hepatocellular carcinoma to achieve complete response results in improved survival

    PubMed Central

    Newell, Pippa H; Wu, YingXing; Hoen, Helena; Uppal, Richa; Thiesing, John Tyler; Sasadeusz, Kevin; Cassera, Maria A; Wolf, Ronald F; Hansen, Paul; Hammill, Chet W

    2015-01-01

    Introduction With technological advances, questions arise regarding how to best fit newer treatment modalities, such as transarterial therapies, into the treatment algorithm for patients with hepatocellular carcinoma (HCC). Methods Between 2005 and 2011, 128 patients initially treated with transarterial radioembolization or chemoembolization using drug-eluting beads were identified. The response was graded retrospectively. Toxicity was measured 1, 3, and 6 months after the first and last treatments. Results Sixty-five patients (53%) were advanced stage. Twenty patients (16%) had an initial complete response, but with additional treatments, this was increased to 46 (36%). Patients with a complete response as their best response to treatment had a median survival [95% confidence interval (CI)] of 5.77 (2.58, upper limit not yet reached) years, significantly longer than those whose best response was a partial response, 1.22 (0.84, 2.06) years and those with stable disease as their best response, 0.34 (0.29, 0.67) years. Repeated treatments did not increase toxicity. Discussion This retrospective review of patients treated for intermediate and advanced stage HCC revealed a significant survival advantage in patients who achieved a complete response. These data support use of a multi-modality approach to intermediate and advanced stage HCC, combining liver-directed treatments as necessary to achieve a complete response. PMID:25580988

  13. 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

  14. 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

  15. 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…

  16. 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…

  17. 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…

  18. Homework Practices and Academic Achievement: The Mediating Role of Self-Efficacy and Perceived Responsibility Beliefs

    ERIC Educational Resources Information Center

    Zimmerman, Barry J.; Kitsantas, Anastasia

    2005-01-01

    The present study investigated the role of students' homework practices in their self-efficacy beliefs regarding their use of specific learning processes (e.g., organizing, memorizing, concentrating, monitoring, etc.), perceptions of academic responsibility, and academic achievement. One hundred and seventy-nine girls from multi-ethnic, mixed…

  19. 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…

  20. 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

  1. Deep molecular responses achieved in patients with CML-CP who are switched to nilotinib after long-term imatinib.

    PubMed

    Hughes, Timothy P; Lipton, Jeffrey H; Spector, Nelson; Cervantes, Francisco; Pasquini, Ricardo; Clementino, Nelma Cristina D; Dorlhiac Llacer, Pedro Enrique; Schwarer, Anthony P; Mahon, Francois-Xavier; Rea, Delphine; Branford, Susan; Purkayastha, Das; Collins, LaTonya; Szczudlo, Tomasz; Leber, Brian

    2014-07-31

    Patients in complete cytogenetic response (CCyR) with detectable BCR-ABL1 after ≥2 years on imatinib were randomized to nilotinib (400 mg twice daily, n = 104) or continued imatinib (n = 103) in the Evaluating Nilotinib Efficacy and Safety in clinical Trials-Complete Molecular Response (ENESTcmr) trial. By 1 and 2 years, confirmed undetectable BCR-ABL1 was achieved by 12.5% vs 5.8% (P = .108) and 22.1% vs 8.7% of patients in the nilotinib and imatinib arms, respectively (P = .0087). Among patients without molecular response 4.5 (BCR-ABL1(IS) ≤0.0032%; MR(4.5)) and those without major molecular response at study start, MR(4.5) by 2 years was achieved by 42.9% vs 20.8% and 29.2% vs 3.6% of patients in the nilotinib and imatinib arms, respectively. No patient in the nilotinib arm lost CCyR, vs 3 in the imatinib arm. Adverse events were more common in the nilotinib arm, as expected with the introduction of a new drug vs remaining on a well-tolerated drug. The safety profile of nilotinib was consistent with other reported studies. In summary, switching to nilotinib enabled more patients with chronic myeloid leukemia in chronic phase (CML-CP) to sustain lower levels of disease burden vs remaining on imatinib. This trial was registered at www.clinicaltrials.gov as #NCT00760877.

  2. Lipid target achievement among patients with very high and high cardiovascular risk in a lipid clinic.

    PubMed

    Barkas, Fotios; Liberopoulos, Evangelos N; Kostapanos, Michael S; Liamis, George; Tziallas, Dimitrios; Elisaf, Moses

    2015-04-01

    This was a retrospective study that assessed achievement of lipid-lowering treatment targets in the setting of a University Hospital Lipid Clinic. Low-density lipoprotein cholesterol (LDL-C) goal attainment according to National Cholesterol Education Program-Adult Treatment Panel III (NCEP ATP III) and European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines was recorded in 1000 consecutive adult patients followed for ≥3 years (mean 8 years). The LDL-C targets according to the NCEP ATP III were attained by 66% and 86% of patients with "very high" (n = 477) and "high" (n = 408) cardiovascular risk, respectively. Fewer patients were within LDL-C goals according to the ESC/EAS guidelines: 25% and 42%. Overall, 92% of the patients were on statins: 67% were on statin monotherapy, while 33% were on combinations with ezetimibe (25%), ω-3 fatty acids (5%), fibrates (4%), or colesevelam (2%). Even in a specialist lipid clinic, a large proportion of patients are not at goal according to the recent ESC/EAS guidelines. PMID:24830420

  3. Perceived job importance and job performance satisfaction of selected clinical nutrition management responsibilities.

    PubMed

    Pratt, Peggy E; Kwon, Junehee; Rew, Martha L

    2005-07-01

    A nationwide survey of clinical nutrition managers was conducted to assess perceived importance of selected job responsibilities and perceived performance satisfaction of those job responsibilities. A questionnaire was developed to achieve the study objectives, validated by an expert panel, and pilot-tested prior to data collection. All members of the American Dietetic Association's Clinical Nutrition Management dietetic practice group (N=1,668) were asked to rate the importance of selected job responsibilities and their satisfaction with those responsibilities using Likert-type scales with descriptions. Results revealed that clinical nutrition managers perceived all job responsibilities listed in the questionnaire to be important (ie, the mean score of each responsibility was >3.0 of a 4.0 scale). Respondents rated regulatory-related job responsibilities as most important and were most satisfied with their performance of these responsibilities. Following regulatory-related responsibilities, clinical nutrition managers perceived patient satisfaction and staff retention to be more important than other responsibilities. In general, clinical nutrition managers were more satisfied with their job performance for job responsibilities that they ranked as more important.

  4. 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

  5. What level of accuracy is achievable for preclinical dose painting studies on a clinical irradiation platform?

    PubMed

    Trani, Daniela; Reniers, Brigitte; Persoon, Lucas; Podesta, Mark; Nalbantov, Georgi; Leijenaar, Ralph T H; Granzier, Marlies; Yaromina, Ala; Dubois, Ludwig; Verhaegen, Frank; Lambin, Philippe

    2015-05-01

    in a rat tumor model on a clinical platform, with a high accuracy achieved in the delivery of complex dose distributions. Our work demonstrates the technical feasibility of this approach and enables future investigations on the therapeutic effect of preclinical dose painting strategies using a state-of-the-art clinical platform.

  6. 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.

  7. 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

  8. 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…

  9. NOTE: On the clinical spatial resolution achievable with protons and heavier charged particle radiotherapy beams

    NASA Astrophysics Data System (ADS)

    Andreo, Pedro

    2009-06-01

    The 'sub-millimetre precision' often claimed to be achievable in protons and light ion beam therapy is analysed using the Monte Carlo code SHIELD-HIT for a broad range of energies. Based on the range of possible values and uncertainties of the mean excitation energy of water and human tissues, as well as of the composition of organs and tissues, it is concluded that precision statements deserve careful reconsideration for treatment planning purposes. It is found that the range of I-values of water stated in ICRU reports 37, 49 and 73 (1984, 1993 and 2005) for the collision stopping power formulae, namely 67 eV, 75 eV and 80 eV, yields a spread of the depth of the Bragg peak of protons and heavier charged particles (carbon ions) of up to 5 or 6 mm, which is also found to be energy dependent due to other energy loss competing interaction mechanisms. The spread is similar in protons and in carbon ions having analogous practical range. Although accurate depth-dose distribution measurements in water can be used at the time of developing empirical dose calculation models, the energy dependence of the spread causes a substantial constraint. In the case of in vivo human tissues, where distribution measurements are not feasible, the problem poses a major limitation. In addition to the spread due to the currently accepted uncertainties of their I-values, a spread of the depth of the Bragg peak due to the varying compositions of soft tissues is also demonstrated, even for cases which could be considered practically identical in clinical practice. For these, the spreads found were similar to those of water or even larger, providing support to international recommendations advising that body-tissue compositions should not be given the standing of physical constants. The results show that it would be necessary to increase the margins of a clinical target volume, even in the case of a water phantom, due to an 'intrinsic basic physics uncertainty', adding to those margins usually

  10. [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

  11. 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.

  12. Clinical errors as a lack of context responsiveness.

    PubMed

    Bugatti, Matteo; Boswell, James F

    2016-09-01

    Although standardized treatments have the potential to decrease clinical errors, within-session responsiveness is complicated and complementary frameworks may be needed to foster enhanced responsiveness in the context of evidence-based treatments. Recent efforts have targeted the enhancement of flexibility and responsiveness in the delivery of manualized treatments, including the development of transdiagnostic treatments (i.e., protocols that are designed to be used across different diagnoses) intended to tailor intervention principles to the needs of individual patients. Context-Responsive Psychotherapy Integration (Constantino, Boswell, Bernecker, & Castonguay, 2013) offers an framework that supports the utilization of evidence-based clinical strategies in response to the identification of specific process markers. Failure to identify or appropriately respond to such markers may result in negative therapeutic process as well as outcomes. This case study uses the context-response psychotherapy integration framework to understand critical moments of clinical decision-making through examining an individual treatment case that unilaterally terminated after seven sessions of transdiagnostic treatment. This illustrative empirical case analysis focuses on three potential clinical errors, as indicated by a lack of responsiveness to three candidate process markers: (a) low outcome expectations, (b) self-strivings, and (c) outcome monitoring. For each clinical error, alternative clinical strategies are discussed. (PsycINFO Database Record

  13. Clinical errors as a lack of context responsiveness.

    PubMed

    Bugatti, Matteo; Boswell, James F

    2016-09-01

    Although standardized treatments have the potential to decrease clinical errors, within-session responsiveness is complicated and complementary frameworks may be needed to foster enhanced responsiveness in the context of evidence-based treatments. Recent efforts have targeted the enhancement of flexibility and responsiveness in the delivery of manualized treatments, including the development of transdiagnostic treatments (i.e., protocols that are designed to be used across different diagnoses) intended to tailor intervention principles to the needs of individual patients. Context-Responsive Psychotherapy Integration (Constantino, Boswell, Bernecker, & Castonguay, 2013) offers an framework that supports the utilization of evidence-based clinical strategies in response to the identification of specific process markers. Failure to identify or appropriately respond to such markers may result in negative therapeutic process as well as outcomes. This case study uses the context-response psychotherapy integration framework to understand critical moments of clinical decision-making through examining an individual treatment case that unilaterally terminated after seven sessions of transdiagnostic treatment. This illustrative empirical case analysis focuses on three potential clinical errors, as indicated by a lack of responsiveness to three candidate process markers: (a) low outcome expectations, (b) self-strivings, and (c) outcome monitoring. For each clinical error, alternative clinical strategies are discussed. (PsycINFO Database Record PMID:27631853

  14. 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

  15. 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.

  16. 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...

  17. 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...

  18. Corticosteroid therapy in ulcerative colitis: Clinical response and predictors

    PubMed Central

    Li, Jin; Wang, Fan; Zhang, Hong-Jie; Sheng, Jian-Qiu; Yan, Wen-Feng; Ma, Min-Xing; Fan, Ru-Ying; Gu, Fang; Li, Chuan-Feng; Chen, Da-Fan; Zheng, Ping; Gu, Yu-Pei; Cao, Qian; Yang, Hong; Qian, Jia-Ming; Hu, Pin-Jin; Xia, Bing

    2015-01-01

    AIM: To evaluate clinical response to initial corticosteroid (CS) treatment in Chinese ulcerative colitis patients (UC) and identify predictors of clinical response. METHODS: Four hundred and twenty-three UC patients who were initially treated with oral or intravenous CS from 2007 to 2011 were retrospectively reviewed at eight inflammatory bowel disease centers in China, and 101 consecutive cases with one-year follow-up were analyzed further for clinical response and predictors. Short-term outcomes within one month were classified as primary response and primary non-response. Long-term outcomes within one year were classified as prolonged CS response, CS dependence and secondary non-response. CS refractoriness included primary and secondary non-response. Multivariate analyses were performed to identify predictors associated with clinical response. RESULTS: Within one month, 95.0% and 5.0% of the cases were classified into primary response and non-response, respectively. Within one year, 41.6% of cases were assessed as prolonged CS response, while 49.5% as CS dependence and 4.0% as secondary non-response. The rate of CS refractoriness was 8.9%, while the cumulative rate of surgery was 6.9% within one year. After multivariate analysis of all the variables, tenesmus was found to be a negative predictor of CS dependence (OR = 0.336; 95%CI: 0.147-0.768; P = 0.013) and weight loss as a predictor of CS refractoriness (OR = 5.662; 95%CI: 1.111-28.857; P = 0.040). After one-month treatment, sustained high Sutherland score (≥ 6) also predicted CS dependence (OR = 2.347; 95%CI: 0.935-5.890; P = 0.014). CONCLUSION: Tenesmus was a negative predictor of CS dependence, while weight loss and sustained high Sutherland score were strongly associated with poor CS response. PMID:25780299

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

    SciTech Connect

    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.

  20. 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

  1. Thai clinical laboratory responsible to economic crisis.

    PubMed

    Sirisali, K; Vattanaviboon, P; Manochiopinij, S; Ananskulwat, W

    1999-01-01

    Nowadays, Thailand encounters a serious economic crisis. A clear consensus has been made that a cost-saving system must be the important tool. Both private and government organizations are engaged in this situation. We studied the cost-saving in the clinical laboratory. A questionnaire was distributed to 45 hospital laboratories located in Bangkok. Results showed that efforts to control the cost are the essential policy. There was a variety of factors contributing to the cost-saving process. The usage of public utility, non-recycle material and unnecessary utility were reconsidered. Besides, capital cost (wages and salary) personnel incentive are assessed. Forty three of the 45 respondents had attempted to reduce the cost via curtailing the unnecessary electricity. Eliminating the needless usage of telephone-call. water and unnecessary material was also an effective strategy. A reduction of 86.9%, 80 % and 80.0% of the mentioned factors respectively, was reported. An inventory system of the reagent, chemical and supplies was focused. Most of the laboratories have a policy on cost-saving by decreased the storage. Twenty eight of the 45 laboratories considered to purchase the cheaper with similar quality reagents instead. And some one would purchase a bulky pack when it is the best bargain. A specific system "contact reagent with a free rent instrument" has been used widely (33.3%). Finally, a new personnel management system has been chosen. Workload has rearranged and unnecessary extra-hour work was abandoned.

  2. 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.

  3. A hybrid approach to achieving both marginal and conditional balances for stratification variables in sequential clinical trials.

    PubMed

    Lin, Yunzhi; Su, Zheng

    2013-01-01

    Various methods exist in the literature for achieving marginal balance for baseline stratification variables in sequential clinical trials. One major limitation with balancing on the margins of the stratification variables is that there is an efficiency loss when the primary analysis is stratified. To preserve the efficiency of a stratified analysis one recently proposed approach balances on the crossing of the stratification variables included in the analysis, which achieves conditional balance for the variables. A hybrid approach to achieving both marginal and conditional balances in sequential clinical trials is proposed, which is applicable to both continuous and categorical stratification variables. Numerical results based on extensive simulation studies and a real dataset show that the proposed approach outperforms the existing ones and is particularly useful when both additive and stratified models are planned for a trial.

  4. Brain Connectivity Predicts Placebo Response across Chronic Pain Clinical Trials

    PubMed Central

    Tétreault, Pascal; Mansour, Ali; Vachon-Presseau, Etienne; Schnitzer, Thomas J.; Apkarian, A. Vania

    2016-01-01

    Placebo response in the clinical trial setting is poorly understood and alleged to be driven by statistical confounds, and its biological underpinnings are questioned. Here we identified and validated that clinical placebo response is predictable from resting-state functional magnetic-resonance-imaging (fMRI) brain connectivity. This also led to discovering a brain region predicting active drug response and demonstrating the adverse effect of active drug interfering with placebo analgesia. Chronic knee osteoarthritis (OA) pain patients (n = 56) underwent pretreatment brain scans in two clinical trials. Study 1 (n = 17) was a 2-wk single-blinded placebo pill trial. Study 2 (n = 39) was a 3-mo double-blinded randomized trial comparing placebo pill to duloxetine. Study 3, which was conducted in additional knee OA pain patients (n = 42), was observational. fMRI-derived brain connectivity maps in study 1 were contrasted between placebo responders and nonresponders and compared to healthy controls (n = 20). Study 2 validated the primary biomarker and identified a brain region predicting drug response. In both studies, approximately half of the participants exhibited analgesia with placebo treatment. In study 1, right midfrontal gyrus connectivity best identified placebo responders. In study 2, the same measure identified placebo responders (95% correct) and predicted the magnitude of placebo’s effectiveness. By subtracting away linearly modeled placebo analgesia from duloxetine response, we uncovered in 6/19 participants a tendency of duloxetine enhancing predicted placebo response, while in another 6/19, we uncovered a tendency for duloxetine to diminish it. Moreover, the approach led to discovering that right parahippocampus gyrus connectivity predicts drug analgesia after correcting for modeled placebo-related analgesia. Our evidence is consistent with clinical placebo response having biological underpinnings and shows that the method can also reveal that active

  5. The placebo response in clinical trials: more questions than answers

    PubMed Central

    Enck, Paul; Klosterhalfen, Sibylle; Weimer, Katja; Horing, Björn; Zipfel, Stephan

    2011-01-01

    Meta-analyses and re-analyses of trial data have not been able to answer some of the essential questions that would allow prediction of placebo responses in clinical trials. We will confront these questions with current empirical evidence. The most important question asks whether the placebo response rates in the drug arm and in the placebo arm are equal. This ‘additive model’ is a general assumption in almost all placebo-controlled drug trials but has rarely been tested. Secondly, we would like to address whether the placebo response is a function of the likelihood of receiving drug/placebo. Evidence suggests that the number of study arms in a trial may determine the size of the placebo and the drug response. Thirdly, we ask what the size of the placebo response is in ‘comparator’ studies with a direct comparison of a (novel) drug against another drug. Meta-analytic and experimental evidence suggests that comparator studies may produce higher placebo response rates when compared with placebo-controlled trials. Finally, we address the placebo response rate outside the laboratory and outside of trials in clinical routine. This question poses a serious challenge whether the drug response in trials can be taken as evidence of drug effects in clinical routine. PMID:21576146

  6. 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.

  7. Clinical Response to Valproate in Patients with Migraine

    PubMed Central

    Ichikawa, Mizuki; Katoh, Hirotaka; Kurihara, Tatsuya

    2016-01-01

    Background and Purpose Valproate is used as a prophylactic drug for migraine, but it is not be effective in all patients. We used medical records to investigate which clinical factors affected the response to valproate in patients with migraine as an original headache, and established a scoring system for predicting the clinical response to prophylactic therapy. Methods We investigated clinical factors from the medical records of 95 consistent responders (CRs) and 24 inconsistent responders (IRs) to valproate. Results Multivariate stepwise logistic regression analysis revealed that a history of hyperlipidemia and hay fever and the complication of depression or other psychiatric disorder were significant factors that independently contributed to a negative response, with odds ratios of 6.024 [no vs. yes; 95% confidence interval (CI)=1.616–22.222], 2.825 (no vs. yes; 95% CI=1.046–7.634), and 2.825 (no vs. yes; 95% CI=1.052–7.576), respectively. A predictive index (PI) of the clinical response to valproate in patients with migraine was calculated using the regression coefficients of these three factors as an integer, and the index was significantly higher for IRs than for CRs (1.46±1.10 vs. 0.69±0.74, mean±SD, p<0.001). Conclusions The obtained PI may represent an appropriate scoring system for predicting the responses in these patients.

  8. Clinical parameters for evaluating biological response modifier therapy.

    PubMed

    Hamblin, T J

    1989-01-01

    Evaluating response in cancer is a well established practice, depending on the recognition of complete response, partial response, stable disease and progressive disease. For chemotherapeutic drugs, only those patients achieving a complete response experience an increase in survival. Partial response merely indicates that the drug has some activity in that disease. What the patient wants is not active drugs but prolonged survival with good quality of life. It is well recognised that tumours may remain dormant for many years, and that even those patients with complete responses to chemotherapy usually have minimal residual disease. It is assumed that such minimal disease is controlled and held in check by a biological process. The principal aim of biological response modifiers is to enhance this effect so as to control an even larger tumour load. It therefore follows that removal of all tumour is not the only benefit, and that stable disease and even slower progression might translate to longer survival. Survival curves are the acid test and we should expect longer survival even for those patients failing to achieve complete response if we are to establish that life imprisonment is as effective in cancer treatment as capital punishment.

  9. 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

  10. Randomization in clinical trials in orthodontics: its significance in research design and methods to achieve it.

    PubMed

    Pandis, Nikolaos; Polychronopoulou, Argy; Eliades, Theodore

    2011-12-01

    Randomization is a key step in reducing selection bias during the treatment allocation phase in randomized clinical trials. The process of randomization follows specific steps, which include generation of the randomization list, allocation concealment, and implementation of randomization. The phenomenon in the dental and orthodontic literature of characterizing treatment allocation as random is frequent; however, often the randomization procedures followed are not appropriate. Randomization methods assign, at random, treatment to the trial arms without foreknowledge of allocation by either the participants or the investigators thus reducing selection bias. Randomization entails generation of random allocation, allocation concealment, and the actual methodology of implementing treatment allocation randomly and unpredictably. Most popular randomization methods include some form of restricted and/or stratified randomization. This article introduces the reasons, which make randomization an integral part of solid clinical trial methodology, and presents the main randomization schemes applicable to clinical trials in orthodontics.

  11. Relationships between Preferred Learning and Clinical Achievement of Baccalaureate Nursing Students.

    ERIC Educational Resources Information Center

    Wilkerson, Norma Neahr

    Paper presented at the Regional achievement in a nursing course in an integrated curriculum were studied. The theoretical framework was based on Kolb's model of experiential learning, which posited four phases: concrete experience, reflective observation, abstract conceptualization, and active experimentation. Kolb's Learning Style Inventory was…

  12. Busulphan is active against neuroblastoma and medulloblastoma xenografts in athymic mice at clinically achievable plasma drug concentrations

    PubMed Central

    Boland, I; Vassal, G; Morizet, J; Terrier-Lacombe, M-J; Valteau-Couanet, D; Kalifa, C; Hartmann, O; Gouyette, A

    1999-01-01

    High-dose busulphan-containing chemotherapy regimens have shown high response rates in children with relapsed or refractory neuroblastoma, Ewing's sarcoma and medulloblastoma. However, the anti-tumour activity of busulfan as a single agent remains to be defined, and this was evaluated in athymic mice bearing advanced stage subcutaneous paediatric solid tumour xenografts. Because busulphan is highly insoluble in water, the use of several vehicles for enteral and parenteral administration was first investigated in terms of pharmacokinetics and toxicity. The highest bioavailability was obtained with busulphan in DMSO administered i.p. When busulphan was suspended in carboxymethylcellulose and given orally or i.p., the bioavailability was poor. Then, in the therapeutic experiments, busulphan in DMSO was administered i.p. on days 0 and 4. At the maximum tolerated total dose (50 mg kg−1), busulphan induced a significant tumour growth delay, ranging from 12 to 34 days in the three neuroblastomas evaluated and in one out of three medulloblastomas. At a dose level above the maximum tolerated dose, busulphan induced complete and partial tumour regressions. Busulphan was inactive in a peripheral primitive neuroectodermal tumour (PNET) xenograft. When busulphan pharmacokinetics in mice and humans were considered, the estimated systemic exposure at the therapeutically active dose in mice (113 μg h ml−1) was close to the mean total systemic exposure in children receiving high-dose busulphan (102.4 μg h ml−1). In conclusion, busulphan displayed a significant anti-tumour activity in neuroblastoma and medulloblastoma xenografts at plasma drug concentrations which can be achieved clinically in children receiving high-dose busulphan-containing regimens. 1999 Cancer Research Campaign PMID:10070870

  13. 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

  14. Clinical predictors of therapeutic response to antipsychotics in schizophrenia.

    PubMed

    Carbon, Maren; Correll, Christoph U

    2014-12-01

    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.

  15. 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

  16. 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

  17. 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.

  18. 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.

  19. Achieving clinical statement interoperability using R-MIM and archetype-based semantic transformations.

    PubMed

    Kilic, Ozgur; Dogac, Asuman

    2009-07-01

    Effective use of electronic healthcare records (EHRs) has the potential to positively influence both the quality and the cost of health care. Consequently, sharing patient's EHRs is becoming a global priority in the healthcare information technology domain. This paper addresses the interoperability of EHR structure and content. It describes how two different EHR standards derived from the same reference information model (RIM) can be mapped to each other by using archetypes, refined message information model (R-MIM) derivations, and semantic tools. It is also demonstrated that well-defined R-MIM derivation rules help tracing the class properties back to their origins when the R-MIMs of two EHR standards are derived from the same RIM. Using well-defined rules also enable finding equivalences in the properties of the source and target EHRs. Yet an R-MIM still defines the concepts at the generic level. Archetypes (or templates), on the other hand, constrain an R-MIM to domain-specific concepts, and hence, provide finer granularity semantics. Therefore, while mapping clinical statements between EHRs, we also make use of the archetype semantics. Derivation statements are inferred from the Web Ontology Language definitions of the RIM, the R-MIMs, and the archetypes. Finally, we show how to transform Health Level Seven clinical statement instances to EHRcom clinical statement instances and vice versa by using the generated mapping definitions.

  20. [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.

  1. Pretreatment Mitochondrial Priming Correlates with Clinical Response to Cytotoxic Chemotherapy

    PubMed Central

    Chonghaile, Triona Ni; Sarosiek, Kristopher A.; Vo, Thanh-Trang; Ryan, Jeremy A.; Tammareddi, Anupama; Moore, Victoria Del Gaizo; Deng, Jing; Anderson, Ken; Richardson, Paul; Tai, Yu-Tzu; Mitsiades, Constantine S.; Matulonis, Ursula A.; Drapkin, Ronny; Stone, Richard; DeAngelo, Daniel J.; McConkey, David J.; Sallan, Stephen E.; Silverman, Lewis; Hirsch, Michelle S.; Carrasco, Daniel Ruben; Letai, Anthony

    2011-01-01

    Cytotoxic chemotherapy targets elements common to all nucleated human cells, such as DNA and microtubules, yet it selectively kills tumor cells. Here we show that clinical response to these drugs correlates with, and may be partially governed by, the pre-treatment proximity of tumor cell mitochondria to the apoptotic threshold, a property called mitochondrial priming. We used BH3 profiling to measure priming in tumor cells from patients with multiple myeloma, acute myelogenous and lymphoblastic leukemia, and ovarian cancer. This assay measures mitochondrial response to peptides derived from pro-apoptotic BH3 domains of proteins critical for death signaling to mitochondria. Patients with highly primed cancers exhibited superior clinical response to chemotherapy. In contrast, chemoresistant cancers and normal tissues were poorly primed. Manipulation of mitochondrial priming might enhance the efficacy of cytotoxic agents. PMID:22033517

  2. [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

  3. Prediction of clinical response to antidepressants in patients with depression: neurophysiology in clinical practice.

    PubMed

    Pogarell, Oliver; Juckel, Georg; Norra, Christine; Leicht, Gregor; Karch, Susanne; Schaaff, Nadine; Folkerts, Malte; Ibrahim, Ahmad; Mulert, Christoph; Hegerl, Ulrich

    2007-04-01

    Brain monoaminergic neurotransmission is involved in the pathophysiology of various psychiatric disorders including depression. Reliable indicators of central monoaminergic activity might be helpful to specifically identify and differentiate dysfunctions in individual patients in order to selectively adjust medication and predict clinical response. In patients with depression, predictors of treatment response to serotonergic versus non-serotonergic (e.g., noradrenergic) antidepressants could be of considerable clinical relevance by avoiding unfavorable factors such as a prolonged duration of the disorder, risk of suicidality and therapy-resistance. Consequently, these tools might help to decrease direct and indirect costs of treatment. The loudness dependence of the N1/P2 component of auditory evoked potentials (LD) has been proposed as a noninvasive neurophysiological indicator of central serotonergic function. This review focuses on recent studies providing evidence for the validity of LD as an indirect serotonergic marker and highlights data on the clinical application in terms of prediction of treatment response in patients with depression.

  4. Achieving collaboration in ethical decision making: strategies for nurses in clinical practice.

    PubMed

    Wocial, L D

    1996-01-01

    Ethical decision making is a process that combines justice and caring in moral reflection to select sound choices. Nurses and physicians often have different perspectives on how to resolve ethical dilemmas. Satisfactory resolution depends on overcoming conflict and achieving collaboration between members of the health care team. Conflict can occur on a number of different levels. For example, it can be between nurses, nurses and physicians or the entire health care team and the patient. This article helps prepare critical care nurses to handle ethical dilemmas in crisis situations by providing them with specific strategies that help promote collaboration in resolving ethical dilemmas. PMID:8715871

  5. Autonomous Information Fading and Provision to Achieve High Response Time in Distributed Information Systems

    NASA Astrophysics Data System (ADS)

    Lu, Xiaodong; Arfaoui, Helene; Mori, Kinji

    In highly dynamic electronic commerce environment, the need for adaptability and rapid response time to information service systems has become increasingly important. In order to cope with the continuously changing conditions of service provision and utilization, Faded Information Field (FIF) has been proposed. FIF is a distributed information service system architecture, sustained by push/pull mobile agents to bring high-assurance of services through a recursive demand-oriented provision of the most popular information closer to the users to make a tradeoff between the cost of information service allocation and access. In this paper, based on the analysis of the relationship that exists among the users distribution, information provision and access time, we propose the technology for FIF design to resolve the competing requirements of users and providers to improve users' access time. In addition, to achieve dynamic load balancing with changing users preference, the autonomous information reallocation technology is proposed. We proved the effectiveness of the proposed technology through the simulation and comparison with the conventional system.

  6. Clinical predictive factors of sildenafil response: a penile hemodynamic study.

    PubMed

    Elhanbly, S M; Elkholy, A A-M; Alghobary, M; Abou Al-Ghar, M

    2015-03-01

    Phosphodiestrase-5 inhibitors are an important line of treatment for erectile dysfunction (ED). To detect the clinical and hemodynamic predictors of sildenafil response, we conducted this study on 124 Egyptian men with ED. All patients were evaluated by thorough history and clinical assessment with measurement of the abridged international index of erectile function-5 (IIEF-5) score. All patients were then subjected to intracavernosal injection (ICI) of trimix and pharmaco-penile duplex ultrasonography (PPDU). Patients were then classified into sildenafil responders and non-responders after six consecutive doses of 100 mg sildenafil. On doing the binary logistic stepwise regression analysis, only ED duration, IIEF-5 score, and response to ICI were the significant independent predictors of sildenafil response. These three parameters together correctly predicted the sildenafil response by 81.5% (p value <0.001). With the receiver operator characteristic curve analysis, the cut-off value of ED duration was 2.5 years and it was 14 for the IIEF-5 score. These findings indicate that ED duration, the IIEF-5 score and response to ICI are more significant predictors of sildenafil response than the more expensive and time-consuming PPDU testing. PMID:25644869

  7. Fluoxetine response in children with autistic spectrum disorders: correlation with familial major affective disorder and intellectual achievement.

    PubMed

    DeLong, G Robert; Ritch, Chad R; Burch, Sherri

    2002-10-01

    One hundred and twenty-nine children, 2 to 8 years old, with idiopathic autistic spectrum disorder diagnosed by standard instruments (Childhood Austim Ratings Scale and Autism Diagnostic Observation Schedule) were treated with fluoxetine (0.15 to 0.5mg/kg) for 5 to 76 months (mean 32 to 36 months), with discontinuation trials. Response criteria are described. Family histories were obtained using the family history method in repeated interviews. Fluoxetine response, family history of major affective disorder, and unusual intellectual achievement, pretreatment language, and hyperlexia were used to define a coherent subgroup of autistic spectrum disorder. Statistical analyses were post hoc. Of the children, 22 (17%) had an excellent response, 67 (52%) good, and 40 (31%) fair/poor. Treatment age did not correlate with response. Fluoxetine response correlated robustly with familial major affective disorder and unusual intellectual achievement, and with hyperlexia in the child. Family history of bipolar disorder and of unusual intellectual achievement correlated strongly. Five children developed bipolar disorder during follow-up. Fluoxetine response, family history of major affective disorder (especially bipolar), unusual achievement, and hyperlexia in the children appear to define a homogeneous autistic subgroup. Bipolar disorder, unusual intellectual achievement, and autistic spectrum disorders cluster strongly in families and may share genetic determinants.

  8. Nutrition and education. IV. Clinical signs of malnutrition and its relationship with socioeconomic, anthropometric, dietetic and educational achievement parameters.

    PubMed

    Ivanovic Marincovich, D

    1992-03-01

    The objective of this study was to determine the prevalence of clinical signs of malnutrition, and to measure the interrelationship with socioeconomic, anthropometric, dietetic and educational achievement parameters. A random sample of 550 Chilean elementary and high school graduates (1:1), of both sexes (1:1), from public and private schools (1:1) and from high, medium and low socioeconomic status (SES) (1:1:1), was chosen in the Metropolitan Area of Santiago, Chile. SES was measured through the Graffar Modified Scale. Clinical signs of malnutrition were assessed according to Jelliffe. Nutritional status was determined by means of anthropometric measurements: percentages of weight/age (W/A), height/age (H/A) and weight for height (W/H) were compared with the WHO Tables; head circumference/age (HC/A) with the Tanner Tables, and branchial anthropometric parameters by applying the Frisancho norms. Standard procedures for the 24 hour dietary recall interviews were used to collect data, and adequacy of intake was assessed by the FAO/WHO pattern. Educational achievement (EA) was measured through the Achievement Evaluation Program, (AEP) and Academic Aptitude Test (AAT) in elementary and high school graduates, respectively. Results showed that apart from caries (87.5%), most prevalent clinical signs of malnutrition were dermatosis (13.4%), follicular hyperkeratosis type I (13.2%), nasolabial dyssebacea (7.9%), lustreless hair (7.7%), angular stomatitis (4.4%) and cheilosis (2.7%). The number of clinical signs of malnutrition was found inversely and significantly associated with SES, H/A, vitamin A and calcium intake, as well as with EA, besides registering a lower nutrient intake, specially for energy, riboflavin and niacin.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. 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

  10. Using biological markers to inform a clinically meaningful treatment response.

    PubMed

    Yehuda, Rachel; Bierer, Linda M; Pratchett, Laura C; Pelcovitz, Michelle

    2010-10-01

    Combat veterans with posttraumatic stress disorder (PTSD) demonstrate less robust improvement following treatments than do civilians with PTSD. This paper discusses a theoretical model for evaluating treatment response based on the extent of change in biological markers of symptom severity or resilience between treatment initiation and termination. Such analysis permits a determination of biological change associated with the liberal criteria commonly used to determine treatment response in combat PTSD, and a comparison of this to the biological change associated with clinical response determined according to the conservative definition more appropriate to civilian PTSD. Interim data supporting the utility of this approach is presented based on preliminary analyses from our work in progress. We propose that future studies consider the unique consequences of combat trauma and develop treatments that incorporate the complex nature of the exposure and response characteristic of a veteran population. PMID:20955338

  11. 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

  12. 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.

  13. 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…

  14. A Cross-Cultural Examination of the Psychometric Properties of Responses to the Achievement Goal Questionnaire

    ERIC Educational Resources Information Center

    Murayama, Kou; Zhou, Mingming; Nesbit, John C.

    2009-01-01

    The psychometric properties of scores from the Achievement Goal Questionnaire were examined in samples of Japanese (N = 326) and Canadian (N = 307) postsecondary students. Previous research found evidence of a four-factor structure of achievement goals in U.S. samples. Using confirmatory factor-analytic techniques, the authors found strong…

  15. The Use of Information from Wrong Responses in Measuring Students' Achievement.

    ERIC Educational Resources Information Center

    Birenbaum, Menucha; Tatsuoka, Kikumi K.

    Much valuable information can be gained by analyzing the students' wrong responses. When a student answers a free response item she/he gives the response which she/he considers to be the correct one. Therefore, diagnosing the algorithm that led the student to his/her answer provides an important source of information for assessing his/her…

  16. Rapid-response impulsivity: definitions, measurement issues, and clinical implications.

    PubMed

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

    2015-04-01

    Impulsivity is a multifaceted construct that is a core feature of multiple psychiatric conditions and personality disorders. However, progress in understanding and treating impulsivity 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 article. 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 (a) selection of RRI measures should be informed by careful consideration of the strengths, limitations, and practical considerations of the available measures; (b) 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 (c) similar considerations be made for human and nonhuman studies in an effort to harmonize and integrate preclinical and clinical research.

  17. Response to lithium in bipolar disorder: clinical and genetic findings.

    PubMed

    Rybakowski, Janusz K

    2014-06-18

    The use of lithium is a cornerstone for preventing recurrences in bipolar disorder (BD). The response of patients with bipolar disorder to lithium has different levels of magnitude. About one-third of lithium-treated patients are excellent lithium responders (ELR), showing total prevention of the episodes. A number of clinical characteristics were delineated in patients with favorable response to lithium as regards to clinical course, family history of mood disorders, and psychiatric comorbidity. We have also demonstrated that temperamental features of hypomania (a hyperthymic temperament) and a lack of cognitive disorganization predict the best results of lithium prophylaxis. A degree of prevention against manic and depressive episodes has been regarded as an endophenotype for pharmacogenetic studies. The majority of data have been gathered from so-called "candidate" gene studies. The candidates were selected on the basis of neurobiology of bipolar disorder and mechanisms of lithium action including, among others, neurotransmission, intracellular signaling, neuroprotection or circadian rhythms. We demonstrated that response to lithium has been connected with the genotype of BDNF gene and serum BDNF levels and have shown that ELR have normal cognitive functions and serum BDNF levels, even after long-term duration of the illness. A number of genome-wide association studies (GWAS) of BD have been also performed in recent years, some of which also focused on lithium response. The Consortium on Lithium Genetics (ConLiGen) has established the large sample for performing the genome-wide association study (GWAS) of lithium response in BD, and the first results have already been published.

  18. 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

  19. Utility of Serum Free Light Chain Measurements in Multiple Myeloma Patients Not Achieving Complete Response to Therapy

    PubMed Central

    Moustafa, Muhamad Alhaj; Rajkumar, S. Vincent; Dispenzieri, Angela; Gertz, Morie A.; Lacy, Martha Q.; Buadi, Francis K.; Hwa, Yi Lisa; Dingli, David; Kapoor, Prashant; Hayman, Suzanne R.; Lust, John A.; Kyle, Robert A.; Kumar, Shaji K.

    2015-01-01

    Normalization of the serum free light chain ratio (FLCr) with the absence of bone marrow monoclonal plasma cells following achievement of a complete response (CR) to therapy denotes a stringent CR in multiple myeloma (MM), and is associated with improved overall survival (OS). However, its value in patients achieving achieving a normalization of FLCr with initial therapy of MM will have an improved outcome, even in the absence of a CR. We retrospectively evaluated 449 patients with newly-diagnosed MM with measurable disease at baseline, who did not achieve a CR with initial therapy. One hundred fifty three patients (34%) had a normal FLCr while 296 (66%) had an abnormal ratio. Patients with a normal FLCr had a longer progression-free survival (PFS) (29 vs. 16 months, P <.001) and OS (91 vs. 58 months, P <.001). Normalization of FLCr retained its prognostic value in a multivariable model. Our results suggest an important role for sFLC measurement in disease monitoring even in patients who achieve only a partial response to therapy. Obtaining a normal FLCr confers a favorable prognosis independent from other factors, supporting the inclusion of sFLC in all levels of response criteria. PMID:25962523

  20. 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…

  1. 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…

  2. 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

  3. 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

  4. Sympathetic skin response: basic mechanisms and clinical applications.

    PubMed

    Vetrugno, Robert; Liguori, Rocco; Cortelli, Pietro; Montagna, Pasquale

    2003-08-01

    Sympathetic skin response (SSR), defined as the momentary change of the electrical potential of the skin, may be spontaneous or reflexively evoked by a variety of internal or by externally applied arousal stimuli. Although the suprasegmental structures influencing the SSR in humans are not well known, SSR has been proposed as a non-invasive approach to investigate the function of the sympathetic system. SSR is easy to apply but current procedures are not sufficiently reliable for diagnostic purposes, and show imperfect correlations both with clinical features and other measurements of autonomic, in particular, sudomotor dysfunction. PMID:12955550

  5. 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…

  6. 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

  7. 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…

  8. 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.

  9. 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…

  10. 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,…

  11. 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…

  12. 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

  13. 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

  14. High frequency wide-band transformer uses coax to achieve high turn ratio and flat response

    NASA Technical Reports Server (NTRS)

    De Parry, T.

    1966-01-01

    Center-tap push-pull transformer with toroidal core helically wound with a single coaxial cable creates a high frequency wideband transformer. This transformer has a high-turn ratio, a high coupling coefficient, and a flat broadband response.

  15. 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.

  16. Rapid-response impulsivity: definitions, measurement issues, and clinical implications.

    PubMed

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

    2015-04-01

    Impulsivity is a multifaceted construct that is a core feature of multiple psychiatric conditions and personality disorders. However, progress in understanding and treating impulsivity 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 article. 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 (a) selection of RRI measures should be informed by careful consideration of the strengths, limitations, and practical considerations of the available measures; (b) 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 (c) similar considerations be made for human and nonhuman studies in an effort to harmonize and integrate preclinical and clinical research. PMID:25867840

  17. 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.

  18. 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

  19. 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.

  20. 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…

  1. 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…

  2. 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…

  3. Detecting qualitative interactions in clinical trials with binary responses.

    PubMed

    Kitsche, Andreas

    2014-01-01

    This study considers the detection of treatment-by-subset interactions in a stratified, randomised clinical trial with a binary-response variable. The focus lies on the detection of qualitative interactions. In addition, the presented method is useful more generally, as it can assess the inconsistency of the treatment effects among strata by using an a priori-defined inconsistency margin. The methodology presented is based on the construction of ratios of treatment effects. In addition to multiplicity-adjusted p-values, simultaneous confidence intervals are recommended to use in detecting the source and the amount of a potential qualitative interaction. The proposed method is demonstrated on a multi-regional trial using the open-source statistical software R. PMID:25049176

  4. [Diffuse large B-cell lymphoma of the testis relapsed 16 years after achieving complete response].

    PubMed

    Nagasaka, Isao; Mitsui, Takeki; Ishizaki, Takuma; Koiso, Hiromi; Yokohama, Akihiko; Saitoh, Takayuki; Hirato, Junko; Igarashi, Tadahiko; Kojima, Masaru; Tsukamoto, Norifumi; Nojima, Yoshihisa; Murakami, Hirokazu; Handa, Hiroshi

    2015-12-01

    Testicular lymphoma is a rare disease, accounting for 1-2% of non-Hodgkin lymphoma and 5-9% of all testicular tumors, and has a high relapse rate with a poor prognosis. We report a patient with testicular diffuse large B-cell lymphoma (DLBCL) who relapsed after being in remission for 16 years. He had undergone orchiectomy of the right testis and was diagnosed as having DLBCL (stage IAE) at 49 years of age. After 3 cycles of CHOP, he achieved a complete remission. Orchiectomy was performed because of a left testicular tumor, and he was again diagnosed with DLBCL at the age of 65. VH3-21 was detected in lymphoma cells at the times of both the first diagnosis and the relapse based on analysis of the variable region of the immunoglobulin heavy chain. Accordingly, the lymphoma cells at relapse were confirmed to be the same clone as that which had been documented at the first diagnosis.

  5. 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.

  6. 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

  7. Achieving a stable time response in polymeric radiation sensors under charge injection by X-rays.

    PubMed

    Intaniwet, Akarin; Mills, Christopher A; Sellin, Paul J; Shkunov, Maxim; Keddie, Joseph L

    2010-06-01

    Existing inorganic materials for radiation sensors suffer from several drawbacks, including their inability to cover large curved areas, lack of tissue-equivalence, toxicity, and mechanical inflexibility. As an alternative to inorganics, poly(triarylamine) (PTAA) diodes have been evaluated for their suitability for detecting radiation via the direct creation of X-ray induced photocurrents. A single layer of PTAA is deposited on indium tin oxide (ITO) substrates, with top electrodes selected from Al, Au, Ni, and Pd. The choice of metal electrode has a pronounced effect on the performance of the device; there is a direct correlation between the diode rectification factor and the metal-PTAA barrier height. A diode with an Al contact shows the highest quality of rectifying junction, and it produces a high X-ray photocurrent (several nA) that is stable during continuous exposure to 50 kV Mo Kalpha X-radiation over long time scales, combined with a high signal-to-noise ratio with fast response times of less than 0.25 s. Diodes with a low band gap, 'Ohmic' contact, such as ITO/PTAA/Au, show a slow transient response. This result can be explained by the build-up of space charge at the metal-PTAA interface, caused by a high level of charge injection due to X-ray-induced carriers. These data provide new insights into the optimum selection of metals for Schottky contacts on organic materials, with wider applications in light sensors and photovoltaic devices.

  8. Understanding the DNA damage response in order to achieve desired gene editing outcomes in mosquitoes.

    PubMed

    Overcash, Justin M; Aryan, Azadeh; Myles, Kevin M; Adelman, Zach N

    2015-02-01

    Mosquitoes are high-impact disease vectors with the capacity to transmit pathogenic agents that cause diseases such as malaria, yellow fever, chikungunya, and dengue. Continued growth in knowledge of genetic, molecular, and physiological pathways in mosquitoes allows for the development of novel control methods and for the continued optimization of existing ones. The emergence of site-specific nucleases as genomic engineering tools promises to expedite research of crucial biological pathways in these disease vectors. The utilization of these nucleases in a more precise and efficient manner is dependent upon knowledge and manipulation of the DNA repair pathways utilized by the mosquito. While progress has been made in deciphering DNA repair pathways in some model systems, research into the nature of the hierarchy of mosquito DNA repair pathways, as well as in mechanistic differences that may exist, is needed. In this review, we will describe progress in the use of site-specific nucleases in mosquitoes, along with the hierarchy of DNA repair in the context of mosquito chromosomal organization and structure, and how this knowledge may be manipulated to achieve precise chromosomal engineering in mosquitoes. PMID:25596822

  9. Understanding the DNA damage response in order to achieve desired gene editing outcomes in mosquitoes.

    PubMed

    Overcash, Justin M; Aryan, Azadeh; Myles, Kevin M; Adelman, Zach N

    2015-02-01

    Mosquitoes are high-impact disease vectors with the capacity to transmit pathogenic agents that cause diseases such as malaria, yellow fever, chikungunya, and dengue. Continued growth in knowledge of genetic, molecular, and physiological pathways in mosquitoes allows for the development of novel control methods and for the continued optimization of existing ones. The emergence of site-specific nucleases as genomic engineering tools promises to expedite research of crucial biological pathways in these disease vectors. The utilization of these nucleases in a more precise and efficient manner is dependent upon knowledge and manipulation of the DNA repair pathways utilized by the mosquito. While progress has been made in deciphering DNA repair pathways in some model systems, research into the nature of the hierarchy of mosquito DNA repair pathways, as well as in mechanistic differences that may exist, is needed. In this review, we will describe progress in the use of site-specific nucleases in mosquitoes, along with the hierarchy of DNA repair in the context of mosquito chromosomal organization and structure, and how this knowledge may be manipulated to achieve precise chromosomal engineering in mosquitoes.

  10. [Diffuse large B-cell lymphoma of the testis relapsed 16 years after achieving complete response].

    PubMed

    Nagasaka, Isao; Mitsui, Takeki; Ishizaki, Takuma; Koiso, Hiromi; Yokohama, Akihiko; Saitoh, Takayuki; Hirato, Junko; Igarashi, Tadahiko; Kojima, Masaru; Tsukamoto, Norifumi; Nojima, Yoshihisa; Murakami, Hirokazu; Handa, Hiroshi

    2015-12-01

    Testicular lymphoma is a rare disease, accounting for 1-2% of non-Hodgkin lymphoma and 5-9% of all testicular tumors, and has a high relapse rate with a poor prognosis. We report a patient with testicular diffuse large B-cell lymphoma (DLBCL) who relapsed after being in remission for 16 years. He had undergone orchiectomy of the right testis and was diagnosed as having DLBCL (stage IAE) at 49 years of age. After 3 cycles of CHOP, he achieved a complete remission. Orchiectomy was performed because of a left testicular tumor, and he was again diagnosed with DLBCL at the age of 65. VH3-21 was detected in lymphoma cells at the times of both the first diagnosis and the relapse based on analysis of the variable region of the immunoglobulin heavy chain. Accordingly, the lymphoma cells at relapse were confirmed to be the same clone as that which had been documented at the first diagnosis. PMID:26725353

  11. An alternative clinical approach to achieve greater anterior than posterior maxillary expansion in cleft lip and palate patients.

    PubMed

    Oliveira, Dauro Douglas; Bartolomeo, Flávia Uchôa Costa; Cardinal, Lucas; Figueiredo, Daniel Santos Fonseca; Palomo, Juan Martin; Andrade, Ildeu

    2014-11-01

    Cleft lip and palate patients commonly present maxillary constriction, particularly in the anterior region. The aim of this case report was to describe an alternative clinical approach that used a smaller Hyrax screw unconventionally positioned to achieve greater anterior than posterior expansion in patients with complete unilateral cleft lip and palate. The idea presented here is to take advantage of a reduced dimension screw to position it anteriorly. When only anterior expansion was needed (patient 1), the appliance was soldered to the first premolar bands and associated to a transpalatal arch cemented to the first molars. However, when overall expansion was required (patient 2), the screw was positioned anteriorly, but soldered to the first molar bands. Intercanine, premolar, and first molar widths were measured on dental casts with a digital caliper. Pre-expansion and postexpansion radiographs and tomographies were also evaluated. A significant anterior expansion and no intermolar width increase were registered in the first patient. Although patient 2 also presented a greater anterior than posterior expansion, a noteworthy expansion occurred at the molar region. The alternative approach to expand the maxilla in cleft patients reported here caused greater anterior than posterior expansion when the Mini-Hyrax was associated to a transpalatal arch, and its reduced dimension also minimized discomfort and facilitated hygiene.

  12. 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

  13. 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

  14. 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

  15. Medical ethos and social responsibility in clinical medicine.

    PubMed

    Francis, C K

    2001-03-01

    The medical profession will face many challenges in the new millenium. 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 on 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 reminders that the racial doctrines that fostered the horrors of the Holocaust and the Tuskegee Syphilis Study have not been removed completely 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 in 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 well-being of the patient and the primacy of the patient-physician relationship against 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 ensure quality health care for the individual patient while effecting societal changes to achieve "health for all."

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

    PubMed

    Francis, C K

    2001-05-01

    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."

  17. 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

  18. 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

  19. 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.

  20. Response of gonococcal clinical isolates to acidic conditions.

    PubMed

    Pettit, R K; McAllister, S C; Hamer, T A

    1999-02-01

    This study examined the response to acidic conditions of four gonococcal isolates -NRL38874 (Proto/IB-2), NRL38884 (Pro/IA-2), NRL38953 (Proto/IB-3) and NRL39029 (Pro/IA-3) - obtained from various sites in patients in whom a diagnosis of pelvic inflammatory disease had been made by laparoscopic examination. Acid tolerance of the clinical isolates was strain and growth phase dependent. Growth of the four strains on solid media was undetectable below pH 5.8. In liquid culture, strain NRL38884 did not survive below pH 5.2; strains NRL38874, NRL38953 and NRL39029 survived to pH 4.5. Between pH 4.2 and pH 5.1, the latter three strains exhibited a peak in survival at pH 4.6-4.7 during log phase, suggesting that there may be a distinct acid tolerance system operating at this pH. SDS-PAGE of whole-cell, total membrane and outer-membrane fractions of the four strains prepared from pH 7.2 and pH 6.1 plate cultures revealed numerous differences in protein composition. Acidic conditions reduced the expression of the reduction modifiable outer-membrane protein Rmp, and induced the expression of many membrane proteins, including gonococcal hsp63. Immunoblotting studies with matched serum samples and strains from patients with pelvic inflammatory disease indicated that IgG recognition of outer-membrane components from strains cultured in acidic and neutral conditions was quite different. The results suggest that the immune system interacts with unique outer-membrane constituents on gonococci colonising sites at different pH.

  1. 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

  2. Clinical parameters model for predicting pathologic complete response following preoperative chemoradiation in patients with esophageal cancer

    PubMed Central

    Ajani, J. A.; Correa, A. M.; Hofstetter, W. L.; Rice, D. C.; Blum, M. A.; Suzuki, A.; Taketa, T.; Welsh, J.; Lin, S. H.; Lee, J. H.; Bhutani, M. S.; Ross, W. A.; Maru, D. M.; Macapinlac, H. A.; Erasmus, J.; Komaki, R.; Mehran, R. J.; Vaporciyan, A. A.; Swisher, S. G.

    2012-01-01

    Background Approximately 25% of patients with esophageal cancer (EC) who undergo preoperative chemoradiation, achieve a pathologic complete response (pathCR). We hypothesized that a model based on clinical parameters could predict pathCR with a high (≥60%) probability. Patients and methods We analyzed 322 patients with EC who underwent preoperative chemoradiation. All the patients had baseline and postchemoradiation positron emission tomography (PET) and pre- and postchemoradiation endoscopic biopsy. Logistic regression models were used for analysis, and cross-validation via the bootstrap method was carried out to test the model. Results The 70 (21.7%) patients who achieved a pathCR lived longer (median overall survival [OS], 79.76 months) than the 252 patients who did not achieve a pathCR (median OS, 39.73 months; OS, P = 0.004; disease-free survival, P = 0.003). In a logistic regression analysis, the following parameters contributed to the prediction model: postchemoradiation PET, postchemoradiation biopsy, sex, histologic tumor grade, and baseline EUST stage. The area under the receiver-operating characteristic curve was 0.72 (95% confidence interval [CI] 0.662–0.787); after the bootstrap validation with 200 repetitions, the bias-corrected AU-ROC was 0.70 (95% CI 0.643–0.728). Conclusion Our data suggest that the logistic regression model can predict pathCR with a high probability. This clinical model could complement others (biomarkers) to predict pathCR. PMID:22831985

  3. 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

  4. 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.

  5. Correlation between pretreatment levels of interferon response genes and clinical responses to an immune response modifier (Imiquimod) in genital warts.

    PubMed

    Arany, I; Tyring, S K; Brysk, M M; Stanley, M A; Tomai, M A; Miller, R L; Smith, M H; McDermott, D J; Slade, H B

    2000-07-01

    Imiquimod (IQ) has been successfully used in treatment of genital warts. In clinical settings, patients responded well but wart reduction rates varied. Our aim was to find a correlation between clinical responses and pretreatment (constitutive) levels of genes that might be involved in the molecular action of IQ. Since IQ is a cytokine inducer, we analyzed levels of expression of genes of the JAK/STAT signaling pathway and their inhibitors as well as interferon response factors (IRFs) in pretreatment biopsy specimens from complete responders (99 to 100% wart reduction rate) versus incomplete responders (75 to 92% wart reduction rate) by reverse transcription-PCR. We found that mRNA levels of signal transducer and activator of transcription 1 (STAT1) and IRF1 were higher in complete responders than in incomplete responders. Incomplete responders expressed larger amounts of STAT3, IRF2, and protein inhibitor of activated STAT1 (PIAS1) mRNAs compared to complete responders before IQ treatment. We hypothesize that high-level expression of STAT1 and IRF1 is advantageous for a better IQ response. The observed differences in constitutive mRNA levels of these genes may be the consequence of alterations in cellular differentiation and/or variable expression of endogenous interferons. Previous in vitro studies showed that keratinocyte differentiation coordinates the balance between positive and negative signals along the JAK/STAT pathway by regulating the IRF1:IRF2 and STAT1:PIAS1 ratios and thus affecting induction of IQ-inducible genes. Specifically, differentiation supports constitutive expression of STAT1 and IRF1 mRNAs but not expression of IRF2 and PIAS1. Our data are in good agreement with studies that showed the importance of STAT1 in cytokine induction and activation of interferon-responsive genes by IQ.

  6. 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

  7. 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.

  8. Aminolevulinic Acid-Photodynamic Therapy of Basal Cell Carcinoma and Factors Affecting the Response to Treatment: A Clinical Trial

    PubMed Central

    Tehranchinia, Zohreh; Rahimi, Hoda; Ahadi, Mahsa Seyed; Ahadi, Maral Seyed

    2013-01-01

    Background: Basal cell carcinoma (BCC) is the most common type of skin cancer in humans. Photodynamic therapy (PDT) is a non-invasive therapeutic modality that may be considered as a valuable treatment option for BCC. This study was designed with the aim of evaluating the efficacy of PDT in treatment of BCC and factors that may affect the response rate. Materials and Methods: This clinical trial was conducted on 12 patients (28 BCC lesions) who were treated with aminulevulinic acid (ALA)-PDT, monthly, up to 6 sessions and the clinical response, cosmetic results, and possible side effects were evaluated. Results: The study was performed on 28 BCC lesions from 12 patients. Complete response was achieved in 9 (32.1%) lesions. Complete response rate was higher in younger patients (P < 0.01) and those with smaller lesions (P < 0.001). Superficial type also had significant higher response rate (P < 0.05). Patients with history of radiotherapy for the treatment of tinea capitis in childhood showed less response (P < 0.05). Cosmetic results were excellent or good in 77.5% cases. After 6 months of follow-up, none of the resolved lesions recurred. Conclusion: PDT would be a good therapeutic option in treatment of BCC with acceptable efficacy and low side effects. Younger patients, superficial BCCs, and smaller lesions show better response to ALA-PDT. History of radiotherapy may be associated with a lower response rate. PMID:23919025

  9. 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…

  10. Achieving appropriate design for developing world heath care: the case of a low-cost autoclave for primary health clinics.

    PubMed

    Cho, Hallie S; Tao, Gregory D; Winter, Amos

    2012-01-01

    In developing world health clinics, incidence of surgical site infection is 2 to 10 times higher than in developed world hospitals. This paper identifies lack of availability of appropriately designed, low-cost autoclaves in developing world health clinics as a major contributing factor to the dramatic gap in surgical site infection rates. The paper describes the process of developing a low-cost autoclave that addresses the unique challenges faced by developing world primary health clinics and discusses how appropriateness of design was determined. The resulting pressure cooker-based autoclave design was fabricated and tested against the CDC specifications. Twelve partnering clinics in Nepal trialed these autoclaves from July until December 2012.

  11. Nonlinear speech analysis algorithms mapped to a standard metric achieve clinically useful quantification of average Parkinson's disease symptom severity

    PubMed Central

    Tsanas, Athanasios; Little, Max A.; McSharry, Patrick E.; Ramig, Lorraine O.

    2011-01-01

    The standard reference clinical score quantifying average Parkinson's disease (PD) symptom severity is the Unified Parkinson's Disease Rating Scale (UPDRS). At present, UPDRS is determined by the subjective clinical evaluation of the patient's ability to adequately cope with a range of tasks. In this study, we extend recent findings that UPDRS can be objectively assessed to clinically useful accuracy using simple, self-administered speech tests, without requiring the patient's physical presence in the clinic. We apply a wide range of known speech signal processing algorithms to a large database (approx. 6000 recordings from 42 PD patients, recruited to a six-month, multi-centre trial) and propose a number of novel, nonlinear signal processing algorithms which reveal pathological characteristics in PD more accurately than existing approaches. Robust feature selection algorithms select the optimal subset of these algorithms, which is fed into non-parametric regression and classification algorithms, mapping the signal processing algorithm outputs to UPDRS. We demonstrate rapid, accurate replication of the UPDRS assessment with clinically useful accuracy (about 2 UPDRS points difference from the clinicians' estimates, p < 0.001). This study supports the viability of frequent, remote, cost-effective, objective, accurate UPDRS telemonitoring based on self-administered speech tests. This technology could facilitate large-scale clinical trials into novel PD treatments. PMID:21084338

  12. Improvements in clinical response between 12 and 24 weeks in patients with rheumatoid arthritis on etanercept therapy with or without methotrexate

    PubMed Central

    Kavanaugh, A; Klareskog, L; van der Heijde, D; Li, J; Freundlich, B; Hooper, M

    2008-01-01

    Background: Whereas many patients respond quickly to treatment with tumour necrosis factor (TNF) inhibitors, some patients may experience significant but delayed responses. Objective: To evaluate the clinical response between 12 and 24 weeks in subjects with rheumatoid arthritis from the Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes. Methods: Clinical response was assessed at 24 weeks in 12-week non-responders, according to American College of Rheumatology (ACR) response criteria. The proportion of subjects who successfully maintained response to 52 weeks was analysed, as were radiographic outcomes. Results: Data from 682 subjects were included in the analysis. Non and partial responders in all three groups (etanercept, methotrexate and etanercept plus methotrexate) at week 12 showed an improvement in responses at week 24. Over 80% of the week 24 ACR20/50/70 responders in the etanercept plus methotrexate arm sustained their response to 52 weeks. In the etanercept arms, a delayed clinical response was not associated with increased radiographic progression at week 52. Conclusion: A significant proportion of non and partial responders to etanercept with or without methotrexate therapy at week 12 achieved a good clinical response or improved their overall clinical response at week 24. Discontinuing TNF inhibitor therapy at 12 weeks may be premature in some rheumatoid arthritis patients. PMID:18535115

  13. Principal Perceptions toward the Leadership Responsibilities and Practices of the Superintendency in High and Low Achievement School Districts with High and Low Superintendent Turnover

    ERIC Educational Resources Information Center

    Colby-Rooney, Danielle M.

    2013-01-01

    The purpose of this study was to determine the perceptions of building principals toward superintendent leadership responsibilities and practices of goal setting, nonnegotiable goals for achievement and instruction, board alignment with support of district goals, monitoring goals for achievement and instruction, use of resources to support the…

  14. 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.

  15. Clinical Predictors of Response to Clozapine in Patients with Treatment Resistant Schizophrenia

    PubMed Central

    A.P., Rajkumar; C., Chitra; S., Bhuvaneshwari; B., Poonkuzhali; A., Kuruvilla; K.S., Jacob

    2011-01-01

    Objectives Despite clozapine’s superior clinical efficacy in Treatment Resistant Schizophrenia (TRS), its adverse effects, need for periodic leukocyte monitoring, cost and variable clinical outcomes make the therapeutic decision making process difficult and mandate a clinical need to predict its treatment response. Hence, we investigated various clinical variables associated with treatment responses and adverse events of clozapine in TRS. Experimental Design We assessed socio-demographic and clinical profiles, premorbid adjustment, traumatic life events, cognition, disability, psychopathology and serum clozapine levels of 101 patients with TRS on stable dose of clozapine using the following instruments: Brief Psychiatric Rating Scale, Abnormal Involuntary Movements Scale, Addenbrooke’s Cognitive Examination—Revised, WHO Disability Assessment Scale-II, Childhood and Recent Traumatic Events Scale, and Premorbid Assessment Scale. We defined clozapine response a priori, adopted a case-control design framework and employed appropriate multivariate analyses. Principal Observations Past history of catatonia (p = 0.005), smoking more than one pack/day (p = 0.008), hyper-somnolence (p = 0.03) and cognitive dysfunction (p = 0.007) were associated with non-response to clozapine. Outcome definitions of non-response to clozapine influenced its association with clinical predictors. Conclusions Clinical variables are useful to predict response to clozapine. Smoking can be a potentially modifiable risk factor. Future longitudinal studies, investigating clinical and pharmacogenetic variables together, are desired.

  16. 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

  17. 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.

  18. [Application of three compartment model and response surface model to clinical anesthesia using Microsoft Excel].

    PubMed

    Abe, Eiji; Abe, Mari

    2011-08-01

    With the spread of total intravenous anesthesia, clinical pharmacology has become more important. We report Microsoft Excel file applying three compartment model and response surface model to clinical anesthesia. On the Microsoft Excel sheet, propofol, remifentanil and fentanyl effect-site concentrations are predicted (three compartment model), and probabilities of no response to prodding, shaking, surrogates of painful stimuli and laryngoscopy are calculated using predicted effect-site drug concentration. Time-dependent changes in these calculated values are shown graphically. Recent development in anesthetic drug interaction studies are remarkable, and its application to clinical anesthesia with this Excel file is simple and helpful for clinical anesthesia.

  19. 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

  20. 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

  1. 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

  2. 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

  3. Association between clinical complete response and pathological complete response after preoperative chemoradiation in patients with gastroesophageal cancer: analysis in a large cohort

    PubMed Central

    Cheedella, N. K. S.; Suzuki, A.; Xiao, L.; Hofstetter, W. L.; Maru, D. M.; Taketa, T.; Sudo, K.; Blum, M. A.; Lin, S. H.; Welch, J.; Lee, J. H.; Bhutani, M. S.; Rice, D. C.; Vaporciyan, A. A.; Swisher, S. G.; Ajani, J. A.

    2013-01-01

    Background Chemoradiation followed by surgery is the preferred treatment of localized gastroesophageal cancer (GEC). Surgery causes considerable life-altering consequences and achievement of clinical complete response (clinCR; defined as postchemoradiation [but presurgery] endoscopic biopsy negative for cancer and positron emission tomographic (PET) scan showing physiologic uptake) is an enticement to avoid/delay surgery. We examined the association between clinCR and pathologic complete response (pathCR). Patients and methods Two hundred eighty-four patients with GEC underwent chemoradiation and esophagectomy. The chi-square test, Fisher exact test, t-test, Kaplan–Meier method, and log-rank test were used. Results Of 284 patients, 218 (77%) achieved clinCR. However, only 67 (31%) of the 218 achieved pathCR. The sensitivity of clinCR for pathCR was 97.1% (67/69), but the specificity was low (29.8%; 64/215). Of the 66 patients who had less than a clinCR, only 2 (3%) had a pathCR. Thus, the rate of pathCR was significantly different in patients with clinCR than in those with less than a clinCR (P < 0.001). Conclusions clinCR is not highly associated with pathCR; the specificity of clinCR for pathCR is too low to be used for clinical decision making on delaying/avoiding surgery. Surgery-eligible GEC patients should be encouraged to undergo surgery following chemoradiation despite achieving a clinCR. PMID:23247658

  4. Host response to nontuberculous mycobacterial infections of current clinical importance.

    PubMed

    Orme, Ian M; Ordway, Diane J

    2014-09-01

    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.

  5. 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

  6. Clinical and biochemical responses to the treatment of milk fever.

    PubMed

    Mullen, P A

    1975-08-01

    One hundred and eighty-six cases of milk fever in 80 herds spread over five counties were used to compare treatment with 8g calcium plus 500 mg magnesium in aspartate with the conventional 12-36g calcium as borogluconate. The data obtained from both the herds and their individual cases show that the treatments gave broadly similar results, and a single intravenous treatment cured 74-7 per cent of cases. It appeared that milk fever was not likely to recur with each succeeding parturition. No breed susceptibility was recognised. No correlation was found between the severity of the clinical signs and the inorganic phosphate concentrations. An incidence of milk fever of 8-79 per cent was recorded.

  7. [Interindividual variation of pharmacokinetic disposition of and clinical responses to opioid analgesics in cancer pain patients].

    PubMed

    Naito, Takafumi; Kawakami, Junichi

    2015-01-01

    Use of prescription opioids for cancer pain according to the World Health Organization analgesic ladder has been accepted in Japan. Although oxycodone and fentanyl are commonly used as first-line analgesics, a few clinical reports have been published on interindividual variations in their pharmacokinetics and clinical responses in cancer patients. (1) Some factors relating to CYP2D6, CYP3A, ATP-binding cassette sub-family B member 1 (ABCB1), and opioid receptor mu 1 (OPRM1) involve oxycodone pharmacokinetics and sensitivity in humans. The relations between their genetic variations and clinical responses to oxycodone are being revealed in limited groups. In our study, the impact of genetic variants and pharmacokinetics on clinical responses to oxycodone were evaluated in Japanese populations. (2) Opioid switching improves the opioid tolerance related to the balance between analgesia and adverse effects. Some patients have difficulty in obtaining better opioid tolerance in recommended conversion ratios. The activities of CYP3A, ABCB1, and OPRM1 contribute to the interindividual variations in clinical responses to fentanyl in cancer patients. However, the variations in opioid switching remain to be clarified in clinical settings. In our study, genetic factors related to interindividual variations in clinical responses in opioid switching to fentanyl were revealed in Japanese populations. In this symposium review, the possibility of approaches to personalized palliative care using opioids based on genetic variants of CYP2D6, CYP3A5, ABCB1, and OPRM1 is discussed.

  8. Clinical and inflammatory response to bloodstream infections in octogenarians

    PubMed Central

    2014-01-01

    Background Given the increasing incidence of bacteraemia causing significant morbidity and mortality in older patients, this study aimed to compare the clinical features, laboratory findings and mortality of patients over the age of 80 to younger adults. Methods This study was a retrospective, observational study. Participants were taken to be all patients aged 18 and above with confirmed culture positive sepsis, admitted to a large metropolitan hospital in the year 2010. Measurements taken included patient demographics (accommodation, age, sex, comorbidities), laboratory investigations (white cell count, neutrophil count, C-reactive protein, microbiology results), clinical features (vital signs, presence of localising symptoms, complications, place of acquisition). Results A total of 1367 patient episodes were screened and 155 met study inclusion criteria. There was no statistically significant difference between likelihood of fever or systolic blood pressure between younger and older populations (p-values of 0.81 and 0.64 respectively). Neutrophil count was higher in the older cohort (p = 0.05). Higher Charlson (J Chronic Dis40(5):373–383, 1987) comorbidity index, greater age and lower systolic blood pressure were found to be statistically significant predictors of mortality (p-values of 0.01, 0.02 and 0.03 respectively). Conclusion The findings of this study indicate older patients are more likely to present without localising features. However, importantly, there is no significant difference in the likelihood of fever or inflammatory markers. This study also demonstrates the importance of the Charlson Index of Comorbidities (J Chronic Dis40(5):373–383, 1987) as a predictive factor for mortality, with age and hypotension being less important but statistically significant predictive factors of mortality. PMID:24754903

  9. Achievement of recommended glucose and blood pressure targets in patients with type 2 diabetes and hypertension in clinical practice – study rationale and protocol of DIALOGUE

    PubMed Central

    2012-01-01

    Background Patients with type 2 diabetes have 2–4 times greater risk for cardiovascular morbidity and mortality than those without, and this is even further aggravated if they also suffer from hypertension. Unfortunately, less than one third of hypertensive diabetic patients meet blood pressure targets, and more than half fail to achieve target HbA1c values. Thus, appropriate blood pressure and glucose control are of utmost importance. Since treatment sometimes fails in clinical practice while clinical trials generally suggest good efficacy, data from daily clinical practice, especially with regard to the use of newly developed anti-diabetic and anti-hypertensive compounds in unselected patient populations, are essential. The DIALOGUE registry aims to close this important gap by evaluating different treatment approaches in hypertensive type 2 diabetic patients with respect to their effectiveness and tolerability and their impact on outcomes. In addition, DIALOGUE is the first registry to determine treatment success based on the new individualized treatment targets recommended by the ADA and the EASD. Methods DIALOGUE is a prospective observational German multicentre registry and will enrol 10,000 patients with both diabetes and hypertension in up to 700 sites. After a baseline visit, further documentations are scheduled at 6, 12 and 24 months. There are two co-primary objectives referring to the most recent guidelines for the treatment of diabetes and hypertension: 1) individual HbA1c goal achievement with respect to anti-diabetic pharmacotherapy and 2) individual blood pressure goal achievement with different antihypertensive treatments. Among the secondary objectives the rate of major cardio-vascular and cerebro-vascular events (MACCE) and the rate of hospitalizations are the most important. Conclusion The registry will be able to gain insights into the reasons for the obvious gap between the demonstrated efficacy and safety of anti-diabetic and anti

  10. The therapeutic effect of clinical trials: understanding placebo response rates in clinical trials – A secondary analysis

    PubMed Central

    Walach, Harald; Sadaghiani, Catarina; Dehm, Cornelia; Bierman, Dick

    2005-01-01

    Background and purpose Placebo response rates in clinical trials vary considerably and are observed frequently. For new drugs it can be difficult to prove effectiveness superior to placebo. It is unclear what contributes to improvement in the placebo groups. We wanted to clarify, what elements of clinical trials determine placebo variability. Methods We analysed a representative sample of 141 published long-term trials (randomized, double-blind, placebo-controlled; duration > 12 weeks) to find out what study characteristics predict placebo response rates in various diseases. Correlational and regression analyses with study characteristics and placebo response rates were carried out. Results We found a high and significant correlation between placebo and treatment response rate across diseases (r = .78; p < .001). A multiple regression model explained 79% of the variance in placebo variability (F = 59.7; p < 0.0001). Significant predictors are, among others, the duration of the study (beta = .31), the quality of the study (beta = .18), the fact whether a study is a prevention trial (beta = .44), whether dropouts have been documented (beta = -.20), or whether additional treatments have been documented (beta = -.17). Healing rates with placebo are lower in the following diagnoses; neoplasms (beta = -.21), nervous diseases (beta = -.10), substance abuse (beta = -.14). Without prevention trials the amount of variance explained is 42%. Conclusion Medication response rates and placebo response rates in clinical trials are highly correlated. Trial characteristics can explain some portion of the variance in placebo healing rates in RCTs. Placebo response in trials is only partially due to methodological artefacts and only partially dependent on the diagnoses treated. PMID:16109176

  11. Clinical response to varying the stimulus parameters in deep brain stimulation for essential tremor.

    PubMed

    Kuncel, Alexis M; Cooper, Scott E; Wolgamuth, Barbara R; Clyde, Merlise A; Snyder, Scott A; Montgomery, Erwin B; Rezai, Ali R; Grill, Warren M

    2006-11-01

    Deep brain stimulation (DBS) of the ventral intermediate nucleus of the thalamus for essential tremor is sometimes limited by side effects. The mechanisms by which DBS alleviates tremor or causes side effects are unclear; thus, it is difficult to select stimulus parameters that maximize the width of the therapeutic window. The goal of this study was to quantify the impact on side effect intensity (SE), tremor amplitude, and the therapeutic window of varying stimulus parameters. Tremor amplitude and SE were recorded at 40 to 90 combinations of pulse width, frequency, and voltage across 14 thalami. Posterior variable inclusion probabilities indicated that frequency and voltage were the most important predictors of both SE and tremor amplitude. The amount of tremor suppression achieved at frequencies of 90 to 100 Hz was not different from that at 160 to 170 Hz. However, the width of the therapeutic window decreased significantly and power consumption increased as frequency was increased above 90 to 100 Hz. Improved understanding of the relationships between stimulus parameters and clinical responses may lead to improved techniques of stimulus parameter adjustment. PMID:16972236

  12. Early Response to Antipsychotic Drug Therapy as a Clinical Marker of Subsequent Response in the Treatment of Schizophrenia

    PubMed Central

    Kinon, Bruce J; Chen, Lei; Ascher-Svanum, Haya; Stauffer, Virginia L; Kollack-Walker, Sara; Zhou, Wei; Kapur, Shitij; Kane, John M

    2010-01-01

    Our objective was to prospectively assess whether early (ie, 2 weeks) response to an antipsychotic predicts later (12-week) response and whether ‘switching' early non-responders to another antipsychotic is a better strategy than ‘staying'. This randomized, double-blind, flexible-dosed, 12-week study enrolled 628 patients diagnosed with schizophrenia or schizoaffective disorder. All initiated treatment with risperidone. Early response was defined as ⩾20% improvement on the Positive and Negative Syndrome Scale (PANSS) total score following 2 weeks of treatment. Early responders (ERs) continued on risperidone, whereas early non-responders (ENRs) were randomized (1 : 1) to continue on risperidone 2–6 mg/day or switch to olanzapine 10–20 mg/day for 10 additional weeks. Compared with ENRs, risperidone ERs showed significantly greater reduction in PANSS total score (end point; p<001). Early response/non-response was highly predictive of subsequent clinical outcomes. Switching risperidone ENRs to olanzapine at week 2 resulted in a small but significantly greater reduction in PANSS total score (end point; p=0.020) and in depressive symptoms (end point; p=0.004); the reduction in PANSS was greater among those who were still moderately ill at 2 weeks. Switching risperidone ENRs to olanzapine also resulted in significantly greater increases in triglycerides, a significantly greater decrease in prolactin, and significantly less treatment-emergent dyskinesia. This is the first study to prospectively show that early response/non-response to an antipsychotic (risperidone) is a reliable clinical marker of subsequent clinical outcomes and that a ‘switching' strategy based on this information may lead to greater clinical improvement than staying on a drug for a longer period in some patients. PMID:19890258

  13. 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.

  14. Survey Response Rates and Survey Administration in Counseling and Clinical Psychology: A Meta-Analysis

    ERIC Educational Resources Information Center

    Van Horn, Pamela S.; Green, Kathy E.; Martinussen, Monica

    2009-01-01

    This article reports results of a meta-analysis of survey response rates in published research in counseling and clinical psychology over a 20-year span and describes reported survey administration procedures in those fields. Results of 308 survey administrations showed a weighted average response rate of 49.6%. Among possible moderators, response…

  15. Clinical response to combined therapy of cyclosporine and prednisone.

    PubMed

    Gensure, Robert C

    2013-12-01

    Reported is a patient with severe alopecia areata, multiple autoimmune diseases (chronic lymphocytic thyroidis, primary ovarian failure), and Down syndrome. She had a poor response to topical treatment with glucocorticoids and minoxidil, but showed some improvement with glucocorticoid injections. At the time of evaluation, she had hair loss on 85-90% of her scalp. She was treated initially with oral prednisone 50 mg per day for 2 weeks, followed by a 3-month course of prednisone 10 mg per day and cyclosporine 125 mg (4 mg kg(-1)) two times per day. She responded well with excellent regrowth of hair on the scalp, and prednisone was tapered and ultimately discontinued. Importantly, her parents noted marked improvement in sense of well-being. Several months after discontinuing treatment, she developed hyperpigmentation on the trunk consistent with confluent and reticulated papillomatosis; she has several known risk factors for this disorder, but it is not clear if this is related to her previous treatment. PMID:24326561

  16. Potent, transient inhibition of BCR-ABL with dasatinib 100 mg daily achieves rapid and durable cytogenetic responses and high transformation-free survival rates in chronic phase chronic myeloid leukemia patients with resistance, suboptimal response or intolerance to imatinib

    PubMed Central

    Shah, Neil P.; Kim, Dong-Wook; Kantarjian, Hagop; Rousselot, Philippe; Llacer, Pedro Enrique Dorlhiac; Enrico, Alicia; Vela-Ojeda, Jorge; Silver, Richard T.; Khoury, Hanna Jean; Müller, Martin C.; Lambert, Alexandre; Matloub, Yousif; Hochhaus, Andreas

    2010-01-01

    Background Dasatinib 100 mg once daily achieves intermittent BCR-ABL kinase inhibition and is approved for chronic-phase chronic myeloid leukemia patients resistant or intolerant to imatinib. To better assess durability of response to and tolerability of dasatinib, data from a 2-year minimum follow-up for a dose-optimization study in chronic-phase chronic myeloid leukemia are reported here. Design and Methods In a phase 3 study, 670 chronic-phase chronic myeloid leukemia patients with resistance, intolerance, or suboptimal response to imatinib were randomized to dasatinib 100 mg once-daily, 50 mg twice-daily, 140 mg once-daily, or 70 mg twice-daily. Results Data from a 2-year minimum follow-up demonstrate that dasatinib 100 mg once daily achieves major cytogenetic response and complete cytogenetic response rates comparable to those in the other treatment arms, and reduces the frequency of key side effects. Comparable 2-year progression-free survival and overall survival rates were observed (80% and 91%, respectively, for 100 mg once daily, and 75%–76% and 88%–94%, respectively, in other arms). Complete cytogenetic responses were achieved rapidly, typically by 6 months. In patients treated with dasatinib 100 mg once daily for 6 months without complete cytogenetic response, the likelihood of achieving such a response by 2 years was 50% for patients who had achieved a partial cytogenetic response, and only 8% or less for patients with minor, minimal, or no cytogenetic response. Less than 3% of patients suffered disease transformation to accelerated or blast phase. Conclusions Intermittent kinase inhibition can achieve rapid and durable responses, indistinguishable from those achieved with more continuous inhibition. PMID:20139391

  17. 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

  18. A Quantitative Synthesis of Response Card Research on Student Participation, Academic Achievement, Classroom Disruptive Behavior, and Student Preference

    ERIC Educational Resources Information Center

    Randolph, Justus J.

    2005-01-01

    Response cards are a teaching and learning tool designed to increase active student response during whole-class instruction. Response cards allow multiple students to write their answers on a white board and get feedback from the teacher during each learning trial. This work is a quantitative synthesis of the English-language student-level…

  19. Heifer body weight gain and reproductive achievement in response to protein and energy supplementation while grazing dormant range forage

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Heifers grazing winter range require supplemental nutrients to compliment dormant forage to achieve optimal growth and performance. A study was conducted to evaluate nutritional environment and effect of different supplementation strategies for developing heifers grazing dormant winter range. Eigh...

  20. Tumor Antigen–Targeted, Monoclonal Antibody–Based Immunotherapy: Clinical Response, Cellular Immunity, and Immunoescape

    PubMed Central

    Ferris, Robert L.; Jaffee, Elizabeth M.; Ferrone, Soldano

    2010-01-01

    Purpose Tumor antigen (TA) –targeted monoclonal antibodies (mAb), rituximab, trastuzumab, and cetuximab, are clinically effective for some advanced malignancies, especially in conjunction with chemotherapy and/or radiotherapy. However, these results are only seen in a subset (20% to 30%) of patients. We discuss the immunologic mechanism(s) underlying these clinical findings and their potential role in the variability in patients' clinical response. Methods We reviewed the evidence indicating that the effects of TA-targeted mAb-based immunotherapy are mediated not only by inhibition of signaling pathways, but also by cell-mediated cytotoxicity triggered by the infused TA-targeted mAb. We analyzed the immunologic variables that can influence the outcome of antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro and in animal model systems. We also analyzed the correlation reported between these variables and the clinical response to mAb-based immunotherapy. Results Of the variables that influence ADCC mediated by TA-targeted mAb, only polymorphisms of Fcγ receptors (FcγR) expressed by patients' lymphocytes were correlated with clinical efficacy. However, this correlation is not absolute and is not observed in all malignancies. Thus other variables may be responsible for the antitumor effects seen in mAb-treated patients. We discuss the evidence that triggering of TA-specific cellular immunity by TA-targeted mAb, in conjunction with immune escape mechanisms used by tumor cells, may contribute to the differential clinical responses to mAb-based immunotherapy. Conclusion Identification of the mechanism(s) underlying the clinical response of patients with cancer treated with TA-targeted mAb is crucial to optimizing their application in the clinic and to selecting the patients most likely to benefit from their use. PMID:20697078

  1. Improvement in latent variable indirect response joint modeling of a continuous and a categorical clinical endpoint in rheumatoid arthritis.

    PubMed

    Hu, Chuanpu; Zhou, Honghui

    2016-02-01

    Improving the quality of exposure-response modeling is important in clinical drug development. The general joint modeling of multiple endpoints is made possible in part by recent progress on the latent variable indirect response (IDR) modeling for ordered categorical endpoints. This manuscript aims to investigate, when modeling a continuous and a categorical clinical endpoint, the level of improvement achievable by joint modeling in the latent variable IDR modeling framework through the sharing of model parameters for the individual endpoints, guided by the appropriate representation of drug and placebo mechanism. This was illustrated with data from two phase III clinical trials of intravenously administered mAb X for the treatment of rheumatoid arthritis, with the 28-joint disease activity score (DAS28) and 20, 50, and 70% improvement in the American College of Rheumatology (ACR20, ACR50, and ACR70) disease severity criteria were used as efficacy endpoints. The joint modeling framework led to a parsimonious final model with reasonable performance, evaluated by visual predictive check. The results showed that, compared with the more common approach of separately modeling the endpoints, it is possible for the joint model to be more parsimonious and yet better describe the individual endpoints. In particular, the joint model may better describe one endpoint through subject-specific random effects that would not have been estimable from data of this endpoint alone.

  2. 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

  3. Integrating Service Learning into the Classroom: Examining the Extent to Which Students Achieve Course Objectives and a Sense of Civic Responsibility by Engaging in Service Learning

    ERIC Educational Resources Information Center

    Phillips, Julie M.

    2011-01-01

    The growing interest in service learning in higher education is connected to the idea that it helps students achieve course objectives and develop a sense of civic responsibility. Thus, it ties into broader goals within the institution of engagement of students and outreach to communities. This research examines students' perceptions of service…

  4. 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…

  5. 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…

  6. 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…

  7. 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

  8. Clinical pharmacokinetics of atypical antipsychotics: a critical review of the relationship between plasma concentrations and clinical response.

    PubMed

    Mauri, Massimo C; Volonteri, Lucia S; Colasanti, Alessandro; Fiorentini, Alessio; De Gaspari, Ilaria F; Bareggi, Silvio R

    2007-01-01

    In the past, the information about the dose-clinical effectiveness of typical antipsychotics was not complete and this led to the risk of extrapyramidal adverse effects. This, together with the intention of improving patients' quality of life and therapeutic compliance, resulted in the development of atypical or second-generation antipsychotics (SGAs). This review will concentrate on the pharmacokinetics and metabolism of clozapine, risperidone, olanzapine, quetiapine, amisulpride, ziprasidone, aripiprazole and sertindole, and will discuss the main aspects of their pharmacodynamics. In psychopharmacology, therapeutic drug monitoring studies have generally concentrated on controlling compliance and avoiding adverse effects by keeping long-term exposure to the minimal effective blood concentration. The rationale for using therapeutic drug monitoring in relation to SGAs is still a matter of debate, but there is growing evidence that it can improve efficacy, especially when patients do not respond to therapeutic doses or when they develop adverse effects. Here, we review the literature concerning the relationships between plasma concentrations of SGAs and clinical responses by dividing the studies on the basis of the length of their observation periods. Studies with clozapine evidenced a positive relationship between plasma concentrations and clinical response, with a threshold of 350-420 ng/mL associated with good clinical response. The usefulness of therapeutic drug monitoring is well established because high plasma concentrations of clozapine can increase the risk of epileptic seizures. Plasma clozapine concentrations seem to be influenced by many factors such as altered cytochrome P450 1A4 activity, age, sex and smoking. The pharmacological effects of risperidone depend on the sum of the plasma concentrations of risperidone and its 9-hydroxyrisperidone metabolite, so monitoring the plasma concentrations of the parent compound alone can lead to erroneous

  9. 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

  10. Effects of Achieving Target Measures in Rheumatoid Arthritis on Functional Status, Quality of Life, and Resource Utilization: Analysis of Clinical Practice Data

    PubMed Central

    Joo, Seongjung; Kawabata, Hugh; Al, Maiwenn J.; Allison, Paul D.; Rutten‐van Mölken, Maureen P. M. H.; Frits, Michelle L.; Iannaccone, Christine K.; Shadick, Nancy A.; Weinblatt, Michael E.

    2016-01-01

    Objective To evaluate associations between achieving guideline‐recommended targets of disease activity, defined by the Disease Activity Score in 28 joints using C‐reactive protein level (DAS28‐CRP) <2.6, the Simplified Disease Activity Index (SDAI) ≤3.3, or the Clinical Disease Activity Index (CDAI) ≤2.8, and other health outcomes in a longitudinal observational study. Methods Other defined thresholds included low disease activity (LDA), moderate (MDA), or severe disease activity (SDA). To control for intraclass correlation and estimate effects of independent variables on outcomes of the modified Health Assessment Questionnaire (M‐HAQ), the EuroQol 5‐domain (EQ‐5D; a quality‐of‐life measure), hospitalization, and durable medical equipment (DME) use, we employed mixed models for continuous outcomes and generalized estimating equations for binary outcomes. Results Among 1,297 subjects, achievement (versus nonachievement) of recommended disease targets was associated with enhanced physical functioning and lower health resource utilization. After controlling for baseline covariates, achievement of disease targets (versus LDA) was associated with significantly enhanced physical functioning based on SDAI ≤3.3 (ΔM‐HAQ −0.047; P = 0.0100) and CDAI ≤2.8 (−0.073; P = 0.0003) but not DAS28‐CRP <2.6 (−0.022; P = 0.1735). Target attainment was associated with significantly improved EQ‐5D (0.022–0.096; P < 0.0030 versus LDA, MDA, or SDA). Patients achieving guideline‐recommended disease targets were 36–45% less likely to be hospitalized (P < 0.0500) and 23–45% less likely to utilize DME (P < 0.0100). Conclusion Attaining recommended target disease‐activity measures was associated with enhanced physical functioning and health‐related quality of life. Some health outcomes were similar in subjects attaining guideline targets versus LDA. Achieving LDA is a worthy clinical objective in some patients. PMID:26238974

  11. 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…

  12. 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…

  13. 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…

  14. The Long and Winding Road to Social Justice: Missouri District Uses Culturally Responsive Instruction to Close the Achievement Gap

    ERIC Educational Resources Information Center

    Ijei, Charlotte; Harrison, Julie

    2010-01-01

    A key component to eliminating the achievement gap is building relationships between educators and students of color. In working toward social justice in schools, the authors encounter people at different places on the continuum. Educators in the large, primarily white, suburban Parkway School District in St. Louis, Missouri, range from the…

  15. 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.

  16. Decreased Sperm Motility Retarded ICSI Fertilization Rate in Severe Oligozoospermia but Good-Quality Embryo Transfer Had Achieved the Prospective Clinical Outcomes

    PubMed Central

    Zheng, Jufeng; Lu, Yongning; Qu, Xianqin; Wang, Peng; Zhao, Luiwen; Gao, Minzhi; Shi, Huijuan; Jin, Xingliang

    2016-01-01

    . Overall rates in all groups were 41.26% clinical pregnancy, 25.74% implantation and 36.32% live birth, which gave live birth to 252 girls and 252 boys. Conclusions The reduction of motile spermatozoa in severe oligozoospermia decreased the rates of fertilization and good-quality embryo. Obtaining and transfer of good-quality embryos was the good prognostic to achieve prospective clinical outcomes regardless of the severity of oligozoospermia. PMID:27661081

  17. 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

  18. Clinical and Virological Responses to Clevudine Therapy of Hepatocelluar Carcinoma Patients with Chronic Hepatitis B

    PubMed Central

    Woo, Sang Myung; Lee, Woo Jin; Kim, Chang-Min

    2011-01-01

    Background/Aims The clinical effects of clevudine have been reported in patients with chronic hepatitis B virus infections (CHIs). In this investigation, we assessed whether clevudine induced biochemical and virological improvements in hepatocellular carcinoma (HCC) patients with CHI. Methods Fifty-four patients who received 30 mg clevudine for more than 24 weeks between 2007 and 2009 at the National Cancer Center Hospital, Korea, were enrolled. Among these cases, 39 had HCC (CHI/HCC group) and 15 did not (CHI group). Results In relation to the CHI group, the CHI/HCC group was older (55.5 years.) and had a higher liver cirrhosis rate (79.5%) (p<0.05). Median changes in serum hepatitis B virus (HBV) DNA levels from baseline at weeks 12, 24, and 36 of treatment in the CHI/HCC group were not significantly different from those of the CHI group (-2.3, -2.7, -2.6 vs -1.7, -1.8, -2.4, respectively). HBV DNA <2,000 copies/mL was achieved in 76.5% of the CHI/HCC group at 24 weeks. Rates of ALT normalization in the CHI/HCC and CHI groups were 62.5% and 66.7%, respectively (p>0.05). Liver function was preserved with clevudine treatment in patients displaying response or stable disease under anti-cancer therapy. Four patients (7.4%) developed viral resistance during clevudine therapy. Among these, one was naïve, and three had previously received antiviral therapy. One CHI/HCC patient (1.9%) discontinued clevudine treatment due to symptomatic myopathy. Conclusions Our findings clearly indicate that clevudine has comparable antiviral and biochemical effects in patients with CHI and with CHI/HCC and preserves the underlying liver function in HBV-related HCC patients. PMID:21461078

  19. m-Chlorophenylpiperazine challenge in borderline personality disorder: relationship of neuroendocrine response, behavioral response, and clinical measures.

    PubMed

    Stein, D J; Hollander, E; DeCaria, C M; Simeon, D; Cohen, L; Aronowitz, B

    1996-09-15

    We have previously found that a subgroup of patients with impulsive personality disorders respond to m-chlorophenylpiperazine (m-CPP) administration with a distinctive spacy/high behavioral reaction and with increased cortisol responses. In this report we analyzed the relationship between behavioral and neuroendocrine responses to m-CPP in an enlarged sample of patients with borderline personality disorder (BPD). We also assessed the association of behavioral and neuroendocrine responses with clinical symptoms and with m-CPP blood levels. We found that in BPD patients the presence of a spacy/high behavioral response was significantly associated with increased prolactin and cortisol responses to m-CPP. In BPD patients increased m-CPP levels were significantly associated with neuroendocrine hypersensitivity and with a spacy/high behavioral response, while in controls increased m-CPP levels were not significantly associated with neuroendocrine hypersensitivity but were significantly associated with dysphoric behavioral responses. Taken together with previous work on m-CPP in obsessive-compulsive disorder, these results are partially consistent with the hypothesis that compulsive and impulsive symptoms fall at opposite ends of a phenomenologic and neurobiologic spectrum.

  20. 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

  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.

  2. Simply the best: teaching gerontological nursing students to teach evidence-based practice. Creating tip sheets can help achieve the goal of implementing EBP in clinical facilities.

    PubMed

    Schoenfelder, Deborah Perry

    2007-08-01

    This article describes a teaching strategy used in an undergraduate gerontological nursing clinical course to familiarize students with evidence-based practice. Students are required to read and summarize an assigned evidence-based practice guideline published by The University of Iowa Gerontological Nursing Interventions Research Center. They then develop a "tip sheet," based on the assigned guideline, to disseminate to health care staff at their practicum sites, which is either a long-term care facility or a hospital-based skilled nursing facility. Nursing students' reactions to the assignment and nursing staff's responses to the tip sheets are discussed.

  3. 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

  4. Hepatitis B Vaccine Antibody Response and the Risk of Clinical AIDS or Death

    PubMed Central

    Landrum, Michael L.; Hullsiek, Katherine Huppler; O'Connell, Robert J.; Chun, Helen M.; Ganesan, Anuradha; Okulicz, Jason F.; Lalani, Tahaniyat; Weintrob, Amy C.; Crum-Cianflone, Nancy F.; Agan, Brian K.

    2012-01-01

    Background Whether seroresponse to a vaccine such as hepatitis B virus (HBV) vaccine can provide a measure of the functional immune status of HIV-infected persons is unknown.This study evaluated the relationship between HBV vaccine seroresponses and progression to clinical AIDS or death. Methods and Findings From a large HIV cohort, we evaluated those who received HBV vaccine only after HIV diagnosis and had anti-HBs determination 1–12 months after the last vaccine dose. Non-response and positive response were defined as anti-HBs <10 and ≥10 IU/L, respectively. Participants were followed from date of last vaccination to clinical AIDS, death, or last visit. Univariate and multivariable risk of progression to clinical AIDS or death were evaluated with Cox regression models. A total of 795 participants vaccinated from 1986–2010 were included, of which 41% were responders. During 3,872 person-years of observation, 122 AIDS or death events occurred (53% after 1995). Twenty-two percent of non-responders experienced clinical AIDS or death compared with 5% of responders (p<0.001). Non-response to HBV vaccine was associated with a greater than 2-fold increased risk of clinical AIDS or death (HR 2.47; 95% CI, 1.38–4.43) compared with a positive response, after adjusting for CD4 count, HIV viral load, HAART use, and delayed type hypersensitivity skin test responses (an in vivo marker of cell-mediated immunity). This association remained evident among those with CD4 count ≥500 cells/mm3 (HR 3.40; 95% CI, 1.39–8.32). Conclusions HBV vaccine responses may have utility in assessing functional immune status and risk stratificating HIV-infected individuals, including those with CD4 count ≥500 cells/mm3. PMID:22457767

  5. 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

  6. Prediction of Response to Treatment in a Randomized Clinical Trial of Marital Therapy

    ERIC Educational Resources Information Center

    Atkins, David C.; Berns, Sara B.; George, William H.; Doss, Brian D.; Gattis, Krista; Christensen, Andrew

    2005-01-01

    This study investigated demographic, intrapersonal, and interpersonal predictors of treatment response in a randomized clinical trial of 134 distressed married couples, which examined traditional (N. S. Jacobson & G. Margolin, 1979) and integrative (N. S. Jacobson & A. Christensen, 1996) behavioral couple therapy. Results based on hierarchical…

  7. 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…

  8. 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…

  9. The Impact of School Libraries on Academic Achievement: A Research Study Based on Responses from Administrators in Idaho

    ERIC Educational Resources Information Center

    Lance, Keith Curry; Rodney, Marcia J.; Schwarz, Bill

    2010-01-01

    Where administrators value strong library programs and can see them doing their part for student success, students are more likely to thrive academically. This is the over-arching conclusion that can be drawn from the latest study of the impact of school libraries--this one in Idaho. The study included survey responses from 176 principals and…

  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. Evaluating the Effectiveness of Response to Intervention: Comparing the Reading Achievement of ELLs and Native English Speakers

    ERIC Educational Resources Information Center

    Sapienza, Philip Kiersten

    2012-01-01

    Teaching reading in the mainstream classroom is a challenge. This challenge is compounded when trying to meet the needs of English language learners. Recently, Response to Intervention (RTI) has been suggested as a framework for classroom teachers to use in order to meet the wide range of needs of their students. The purpose of this study was to…

  13. 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

  14. 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

  15. The effects of violent media on adolescent inkblot responses: implications for clinical and forensic assessments.

    PubMed

    Hess, T H; Hess, K D; Hess, A K

    1999-04-01

    Two experiments were conducted to assess the degree to which violent media stimulate violent fantasy as depicted on inkblot responses. In Experiment I, 41 gifted high school students were exposed to a bucolic or violent film clip and then were asked to produce inkblot responses. In Experiment II, a second sample of 43 additional students were exposed to a verbal description of the bucolic or violent scene to assess whether the "hot" or "cooler" media (McLuhan, 1964) had different effects on the inkblot responses. In both experiments, the media exposure led to increased levels of violent responses, and in both cases males produced more violent responses. There was no sex by media interaction effect. Implications for clinical and forensic assessments are presented.

  16. 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

  17. 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

  18. 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.

  19. The importance of molecular profiling in predicting response to epidermal growth factor receptor family inhibitors in non-small-cell lung cancer: focus on clinical trial results.

    PubMed

    Tsao, Anne S; Papadimitrakopoulou, Vassiliki

    2013-07-01

    In recent years, the epidermal growth factor receptor (EGFR) family has become a key focus of non-small-cell lung cancer biology and targeted therapies, such as the reversible EGFR tyrosine kinase inhibitors erlotinib and gefitinib. Initially, response to these agents was associated with certain demographic and clinical characteristics; subsequently, it was discovered that these subgroups were more likely to harbor specific mutations in the EGFR gene that enhanced tumor response. However, the presence of these mutations does not equate to therapeutic success. Other aspects of EGFR family signaling, including other types of EGFR mutations, EGFR protein expression, EGFR gene amplification, mediators of downstream signaling, and other receptors with similar downstream pathways may all play a role in response or resistance to treatment. The identification of these and other molecular determinants is driving the development of novel therapies designed to achieve improved clinical outcomes in patients.

  20. 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

  1. 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.

  2. Traumatic Reticuloperitonitis in Water Buffalo (Bubalus bubalis): Clinical Findings and the Associated Inflammatory Response.

    PubMed

    El-Ashker, Maged; Salama, Mohamed; El-Boshy, Mohamed

    2013-01-01

    The present study was carried out to describe the clinical picture of traumatic reticuloperitonitis (TRP) in water buffalo (Bubalus bubalis) and to evaluate the inflammatory and immunologic responses for this clinical condition. Twenty-two buffalo with acute local TRP were monitored in our study. Additionally, 10 clinically healthy buffalo were randomly selected and served as controls. Acute local TRP was initially diagnosed by clinical examination and confirmed by ultrasonographic (USG) examination and/or necropsy findings. Blood samples were collected from all examined buffalo to measure the respective levels of tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, IL-6, IL-10 and interferon gamma (INF)-γ, serum amyloid A (SAA), C-reactive protein (CRP), haptoglobin (Hp), fibrinogen (Fb), and serum sialic acid (SSA). It was found that TNF-α, IL-1β, IL-6, IL-10, SAA, CRP, Hp, Fb, and SSA were significantly higher in buffalo with TRP than the controls. Our findings suggest that the examined immunologic variables were helpful in documenting the inflammatory response in buffalo with TRP. However, their diagnostic usefulness only becomes apparent when considered in tandem with the clinical findings for any given animal, its anamnesis, and a subsequent USG assessment. Due to the frequent complications of TRP, more accurate indicators of its occurrence and severity would be useful.

  3. Recruiting faculty with clinical responsibilities: factors that influence a decision to accept an academic position.

    PubMed

    Grauer, Gregory F

    2005-01-01

    The current opportunities for veterinary clinical specialists in private practice and industry have made recruiting and retaining faculty a major focus for most clinical academic departments. To gain a better understanding of the importance of the various factors considered in accepting an academic position, an electronic survey was distributed to newly hired veterinary faculty with clinical responsibilities. The results suggest that the perceived climate and collegiality within the prospective hiring department is the most important factor influencing the decision to accept an academic position. Salary is the second most important factor. Institutional support for the newly hired faculty member and the reputation and quality of the prospective institution rank as more important than the perceived quality of the local community and the geographic location of the institution. The search process and administrative support are the least important factors. There were no differences between the responses of faculty hired into tenure-track positions and those of faculty hired into clinical-track positions. Focusing on the advantages of a collegial environment, enhancing compensation packages, and using creative and flexible appointments may improve faculty recruitment and retention in clinical academic departments.

  4. Response to placebo in clinical epilepsy trials--Old ideas and new insights.

    PubMed

    Goldenholz, Daniel M; Goldenholz, Shira R

    2016-05-01

    Randomized placebo-controlled trials are a mainstay of modern clinical epilepsy research; the success or failure of innovative therapies depends on proving superiority to a placebo. Consequently, understanding what drives response to placebo (including the "placebo effect") may facilitate evaluation of new therapies. In this review, part one will explore observations about placebos specific to epilepsy, including the relatively higher placebo response in children, apparent increase in placebo response over the past several decades, geographic variation in placebo effect, relationship to baseline epilepsy characteristics, influence of nocebo on clinical trials, the possible increase in (SUDEP) in placebo arms of trials, and patterns that placebo responses appear to follow in individual patients. Part two will discuss the principal causes of placebo responses, including regression to the mean, anticipation, classical conditioning, the Hawthorne effect, expectations from symbols, and the natural history of disease. Included in part two will be a brief overview of recent advances using simulations from large datasets that have afforded new insights into causes of epilepsy-related placebo responses. In part three, new developments in study design will be explored, including sequential parallel comparison, two-way enriched design, time to pre-randomization, delayed start, and cohort reduction techniques. PMID:26921852

  5. Volumetric Response beyond Six Months of Cardiac Resynchronization Therapy and Clinical Outcome

    PubMed Central

    van ’t Sant, Jetske; Fiolet, Aernoud T. L.; ter Horst, Iris A. H.; Cramer, Maarten J.; Mastenbroek, Mirjam H.; van Everdingen, Wouter M.; Mast, Thomas P.; Doevendans, Pieter A.

    2015-01-01

    Aims Response to cardiac resynchronization therapy (CRT) is often assessed six months after implantation. Our objective was to assess the number of patients changing from responder to non-responder between six and 14 months, so-called late non-responders, and compare them to patients who were responder both at six and 14 months, so-called stable responders. Furthermore, we assessed predictive values of six and 14-month response concerning clinical outcome. Methods 105 patients eligible for CRT were enrolled. Clinical, laboratory, ECG, and echocardiographic parameters and patient-reported health status (Kansas City Cardiomyopathy Questionnaire [KCCQ]) were assessed before, and six and 14 months after implantation. Response was defined as ≥15% LVESV decrease as compared to baseline. Major adverse cardiac events (MACE) were registered until 24 months after implantation. Predictive values of six and 14-month response for MACE were examined. Results In total, 75 (71%) patients were six-month responders of which 12 (16%) patients became late non-responder. At baseline, late non-responders more often had ischemic cardiomyopathy and atrial fibrillation, higher BNP and less dyssynchrony compared to stable responders. At six months, late non-responders showed significantly less LVESV decrease, and higher creatinine levels. Mean KCCQ scores of late non-responders were lower than those of stable responders at every time point, with the difference being significant at 14 months. The 14 months response was a better predictor of MACE than six months response. Conclusions The assessment of treatment outcomes after six months of CRT could be premature and response rates beyond might better correlate to long-term clinical outcome. PMID:25933068

  6. 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.

  7. New roles and responsibilities of NHS chief executives in relation to quality and clinical governance

    PubMed Central

    Sausman, C.

    2001-01-01

    The role of the chief executive in the NHS is to act as organisational head, with financial and managerial responsibility, and now responsibility has been extended to include clinical standards as part of the duty of quality and the introduction of clinical governance. These new responsibilities have implications for relations with staff inside the organisation and, in particular, with clinicians, as well as adding to the overall public accountability of chief executives. As well as increasing expectations of chief executives to meet performance objectives and other targets within the organisation, their role remains relatively new and sometimes contentious in the health service, forming part of the history of NHS management reform. The developing role of chief executives and the complex world in which they operate in the health service is discussed. It is suggested that support from colleagues at both the organisational and national levels is required to help them discharge their new responsibilities, together with a greater focus on the development of their role and skills. Key Words: NHS chief executives; management reform; clinical governance PMID:11700374

  8. 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.

  9. Hemodynamic, Functional, and Clinical Responses to Pulmonary Artery Denervation in Patients With Pulmonary Arterial Hypertension of Different Causes

    PubMed Central

    Zhang, Hang; Xie, Du-Jiang; Zhang, Juan; Zhou, Ling; Rothman, Alexander M.K.

    2015-01-01

    Background— The mechanisms underlying pulmonary arterial hypertension (PAH) are multifactorial. The efficacy of pulmonary artery denervation (PADN) for idiopathic PAH treatment has been evaluated. This study aimed to analyze the hemodynamic, functional, and clinical responses to PADN in patients with PAH of different causes. Methods and Results— Between April 2012 and April 2014, 66 consecutive patients with a resting mean pulmonary arterial pressure ≥25 mm Hg treated with PADN were prospectively followed up. Target drugs were discontinued after the PADN procedure. Hemodynamic response and 6-minute walk distance were repeatedly measured within the 1 year post PADN follow-up. The clinical end point was the occurrence of PAH-related events at the 1-year follow-up. There were no PADN-related complications. Hemodynamic success (defined as the reduction in mean pulmonary arterial pressure by a minimal 10% post PADN) was achieved in 94% of all patients, with a mean absolute reduction in systolic pulmonary arterial pressure and mean pulmonary arterial pressure within 24 hours of −10 mm Hg and −7 mm Hg, respectively. The average increment in 6-minute walk distance after PADN was 94 m. Worse PAH-related events occurred in 10 patients (15%), mostly driven by the worsening of PAH (12%). There were 8 (12%) all-cause deaths, with 6 (9%) PAH-related deaths. Conclusions— PADN was safe and feasible for the treatment of PAH. The PADN procedure was associated with significant improvements in hemodynamic function, exercise capacity, and cardiac function and with less frequent PAH-related events and death at 1 year after PADN treatment. Further randomized studies are required to confirm the efficacy of PADN for PAH. Clinical Trial Registration— URL: http://www.chictr.trc.com.cn. Unique identifier: chiCTR-ONC-12002085. PMID:26553699

  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. 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

  12. Response Assessment and Magnetic Resonance Imaging Issues for Clinical Trials Involving High-Grade Gliomas.

    PubMed

    Boxerman, Jerrold L; Ellingson, Benjamin M

    2015-06-01

    There exist multiple challenges associated with the current response assessment criteria for high-grade gliomas, including the uncertain role of changes in nonenhancing T2 hyperintensity, and the phenomena of pseudoresponse and pseudoprogression in the setting of antiangiogenic and chemoradiation therapies, respectively. Advanced physiological magnetic resonance imaging (MRI), including diffusion and perfusion (dynamic susceptibility contrast MRI and dynamic contrast-enhanced MRI) sensitive techniques for overcoming response assessment challenges, has been proposed, with their own potential advantages and inherent shortcomings. Measurement variability exists for conventional and advanced MRI techniques, necessitating the standardization of image acquisition parameters in order to establish the utility of these imaging methods in multicenter trials for high-grade gliomas. This review chapter highlights the important features of MRI in clinical brain tumor trials, focusing on the current state of response assessment in brain tumors, advanced imaging techniques that may provide additional value for determining response, and imaging issues to be considered for multicenter trials.

  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. Past and present achievements, and future direction of the Gastrointestinal Oncology Study Group (GIOSG), a Division of Japan Clinical Oncology Group (JCOG).

    PubMed

    Boku, Narikazu

    2011-12-01

    Initially, Gastrointestinal Study Group in Japan Clinical Oncology Group (GIOSG/JCOG) focused on gastric cancer. In 1980s, fluoropyrimidine, cisplatin and mitomycin C were key drugs. A randomized Phase II trial (JCOG8501) comparing futrafur plus mitomycin C and uracil plus futrafur and mitomycin C showed a higher response rate of uracil plus futrafur and mitomycin C than futrafur plus mitomycin C. From the results of two Phase II trials of etoposide, adriamycin and cisplatin, and cisplatin plus 5-fluorouracil, uracil plus futrafur and mitomycin C and cisplatin plus 5-fluorouracil were adopted for the test arms of the Phase III trial (JCOG9205) comparing with continuous infusion of 5-fluorouracil as a control arm. Neither cisplatin plus 5-fluorouracil nor uracil plus futrafur and mitomycin C showed a survival benefit over continuous infusion of 5-fluorouracil. In late 1990s, new agents, irinotecan and S-1, were developed for gastric cancer in Japan. GIOSG conducted a Phase III trial (JCOG9912) investigating superiority of irinotecan plus cisplatin and non-inferiority of monotherapy with S-1 compared with continuous infusion of 5-fluorouracil, and S-1 succeeded in showing non-inferiority. Then, SPIRITS trial showed a survival benefit of S-1 plus cisplatin over S-1, resulting in the establishment of a standard care for advanced gastric cancer in Japan. GIOSG have merged with Gastric Cancer Study Group as the Stomach Cancer Study Group (SCSG) from 2011. Recent progress in the development of new drugs has been remarkable. From the point of the roles shared with many other study groups for clinical trials, including registration trials of new drugs conducted by pharmaceutical companies, SCSG should recognize its role and conduct clinical trials with high quality for establishing new standard treatment.

  15. Histone deacetylase inhibitor romidepsin induces HIV expression in CD4 T cells from patients on suppressive antiretroviral therapy at concentrations achieved by clinical dosing.

    PubMed

    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

    2014-04-01

    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.

  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. CTLA4 blockade induces frequent tumor infiltration by activated lymphocytes regardless of clinical responses in humans

    PubMed Central

    Huang, Rong Rong; Jalil, Jason; Economou, James S.; Chmielowski, Bartosz; Koya, Richard C.; Mok, Stephen; Sazegar, Hooman; Seja, Elizabeth; Villanueva, Arturo; Gomez-Navarro, Jesus; Glaspy, John A.; Cochran, Alistair J.; Ribas, Antoni

    2011-01-01

    Background CTLA4 blocking monoclonal antibodies provide durable clinical benefit in a subset of patients with advanced melanoma mediated by intratumoral lymphocytic infiltrates. A key question is defining if the intratumoral infiltration is a differentiating factor between patients with and without tumor responses. Methods Paired baseline and post-dosing tumor biopsies from 19 subjects, including three patients with an objective tumor response, were prospectively collected from patients with metastatic melanoma receiving the anti-CTLA4 antibody tremelimumab within a clinical trial with primary endpoint of quantitating CD8+ cytotoxic T lymphocyte (CTL) infiltration in tumors. Samples were analyzed for cell density using automated imaging capture, and further characterized for functional lymphocyte properties by assessing the cell activation markers HLA-DR and CD45RO, the cell proliferation marker Ki67 and the T regulatory cell marker FOXP3. Results There was a highly significant increase in intratumoral infiltration by CD8+ cells in biopsies taken after tremelimumab treatment. This included increases between 1-fold and 100-fold changes in 14 out of 18 evaluable cases regardless of clinical tumor response or progression. There was no difference between the absolute number, location or cell density of infiltrating cells between clinical responders and patients with non-responding lesions that showed acquired intratumoral infiltrates. There were similar levels of expression of T cell activation markers (CD45RO, HLA-DR) in both groups, and no difference in markers for cell replication (Ki67) or the suppressor cell marker FOXP3. Conclusion CTLA4 blockade induces frequent increases in intratumoral T cell infiltration despite which only a minority of patients have objective tumor responses. PMID:21558401

  18. Clinical response and relapse in patients with chronic low back pain following osteopathic manual treatment: results from the OSTEOPATHIC Trial.

    PubMed

    Licciardone, John C; Aryal, Subhash

    2014-12-01

    Clinical response and relapse following a regimen of osteopathic manual treatment (OMT) were assessed in patients with chronic low back pain (LBP) within the OSTEOPATHIC Trial, a randomized, double-blind, sham-controlled study. Initial clinical response and subsequent stability of response, including final response and relapse status at week 12, were determined in 186 patients with high baseline pain severity (≥50 mm on a 100-mm visual analogue scale). Substantial improvement in LBP, defined as 50% or greater pain reduction relative to baseline, was used to assess clinical response at weeks 1, 2, 4, 6, 8, and 12. Sixty-two (65%) patients in the OMT group attained an initial clinical response vs. 41 (45%) patients in the sham OMT group (risk ratio [RR], 1.45; 95% confidence interval [CI], 1.11-1.90). The median time to initial clinical response to OMT in these patients was 4 weeks. Among patients with an initial clinical response prior to week 12, 13 (24%) patients in the OMT group vs. 18 (51%) patients in the sham OMT group relapsed (RR, 0.47; 95% CI, 0.26-0.83). Overall, 49 (52%) patients in the OMT group attained or maintained a clinical response at week 12 vs. 23 (25%) patients in the sham OMT group (RR, 2.04; 95% CI, 1.36-3.05). The large effect size for short-term efficacy of OMT was driven by stable responders who did not relapse.

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

    PubMed

    Light, Gregory A; Swerdlow, Neal R

    2015-05-01

    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 nonpharmacologic interventions and accounts for substantial portions of variance in clinical, cognitive, and psychosocial functioning in schizophrenia (SZ). This measure has recently been validated for use in large-scale multisite clinical studies of SZ. Finally, 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

  20. 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

  1. 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

  2. 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

  3. Clinical risk factors associated with anti-epileptic drug responsiveness in canine epilepsy.

    PubMed

    Packer, Rowena M A; Shihab, Nadia K; Torres, Bruno B J; Volk, Holger A

    2014-01-01

    The nature and occurrence of remission, and conversely, pharmacoresistance following epilepsy treatment is still not fully understood in human or veterinary medicine. As such, predicting which patients will have good or poor treatment outcomes is imprecise, impeding patient management. In the present study, we use a naturally occurring animal model of pharmacoresistant epilepsy to investigate clinical risk factors associated with treatment outcome. Dogs with idiopathic epilepsy, for which no underlying cause was identified, were treated at a canine epilepsy clinic and monitored following discharge from a small animal referral hospital. Clinical data was gained via standardised owner questionnaires and longitudinal follow up data was gained via telephone interview with the dogs' owners. At follow up, 14% of treated dogs were in seizure-free remission. Dogs that did not achieve remission were more likely to be male, and to have previously experienced cluster seizures. Seizure frequency or the total number of seizures prior to treatment were not significant predictors of pharmacoresistance, demonstrating that seizure density, that is, the temporal pattern of seizure activity, is a more influential predictor of pharmacoresistance. These results are in line with clinical studies of human epilepsy, and experimental rodent models of epilepsy, that patients experiencing episodes of high seizure density (cluster seizures), not just a high seizure frequency pre-treatment, are at an increased risk of drug-refractoriness. These data provide further evidence that the dog could be a useful naturally occurring epilepsy model in the study of pharmacoresistant epilepsy.

  4. 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

  5. Proteomics of inflammatory and oxidative stress response in cows with subclinical and clinical mastitis.

    PubMed

    Turk, Romana; Piras, Cristian; Kovačić, Mislav; Samardžija, Marko; Ahmed, Hany; De Canio, Michele; Urbani, Andrea; Meštrić, Zlata Flegar; Soggiu, Alessio; Bonizzi, Luigi; Roncada, Paola

    2012-07-19

    Cow serum proteome was evaluated by three different complementary approaches in the control group, subclinical and clinical mastitis in order to possibly find differential protein expression useful for a better understanding of the pathophysiology of mastitis as well as for an early diagnosis of the disease. The systemic inflammatory and oxidative stress response in cows with subclinical and clinical mastitis were observed. The collected evidence shows a differential protein expression of serpin A3-1, vitronectin-like protein and complement factor H in subclinical mastitis in comparison with the control. It was also found a differential protein expression of inter-alpha-trypsin inhibitor heavy chain H4, serpin A3-1, C4b-binding protein alpha chain, haptoglobin and apolipoprotein A-I in clinical mastitis compared to the control. Among the inflammatory proteins up-regulated in clinical mastitis, vitronectin is over-expressed in both subclinical and clinical mastitis indicating a strong bacterial infection. This suggests vitronectin as an important mediator in the pathogenesis of the onset of mastitis as well as a valuable marker for diagnosis of the subclinical form of the disease. Obtained data could be useful for the detection of mastitis during the subclinical phase and for a better comprehension of the pathophysiological mechanisms involved in the onset of the disease.

  6. 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.

  7. Plasma levels and clinical response with imipramine in a study comparing efficacy with mianserin and nomifensine

    PubMed Central

    Montgomery, S. A.; Roy, D.; Wynne-Willson, S.; Robinson, C.; Montgomery, D. B.

    1983-01-01

    1 The comparative antidepressant efficacy of 150 mg imipramine, 60 mg mianserin and 150 mg nomifensine was studied in 45 depressed patients in a six week double-blind investigation. 2 In the efficacy analysis of 41 patients completing the study there was no overall significant difference in efficacy between the groups. Individual group comparisons showed no significant difference in response between mianserin and nomifensine, and mianserin and imipramine. There was a significant (z=1.99, P<0.05) improved response in the imipramine compared with the nomifensine treated group. The imipramine treated group were significantly older. 3 No significant plasma concentration/clinical response relationships were demonstrated with nomifensine, mianserin, imipramine or desipramine. 4 Plasma level monitoring of imipramine recommended by some investigators does not seem to be appropriate. PMID:6337608

  8. Drug-Related Hyponatremic Encephalopathy: Rapid Clinical Response Averts Life-Threatening Acute Cerebral Edema

    PubMed Central

    Siegel, Arthur J.; Forte, Sophie S.; Bhatti, Nasir A.; Gelda, Steven E.

    2016-01-01

    Patient: Female, 63 Final Diagnosis: Drug-induced hyponatremic encephalopathy Symptoms: Seizures • coma Medication: Hypertonic 3% saline infusion Clinical Procedure: — Specialty: Internal Medicine Objective: Unusual clinical course Background: Drug-induced hyponatremia characteristically presents with subtle psychomotor symptoms due to its slow onset, which permits compensatory volume adjustment to hypo-osmolality in the central nervous system. Due mainly to the syndrome of inappropriate antidiuretic hormone secretion (SIADH), this condition readily resolves following discontinuation of the responsible pharmacological agent. Here, we present an unusual case of life-threatening encephalopathy due to adverse drug-related effects, in which a rapid clinical response facilitated emergent treatment to avert life-threatening acute cerebral edema. Case Report: A 63-year-old woman with refractory depression was admitted for inpatient psychiatric care with a normal physical examination and laboratory values, including a serum sodium [Na+] of 144 mEq/L. She had a grand mal seizure and became unresponsive on the fourth day of treatment with the dual serotonin and norepinephrine reuptake inhibitor [SNRI] duloxetine while being continued on a thiazide-containing diuretic for a hypertensive disorder. Emergent infusion of intravenous hypertonic (3%) saline was initiated after determination of a serum sodium [Na+] of 103 mEq/L with a urine osmolality of 314 mOsm/kg H20 and urine [Na+] of 12 mEq/L. Correction of hyposmolality in accordance with current guidelines resulted in progressive improvement over several days, and she returned to her baseline mental status. Conclusions: Seizures with life-threatening hyponatremic encephalopathy in this case likely resulted from co-occurring SIADH and sodium depletion due to duloxetine and hydrochlorothiazide, respectively. A rapid clinical response expedited diagnosis and emergent treatment to reverse life-threatening acute cerebral edema

  9. Functional diffusion map: a noninvasive MRI biomarker for early stratification of clinical brain tumor response.

    PubMed

    Moffat, Bradford A; Chenevert, Thomas L; Lawrence, Theodore S; Meyer, Charles R; Johnson, Timothy D; Dong, Qian; Tsien, Christina; Mukherji, Suresh; Quint, Douglas J; Gebarski, Stephen S; Robertson, Patricia L; Junck, Larry R; Rehemtulla, Alnawaz; Ross, Brian D

    2005-04-12

    Assessment of radiation and chemotherapy efficacy for brain cancer patients is traditionally accomplished by measuring changes in tumor size several months after therapy has been administered. The ability to use noninvasive imaging during the early stages of fractionated therapy to determine whether a particular treatment will be effective would provide an opportunity to optimize individual patient management and avoid unnecessary systemic toxicity, expense, and treatment delays. We investigated whether changes in the Brownian motion of water within tumor tissue as quantified by using diffusion MRI could be used as a biomarker for early prediction of treatment response in brain cancer patients. Twenty brain tumor patients were examined by standard and diffusion MRI before initiation of treatment. Additional images were acquired 3 weeks after initiation of chemo- and/or radiotherapy. Images were coregistered to pretreatment scans, and changes in tumor water diffusion values were calculated and displayed as a functional diffusion map (fDM) for correlation with clinical response. Of the 20 patients imaged during the course of therapy, 6 were classified as having a partial response, 6 as stable disease, and 8 as progressive disease. The fDMs were found to predict patient response at 3 weeks from the start of treatment, revealing that early changes in tumor diffusion values could be used as a prognostic indicator of subsequent volumetric tumor response. Overall, fDM analysis provided an early biomarker for predicting treatment response in brain tumor patients. PMID:15805192

  10. Radiographic Progression of Patients With Psoriatic Arthritis Who Achieve Minimal Disease Activity in Response to Golimumab Therapy: Results Through 5 Years of a Randomized, Placebo‐Controlled Study

    PubMed Central

    van der Heijde, Désirée; Beutler, Anna; Gladman, Dafna; Mease, Philip; Krueger, Gerald G.; McInnes, Iain B.; Helliwell, Philip; Coates, Laura C.; Xu, Stephen

    2016-01-01

    Objective To evaluate long‐term outcomes in psoriatic arthritis (PsA) patients who achieved or did not achieve minimal disease activity (MDA) through 5 years of golimumab treatment in the GO‐REVEAL trial. Methods The GO‐REVEAL trial was a phase III, randomized, double‐blind trial with placebo‐control through week 24 followed by an open‐label extension of golimumab 50/100 mg treatment up to 5 years. In these post‐hoc analyses, MDA was defined by the presence of ≥5 of 7 PsA outcome measures (≤1 swollen joint, ≤1 tender joint, Psoriasis Area and Severity Index [PASI] ≤1, patient pain score ≤15, patient global disease activity score ≤20 [range 0–100], Health Assessment Questionnaire disability index [HAQ DI] ≤0.5, and ≤1 tender enthesis point). Results Treatment with golimumab yielded significantly higher MDA response rates versus patients randomized to placebo at week 14 (23.5% versus 1.0%; P < 0.0001), week 24 (28.1% versus 7.7%; P < 0.0001), and week 52 (42.4% versus 30.2%; P = 0.037). MDA was achieved at least once by ∼50% of golimumab‐treated patients overall. Irrespective of treatment randomization, achievement of MDA at ≥3 and ≥4 consecutive visits was associated with significantly less radiographic progression and more improvement in MDA components allowing specific assessment of physical function (HAQ DI) and overall disease activity (patient global assessment of disease activity) at week 256 versus patients not achieving MDA. Logistic regression analyses indicated that a 1‐unit higher baseline HAQ DI score yielded a significantly lower likelihood of achieving MDA at ≥3 (odds ratio 0.514 [95% confidence interval 0.321–0.824]; P = 0.006) and ≥4 (odds ratio 0.480 [95% confidence interval 0.290–0.795]; P = 0.004) consecutive visits. Conclusion Among golimumab‐treated PsA patients, better long‐term functional improvement, patient global assessment, and radiographic outcomes were observed when

  11. Clinical response to chemotherapy in oesophageal adenocarcinoma patients is linked to defects in mitochondria.

    PubMed

    Aichler, Michaela; Elsner, Mareike; Ludyga, Natalie; Feuchtinger, Annette; Zangen, Verena; Maier, Stefan K; Balluff, Benjamin; Schöne, Cédrik; Hierber, Ludwig; Braselmann, Herbert; Meding, Stephan; Rauser, Sandra; Zischka, Hans; Aubele, Michaela; Schmitt, Manfred; Feith, Marcus; Hauck, Stefanie M; Ueffing, Marius; Langer, Rupert; Kuster, Bernhard; Zitzelsberger, Horst; Höfler, Heinz; Walch, Axel K

    2013-08-01

    Chemotherapeutic drugs kill cancer cells, but it is unclear why this happens in responding patients but not in non-responders. Proteomic profiles of patients with oesophageal adenocarcinoma may be helpful in predicting response and selecting more effective treatment strategies. In this study, pretherapeutic oesophageal adenocarcinoma biopsies were analysed for proteomic changes associated with response to chemotherapy by MALDI imaging mass spectrometry. Resulting candidate proteins were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and investigated for functional relevance in vitro. Clinical impact was validated in pretherapeutic biopsies from an independent patient cohort. Studies on the incidence of these defects in other solid tumours were included. We discovered that clinical response to cisplatin correlated with pre-existing defects in the mitochondrial respiratory chain complexes of cancer cells, caused by loss of specific cytochrome c oxidase (COX) subunits. Knockdown of a COX protein altered chemosensitivity in vitro, increasing the propensity of cancer cells to undergo cell death following cisplatin treatment. In an independent validation, patients with reduced COX protein expression prior to treatment exhibited favourable clinical outcomes to chemotherapy, whereas tumours with unchanged COX expression were chemoresistant. In conclusion, previously undiscovered pre-existing defects in mitochondrial respiratory complexes cause cancer cells to become chemosensitive: mitochondrial defects lower the cells' threshold for undergoing cell death in response to cisplatin. By contrast, cancer cells with intact mitochondrial respiratory complexes are chemoresistant and have a high threshold for cisplatin-induced cell death. This connection between mitochondrial respiration and chemosensitivity is relevant to anticancer therapeutics that target the mitochondrial electron transport chain.

  12. 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

  13. Evaluation of the response to treatment and clinical evolution in patients with burning mouth syndrome

    PubMed Central

    Rodríguez-de Rivera-Campillo, Eugenia

    2013-01-01

    Objective: the aim of this study is to investigate the clinical evolution, the spontaneous remission of the symptomatology and the response to different treatments in a group of burning mouth syndrome patients. Study Design: the sample was formed by a group of patients that were visited in the Unit of Oral Medicine of the Dentistry Clinic of the University of Barcelona, from the year 2000 to 2011. After revising the clinical records of all the patients that had been under control for a period of time of 18 months or longer, they were contacted by telephone. In the telephone interview, they were questioned about the symptomatology evolution and the response to the treatments received, noting down the data in a questionnaire previously performed. Results: the average duration of the symptoms was 6.5 years (+/-2.5 years). The most frequent treatments were: chlorhexidine mouthrinses, oral benzodiazepines, topical clonazepam, antiinflamatory drugs, antidepressants, antifungicals, vitamins, psycotherapy, salivary substitutes and topical corticoids. The specialists that were consulted with a higher frequency were: dermatologists (30%), othorrynolaringologists (10%) and psychiatrists (3%). In 41 patients the oral symptoms did not improve, 35 reported partial improvements, 12 patients worsened, and only in 3 patients the symptoms remitted. Conclusions: In three of the 91 patients studied the symptoms remitted spontaneously within the five years of treatment. Only 42% of the study population had improved the symptomatology significantly, and this improvement would reach 60% if clonazepam were associated to psychotherapy. Key words:Burning mouth syndrome, stomatodynia, oral pain, clonazepam. PMID:23229252

  14. 1995 survey of salaries & responsibilities for hospital biomedical/clinical engineering & technology personnel.

    PubMed

    Brush, L C

    1995-01-01

    The Journal of Clinical Engineering conducted its tenth annual survey of the salaries paid to biomedical/clinical engineering and technology personnel in U.S. hospitals. This paper reports the salary and work responsibility data obtained from 1,091 professionals in relationship to: Certification; Region of the U.S.; Teaching versus Nonteaching Facilities; Years of Experience; Education; Union Membership; and Gender. Data are included on Wage Increases and Job Responsibilities. Data are as of 12/31/94 and are compared to 12/31/93. The average BMET I has 3.2 years of experience and earns $25,460 +/- $6,600 (std. dev.). The average BMET II has 7.4 years of experience and earns $31,745 +/- $8,500. The average BMET III has 13.3 years of experience and earns $39,383 +/- $7,600. The average BMET Specialist has 13.3 years of experience and earns $43,090 /+- $1,700. The average BMET Supervisor has 14.7 years of experience and earns $42,930 /+- $7,600. The average Clinical Engineer has 10 years of experience and earns $43,169 /+- $11,100. CE Supervisors have an average 13.1 years of experience and an average salary of $47,776 /+- $11,300. The overall group or department Director or Manager has 15.5 years of experience and earns $51,982 /+- $14,000 on average. PMID:10144455

  15. 1996 survey of salaries & responsibilities for hospital biomedical/clinical engineering & technology personnel.

    PubMed

    Nighswonger, G F

    1996-01-01

    The Journal of Clinical Engineering conducted its eleventh annual survey of the salaries paid to biomedical/clinical engineering and technology personnel in U.S. hospitals. This paper reports the salary and work responsibility data obtained from 907 professionals in relationship to: Certification; Region of the U.S.; Teaching versus Nonteaching Facilities; Years of Experience; Education; Union Membership; and Gender. Data are included on Wage Increases and Job Responsibilities. Data are as of 12/31/95 and are compared with data as of 12/31/94. The average BMET I has 3.6 years of experience and earns $24,439 + $5,800 (nationwide mean + standard deviation). The average BMET II has 7.4 years of experience and earns $32,592 + $7,300. The average BMET III has 14.7 years of experience and earns $39,844 + $7,100. The average BMET Specialist has 16.1 years of experience and earns $44,484 + $10,400. The average BMET Supervisor has 15.4 years of experience and earns $42,939 + $8,500. The average Clinical Engineer has 11.7 years of experience and earns $44,844 + $9,600. CE Supervisors average 15.9 years of experience and have an average salary of $49,053 + $12,100. The overall group or department Director or Manager has 16.6 years of experience and earns $52,120 + $12,900 on average. PMID:10159651

  16. 1997 survey of salaries & responsibilities for hospital biomedical clinical engineering & technology personnel.

    PubMed

    Nighswonger, G F

    1997-01-01

    The Journal of Clinical Engineering conducted its twelfth annual survey of the salaries paid to biomedical/clinical engineering and technology personnel in U.S. hospitals. This paper reports the salary and work responsibility data obtained from 276 professionals in relationship to: region of the U.S.; teaching versus nonteaching facilities; years of experience; education; certification; union membership; and gender. Data are included on wage increases and job responsibilities as of 12/31/96, and are compared with data as of 12/31/95. The average BMET I has 2.9 years of experience and earns $26,126 +/- $5,800 (nationwide mean +/- standard deviation). The average BMET II has 8.29 years of experience and ears $34,687 +/- $6,300. The average BMET III has 12.7 years of experience and earns $40,960 +/- $6,900. The average BMET Specialist has 16.7 years of experience and earns $46,131 +/- $9,100. The average BMET Supervisor has 15.0 years of experience and ears $44,248 +/- 47,700. The average Clinical Engineer has 13.6 years of experience and earns $44,839 +/- $10,000. CE Supervisors have an average of 21.6 years of experience and an average salary of $59,789 +/- $13,100. The overall group or department Director or Manager has 17.5 years of experience and earns $55,325 +/- $16,200 on average. PMID:10169899

  17. 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.

  18. 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.

  19. 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.…

  20. 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

  1. Peptide vaccines in breast cancer: The immunological basis for clinical response.

    PubMed

    Peres, Lívia de Paula; da Luz, Felipe Andrés Cordero; Pultz, Brunna dos Anjos; Brígido, Paula Cristina; de Araújo, Rogério Agenor; Goulart, Luiz Ricardo; Silva, Marcelo José Barbosa

    2015-12-01

    This review discusses peptide-based vaccines in breast cancer, immune responses and clinical outcomes, which include studies on animal models and phase I, phase I/II, phase II and phase III clinical trials. Peptide-based vaccines are powerful neoadjuvant immunotherapies that can directly target proteins expressed in tumor cells, mainly tumor-associated antigens (TAAs). The most common breast cancer TAA epitopes are derived from MUC1, HER2/neu and CEA proteins. Peptides derived from TAAs could be successfully used to elicit CD8 and CD4 T cell-specific responses. Thus, choosing peptides that adapt to natural variations of human leukocyte antigen (HLA) genes is critical. The most attractive advantage is that the target response is more specific and less toxic than for other therapies and vaccines. Prominent studies on NeuVax - E75 (epitope for HER2/neu and GM-CSF) in breast cancer and DPX-0907 (HLA-A2-TAAs) expressed in breast cancer, ovarian and prostate cancer have shown the efficacy of peptide-based vaccines as neoadjuvant immunotherapy against cancer. Future peptide vaccine strategies, although a challenge to be applied in a broad range of breast cancers, point to the development of degenerate multi-epitope immunogens against multiple targets.

  2. 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.

  3. Predictors of Taiwanese baccalaureate nursing students' physio-psycho-social responses during clinical practicum.

    PubMed

    Chen, Ya-Wen; Hung, Chich-Hsiu

    2014-01-01

    The nursing educational process may contribute to stress in nursing students, particularly during clinical rotations. This descriptive study explored the relationships between perceived stress, coping behaviors, personality traits, and physio-psycho-social responses in a clinical practicum among baccalaureate nursing students and identified predictors for physio-psycho-social responses. A cross-sectional design was employed. One hundred and one juniors enrolled in a four-year baccalaureate nursing program in Taiwan participated in this study. Four structured questionnaires were utilized to collect data. Multiple regression analysis showed that three predictors accounted for 53.2% of the variance in students' physio-psycho-social responses, including perceived stress, students' gender, and personality traits. The implication for nursing educators is providing immediate assistance and appropriate support to guide students through difficult learning when they need. Nursing instructors also should pay attention to students' gender-linked differences and be aware of individuals' personality traits, especially those with emotional instability, unsocial behaviors, and depressive signs.

  4. Impact of imaging measurements on response assessment in glioblastoma clinical trials

    PubMed Central

    Reardon, David A.; Ballman, Karla V.; Buckner, Jan C.; Chang, Susan M.; Ellingson, Benjamin M.

    2014-01-01

    We provide historical and scientific guidance on imaging response assessment for incorporation into clinical trials to stimulate effective and expedited drug development for recurrent glioblastoma by addressing 3 fundamental questions: (i) What is the current validation status of imaging response assessment, and when are we confident assessing response using today's technology? (ii) What imaging technology and/or response assessment paradigms can be validated and implemented soon, and how will these technologies provide benefit? (iii) Which imaging technologies need extensive testing, and how can they be prospectively validated? Assessment of T1 +/− contrast, T2/FLAIR, diffusion, and perfusion-imaging sequences are routine and provide important insight into underlying tumor activity. Nonetheless, utility of these data within and across patients, as well as across institutions, are limited by challenges in quantifying measurements accurately and lack of consistent and standardized image acquisition parameters. Currently, there exists a critical need to generate guidelines optimizing and standardizing MRI sequences for neuro-oncology patients. Additionally, more accurate differentiation of confounding factors (pseudoprogression or pseudoresponse) may be valuable. Although promising, diffusion MRI, perfusion MRI, MR spectroscopy, and amino acid PET require extensive standardization and validation. Finally, additional techniques to enhance response assessment, such as digital T1 subtraction maps, warrant further investigation. PMID:25313236

  5. 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.

  6. 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

  7. 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

  8. 1988 survey of hospital salaries & job responsibilities for clinical engineers & biomedical technicians.

    PubMed

    Pacela, A F

    1988-01-01

    The Journal of Clinical Engineering has conducted its third survey of the salaries paid to Clinical Engineers and Biomedical Engineering Technicians in U.S. hospitals. This paper reports the salary and work responsibility data obtained from 1,420 professionals in relationship to: Certification; Region of the U.S.; Teaching Versus Nonteaching Facilities; Years of Experience; Education; Union Membership; and Gender. Data are included on Wage Increases and Job Responsibilities. This was the largest salary survey ever obtained in this field. The average BMET I has 2.4 years of experience and earns $19,400 +/- $3,400 (Std. Dev.). The average BMET II has 5.6 years of experience and earns $24,400 +/- $4,700. The average BMET III has 10.2 years of experience and earns $29,300 +/- $5,300. The average BMET Supervisor has 13.1 years of experience and earns $33,600 +/- $5,600. The average Clinical Engineer has 9.4 years of experience and earns $33,500 +/- $7,400. CE Supervisors are the highest paid in the field with an average 13.2 years of experience and an average salary of $43,900 +/- $11,400. Wages remain the highest on the West Coast and lowest in the Southeast. From 1986 to 1987, the nationwide average wages increased for CE Supervisors (+6.6%), BMET Supervisors (+3.1%) and BMET Is (+2.1%) but decreased for nonsupervisory Clinical Engineers (-2.1%), BMET IIs (-.4%) and BMET IIIs (-.7%). the highest quartile of CE Supervisors now earns between $48,900 and $99,000 per year. While certified individuals earn from $532 to $10,670 more than noncertified, a part of this difference is attributable to additional years of experience. PMID:10288947

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

    PubMed

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

    2015-04-21

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

  10. Clinical evaluation of the vector algorithm for neonatal hearing screening using automated auditory brainstem response.

    PubMed

    Keohane, Bernie M; Mason, Steve M; Baguley, David M

    2004-02-01

    A novel auditory brainstem response (ABR) detection and scoring algorithm, entitled the Vector algorithm is described. An independent clinical evaluation of the algorithm using 464 tests (120 non-stimulated and 344 stimulated tests) on 60 infants, with a mean age of approximately 6.5 weeks, estimated test sensitivity greater than 0.99 and test specificity at 0.87 for one test. Specificity was estimated to be greater than 0.95 for a two stage screen. Test times were of the order of 1.5 minutes per ear for detection of an ABR and 4.5 minutes per ear in the absence of a clear response. The Vector algorithm is commercially available for both automated screening and threshold estimation in hearing screening devices.

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

    PubMed

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

    2015-10-15

    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.

  12. Clinical manifestations and treatment response of steroid in pediatric Hashimoto encephalopathy.

    PubMed

    Yu, Hee Joon; Lee, Jeehun; Seo, Dae Won; Lee, Munhyang

    2014-07-01

    Hashimoto encephalopathy is a steroid-responsive encephalopathy associated with elevated titers of antithyroid antibodies. Clinical symptoms are characterized by behavioral and cognitive changes, speech disturbance, seizures, myoclonus, psychosis, hallucination, involuntary movements, cerebellar signs, and coma. The standard treatment is the use of corticosteroids along with the treatment of any concurrent dysthyroidism. Other options are immunoglobulins and plasmapheresis. We described symptoms and outcomes on 3 teenage girls with Hashimoto encephalopathy. Presenting symptoms were seizure or altered mental status. One patient took levothyroxine due to hypothyroidism before presentation of Hashimoto encephalopathy. After confirmation of elevated antithyroid antibodies, all patients were treated with steroids. One patient needed plasmapheresis because of the lack of response to steroids and immunoglobulins. Hashimoto encephalopathy should be considered in any patient presenting with acute or subacute unexplained encephalopathy and seizures. Even though the use of steroids is the first line of treatment, plasmapheresis can rescue steroid-resistant patients.

  13. TGF-α and IL-6 plasma levels selectively identify CML patients who fail to achieve an early molecular response or progress in the first year of therapy.

    PubMed

    Nievergall, E; Reynolds, J; Kok, C H; Watkins, D B; Biondo, M; Busfield, S J; Vairo, G; Fuller, K; Erber, W N; Sadras, T; Grose, R; Yeung, D T; Lopez, A F; Hiwase, D K; Hughes, T P; White, D L

    2016-06-01

    Early molecular response (EMR, BCR-ABL1 (IS)⩽10% at 3 months) is a strong predictor of outcome in imatinib-treated chronic phase chronic myeloid leukemia (CP-CML) patients, but for patients who transform early, 3 months may be too late for effective therapeutic intervention. Here, we employed multiplex cytokine profiling of plasma samples to test newly diagnosed CP-CML patients who subsequently received imatinib treatment. A wide range of pro-inflammatory and angiogenesis-promoting cytokines, chemokines and growth factors were elevated in the plasma of CML patients compared with that of healthy donors. Most of these normalized after tyrosine kinase inhibitor treatment while others remained high in remission samples. Importantly, we identified TGF-α and IL-6 as novel biomarkers with high diagnostic plasma levels strongly predictive of subsequent failure to achieve EMR and deep molecular response, as well as transformation to blast crisis and event-free survival. Interestingly, high TGF-α alone can also delineate a poor response group raising the possibility of a pathogenic role. This suggests that the incorporation of these simple measurements to the diagnostic work-up of CP-CML patients may enable therapy intensity to be individualized early according to the cytokine-risk profile of the patient. PMID:26898188

  14. 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

  15. 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.

  16. Immunological and clinical response of coyotes (Canis latrans) to experimental inoculation with Yersinia pestis.

    PubMed

    Baeten, Laurie A; Pappert, Ryan; Young, John; Schriefer, Martin E; Gidlewski, Thomas; Kohler, Dennis; Bowen, Richard A

    2013-10-01

    Multiple publications have reported the use of coyotes (Canis latrans) in animal-based surveillance efforts for the detection of Yersinia pestis. Coyotes are likely exposed via flea bite or oral routes and are presumed to be resistant to the development of clinical disease. These historic data have only been useful for the evaluation of the geographic distribution of Y. pestis in the landscape. Because the canid immunologic response to Y. pestis has not been thoroughly characterized, we conducted experimental inoculation of captive-reared, juvenile coyotes (n = 8) with Y. pestis CO92 via oral or intradermal routes. We measured the humoral response to Y. pestis fraction 1 capsular protein (anti-F1) and found a significant difference between inoculation groups in magnitude and duration of antibody production. The anti-F1 titers in animals exposed intradermally peaked at day 10 postinoculation (PI; range = 1∶32 to 1∶128) with titers remaining stable at 1∶32 through week 12. In contrast, orally inoculated animals developed higher titers (range = 1∶256 to 1∶1,024) that remained stable at 1∶256 to 1∶512 through week 6. No clinical signs of disease were observed, and minimal changes were noted in body temperature, white blood cell counts, and acute phase proteins during the 7 days PI. Gross pathology was unremarkable, and minimal changes were noted in histopathology at days 3 and 7 PI. Rechallenge at 14 wk PI via similar dosage and routes resulted in marked differences in antibody response between groups. Animals in the orally inoculated group produced a striking increase in anti-F1 titers (up to 1∶4,096) within 3 days, whereas there was minimal to no increase in antibody response in the intradermal group. Information gathered from this experimental trial may provide additional insight into the spatial and temporal evaluation of coyote plague serology.

  17. CTLA-4 blockade enhances polyfunctional NY-ESO-1 specific T cell responses in metastatic melanoma patients with clinical benefit.

    PubMed

    Yuan, Jianda; Gnjatic, Sacha; Li, Hao; Powel, Sarah; Gallardo, Humilidad F; Ritter, Erika; Ku, Geoffrey Y; Jungbluth, Achim A; Segal, Neil H; Rasalan, Teresa S; Manukian, Gregor; Xu, Yinyan; Roman, Ruth-Ann; Terzulli, Stephanie L; Heywood, Melanie; Pogoriler, Evelina; Ritter, Gerd; Old, Lloyd J; Allison, James P; Wolchok, Jedd D

    2008-12-23

    Blockade of inhibitory signals mediated by cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) has been shown to enhance T cell responses and induce durable clinical responses in patients with metastatic melanoma. The functional impact of anti-CTLA-4 therapy on human immune responses is still unclear. To explore this, we analyzed immune-related adverse events and immune responses in metastatic melanoma patients treated with ipilimumab, a fully human anti-CTLA-4 monoclonal antibody. Fifteen patients were selected on the basis of availability of suitable specimens for immunologic monitoring, and eight of these showed evidence of clinical benefit. Five of the eight patients with evidence of clinical benefit had NY-ESO-1 antibody, whereas none of seven clinical non-responders was seropositive for NY-ESO-1. All five NY-ESO-1 seropositive patients had clearly detectable CD4(+) and CD8(+) T cells against NY-ESO-1 following treatment with ipilimumab. One NY-ESO-1 seronegative clinical responder also had a NY-ESO-1 CD4(+) and CD8(+) T cell response, possibly related to prior vaccination with NY-ESO-1. Among five clinical non-responders analyzed, only one had a NY-ESO-1 CD4(+) T cell response and this patient did not have detectable anti-NY-ESO-1 antibody. Overall, NY-ESO-1-specific T cell responses increased in frequency and functionality during anti-CTLA-4 treatment, revealing a polyfunctional response pattern of IFN-gamma, MIP-1beta and TNF-alpha. We therefore suggest that CTLA-4 blockade enhanced NY-ESO-1 antigen-specific B cell and T cell immune responses in patients with durable objective clinical responses and stable disease. These data provide an immunologic rationale for the efficacy of anti-CTLA-4 therapy and call for immunotherapeutic designs that combine NY-ESO-1 vaccination with CTLA-4 blockade.

  18. Interleukin-6 and its relation to the humoral immune response and clinical parameters in burned patients.

    PubMed

    Nijsten, M W; Hack, C E; Helle, M; ten Duis, H J; Klasen, H J; Aarden, L A

    1991-06-01

    The cytokine interleukin-6, which has been shown to be increased in patients with burn injuries, is produced by activated monocytes and endothelial cells and has many in vitro activities, including stimulation of acute-phase protein synthesis in hepatocytes, immunoglobulin synthesis in B lymphocytes, and stimulation of growth of megakaryocytes. In 13 patients with a mean of 31% full-thickness burns, we studied the relation of serum interleukin-6 to clinical parameters and parameters of the acute-phase response and immunoglobulin production. Interleukin-6 was already elevated within hours after the injury was sustained, and it remained elevated for several weeks. All components of the acute-phase response were observed: fever, tachycardia, leukocytosis with an associated left shift, elevation of C-reactive protein and alpha 1-antitrypsin, and a decrease in albumin levels. In the second week after burn injury, immunoglobulin M levels peaked, followed by a prolonged elevation of immunoglobulin G levels. Thrombocyte counts initially decreased and rebounded to supranormal levels after 2 weeks. Interleukin-6 levels were positively correlated with acute-phase responses. We believe that the production of interleukin-6 induces the synthesis of acute-phase proteins. High interleukin-6 levels may also be an etiologic factor in the marked immunoglobulin response observed. Likewise, the relation between the megakaryocyte-promoting activity of interleukin-6 and the rebound thrombocytosis requires further investigation.

  19. 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.

  20. Preexisting neutralizing antibody responses distinguish clinically inapparent and apparent dengue virus infections in a Sri Lankan pediatric cohort.

    PubMed

    Corbett, Kizzmekia S; Katzelnick, Leah; Tissera, Hasitha; Amerasinghe, Ananda; de Silva, Aruna Dharshan; de Silva, Aravinda M

    2015-02-15

    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.

  1. 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

  2. Sex-ratio adjustment in response to local mate competition is achieved through an alteration of egg size in a haplodiploid spider mite.

    PubMed

    Macke, Emilie; Magalhães, Sara; Bach, Fabien; Olivieri, Isabelle

    2012-11-22

    Sex-ratio adjustments are commonly observed in haplodiploid species. However, the underlying proximate mechanisms remain elusive. We investigated these mechanisms in Tetranychus urticae, a haplodiploid spider mite known to adjust sex ratio in response to the level of local mate competition (LMC). In this species, egg size determines fertilization probability, with larger eggs being more likely to be fertilized, and thus become female. We explored the hypothesis that sex-ratio adjustment is achieved through adjustment of egg size. By using spider mites from a large population, we found that females produced not only a higher proportion of daughters under high levels of LMC, but also larger eggs. Moreover, in populations experimentally evolving under varying levels of LMC, both the proportion of females and the egg size increased with LMC intensity. These results suggest that sex-ratio adjustment in spider mites is mediated by egg size, although the causal relationship remains to be tested.

  3. 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

  4. Clinical laboratory response to a mock outbreak of invasive bacterial infections: a preparedness study.

    PubMed

    Olsen, Randall J; 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

    2014-12-01

    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.

  5. 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

  6. [Clinical assessment of a monitor "MedStorm" (Norway) of galvanic skin response correlates with preoperative stress].

    PubMed

    2011-01-01

    Clinical trials were performed by Russian anesthesiologists of pain monitor based on measuring galvanic skin response (skin conductance). 5 pations were studied the monitor showed lower sensitivity to assess the level of analgesia during combined anesthesia which allows to not recommend it for use in clinical practice. PMID:22379919

  7. 1994 survey of salaries & responsibilities for hospital biomedical/clinical engineering & technology personnel.

    PubMed

    Pacela, A F

    1994-01-01

    The Journal of Clinical Engineering has conducted its ninth annual survey of the salaries paid to biomedical/clinical engineering and technology personnel in U.S. hospitals. This paper reports the salary and work responsibility data obtained from 1,335 professionals in relationship to: Certification; Region of the U.S.; Teaching versus Nonteaching Facilities; Years of Experience; Education; Union Membership; and Gender. Data are included on Wage Increases and Job Responsibilities. Data are as of 12/31/93 and are compared to 12/31/92. The average BMET I has 3.7 years of experience and earns $25,464 +/- $4,838 (Std. Dev.). The average BMET II has 7.3 years of experience and earns $31,217 +/- $6,069. The average BMET III has 13.2 years of experience and earns $38,095 +/- $6,187. The average BMET Specialist has 14.3 years of experience and earns $43,017 +/- $9,322. The average BMET Supervisor has 14.2 years of experience and earns $41,194 +/- $7,844. The average Clinical Engineer has 8.4 years of experience and earns $42,392 +/- $7,630. CE Supervisors have an average 13.1 years of experience and an average salary of $47,403 +/- $9,561. The overall group or department Director or Manager has 15.5 years of experience and earns $52,245 +/- $13,567 on average. Wages are the highest on the East and West Coasts. The lowest wages are in the Southeast and Southwest. BMET wages advanced up to 5.1%, year to year. The highest quartile of Director/Managers now earns between $59,000 and $101,000 per year. Certified individuals variously earn up to $5,188 more than noncertified. PMID:10135176

  8. 1991 survey of hospital salaries & job responsibilities for clinical engineers & biomedical technicians.

    PubMed

    Pacela, A F

    1991-01-01

    The Journal of Clinical Engineering has conducted its sixth survey of the salaries paid to Clinical Engineers and Biomedical Equipment Technicians in U.S. hospitals. This paper reports the salary and work responsibility data obtained from 1,316 professionals in relationship to: Certification; Region of the U.S.; Teaching Versus Nonteaching Facilities; Years of Experience; Education; Union Membership; and Gender. Data are included on Wage Increases and Job Responsibilities. Data are as of 12/31/90 and are compared to 12/31/89. The average BMET I has 2.2 years of experience and earns $22,043 +/- $4,212 (Std. Dev.). The average BMET II has 6.5 years of experience and earns $27,627 +/- $5,466. The average BMET III has 11.6 years of experience and earns $33,843 +/- $6,099. The average BMET Supervisor has 13.5 years of experience and earns $38,159 +/- $7,701. The average Clinical Engineer has 8.5 years of experience and earns $39,127 +/- $7,884. CE Supervisors are the highest paid in the field with an average 13.9 years of experience and an average salary of $51,050 +/- $12,465. Wages are the highest on the West Coast. This year, the lowest wages were in the Southwest. From 1989 to 1990, the wage ranges for all job types increased substantially: BMET Is, +13.4%; BMET IIs, +5.3%; BMET IIIs, +8.0%; BMET Supervisors, +7.9%; CEs, +5.7%; CE Supervisors, +10.4%; and Supervisor, Other, +6.0%. The highest quartile of CE Supervisors now earns between $56,700 and $100,000 per year. While certified individuals earn $158 to $5,702 more than noncertified, this is attributable, in part, to additional years of experience. PMID:10111394

  9. 1990 survey of hospital salaries & job responsibilities for clinical engineers & biomedical technicians.

    PubMed

    Pacela, A F

    1990-01-01

    The Journal of Clinical Engineering has conducted its fifth survey of the salaries paid to Clinical Engineers and Biomedical Equipment Technicians in U.S. hospitals. This paper reports the salary and work responsibility data obtained from 1,453 professionals in relationship to: Certification; Region of the U.S.; Teaching Versus Nonteaching Facilities; Years of Experience; Education; Union Membership; and Gender. Data are included on Wage Increases and Job Responsibilities. All data are as of 12/31/89. The average BMET I has 3.3 years of experience and earns $19,394 +/- $4,144 (Std. Dev.). The average BMET II has 6.4 years of experience and earns $26,166 +/- $4,900. The average BMET III has 11.7 years of experience and earns $31,334 +/- $4,977. The average BMET Supervisor has 12.9 years of experience and earns $35,371 +/- $6,416. The average Clinical Engineer has 9.5 years of experience and earns $36,971 +/- $7,515. CE Supervisors are the highest paid in the field with an average 13.3 years of experience and an average salary of $46,265 +/- $11,115. Wages remain the highest on the West Coast and lowest in the Southeast. From 1988 to 1989, the wage ranges for all job types except BMET Is increased: BMET IIs, +1.9%; BMET IIIs, +3.0%; BMET Supervisors, +3.2%; CEs, +3.9%; and CE Supervisors, +1.8%. The highest quartile of CE Supervisors now earns between $52,000 and $95,000 per year. While certified individuals earn $521 to $4,953 more than noncertified, this is attributable in part to years of experience. PMID:10105927

  10. 1989 Survey of hospital salaries & job responsibilities for clinical engineers & biomedical technicians.

    PubMed

    Pacela, A F

    1989-01-01

    The Journal of Clinical Engineering has conducted its fourth survey of the salaries paid to Clinical Engineers and Biomedical Equipment Technicians in U.S. hospitals. This paper reports the salary and work responsibility data obtained from 1,350 professionals in relationship to: Certification; Region of the U.S.; Teaching Versus Nonteaching Facilities; Years of Experience; Education; Union Membership; and Gender. Data are included on Wage Increases and Job Responsibilities. All data are as of 12/31/88. The average BMET I has 2.8 years of experience and earns $19,494 +/- $4,069 (Std. Dev.). The average BMET II has 6.1 years of experience and earns $25,743 +/- $5,176. The average BMET III has 10.5 years of experience and earns $30,434 +/- $5,432. The average BMET Supervisor has 13.0 years of experience and earns $34,339 +/- $5,896. The average Clinical Engineer has 9.8 years of experience and earns $35,605 +/- $4,345. CE Supervisors are the highest paid in the field with an average 12.9 years of experience and an average salary of $45,461 +/- $11,831. Wages remain the highest on the West Coast and lowest in the Southeast. From 1987 to 1988, the wages ranges for all job types increased: BMET Is, +.52%; BMET IIs, +5.3%; BMET IIIs, +3.8%; BMET Supervisors, +2.1%; CEs, +6.3%; and CE Supervisors, +3.6%. The highest quartile of CE Supervisors now earns between $52,200 and $117,700 per year. While certified individuals earn $1,108 to $4,619 more than noncertified, this is attributable in part to years of experience. PMID:10294417

  11. RHAMM-R3 peptide vaccination in patients with acute myeloid leukemia, myelodysplastic syndrome, and multiple myeloma elicits immunologic and clinical responses.

    PubMed

    Schmitt, Michael; Schmitt, Anita; Rojewski, Markus T; Chen, Jinfei; Giannopoulos, Krzysztof; Fei, Fei; Yu, Yingzhe; Götz, Marlies; Heyduk, Marta; Ritter, Gerd; Speiser, Daniel E; Gnjatic, Sacha; Guillaume, Philippe; Ringhoffer, Mark; Schlenk, Richard F; Liebisch, Peter; Bunjes, Donald; Shiku, Hiroshi; Dohner, Hartmut; Greiner, Jochen

    2008-02-01

    The receptor for hyaluronic acid-mediated motility (RHAMM) is an antigen eliciting both humoral and cellular immune responses in patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and multiple myeloma (MM). We initiated a phase 1 clinical trial vaccinating 10 patients with R3 (ILSLELMKL), a highly immunogenic CD8(+) T-cell epitope peptide derived from RHAMM. In 7 of 10 patients, we detected an increase of CD8(+)/HLA-A2/RHAMM R3 tetramer(+)/CD45RA(+)/CCR7(-)/CD27(-)/CD28(-) effector T cells in accordance with an increase of R3-specific CD8(+) T cells in enzyme linked immunospot (ELISpot) assays. In chromium release assays, a specific lysis of RHAMM-positive leukemic blasts was shown. Three of 6 patients with myeloid disorders (1/3 AML, 2/3 MDS) achieved clinical responses: one patient with AML and one with MDS showed a significant reduction of blasts in the bone marrow after the last vaccination. One patient with MDS no longer needed erythrocyte transfusions after 4 vaccinations. Two of 4 patients with MM showed a reduction of free light chain serum levels. Taken together, RHAMM-R3 peptide vaccination induced both immunologic and clinical responses, and therefore RHAMM constitutes a promising target for further immunotherapeutic approaches. This study is registered at http://ISRCTN.org as ISRCTN32763606 and is registered with EudraCT as 2005-001706-37. PMID:17978170

  12. Epidemiological and clinical features, response to HAART, and survival in HIV-infected patients diagnosed at the age of 50 or more

    PubMed Central

    Nogueras, MaMercedes; Navarro, Gemma; Antón, Esperança; Sala, Montserrat; Cervantes, Manel; Amengual, MaJosé; Segura, Ferran

    2006-01-01

    Background Over the last years, the mean age of subjects with HIV infection and AIDS is increasing. Moreover, some epidemiological and clinical differences between younger and older HIV-infected individuals have been observed. However, since introduction of HAART therapy, there are controversial results regarding their response to HAART. The aim of the present study is to evaluate epidemiological and clinical features, response to HAART, and survival in elderly HIV-infected patients with regard to younger HIV-infected patients. Methods A prospective cohort study (1998–2003) was performed on patients from Sabadell Hospital, in Northeast of Spain. The cohort includes newly attended HIV-infected patients since January 1, 1998. For the purpose of this analysis, data was censured at December 31, 2003. Taking into account age at time of diagnosis, it was considered 36 HIV-positive people aged 50 years or more (Group 1, G1) and 419 HIV-positive people aged 13–40 years (Group 2, G2). Epidemiological, clinical, biological and therapy data are recorded. Statistical analysis was performed using Chi-squared test and Fisher exact test, Mann-Whitney U test, Kaplan-Meier, Log Rank test, and Two-Way ANOVA from random factors. Results G1 showed higher proportion of men than G2. The most common risk factors in G1 were heterosexual transmission (P = 0.01) and having sex with men or women (P < 0.001). G1 and G2 show parallel profiles through the time regarding immunological response (P = 0.989) and virological response (P = 0.074). However, older people showed lower CD4 cell counts at first clinic visit (P < 0.001) and, eventually, they did not achieve the same counts as G2. G1 presented faster progression to AIDS (P < 0.001) and shorter survival (P < 0.001). Conclusion Older patients have different epidemiological features. Their immunological and virological responses are good. However, older patients do not achieve the same CD4 cell counts likely due to they have lower counts

  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. 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

  17. 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

  18. Age modifies the immunologic response and clinical presentation of American tegumentary leishmaniasis.

    PubMed

    Carvalho, Augusto M; Amorim, Camila F; Barbosa, Juliana L S; Lago, Alexsandro S; Carvalho, Edgar M

    2015-06-01

    Leishmania (Viannia) braziliensis is the main causal agent of American tegumentary leishmaniasis (ATL) that may present as cutaneous, mucosal, or disseminated cutaneous leishmaniasis. The disease is highly prevalent in young males and there is a lack of studies of ATL in the elderly. Herein, we compared clinical manifestations, immunologic response, and response to antimony therapy between patients > 60 years of age (N = 58) and patients who were 21-30 years of age (N = 187). The study was performed in Corte de Pedra, Bahia, Brazil, a well-known area of L. braziliensis transmission. Cytokine production by cultured peripheral blood mononuclear cells stimulated with soluble Leishmania antigen was performed. Elderly subjects more frequently had a previous history of cutaneous leishmaniasis, large lesions, or mucosal leishmaniasis, and they were less likely to have lymphadenopathy. There was no difference regarding gender and response to therapy. Peripheral blood mononuclear cells from elderly subjects produced a similar amount of tumor necrosis factor than young patients but they produced less interferon-gamma and more interleukin-10 than young subjects. We concluded that elderly patients with cutaneous leishmaniasis should be searched for mucosal or disseminated leishmaniasis. The decreased interferon-gamma production and increase in interleukin-10 observed in elderly patients may contribute to parasite persistence and L. braziliensis infection dissemination.

  19. 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

  20. 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

  1. Age Modifies the Immunologic Response and Clinical Presentation of American Tegumentary Leishmaniasis

    PubMed Central

    Carvalho, Augusto M.; Amorim, Camila F.; Barbosa, Juliana L. S.; Lago, Alexsandro S.; Carvalho, Edgar M.

    2015-01-01

    Leishmania (Viannia) braziliensis is the main causal agent of American tegumentary leishmaniasis (ATL) that may present as cutaneous, mucosal, or disseminated cutaneous leishmaniasis. The disease is highly prevalent in young males and there is a lack of studies of ATL in the elderly. Herein, we compared clinical manifestations, immunologic response, and response to antimony therapy between patients > 60 years of age (N = 58) and patients who were 21–30 years of age (N = 187). The study was performed in Corte de Pedra, Bahia, Brazil, a well-known area of L. braziliensis transmission. Cytokine production by cultured peripheral blood mononuclear cells stimulated with soluble Leishmania antigen was performed. Elderly subjects more frequently had a previous history of cutaneous leishmaniasis, large lesions, or mucosal leishmaniasis, and they were less likely to have lymphadenopathy. There was no difference regarding gender and response to therapy. Peripheral blood mononuclear cells from elderly subjects produced a similar amount of tumor necrosis factor than young patients but they produced less interferon-gamma and more interleukin-10 than young subjects. We concluded that elderly patients with cutaneous leishmaniasis should be searched for mucosal or disseminated leishmaniasis. The decreased interferon-gamma production and increase in interleukin-10 observed in elderly patients may contribute to parasite persistence and L. braziliensis infection dissemination. PMID:25918209

  2. 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

  3. Comparative Transcriptional Analysis of Clinically Relevant Heat Stress Response in Clostridium difficile Strain 630

    PubMed Central

    Ternan, Nigel G.; Jain, Shailesh; Srivastava, Malay; McMullan, Geoff

    2012-01-01

    Clostridium difficile is considered to be one of the most important causes of health care-associated infections worldwide. In order to understand more fully the adaptive response of the organism to stressful conditions, we examined transcriptional changes resulting from a clinically relevant heat stress (41°C versus 37°C) in C. difficile strain 630 and identified 341 differentially expressed genes encompassing multiple cellular functional categories. While the transcriptome was relatively resilient to the applied heat stress, we noted upregulation of classical heat shock genes including the groEL and dnaK operons in addition to other stress-responsive genes. Interestingly, the flagellin gene (fliC) was downregulated, yet genes encoding the cell-wall associated flagellar components were upregulated suggesting that while motility may be reduced, adherence – to mucus or epithelial cells – could be enhanced during infection. We also observed that a number of phage associated genes were downregulated, as were genes associated with the conjugative transposon Tn5397 including a group II intron, thus highlighting a potential decrease in retromobility during heat stress. These data suggest that maintenance of lysogeny and genome wide stabilisation of mobile elements could be a global response to heat stress in this pathogen. PMID:22860125

  4. 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

  5. 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

  6. A multicenter clinical study evaluating the confirmed complete molecular response rate in imatinib-treated patients with chronic phase chronic myeloid leukemia by using the international scale of real-time quantitative polymerase chain reaction

    PubMed Central

    Shinohara, Yoshinori; Takahashi, Naoto; Nishiwaki, Kaichi; Hino, Masayuki; Kashimura, Makoto; Wakita, Hisashi; Hatano, Yoshiaki; Hirasawa, Akira; Nakagawa, Yasuaki; Itoh, Kuniaki; Masuoka, Hidekazu; Aotsuka, Nobuyuki; Matsuura, Yasuhiro; Takahara, Sinobu; Sano, Koji; Kuroki, Jun; Hata, Tomoko; Nakamae, Hirohisa; Mugitani, Atsuko; Nakane, Takahiko; Miyazaki, Yasushi; Niioka, Takenori; Miura, Masatomo; Sawada, Kenichi

    2013-01-01

    Achievement of complete molecular response in patients with chronic phase chronic myeloid leukemia has been recognized as an important milestone in therapy cessation and treatment-free remission; the identification of predictors of complete molecular response in these patients is, therefore, important. This study evaluated complete molecular response rates in imatinib-treated chronic phase chronic myeloid leukemia patients with major molecular response by using the international standardization for quantitative polymerase chain reaction analysis of the breakpoint cluster region-Abelson1 gene. The correlation of complete molecular response with various clinical, pharmacokinetic, and immunological parameters was determined. Complete molecular response was observed in 75/152 patients (49.3%). In the univariate analysis, Sokal score, median time to major molecular response, ABCG2 421C>A, and regulatory T cells were significantly lower in chronic phase chronic myeloid leukemia patients with complete molecular response than in those without complete molecular response. In the multivariate analysis, duration of imatinib treatment (odds ratio: 1.0287, P=0.0003), time to major molecular response from imatinib therapy (odds ratio: 0.9652, P=0.0020), and ABCG2 421C/C genotype (odds ratio: 0.3953, P=0.0284) were independent predictors of complete molecular response. In contrast, number of natural killer cells, BIM deletion polymorphisms, and plasma trough imatinib concentration were not significantly associated with achieving a complete molecular response. Several predictive markers for achieving complete molecular response were identified in this study. According to our findings, some chronic myeloid leukemia patients treated with imatinib may benefit from a switch to second-generation tyrosine kinase inhibitors (ClinicalTrials.gov, UMIN000004935). PMID:23716542

  7. A multicenter clinical study evaluating the confirmed complete molecular response rate in imatinib-treated patients with chronic phase chronic myeloid leukemia by using the international scale of real-time quantitative polymerase chain reaction.

    PubMed

    Shinohara, Yoshinori; Takahashi, Naoto; Nishiwaki, Kaichi; Hino, Masayuki; Kashimura, Makoto; Wakita, Hisashi; Hatano, Yoshiaki; Hirasawa, Akira; Nakagawa, Yasuaki; Itoh, Kuniaki; Masuoka, Hidekazu; Aotsuka, Nobuyuki; Matsuura, Yasuhiro; Takahara, Sinobu; Sano, Koji; Kuroki, Jun; Hata, Tomoko; Nakamae, Hirohisa; Mugitani, Atsuko; Nakane, Takahiko; Miyazaki, Yasushi; Niioka, Takenori; Miura, Masatomo; Sawada, Kenichi

    2013-09-01

    Achievement of complete molecular response in patients with chronic phase chronic myeloid leukemia has been recognized as an important milestone in therapy cessation and treatment-free remission; the identification of predictors of complete molecular response in these patients is, therefore, important. This study evaluated complete molecular response rates in imatinib-treated chronic phase chronic myeloid leukemia patients with major molecular response by using the international standardization for quantitative polymerase chain reaction analysis of the breakpoint cluster region-Abelson1 gene. The correlation of complete molecular response with various clinical, pharmacokinetic, and immunological parameters was determined. Complete molecular response was observed in 75/152 patients (49.3%). In the univariate analysis, Sokal score, median time to major molecular response, ABCG2 421C>A, and regulatory T cells were significantly lower in chronic phase chronic myeloid leukemia patients with complete molecular response than in those without complete molecular response. In the multivariate analysis, duration of imatinib treatment (odds ratio: 1.0287, P=0.0003), time to major molecular response from imatinib therapy (odds ratio: 0.9652, P=0.0020), and ABCG2 421C/C genotype (odds ratio: 0.3953, P=0.0284) were independent predictors of complete molecular response. In contrast, number of natural killer cells, BIM deletion polymorphisms, and plasma trough imatinib concentration were not significantly associated with achieving a complete molecular response. Several predictive markers for achieving complete molecular response were identified in this study. According to our findings, some chronic myeloid leukemia patients treated with imatinib may benefit from a switch to second-generation tyrosine kinase inhibitors (ClinicalTrials.gov, UMIN000004935).

  8. A Single Nucleotide Polymorphism in cBIM Is Associated with a Slower Achievement of Major Molecular Response in Chronic Myeloid Leukaemia Treated with Imatinib

    PubMed Central

    Augis, Vanessa; Airiau, Kelly; Josselin, Marina; Turcq, Béatrice; Mahon, François-Xavier; Belloc, Francis

    2013-01-01

    Purpose BIM is essential for the response to tyrosine-kinase inhibitors (TKI) in chronic myeloid leukaemia (CML) patients. Recently, a deletion polymorphism in intron 2 of the BIM gene was demonstrated to confer an intrinsic TKI resistance in Asian patients. The present study aimed at identifying mutations in the BIM sequence that could lead to imatinib resistance independently of BCR-ABL mutations. Experimental Design BIM coding sequence analysis was performed in 72 imatinib-treated CML patients from a French population of our centre and in 29 healthy controls (reference population) as a case-control study. Real-time quantitative PCR (RT qPCR) was performed to assess Bim expression in our reference population. Results No mutation with amino-acid change was found in the BIM coding sequence. However, we observed a silent single nucleotide polymorphism (SNP) c465C>T (rs724710). A strong statistical link was found between the presence of the T allele and the high Sokal risk group (p = 0.0065). T allele frequency was higher in non responsive patients than in the reference population (p = 0.0049). Similarly, this T allele was associated with the mutation frequency on the tyrosine kinase domain of BCR-ABL (p<0.001) and the presence of the T allele significantly lengthened the time to achieve a major molecular response (MMR). Finally, the presence of the T allele was related to a decreased basal expression of the Bim mRNA in the circulating mononuclear cells of healthy controls. Conclusion These results suggest that the analysis of the c465C>T SNP of BIM could be useful for predicting the outcome of imatinib-treated CML patients. PMID:24223824

  9. 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

  10. Clinical responses with T lymphocytes targeting malignancy-associated κ light chains

    PubMed Central

    Ramos, Carlos A.; Savoldo, Barbara; Torrano, Vicky; Ballard, Brandon; Zhang, Huimin; Dakhova, Olga; Liu, Enli; Carrum, George; Kamble, Rammurti T.; Gee, Adrian P.; Mei, Zhuyong; Wu, Meng-Fen; Liu, Hao; Grilley, Bambi; Rooney, Cliona M.; Brenner, Malcolm K.; Heslop, Helen E.; Dotti, Gianpietro

    2016-01-01

    BACKGROUND. Treatment of B cell malignancies with adoptive transfer of T cells with a CD19-specific chimeric antigen receptor (CAR) shows remarkable clinical efficacy. However, long-term persistence of T cells targeting CD19, a pan–B cell marker, also depletes normal B cells and causes severe hypogammaglobulinemia. Here, we developed a strategy to target B cell malignancies more selectively by taking advantage of B cell light Ig chain restriction. We generated a CAR that is specific for the κ light chain (κ.CAR) and therefore recognizes κ-restricted cells and spares the normal B cells expressing the nontargeted λ light chain, thus potentially minimizing humoral immunity impairment. METHODS. We conducted a phase 1 clinical trial and treated 16 patients with relapsed or refractory κ+ non-Hodgkin lymphoma/chronic lymphocytic leukemia (NHL/CLL) or multiple myeloma (MM) with autologous T cells genetically modified to express κ.CAR (κ.CARTs). Other treatments were discontinued in 11 of the 16 patients at least 4 weeks prior to T cell infusion. Six patients without lymphopenia received 12.5 mg/kg cyclophosphamide 4 days before κ.CART infusion (0.2 × 108 to 2 × 108 κ.CARTs/m2). No other lymphodepletion was used. RESULTS. κ.CART expansion peaked 1–2 weeks after infusion, and cells remained detectable for more than 6 weeks. Of 9 patients with relapsed NHL or CLL, 2 entered complete remission after 2 and 3 infusions of κ.CARTs, and 1 had a partial response. Of 7 patients with MM, 4 had stable disease lasting 2–17 months. No toxicities attributable to κ.CARTs were observed. CONCLUSION. κ.CART infusion is feasible and safe and can lead to complete clinical responses. TRIAL REGISTRATION. ClinicalTrials.gov NCT00881920. FUNDING. National Cancer Institute (NCI) grants 3P50CA126752 and 5P30CA125123 and Leukemia and Lymphoma Society (LLS) Specialized Centers of Research (SCOR) grant 7018. PMID:27270177

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. 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

  16. RARtool: A MATLAB Software Package for Designing Response-Adaptive Randomized Clinical Trials with Time-to-Event Outcomes

    PubMed Central

    Ryeznik, Yevgen; Sverdlov, Oleksandr; Wong, Weng Kee

    2016-01-01

    Response-adaptive randomization designs are becoming increasingly popular in clinical trial practice. In this paper, we present RARtool, a user interface software developed in MATLAB for designing response-adaptive randomized comparative clinical trials with censored time-to-event outcomes. The RARtool software can compute different types of optimal treatment allocation designs, and it can simulate response-adaptive randomization procedures targeting selected optimal allocations. Through simulations, an investigator can assess design characteristics under a variety of experimental scenarios and select the best procedure for practical implementation. We illustrate the utility of our RARtool software by redesigning a survival trial from the literature. PMID:26997924

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

    PubMed Central

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

    2015-01-01

    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

  18. 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

  19. Needle EMG Response of Lumbar Multifidus to Manipulation in the Presence of Clinical Instability.

    PubMed

    Tunnell, John

    2009-01-01

    A proposed mechanism for the persistence of low back pain due to clinical instability is a decrease in control of local spinal musculature, more specifically decreased recruitment of multifidus. Altered segmental mechanoreceptor input has been proposed as a contributing factor responsible for a decrease in local muscle recruitment. In this case report, immediate changes in the recruitment of the deep multifidus following manipulation were examined using needle EMG and isometric testing of trunk rotational force. Trunk rotational force appeared to improve while the multifidus demonstrated a decrease in activity as measured by needle EMG. No specific conclusions can be drawn from this report; however, the results do suggest that immediate multifidus function may be influenced with manipulation, resulting in improved muscular control of the trunk. PMID:20046558

  20. 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.

  1. Catatonia in DSM 5: controversies regarding its psychopathology, clinical presentation and treatment response.

    PubMed

    Ungvari, Gabor S

    2014-12-01

    Over the past two decades, there has been an upsurge of interest in catatonia, which is reflected in the attention it received in DSM 5, where it appears as a separate subsection of the Schizophrenia Spectrum and Other Psychotic Disorders (APA, 2013). This commentary argues that due to the lack of solid scientific evidence, the extended coverage of catatonia in DSM 5 was a premature, and consequently, a necessarily ambiguous decision. The psychopathological foundations of the modern catatonia concept are lacking therefore its boundaries are fuzzy. There are only a few, methodologically sound clinical, treatment response and small-scale neurobiological studies. The widely recommended use of benzodiazepines for the treatment of catatonia is based on case reports and open-label studies instead of placebo-controlled, randomized trials. In conclusion, the catatonic concept espoused by DSM 5 is necessarily vague reflecting the current state of knowledge.

  2. Local and systemic immune response in pigs during subclinical and clinical swine influenza infection.

    PubMed

    Pomorska-Mól, M; Kwit, K; Markowska-Daniel, I; Kowalski, C; Pejsak, Z

    2014-10-01

    Local and systemic immune responses in pigs intranasally (IN) and intratracheally (IT) inoculated with swine influenza virus (SIV) were studied. No clinical signs were observed in IN-inoculated pigs, while IT-inoculated pigs developed typical signs of influenza. Significantly higher titres of specific antibodies and changes of haematological parameters were found only in IT-inoculated pigs. Because positive correlations between viral titre, local cytokine concentration, and lung pathology have been observed, we hypothesise that both viral load and the local secretion of cytokines play a role in the induction of lung lesions. It could be that a higher replication of SIV stimulates immune cells to secrete higher amounts of cytokines. The results of the present study indicate that pathogenesis of SIV is dependent on both, the damage caused to the lung parenchyma directly by virus, and the effects on the cells of the host's immune system.

  3. Clinical, histopathological and metabolic responses following exercise in Arabian horses with a history of exertional rhabdomyolysis.

    PubMed

    McKenzie, E C; Eyrich, L V; Payton, M E; Valberg, S J

    2016-10-01

    A previous report suggests a substantial incidence of exertional rhabdomyolysis (ER) in Arabian horses performing endurance racing. This study compared formalin histopathology and clinical and metabolic responses to a standardised field exercise test (SET) between Arabians with and without ER. Arabian horses with (n = 10; age 15.4 ± 5.6 years) and without (n = 9; 12.9 ± 6.1 years) prior ER were stall-rested for 24-48 h, after which paired ER and control horses were fitted with a telemetric ECG and performed a 47 min submaximal SET. Plasma glucose, lactate, electrolyte and total protein concentrations and packed cell volume were measured before and immediately after exercise. Blood and percutaneous gluteal muscle samples were also obtained before and 3 h after exercise for measurement of plasma creatine kinase (CK) activity and muscle glycogen concentration, respectively. Histopathologic analysis of formalin-fixed pre-exercise muscle sections was performed. Data were analyzed by ANOVA and non-parametric tests (P <0.05). No horses displayed clinical signs of ER during exercise, and plasma CK increased similarly in ER and control Arabians. Muscle glycogen, heart rate, and remaining plasma variables did not differ between horses with ER and control horses. Horses with ER had more internalised nuclei in mature myofibers, more aggregates of cytoplasmic glycogen and desmin, and higher myopathic scores than control horses. Although many horses with ER had histopathologic evidence of chronic myopathy, muscle glycogen concentrations and metabolic exercise responses were normal. Results did not support a consistent metabolic myopathy or a glycogen storage disorder in Arabians with ER. PMID:27687952

  4. Clinical, histopathological and metabolic responses following exercise in Arabian horses with a history of exertional rhabdomyolysis.

    PubMed

    McKenzie, E C; Eyrich, L V; Payton, M E; Valberg, S J

    2016-10-01

    A previous report suggests a substantial incidence of exertional rhabdomyolysis (ER) in Arabian horses performing endurance racing. This study compared formalin histopathology and clinical and metabolic responses to a standardised field exercise test (SET) between Arabians with and without ER. Arabian horses with (n = 10; age 15.4 ± 5.6 years) and without (n = 9; 12.9 ± 6.1 years) prior ER were stall-rested for 24-48 h, after which paired ER and control horses were fitted with a telemetric ECG and performed a 47 min submaximal SET. Plasma glucose, lactate, electrolyte and total protein concentrations and packed cell volume were measured before and immediately after exercise. Blood and percutaneous gluteal muscle samples were also obtained before and 3 h after exercise for measurement of plasma creatine kinase (CK) activity and muscle glycogen concentration, respectively. Histopathologic analysis of formalin-fixed pre-exercise muscle sections was performed. Data were analyzed by ANOVA and non-parametric tests (P <0.05). No horses displayed clinical signs of ER during exercise, and plasma CK increased similarly in ER and control Arabians. Muscle glycogen, heart rate, and remaining plasma variables did not differ between horses with ER and control horses. Horses with ER had more internalised nuclei in mature myofibers, more aggregates of cytoplasmic glycogen and desmin, and higher myopathic scores than control horses. Although many horses with ER had histopathologic evidence of chronic myopathy, muscle glycogen concentrations and metabolic exercise responses were normal. Results did not support a consistent metabolic myopathy or a glycogen storage disorder in Arabians with ER.

  5. 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

  6. 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

  7. Clinical Outcome of HIV-Infected Patients with Discordant Virological and Immunological Response to Antiretroviral Therapy

    PubMed Central

    Zoufaly, A.; an der Heiden, M.; Kollan, C.; Bogner, J. R.; Fätkenheuer, G.; Wasmuth, J. C.; Stoll, M.; Hamouda, O.

    2011-01-01

    Background. A subgroup of human immunodeficiency virus type 1 (HIV-1)–infected patients with severe immunodeficiency show persistently low CD4+ cell counts despite sustained viral suppression. It is unclear whether this immuno-virological discordance translates into an increased risk for clinical events. Methods. Data analysis from a large multicenter cohort incorporating 14,433 HIV-1–infected patients in Germany. Treatment-naive patients beginning antiretroviral therapy (ART) with CD4+ cell counts <200 cells/μL who achieved complete and sustained viral suppression <50 copies/mL (n = 1318) were stratified according to the duration of immuno-virological discordance (failure to achieve a CD4+ cell count ≥200 cells/μL). Groups were compared by descriptive and Poisson statistics. The time-varying discordance status was analyzed in a multivariable Cox model. Results. During a total of 5038 person years of follow-up, 42 new AIDS events occurred. The incidence rate of new AIDS events was highest in the initial 6 months of complete viral suppression (immuno-virological discordance group, 55.06; 95% confidence interval [CI], 30.82–90.82; and immune responder group, 24.54; 95% CI, 10.59–48.35) and decreased significantly by 65% per year in patients with immuno-virological discordance (incidence risk ratio, 0.35; 95% CI, 0.14–0.92; P = .03). Immuno-virological discordance and prior AIDS diagnosis were independently associated with new AIDS events (hazard ratio, 3.10; 95% CI, 1.09–8.82; P = .03). Conclusion. Compared with immune responders, patients with immuno-virological discordance seem to remain at increased risk for AIDS. Absolute risk is greatly reduced after the first 6 months of complete viral suppression. PMID:21208929

  8. Relationship of Cognition to Clinical Response in First-Episode Schizophrenia Spectrum Disorders.

    PubMed

    Trampush, Joey W; Lencz, Todd; DeRosse, Pamela; John, Majnu; Gallego, Juan A; Petrides, Georgios; Hassoun, Youssef; Zhang, Jian-Ping; Addington, Jean; Kellner, Charles H; Tohen, Mauricio; Burdick, Katherine E; Goldberg, Terry E; Kane, John M; Robinson, Delbert G; Malhotra, Anil K

    2015-11-01

    First-episode schizophrenia (FES) spectrum disorders are associated with pronounced cognitive dysfunction across all domains. However, less is known about the course of cognitive functioning, following the first presentation of psychosis, and the relationship of cognition to clinical course during initial treatment. The present longitudinal study examined the magnitude of neurocognitive impairment, using the MATRICS Consensus Cognitive Battery, in patients experiencing their first episode of psychosis at baseline and after 12 weeks of randomized antipsychotic treatment with either aripiprazole or risperidone. At baseline, FES patients evidenced marked impairments in cognitive functioning. Notably, performance on the mazes task of planning and reasoning significantly predicted the likelihood of meeting stringent criteria for positive symptom remission during the first 12 weeks of the trial. Performance on indices of general cognitive function, working memory, and verbal learning improved over time, but these improvements were mediated by improvements in both positive and negative symptoms. We did not detect any differential effects of antipsychotic medication assignment (aripiprazole vs risperidone) on cognitive functioning. Our results suggest that a brief paper-and-pencil measure reflecting planning/reasoning abilities may index responsivity to antipsychotic medication. However, improvements in cognitive functioning over time were related to clinical symptom improvement, reflecting "pseudospecificity."

  9. 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.

  10. 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

  11. 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…

  12. BR 04-2 CONCENTRATION-RESPONSE MODELING OF ANTIHYPERTENSIVE DRUGS - IMPLICATION IN CLINICAL DEVELOPMENT.

    PubMed

    Yim, Dong-Seok

    2016-09-01

    In the early phase of clinical development of antihypertensive drugs, quantitative modeling to predict their dose-concentration-response relationship is important to plan future clinical development and finding optimal dosage regimen at marketing approval. Two cases of concentration-response models of antihypertensive are presented here.Case 1: Carvedilol is a α1- and nonselective β- adrenergic receptor antagonist currently used for the management of mild-to-moderate essential hypertension and congestive heart failure. The aim of this study was to perform a population pharmacokinetic-pharmacodynamic (PK-PD) model that describes PK and PD (systolic blood pressure (SBP) and diastolic blood pressure (DBP)) of both IR and SR formulations of carvedilol. For population PD modeling, the sequential PK-PD modeling approach (i.e., IPP approach) was used and the turnover model incorporating cosine functions for circadian rhythm was best described the SBP and DBP changes. In conclusion, the population PK-PD model adequately explained the observed data from two different formulations.Case 2: Fimasartan is a non-peptide angiotensin II receptor antagonist which selectively blocks the AT1 receptor. Population pharmacokinetic-pharmacodynamic (PK-PD) analysis of fimasartan was performed to evaluate the food effect on mechanistic PK-PD relationship, using data from a food interaction study in 24 healthy subjects. A two-compartment linear PK model with zero-order (fasted) or Weibull (fed with high fat diet) absorption best described the PK of fimasartan. Relative bioavailability decreased by 37% when the subjects were given high fat diet. The turnover PK-PD model combined with pre-defined cosine function for circadian rhythm described the BP changes measured within 24 hours after dosing better than the effect compartment or transduction models. To predict the influence of high fat diet on the blood pressure lowering effect of fimasartan in healthy subjects, we simulated the BP

  13. 1993 survey of salaries & responsibilities for hospital biomedical/clinical engineering & technology personnel.

    PubMed

    Pacela, A F

    1993-01-01

    The Journal of Clinical Engineering has conducted its eighth annual survey of the salaries paid to biomedical/clinical engineering and technology personnel in U.S. hospitals. This paper reports the salary and work responsibility data obtained from 1,497 professionals in relationship to: Certification; Region of the U.S.; Teaching versus Nonteaching Facilities; Years of Experience; Education; Union Membership; and Gender. Data are included on Wage Increases and Job Responsibilities. Data are as of 12/31/92 and are compared to 12/31/91. Last year, new job categories were introduced for the overall department or group Director or Manager and the BMET Specialist. The average BMET I has 3.1 years of experience and earns $24,418 +/- $4,615 (Std. Dev.). The average BMET II has 6.8 years of experience and earns $29,853 +/- $5,782. The average BMET III has 13.3 years of experience and earns $37,205 +/- $6,269. The average BMET Specialist has 13.9 years of experience and earns $42,808 +/- $9,420. The average BMET Supervisor has 13.4 years of experience and earns $39,206 +/- $7,709. The average Clinical Engineer has 9.1 years of experience and earns $40,121 +/- $8,242. CE Supervisors have an average 12.1 years of experience and an average salary of $47,353 +/- $15,501. The overall group or department Director or Manager has 15.7 years of experience and earns $51,237 +/- $16,381 on average. Wages are the highest on the East and West Coasts. Again this year, the lowest wages were in the Southeast. BMET wages advanced up to 4.6%, year to year. The highest quartile of Director/Managers now earns between $56,000 and $212,000 per year. Certified individuals variously earn up to $7,995 more than noncertified. PMID:10127344

  14. 1992 survey of salaries & responsibilities for hospital biomedical/clinical engineering & technology personnel.

    PubMed

    Pacela, A F

    1992-01-01

    The Journal of Clinical Engineering has conducted its seventh annual survey of the salaries paid to biomedical/clinical engineering and technology personnel in U.S. hospitals. This paper reports the salary and work responsibility data obtained from 1,482 professionals in relationship to: Certification; Region of the U.S.; Teaching versus Nonteaching Facilities; Years of Experience; Education; Union Membership; and Gender. Data are included on Wage Increases and Job Responsibilities. Data are as of 12/31/91 and are compared to 12/31/90. This year, new job categories were introduced for the overall department or group Director or Manager and the BMET Specialist. The average BMET I has 2.4 years of experience and earns $23,647 +/- $4,442 (Std. Dev.). The average BMET II has 6.6 years of experience and earns $30,128 +/- $5,696. The average BMET III has 12.9 years of experience and earns $35,855 +/- $5,942. The average BMET Specialist has 13.5 years of experience and earns $40,910 +/- $8,938. The average BMET Supervisor has 13.3 years of experience and earns $37,905 +/- $6,786. The average Clinical Engineer has 7.4 years of experience and earns $40,413 +/- $7,899. CE Supervisors have an average 12.2 years of experience and an average salary of $46,927 +/- $9,935. The overall group or department Director or Manager has 15 years of experience and earns $49,096 +/- $17,333 on average. Wages are the highest on the West Coast. This year, the lowest wages were in the Southeast. Because of survey changes in supervisor survey categories, year-to-year changes for supervisor wages cannot be evaluated. BMET wages, however, advanced 6% to 9%, year to year. The highest quartile of Director/Managers now earns between $53,000 and $245,000 per year. Certified individuals generally earn up to $3,257 more than noncertified, except for BMET Specialists where the certified respondents earned less than the noncertified. PMID:10119543

  15. BR 04-2 CONCENTRATION-RESPONSE MODELING OF ANTIHYPERTENSIVE DRUGS - IMPLICATION IN CLINICAL DEVELOPMENT.

    PubMed

    Yim, Dong-Seok

    2016-09-01

    In the early phase of clinical development of antihypertensive drugs, quantitative modeling to predict their dose-concentration-response relationship is important to plan future clinical development and finding optimal dosage regimen at marketing approval. Two cases of concentration-response models of antihypertensive are presented here.Case 1: Carvedilol is a α1- and nonselective β- adrenergic receptor antagonist currently used for the management of mild-to-moderate essential hypertension and congestive heart failure. The aim of this study was to perform a population pharmacokinetic-pharmacodynamic (PK-PD) model that describes PK and PD (systolic blood pressure (SBP) and diastolic blood pressure (DBP)) of both IR and SR formulations of carvedilol. For population PD modeling, the sequential PK-PD modeling approach (i.e., IPP approach) was used and the turnover model incorporating cosine functions for circadian rhythm was best described the SBP and DBP changes. In conclusion, the population PK-PD model adequately explained the observed data from two different formulations.Case 2: Fimasartan is a non-peptide angiotensin II receptor antagonist which selectively blocks the AT1 receptor. Population pharmacokinetic-pharmacodynamic (PK-PD) analysis of fimasartan was performed to evaluate the food effect on mechanistic PK-PD relationship, using data from a food interaction study in 24 healthy subjects. A two-compartment linear PK model with zero-order (fasted) or Weibull (fed with high fat diet) absorption best described the PK of fimasartan. Relative bioavailability decreased by 37% when the subjects were given high fat diet. The turnover PK-PD model combined with pre-defined cosine function for circadian rhythm described the BP changes measured within 24 hours after dosing better than the effect compartment or transduction models. To predict the influence of high fat diet on the blood pressure lowering effect of fimasartan in healthy subjects, we simulated the BP

  16. Transferring responsibility and accountability in maternity care: clinicians defining their boundaries of practice in relation to clinical handover

    PubMed Central

    Chin, Georgiana S M; Warren, Narelle; Kornman, Louise; Cameron, Peter

    2012-01-01

    Objective This exploratory study reports on maternity clinicians’ perceptions of transfer of their responsibility and accountability for patients in relation to clinical handover with particular focus transfers of care in birth suite. Design A qualitative study of semistructured interviews and focus groups of maternity clinicians was undertaken in 2007. De-indentified data were transcribed and coded using the constant comparative method. Multiple themes emerged but only those related to responsibility and accountability are reported in this paper. Setting One tertiary Australian maternity hospital. Participants Maternity care midwives, nurses (neonatal, mental health, bed managers) and doctors (obstetric, neontatology, anaesthetics, internal medicine, psychiatry). Primary outcome measures Primary outcome measures were the perceptions of clinicians of maternity clinical handover. Results The majority of participants did not automatically connect maternity handover with the transfer of responsibility and accountability. Once introduced to this concept, they agreed that it was one of the roles of clinical handover. They spoke of complete transfer, shared and ongoing responsibility and accountability. When clinicians had direct involvement or extensive clinical knowledge of the patient, blurring of transition of responsibility and accountability sometimes occurred. A lack of ‘ownership’ of a patient and their problems were seen to result in confusion about who was to address the clinical issues of the patient. Personal choice of ongoing responsibility and accountability past the handover communication were described. This enabled the off-going person to rectify an inadequate handover or assist in an emergency when duty clinicians were unavailable. Conclusions There is a clear lack of consensus about the transition of responsibility and accountability—this should be explicit at the handover. It is important that on each shift and new workplace environment

  17. Abnormal plasma monoamine metabolism in schizophrenia and its correlation with clinical responses to risperidone treatment.

    PubMed

    Cai, Hua-Lin; Fang, Ping-Fei; Li, Huan-De; Zhang, Xiang-Hui; Hu, Li; Yang, Wen; Ye, Hai-Sen

    2011-07-30

    Abnormalities in plasma monoamine metabolism reflect partly the illness of schizophrenia and sometimes the symptoms. Such studies have been repeatedly reported but have rarely taken both metabolites and parent amines or inter-amine activity ratios into account. In this study, the monoamines, their metabolites, turnovers and between-metabolite ratios in plasma were measured longitudinally in 32 schizophrenic patients treated with risperidone for 6 weeks, to examine possible biochemical alterations in schizophrenia, and to examine the association between treatment responses and psychopathology assessed according to the Positive and Negative Syndrome Scale (PANSS). The results showed lower level of plasma 3,4-dihydroxyphenylacetic acid (DOPAC) in relapsed versus first-episode schizophrenic patients, higher norepinephrine (NE) turnover rate (TR) in undifferentiated in comparison to paranoid schizophrenic patients and relatively higher metabolic activity of dopamine (DA) to serotonin (5-HT) in first-episode versus relapsed schizophrenic patients. Risperidone treatment induced a decrement of plasma DA levels and increments of plasma DOPAC and DA TR in the total group of schizophrenic patients. The turnover rate of 5-HT was was reduced in undifferentiated and relapsed subgroups of schizophrenic patients. The linkages between 5-HT TR, DA/NE relative activity and clinical symptomatology were also identified. These findings are consistent with an involvement of these systems in the pathogenesis of schizophrenia as well as in the responses to treatment, and the usefulness of certain biochemical indices as markers for subgrouping.

  18. Cryptosporidiosis in HIV/AIDS patients in Kenya: clinical features, epidemiology, molecular characterization and antibody responses.

    PubMed

    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

    2014-08-01

    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.

  19. The cardiac component of the orienting response: effects of signal intensity, clinical interpretation, and procedural limitations.

    PubMed

    Borton, T E; Moore, W H

    1979-02-01

    The effects of stimulus intensity on the cardiac component of the orienting response were explored in male and female subjects. The acoustic stimuli were 10 recorded repetitions of an identical consonant vowel cluster spoken by an adult male. Heart rate data were obtained for both subject groups at three sensation levels across the baseline heart rate and at 10 stimulus presentation trials. A significant main effect was noted for trials. Significant linear and quadratic trend components were observed, reflecting habituation of the orienting response as a function of trials, and indicating the nonmonotonicity of heart rate change over trials. A lower mean heart rate was observed for Condition Two (20 dB SL) than for either of the other conditions, 10 dB and 30 dB SL respectively. Analysis of group variability and individual subjects' heart rate data suggested limitations in generalizing from group to individual data, as well as a need for further investigation if proper interpretation of single subject heart rate data are to be useful in the clinical situation.

  20. 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

  1. Relationship Between the Clinical Components of the Boder Test of Reading-Spelling Patterns and the Stanford Achievement Test: Validity of the Boder.

    ERIC Educational Resources Information Center

    Hooper, Stephen R.

    1988-01-01

    Investigated the concurrent validity of the diagnostic components of the Boder Test of Reading-Spelling Patterns with the reading and spelling measures of the Stanford Achievement Reading Test (SAT) in 87 reading-disabled elementary school students. Results indicated the relationship between the reading components of the Boder and SAT were…

  2. Assessment of Current Knowledge about the Effectiveness of School Desegregation Strategies. Volume V. A Review of the Empirical Research on Desegregation: Community Response, Race Relations, Academic Achievement and Resegregation.

    ERIC Educational Resources Information Center

    Rossell, Christine; And Others

    This literature review considers the impact of desegregation on community response, racial relations, academic achievement and resegregation. Chapter one examines the effectiveness of desegregation plans in reducing racial isolation and white flight, and in promoting a positive community response. Desegregation school practices and effects on…

  3. Variables affecting clinical response to treatment of facial port-wine stains by flash lamp-pumped pulsed dye laser: the importance of looking beyond the skin.

    PubMed

    Bencini, Pier Luca; Cazzaniga, Simone; Galimberti, Michela Gianna; Zane, Cristina; Naldi, Luigi

    2014-07-01

    The response of port-wine stains (PWS) to conventional laser treatment in adults is difficult to predict. To assess the influence of local or systemic hemodynamic variables on the clearance of PWS by using flash lamp-pumped pulsed (FLPP) dye laser. All consecutive patients ages 18 years or older undergoing laser treatment for a facial PWS were eligible. Laser sessions were scheduled every 8 weeks. All patients were evaluated based on a standard scale with four evaluation categories, from no or minimal improvement to total or almost total clearance. Clearance was achieved by 50.1 % (95 % confidence interval 35.6-64.7) of patients after a maximum of 15 treatment sessions. In multivariate analysis, increased age, a newly described Type III capillaroscopic pattern, and presence of lesions in dermatome V2 were all associated with a reduced clinical response to treatment. In a model restricted to demographic pattern and patient characteristics, arterial hypertension was also associated with a lower clinical response. A strong association was found between arterial hypertension and the Type III capillaroscopic pattern. Age, arterial hypertension, capillaroscopic pattern, and body location should be considered when planning laser treatment of PWS.

  4. 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

  5. Low high-density lipoprotein cholesterol is a residual risk factor associated with long-term clinical outcomes in diabetic patients with stable coronary artery disease who achieve optimal control of low-density lipoprotein cholesterol.

    PubMed

    Ogita, Manabu; Miyauchi, Katsumi; Miyazaki, Tadashi; Naito, Ryo; Konishi, Hirokazu; Tsuboi, Shuta; Dohi, Tomotaka; Kasai, Takatoshi; Yokoyama, Takayuki; Okazaki, Shinya; Kurata, Takeshi; Daida, Hiroyuki

    2014-01-01

    Diabetes mellitus is recognized an independent risk factor for coronary artery disease (CAD) and mortality. Clinical trials have shown that statins significantly reduce cardiovascular events in diabetic patients. However, residual cardiovascular risk persists despite the achievement of target low-density lipoprotein cholesterol (LDL-C) levels with statin. High-density lipoprotein cholesterol (HDL-C) is an established coronary risk factor that is independent of LDL-C levels. We evaluated the impact of HDL-C on long-term mortality in diabetic patients with stable CAD who achieved optimal LDL-C. We enrolled 438 consecutive diabetic patients who were scheduled for percutaneous coronary intervention between 2004 and 2007 at our institution. We identified 165 patients who achieved target LDL-C <100 mg/dl. Patients were stratified into two groups according to HDL-C levels (low HDL-C group, baseline HDL-C <40 mg/dl; high HDL-C group, ≥40 mg/dl). Major adverse cardiac events (MACE) that included all-cause death, acute coronary syndrome, and target lesion revascularization were evaluated between the two groups. The median follow-up period was 946 days. The rate of MACE was significantly higher in diabetic patients with low-HDL-C who achieved optimal LDL-C (6.9 vs 17.9 %, log-rank P = 0.030). Multivariate Cox regression analysis showed that HDL-C is significantly associated with clinical outcomes (adjusted hazard ratio for MACE 1.33, 95 % confidence interval 1.01-1.75, P = 0.042). Low HDL-C is a residual risk factor that is significantly associated with long-term clinical outcomes among diabetic patients with stable CAD who achieve optimal LDL-C levels.

  6. Refractory myasthenia gravis – clinical profile, comorbidities and response to rituximab

    PubMed Central

    Sudulagunta, Sreenivasa Rao; Sepehrar, Mona; Sodalagunta, Mahesh Babu; Settikere Nataraju, Aravinda; Bangalore Raja, Shiva Kumar; Sathyanarayana, Deepak; Gummadi, Siddharth; Burra, Hemanth Kumar

    2016-01-01

    Introduction: Myasthenia gravis (MG) is an antibody mediated autoimmune neuromuscular disorder characterized by fatigable muscle weakness. A proportion of myasthenia gravis patients are classified as refractory due to non responsiveness to conventional treatment. This retrospective study was done to evaluate clinical profile, epidemiological, laboratory, and features of patients with MG and mode of management using rituximab and complications. Methods: Data of myasthenia gravis patients admitted or presented to outpatient department (previous medical records) with MG between January 2008 and January 2016 were included. A total of 512 patients fulfilled the clinical and diagnostic criteria of myasthenia gravis of which 76 patients met the diagnostic certainty for refractory myasthenia gravis and were evaluated. Results: Out of 76 refractory MG patients, 53 (69.73%) patients fulfilled all the three defined criteria. The median age of onset of the refractory MG group was 36 years with a range of 27–53 years. In our study 25 patients (32.89%) belonged to the age group of 21–30 years. Anti-MuSK antibodies were positive in 8 non-refractory MG patients (2.06%) and 36 refractory MG patients (47.36%). Mean HbA1C was found to be 8.6±2.33. The dose of administered prednisone decreased by a mean of 59.7% (p=3.3x10–8) to 94.6% (p=2.2x10–14) after the third cycle of rituximab treatment. Conclusion: The refractory MG patients are most commonly female with an early age of onset, anti-MuSK antibodies, and thymomas. Refractory MG patients have higher prevalence and poor control (HbA1C >8%) of diabetes mellitus and dyslipidemia probably due to increased steroid usage. Rituximab is very efficient in treatment of refractory MG with adverse effects being low. PMID:27790079

  7. 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

  8. 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

  9. 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

  10. Factors associated with early response to olanzapine and clinical and functional outcomes of early responders treated for schizophrenia in the People’s Republic of China

    PubMed Central

    Ye, Wenyu; Montgomery, William; Kadziola, Zbigniew; Liu, Li; Xue, Haibo; Stensland, Michael D; Treuer, Tamas

    2014-01-01

    Background The aims of this analysis were to identify factors associated with early response (at 4 weeks) to olanzapine treatment and to assess whether early response is associated with better longer-term outcomes for patients with schizophrenia in the People’s Republic of China. Methods A post hoc analysis of a multi-country, 6-month, prospective, observational study of outpatients with schizophrenia or bipolar mania who initiated or switched to treatment with oral olanzapine was conducted using data from the Chinese schizophrenia subgroup (n=330). Factors associated with early response were identified using a stepwise logistic regression with baseline clinical characteristics, baseline participation in a weight control program, and adherence with antipsychotics during the first 4 weeks of treatment. Mixed models for repeated measures with baseline covariates were used to compare outcomes over time between early responders and early nonresponders to olanzapine. Results One hundred and thirty patients (40%) achieved an early response. Early response was independently predicted by higher baseline Clinical Global Impressions-Severity score (odds ratio [OR] 1.51, 95% confidence interval [CI] 1.15–1.97), fewer years since first diagnosis (OR 0.94, CI 0.90–0.98), a greater number of social activities (OR 1.22, CI 1.05–1.40), participation in a weight control program (OR 1.81, CI 1.04–3.15), and high adherence with antipsychotics during the first 4 weeks of treatment (OR 2.98, CI 1.59–5.58). Relative to early nonresponders, early responders were significantly more likely to meet treatment response criteria at endpoint, had significantly greater symptom improvement (Clinical Global Impressions-Severity), and had significantly greater improvement in functional outcomes (all P<0.05). Conclusion High levels of adherence to prescribed antipsychotics and participation in a weight control program were associated with early response to olanzapine in Chinese patients

  11. Hyperprolactinemia in men: clinical and biochemical features and response to treatment.

    PubMed

    De Rosa, Michele; Zarrilli, Stefano; Di Sarno, Antonella; Milano, Nicola; Gaccione, Maria; Boggia, Bartolomeo; Lombardi, Gaetano; Colao, Annamaria

    2003-01-01

    Hyperprolactinemia induces hypogonadism by inhibiting gonadotropin-releasing hormone pulsatile secretion and, consequently, follicle-stimulating hormone, luteinizing hormone, and testosterone pulsatility. This leads to spermatogenic arrest, impaired motility, and sperm quality and results in morphologic alterations of the testes similar to those observed in prepubertal testes. Men with hyperprolactinemia present more frequently with a macroadenoma than a microadenoma. Symptoms directly related to hypogonadism are prevalent. In men hypogonadism leads to impaired libido, erectile dysfunction, diminished ejaculate volume, and oligospermia. It is present in 16% of patients with erectile dysfunction and in approx 11% of men with oligospermia. Treatment with bromocriptine or cabergoline (CAB) is effective in men with prolactinomas, with a response that is in general comparable to treatment in women. Seminal fluid abnormalities rapidly improve with CAB treatment, while other dopaminergic compounds require longer periods of treatment. Moreover, to improve gonadal function in men, the integrity of the hypothalamic-pituitary-gonadal axis is necessary. New promising data indicate that a substantial proportion of patients with either micro- or macroprolactinoma do not present hyperprolactinemia after long-term withdrawal from CAB. Whether this corresponds to a definitive cure is still unknown, but treatment withdrawal should be attempted in patients achieving normalization of prolactin levels and disappearance of tumor mass to investigate this issue.

  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. Substance use in a school-based clinic population: use of the randomized response technique to estimate prevalence.

    PubMed

    Fisher, M; Kupferman, L B; Lesser, M

    1992-06-01

    Students attending school-based clinics acknowledge only minimal involvement with drug or alcohol use. In order to explain this unanticipated finding, we used a statistical method called randomized response to study adolescents in one school-based clinic. The sample consisted of 133 students (57% female; 75% black, 20% Hispanic, 5% other; and 58% grades 9-10, 42% grades 11-12). Using both lifetime and 30-day prevalence rates, these students revealed more cigarette smoking and alcohol use on randomized response than they had on questionnaires completed earlier the same academic year, minimal involvement with either marijuana or cocaine use by either method, and a similar amount of sexual activity by both methods. This study demonstrates that randomized response can be a useful method to generate more truthful group responses from adolescents. PMID:1610843

  15. Translating the therapeutic potential of neurotrophic factors to clinical 'proof of concept': a personal saga achieving a career-long quest.

    PubMed

    Bartus, Raymond T

    2012-11-01

    While the therapeutic potential of neurotrophic factors has been well-recognized for over two decades, attempts to translate that potential to the clinic have been disappointing, largely due to significant delivery obstacles. Similarly, gene therapy (or gene transfer) emerged as a potentially powerful, new therapeutic approach nearly two decades ago and despite its promise, also suffered serious setbacks when applied to the human clinic. As advances continue to be made in both fields, ironically, they may now be poised to complement each other to produce a translational breakthrough. The accumulated data argue that gene transfer provides the 'enabling technology' that can solve the age-old delivery problems that have plagued the translation of neurotrophic factors as treatments for chronic central nervous system diseases. A leading translational program applying gene transfer to deliver a neurotrophic factor to rejuvenate and protect degenerating human neurons is CERE-120 (AAV2-NRTN). To date, over two dozen nonclinical studies and three clinical trials have been completed. A fourth (pivotal) clinical trial has completed all dosing and is currently evaluating safety and efficacy. In total, eighty Parkinson's disease (PD) subjects have thus far been dosed with CERE-120 (some 7 years ago), representing over 250 cumulative patient-years of exposure, with no serious safety issues identified. In a completed sham-surgery, double-blinded controlled trial, though the primary endpoint (the Unified Parkinson's Disease Rating Scale (UDPRS) motor off score measured at 12 months) did not show benefit from CERE-120, several important motor and quality of life measurements did, including the same UPDRS-motor-off score, pre-specified to also be measured at a longer, 18-month post-dosing time point. Importantly, not a single measurement favored the sham control group. This study therefore, provided important, well-controlled evidence establishing 'clinical proof of concept' for

  16. Genetic and clinical biomarkers of tocilizumab response in patients with rheumatoid arthritis.

    PubMed

    Maldonado-Montoro, Mar; Cañadas-Garre, Marisa; González-Utrilla, Alfonso; Plaza-Plaza, José Cristian; Calleja-Hernández, Miguel Ángel

    2016-09-01

    The aim of this study was to investigate the influence of clinical and genetic factors on response to tocilizumab (TCZ) response, remission, low disease activity (LDA) and DAS28 improvement. A retrospective cohort study in 79 RA patients treated with TCZ during 6/18 months of therapy was conducted. CD69(rs11052877), GALNT18(rs4910008), CLEC2D(rs1560011), KCNMB1(rs703505), ENOX1(rs9594987), rs10108210, and rs703297 gene polymorphisms, identified in a recent GWAS as putative predictors of TCZ response, were analysed. Variables independently associated to satisfactory EULAR response at 6 months were GALNT18-CC genotype (ORCC/T-:12.8; CI95%:1.5,108.7; p=0.02), CD69 gene polymorphism (ORAA/GG:17.2; CI95%:2.5,119.6; p=0.004) and lower number of previous biological therapy, BT (OR: 0.45; CI95%:0.3, 0.7; p=0.001). The factors independently associated to higher remission were lower number of previous BT (OR:0.56; CI95%:0.38, 0.82; p=0.003), and GALNT18 CC genotype (ORCT/CC:0.09; CI95%:0.02,0.45;p=0.004; ORTT/CC:0.14; CI95%:0.02,0.79; p=0.026). The A-allele of CD69 (ORA_/GG:6.68;CI95%:1.68,26.51;p=0.007) and lower number of previous BT (OR:0.50; CI95%:0.32,0.77; p=0.002) were independent factors capable to predict higher LDA rates at 6 months. Independent factors associated to higher improvement in DAS28 at 6 months were CD69-AA genotype (B=-0.56; CI95%:-1.09, -0.03; p=0.039), GALNT18-CC genotype (B=-0.88;CI95%:-1.49, -0.27; p=0.005), subcutaneous administration (B=1.03; CI95%:0.44,1.62; p=0.001) and higher baseline DAS28 (B=0.82; CI95%:0.59, 1.05; p=4.9×10(-10)). Lower number of previous BT was the only independent predictor of satisfactory EULAR response (OR:0.60; CI95%:0.34,0.88; p=0.010) and higher remission (OR:0.65; CI95%:0.46,0.93; p=0.018) at 18 months. The C-allele of GALNT18 (ORC-/TT:4.60; CI95%:1.16, 18.27; p=0.03) and lower number of previous BT (OR:0.47; CI95%:0.29,0.74; p=0.001) were independent factors capable to predict higher LDA rates at 18 months. In

  17. General Rules for the Clinical and Pathological Study of Primary Liver Cancer, Nationwide Follow-Up Survey and Clinical Practice Guidelines: The Outstanding Achievements of the Liver Cancer Study Group of Japan.

    PubMed

    Kudo, Masatoshi; Kitano, Masayuki; Sakurai, Toshiharu; Nishida, Naoshi

    2015-10-01

    This review outlines the significance of establishing general rules, a nationwide follow-up survey, and clinical practice guidelines for liver cancer in Japan. The general rules are an essential part of hepatocellular carcinoma (HCC) treatment, enabling a 'common language' to be used in daily clinical practice and for the nationwide follow-up survey. The Japanese General Rules for the Clinical and Pathological Study of Primary Liver Cancer, which provide detailed descriptions of HCC, are excellent and are unique to Japan. Items in the General Rules for the Clinical and Pathological Study of Primary Liver Cancer are used substantially in another important project, the Nationwide Follow-Up Survey of Primary Liver Cancer, which has been rigorously undertaken with great effort by the Liver Cancer Study Group of Japan biannually since 1969. Both evidence-based and consensus-based treatment algorithms for HCC are used to complement each other in clinical practice in Japan.

  18. Neural basis of new clinical vestibular tests: otolithic neural responses to sound and vibration.

    PubMed

    Curthoys, Ian S; Vulovic, Vedran; Burgess, Ann M; Manzari, Leonardo; Sokolic, Ljiljana; Pogson, Jacob; Robins, Mike; Mezey, Laura E; Goonetilleke, Samanthi; Cornell, Elaine D; MacDougall, Hamish G

    2014-05-01

    Extracellular single neuron recording and labelling studies of primary vestibular afferents in Scarpa's ganglion have shown that guinea-pig otolithic afferents with irregular resting discharge are preferentially activated by 500 Hz bone-conducted vibration (BCV) and many also by 500 Hz air-conducted sound (ACS) at low threshold and high sensitivity. Very few afferent neurons from any semicircular canal are activated by these stimuli and then only at high intensity. Tracing the origin of the activated neurons shows that these sensitive otolithic afferents originate mainly from a specialized region, the striola, of both the utricular and saccular maculae. This same 500 Hz BCV elicits vestibular-dependent eye movements in alert guinea-pigs and in healthy humans. These stimuli evoke myogenic potentials, vestibular-evoked myogenic potentials (VEMPs), which are used to test the function of the utricular and saccular maculae in human patients. Although utricular and saccular afferents can both be activated by BCV and ACS, the differential projection of utricular and saccular afferents to different muscle groups allows for differentiation of the function of these two sensory regions. The basic neural data support the conclusion that in human patients in response to brief 500 Hz BCV delivered to Fz (the midline of the forehead at the hairline), the cervical VEMP indicates predominantly saccular function and the ocular VEMP indicates predominantly utricular function. The neural, anatomical and behavioural evidence underpins clinical tests of otolith function in humans using sound and vibration.

  19. Neural basis of new clinical vestibular tests: otolithic neural responses to sound and vibration.

    PubMed

    Curthoys, Ian S; Vulovic, Vedran; Burgess, Ann M; Manzari, Leonardo; Sokolic, Ljiljana; Pogson, Jacob; Robins, Mike; Mezey, Laura E; Goonetilleke, Samanthi; Cornell, Elaine D; MacDougall, Hamish G

    2014-05-01

    Extracellular single neuron recording and labelling studies of primary vestibular afferents in Scarpa's ganglion have shown that guinea-pig otolithic afferents with irregular resting discharge are preferentially activated by 500 Hz bone-conducted vibration (BCV) and many also by 500 Hz air-conducted sound (ACS) at low threshold and high sensitivity. Very few afferent neurons from any semicircular canal are activated by these stimuli and then only at high intensity. Tracing the origin of the activated neurons shows that these sensitive otolithic afferents originate mainly from a specialized region, the striola, of both the utricular and saccular maculae. This same 500 Hz BCV elicits vestibular-dependent eye movements in alert guinea-pigs and in healthy humans. These stimuli evoke myogenic potentials, vestibular-evoked myogenic potentials (VEMPs), which are used to test the function of the utricular and saccular maculae in human patients. Although utricular and saccular afferents can both be activated by BCV and ACS, the differential projection of utricular and saccular afferents to different muscle groups allows for differentiation of the function of these two sensory regions. The basic neural data support the conclusion that in human patients in response to brief 500 Hz BCV delivered to Fz (the midline of the forehead at the hairline), the cervical VEMP indicates predominantly saccular function and the ocular VEMP indicates predominantly utricular function. The neural, anatomical and behavioural evidence underpins clinical tests of otolith function in humans using sound and vibration. PMID:24754528

  20. Clinical usefulness of maternal odor in newborns: soothing and feeding preparatory responses.

    PubMed

    Sullivan, R M; Toubas, P

    1998-12-01

    This study assessed the responsiveness of newborn breast- and bottle-fed infants to presentations of maternal odor. Maternal odor was presented for 1 min to crying, sleeping or awake newborns. The odors were: (1) own mother's odor - presentation of a hospital gown worn by the baby's mother, (2) other mother's odor - presentation of a hospital gown of another newborn baby's mother, (3) clean gown - presentation of a clean hospital gown and (4) no gown - no gown presented. The results indicated that crying babies stopped crying when either own mother or other mother odor was presented. Awake babies responded specifically to their own mother's odor by increasing mouthing. These results suggest that the practice of presenting the mother's odor to a distressed infant is of clinical usefulness since it was capable of attenuating crying. The results also characterized a role for maternal odor with respect to feeding since presentation of the infant's own mother odor increased mouthing. Thus, presentation of maternal odor may also be useful in enhancing nipple acceptance and feeding in newborns. PMID:9784631

  1. 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

  2. Pityriasis Lichenoides-like Mycosis Fungoides: Clinical and Histologic Features and Response to Phototherapy

    PubMed Central

    Jang, Min Soo; Kang, Dong Young; Park, Jong Bin; Kim, Joon Hee; Park, Kwi Ae; Rim, Hark

    2016-01-01

    Background Pityriasis lichenoides (PL)-like skin lesions rarely appear as a specific manifestation of mycosis fungoides (MF). Objective We investigated the clinicopathological features, immunophenotypes, and treatments of PL-like MF. Methods This study included 15 patients with PL-like lesions selected from a population of 316 patients diagnosed with MF at one institution. Results The patients were between 4 and 59 years of age. Four patients were older than 20 years of age. All of the patients had early-stage MF. In all patients, the atypical lymphocytic infiltrate had a perivascular distribution with epidermotropism. The CD4/CD8 ratio was <1 in 12 patients. Thirteen patients were treated with either narrowband ultraviolet B (NBUVB) or psoralen+ultraviolet A (PUVA), and all of them had complete responses. Conclusion PL-like MF appears to have a favorable prognosis and occurrence of this variant in adults is uncommon. MF should be suspected in the case of a PL-like skin eruption. Therefore, biopsy is required to confirm the diagnosis of PL-like MF, and NBUVB is a clinically effective treatment. PMID:27746631

  3. 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

  4. An adaptive response of Enterobacter aerogenes to imipenem: regulation of porin balance in clinical isolates.

    PubMed

    Lavigne, Jean-Philippe; Sotto, Albert; Nicolas-Chanoine, Marie-Hélène; Bouziges, Nicole; Pagès, Jean-Marie; Davin-Regli, Anne

    2013-02-01

    Imipenem (IPM) is a carbapenem antibiotic frequently used in severe hospital infections. Several reports have mentioned the emergence of resistant isolates exhibiting membrane modifications. A study was conducted between September 2005 and August 2007 to survey infections due to Enterobacter aerogenes in patients hospitalised in a French university hospital. Resistant E. aerogenes clinical isolates obtained from patients treated with IPM and collected during the 3 months following initiation of treatment were phenotypically and molecularly characterised for β-lactamases, efflux pumps activity and outer membrane proteins. Among the 339 patients infected with E. aerogenes during the study period, 41 isolates (12.1%) were resistant to extended-spectrum cephalosporins and 17 patients (5.0%) were treated with IPM. The isolates from these 17 patients presented TEM-24 and basal efflux expression. Following IPM treatment, an IPM-intermediate-susceptible (IPM-I) isolate emerged in 11 patients and an IPM-resistant (IPM-R) isolate in 6 patients. A change in the porin balance (Omp35/Omp36) was observed in IPM-I isolates exhibiting ertapenem resistance. Finally, a porin deficiency (Omp35 and Omp36 absence) was detected in IPM-R isolates associated with efflux pump expression. This study indicates that the alteration in porin expression, including the shift of porin expression and lack of porins, contribute to the E. aerogenes adaptive response to IPM treatment.

  5. Clinical and parasitological response to oral chloroquine and primaquine in uncomplicated human Plasmodium knowlesi infections

    PubMed Central

    2010-01-01

    Background Plasmodium knowlesi is a cause of symptomatic and potentially fatal infections in humans. There are no studies assessing the detailed parasitological response to treatment of knowlesi malaria infections in man and whether antimalarial resistance occurs. Methods A prospective observational study of oral chloroquine and primaquine therapy was conducted in consecutive patients admitted to Kapit Hospital, Sarawak, Malaysian Borneo with PCR-confirmed single P. knowlesi infections. These patients were given oral chloroquine for three days, and at 24 hours oral primaquine was administered for two consecutive days, primarily as a gametocidal agent. Clinical and parasitological responses were recorded at 6-hourly intervals during the first 24 hours, daily until discharge and then weekly to day 28. Vivax malaria patients were studied as a comparator group. Results Of 96 knowlesi malaria patients who met the study criteria, 73 were recruited to an assessment of the acute response to treatment and 60 completed follow-up over 28 days. On admission, the mean parasite stage distributions were 49.5%, 41.5%, 4.0% and 5.6% for early trophozoites, late trophozoites, schizonts and gametocytes respectively. The median fever clearance time was 26.5 [inter-quartile range 16-34] hours. The mean times to 50% (PCT50) and 90% (PCT90) parasite clearance were 3.1 (95% confidence intervals [CI] 2.8-3.4) hours and 10.3 (9.4-11.4) hours. These were more rapid than in a group of 23 patients with vivax malaria 6.3 (5.3-7.8) hours and 20.9 (17.6-25.9) hours; P = 0.02). It was difficult to assess the effect of primaquine on P. knowlesi parasites, due to the rapid anti-malarial properties of chloroquine and since primaquine was administered 24 hours after chloroquine. No P. knowlesi recrudescences or re-infections were detected by PCR. Conclusions Chloroquine plus primaqine is an inexpensive and highly effective treatment for uncomplicated knowlesi malaria infections in humans and there is

  6. Response of Holstein cows with milk fever to first treatment using two calcium regimens: a retrospective clinical study.

    PubMed

    Sasaki, Kouya; Sasaki, Kazuya; Sato, Yukiko; Devkota, Bhuminand; Furuhama, Kazuhisa; Yamagishi, Norio

    2013-01-01

    The responses of 64 Holstein cows with milk fever to first treatment with 500 ml of either of 2 intravenous calcium (Ca) solutions, one containing Ca alone (group A, n = 32) or 1 containing Ca, phosphate and magnesium (group B, n = 32), were evaluated by selected clinical signs and serum biochemical data. Based on the cow's ability to stand, treatment response was categorized into "immediate response" (stood after single treatment), "delayed response" (stood after repeated treatments) and "non-response" (slaughtered despite repeated treatments). No significant differences among the response categories were found between the two groups, suggesting that the solution containing Ca borogluconate alone was sufficient for the first treatment of milk fever.

  7. Studying Mental Health Counselor Clinical Judgment: A Response to Falvey and Colleagues.

    ERIC Educational Resources Information Center

    Strohmer, Douglas C.; Spengler, Paul M.

    1993-01-01

    Reviews material related to American Mental Health Counselors Association Clinical Judgment Project. Recommendations include invoking more sensitive analyses of clinical judgment process, establishing defensible diagnostic and treatment criteria, attending to threats to statistical conclusion validity, and increasing attention to counselor…

  8. 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...

  9. A Clinic-Based Lifestyle Intervention for Pediatric Obesity: Efficacy and Behavioral and Biochemical Predictors of Response

    PubMed Central

    Madsen, Kristine A.; Garber, Andrea K.; Mietus-Snyder, Michele L.; Orrell-Valente, Joan K.; Tran, Cam-Tu; Wlasiuk, Lidya; Matos, Renee I.; Neuhaus, John; Lustig, Robert H.

    2010-01-01

    Aim To examine efficacy and predictors of response to a lifestyle intervention for obese youth. Methods Retrospective chart review of 214 children and adolescents aged 8-19 years. Linear regression identified baseline predictors of response (Δ BMI z-score) at first and ultimate follow-up visits. Results Mean Δ BMI z-score from baseline was -0.04 (p <0.001) at first follow-up and -0.09 (p <0.001) at ultimate follow-up (median time 10 mo) among 156 children and adolescents. Higher baseline BMI z-score predicted poor response at first and ultimate follow-up, explaining 10% of variance in response. Fasting insulin explained 6% of response variance at first follow-up. Δ BMI z-score at the first visit along with baseline BMI z-score explained up to 50% of variance in response at ultimate visit. Conclusion Clinic-based interventions improve weight status. Baseline variables predict only a small proportion of response; response at the first visit is a more meaningful tool to guide clinical decisions. PMID:19960890

  10. 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

  11. 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…

  12. 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

    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

  13. 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

  14. Statistical methods for clinical verification of dose response parameters related to esophageal stricture and AVM obliteration from radiotherapy

    NASA Astrophysics Data System (ADS)

    Mavroidis, Panayiotis; Lind, Bengt K.; Theodorou, Kyriaki; Laurell, Göran; Fernberg, Jan-Olof; Lefkopoulos, Dimitrios; Kappas, Constantin; Brahme, Anders

    2004-08-01

    The purpose of this work is to provide some statistical methods for evaluating the predictive strength of radiobiological models and the validity of dose-response parameters for tumour control and normal tissue complications. This is accomplished by associating the expected complication rates, which are calculated using different models, with the clinical follow-up records. These methods are applied to 77 patients who received radiation treatment for head and neck cancer and 85 patients who were treated for arteriovenous malformation (AVM). The three-dimensional dose distribution delivered to esophagus and AVM nidus and the clinical follow-up results were available for each patient. Dose-response parameters derived by a maximum likelihood fitting were used as a reference to evaluate their compatibility with the examined treatment methodologies. The impact of the parameter uncertainties on the dose-response curves is demonstrated. The clinical utilization of the radiobiological parameters is illustrated. The radiobiological models (relative seriality and linear Poisson) and the reference parameters are validated to prove their suitability in reproducing the treatment outcome pattern of the patient material studied (through the probability of finding a worse fit, area under the ROC curve and khgr2 test). The analysis was carried out for the upper 5 cm of the esophagus (proximal esophagus) where all the strictures are formed, and the total volume of AVM. The estimated confidence intervals of the dose-response curves appear to have a significant supporting role on their clinical implementation and use.

  15. All the Vice Chancellor’s Neuroscientists: Unity to Achieve Success in Solving Malaysia’s Diseases via Upgrading Clinical Services and Neuroscience Research

    PubMed Central

    Abdullah, Jafri Malin

    2013-01-01

    President Obama of the United States of America announced this April the Brain Research Through Advancing Innovative Neurotechnologies (BRAIN for short) investment, while Professor Henry Markram’s team based in the European Union will spend over a billion euros on the Human Brain Project, breaking through the unknowns in the fifth science of the decade: Neuroscience. Malaysia's growth in the same field needs to be augmented, and thus the Universiti Sains Malaysia’s vision is to excel in the field of clinical brain sciences, mind sciences and neurosciences. This will naturally bring up the level of research in the country simultaneously. Thus, a center was recently established to coordinate this venture. The four-year Integrated Neuroscience Program established recently will be a sustainable source of neuroscientists for the country. We hope to establish ourselves by 2020 as a global university with neurosciences research as an important flagship. PMID:23966818

  16. Clinical Response, Outbreak Investigation, and Epidemiology of the Fungal Meningitis Epidemic in the United States: Systematic Review.

    PubMed

    Abbas, Kaja M; Dorratoltaj, Nargesalsadat; O'Dell, Margaret L; Bordwine, Paige; Kerkering, Thomas M; Redican, Kerry J

    2016-02-01

    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

  17. Clinical impact of time of day on acute exercise response in COPD.

    PubMed

    Chan-Thim, Emilie; Dumont, Marie; Moullec, Grégory; Rizk, Amanda K; Wardini, Rima; Trutschnigg, Barbara; Paquet, Jean; de Lorimier, Myriam; Parenteau, Simon; Pepin, Véronique

    2014-04-01

    The purpose of this pilot study was to determine the impact of time of day on the acute response to incremental exercise in chronic obstructive pulmonary disease (COPD). Fourteen subjects (nine men) aged 71 ± 7 years with moderate to severe airflow obstruction (FEV1: 58 ± 13% predicted) followed a counterbalanced randomized design, performing three symptom-limited incremental cycling tests at 8:00, 12:00, and 16:00 hours on different days, each preceded by a spirometry. COPD medications were withdrawn prior to testing. No overall time effect was found for peak exercise capacity (p = 0.22) or pulmonary function (FEV1, p = 0.56; FVC, p = 0.79). However, a large effect size (f = 0.48) was observed for peak exercise capacity and several pulmonary function parameters. For peak exercise capacity, the average within-subject coefficient of variation was 5.5 ± 3.9% and the average amplitude of change was 7 ± 5W. Seven subjects (50%) showed diurnal changes at levels equal to or beyond the minimal clinically important difference for both peak exercise capacity and pulmonary function. In this sub-group, peak exercise capacity was greatest at 16:00 hours (p = 0.03, ƒ = 1.04). No systematic time-of-day effect on peak exercise capacity was obtained in COPD patients in the present pilot study. However, based on the observed effect size and on the average amplitude of change and within-subject variations seen across testing times, the guidelines recommendation that time of day be standardized for repeat exercise testing in COPD should be maintained.

  18. 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

  19. 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

  20. 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

  1. The clinical response to gluten challenge: a review of the literature.

    PubMed

    Bruins, Maaike J

    2013-11-19

    The aim of this review was to identify, evaluate and summarize all relevant studies reporting on the clinical response to gluten challenge by adult or pediatric patients with suspected or diagnosed coeliac disease (CD) on a gluten-free diet. We evaluated the effect of gluten challenge on changes in symptoms, intestinal mucosa histology, and serum antibodies. A systematic electronic search was performed for studies published as of 1966 using PubMed and Scopus databases. In the reviewed studies, doses ranged from 0.2 to 30 g/day of wheat gluten or comprised a gluten-containing diet. The onset of symptoms upon gluten intake varied largely from days to months and did not parallel serum antibody or histological changes. Within 3 months of gluten challenge, 70%-100% of pediatric CD patients became positive for AGA-IgA and EMA-IgA antibodies and 50%-70% for AGA-IgG. A limited number of trials suggest that no more than half of adult patients developed positive AGA-IgA, EMA-IgA, tTG-IgA or DGP-IgA/IgG titers. Approximately 50%-100% of pediatric and adult patients experienced mucosal relapse of gluten provocation within 3 months, which was preceded by increased mucosal intra-epithelial lymphocytes within several days of challenge. A 3-month high-dose gluten challenge should be suitable to diagnose the majority of CD patients. In some cases prolonged challenge may be needed to verify diagnosis. Combination testing for antibodies and mucosal histology may fasten the diagnosis.

  2. Cross-section Trichometry: A Clinical Tool for Assessing the Progression and Treatment Response of Alopecia

    PubMed Central

    Wikramanayake, Tongyu Cao; Mauro, Lucia M; Tabas, Irene A; Chen, Anne L; Llanes, Isabel C; Jimenez, Joaquin J

    2012-01-01

    Background: To properly assess the progression and treatment response of alopecia, one must measure the changes in hair mass, which is influenced by both the density and diameter of hair. Unfortunately, a convenient device for hair mass evaluation had not been available to dermatologists until the recent introduction of the cross-section trichometer, which directly measures the cross-sectional area of an isolated bundle of hair. Objective: We sought to evaluate the accuracy and sensitivity of the HairCheck® device, a commercial product derived from the original cross-section trichometer. Materials and Methods: Bundles of surgical silk and human hair were used to evaluate the ability of the HairCheck® device to detect and measure small changes in the number and diameter of strands, and bundle weight. Results: Strong correlations were observed between the bundle's cross-sectional area, displayed as the numeric Hair Mass Index (HMI), the number of strands, the silk/hair diameter, and the bundle dry weight. Conclusion: HMI strongly correlated with the number and diameter of silk/hair, and the weight of the bundle, suggesting that it can serve as a valid indicator of hair mass. We have given the name cross-section trichometry (CST) to the methodology of obtaining the HMI using the HairCheck® system. CST is a simple modality for the quantification of hair mass, and may be used as a convenient and useful tool to clinically assess changes in hair mass caused by thinning, shedding, breakage, or growth in males and females with progressive alopecia or those receiving alopecia treatment. PMID:23766610

  3. Staging of the baboon response to group A streptococci administered intramuscularly: a descriptive study of the clinical symptoms and clinical chemical response patterns.

    PubMed

    Taylor, F B; Bryant, A E; Blick, K E; Hack, E; Jansen, P M; Kosanke, S D; Stevens, D L

    1999-07-01

    Group A streptococcal infections, ranging from necrotizing fasciitis and myositis to toxic shock syndrome, have increased over the last 10 years. We developed the first primate model of necrotizing fasciitis and myositis. Thirteen baboons were inoculated intramuscularly with group A streptococci (GAS). Eleven animals survived for > or = 11 days before sacrifice, and two animals died within 2 days. The site of inoculation of the survivors exhibited an intense neutrophilic influx (stage I), followed by a lymphoplasmacytic influx (stages II and III). This was accompanied by the appearance of markers of an acute and then a chronic systemic inflammatory response. In contrast, the site of inoculation of the two nonsurvivors exhibited intravascular aggregates of neutrophils at its margin with no influx of neutrophils and with extensive bacterial colonization. We conclude that GAS inoculation induces a local and systemic acute neutrophilia followed by a chronic lymphoplasmacytic response; failure, initially, of neutrophilic influx into the site of inoculation predisposes to systemic GAS sepsis and death; and this three-stage primate model approximates the human disease.

  4. Differential clinical characteristics, medication usage, and treatment response of bipolar disorder in the US versus The Netherlands and Germany.

    PubMed

    Post, Robert M; Leverich, Gabriele S; Altshuler, Lori L; Frye, Mark A; Suppes, Trisha; Keck, Paul E; McElroy, Susan L; Nolen, Willem A; Kupka, Ralph; Grunze, Heinz; Walden, Joerg; Rowe, Mike

    2011-03-01

    Increased early-onset bipolar illness was seen in the US compared with the Netherlands and Germany (abbreviated here as Europe), but other clinical characteristics, medication use, and treatment response have not been systematically explored. Outpatients with bipolar disorder were treated naturalistically and followed prospectively at four sites in the US and three in Europe. Data and clinical characteristics were collected from patient questionnaires, and medication usage and good-to-excellent response to treatment for at least 6 months ascertained from daily clinician ratings on the National Institutes of Mental Health-Life Chart Method. Almost all clinical characteristics earlier associated with a poor treatment response were more prevalent in the US than in Europe, including early onset, environmental adversity, rapid cycling, more than 20 prior episodes, comorbid anxiety and substance abuse disorders, and a positive parental history for an affective disorder. Lithium was used more frequently in Europe than in the US and had a higher rate of success, whereas valproate was used more in the US, with a trend toward higher success in Europe. Antidepressants were used more in the US, but had extremely low success rates. Many other agents were deployed differently on the two continents, but success rates were consistently lower in the US than in Europe. In conclusion, clinical characteristics and patterns of medication usage and effectiveness differed markedly in the two continents suggesting the need for uncovering explanations and considering the two populations as heterogeneous in the future pharmacological studies.

  5. 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

  6. [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

  7. Addressing the Inflammatory Response to Clinically Relevant Polymers by Manipulating the Host Response Using ITIM Domain-Containing Receptors

    PubMed Central

    Slee, Joshua B.; Christian, Abigail J.; Levy, Robert J.; Stachelek, Stanley J.

    2014-01-01

    Tissue contacting surfaces of medical devices initiate a host inflammatory response, characterized by adsorption of blood proteins and inflammatory cells triggering the release of cytokines, reactive oxygen species (ROS) and reactive nitrogen species (RNS), in an attempt to clear or isolate the foreign object from the body. This normal host response contributes to device-associated pathophysiology and addressing device biocompatibility remains an unmet need. Although widespread attempts have been made to render the device surfaces unreactive, the establishment of a completely bioinert coating has been untenable and demonstrates the need to develop strategies based upon the molecular mechanisms that define the interaction between host cells and synthetic surfaces. In this review, we discuss a family of transmembrane receptors, known as immunoreceptor tyrosine-based inhibitory motif (ITIM)-containing receptors, which show promise as potential targets to address aberrant biocompatibility. These receptors repress the immune response and ensure that the intensity of an immune response is appropriate for the stimuli. Particular emphasis will be placed on the known ITIM-containing receptor, Signal Regulatory Protein Alpha (SIRPhα), and its cognate ligand CD47. In addition, this review will discuss the potential of other ITIM-containing proteins as targets for addressing the aberrant biocompatibility of polymeric biomaterials. PMID:25705515

  8. 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

  9. 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

  10. 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)

  11. 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...

  12. 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

  13. 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…

  14. Achievement and High School Completion Rates of Hispanic Students with No English Language Skills Compared to Hispanic Students with Some English Language Skills Attending the Same High School in an Immigrant Responsive City

    ERIC Educational Resources Information Center

    Garrison, Joanne M.

    2012-01-01

    The purpose of the study was to determine achievement and high school completion rates of Hispanic students (n = 13) with no English language skills compared to Hispanic students (n = 11) with some English language skills attending the same high school in an immigrant responsive city. All students were in attendance in the research school…

  15. Improving the power of clinical trials of rheumatoid arthritis by using data on continuous scales when analysing response rates: an application of the augmented binary method

    PubMed Central

    Jenkins, Martin

    2016-01-01

    Objective. In clinical trials of RA, it is common to assess effectiveness using end points based upon dichotomized continuous measures of disease activity, which classify patients as responders or non-responders. Although dichotomization generally loses statistical power, there are good clinical reasons to use these end points; for example, to allow for patients receiving rescue therapy to be assigned as non-responders. We adopt a statistical technique called the augmented binary method to make better use of the information provided by these continuous measures and account for how close patients were to being responders. Methods. We adapted the augmented binary method for use in RA clinical trials. We used a previously published randomized controlled trial (Oral SyK Inhibition in Rheumatoid Arthritis-1) to assess its performance in comparison to a standard method treating patients purely as responders or non-responders. The power and error rate were investigated by sampling from this study. Results. The augmented binary method reached similar conclusions to standard analysis methods but was able to estimate the difference in response rates to a higher degree of precision. Results suggested that CI widths for ACR responder end points could be reduced by at least 15%, which could equate to reducing the sample size of a study by 29% to achieve the same statistical power. For other end points, the gain was even higher. Type I error rates were not inflated. Conclusion. The augmented binary method shows considerable promise for RA trials, making more efficient use of patient data whilst still reporting outcomes in terms of recognized response end points. PMID:27338084

  16. 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.

  17. 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…

  18. 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

  19. 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

  20. 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....

  1. 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.

  2. Clinical Comparison of the Auditory Steady-State Response with the Click Auditory Brainstem Response in Infants

    PubMed Central

    Lee, Hyo Sook; Ahn, Joong Ho; Chung, Jong Woo; Yoon, Tae Hyun

    2008-01-01

    Objectives Our goal was to determine the effectiveness of using the auditory steady state response (ASSR) as a measure of hearing thresholds in infants who are suspected of having significant hearing loss, as compared with using the click-auditory brainstem response (C-ABR). Methods We retrospectively analyzed the audiologic profiles of 76 infants (46 boys and 30 girls, a total of 151 ears) who ranged in age from 1 to 12 months (average age: 5.7 months). The auditory evaluations in 76 infants who were suspected of having hearing loss were done via the C-ABR and ASSR. In addition, for reference, the mean ASSR thresholds were compared to those of 39 ears of infants and 39 ears of adults with normal hearing at 0.5, 1, 2, and 4 kHz. Results The highest correlation between the C-ABR and ASSR thresholds was observed at an average of 2-4 kHz (r=0.94). On comparison between the hearing of infants and adults at 0.5, 1, 2, and 4 kHz, the mean ASSR threshold in infants was 12, 7, 8, and 7 dB higher, respectively, than that in adults. Conclusion ASSR testing may provide additional audiometric information for accurately predicting the hearing sensitivity, and this is essential for the management of infants with severe to profound hearing loss. PMID:19434265

  3. 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

  4. 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

  5. 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

  6. 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

  7. Clinical Model for Predicting Hepatocellular Carcinomas in Patients with Post-Sustained Virologic Responses of Chronic Hepatitis C: A Case Control Study

    PubMed Central

    Zeng, Qing-Lei; Li, Bing; Zhang, Xue-Xiu; Chen, Yan; Fu, Yan-Ling; Lv, Jun; Liu, Yan-Min; Yu, Zu-Jiang

    2016-01-01

    Background/Aims No clinical model exists to predict the occurrence of hepatocellular carcinoma in sustained virologic response-achieving (HCC after SVR) patients with chronic hepatitis C (CHC). Methods We performed a case-control study using a clinical database to research the risk factors for HCC after SVR. A predictive model based on risk factors was established, and the area under the receiver operating characteristic curve (AUC) was calculated. Results In the multivariate model, an initial diagnosis of compensated cirrhosis and post-SVR albumin reductions of 1 g/L were associated with 21.7-fold (95% CI, 4.2 to 112.3; p<0.001) and 1.3-fold (95% CI, 1.1 to 1.7; p=0.004) increases in the risk of HCC after SVR, respectively. A predictive model based on an initial diagnosis of compensated cirrhosis (yes, +1; no, 0) and post-SVR albumin ≤36.0 g/L (yes, +1; not, 0) predicted the occurrence of HCC after SVR with a cutoff value of >0, an AUC of 0.880, a sensitivity of 0.833, a specificity of 0.896, and a negative predictive value of 0.956. Conclusions An initial diagnosis of compensated cirrhosis combined with a post-SVR albumin value of ≤36.0 g/L predicts the occurrence of HCC after SVR in patients with CHC. PMID:27257023

  8. 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,...

  9. 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...

  10. 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

  11. Effect of Anti-TNF Antibodies on Clinical Response in Rheumatoid Arthritis Patients: A Meta-Analysis.

    PubMed

    Wu, Chunxiao; Wang, Shengxu; Xian, Peifeng; Yang, Lu; Chen, Ying; 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

  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. 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.

  14. Equipoise and the duty of care in clinical research: a philosophical response to our critics.

    PubMed

    Miller, Paul B; Weijer, Charles

    2007-01-01

    Franklin G. Miller and colleagues have stimulated renewed interest in research ethics through their work criticizing clinical equipoise. Over three years and some twenty articles, they have also worked to articulate a positive alternative view on norms governing the conduct of clinical research. Shared presuppositions underlie the positive and critical dimensions of Miller and colleagues' work. However, recognizing that constructive contributions to the field ought to enjoy priority, we presently scrutinize the constructive dimension of their work. We argue that it is wanting in several respects.

  15. Validation of the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI): characterizing disease severity and assessing responsiveness to clinical change

    PubMed Central

    Anyanwu, C.O.; Fiorentino, D.; Chung, L.; Dzuong, C.; Wang, Y.; Okawa, J.; Carr, K.; Propert, K.J.; Werth, V.P.

    2015-01-01

    Summary Background The Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) was developed for use in clinical trials and longitudinal patient assessment. Objectives To characterize disease severity using the CDASI and assess responsiveness of this instrument to clinically meaningful changes in disease activity. Methods Patients with cutaneous dermatomyositis at the University of Pennsylvania (UPenn, n = 93) and Stanford University (Stanford, n = 106) were prospectively evaluated using the CDASI, physician global assessment (PGA) Likert scales, and visual analog scale (VAS). Data was analyzed using logistic regression models and receiver operating characteristic curves to select cut-offs. Results Baseline CDASI activity scores for the patients evaluated at UPenn ranged from 0 to 47 (median 17), and baseline PGA VAS scores ranged from 0 to 9.6 (median 1.1). At UPenn a CDASI activity score of 19 differentiated mild from moderate and severe disease. At Stanford baseline CDASI scores ranged from 0 to 48 (median 21), baseline PGA VAS scores ranged from 0 to 9.7 (median 4.2) and CDASI activity scores of 14 or less characterized mild disease. When a 2 cm change in the PGA VAS was regarded as a clinically significant improvement, a 4-point (UPenn) or 5-point (Stanford) change in CDASI reflected a minimal clinically significant response. Conclusions The CDASI is a valid and responsive measure that can be used to characterize cutaneous dermatomyositis severity and detect improvement in disease activity. Variations in cutoffs may be due to differences in disease severity between the two populations or inter-rater variations in use of the external gold measures. PMID:25994337

  16. High progesterone levels in women with high ovarian response do not affect clinical outcomes: a retrospective cohort study

    PubMed Central

    2014-01-01

    Background The potentially detrimental role of progesterone during the follicular phase has been a matter of controversy for several years; however, few studies have analyzed the effects of combined raised estradiol and progesterone levels on pregnancy outcomes. The aim of the present study was to determine the influence of high progesterone levels on clinical outcomes in the context of high ovarian response. Methods We performed a retrospective cohort study that included 2850 women classified as high responders. The women were subdivided into six groups depending on their progesterone concentration on the day of human chorionic gonadotropin (hCG) administration: <0.5 ng/ml (1.81 ng/ml (>p90). Ovarian response was classified as high when > =20 oocytes were retrieved or when estradiol was > =3000 pg/ml. Clinical outcomes of each subgroup were analyzed. We also examined data from frozen-thawed embryo transfers. Results were analyzed with Student’s t- test to compare continuous variables and chi-squared test to compare proportions. A p-value of < =0.05 was considered statistically significant. Results The progesterone concentration increased with ovarian response, and elevated progesterone did not show a significant clinical impact on implantation rate and pregnancy rates. These data provide evidence that progesterone levels higher than 1.8 ng/ml do not have detrimental effect on oocyte quality or endometrial receptivity. Conclusions These data allow us to conclude that high progesterone levels correlate significantly with high estradiol levels and that in high responder women; progesterone levels do not show a significant clinical impact on results. PMID:25064138

  17. An exploratory study on the elements that might affect medical students' and residents' responsibility during clinical training.

    PubMed

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

    2014-01-01

    We are now more or less confronting a "challenge of responsibility" among both undergraduate and postgraduate medical students and some recent alumni from medical schools in Iran. This ethical problem calls for urgent etiologic and pathologic investigations into the problem itself and the issues involved. This study aimed to develop a thematic conceptual framework to study factors that might affect medical trainees' (MTs) observance of responsibility during clinical training. A qualitative descriptive methodology involving fifteen in-depth semi-structured interviews was used to collect the data. Interviews were conducted with both undergraduate and postgraduate MTs as well as clinical experts and experienced nurses. Interviews were audio-recorded and then transcribed. The data was analyzed using thematic content analysis. The framework derived from the data included two main themes, namely "contextual conditions" and "intervening conditions". Within each theme, participants recurrently described "individual" and "non-individual or system" based factors that played a role in medical trainees' observance of responsibility. Overall, contextual conditions provide MTs with a "primary or basic responsibility" which is then transformed into a "secondary or observed responsibility" under the influence of intervening conditions. In conclusion three measures were demonstrated to be very important in enhancing Iranian MTs' observance of responsibility: a) to make and implement stricter and more exact admission policies for medical colleges, b) to improve and revise the education system in its different dimensions such as management, structure, etc. based on regular and systematic evaluations, and c) to establish, apply and sustain higher standards throughout the educational environment. PMID:25512829

  18. 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…

  19. Public School Response to Special Education Vouchers: The Impact of Florida's McKay Scholarship Program on Disability Diagnosis and Student Achievement in Public Schools

    ERIC Educational Resources Information Center

    Winters, Marcus A.; Greene, Jay P.

    2011-01-01

    The authors expand on research evaluating public school response to school choice policies by considering the particular influence of voucher programs for disabled students--a growing type of choice program that may have different implications for public school systems from those of more conventional choice programs. The authors provide a…

  20. Applying New Methods to the Measurement of Fidelity of Implementation: Examining the Critical Ingredients of the Responsive Classroom Approach in Relation to Mathematics Achievement

    ERIC Educational Resources Information Center

    Abry, Tashia D. S.; Rimm-Kaufman, Sara E.; Larsen, Ross A.; Brewer, Alix J.

    2011-01-01

    The present study examines data collected during the second year of a three-year longitudinal cluster randomized controlled trial, the Responsive Classroom Efficacy Study (RCES). In the context of and RCT, the research questions address naturally occurring variability in the independent variables of interest (i.e., teachers' (fidelity of…

  1. A cardiac evoked response algorithm providing threshold tracking: a North American multicenter study. Clinical Investigators of the Microny-Regency Clinical Evaluation Study.

    PubMed

    Lau, C; Cameron, D A; Nishimura, S C; Ahern, T; Freedman, R A; Ellenbogen, K; Greenberg, S; Baker, J; Meacham, D

    2000-06-01

    The purpose of this study was to evaluate a pacing system using the recognition of cardiac evoked response for the automatic adjustment of pacing output. Patients were prospectively followed after primary implantation of VVIR pacemakers using AutoCapture (St. Jude Medical CRMD). Sensing and pacing thresholds, polarization signal, evoked response, and AutoCapture performance were evaluated with serial visits and 24-hour Holter monitoring. Three hundred ninety-eight patients (mean age 71 +/- 15 years) were followed for an average duration of 1 year (3 days-1.75 years) with the algorithm functional in > 90% of patients. Backup pacing in the event of exit block was confirmed in all patients. Pacing thresholds remained stable at 0.89 +/- 0.34 V with a pulse width of 0.31 ms (with chronic output autoset at 0.3 V above the actual threshold). Evoked response exhibited a small but statistically significant increase with time (8.92 mV at implant, 9.60 mV at 12 months), however, this finding did not result in any change in AutoCapture function during our follow-up period. The polarization signal remained stable with minimal variation (1.12 mV at implant, 1.18 at 12 months). No clinical adverse events were observed using the AutoCapture algorithm. In this initial experience with the AutoCapture algorithm the evoked response and polarization measurements remained adequate, allowing the system to function in the majority of patients with safe, low output pacing. High energy backup pacing provided an added safety feature over fixed output devices in cases of unexpected threshold rises. Longer follow-up is required for continued long-term validation of the algorithm. PMID:10879378

  2. Surge capacity for response to bioterrorism in hospital clinical microbiology laboratories.

    PubMed

    Shapiro, Daniel S

    2003-12-01

    Surge capacity is the ability to rapidly mobilize to meet an increased demand. While large amounts of federal funding have been allocated to public health laboratories, little federal funding has been allocated to hospital microbiology laboratories. There are concerns that hospital laboratories may have inadequate surge capacities to deal with a significant bioterrorism incident. A workflow analysis of a clinical microbiology laboratory that serves an urban medical center was performed to identify barriers to surge capacity in the setting of a bioterrorism event and to identify solutions to these problems. Barriers include a national shortage of trained medical technologists, the inability of clinical laboratories to deal with a dramatic increase in the number of blood cultures, a delay while manufacturers increase production of critical products and then transport and deliver these products to clinical laboratories, and a shortage of class II biological safety cabinets. Federal funding could remedy staffing shortages by making the salaries of medical technologists comparable to those of similarly educated health care professionals and by providing financial incentives for students to enroll in clinical laboratory science programs. Blood culture bottles, and possibly continuous-monitoring blood culture instruments, should be added to the national antibiotic stockpile. Federal support must ensure that companies that manufacture essential laboratory supplies are capable of rapidly scaling up production. Hospitals must provide increased numbers of biological safety cabinets and amounts of space dedicated to clinical microbiology laboratories. Laboratories should undertake limited cross-training of technologists, ensure that adequate packaging supplies are available, and be able to move to a 4-day blood culture protocol.

  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. Graded Achievement, Tested Achievement, and Validity

    ERIC Educational Resources Information Center

    Brookhart, Susan M.

    2015-01-01

    Twenty-eight studies of grades, over a century, were reviewed using the argument-based approach to validity suggested by Kane as a theoretical framework. The review draws conclusions about the meaning of graded achievement, its relation to tested achievement, and changes in the construct of graded achievement over time. "Graded…

  5. 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

  6. HI responses induced by seasonal influenza vaccination are associated with clinical protection and with seroprotection against non-homologous strains.

    PubMed

    Luytjes, Willem; Enouf, Vincent; Schipper, Maarten; Gijzen, Karlijn; Liu, Wai Ming; van der Lubben, Mariken; Meijer, Adam; van der Werf, Sylvie; Soethout, Ernst C

    2012-07-27

    Vaccination against influenza induces homologous as well as cross-specific hemagglutination inhibiting (HI) responses. Induction of cross-specific HI responses may be essential when the influenza strain does not match the vaccine strain, or even to confer a basic immune response against a pandemic influenza virus. We carried out a clinical study to evaluate the immunological responses after seasonal vaccination in healthy adults 18-60 years of age, receiving the yearly voluntary vaccination during the influenza season 2006/2007. Vaccinees of different age groups were followed for laboratory confirmed influenza (LCI) and homologous HI responses as well as cross-specific HI responses against the seasonal H1N1 strain of 2008 and pandemic H1N1 virus of 2009 (H1N1pdm09) were determined. Homologous HI titers that are generally associated with protection (i.e. seroprotective HI titers ≥40) were found in more than 70% of vaccinees. In contrast, low HI titers before and after vaccination were significantly associated with seasonal LCI. Cross-specific HI titers ≥40 against drifted seasonal H1N1 were found in 69% of vaccinees. Cross-specific HI titers ≥40 against H1N1pdm09 were also significantly induced, especially in the youngest age group. More specifically, cross-specific HI titers ≥40 against H1N1pdm09 were inversely correlated with age. We did not find a correlation between the subtype of influenza which was circulating at the age of birth of the vaccinees and cross-specific HI response against H1N1pdm09. These data indicate that the HI titers before and after vaccination determine the vaccination efficacy. In addition, in healthy adults between 18 and 60 years of age, young adults appear to be best able to mount a cross-protective HI response against H1N1pdm09 or drifted seasonal influenza after seasonal vaccination.

  7. Post-marketing survey on clinical response to interferon beta in relapsing multiple sclerosis: the Roman experience.

    PubMed

    Pozzilli, C; Prosperini, L; Sbardella, E; De Giglio, L; Onesti, E; Tomassini, V

    2005-12-01

    Safety, tolerability and efficacy profiles of interferon beta (IFNbeta) therapy in relapsing multiple sclerosis (MS) has been widely verified both in trial settings and in daily clinical practice. However, for a variable percentage of treated patients, it remains only partially effective. In this study, we reported the post-marketing experience of the efficacy of IFNbeta therapy for a large cohort of MS patients regularly attending the MS Outpatient Clinic of "La Sapienza University" in Rome. In this cohort we also sought clinical and paraclinical variables responsible for the clinical course of MS during IFNbeta therapy. Patients that received treatment with one of the IFNbeta formulations for at least 1 year were included. Clinical outcomes (i. e., relapses and disability score) were monitored throughout the entire study period. Magnetic resonance imaging (MRI) scans were performed twice for each subject: at baseline and after 1 year of therapy. The occurrence of more than one relapse during the study period or a sustained disability progression in the Expanded Disability Status Scale (EDSS) score were considered as criteria for the definition of suboptimal clinical response to IFNbeta therapy. During IFNbeta therapy (number of patients 242, mean length of treatment 4.3+/-2.3 years) a reduction in the annualised relapse rate of 59% (p<0.001) was observed. Eighty-six patients (35%) fulfilled the criterion for defining "suboptimal responder" on the basis of relapses, and 69 (28.5%) did the same on the basis of EDSS sustained progression. Twenty-seven (11.1%) patients showed both an EDSS progression and two or more relapses. The presence of T1-enhancing lesions and new T2 hyperintense lesions on the scan performed after the first year of therapy were the best MRI features associated with both the occurrence of relapses during the treatment period (OR for enhancing lesions and relapses 3.6; OR for new T2 lesion and relapses 2.8). The present post-marketing experience

  8. 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

  9. Protective T Cell and Antibody Immune Responses against Hepatitis C Virus Achieved Using a Biopolyester-Bead-Based Vaccine Delivery System.

    PubMed

    Martínez-Donato, G; Piniella, B; Aguilar, D; Olivera, S; Pérez, A; Castañedo, Y; Alvarez-Lajonchere, L; Dueñas-Carrera, S; Lee, J W; Burr, N; Gonzalez-Miro, M; Rehm, B H A

    2016-04-01

    Hepatitis C virus (HCV) infection is a major worldwide problem. Chronic hepatitis C is recognized as one of the major causes of cirrhosis, hepatocellular carcinoma, and liver failure. Although new, directly acting antiviral therapies are suggested to overcome the low efficacy and adverse effects observed for the current standard of treatment, an effective vaccine would be the only way to certainly eradicate HCV infection. Recently, polyhydroxybutyrate beads produced by engineered Escherichia coli showed efficacy as a vaccine delivery system. Here, an endotoxin-free E. coli strain (ClearColi) was engineered to produce polyhydroxybutyrate beads displaying the core antigen on their surface (Beads-Core) and their immunogenicity was evaluated in BALB/c mice. Immunization with Beads-Core induced gamma interferon (IFN-γ) secretion and a functional T cell immune response against the HCV Core protein. With the aim to target broad T and B cell determinants described for HCV, Beads-Core mixed with HCV E1, E2, and NS3 recombinant proteins was also evaluated in BALB/c mice. Remarkably, only three immunization with Beads-Core+CoE1E2NS3/Alum (a mixture of 0.1 μg Co.120, 16.7 μg E1.340, 16.7 μg E2.680, and 10 μg NS3 adjuvanted in aluminum hydroxide [Alum]) induced a potent antibody response against E1 and E2 and a broad IFN-γ secretion and T cell response against Core and all coadministered antigens. This immunological response mediated protective immunity to viremia as assessed in a viral surrogate challenge model. Overall, it was shown that engineered biopolyester beads displaying foreign antigens are immunogenic and might present a particulate delivery system suitable for vaccination against HCV.

  10. Protective T Cell and Antibody Immune Responses against Hepatitis C Virus Achieved Using a Biopolyester-Bead-Based Vaccine Delivery System

    PubMed Central

    Piniella, B.; Aguilar, D.; Olivera, S.; Pérez, A.; Castañedo, Y.; Alvarez-Lajonchere, L.; Dueñas-Carrera, S.; Lee, J. W.; Burr, N.; Gonzalez-Miro, M.; Rehm, B. H. A.

    2016-01-01

    Hepatitis C virus (HCV) infection is a major worldwide problem. Chronic hepatitis C is recognized as one of the major causes of cirrhosis, hepatocellular carcinoma, and liver failure. Although new, directly acting antiviral therapies are suggested to overcome the low efficacy and adverse effects observed for the current standard of treatment, an effective vaccine would be the only way to certainly eradicate HCV infection. Recently, polyhydroxybutyrate beads produced by engineered Escherichia coli showed efficacy as a vaccine delivery system. Here, an endotoxin-free E. coli strain (ClearColi) was engineered to produce polyhydroxybutyrate beads displaying the core antigen on their surface (Beads-Core) and their immunogenicity was evaluated in BALB/c mice. Immunization with Beads-Core induced gamma interferon (IFN-γ) secretion and a functional T cell immune response against the HCV Core protein. With the aim to target broad T and B cell determinants described for HCV, Beads-Core mixed with HCV E1, E2, and NS3 recombinant proteins was also evaluated in BALB/c mice. Remarkably, only three immunization with Beads-Core+CoE1E2NS3/Alum (a mixture of 0.1 μg Co.120, 16.7 μg E1.340, 16.7 μg E2.680, and 10 μg NS3 adjuvanted in aluminum hydroxide [Alum]) induced a potent antibody response against E1 and E2 and a broad IFN-γ secretion and T cell response against Core and all coadministered antigens. This immunological response mediated protective immunity to viremia as assessed in a viral surrogate challenge model. Overall, it was shown that engineered biopolyester beads displaying foreign antigens are immunogenic and might present a particulate delivery system suitable for vaccination against HCV. PMID:26888185

  11. Event-related potentials. Do they reflect central serotonergic neurotransmission and do they predict clinical response to serotonin agonists?

    PubMed

    Hegerl, U; Gallinat, J; Juckel, G

    2001-01-01

    The increasing knowledge concerning anatomical structures and cellular processes underlying event-related potentials (ERP) as well as methodological advances in ERP data analysis (e.g. dipole source analysis) begin to bridge the gap between ERP and neurochemical aspects. Reliable indicators of the serotonin system are urgently needed because of its role in pathophysiology and as target of pharmacotherapeutic interventions in psychiatric disorders. Converging arguments from preclinical and clinical studies support the hypothesis that the loudness dependence of the auditory evoked N1/P2-response (LDAEP) is regulated by the level of central serotonergic neurotransmission. Dipole source analysis represents an important methodological advance in this context, because the two N1/P2-subcomponents, generated by the primary and secondary auditory cortex known to be differentially innervated by serotonergic fibers, can be separated. A pronounced LDAEP of primary auditory cortices is supposed to reflect low central serotonergic neurotransmission, and vice versa. LDAEP is a parameter with potential clinical value since subgroups of patients with a serotonergic dysfunction can be identified and can be treated more specifically. In depressed patients, a significant relationship between strong LDAEP, indicating low serotonergic function, and a favorable response to SSRI has been found. Additionally, there is evidence from several studies with patients with affective disorders implicating a strong LDAEP as a predictor of favorable response to a preventive lithium treatment. PMID:11172876

  12. 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.

  13. 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

  14. Safety and clinical response of intraventricular caspofungin for Scedosporium apiospermum complex central nervous system infection.

    PubMed

    Williams, John R; Tenforde, Mark W; Chan, Jeannie D; Ko, Andrew; Graham, Susan M

    2016-09-01

    We present a 71-year old woman treated with 14 days of 5 mg intraventricular caspofungin for Scedosporium apiospermum complex meningoencephalitis diagnosed after spinal fusion and instrumentation. Cerebrospinal fluid studies improved during therapy and intraventricular administration was well tolerated. Within weeks of discontinuation, the patient experienced clinical deterioration with disease progression. There are sparse data on the efficacy and safety of administering intraventricular caspofungin. While apparently safe, intraventricular caspofungin was insufficient for disease control in this case. PMID:27656356

  15. 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

  16. 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

  17. Clinical response of captive common wombats (Vombatus ursinus) infected with Sarcoptes scabiei var. wombati.

    PubMed

    Skerratt, Lee F

    2003-01-01

    Seven common wombats (Vombatus ursinus) were exposed and two of these were re-exposed to Sarcoptes scabiei var. wombati (Acari: Sarcoptidae). For wombats exposed for the first time, five exposed to 5,000 mites on their shoulder developed moderate to severe parakeratotic mange after 11 wk compared with two given 1,000 mites that developed mild clinical signs of mange after 11 wk. For re-exposed wombats, one of two given 5,000 mites developed mild parakeratotic mange and the other developed severe parakeratotic mange. Initial signs of mange were erythema followed by parakeratosis, alopecia, excoriation and fissuring of parakeratotic crust and skin. Erythema usually became apparent within 14 days after exposure (DAE) or within 24 hrs of re-exposure. Parakeratosis was visible 14-21 DAE and alopecia first occurred 35-77 DAE. Clinical signs increased in severity over time and lesions spread slowly from the site of exposure. Mangy wombats scratched excessively, lost weight, and exhibited a significant neutrophilia compared with control wombats. Treatment of mange with three injections of ivermectin, 300 micrograms/kg, 10 days apart led to complete resolution of clinical signs. However mites were not entirely eliminated until wombats received a second regime of treatment. PMID:12685082

  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. 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.

  20. Clinical response of captive common wombats (Vombatus ursinus) infected with Sarcoptes scabiei var. wombati.

    PubMed

    Skerratt, Lee F

    2003-01-01

    Seven common wombats (Vombatus ursinus) were exposed and two of these were re-exposed to Sarcoptes scabiei var. wombati (Acari: Sarcoptidae). For wombats exposed for the first time, five exposed to 5,000 mites on their shoulder developed moderate to severe parakeratotic mange after 11 wk compared with two given 1,000 mites that developed mild clinical signs of mange after 11 wk. For re-exposed wombats, one of two given 5,000 mites developed mild parakeratotic mange and the other developed severe parakeratotic mange. Initial signs of mange were erythema followed by parakeratosis, alopecia, excoriation and fissuring of parakeratotic crust and skin. Erythema usually became apparent within 14 days after exposure (DAE) or within 24 hrs of re-exposure. Parakeratosis was visible 14-21 DAE and alopecia first occurred 35-77 DAE. Clinical signs increased in severity over time and lesions spread slowly from the site of exposure. Mangy wombats scratched excessively, lost weight, and exhibited a significant neutrophilia compared with control wombats. Treatment of mange with three injections of ivermectin, 300 micrograms/kg, 10 days apart led to complete resolution of clinical signs. However mites were not entirely eliminated until wombats received a second regime of treatment.

  1. Impaired Physical Performance and Clinical Responses after a Recreational Bodybuilder's Self-Administration of Steroids: A Case Report.

    PubMed

    Veras, Katherine; Silva-Junior, Fernando Lopes; Lima-Silva, Adriano Eduardo; De-Oliveira, Fernando Roberto; Pires, Flávio Oliveira

    2015-12-01

    We reported clinical and physical responses to 7 weeks of anabolic-androgenic steroid (AAS) self-administration in a male recreational bodybuilder. He was self-administrating a total of 3,250 mg of testosterone when his previous and current clinical and physical trials records were revisited. Body shape, performance, and biochemistry results were clustered into three phases labeled PRE (before the self-use), POST I (immediately at the cessation of the 7-week administration), and POST II (12 weeks after the cessation). Elevated testosterone and estradiol levels were observed in the POST I phase, while hepatic and renal functions remained altered in the POST II phase. Body mass and body fat percentages increased throughout the three phases. When adjusted according to body mass, drops in aerobic and anaerobic power and capacity (2.1% to 12.9%) were observed across the phases. This case report shows that overall performance decreased when a bodybuilding practitioner self-administered AAS.

  2. A phase Ib multiple ascending dose study evaluating safety, pharmacokinetics, and early clinical response of brodalumab, a human anti-IL-17R antibody, in methotrexate-resistant rheumatoid arthritis

    PubMed Central

    2013-01-01

    Introduction The aim of this study was to evaluate the safety, pharmacokinetics, and clinical response of brodalumab (AMG 827), a human, anti-IL-17 receptor A (IL-17RA) monoclonal antibody in subjects with moderate-to-severe rheumatoid arthritis (RA). Methods This phase Ib, randomized, placebo-controlled, double-blind multiple ascending dose study enrolled subjects with moderate to severe RA (≥6/66 swollen and ≥8/68 tender joints). Subjects were randomized 3:1 to receive brodalumab (50 mg, 140 mg, or 210 mg subcutaneously every two weeks for 6 doses per group; or 420 mg or 700 mg intravenously every 4 weeks for two doses per group) or placebo. Endpoints included incidence of adverse events (AEs) and pharmacokinetics. Exploratory endpoints included pharmacodynamics, and improvements in RA clinical metrics. Results Forty subjects were randomized to investigational product; one subject discontinued due to worsening of RA (placebo). The study was not designed to assess efficacy. AEs were reported by 70% (7/10) of placebo subjects and 77% (22/30) of brodalumab subjects. Three serious AEs were reported in two subjects; there were no opportunistic infections. Brodalumab treatment resulted in inhibition of IL-17 receptor signaling and receptor occupancy on circulating leukocytes. No treatment effects were observed with individual measures of RA disease activity. On day 85 (week 13) 37% (11/30) of brodalumab subjects and 22% (2/9) of placebo subjects achieved ACR20; 7% (2/30) brodalumab subjects and 11% (1/9) of placebo subjects achieved ACR50; and 0% (0/30) brodalumab subjects and 0% (0/9) of placebo subjects achieved ACR70. Conclusions Multiple dose administration of brodalumab was tolerated in subjects with active RA. There was no evidence of a clinical response to brodalumab in subjects with RA. Trial registration ClinicalTrials.gov, NCT00771030 PMID:24286136

  3. Broad Anti-Hepatitis C Virus (HCV) Antibody Responses Are Associated with Improved Clinical Disease Parameters in Chronic HCV Infection

    PubMed Central

    Swann, Rachael E.; Cowton, Vanessa M.; Robinson, Mark W.; Cole, Sarah J.; Barclay, Stephen T.; Mills, Peter R.; Thomson, Emma C.; McLauchlan, John

    2016-01-01

    ABSTRACT During hepatitis C virus (HCV) infection, broadly neutralizing antibody (bNAb) responses targeting E1E2 envelope glycoproteins are generated in many individuals. It is unclear if these antibodies play a protective or a pathogenic role during chronic infection. In this study, we investigated whether bNAb responses in individuals with chronic infection were associated with differences in clinical presentation. Patient-derived purified serum IgG was used to assess the breadth of HCV E1E2 binding and the neutralization activity of HCV pseudoparticles. The binding and neutralization activity results for two panels bearing viral envelope proteins representing either an intergenotype or an intragenotype 1 group were compared. We found that the HCV load was negatively associated with strong cross-genotypic E1E2 binding (P = 0.03). Overall, we observed only a modest correlation between total E1E2 binding and neutralization ability. The breadth of intergenotype neutralization did not correlate with any clinical parameters; however, analysis of individuals with genotype 1 (gt1) HCV infection (n = 20), using an intragenotype pseudoparticle panel, found a strong association between neutralization breadth and reduced liver fibrosis (P = 0.006). A broad bNAb response in our cohort with chronic infection was associated with a single nucleotide polymorphism (SNP) in the HLA-DQB1 gene (P = 0.038), as previously reported in a cohort with acute disease. Furthermore, the bNAbs in these individuals targeted more than one region of E2-neutralizing epitopes, as assessed through cross-competition of patient bNAbs with well-characterized E2 antibodies. We conclude that the bNAb responses in patients with chronic gt1 infection are associated with lower rates of fibrosis and host genetics may play a role in the ability to raise such responses. IMPORTANCE Globally, there are 130 million to 150 million people with chronic HCV infection. Typically, the disease is progressive and is a

  4. Long-Term Treatment Outcomes of Patients Infected With Hepatitis C Virus: A Systematic Review and Meta-analysis of the Survival Benefit of Achieving a Sustained Virological Response

    PubMed Central

    Simmons, Bryony; Saleem, Jawaad; Heath, Katherine; Cooke, Graham S.; Hill, Andrew

    2015-01-01

    Background. Achievement of a sustained virologic response (SVR) after treatment for Hepatitis C infection is associated with improved outcomes. This meta-analysis aimed to determine the impact of SVR on long-term mortality risk compared with nonresponders in a range of populations. Methods. An electronic search identified all studies assessing all-cause mortality in SVR and non-SVR patients. Eligible articles were stratified into general, cirrhotic, and populations coinfected with human immunodeficiency virus. The adjusted hazard ratio (95% confidence interval [CI]) for mortality in patients achieving SVR vs non-SVR, and pooled estimates for the 5-year mortality in each group were calculated. Results. 31 studies (n = 33 360) were identified as suitable for inclusion. Median follow-up time was 5.4 years (interquartile range, 4.9–7.5) across all studies. The adjusted hazard ratio of mortality for patients achieving SVR vs non-SVR was 0.50 (95% CI, .37–.67) in the general population, 0.26 (95% CI, .18–.74) in the cirrhotic group, and 0.21 (.10–.45) in the coinfected group. The pooled 5-year mortality rates were significantly lower for patients achieving SVR compared with non-SVR in all 3 populations. Conclusions. The results suggest that there is a significant survival benefit of achieving an SVR compared with unsuccessful treatment in a range of populations infected with hepatitis C virus. PMID:25987643

  5. 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.

  6. 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

  7. Improvement of clinical response in allergic rhinitis patients treated with an oral immunostimulating bacterial lysate: in vivo immunological effects.

    PubMed

    Banche, G; Allizond, V; Mandras, N; Garzaro, M; Cavallo, G P; Baldi, C; Scutera, S; Musso, T; Roana, J; Tullio, V; Carlone, N A; Cuffini, A M

    2007-01-01

    Allergic rhinitis is known to be one of the most common chronic diseases in the industrialized world. According to the concept that allergic rhinitis patients generally suffer from an immune deficit, in order to stimulate specifically or aspecifically their immune system, immunomodulating agents from various sources, such as synthetic compounds, tissue extracts or a mixture of bacterial extracts, have been used. The aim of the present trial is to evaluate the efficacy of the treatment with an immunostimulating vaccine consisting of a polyvalent mechanical bacterial lysate (PMBL) in the prophylaxis of allergic rhinitis and subsequently to analyze its in vivo effects on immune responses. 41 allergic rhinitis patients were enrolled: 26 patients were randomly assigned to the group for PMBL sublingual treatment and 15 others to the group for placebo treatment. For all 26 patients blood samples were drawn just before (T0) and after 3 months of PMBL treatment (T3) to evaluate plasma IgE levels (total and allergen-specific) and the cytokine production involved in the allergic response (IL-4, IFN-gamma). The results of our study indicate that PMBL is effective in vivo in the reduction or in the elimination of the symptoms in rhinitis subjects during the treatment period in comparison to a non-immunostimulating treatment. A significant and clinically relevant improvement was found in 61.5%, a stationary clinical response was registered in 38.4% and no negative side effects associated with the medication or worsening were recorded. At the end of a 3-month follow up period the clinical picture remained the same as that observed at T3. PMBL treatment did not affect the serum IgE levels (either total or allergen-specific) and did not induce significant changes in IFN-gamma concentration. In contrast, PMBL therapy may be accompanied, in some patients, by a potential immunomodulating activity by decreasing IL-4 cytokine expression. PMID:17346436

  8. Clinical importance of spherical and chromatic aberration on the accommodative response in contact lens wear

    NASA Astrophysics Data System (ADS)

    Wahlberg, M.; Lindskoog Pettersson, A.; Rosén, R.; Nilsson, M.; Unsbo, P.; Brautaset, R.

    2011-11-01

    The aim of this study was to evaluate the accommodation response under both mono- and polychromatic light while varying the amount of spherical aberration. It is thought that chromatic and spherical aberrations are directional cues for the accommodative system and could affect response time, velocity or lag. Spherical aberration is often eliminated in modern contact lenses in order to enhance image quality in the unaccommodated eye. This study was divided into two parts. The first part was done to evaluate the amount of spherical and other Zernike aberrations in the unaccommodated eye when uncorrected and with two types of correction (trial lens and spherical-aberration controlled contact lens) and the second part evaluated the dynamic accommodation responses obtained when wearing each of the corrections under polychromatic and monochromatic conditions. Measurements of accommodation showed no significant differences in time, velocity and lag of accommodation after decreasing the spherical aberration with a contact lens, neither in monochromatic nor polychromatic light. It is unlikely that small to normal changes of spherical aberration in white light or monochromatic mid-spectral light affect directional cues for the accommodative system, not in white light or mid-spectral monochromatic light, since the accommodative response did not show any change.

  9. 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

  10. 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

  11. Evaluation of factors contributing to the achievement of students participating in a culturally responsive curriculum in Hawai`i public schools

    NASA Astrophysics Data System (ADS)

    Bowditch, Scott A.

    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 science self-efficacy, (b) perceived frequency of behaviors valued by members of the Hawaiian community and (c) frequency of perceptions of behaviors conducive to learning. Initial validation for the three-factor construct was obtained using Exploratory Factor Analysis and further validated utilizing Confirmatory Factor Analysis with an oblique rotation and 24 items were found to measure the three aspects with a multicultural group of 332 students on Oahu and Hawai'i island. A multi-level analysis was conducted by (a) testing for internal consistency and growth patterns over time utilizing Confirmatory Factor Analysis, (b) developing a 2-level model using a Growth Curve Modeling approach as the final method of measuring growth over time and analyzing the differences between treatment and control groups. Results indicated a significant change ( p < .05) in science self-efficacy and frequency of pono behaviors (p <.05), as well as significant gains in overall GPA (p < .01) in the treatment group. These positive findings suggest that when curriculum developers in Hawai'i are more culturally conscious, it may benefit all learners.

  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.

  13. Oral contraceptive-induced menstrual migraine. Clinical aspects and response to frovatriptan.

    PubMed

    Allais, Gianni; Bussone, Gennaro; Airola, Gisella; Borgogno, Paola; Gabellari, Ilaria Castagnoli; De Lorenzo, Cristina; Pavia, Elena; Benedetto, Chiara

    2008-05-01

    Oral contraceptive-induced menstrual migraine (OCMM) is a poorly defined migraine subtype mainly triggered by the cyclic pill suspension. In this pilot, open-label trial we describe its clinical features and evaluate the efficacy of frovatriptan in the treatment of its acute attack. During the first 3 months of the study 20 women (mean age 32.2+/-7.0, range 22-46) with a 6-month history of pure OCMM recorded, in monthly diary cards, clinical information about their migraine. During the 4th menstrual cycle they treated an OCMM attack with frovatriptan 2.5 mg. The majority of attacks were moderate/severe and lasted 25-72 h or more, in the presence of usual treatment. Generally an OCMM attack appeared within the first 5 days after the pill suspension, but in 15% of cases it started later. After frovatriptan administration, headache intensity progressively decreased (2.4 at onset, 1.6 after 2 h, 1.1 after 4 h and 0.8 after 24 h; p=0.0001). In 55% of patients pain relief was reported after 2 h. Ten percent of subjects were pain-free subjects after 2 h, 35% after 4 h and 60% after 24 h (p=0.003 for trend); 36% relapsed within 24 h. Rescue medication was needed by 35% of patients; 50% of frovatriptan-treated required a second dose. Concomitant nausea and/or vomiting, photophobia and phonophobia decreased significantly after drug intake. OCMM is a severe form of migraine; actually its clinical features are not always exactly identified by the ICHD-II classification. However, treatment with frovatriptan 2.5 mg might be effective in its management.

  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. VGKC-complex/LGI1-antibody encephalitis: clinical manifestations and response to immunotherapy.

    PubMed

    Shin, Yong-Won; Lee, Soon-Tae; Shin, Jung-Won; Moon, Jangsup; Lim, Jung-Ah; Byun, Jung-Ick; Kim, Tae-Joon; Lee, Keon-Joo; Kim, Young-Su; Park, Kyung-Il; Jung, Keun-Hwa; Lee, Sang Kun; Chu, Kon

    2013-12-15

    Leucine-rich glioma inactivated 1 (LGI1) was recently identified as a target protein in autoimmune synaptic encephalitis, a rare condition associated with autoantibodies against structures in the neuronal synapse. Studies dealing with LGI1 are small in number and the various outcomes of different therapeutic regimens are not well studied. Here, we analyzed clinical characteristics of 14 patients with LGI1 antibodies, and outcomes according to therapeutic strategies. Most patients exhibited abnormal brain positron emission tomography and that patients treated with steroids alone were more likely to relapse and had less favorable outcomes than those treated with steroids and intravenous immunoglobulins.

  16. Clinical Research in Vulnerable Populations: Variability and Focus of Institutional Review Boards’ Responses

    PubMed Central

    Lutz, Nadine; Bürger, Friederike; Luntz, Steffen; Hinderhofer, Katrin; Bendszus, Martin; Hoffmann, Georg F.; Ries, Markus

    2015-01-01

    Background Children and patients with cognitive deficits may find it difficult to understand the implication of research. In the European Union (EU), clinical studies outside the EU directives concerning medicinal products or medical devices, i.e., “miscellaneous clinical studies”, have no legally mandated timelines for institutional review boards’ (IRB) decisions. Goal To evaluate the review process of IRBs for two different “miscellaneous” multicenter clinical research protocols involving vulnerable subjects (children and adult stroke patients). Methods Descriptive and comparative statistics. Protocol 1 is a prospective, multicenter, cross-sectional screening study of a symptomatic pediatric population at risk for Fabry disease involving genetic testing (NCT02152189). Protocol 2 is a prospective, multicenter, randomized, controlled, open-label, blinded endpoint post-market study to evaluate the effectiveness of stent retrievers (NCT02135926). After having obtained positive initial IRB votes at the main study site, both protocols were subsequently submitted to the remaining IRBs. Results Protocol 1 was submitted to 19 IRBs. No IRB objected to the study. Median time-to-final vote was 34 (IQR 10–65; range 0 to 130) days. Two IRBs accepted the coordinating center’s IRB votes without re-evaluation. Changes to the informed consent documents were asked by 7/19 IRBs, amendments to the protocol by 2. Protocol 2 was submitted to 16 IRBs. Fifteen decisions were made. No IRB objected to the study. Median time-to final vote was 59 (IQR 10 to 65; range 0 to 128) days, which was not statistically significantly different compared with protocol 1 (Wilcoxon test). Two IRBs accepted a previous IRB decision and did not conduct an independent review. Eight/16 IRBs required changes to the informed consent documents; two IRBs recommended an amendment of the protocol. Conclusion Both clinical research protocols involving vulnerable populations were well accepted. IRB

  17. FDG PET/CT response in diffuse large B-cell lymphoma: Reader variability and association with clinical outcome.

    PubMed

    Han, Eun Ji; O, Joo Hyun; Yoon, Hyukjin; Jung, Seung Eun; Park, Gyeongsin; Choi, Byung Ock; Cho, Seok-Goo

    2016-09-01

    F-18-fluoro-2-deoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is essential for monitoring response to treatment in patients with diffuse large B-cell lymphoma (DLBCL) and qualitative interpretation is commonly applied in clinical practice. We aimed to evaluate the interobserver agreements of qualitative PET/CT response in patients with DLBCL and the predictive value of PET/CT results for clinical outcome.PET/CT images were obtained for patients with DLBCL 3 times: at baseline, after 3 cycles of first-line chemotherapy (interim), and after completion of chemotherapy. Two nuclear medicine physicians (with 3 and 8 years of experience with PET/CT) retrospectively assessed response to chemotherapy blinded to the clinical outcome using International Harmonization Project (IHP) criteria and Deauville 5-point score. The associations between PET/CT results and progression-free survival (PFS) and overall survival (OS) were assessed using Cox regression analysis.A total of 112 PET/CT images were included from 59 patients with DLBCL (36 male, 23 female; mean age 53 ± 14 years). Using the IHP criteria, interobserver agreement was substantial (Cohen κ = 0.76) with absolute agreement consistency of 89%. Using the Deauville score, interobserver agreement was moderate (Cohen weighted κ = 0.54) and absolute consistency was 62%. The most common cause of disagreements was discordant interpretation of residual tumor uptake. With median follow-up period of 60 months, estimated 5-year PFS and OS were 81% and 92%, respectively. Neither interim nor posttreatment PET/CT results by both readers were significantly associated with PFS. Interim PET/CT result by the more experienced reader using Deauville score was a significant factor for OS (P = 0.019).Moderate-to-substantial interobserver agreement was observed for response assessments according to qualitative PET/CT criteria, and interim PET/CT result could predict OS in patients with DLBCL. Further

  18. Clinical Profile and Chemotherapy Response in Children with Hodgkin Lymphoma at a Tertiary Care Centre

    PubMed Central

    Das, Rashmi Ranjan; Puri, Kirti; Singh, Prashant

    2015-01-01

    Introduction Optimal treatment strategy in children with advance stage Hodgkin Lymphoma (HL) still remains controversial. Aim To evaluate the clinical profile and the efficacy of chemotherapy (CT) as a treatment modality in paediatric HL. Material and Methods Retrospective case record evaluation of paediatric HL cases over 5 years (October 2005 to October 2010) period. Results Thirty five cases (31 boys) with a median age of eight years were studied. 24 cases were <10-year-old, and 23 had late stage disease (stage III to IV). B-symptoms were present in 60%, bulky mediastinal disease in 25.7%, and spleen involvement in 60% cases. None had bone marrow involvement. Most common histological type was nodular sclerosis (28.6%). Most cases received ABVD/COPP or ABVD regimen. Two cases needed BEACOPP due to progressive disease, and 4 needed low-dose involved field radiotherapy (RT). At a mean (SD) extended event-free follow-up of 42.7(±17.1) months, four cases relapsed (one was lost to follow-up, and three were treated with chemotherapy and low-dose involved field RT). None died due to the disease. Conclusion Present study found systemic CT alone to be an effective therapy in childhood Hodgkin lymphoma. However, a small sample in present study limits the generalisability of these findings. The findings needs to be replicated in larger population, preferably randomized clinical trials, before any firm conclusion can be made. PMID:26674594

  19. Clinical impact of time-of-flight and point response modeling in PET reconstructions: a lesion detection study

    NASA Astrophysics Data System (ADS)

    Schaefferkoetter, Joshua; Casey, Michael; Townsend, David; El Fakhri, Georges

    2013-03-01

    Time-of-flight (TOF) and point spread function (PSF) modeling have been shown to improve PET reconstructions, but the impact on physicians in the clinical setting has not been thoroughly investigated. A lesion detection and localization study was performed using simulated lesions in real patient images. Four reconstruction schemes were considered: ordinary Poisson OSEM (OP) alone and combined with TOF, PSF, and TOF + PSF. The images were presented to physicians experienced in reading PET images, and the performance of each was quantified using localization receiver operating characteristic. Numerical observers (non-prewhitening and Hotelling) were used to identify optimal reconstruction parameters, and observer SNR was compared to the performance of the physicians. The numerical models showed good agreement with human performance, and best performance was achieved by both when using TOF + PSF. These findings suggest a large potential benefit of TOF + PSF for oncology PET studies, especially in the detection of small, low-intensity, focal disease in larger patients.

  20. A covariate adjusted two-stage allocation design for binary responses in randomized clinical trials.

    PubMed

    Bandyopadhyay, Uttam; Biswas, Atanu; Bhattacharya, Rahul

    2007-10-30

    In the present work, we develop a two-stage allocation rule for binary response using the log-odds ratio within the Bayesian framework allowing the current allocation to depend on the covariate value of the current subject. We study, both numerically and theoretically, several exact and limiting properties of this design. The applicability of the proposed methodology is illustrated by using some data set. We compare this rule with some of the existing rules by computing various performance measures.

  1. Machine Learning Approaches for Integrating Clinical and Imaging Features in LLD Classification and Response Prediction

    PubMed Central

    Patel, Meenal J.; Andreescu, Carmen; Price, Julie C.; Edelman, Kathryn L.; Reynolds, Charles F.; Aizenstein, Howard J.

    2015-01-01

    Objective Currently, depression diagnosis relies primarily on behavioral symptoms and signs, and treatment is guided by trial and error instead of evaluating associated underlying brain characteristics. Unlike past studies, we attempted to estimate accurate prediction models for late-life depression diagn