42 CFR 493.1419 - Standard; Clinical consultant responsibilities.

Science.gov (United States)

2010-10-01

... Testing Laboratories Performing Moderate Complexity Testing § 493.1419 Standard; Clinical consultant... 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...

Evaluation of Clinical and Pathological Response after Two Cycles ...

African Journals Online (AJOL)

Results: The clinical response rate was 83%; 11 patients (11.2%) had a complete clinical remission (cCR); 71 had a partial remission (72.4%); 13 had stable disease (13.3%), and 3 had progressive disease (3.1%). Seven patients had complete pathological response. Conclusion: Neoadjuvant chemotherapy can achieve a ...

Static contribution of the higher modes in the dynamic response of structures

International Nuclear Information System (INIS)

Barbosa, H.J.C.

1982-03-01

In the dynamic response of structures by the modal superposition method usually only the lower modes are taken into account and a procedure that could estimate the contribution due to the higher modes without calculating them would be useful. The technique which consists of assuming that the higher modes respond statically is discussed here. Structures subjected to support motion which are analysed by response spectra techniques are considered and some numerical results are presented. (Author) [pt

42 CFR 493.1457 - Standard; Clinical consultant responsibilities.

Science.gov (United States)

2010-10-01

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

Partial clinical response to anakinra in severe palmoplantar pustular psoriasis.

Science.gov (United States)

Tauber, M; Viguier, M; Alimova, E; Petit, A; Lioté, F; Smahi, A; Bachelez, H

2014-09-01

Palmoplantar pustular psoriasis is a clinical psoriasis variant characterised by a high impact on quality of life and poor response to biologics approved for plaque type psoriasis.The recombinant interleukin-1 (IL-1) receptor antagonist anakinra has been recently used for the treatment of isolated refractory cases of generalised pustular psoriasis with contrasted results. To report the clinical response in two patients treated with anakinra as salvage therapy in two patients with severe palmoplantar pustular psoriasis refractory to currently available antipsoriatic systemic therapies. Anakinra was given subcutaneously at the daily dose of 100 mg, and clinical response was evaluated using the palmoplantar psoriasis area and severity index (PPPASI). Only partial and transient responses were observed in both patients, who had to stop anakinra due to lack of efficacy and to side effects. Anakinra appears to provide only partial clinical improvement in refractory palmoplantar pustular psoriasis. Prospective clinical studies on larger populations are warranted to investigate more accurately both efficacy and safety of IL-1-inhibiting strategies in pustular psoriasis. © 2014 British Association of Dermatologists.

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

Science.gov (United States)

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. © 2014 Wiley Periodicals, Inc.

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

Directory of Open Access Journals (Sweden)

Maged El-Ashker

2013-01-01

Full Text Available 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.

Clinical research in dermatology: resources and activities associated with a higher scientific productivity.

Science.gov (United States)

Molina-Leyva, Alejandro; Descalzo, Miguel A; García-Doval, Ignacio

2018-03-06

Clinical research papers and their derived metrics can be useful to assess the scientific production of medical and research centers. Diverse factors are probably associated to differences in scientific production. But there are scarce studies analyzing them. Resources are limited and have to be distributed efficiently. The objective of this study is to explore what resources and activities are potentially associated with a higher scientific productivity. A bibliometric study was performed to obtain information about scientific productivity. Papers included had to meet criteria to be considered clinical research in dermatology, additionally had to be published between the years 2005-2014, had to be included in Pubmed or Embase and had to include a Spanish center of dermatology as the correspondence address. Information about research resources and activities of the year 2015 was gathered by means of an online survey sent to the authors identified in the bibliometric study. The search strategy returned 8617 papers and only 1104 of them (12.81%) met the inclusion criteria. 63 out of 113 centers responded to the survey (55.75%). Factors associated with a higher scientific productivity were: the size of the resident program, the amount of time specifically dedicated to research, a lower clinical workload, and the number of clinical trials performed in the last year. We have demonstrated that some factors are associated with a higher scientific productivity. Residency program, more research staff, clinical workload redistribution and research motivation/initiatives are key strategies that could improve scientific productivity of a center.

Educational climate seems unrelated to leadership skills of clinical consultants responsible of postgraduate medical education in clinical departments.

Science.gov (United States)

Malling, Bente; Mortensen, Lene S; Scherpbier, Albert J J; Ringsted, Charlotte

2010-09-21

The educational climate is crucial in postgraduate medical education. Although leaders are in the position to influence the educational climate, the relationship between leadership skills and educational climate is unknown. This study investigates the relationship between the educational climate in clinical departments and the leadership skills of clinical consultants responsible for education. The study was a trans-sectional correlation study. The educational climate was investigated by a survey among all doctors (specialists and trainees) in the departments. Leadership skills of the consultants responsible for education were measured by multi-source feedback scores from heads of departments, peer consultants, and trainees. Doctors from 42 clinical departments representing 21 specialties participated. The response rate of the educational climate investigation was moderate 52% (420/811), Response rate was high in the multisource-feedback process 84.3% (420/498). The educational climate was scored quite high mean 3.9 (SD 0.3) on a five-point Likert scale. Likewise the leadership skills of the clinical consultants responsible for education were considered good, mean 5.4 (SD 0.6) on a seven-point Likert scale. There was no significant correlation between the scores concerning the educational climate and the scores on leadership skills, r = 0.17 (p = 0.29). This study found no relation between the educational climate and the leadership skills of the clinical consultants responsible for postgraduate medical education in clinical departments with the instruments used. Our results indicate that consultants responsible for education are in a weak position to influence the educational climate in the clinical department. Further studies are needed to explore, how heads of departments and other factors related to the clinical organisation could influence the educational climate.

Gender differences in binaural speech-evoked auditory brainstem response: are they clinically significant?

Science.gov (United States)

Jalaei, Bahram; Azmi, Mohd Hafiz Afifi Mohd; Zakaria, Mohd Normani

2018-05-17

Binaurally evoked auditory evoked potentials have good diagnostic values when testing subjects with central auditory deficits. The literature on speech-evoked auditory brainstem response evoked by binaural stimulation is in fact limited. Gender disparities in speech-evoked auditory brainstem response results have been consistently noted but the magnitude of gender difference has not been reported. The present study aimed to compare the magnitude of gender difference in speech-evoked auditory brainstem response results between monaural and binaural stimulations. A total of 34 healthy Asian adults aged 19-30 years participated in this comparative study. Eighteen of them were females (mean age=23.6±2.3 years) and the remaining sixteen were males (mean age=22.0±2.3 years). For each subject, speech-evoked auditory brainstem response was recorded with the synthesized syllable /da/ presented monaurally and binaurally. While latencies were not affected (p>0.05), the binaural stimulation produced statistically higher speech-evoked auditory brainstem response amplitudes than the monaural stimulation (p0.80), substantive gender differences were noted in most of speech-evoked auditory brainstem response peaks for both stimulation modes. The magnitude of gender difference between the two stimulation modes revealed some distinct patterns. Based on these clinically significant results, gender-specific normative data are highly recommended when using speech-evoked auditory brainstem response for clinical and future applications. The preliminary normative data provided in the present study can serve as the reference for future studies on this test among Asian adults. Copyright © 2018 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

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

Directory of Open Access Journals (Sweden)

Walach Harald

2005-08-01

Full Text Available Abstract 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 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.

Social Responsibility Performance of Educational Institutions of Higher Learning in Nigeria

OpenAIRE

Justin M. Odinioha Gabriel; Wadike, George

2013-01-01

Over the years, society has witnessed an unprecedented neglect in the area of corporate social responsibility; this situation has diversely been greeted with several conflicts between host communities and the guest enterprises resulting in kidnapping, hostage takings, total shutdown of company facilities and eventual financial losses. In this paper, we examined the social responsibility performance of higher educational institutions in Nigeria. Four research questions were asked to produce th...

Corporate Social Responsibility: Practices of Ethics in Higher Education Institutions

Science.gov (United States)

Law, Marla S.

2016-01-01

The purpose of this study was to explore and examine perceptions among public and private higher education leaders in Pennsylvania regarding their institutions Corporate Social Responsibility (CSR) codes of conduct, ethics training programs, and practices of ethics. Highly publicized misconduct incidents warranted the need for scrutiny of the…

Childhood asthma clusters and response to therapy in clinical trials.

Science.gov (United States)

Chang, Timothy S; Lemanske, Robert F; Mauger, David T; Fitzpatrick, Anne M; Sorkness, Christine A; Szefler, Stanley J; Gangnon, Ronald E; Page, C David; Jackson, Daniel J

2014-02-01

Childhood asthma clusters, or subclasses, have been developed by computational methods without evaluation of clinical utility. To replicate and determine whether childhood asthma clusters previously identified computationally in the Severe Asthma Research Program (SARP) are associated with treatment responses in Childhood Asthma Research and Education (CARE) Network clinical trials. A cluster assignment model was determined by using SARP participant data. A total of 611 participants 6 to 18 years old from 3 CARE trials were assigned to SARP pediatric clusters. Primary and secondary outcomes were analyzed by cluster in each trial. CARE participants were assigned to SARP clusters with high accuracy. Baseline characteristics were similar between SARP and CARE children of the same cluster. Treatment response in CARE trials was generally similar across clusters. However, with the caveat of a smaller sample size, children in the early-onset/severe-lung function cluster had best response with fluticasone/salmeterol (64% vs 23% 2.5× fluticasone and 13% fluticasone/montelukast in the Best ADd-on Therapy Giving Effective Responses trial; P = .011) and children in the early-onset/comorbidity cluster had the least clinical efficacy to treatments (eg, -0.076% change in FEV1 in the Characterizing Response to Leukotriene Receptor Antagonist and Inhaled Corticosteroid trial). In this study, we replicated SARP pediatric asthma clusters by using a separate, large clinical trials network. Early-onset/severe-lung function and early-onset/comorbidity clusters were associated with differential and limited response to therapy, respectively. Further prospective study of therapeutic response by cluster could provide new insights into childhood asthma treatment. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Clinical implications of heterogeneity of tumor response to radiation therapy

International Nuclear Information System (INIS)

Suit, H.; Skates, S.; Taghian, A.; Okunieff, P.; Efird, J.T.

1992-01-01

Heterogeneity of response of tumor tissue to radiation clearly exists. Major parameters include histopathologic type, size (number of tumor rescue units (TRUs)), hemoglobin concentration, cell proliferation kinetics and immune rejection reaction by host. Further, normal and presumably tumor tissue response is altered in certain genetic diseases, e.g. ataxia telangiectasia. Any assessment of response of tumor tissue to a new treatment method or the testing of a new clinical response predictor is optimally based upon a narrow strata, viz., uniform with respect to known parameters of response, e.g. size, histological type. Even among tumors of such a clinical defined narrow strata, there will be residual heterogeneity with respect to inherent cellular radiation sensitivity, distributions of pO 2 , (SH), cell proliferation, etc. (author). 39 refs., 7 figs., 3 tabs

Safety, Clinical Response, and Microbiome Findings Following Fecal Microbiota Transplant in Children With Inflammatory Bowel Disease.

Science.gov (United States)

Goyal, Alka; Yeh, Andrew; Bush, Brian R; Firek, Brian A; Siebold, Leah M; Rogers, Matthew Brian; Kufen, Adam D; Morowitz, Michael J

2018-01-18

The role of fecal microbiota transplant (FMT) in the treatment of pediatric inflammatory bowel disease (IBD) is unknown. The aims of this study were to assess safety, clinical response, and gut microbiome alterations in children with Crohn's disease (CD), ulcerative colitis (UC), or indeterminate colitis (IC). In this open-label, single-center prospective trial, patients with IBD refractory to medical therapy underwent a single FMT by upper and lower endoscopy. Adverse events, clinical response, gut microbiome, and biomarkers were assessed at baseline, 1 week, 1 month, and 6 months following FMT. Twenty-one subjects were analyzed, with a median age of 12 years, of whom 57% and 28% demonstrated clinical response at 1 and 6 months post-FMT, respectively. Two CD patients were in remission at 6 months. Adverse events attributable to FMT were mild to moderate and self-limited. Patients prior to FMT showed decreased species diversity and significant microbiome compositional differences characterized by increased Enterobacteriaceae, Enterococcus, Haemophilus, and Fusobacterium compared with donors and demonstrated increased species diversity at 30 days post-FMT. At 6 months, these changes shifted toward baseline. Clinical responders had a higher relative abundance of Fusobacterium and a lower diversity at baseline, as well as a greater shift toward donor-like microbiome after FMT compared with nonresponders. A single FMT is relatively safe and can result in a short-term response in young patients with active IBD. Responders possessed increased Fusobacterium prior to FMT and demonstrated more significant microbiome changes compared with nonresponders after FMT. Microbiome characteristics may help in predicting response. © 2018 Crohn’s & Colitis Foundation of America. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Trends and EIE higher education response to the current global technical challenges

DEFF Research Database (Denmark)

Poboroniuc, Marian; Livint, Gheorghe; Friesel, Anna

2014-01-01

Education Institutions (SALEIE), an EU supported project, gathers together a global team aiming to provide higher education models in the EIE disciplines that can respond to the key global technical challenges. This paper deals with findings within the SALEIE project's work package WP3 (Global Challenges......), namely: state-of-the-art in implementation of the Bologna recommendation for Bachelor and Master, technical challenges that the EIE higher education faces nowadays, and existing models in EIE higher education and their degree of response to key global technical challenges....

Intermittent Theta Burst Stimulation Increases Reward Responsiveness in Individuals with Higher Hedonic Capacity.

Science.gov (United States)

Duprat, Romain; De Raedt, Rudi; Wu, Guo-Rong; Baeken, Chris

2016-01-01

Repetitive transcranial magnetic stimulation over the left dorsolateral prefrontal cortex (DLPFC) has been documented to influence striatal and orbitofrontal dopaminergic activity implicated in reward processing. However, the exact neuropsychological mechanisms of how DLPFC stimulation may affect the reward system and how trait hedonic capacity may interact with the effects remains to be elucidated. In this sham-controlled study in healthy individuals, we investigated the effects of a single session of neuronavigated intermittent theta burst stimulation (iTBS) on reward responsiveness, as well as the influence of trait hedonic capacity. We used a randomized crossover single session iTBS design with an interval of 1 week. We assessed reward responsiveness using a rewarded probabilistic learning task and measured individual trait hedonic capacity (the ability to experience pleasure) with the temporal experience of pleasure scale questionnaire. As expected, the participants developed a response bias toward the most rewarded stimulus (rich stimulus). Reaction time and accuracy for the rich stimulus were respectively shorter and higher as compared to the less rewarded stimulus (lean stimulus). Active or sham stimulation did not seem to influence the outcome. However, when taking into account individual trait hedonic capacity, we found an early significant increase in the response bias only after active iTBS. The higher the individual's trait hedonic capacity, the more the response bias toward the rich stimulus increased after the active stimulation. When taking into account trait hedonic capacity, one active iTBS session over the left DLPFC improved reward responsiveness in healthy male participants with higher hedonic capacity. This suggests that individual differences in hedonic capacity may influence the effects of iTBS on the reward system.

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

Science.gov (United States)

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

2011-03-28

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

Information needs for the rapid response team electronic clinical tool.

Science.gov (United States)

Barwise, Amelia; Caples, Sean; Jensen, Jeffrey; Pickering, Brian; Herasevich, Vitaly

2017-10-02

Information overload in healthcare is dangerous. It can lead to critical errors and delays. During Rapid Response Team (RRT) activations providers must make decisions quickly to rescue patients from physiological deterioration. In order to understand the clinical data required and how best to present that information in electronic systems we aimed to better assess the data needs of providers on the RRT when they respond to an event. A web based survey to evaluate clinical data requirements was created and distributed to all RRT providers at our institution. Participants were asked to rate the importance of each data item in guiding clinical decisions during a RRT event response. There were 96 surveys completed (24.5% response rate) with fairly even distribution throughout all clinical roles on the RRT. Physiological data including heart rate, respiratory rate, and blood pressure were ranked by more than 80% of responders as being critical information. Resuscitation status was also considered critically useful by more than 85% of providers. There is a limited dataset that is considered important during an RRT. The data is widely available in EMR. The findings from this study could be used to improve user-centered EMR interfaces.

Medical student resilience and stressful clinical events during clinical training.

Science.gov (United States)

Houpy, Jennifer C; Lee, Wei Wei; Woodruff, James N; Pincavage, Amber T

2017-01-01

Medical students face numerous stressors during their clinical years, including difficult clinical events. Fostering resilience is a promising way to mitigate negative effects of stressors, prevent burnout, and help students thrive after difficult experiences. However, little is known about medical student resilience. To characterize medical student resilience and responses to difficult clinical events during clinical training. Sixty-two third-year (MS3) and 55 fourth-year (MS4) University of Chicago medical students completed surveys in 2016 assessing resilience (Connor Davidson Resilience Scale, CD-RISC 10), symptoms of burnout, need for resilience training, and responses to difficult clinical events. Medical student mean resilience was lower than in a general population sample. Resilience was higher in males, MS4s, those without burnout symptoms, and students who felt able to cope with difficult clinical events. When students experienced difficult events in the clinical setting, the majority identified poor team dynamics among the most stressful, and agreed their wellbeing was affected by difficult clinical events. A majority also would prefer to discuss these events with their team later that day. Students discussed events with peers more than with attendings or residents. Students comfortable discussing stress and burnout with peers had higher resilience. Most students believed resilience training would be helpful and most beneficial during MS3 year. Clinical medical student resilience was lower than in the general population but higher in MS4s and students reporting no burnout. Students had some insight into their resilience and most thought resilience training would be helpful. Students discussed difficult clinical events most often with peers. More curricula promoting medical student resilience are needed.

Hospital in the Home nurses' recognition and response to clinical deterioration.

Science.gov (United States)

Gray, Erika; Currey, Judy; Considine, Julie

2018-05-01

To obtain an understanding of how Hospital in the Home (HITH) nurses recognise and respond to clinical deterioration in patients receiving care at home or in their usual place of residence. Recognising and responding to clinical deterioration is an international safety priority and a key nursing responsibility. Despite an increase in care delivery in home environments, how HITH nurses recognise and respond to clinical deterioration is not yet fully understood. A prospective, descriptive exploratory design was used. A survey containing questions related to participant characteristics and 10 patient scenarios was used to collect data from 47 nurses employed in the HITH units of three major health services in Melbourne, Australia. The 10 scenarios reflected typical HITH patients and included medical history and clinical assessment findings (respiratory rate, oxygen saturation, heart rate, blood pressure, temperature, conscious state and pain score). The three major findings from this study were that: (i) nurse and patient characteristics influenced HITH nurses' assessment decisions; (ii) the cues used by HITH nurses to recognise clinical deterioration varied according to the clinical context; and (iii) although HITH nurses work in an autonomous role, they engage in collaborative practice when responding to clinical deterioration. Hospital in the Home nurses play a fundamental role in patient assessment, and the context in which they recognise and respond to deterioration is markedly different to that of hospital nurses. The assessment, measurement and interpretation of clinical data are a nursing responsibility that is crucial to early recognition and response to clinical deterioration. The capacity of HITH services to care for increasing numbers of patients in their home environment, and to promptly recognise and respond to clinical deterioration should it occur, is fundamental to safety within the healthcare system. Hospital in the Home nurses are integral to a

A method to adjust radiation dose-response relationships for clinical risk factors

DEFF Research Database (Denmark)

Appelt, Ane Lindegaard; Vogelius, Ivan R

2012-01-01

Several clinical risk factors for radiation induced toxicity have been identified in the literature. Here, we present a method to quantify the effect of clinical risk factors on radiation dose-response curves and apply the method to adjust the dose-response for radiation pneumonitis for patients...

Extension as expression of social responsibility for higher education

Directory of Open Access Journals (Sweden)

Ricardo Antonio de Marco

2016-05-01

Full Text Available The National System of Higher Education Assessment 2004 in Axis 2, Institutional Development and its dimensions 1 and 3: Mission and Institutional Development Plan (IDP and the Social Responsibility of the institution highlights the need for universities to incorporate in their activities teaching, research and extension practices that demonstrate their positive involvement in social development. In this sense, this article aims to evaluate the practice of university extension contributes to the consolidation of University Social Responsibility. was used as a method descriptive research and documentary analysis found that the institutional documents of the University of the West of Santa Catarina: mission, vision and values; Institutional Development Plan and the extension project of the University of Chapecó Best Age (UMIC; and the National System of Higher Education Evaluation. From this inference, it was revealed that UNOESC in its constitutive principles and official documents value-oriented civic education for social inclusion. It was found that the consolidation of MSW necessarily involves watchful eye of management to the principles of indivisibility of teaching, research and extension, components and ended the universities, which when not properly executed, counter and violate the legal provision; that inter- and transdisciplinary nature of extension projects, such as UMIC, have strong contribution to the consolidation of MSW; parallel, left clear that isolation Extension projects like UMIC not reach the fullness of the social commitment of universities, suggesting that inseparability is present with the incorporation of actions that promote social development.

Clinical relevance of the ROC and free-response paradigms for comparing imaging system efficacies

International Nuclear Information System (INIS)

Chakraborty, D. P.

2010-01-01

Observer performance studies are widely used to assess medical imaging systems. Unlike technical/engineering measurements observer performance include the entire imaging chain and the radiologist. However, the widely used receiver operating characteristic (ROC) method ignores lesion localisation information. The free-response ROC (FROC) method uses the location information to appropriately reward or penalise correct or incorrect localizations, respectively. This paper describes a method for improving the clinical relevance of FROC studies. The method consists of assigning appropriate risk values to the different lesions that may be present on a single image. A high-risk lesion is one that is critical to detect and act upon, and is assigned a higher risk value than a low-risk lesion, one that is relatively innocuous. Instead of simply counting the number of lesions that are detected, as is done in conventional FROC analysis, a risk-weighted count is used. This has the advantage of rewarding detections of high-risk lesions commensurately more than detections of lower risk lesions. Simulations were used to demonstrate that the new method, termed case-based analysis, results in a higher figure of merit for an expert who detects more high-risk lesions than a naive observer who detects more low-risk lesions, even though both detect the same total number of lesions. Conventional free-response analysis is unable to distinguish between the two types of observers. This paper also comments on the issue of clinical relevance of ROC analysis vs. FROC for tasks that involve lesion localisation. (authors)

Susceptibility of functional impairment scales to noncredible responses in the clinical evaluation of adult ADHD.

Science.gov (United States)

Fuermaier, Anselm B M; Tucha, Oliver; Koerts, Janneke; Butzbach, Marah; Weisbrod, Matthias; Aschenbrenner, Steffen; Tucha, Lara

2018-05-01

A growing body of research questions the reliance of symptom self-reports in the clinical evaluation of attention-deficit/hyperactivity disorder (ADHD) in adulthood. A recent study suggested that also impairment reports are vulnerable to noncredible responses, as derived from a simulation design using a global functional impairment scale. The present study aims to add evidence to this issue, by using an ADHD specific impairment scale in a simulation design on large samples. Impairment ratings on the Weiss Functional Impairment Rating Scale (WFIRS) of 62 patients with ADHD were compared to 142 healthy individuals who were instructed to show normal behavior. Furthermore, impairment ratings of patients with ADHD were compared to ratings of 330 healthy individuals who were randomly assigned to one of four simulation conditions that were instructed to complete the scale as if they had ADHD. Patients with ADHD reported higher levels of impairment than the healthy control group in all domains of life. Furthermore, individuals instructed to feign ADHD indicated higher levels of impairments in most domains of life compared to control participants and genuine patients with ADHD. The group differences between individuals feigning ADHD and individuals with genuine ADHD, however, were only small to moderate. Further analyses revealed that the WFRIS was not useful to successfully differentiate genuine from feigned ADHD. The present study confirms the conclusion that self-reported impairments are susceptible to noncredible responses and should be used with caution in the clinical evaluation of adult ADHD.

Selection of response criteria for clinical trials of sarcoma treatment.

Science.gov (United States)

Schuetze, Scott M; Baker, Laurence H; Benjamin, Robert S; Canetta, Renzo

2008-01-01

Soft tissue sarcomas are a heterogeneous group of malignancies arising from mesenchymal tissues. A large number of new therapies are being evaluated in patients with sarcomas, and consensus criteria defining treatment responses are essential for comparison of results from studies completed by different research groups. The 1979 World Health Organization (WHO) handbook set forth operationally defined criteria for response evaluation in solid tumors that were updated in 2000 with the publication of the Response Evaluation Criteria in Solid Tumors (RECIST). There have been significant advances in tumor imaging, however, that are not reflected in the RECIST. For example, computed tomography (CT) slice thickness has been reduced from 10 mm to < or =2.5 mm, allowing for more reproducible and accurate measurement of smaller lesions. Combination of imaging techniques, such as positron emission tomography with fluorine-18-fluorodeoxyglucose (18FDG-PET) and CT can provide investigators and clinicians with both anatomical and functional information regarding tumors, and there is now a large body of evidence demonstrating the effectiveness of PET/CT and other newer imaging methods for the detection and staging of tumors as well as early determination of responses to therapy. The application of newer imaging methods has the potential to decrease both the sample sizes required for, and duration of, clinical trials by providing an early indication of therapeutic response that is well correlated with clinical outcomes, such as time to tumor progression or overall survival. The results summarized in this review support the conclusion that the RECIST and the WHO criteria for evaluation of response in solid tumors need to be modernized. In addition, there is a current need for prospective trials to compare new response criteria with established endpoints and to validate imaging-based response rates as surrogate endpoints for clinical trials of new agents for sarcoma and other solid

A clinical clerkship collaborative program in Taiwan: Acquiring core clinical competencies through patient care responsibility

Directory of Open Access Journals (Sweden)

Yong A. Wang

2016-06-01

Conclusion: This pilot collaborative program presented a successful model for clinical education in the teaching of core clinical competencies through direct patient care responsibilities at the clerkship stage. It is hoped that the project will become a catalyst for medical education reform in Taiwan and regions with similar traditions.

Bladder cancer treatment response assessment with radiomic, clinical, and radiologist semantic features

Science.gov (United States)

Gordon, Marshall N.; Cha, Kenny H.; Hadjiiski, Lubomir M.; Chan, Heang-Ping; Cohan, Richard H.; Caoili, Elaine M.; Paramagul, Chintana; Alva, Ajjai; Weizer, Alon Z.

2018-02-01

We are developing a decision support system for assisting clinicians in assessment of response to neoadjuvant chemotherapy for bladder cancer. Accurate treatment response assessment is crucial for identifying responders and improving quality of life for non-responders. An objective machine learning decision support system may help reduce variability and inaccuracy in treatment response assessment. We developed a predictive model to assess the likelihood that a patient will respond based on image and clinical features. With IRB approval, we retrospectively collected a data set of pre- and post- treatment CT scans along with clinical information from surgical pathology from 98 patients. A linear discriminant analysis (LDA) classifier was used to predict the likelihood that a patient would respond to treatment based on radiomic features extracted from CT urography (CTU), a radiologist's semantic feature, and a clinical feature extracted from surgical and pathology reports. The classification accuracy was evaluated using the area under the ROC curve (AUC) with a leave-one-case-out cross validation. The classification accuracy was compared for the systems based on radiomic features, clinical feature, and radiologist's semantic feature. For the system based on only radiomic features the AUC was 0.75. With the addition of clinical information from examination under anesthesia (EUA) the AUC was improved to 0.78. Our study demonstrated the potential of designing a decision support system to assist in treatment response assessment. The combination of clinical features, radiologist semantic features and CTU radiomic features improved the performance of the classifier and the accuracy of treatment response assessment.

Social Responsibility in Intra-organisational Procedures of Higher Education Institutions with AACSB Accreditation

OpenAIRE

Dzięgiel, Andżelika; Wojciechowska, Anna

2017-01-01

This paper aims to identify the core elements of social responsibility which have been applied in intraorganisational procedures of higher education institutions with AACSB Accreditation. The concept of corporate social responsibility (CSR) in entrepreneurial strategies means taking into account their social interests and environmental protection, as well as, relationships with different groups of stakeholders. In contemporary business, CSR activities are very important. Therefore, universiti...

Worldviews and Quality in Higher Education: a dichotomy between productivity and social responsibility

Directory of Open Access Journals (Sweden)

Julio Bertolin

2013-11-01

Full Text Available This paper addresses and analyzes concepts that have been often used by important stakeholders to refer to challenges and to quality in higher education. The aim is to identify the conceptualizations of quality in higher education that underlie the use of different concepts such as efficiency and equity. Based on publications by important multilateral organizations, these terms are correlated with the conceptualizations of higher education and, at the political level, with two major contemporary socioeconomic models: neoliberalism and social welfare state. Finally, two ideological tendencies for the understanding of quality in higher education are presented: quality as productivity and quality as social responsibility.

Attitudes towards Study Effort Response to Higher Grading Standards: Do Gender and Personality Distinctions Matter?

Science.gov (United States)

Fallan, Lars; Opstad, Leiv

2012-01-01

The purpose of this paper is to explore how gender and personality preferences affect student attitudes towards effort response to higher grading standards. Data collected from 150 economics and business students at a Scandinavian business school reveals that higher grading standards enhance effort and time devoted to learning to a higher degree…

Learning in clinical practice: Stimulating and discouraging response to social comparison.

Science.gov (United States)

Raat, Janet; Kuks, Jan; Cohen-Schotanus, Janke

2010-01-01

Social comparison theory is relevant for learning in general. In a clinical context, we examined four hypotheses concerning: preferred other to compare with, preferred direction of comparison, response to social comparison and influence of personal social comparison orientation (SCO). To investigate the relevance of social comparison for clinical workplace learning. Students (n = 437) from nine different hospitals completed two questionnaires measuring their SCO and the direction of and response to their comparisons. t-tests were used to analyse the data. Students substantially did compare. They preferred to compare with peer students more than with residents or staff, and with peers doing better more than with peers doing worse. Their response to social comparison was more often stimulating for learning than discouraging. Students high in SCO reported a stronger stimulating and discouraging response to their comparisons than students low in SCO. Social comparison does play a role in clinical workplace learning. The mainly stimulating response to social comparison indicates a positive learning influence. The preferred comparison with peers emphasizes the role of peers in the learning process. Further research should focus on student comparison behaviour and on situations that strengthen the positive effects of social comparison and reduce the negative or obstructing ones.

Admission Privileges and Clinical Responsibilities for Interventional Radiologists

Energy Technology Data Exchange (ETDEWEB)

Al-Kutoubi, Aghiad, E-mail: mk00@aub.edu.lb [The American University of Beirut Medical Center, IR Division, The Department of Diagnostic Radiology (Lebanon)

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.

Admission Privileges and Clinical Responsibilities for Interventional Radiologists

International Nuclear Information System (INIS)

Al-Kutoubi, Aghiad

2015-01-01

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

Immunization with avian metapneumovirus harboring chicken Fc induces higher immune responses.

Science.gov (United States)

Paudel, Sarita; Easwaran, Maheswaran; Jang, Hyun; Jung, Ho-Kyoung; Kim, Joo-Hun; Shin, Hyun-Jin

2016-07-15

In this study, we evaluated the immune responses of avian metapneumovirus harboring chicken Fc molecule. Stable Vero cells expressing chicken Fc chimera on its surface (Vero-cFc) were established, and we confirmed that aMPV grown in Vero-cFc incorporated host derived chimera Fc into the aMPV virions. Immunization of chicken with aMPV-cFc induced higher level of antibodies and inflammatory cytokines; (Interferon (IFN)-γ and Interleukin (IL)-1β) compared to those of aMPV. The increased levels of antibodies and inflammatory cytokines in chicken immunized with aMPV-cFc were statistically significantly (p<0.05) to that of aMPV and control. The aMPV-cFc group also generated the highest neutralizing antibody response. After challenges, chickens immunized with aMPV-cFc showed much less pathological signs in nasal turbinates and trachea so that we could confirm aMPV-cFc induced higher protection than that of aMPV. The greater ability of aMPV harboring chicken Fc to that of aMPV presented it as a possible vaccine candidate. Copyright © 2016 Elsevier B.V. All rights reserved.

Acknowledging and allocating responsibility for clinical inertia in the management of Type 2 diabetes in primary care: a qualitative study.

Science.gov (United States)

Zafar, A; Stone, M A; Davies, M J; Khunti, K

2015-03-01

Failure to intensify treatment in patients with Type 2 diabetes with suboptimal blood glucose control has been termed clinical inertia and has been shown to contribute to poorer patient outcomes. We aimed to identify and explore perceptions about clinical inertia from the perspective of primary healthcare providers. A qualitative study was conducted in Leicestershire and Northamptonshire, UK. Purposive sampling was based on healthcare providers working in primary care settings with 'higher' and 'lower' target achievement based on routine data. Twenty semi-structured interviews were conducted, face-to-face or by telephone. Thematic analysis was informed by the constant comparative approach. An important broad theme that emerged during the analysis was related to attribution and explanation of responsibility for clinical inertia. This included general willingness to accept a degree of responsibility for clinical inertia. In some cases, however, participants had inaccurate perceptions about levels of target achievement in their primary care centres, as indicated by routine data. Participants sought to lessen their own sense of accountability by highlighting patient-level barriers such as comorbidities and human fallibility, and also system-level barriers, particularly time constraints. Perceptions about ways of addressing the problem of clinical inertia were not seen as straightforward, further emphasizing a complex and cumulative pattern of barriers. In order to understand and address the problem of clinical inertia, provider, patient- and system-level barriers should be considered together rather than as separate issues. Acknowledgement of responsibility should be regarded positively as a motivator for change. © 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.

Radiological response and clinical outcome in patients with femoral bone metastases after radiotherapy

International Nuclear Information System (INIS)

Harada, Hideyuki; Katagiri, Hirohisa; Kamata, Minoru

2010-01-01

We evaluated the radiological response and clinical outcome in patients with femoral bone metastases after radiotherapy. 102 consecutive patients with femoral metastases without pathological fracture were treated by surgery or radiotherapy between 2002 and 2005. Twelve of them initially treated with surgery were excluded from this study. The remaining 90 patients with 102 lesions underwent radiation therapy as the initial treatment. Twelve patients who died within 30 days by disease progression and 6 who were lost to follow-up were excluded. The remaining 72 patients with 84 lesions including 43 impending fractures were enrolled in this analysis. Radiological changes were categorized into complete response, partial response, no change, and progressive disease based on plain radiograph findings. Pain relief was reviewed for 77 painful lesions. The median radiation dose was 30 Gy. No re-irradiation was performed. 35 lesions (42%) achieved radiological responses median 3 months after radiotherapy. Pain relief was obtained in 36 of 77 lesions (47%). There was no significant correlation between radiological response and pain relief (P=0.166). Eleven lesions eventually required surgery and considered as treatment failure. The treatment failure rate in the radiological progressive disease (PD) group (8/19, 42%) was significantly higher than that in the non-PD group (3/65, 5%) (P<0.001). Among 43 impending fracture lesions, 15 lesions (36%) experienced radiological response and 35 lesions (81%) required no surgical interventions. Our data suggest that radiotherapy can enable metastatic bone healing and avoid surgery in many lesions. However, radiological PD lesions often require surgery after radiotherapy. (author)

Correlation between ability of biofilm formation with their responsible genes and MDR patterns in clinical and environmental Acinetobacter baumannii isolates.

Science.gov (United States)

Bardbari, Ali Mohammadi; Arabestani, Mohammad Reza; Karami, Manoochehr; Keramat, Fariba; Alikhani, Mohammad Yousef; Bagheri, Kamran Pooshang

2017-07-01

Acinetobacter baumannii potential to form biofilm and exhibit multiple antibiotic resistances may be responsible in its survival in hospital environment. Accordingly, our study was aimed to determine the correlation between ability of biofilm formation and the frequency of biofilm related genes with antibiotic resistance phenotypes, and also the categorization of their patterns in clinical and environmental isolates. A total of 75 clinical and 32 environmental strains of the A. baumannii were collected and identified via API 20NE. Antibiotic susceptibility was evaluated by disk diffusion and microdilution broth methods. Biofilm formation assay was performed by microtiter plate method. OXA types and biofilm related genes including Bla OXA-51 , Bla OXA-23 , Bla OXA-24 , Bla OXA-58 , bap, bla PER-1 , and ompA were amplified by PCR. The rate of MDR A. baumannii in clinical isolates (100%) was higher than environmental (81.2%) isolates (p baumannii isolates was associated with biofilm formation. There was a significant correlation between multiple drug resistance and biofilm formation. The clinical isolates had a higher ability to form strong biofilms compared to the environmental samples. Copyright © 2017 Elsevier Ltd. All rights reserved.

Patients' Positive and Negative Responses to Reading Mental Health Clinical Notes Online.

Science.gov (United States)

Denneson, Lauren M; Chen, Jason I; Pisciotta, Maura; Tuepker, Anais; Dobscha, Steven K

2018-05-01

This study describes responses to OpenNotes, clinical notes available online, among patients receiving mental health care and explores whether responses vary by patient demographic or clinical characteristics. Survey data from 178 veterans receiving mental health treatment at a large Veterans Affairs medical center included patient-reported health self-efficacy, health knowledge, alliance with clinicians, and negative emotional responses after reading OpenNotes. Health care data were extracted from the patient care database. Reading OpenNotes helped many participants feel in control of their health care (49%) and have more trust in clinicians (45%), although a few (8%) frequently felt upset after reading their notes. In multivariate models, posttraumatic stress disorder was associated with increased patient-clinician alliance (p=.046) but also with negative emotional responses (p<.01). Patients receiving mental health care frequently reported benefits from reading OpenNotes, yet some experienced negative responses.

Data quality assurance: an analysis of patient non-response.

Science.gov (United States)

Derby, Dustin C; Haan, Andrea; Wood, Kurt

2011-01-01

Patient satisfaction is paramount to maintaining high clinical quality assurance. This study seeks to compare response rates, response bias, and the completeness of data between paper and electronic collection modes of a chiropractic patient satisfaction survey. A convenience sample of 206 patients presenting to a chiropractic college clinic were surveyed concerning satisfaction with their chiropractic care. Paper (in-clinic and postal) and electronic modes of survey administration were compared for response rates and non-response bias. The online data collection mode resulted in fewer non-responses and a higher response rate, and did not evince response bias when compared to paper modes. The postal paper mode predicted non-response rates over the in-clinic paper and online modalities and exhibited a gender bias. This current study was a single clinic study; future studies should consider multi-clinic data collections. Busy clinic operations and available staff resources restricted the ability to conduct a random sampling of patients or to invite all eligible patients, therefore limiting the generalizability of collected survey data. Results of this study will provide data to aid development of survey protocols that efficiently, account for available human resources, and are convenient for patients while allowing for the most complete and accurate data collection possible in an educational clinic setting. Understanding patient responses across survey modes is critical for the cultivation of quality business intelligence within college teaching clinic settings. This study bridges measurement evidence from three popular data collection modalities and offers support for higher levels of quality for web-based data collection.

Conceptual DFT: the chemical relevance of higher response functions.

Science.gov (United States)

Geerlings, P; De Proft, F

2008-06-07

In recent years conceptual density functional theory offered a perspective for the interpretation/prediction of experimental/theoretical reactivity data on the basis of a series of response functions to perturbations in the number of electrons and/or external potential. This approach has enabled the sharp definition and computation, from first principles, of a series of well-known but sometimes vaguely defined chemical concepts such as electronegativity and hardness. In this contribution, a short overview of the shortcomings of the simplest, first order response functions is illustrated leading to a description of chemical bonding in a covalent interaction in terms of interacting atoms or groups, governed by electrostatics with the tendency to polarize bonds on the basis of electronegativity differences. The second order approach, well known until now, introduces the hardness/softness and Fukui function concepts related to polarizability and frontier MO theory, respectively. The introduction of polarizability/softness is also considered in a historical perspective in which polarizability was, with some exceptions, mainly put forward in non covalent interactions. A particular series of response functions, arising when the changes in the external potential are solely provoked by changes in nuclear configurations (the "R-analogues") are also systematically considered. The main part of the contribution is devoted to third order response functions which, at first sight, may be expected not to yield chemically significant information, as turns out to be for the hyperhardness. A counterexample is the dual descriptor and its R analogue, the initial hardness response, which turns out to yield a firm basis to regain the Woodward-Hoffmann rules for pericyclic reactions based on a density-only basis, i.e. without involving the phase, sign, symmetry of the wavefunction. Even the second order nonlinear response functions are shown possibly to bear interesting information, e

Incorporating social groups' responses in a descriptive model for second- and higher-order impact identification

International Nuclear Information System (INIS)

Sutheerawatthana, Pitch; Minato, Takayuki

2010-01-01

The response of a social group is a missing element in the formal impact assessment model. Previous discussion of the involvement of social groups in an intervention has mainly focused on the formation of the intervention. This article discusses the involvement of social groups in a different way. A descriptive model is proposed by incorporating a social group's response into the concept of second- and higher-order effects. The model is developed based on a cause-effect relationship through the observation of phenomena in case studies. The model clarifies the process by which social groups interact with a lower-order effect and then generate a higher-order effect in an iterative manner. This study classifies social groups' responses into three forms-opposing, modifying, and advantage-taking action-and places them in six pathways. The model is expected to be used as an analytical tool for investigating and identifying impacts in the planning stage and as a framework for monitoring social groups' responses during the implementation stage of a policy, plan, program, or project (PPPPs).

Educational climate seems unrelated to leadership skills of clinical consultants responsible of postgraduate medical education in clinical departments

DEFF Research Database (Denmark)

Malling, Bente Vigh; Mortensen, Lene S.; Scherpbier, Albert J J

2010-01-01

The educational climate is crucial in postgraduate medical education. Although leaders are in the position to influence the educational climate, the relationship between leadership skills and educational climate is unknown. This study investigates the relationship between the educational climate...... in clinical departments and the leadership skills of clinical consultants responsible for education....

Hypertensive response to exercise: mechanisms and clinical implication

OpenAIRE

Kim, Darae; Ha, Jong-Won

2016-01-01

A hypertensive response to exercise (HRE) is frequently observed in individuals without hypertension or other cardiovascular disease. However, mechanisms and clinical implication of HRE is not fully elucidated. Endothelial dysfunction and increased stiffness of large artery contribute to development of HRE. From neurohormonal aspects, excess stimulation of sympathetic nervous system and augmented rise of angiotensin II seems to be important mechanism in HRE. Increasing evidences indicates tha...

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

Science.gov (United States)

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

Social Responsibility in Intra-organisational Procedures of Higher Education Institutions with AACSB Accreditation

Directory of Open Access Journals (Sweden)

Andżelika Dzięgiel

2016-10-01

Full Text Available This paper aims to identify the core elements of social responsibility which have been applied in intraorganisational procedures of higher education institutions with AACSB Accreditation. The concept of corporate social responsibility (CSR in entrepreneurial strategies means taking into account their social interests and environmental protection, as well as, relationships with different groups of stakeholders. In contemporary business, CSR activities are very important. Therefore, universities, especially those with prestigious accreditations, should also act in accordance with the rules prevailing in the business market. The Association to Advance Collegiate School of Business (AACSB is a global, nonprofit membership organisation of educational institutions, businesses, and other entities. Higher education institutions with certificates represent the highest standard of achievement for business schools all over the world. For the research and analysis, there have been selected six universities from three countries: the United States, the United Kingdom and New Zealand. According to the international standard ISO 26000 dated as of 2010, social responsibility involves seven core subjects: organisational governance, human rights, labour practices, environment, fair operating practices, customer issues, community involvement and development. All these aspects were researched in intraorganisational procedures of selected higher education institutions with AACSB Accreditation. It is a comprehensive and objective comparison of several educational institutions in the world in terms of their implemented CSR activities. The results of the research show that the institutions under the study established a wide range of procedures for respecting CSR. They took into account transparency, respect to the law, human rights, labour practices and organisational governance. While they pay less attention to the environmental issues, fair operating practices and

Typhoid fever in young children in Bangladesh: clinical findings, antibiotic susceptibility pattern and immune responses.

Directory of Open Access Journals (Sweden)

Farhana Khanam

2015-04-01

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

Physicians’ Professionally Responsible Power: A Core Concept of Clinical Ethics

Science.gov (United States)

McCullough, Laurence B.

2016-01-01

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

Placebo response in binge eating disorder: a pooled analysis of 10 clinical trials from one research group.

Science.gov (United States)

Blom, Thomas J; Mingione, Carolyn J; Guerdjikova, Anna I; Keck, Paul E; Welge, Jeffrey A; McElroy, Susan L

2014-03-01

The aim of this study was to gain further understanding of placebo response in binge eating disorder. We pooled participant-level data from 10 double-blind, placebo-controlled, randomized trials of medications for binge eating disorder. The primary outcomes were response (75% reduction in binge eating episodes), cessation of binge eating episodes, change in mean weekly binge eating episodes and binge eating episodes per week. Of 234 participants receiving placebo, 89 (38%) were responders and 59 (26%) attained cessation. Placebo-treated participants significantly reduced their binge eating. The mean (SD) binge eating episodes per week at baseline was 5.2 (3.2) and at endpoint was 2.2 (2.6). Lower baseline binge eating episode frequency and longer study participation were significantly associated with response and cessation. Less severe eating pathology at baseline was associated with higher placebo response and cessation rates. Future clinical trials may want to stipulate that participants exceed a threshold of illness severity, which may lead to better placebo and drug separation. Copyright © 2014 John Wiley & Sons, Ltd and Eating Disorders Association.

Clinical, Radiologic, and Legal Significance of "Extensor Response" in Posttraumatic Coma.

Science.gov (United States)

Firsching, Raimund; Woischneck, Dieter; Langejürgen, Alexander; Parreidt, Andreas; Bondar, Imre; Skalej, Martin; Röhl, Friedrich; Voellger, Benjamin

2015-11-01

The timely detection of neurologic deterioration can be critical for the survival of a neurosurgical patient following head injury. Because little reliable evidence is available on the prognostic value of the clinical sign "extensor response" in comatose posttraumatic patients, we investigated the correlation of this clinical sign with outcome and with early radiologic findings from magnetic resonance imaging (MRI). This retrospective analysis of prospectively obtained data included 157 patients who had remained in a coma for a minimum of 24 hours after traumatic brain injury. All patients received a 1.5-T MRI within 10 days (median: 2 days) of the injury. The correlations between clinical findings 12 and 24 hours after the injury-in particular, extensor response and pupillary function, MRI findings, and outcome after 1 year-were investigated. Statistical analysis included contingency tables, Fisher exact test, odds ratios (ORs) with confidence intervals (CIs), and weighted κ values. There were 48 patients with extensor response within the first 24 hours after the injury. Patients with extensor response (World Federation of Neurosurgical Societies coma grade III) statistically were significantly more likely to harbor MRI lesions in the brainstem when compared with patients in a coma who had no further deficiencies (coma grade I; p = 0.0004 by Fisher exact test, OR 10.8 with 95% CI, 2.7-42.5) and patients with unilateral loss of pupil function (coma grade II; p = 0.0187, OR 2.8 with 95% CI, 1.2-6.5). The correlation of brainstem lesions as found by MRI and outcome according to the Glasgow Outcome Scale after 1 year was also highly significant (p ≤ 0.016). The correlation of extensor response and loss of pupil function with an unfavorable outcome and with brainstem lesions revealed by MRI is highly significant. Their sudden onset may be associated with the sudden onset of brainstem dysfunction and should therefore be regarded as one of the most

Clinical predictors of acute response to transcranial direct current stimulation (tDCS) in major depression.

Science.gov (United States)

D'Urso, Giordano; Dell'Osso, Bernardo; Rossi, Rodolfo; Brunoni, Andre Russowsky; Bortolomasi, Marco; Ferrucci, Roberta; Priori, Alberto; de Bartolomeis, Andrea; Altamura, Alfredo Carlo

2017-09-01

Transcranial direct current stimulation (tDCS) is a promising neuromodulation intervention for poor-responding or refractory depressed patients. However, little is known about predictors of response to this therapy. The present study aimed to analyze clinical predictors of response to tDCS in depressed patients. Clinical data from 3 independent tDCS trials on 171 depressed patients (including unipolar and bipolar depression), were pooled and analyzed to assess predictors of response. Depression severity and the underlying clinical dimensions were measured using the Hamilton Depression Rating Scale (HDRS) at baseline and after the tDCS treatment. Age, gender and diagnosis (bipolar/unipolar depression) were also investigated as predictors of response. Linear mixed models were fitted in order to ascertain which HDRS factors were associated with response to tDCS. Age, gender and diagnosis did not show any association with response to treatment. The reduction in HDRS scores after tDCS was strongly associated with the baseline values of "Cognitive Disturbances" and "Retardation" factors, whilst the "Anxiety/Somatization" factor showed a mild association with the response. Open-label design, the lack of control group, and minor differences in stimulation protocols. No differences in response to tDCS were found between unipolar and bipolar patients, suggesting that tDCS is effective for both conditions. "Cognitive disturbance", "Retardation", and "Anxiety/Somatization", were identified as potential clinical predictors of response to tDCS. These findings point to the pre-selection of the potential responders to tDCS, therefore optimizing the clinical use of this technique and the overall cost-effectiveness of the psychiatric intervention for depressed patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Does a family history of RA influence the clinical presentation and treatment response in RA?

Science.gov (United States)

Frisell, Thomas; Saevarsdottir, Saedis; Askling, Johan

2016-06-01

To assess whether family history of rheumatoid arthritis (RA), among the strongest risk factors for developing RA, also carries information on the clinical presentation and treatment response. The prospective Swedish Rheumatology register was linked to family history of RA, defined as diagnosed RA in any first-degree relative, ascertained through the Swedish Multi-Generation and Patient registers. Clinical presentation was examined among patients with early RA 2000-2011 (symptom onset clinical characteristics, drug survival, European League Against Rheumatism (EULAR) response and change in disease activity at 3 and 6 months was estimated using linear and generalised logistic regression models. Correlation in relatives' response measures was also assessed. Patients with early RA with family history of RA were more often rheumatoid factor positive, but with no other clinically meaningful differences in their clinical presentation. Family history of RA did not predict response to MTX or TNFi, with the possible exception of no versus good EULAR response to TNFi at 6 months (OR=1.4, 95% CI 1.1 to 1.7). Having a relative who discontinued TNFi within a year increased the odds of doing the same (OR=3.7, 95% CI 1.8 to 7.5), although we found no significant familial correlations in change in disease activity measures. Family history of RA did not modify the clinical presentation of RA or predict response to standard treatment with MTX or TNFi. Treatment response, particularly drug survival, may itself be familial. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Association between frequent cardiac resynchronization therapy optimization and long-term clinical response: a post hoc analysis of the Clinical Evaluation on Advanced Resynchronization (CLEAR) pilot study

Science.gov (United States)

Delnoy, Peter Paul; Ritter, Philippe; Naegele, Herbert; Orazi, Serafino; Szwed, Hanna; Zupan, Igor; Goscinska-Bis, Kinga; Anselme, Frederic; Martino, Maria; Padeletti, Luigi

2013-01-01

Aims The long-term clinical value of the optimization of atrioventricular (AVD) and interventricular (VVD) delays in cardiac resynchronization therapy (CRT) remains controversial. We studied retrospectively the association between the frequency of AVD and VVD optimization and 1-year clinical outcomes in the 199 CRT patients who completed the Clinical Evaluation on Advanced Resynchronization study. Methods and results From the 199 patients assigned to CRT-pacemaker (CRT-P) (New York Heart Association, NYHA, class III/IV, left ventricular ejection fraction failure-related hospitalization, NYHA functional class, and Quality of Life score, at 1 year. Systematic CRT optimization was associated with a higher percentage of improved patients based on the composite endpoint (85% in Group 1 vs. 61% in Group 2, P < 0.001), with fewer deaths (3% in Group 1 vs. 14% in Group 2, P = 0.014) and fewer hospitalizations (8% in Group 1 vs. 23% in Group 2, P = 0.007), at 1 year. Conclusion These results further suggest that AVD and VVD frequent optimization (at implant, at 3 and 6 months) is associated with improved long-term clinical response in CRT-P patients. PMID:23493410

Immunologic and clinical responses to "Monday morning miseries" antigens.

Science.gov (United States)

Cernelc, S; Stropnik, Z

1987-01-01

Authors analysed 96 workers exposed to air conditioning system (Group A), and 71 workers (Group B) breathing normal ambient air. 38 workers in group A had a positive clinical history of "Monday morning miseries". Eight cases with the diagnosis hypersensitivity pneumonitis, acute and chronic form was based on environmental history, clinical investigations, physical examination, Chest-X-ray examination, immunological test "in vivo" and "in vitro" with common allergens and antigen "Monday morning miseries", ELISA, spirometry and PEFR (Peak Expiratory Flow-Rate) measurements. Exposure to contaminated air may be responsible for morbidity and reduced performance of workers.

Seronegative and seropositive autoimmune autonomic ganglionopathy (AAG): Same clinical picture, same response to immunotherapy.

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Tijero, Beatriz; Del Pino, Rocio; Pérez-Concha, Tomás; Acera, Maria Angeles; Gabilondo, Iñigo; Berganzo, Koldo; Graus, Frances; Martinez-Alday, Jesus Daniel; Barcena, Joseba; Gómez-Esteban, Juan Carlos

2018-06-15

Two patients with a syndrome of pandisautonomia with clinical criteria of AAG are provided. Both patients present a similar clinical picture and response to immunosuppressive treatment. One of them has positive antibodies against the ganglionic nicotinic acetylcholine (gAChr) and the other does not. This brief article serves to reflect the spectrum of AAG, at a clinical level, in laboratory tests and in the response to immunotherapy, independently of the presence of positive gAChr antibodies. Copyright © 2018 Elsevier B.V. All rights reserved.

Determinants of Diuretic Responsiveness and Associated Outcomes During Acute Heart Failure Hospitalization: An Analysis From the NHLBI Heart Failure Network Clinical Trials.

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Kiernan, Michael S; Stevens, Susanna R; Tang, W H Wilson; Butler, Javed; Anstrom, Kevin J; Birati, Edo Y; Grodin, Justin L; Gupta, Divya; Margulies, Kenneth B; LaRue, Shane; Dávila-Román, Victor G; Hernandez, Adrian F; de Las Fuentes, Lisa

2018-03-01

Poor response to loop diuretic therapy is a marker of risk during heart failure hospitalization. We sought to describe baseline determinants of diuretic response and to further explore the relationship between this response and clinical outcomes. Patient data from the National Heart, Lung, and Blood Institute Heart Failure Network ROSE-AHF and CARRESS-HF clinical trials were analyzed to determine baseline determinants of diuretic response. Diuretic efficiency (DE) was defined as total 72-hour fluid output per total equivalent loop diuretic dose. Data from DOSE-AHF was then used to determine if these predictors of DE correlated with response to a high- versus low-dose diuretic strategy. At 72 hours, the high-DE group had median fluid output of 9071 ml (interquartile range: 7240-11775) with median furosemide dose of 320 mg (220-480) compared with 8030 ml (6300-9915) and 840 mg (600-1215) respectively for the low DE group. Cystatin C was independently associated with DE (odds ratio 0.36 per 1mg/L increase; 95% confidence interval: 0.24-0.56; P failure hospitalization. Higher loop diuretic doses are required for therapeutic decongestion in patients with renal insufficiency. Poor response identifies a high-risk population. Copyright © 2018 Elsevier Inc. All rights reserved.

CCR 20th Anniversary Commentary: Immune-Related Response Criteria--Capturing Clinical Activity in Immuno-Oncology.

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Hoos, Axel; Wolchok, Jedd D; Humphrey, Rachel W; Hodi, F Stephen

2015-11-15

To evaluate antitumor responses to chemotherapeutic agents, investigators would typically rely upon Response Evaluation Criteria in Solid Tumors (RECIST) or modified WHO criteria, which do not comprehensively capture responses with immunotherapeutic agents. In the December 1, 2009, issue of Clinical Cancer Research, Wolchok and colleagues reported their development of novel criteria, designated "Immune-related Response Criteria" (irRC), designed to better capture the response patterns observed with immunotherapies. Broad use of the irRC since then has allowed for a more comprehensive evaluation of immunotherapies in clinical trials, indicating that their concepts can be used in conjunction with either RECIST or WHO, and has shown irRC to be a powerful tool for improved clinical investigation. See related article by Wolchok et al., Clin Cancer Res 2009;15(23) December 1, 2009;7412-20. ©2015 American Association for Cancer Research.

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

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Sousa Rejane

2012-05-01

Full Text Available Abstract 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 p p p  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.

A novel approach to measuring response and remission in schizophrenia in clinical trials.

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Aboraya, Ahmed; Leucht, Stefan; Nasrallah, Henry A; Samara, Myrto; Haro, Josep Maria; Elshazly, Ahmed; Zangeneh, Masood

2017-12-01

Pharmaceutical companies conduct clinical trials to show the efficacy and safety of new medications for the treatment of schizophrenia. After the new medications are marketed, clinicians treating patients with schizophrenia discover that a considerable number of patients do not respond to these new medications. The goals of the review are to examine the methodology and design of recent antipsychotic clinical trials, identify common flaws, and propose guidelines to fix the flaws and improve the quality of future clinical trials of antipsychotic medications. A review of recent antipsychotic clinical trials was conducted using a PubMed search. Ten recent trials published in the past four years were reviewed and their methods analyzed and critiqued. The authors identified six major methodological flaws that may explain the suboptimal response in many patients after a drug is approved. Most of the flaws are related to eligibility criteria, the misuse of the Positive and Negative Syndromes Scale (PANSS) and the lack of consensus on how to define remission, response and exacerbation in schizophrenia. Proposed guidelines for a more rigorous use of the PANSS are presented and recommendations are proposed for using uniform criteria for remission, response and exacerbation in schizophrenia. The authors recommend using standardized diagnostic interviews to screen patients for eligibility criteria and using the PANSS according to the author's recommendations and the proposed guidelines. Uniform criteria to define remission, response and exacerbation are recommended for clinical trials examining the efficacy and safety of antipsychotic drugs in schizophrenia. Copyright © 2017 Elsevier B.V. All rights reserved.

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

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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. © The Author 2015. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Higher hydrocortisone dose increases bilirubin in hypopituitary patients- results from an RCT.

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Werumeus Buning, Jorien; Kootstra-Ros, Jenny E; Brummelman, Pauline; van den Berg, Gerrit; van der Klauw, Melanie; Wolffenbuttel, Bruce H R; van Beek, André P; Dullaart, Robin P F

2016-05-01

Bilirubin has anti-oxidative and anti-inflammatory properties, which may explain its proposed protective effects on the development of cardiometabolic disorders. Glucocorticoids affect heme oxygenase regulation in vitro, which plays a key role in bilirubin production. Effects of variations in glucocorticoid exposure on circulating bilirubin levels in humans are unknown. Here we tested whether a higher hydrocortisone replacement dose affects circulating bilirubin in hypopituitary patients. A randomized double-blind cross-over study (ClinicalTrials.gov, number NCT01546992) was performed in 47 patients with secondary adrenal failure [10-week exposure to a higher hydrocortisone dose (0·4-0·6 mg/kg body weight) vs. 10 weeks of a lower hydrocortisone dose (0·2-0·3 mg/kg body weight)]. Plasma total bilirubin was increased by 10% from 7 to 8 μM in response to the higher hydrocortisone dose (P = 0·033). This effect was inversely related to age (P = 0·042), but was unaffected by sex, obesity and (replacement for) other hormonal insufficiencies. The higher hydrocortisone dose also resulted in lower alkaline phosphatase (P = 0·006) and aspartate aminotransferase activities (P = 0·001). Bilirubin is modestly increased in response to higher glucocorticoid exposure in humans, in conjunction with lower alkaline phosphatase and aspartate aminotransferase activities, which are supposed to represent biomarkers of a pro-inflammatory state and enhanced liver fat accumulation. © 2016 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.

Rational Design Approach for Enhancing Higher-Mode Response of a Microcantilever in Vibro-Impacting Mode

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Ieva Migliniene

2017-12-01

Full Text Available This paper proposes an approach for designing an efficient vibration energy harvester based on a vibro-impacting piezoelectric microcantilever with a geometric shape that has been rationally modified in accordance with results of dynamic optimization. The design goal is to increase the amplitudes of higher-order vibration modes induced during the vibro-impact response of the piezoelectric transducer, thereby providing a means to improve the energy conversion efficiency and power output. A rational configuration of the energy harvester is proposed and it is demonstrated that the new design retains essential modal characteristics of the optimal microcantilever structures, further providing the added benefit of less costly fabrication. The effects of structural dynamics associated with advantageous exploitation of higher vibration modes are analyzed experimentally by means of laser vibrometry as well as numerically via transient simulations of microcantilever response to random excitation. Electrical characterization results indicate that the proposed harvester outperforms its conventional counterpart (based on the microcantilever of the constant cross-section in terms of generated electrical output. Reported results may serve for the development of impact-type micropower generators with harvesting performance that is enhanced by virtue of self-excitation of large intensity higher-order mode responses when the piezoelectric transducer is subjected to relatively low-frequency excitation with strongly variable vibration magnitudes.

Effect of higher muscle coactivation on standing postural response to perturbation in older adults.

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Nagai, Koutatsu; Okita, Yusuke; Ogaya, Shinya; Tsuboyama, Tadao

2017-04-01

Although several studies have reported that muscle coactivation during postural control increases with age, the effect of higher muscle coactivation on standing postural response to perturbation is unknown. To investigate whether higher muscle coactivation affects standing postural response to perturbation in older adults. Thirty-four community-dwelling older participants were randomly assigned either to the coactivation group (CG), where muscle coactivation was increased intentionally, or to the non-coactivation group (NCG). The participants were instructed to stand on a force plate that moved forward or backward. Electromyography data were collected from the lower leg muscles. We requested the participants in the CG to increase the activity of their tibialis anterior, and to maintain this posture during the tasks. We moved the force plate with a constant amplitude and velocity, and measured kinematic data with a camera during the tasks. During forward transfer, the knee extension and hip flexion decreased in the CG after perturbation compared to NCG, and the trunk extension angle increased. The center of pressure (COP) displacement decreased around the peak of the movement in the CG compared to NCG. During backward transfer, ankle dorsal and knee flexion changed after perturbation in the CG compared to NCG. Our study found that higher muscle coactivation inhibits lower limb and COP movement as well as increases trunk tilt and the risk for falls during forward perturbations. Postural control with higher coactivation appears to be inefficient for maintaining balance during the backward sway of posture.

RBE and clinical response in radiotherapy with neutron beams

International Nuclear Information System (INIS)

Ellis, F.

1984-01-01

Consideration of the clinical results reported, when a cyclotron produced neutron beam was used for treatments in the pelvis region, suggested that a constant RBE of 3 should not have been used for all neutron doses. Instead a variable RBE, which increased from approximately 3 to 8 (with decreasing dose), should have been used. Although some of these RBE values are much higher than 3, they have been observed in clinical practice. An ''equivalent photon'' isodose plan was produced by employing a variable RBE and, by taking a TDF limit of 86 for bowel, an isoeffect plan was produced. This shows that in the clinical situation under consideration much of the pelvis was overdosed. Doses to tumour cells and late effects are also briefly considered. It is suggested that, in neutron therapy, both an ''equivalent photon'' isodose plan and an isoeffect plan should be produced prior to treatment. (author)

Immunological, clinical, haematological and oxidative responses to long distance transportation in horses.

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Padalino, Barbara; Raidal, Sharanne Lee; Carter, Nicole; Celi, Pietro; Muscatello, Gary; Jeffcott, Leo; de Silva, Kumudika

2017-12-01

Horses are transported frequently and often over long distances. Transportation may represent a physiological stressor with consequential health and welfare implications. This study reports the effects of a long distance journey on immunological, clinical, haematological, inflammatory and oxidative parameters in an Experimental Group (EG) of ten horses, comparing them with six horses of similar age and breed used as a non-transported Control Group (CG). Clinical examination and blood sampling were performed twice on all horses: immediately after unloading for the EG, and at rest on the same day for the CG (day 1); at rest on the same day one week later for both groups (day 7). On day 1 EG horses showed increased heart and respiratory rates (Ptransportation induced an acute phase response impairing the cell-mediated immune response. Clinical examinations, including assessing CRT and body weight loss, and the monitoring of redox balance may be useful in evaluating the impact of extensive transport events on horses. A better understanding of the link between transportation stress, the immune system and the acute phase response is likely to inform strategies for enhancing the welfare of transported horses. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of response format for clinical vignettes on reporting quality of physician practice

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Durieux Pierre

2009-07-01

Full Text Available Abstract Background Clinical vignettes have been used widely to compare quality of clinical care and to assess variation in practice, but the effect of different response formats has not been extensively evaluated. Our objective was to compare three clinical vignette-based survey response formats – open-ended questionnaire (A, closed-ended (multiple-choice questionnaire with deceptive response items mixed with correct items (B, and closed-ended questionnaire with only correct items (C – in rheumatologists' pre-treatment assessment for tumor-necrosis-factor (TNF blocker therapy. Methods Study design: Prospective randomized study. Setting: Rheumatologists attending the 2004 French Society of Rheumatology meeting. Physicians were given a vignette describing the history of a fictitious woman with active rheumatoid arthritis, who was a candidate for therapy with TNF blocking agents, and then were randomized to receive questionnaire A, B, or C, each containing the same four questions but with different response formats, that asked about their pretreatment assessment. Measurements: Long (recommended items and short (mandatory items checklists were developed for pretreatment assessment for TNF-blocker therapy, and scores were expressed on the basis of responses to questionnaires A, B, and C as the percentage of respondents correctly choosing explicit items on these checklists. Statistical analysis: Comparison of the selected items using pairwise Chi-square tests with Bonferonni correction for variables with statistically significant differences. Results Data for all surveys distributed (114 As, 118 Bs, and 118 Cs were complete and available for analysis. The percentage of questionnaire A, B, and C respondents for whom data was correctly complete for the short checklist was 50.4%, 84.0% and 95.0%, respectively, and was 0%, 5.0% and 5.9%, respectively, for the long version. As an example, 65.8%, 85.7% and 95.8% of the respondents of A, B, and C

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

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

2016-07-07

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. © 2016 by The American Society of Hematology.

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

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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.

SU-E-T-256: Radiation Dose Responses for Chemoradiation Therapy of Pancreatic Cancer: An Analysis of Compiled Clinical Data Using Biophysical Models.

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Moraru, I; Tai, A; Erickson, B; Li, X

2012-06-01

We have analyzed recent clinical data obtained from chemoradiation of unresectable, locally advanced pancreatic cancer in order to examine possible benefits from radiotherapy (RT) dose escalation as well as to propose possible dose escalated fractionation schemes. A modified linear quadratic (LQ) model was used to fit clinical tumor response data from chemoradiation treatments using different fractionations. Biophysical radiosensitivy parameters, a and α/β, tumor potential doubling time, Td, and delay time for tumor doubling during treatment, Tk, were extracted from the fits and were used to calculate feasible fractionation schemes for dose escalations. Examination of published data from 20 institutions showed no clear indication of improved survival with raised radiation dose. However, an enhancement in tumor response was observed for higher irradiation doses, an important and promising clinical Result with respect to palliation and quality of life. The radiobiological parameter estimates obtained from the analysis are: α/β = 10 ± 3 Gy, a = 0.010 ± 0.003 Gŷ-1, Td = 56 ± 5 days and Tk = 7 ± 2 days. Possible dose escalation schemes are proposed based on the calculation of the biologically equivalent dose (BED) required for a 50% tumor response rate. From the point of view of tumor response, escalation of the administered radiation dose leads to a potential clinical benefit, which when combined with normal tissue complication analyses may Result in improved treatments for certain patients with advanced pancreatic cancer. Based on this analysis, a dose escalation trial with 2.25 Gy/fraction up to 69.75 Gy is being initiated for unresectable pancreatic cancer at our institution. Partially supported by MCW Cancer Center Meinerz Foundation. © 2012 American Association of Physicists in Medicine.

Clinical and radiological characteristics of central pulmonary adenocarcinoma: a comparison with central squamous cell carcinoma and small cell lung cancer and the impact on treatment response

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Wang Z

2018-05-01

Full Text Available Zhe Wang,1,2 Minghuan Li,2 Yong Huang,3 Li Ma,3 Hui Zhu,2 Li Kong,2 Jinming Yu2 1School of Medicine, Shandong University, Jinan, Shandong, China; 2Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, Shandong, China; 3Department of Radiology, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, Shandong, China Purpose: The proportion of central pulmonary adenocarcinoma (ADC in central-type lung cancer has been gradually increasing due to the overall increasing incidence of pulmonary ADC. But the clinical and radiological characteristics of central ADCs remain unclear. In this study, we compared the clinical and radiological characteristics of central ADCs with those of small cell lung cancers (SCLCs and squamous cell carcinomas (SQCCs and investigated the impact of these characteristics on patients’ treatment response. Patients and methods: The medical records of 302 consecutive patients with central lung cancer from July 2014 to September 2016 were retrospectively reviewed. There were 99 patients with ADC, 95 with SQCC and 108 with SCLC. Computed tomography images were interpreted by two radiologists. Treatment response was determined by Response Evaluation Criteria In Solid Tumors 1.1. Results: Univariate analyses found that younger age, female sex, no history of smoking, higher levels of carcinoembryonic antigen (CEA, contralateral hilum lymphadenopathy, contralateral lung metastasis, pleural nodules and pleural metastasis to the interlobular fissure were significantly correlated with central ADC. Multivariate logistic regression analyses revealed that compared with central SQCC, female sex, younger age, no history of smoking, higher levels of CEA and contralateral hilum lymphadenopathy were the significantly independent indicators of central pulmonary ADC. Furthermore, compared with central SCLC, younger age, higher levels of CEA and cytokeratin 19 fragment (Cyfra21-1, lower

Study on Professors’ Perception With Respect to Higher Education Institutions’ Socially Responsible Initiatives

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Adriano Stadler

2017-01-01

Full Text Available The organization’s socially responsible actions integration and stakeholders’ demands is an increasingly encouraged practice by the market (Calabrese, Costa & Rosati, 2016. This article looks at the perception that the professor holds on the Higher Education Institution’s (HEI socially responsible initiatives. Thus, a descriptive quantitative approach with non-probabilistic sample, accessibility and convenience was developed. The literature outlined the corporate social responsibility’s (CSR main concepts, theories applications and stakeholders. Empirical research collected data from the HEI’s professors, through closed questionnaires. Descriptive analysis and multivariate statistics (cluster and factorial analysis provided empirical evidence to the research. Results show the high concordance of professors in relation to the analysis categories: Economic, Legal, Ethical and Philanthropic, all of which are considered in this study, according to Carroll (2011. The sharpest legal dimension is given to the professors’ perception. Philanthropic responsibility showed the lowest agreement, coming out to the Carroll (2011 studies, which have supported this work.

Clinical utility of pretreatment prediction of chemoradiotherapy response in rectal cancer: a review.

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Yoo, Byong Chul; Yeo, Seung-Gu

2017-03-01

Approximately 20% of all patients with locally advanced rectal cancer experience pathologically complete responses following neoadjuvant chemoradiotherapy (CRT) and standard surgery. The utility of radical surgery for patients exhibiting good CRT responses has been challenged. Organ-sparing strategies for selected patients exhibiting complete clinical responses include local excision or no immediate surgery. The subjects of this tailored management are patients whose presenting disease corresponds to current indications of neoadjuvant CRT, and their post-CRT tumor response is assessed by clinical and radiological examinations. However, a model predictive of the CRT response, applied before any treatment commenced, would be valuable to facilitate such a personalized approach. This would increase organ preservation, particularly in patients for whom upfront CRT is not generally prescribed. Molecular biomarkers hold the greatest promise for development of a pretreatment predictive model of CRT response. A combination of clinicopathological, radiological, and molecular markers will be necessary to render the model robust. Molecular research will also contribute to the development of drugs that can overcome the radioresistance of rectal tumors. Current treatments for rectal cancer are based on the expected prognosis given the presenting disease extent. In the future, treatment schemes may be modified by including the predicted CRT response evaluated at presentation.

The new criteria of clinical response for the primary tumor based on the findings of histological response after chemoradiation therapy in esophageal cancer

International Nuclear Information System (INIS)

Okumura, Hiroshi; Natsugoe, Shoji; Yokomakura, Naoya; Matsumoto, Masataka; Aikou, Takashi

2005-01-01

The incidence of chemoradiation therapy (CRT) increased in order to improve the surgical resectabilty and clinical outcome. It is important to accurately assess the effect of CRT for selecting further treatment and predicting prognosis. We tried to make the new criteria for imaging diagnosis after we reevaluated the discrepancy between clinical and histological effect of CRT. Subjects were 36 patients with advanced esophageal cancer who underwent esophagectomy with lymphadenectomy after CRT that consisted of 5-fluorouracil plus cisplatin and 40 Gy of radiation. The clinical and histological response was firstly evaluated based on esophageal disease guidelines for clinical and pathologic studies on carcinoma of the esophagus by the Japanese Society of Clinical response in imaging was reassessed based on the histological response. The number of tumors judged as clinical complete response/partial response/no change (CR/PR/NC) was 0/26/10, and the histological grading 1/2/3 was 17/11/8, respectively. Imaging for Grade 1 tumors showed the existence of viable cancer cells in biopsy specimen. Of 16 patients with such finding, 14 (88%) were histologically judged as Grade 1. Imaging characteristics for grade 3 tumors was more than a 75% reduction in esophagography, and the existence of scar formation by esophagoscopy. All five (100%) patients with these findings were histologically judged as Grade 3. The findings of grade 1 and 3 based on new criteria were independent predictive factors for CRT effect. According to new criteria, it was possible to predict the histological effect by the combination of esophagography and endoscopy in more than 80% of patients after CRT. Our new criteria may offer important information on the selection of further treatment or the prediction of prognosis after CRT in patients with esophageal cancer. (author)

Genetic and clinical predictors of ovarian response in assisted reproductive technology

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Wiweko, B.; Damayanti, I.; Suryandari, D.; Natadisastra, M.; Pratama, G.; Sumapraja, K.; Meutia, K.; Iffanolia, P.; Harzief, A. K.; Hestiantoro, A.

2017-08-01

Several factors are known to influence ovarian response to rFSH stimulation such as age, antral follicle count (AFC), and basal FSH level, Mutation of allele Ser680Asn in FSHR gene was responsible to ovarian resistance toward exogenous FSH. The aim of this study is to develop a prediction model of ovarian response to COS in IVF. This study was a prospective cohort study. One hundred and thirteen women undergoing their first cycle of IVF in Yasmin IVF Clinic Jakarta were recruited to this study. Clinical datas included were age, BMI, and AFC. Basal FSH and E2 as well as serum AMH was measured from peripheral blood taken at second day of cycle. Bsr-1 enzyme is used to identify the polymorphism in exon 10 position 680 with RFLP technique. Three genotype polymorphism, Asn/Asn (255 bp ribbon), Asn/Ser (97 bp and 158 bp), and Ser/Ser (97 bp, 158 bp, and 255 bp). AFC has the highest predictor for ovarian response with AUC 0.922 (CI 95% 0.833-1.000). AMH also showed high predicting value (AUC 0.843 CI 95% 0.663-1.000). The multivariate analysis revealed combination of AFC, AMH, age, and basal FSH is a good model for ovarian response prediction (AUC=0.97). No significant relation between Asn/Asn, Asn/Ser, or Ser/Ser genotype FSHR polymorphism with ovarian response (p = 0.866) and total dose of rRSH (p = 0.08). This study showed that model combination of AFC, AMH, patient’s age and basal FSH are very good to predict number of mature oocytes.

Interactive Voice/Web Response System in clinical research.

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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.

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

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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 HbA 1C 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 (HbA 1C >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.

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

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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

Human In Silico Drug Trials Demonstrate Higher Accuracy than Animal Models in Predicting Clinical Pro-Arrhythmic Cardiotoxicity.

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Passini, Elisa; Britton, Oliver J; Lu, Hua Rong; Rohrbacher, Jutta; Hermans, An N; Gallacher, David J; Greig, Robert J H; Bueno-Orovio, Alfonso; Rodriguez, Blanca

2017-01-01

Early prediction of cardiotoxicity is critical for drug development. Current animal models raise ethical and translational questions, and have limited accuracy in clinical risk prediction. Human-based computer models constitute a fast, cheap and potentially effective alternative to experimental assays, also facilitating translation to human. Key challenges include consideration of inter-cellular variability in drug responses and integration of computational and experimental methods in safety pharmacology. Our aim is to evaluate the ability of in silico drug trials in populations of human action potential (AP) models to predict clinical risk of drug-induced arrhythmias based on ion channel information, and to compare simulation results against experimental assays commonly used for drug testing. A control population of 1,213 human ventricular AP models in agreement with experimental recordings was constructed. In silico drug trials were performed for 62 reference compounds at multiple concentrations, using pore-block drug models (IC 50 /Hill coefficient). Drug-induced changes in AP biomarkers were quantified, together with occurrence of repolarization/depolarization abnormalities. Simulation results were used to predict clinical risk based on reports of Torsade de Pointes arrhythmias, and further evaluated in a subset of compounds through comparison with electrocardiograms from rabbit wedge preparations and Ca 2+ -transient recordings in human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs). Drug-induced changes in silico vary in magnitude depending on the specific ionic profile of each model in the population, thus allowing to identify cell sub-populations at higher risk of developing abnormal AP phenotypes. Models with low repolarization reserve (increased Ca 2+ /late Na + currents and Na + /Ca 2+ -exchanger, reduced Na + /K + -pump) are highly vulnerable to drug-induced repolarization abnormalities, while those with reduced inward current density

Human In Silico Drug Trials Demonstrate Higher Accuracy than Animal Models in Predicting Clinical Pro-Arrhythmic Cardiotoxicity

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Elisa Passini

2017-09-01

Full Text Available Early prediction of cardiotoxicity is critical for drug development. Current animal models raise ethical and translational questions, and have limited accuracy in clinical risk prediction. Human-based computer models constitute a fast, cheap and potentially effective alternative to experimental assays, also facilitating translation to human. Key challenges include consideration of inter-cellular variability in drug responses and integration of computational and experimental methods in safety pharmacology. Our aim is to evaluate the ability of in silico drug trials in populations of human action potential (AP models to predict clinical risk of drug-induced arrhythmias based on ion channel information, and to compare simulation results against experimental assays commonly used for drug testing. A control population of 1,213 human ventricular AP models in agreement with experimental recordings was constructed. In silico drug trials were performed for 62 reference compounds at multiple concentrations, using pore-block drug models (IC50/Hill coefficient. Drug-induced changes in AP biomarkers were quantified, together with occurrence of repolarization/depolarization abnormalities. Simulation results were used to predict clinical risk based on reports of Torsade de Pointes arrhythmias, and further evaluated in a subset of compounds through comparison with electrocardiograms from rabbit wedge preparations and Ca2+-transient recordings in human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs. Drug-induced changes in silico vary in magnitude depending on the specific ionic profile of each model in the population, thus allowing to identify cell sub-populations at higher risk of developing abnormal AP phenotypes. Models with low repolarization reserve (increased Ca2+/late Na+ currents and Na+/Ca2+-exchanger, reduced Na+/K+-pump are highly vulnerable to drug-induced repolarization abnormalities, while those with reduced inward current density

Clinical Manifestations of an Anti-Drug Antibody Response: Autoimmune Reactions.

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Swanson, Steven J

2014-12-01

Antibodies can be generated against a therapeutic protein upon administration to human subjects. When the therapeutic protein closely mimics one of the subject's endogenous proteins, those antibodies might bind to the endogenous protein in addition to the therapeutic protein. This scenario results when tolerance to the endogenous protein is broken. The consequences of breaking tolerance include an autoimmune response where antibodies are generated against the endogenous protein. These autoantibodies could have significant clinical relevance depending on several factors, including the redundancy of action of the endogenous protein as well as the concentration, binding affinity, and neutralizing potential of the antibodies. The consequences of a therapeutic-protein-induced autoimmune reaction can be challenging to manage as the stimulus for further perpetuation of the immune response can shift from the therapeutic protein to the endogenous protein. The potential for inducing an autoimmune response is one of the reasons that the immune response to a therapeutic protein should be monitored if it persists through the end of the study.

Long-term clinical outcome of human immunodeficiency virus-infected patients with discordant immunologic and virologic responses to a protease inhibitor-containing regimen.

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Piketty, C; Weiss, L; Thomas, F; Mohamed, A S; Belec, L; Kazatchkine, M D

2001-05-01

Within a prospective cohort of 150 human immunodeficiency virus (HIV)-infected patients who began first-line protease inhibitor therapy in 1996, the outcome of 42 patients with discrepant virologic and immunologic responses to antiretroviral treatment at 12 months was analyzed at 30 months of treatment. The incidence of AIDS-defining events and deaths (14%) in the group of patients with immunologic responses in the absence of a virologic response was higher than that in full-responder patients (2%); yet, the incidence in this group was lower than that in patients with no immunologic response, despite a virologic response (21%), and was lower than that in patients without an immunologic or virologic response (67%; P<.0001, log-rank test). Differences in outcome were significant (relative risk, 6.9; 95% confidence interval, 1.9-39.3) when factors for progression were compared with those of responder patients. The results support the relevance of the CD4 cell marker over plasma HIV load for predicting clinical outcome in patients who do not achieve full immunologic and virologic responses.

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

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Casimiro de Deus Cardoso, Cejana; Giordani, Adelmo Jose [Department of Clinical and Experimental Oncology, Division of Radiotherapy, Federal University of Sao Paulo, Sao Paulo, SP (Brazil); Borri Wolosker, Angela Maria [Department of Radiology, Federal University of Sao Paulo, Sao Paulo, SP (Brazil); Souhami, Luis [Department of Radiotherapy, McGill University Heath Centre, Montreal, Quebec (Canada); Gois Manso, Paulo [Department of Ophthalmology, Federal University of Sao Paulo, Sao Paulo, SP (Brazil); Souza Dias, Rodrigo; Comodo Segreto, Helena Regina [Department of Clinical and Experimental Oncology, Division of Radiotherapy, Federal University of Sao Paulo, Sao Paulo, SP (Brazil); Araujo Segreto, Roberto, E-mail: segreto.dmed@epm.br [Department of Clinical and Experimental Oncology, Division of Radiotherapy, Federal University of Sao Paulo, Sao Paulo, SP (Brazil)

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.

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

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Wieser Martin

2012-05-01

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

Criteria for evaluating response and outcome in clinical trials for children with juvenile myelomonocytic leukemia.

LENUS (Irish Health Repository)

Niemeyer, Charlotte M

2015-01-01

Juvenile myelomonocytic leukemia is a rare myeloproliferative disease in young children. While hematopoietic stem cell transplantation remains the only curative therapeutic option for most patients, children with juvenile myelomonocytic leukemia increasingly receive novel agents in phase I-II clinical trials as pre-transplant therapy or therapy for relapse after transplantation. However, response criteria or definitions of outcome for standardized evaluation of treatment effect in patients with juvenile myelomonocytic leukemia are currently lacking. Here we propose criteria to evaluate the response to the non-transplant therapy and definitions of remission status after hematopoietic stem cell transplantation. For the evaluation of non-transplant therapy, we defined 6 clinical variables (white blood cell count, platelet count, hematopoietic precursors and blasts in peripheral blood, bone marrow blast percentage, spleen size and extramedullary disease) and 3 genetic variables (cytogenetic, molecular and chimerism response) which serve to describe the heterogeneous picture of response to therapy in each individual case. It is hoped that these criteria will facilitate the comparison of results between clinical trials in juvenile myelomonocytic leukemia.

The influence of innate and adaptative immune responses on the differential clinical outcomes of leprosy.

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Fonseca, Adriana Barbosa de Lima; Simon, Marise do Vale; Cazzaniga, Rodrigo Anselmo; de Moura, Tatiana Rodrigues; de Almeida, Roque Pacheco; Duthie, Malcolm S; Reed, Steven G; de Jesus, Amelia Ribeiro

2017-02-06

Leprosy is a chronic infectious disease caused by Mycobacterium leprae. According to official reports from 121 countries across five WHO regions, there were 213 899 newly diagnosed cases in 2014. Although leprosy affects the skin and peripheral nerves, it can present across a spectrum of clinical and histopathological forms that are strongly influenced by the immune response of the infected individuals. These forms comprise the extremes of tuberculoid leprosy (TT), with a M. leprae-specific Th1, but also a Th17, response that limits M. leprae multiplication, through to lepromatous leprosy (LL), with M. leprae-specific Th2 and T regulatory responses that do not control M. leprae replication but rather allow bacterial dissemination. The interpolar borderline clinical forms present with similar, but less extreme, immune biases. Acute inflammatory episodes, known as leprosy reactions, are complications that may occur before, during or after treatment, and cause further neurological damages that can cause irreversible chronic disabilities. This review discusses the innate and adaptive immune responses, and their interactions, that are known to affect pathogenesis and influence the clinical outcome of leprosy.

Effects of a higher dose of near-infrared light on clinical signs and neuroprotection in a monkey model of Parkinson's disease.

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Moro, Cécile; El Massri, Nabil; Darlot, Fannie; Torres, Napoleon; Chabrol, Claude; Agay, Diane; Auboiroux, Vincent; Johnstone, Daniel M; Stone, Jonathan; Mitrofanis, John; Benabid, Alim-Louis

2016-10-01

We have reported previously that intracranial application of near-infrared light (NIr) - when delivered at the lower doses of 25J and 35J - reduces clinical signs and offers neuroprotection in a subacute MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) monkey model of Parkinson's disease. In this study, we explored whether a higher NIr dose (125J) generated beneficial effects in the same MPTP monkey model (n=15). We implanted an NIr (670nm) optical fibre device within a midline region of the midbrain in macaque monkeys, close to the substantia nigra of both sides. MPTP injections (1.8-2.1mg/kg) were made over a five day period, during which time the NIr device was turned on and left on continuously throughout the ensuing three week survival period. Monkeys were evaluated clinically and their brains processed for immunohistochemistry and stereology. Our results showed that the higher NIr dose did not have any toxic impact on cells at the midbrain implant site. Further, this NIr dose resulted in a higher number of nigral tyrosine hydroxylase immunoreactive cells when compared to the MPTP group. However, the higher NIr dose monkeys showed little evidence for an increase in mean clinical score, number of nigral Nissl-stained cells and density of striatal tyrosine hydroxylase terminations. In summary, the higher NIr dose of 125J was not as beneficial to MPTP-treated monkeys as compared to the lower doses of 25J and 35J, boding well for strategies of NIr dose delivery and device energy consumption in a future clinical trial. Copyright © 2016 Elsevier B.V. All rights reserved.

Clinical decision-making: midwifery students' recognition of, and response to, post partum haemorrhage in the simulation environment.

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Scholes, Julie; Endacott, Ruth; Biro, MaryAnne; Bulle, Bree; Cooper, Simon; Miles, Maureen; Gilmour, Carole; Buykx, Penny; Kinsman, Leigh; Boland, Rosemarie; Jones, Jan; Zaidi, Fawzia

2012-03-23

This paper reports the findings of a study of how midwifery students responded to a simulated post partum haemorrhage (PPH). Internationally, 25% of maternal deaths are attributed to severe haemorrhage. Although this figure is far higher in developing countries, the risk to maternal wellbeing and child health problem means that all midwives need to remain vigilant and respond appropriately to early signs of maternal deterioration. Simulation using a patient actress enabled the research team to investigate the way in which 35 midwifery students made decisions in a dynamic high fidelity PPH scenario. The actress wore a birthing suit that simulated blood loss and a flaccid uterus on palpation. The scenario provided low levels of uncertainty and high levels of relevant information. The student's response to the scenario was videoed. Immediately after, they were invited to review the video, reflect on their performance and give a commentary as to what affected their decisions. The data were analysed using Dimensional Analysis. The students' clinical management of the situation varied considerably. Students struggled to prioritize their actions where more than one response was required to a clinical cue and did not necessarily use mnemonics as heuristic devices to guide their actions. Driven by a response to single cues they also showed a reluctance to formulate a diagnosis based on inductive and deductive reasoning cycles. This meant they did not necessarily introduce new hypothetical ideas against which they might refute or confirm a diagnosis and thereby eliminate fixation error. The students response demonstrated that a number of clinical skills require updating on a regular basis including: fundal massage technique, the use of emergency standing order drugs, communication and delegation of tasks to others in an emergency and working independently until help arrives. Heuristic devices helped the students to evaluate their interventions to illuminate what else could

Clinical decision-making: midwifery students' recognition of, and response to, post partum haemorrhage in the simulation environment

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Scholes Julie

2012-03-01

Full Text Available Abstract Background This paper reports the findings of a study of how midwifery students responded to a simulated post partum haemorrhage (PPH. Internationally, 25% of maternal deaths are attributed to severe haemorrhage. Although this figure is far higher in developing countries, the risk to maternal wellbeing and child health problem means that all midwives need to remain vigilant and respond appropriately to early signs of maternal deterioration. Methods Simulation using a patient actress enabled the research team to investigate the way in which 35 midwifery students made decisions in a dynamic high fidelity PPH scenario. The actress wore a birthing suit that simulated blood loss and a flaccid uterus on palpation. The scenario provided low levels of uncertainty and high levels of relevant information. The student's response to the scenario was videoed. Immediately after, they were invited to review the video, reflect on their performance and give a commentary as to what affected their decisions. The data were analysed using Dimensional Analysis. Results The students' clinical management of the situation varied considerably. Students struggled to prioritise their actions where more than one response was required to a clinical cue and did not necessarily use mnemonics as heuristic devices to guide their actions. Driven by a response to single cues they also showed a reluctance to formulate a diagnosis based on inductive and deductive reasoning cycles. This meant they did not necessarily introduce new hypothetical ideas against which they might refute or confirm a diagnosis and thereby eliminate fixation error. Conclusions The students response demonstrated that a number of clinical skills require updating on a regular basis including: fundal massage technique, the use of emergency standing order drugs, communication and delegation of tasks to others in an emergency and working independently until help arrives. Heuristic devices helped the

Relationship between time to clinical response and outcomes among Pneumonia Outcomes Research Team (PORT) risk class III and IV hospitalized patients with community-acquired pneumonia who received ceftriaxone and azithromycin.

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Zasowski, Evan; Butterfield, Jill M; McNutt, Louise-Ann; Cohen, Jason; Cosler, Leon; Pai, Manjunath P; Gottwald, Joseph; Chen, Wen Zhen; Lodise, Thomas P

2014-07-01

Recent Food and Drug Administration (FDA) guidance endorses the use of an early clinical response endpoint as the primary outcome for community-acquired bacterial pneumonia (CABP) trials. While antibiotics will now be approved for CABP, in practice they will primarily be used to treat patients with community-acquired pneumonia (CAP). More importantly, it is unclear how achievement of the new FDA CABP early response endpoint translates into clinically applicable real-world outcomes for patients with CAP. To address this, a retrospective cohort study was conducted among adult patients who received ceftriaxone and azithromycin for CAP of Pneumonia Outcomes Research Team (PORT) risk class III and IV at an academic medical center. The clinical response was defined as clinical stability for 24 h with improvement in at least one pneumonia symptom and with no symptom worsening. A classification and regression tree (CART) was used to determine the delay in response time, measured in days, associated with the greatest risk of a prolonged hospital length of stay (LOS) and adverse outcomes (in-hospital mortality or 30-day CAP-related readmission). A total of 250 patients were included. On average, patients were discharged 2 days following the achievement of a clinical response. In the CART analysis, adverse clinical outcomes were higher among day 5 nonresponders than those who responded by day 5 (22.4% versus 6.9%, P = 0.001). The findings from this study indicate that time to clinical response, as defined by the recent FDA guidance, is a reasonable prognostic indicator of real-world effectiveness outcomes among hospitalized PORT risk class III and IV patients with CAP who received ceftriaxone and azithromycin. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Impact of genetic polymorphisms on clinical response to antithrombotics

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Kena J Lanham

2010-06-01

Full Text Available Kena J Lanham1,2, Julie H Oestreich3, Steven P Dunn1,2, Steven R Steinhubl41Pharmacy Services, UK HealthCare, University of Kentucky, Lexington, Kentucky, USA; 2Department of Pharmacy Practice and Science, College of Pharmacy, University of Kentucky, Lexington, Kentucky, USA; 3Department of Pharmacy Practice, College of Pharmacy, University of Nebraska, Omaha, Nebraska, USA; 4The Medicines Company, Zurich, Switzerland and The Geisinger Clinic, Danville, Pennsylvania, USAAbstract: Antithrombotic therapy, including anticoagulants as well as antiplatelet drugs, is an important component in the treatment of cardiovascular disease. Variability in response to such medications, of which pharmacogenetic response is a major source, can decrease or enhance the benefits expected. This review is a comprehensive assessment of the literature published to date on the effects of genetic polymorphisms on the actions of a variety of antithrombotic medications, including warfarin, clopidogrel, prasugrel, and aspirin. Literature evaluating surrogate markers in addition to the impact of pharmacogenetics on clinical outcomes has been reviewed. The results of the studies are conflicting as to what degree pharmacogenetics will affect medication management in cardiovascular disease. Additional research is necessary to discover, characterize, and prospectively evaluate genetic and non-genetic factors that impact antithrombotic treatment in order to maximize the effectiveness and limit the harmful effects of these valuable agents.Keywords: aspirin, warfarin, clopidogrel, prasugrel, pharmacogenetic, antithrombotic, antiplatelet

Analysis of immunological profile, clinical features and response to treatment in pemphigus.

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Bardazzi, Federico; Balestri, Riccardo; Ismaili, Alma; LA Placa, Michelangelo; Barisani, Alessia; Patrizi, Annalisa

2017-12-01

Pemphigus is an autoimmune disease, characterized by the presence of serum autoantibodies against Desmoglein (Dsg) 1 and 3. It can affect the skin and/or the mucous membranes. Some authors found a correlation between the serum levels of autoantibodies, disease activity and clinical phenotype of pemphigus. Anti Dsg1 autoantibodies appear related to cutaneous phenotype, anti Dsg3 autoantibodies to mucosal involvement. From 2011 to 2014, in patients with pemphigus, the serum levels of anti-Dsg1 and 3 antibodies were determined with enzyme-linked immuno-sorbent assay at diagnosis and after 6 months of different therapies. The correlations between levels of autoantibodies, clinical phenotype, clinical activity and response to therapy, were investigated. Thirty-five patients were included. Clinical phenotypes were: mucosal in 17 patients; mucous-cutaneous in 11; and cutaneous in 7. The status of anti-Dsg1 autoantibodies was significantly related to the cutaneous and mucous-cutaneous phenotypes both at diagnosis and after 6 months. The status of anti-Dsg3 autoantibodies was significantly related to the mucosal and mucous-cutaneous phenotypes only at first evaluation. No significant correlations were found between disease activity and the status of autoantibodies. No significant variations of autoantibody levels (between first and second sample) were found with regard to different therapies, except for the variation of anti-Dsg1 autoantibodies in one patient treated with systemic steroids and methotrexate. A correlation between serum levels of autoantibodies and clinical phenotype was found. Further studies over a longer follow-up period may better characterize the correlation between autoantibody levels, clinical activity and response to different therapies of pemphigus.

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

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Aurea Lima

2015-06-01

Full Text Available 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.

Clinical responsibility, accountability, and risk aversion in mental health nursing: a descriptive, qualitative study.

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Manuel, Jenni; Crowe, Marie

2014-08-01

A number of recent, highly-publicized, perceived health-care service failures have raised concerns about health professionals' accountabilities. Relevant to these concerns, the present study sought to examine how mental health nurses understood clinical responsibility and its impact on their practice. A descriptive, qualitative design was used, and a convenience sample of 10 mental health nurses was recruited from specialist inpatient and outpatient mental health settings in Canterbury, New Zealand. Data were collected using semistructured interviews, and the transcriptions were analysed using an inductive, descriptive approach. Three major themes were identified: being accountable, fostering patient responsibility, and shifting responsibility. Being accountable involved weighing up patients' therapeutic needs against the potential for blame in an organizational culture of risk management. Fostering patient responsibility described the process of deciding in what situations patients could take responsibility for their behaviour. Shifting responsibility described the culture of defensive practice fostered by the organizational culture of risk aversion. The present study highlighted the challenges mental health nurses experience in relation to clinical responsibility in practice, including the balancing required between the needs of patients, the needs of the organization, and the perceived need for self-protection. © 2014 Australian College of Mental Health Nurses Inc.

The effectiveness of nurse education and training for clinical alarm response and management: a systematic review.

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Yue, Liqing; Plummer, Virginia; Cross, Wendy

2017-09-01

To identify the effectiveness of education interventions provided for nurses for clinical alarm response and management. Some education has been undertaken to improve clinical alarm response, but the evidence for evaluating effectiveness for nurse education interventions is limited. Systematic review. A systematic review of experimental studies published in English from 2005-2015 was conducted in four computerised databases (MEDLINE, EMBASE, CINAHL and Scopus). After identification, screening and appraisal using Joanna Briggs Institute instruments, quality research papers were selected, data extraction and analysis followed. Five studies met the inclusion criteria for alarm response and no articles were concerned with clinical alarm education for management. All had different types and methods of interventions and statistical pooling was not possible. Response accuracy, response time and perceptions were consistent when different interventions were adopted. A positive effect was identified when learning about general alarms, single alarms, sequential alarms and medium-level alarms for learning as the primary task. Nurses who were musically trained had a faster and more accurate alarm response. Simulation interventions had a positive effect, but the effect of education provided in the care unit was greater. Overall, clinical alarm awareness was improved through education activities. Nurses are the main users of healthcare alarms and work in complex environments with high numbers of alarms, including nuisance alarms and other factors. Alarm-related adverse events are common. The findings of a small number of experimental studies with diverse evidence included consideration of various factors when formulating education strategies. The factors which influence effectiveness of nurse education are nurse demographics, nurse participants with musical training, workload and characteristics of alarms. Education interventions based in clinical practice settings increase

Predictive Factors of Clinical Response of Infliximab Therapy in Active Nonradiographic Axial Spondyloarthritis Patients

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Zhiming Lin

2015-01-01

Full Text Available Objectives. To evaluate the efficiency and the predictive factors of clinical response of infliximab in active nonradiographic axial spondyloarthritis patients. Methods. Active nonradiographic patients fulfilling ESSG criteria for SpA but not fulfilling modified New York criteria were included. All patients received infliximab treatment for 24 weeks. The primary endpoint was ASAS20 response at weeks 12 and 24. The abilities of baseline parameters and response at week 2 to predict ASAS20 response at weeks 12 and 24 were assessed using ROC curve and logistic regression analysis, respectively. Results. Of 70 axial SpA patients included, the proportions of patients achieving an ASAS20 response at weeks 2, 6, 12, and 24 were 85.7%, 88.6%, 87.1%, and 84.3%, respectively. Baseline MRI sacroiliitis score (AUC = 0.791; P=0.005, CRP (AUC = 0.75; P=0.017, and ASDAS (AUC = 0.778, P=0.007 significantly predicted ASAS20 response at week 12. However, only ASDAS (AUC = 0.696, P=0.040 significantly predicted ASAS20 response at week 24. Achievement of ASAS20 response after the first infliximab infusion was a significant predictor of subsequent ASAS20 response at weeks 12 and 24 (wald χ2=6.87, P=0.009, and wald χ2=5.171, P=0.023. Conclusions. Infliximab shows efficiency in active nonradiographic axial spondyloarthritis patients. ASDAS score and first-dose response could help predicting clinical efficacy of infliximab therapy in these patients.

The expanding spectrum of clinically-distinctive, immunotherapy-responsive autoimmune encephalopathies

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Sarosh R Irani

2012-04-01

Full Text Available The autoimmune encephalopathies are a group of conditions that are associated with autoantibodies against surface neuronal proteins, which are likely to mediate the disease. They are established as a frequent cause of encephalitis. Characteristic clinical features in individual patients often allow the specificity of the underlying antibody to be confidently predicted. Antibodies against the VGKC-complex, mainly LGI1(leucine-rich glioma-inactivated 1, CASPR2 (contactin-associated protein 2, and contactin-2, and NMDA (N-methyl, D-aspartate -receptor are the most frequently established serological associations. In the minority of cases, an underlying tumour can be responsible. Early administration of immunotherapies, and tumour removal, where it is relevant, offer the greatest chance of improvement. Prolonged courses of immunotherapies may be required, and clinical improvements often correlate well with the antibody levels. In the present article, we have summarised recent developments in the clinical and laboratory findings within this rapidly expanding field.

Professional and personal responsibility in higher education - An inquiry from a standpoint of pragmatismand discourse theory

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Carsten Ljunggren

2008-01-01

Full Text Available In recent years, reports have drawn attention to an ongoing instrumentalization of academic actions, governed by economic power. In the light of these reports higher education in Sweden is analysed combining Deweyan pragmatism with the discourse theory of Laclau and Mouffe to construct a theoretical conception of professional and personal responsibility. At the beginning of the 1990s and the 21st Century, it is possible to observe a discursive domain filled with variations in language use – the existence of a classical academic discourse, a discourse of Bildung, a discourse of democracy and a discourse of economic globalization – that causes both conflicts and openness regarding the meaning of higher education and professional responsibility. The closer we get to 2007, the more this variation in language use is reduced and the narrower the meaning we find, owing to the hegemonic tendencies of the discourse of economic globalization.

Clinical responses to ERK inhibition in BRAFV600E-mutant colorectal cancer predicted using a computational model.

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Kirouac, Daniel C; Schaefer, Gabriele; Chan, Jocelyn; Merchant, Mark; Orr, Christine; Huang, Shih-Min A; Moffat, John; Liu, Lichuan; Gadkar, Kapil; Ramanujan, Saroja

2017-01-01

Approximately 10% of colorectal cancers harbor BRAF V600E mutations, which constitutively activate the MAPK signaling pathway. We sought to determine whether ERK inhibitor (GDC-0994)-containing regimens may be of clinical benefit to these patients based on data from in vitro (cell line) and in vivo (cell- and patient-derived xenograft) studies of cetuximab (EGFR), vemurafenib (BRAF), cobimetinib (MEK), and GDC-0994 (ERK) combinations. Preclinical data was used to develop a mechanism-based computational model linking cell surface receptor (EGFR) activation, the MAPK signaling pathway, and tumor growth. Clinical predictions of anti-tumor activity were enabled by the use of tumor response data from three Phase 1 clinical trials testing combinations of EGFR, BRAF, and MEK inhibitors. Simulated responses to GDC-0994 monotherapy (overall response rate = 17%) accurately predicted results from a Phase 1 clinical trial regarding the number of responding patients (2/18) and the distribution of tumor size changes ("waterfall plot"). Prospective simulations were then used to evaluate potential drug combinations and predictive biomarkers for increasing responsiveness to MEK/ERK inhibitors in these patients.

Effects of diabetes mellitus on the clinical presentation and treatment response in tuberculosis.

Science.gov (United States)

Leung, Chi C; Yew, Wing W; Mok, Thomas Y W; Lau, Kam S; Wong, Chi F; Chau, Chi H; Chan, Chi K; Chang, Kwok C; Tam, Greta; Tam, Cheuk M

2017-08-01

With the colliding global epidemics of diabetes mellitus (DM) and tuberculosis (TB), we studied the effects of DM on the presentation of TB and its response to treatment. Consecutive TB patients from 2006 to 2010 in a territory-wide treatment programme offering 9-month extended treatment for TB patients with DM were examined and followed up prospectively to assess their treatment response. Successful treatment completers were tracked through the TB registry and death registry for relapse, death or till 31 December 2014, whichever was the earliest. DM was independently associated with more chest symptoms (adjusted OR (AOR): 1.13) and systemic symptoms (AOR: 1.30) but less with other site-specific symptoms (AOR: 0.58) at TB presentation. There was more frequent pulmonary involvement (AOR: 1.69), with more extensive lung lesion (AOR: 1.25), lung cavity (AOR: 2.00) and positive sputum smear (AOR: 1.83) and culture (AOR: 1.38), but no difference in the proportion of retreatment cases or isoniazid and/or rifampicin resistance. After treatment initiation, there was higher overall incidence (AOR: 1.38) of adverse effects (mainly gastrointestinal symptoms, renal impairment and peripheral neuropathy but less fever and skin hypersensitivity reactions), more smear non-conversion (AOR: 1.59) and culture non-conversion (AOR: 1.40) at 2 months, and lower combined cure/treatment completion rate at 12 months (AOR: 0.79), but no difference in the relapse rate after having successfully completed treatment. DM adversely affected the clinical presentation and treatment response of TB, but there was no difference in the drug resistance and relapse rates. © 2017 Asian Pacific Society of Respirology.

Cell-mediated immune response: a clinical review of the therapeutic potential of human papillomavirus vaccination.

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Meyer, Sonja Izquierdo; Fuglsang, Katrine; Blaakaer, Jan

2014-12-01

This clinical review aims to assess the efficacy of human papillomavirus 16/18 (HPV16/18) vaccination on the cell-mediated immune response in women with existing cervical intraepithelial neoplasia or cervical cancer induced by HPV16 or HPV18. A focused and thorough literature search conducted in five different databases found 996 publications. Six relevant articles were chosen for further review. In total, 154 patients (>18 years of age) were enrolled in prospective study trials with 3-15 months of follow up. The vaccine applications were administered two to four times. The vaccines contained different combinations of HPV16 and HPV18 and early proteins, E6 and E7. The primary outcome was the cell-mediated immune response. Correlation to clinical outcome (histopathology) and human leukocyte antigen genes were secondary endpoints. All vaccines triggered a detectable cell-mediated immune response, some of which were statistically significant. Correlations between immunological response and clinical outcome (histopathology) were not significant, so neoplasms may not be susceptible to vaccine-generated cytotoxic T cells (CD8(+)). Prophylactic HPV vaccines have been introduced to reduce the incidence of cervical cancer in young women. Women already infected with HPV could benefit from a therapeutic HPV vaccination. Hence, it is important to continue the development of therapeutic HPV vaccines to lower the rate of HPV-associated malignancies and crucial to evaluate vaccine efficacy clinically. This clinical review represents an attempt to elucidate the theories supporting the development of an HPV vaccine with a therapeutic effect on human papillomavirus-induced malignancies of the cervix. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

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

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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

Alexithymia is associated with attenuated automatic brain response to facial emotion in clinical depression.

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Suslow, Thomas; Kugel, Harald; Rufer, Michael; Redlich, Ronny; Dohm, Katharina; Grotegerd, Dominik; Zaremba, Dario; Dannlowski, Udo

2016-02-04

Alexithymia is a clinically relevant personality trait related to difficulties in recognizing and describing emotions. Previous studies examining the neural correlates of alexithymia have shown mainly decreased response of several brain areas during emotion processing in healthy samples and patients suffering from autism or post-traumatic stress disorder. In the present study, we examined the effect of alexithymia on automatic brain reactivity to negative and positive facial expressions in clinical depression. Brain activation in response to sad, happy, neutral, and no facial expression (presented for 33 ms and masked by neutral faces) was measured by functional magnetic resonance imaging at 3 T in 26 alexithymic and 26 non-alexithymic patients with major depression. Alexithymic patients manifested less activation in response to masked sad and happy (compared to neutral) faces in right frontal regions and right caudate nuclei than non-alexithymic patients. Our neuroimaging study provides evidence that the personality trait alexithymia has a modulating effect on automatic emotion processing in clinical depression. Our findings support the idea that alexithymia could be associated with functional deficits of the right hemisphere. Future research on the neural substrates of emotion processing in depression should assess and control alexithymia in their analyses.

Platelet aggregation responses in clinically healthy adult llamas.

Science.gov (United States)

Gilbert, Rosanne M; Bird, Karyn E; Kutzler, Michelle A

2009-03-01

Limited information exists regarding hemostasis in camelids despite the importance of platelet function testing in the accurate identification of platelet disorders. As further importation of llamas to North America is restricted, variability in breeding stock will continue to decrease, potentially leading to an increase in heritable bleeding disorders. The objective of this study was to measure platelet aggregation responses in clinically healthy llamas and provide baseline data to which abnormal platelet function may be compared in the future. Blood samples were collected from 39 healthy adult llamas, citrated, and centrifuged to produce platelet-rich plasma (PRP). Within 4 hours of the blood draw, 20 microL of each agonist reagent were added to 180 microL of PRP. Final concentrations of agonists were 2 x 10(-5) M ADP, 0.19 mg collagen/mL PRP, 1 x 10(-4) M epinephrine, and 500 microg arachidonic acid/mL PRP. Llama platelets were most responsive to ADP and collagen, with a maximum percent aggregation (mean+/-SD) of 71.3+/-18.6% and 55.8+/-19% and aggregation rates of 9.5+/-3.9 and 6.7+/-3.7 cm/min, respectively. Llama platelet aggregation in response to epinephrine and arachidonic acid was minimal to absent. This study is the first of its kind to establish baseline values for platelet aggregation in healthy adult llamas.

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

Science.gov (United States)

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

Use of Portable Digital Devices to Analyze Autonomic Stress Response in Psychology Objective Structured Clinical Examination.

Science.gov (United States)

Beltrán-Velasco, Ana Isabel; Bellido-Esteban, Alberto; Ruisoto-Palomera, Pablo; Clemente-Suárez, Vicente Javier

2018-01-12

The aim of the present study was to explore changes in the autonomic stress response of Psychology students in a Psychology Objective Structured Clinical Examination (OSCE) and their relationship with OSCE performance. Variables of autonomic modulation by the analysis of heart rate variability in temporal, frequency and non-linear domains, subjective perception of distress strait and academic performance were measured before and after the two different evaluations that composed the OSCE. A psychology objective structured clinical examination composed by two different evaluation scenarios produced a large anxiety anticipatory response, a habituation response in the first of the evaluation scenarios and a in the entire evaluation, and a no habituation response in the second evaluation scenario. Autonomic modulation parameters do not correlate with academic performance of students.

Sunitinib in urothelial cancer: clinical, pharmacokinetic, and immunohistochemical study of predictors of response.

LENUS (Irish Health Repository)

Gallagher, David J

2012-02-01

BACKGROUND: Sunitinib has activity in patients with metastatic urothelial cancer (UC), but most patients do not respond. OBJECTIVE: To identify predictors of response to sunitinib. DESIGN, SETTING, AND PARTICIPANTS: Seventy-seven patients with advanced UC received sunitinib on one of two schedules at a single institution. Blood pressure (BP), immunohistochemistry (IHC), and pharmacokinetic (PK) results were correlated with response to sunitinib. MEASUREMENTS: BP was assessed on day 1 and 28 of each cycle and on day 14 of cycle 1. IHC was performed on 55 samples from 38 cases using mammalian target of rapamycin and hypoxia-inducible factor (HIF) pathway marker antibodies. Blood samples for PK analysis were collected from 15 patients at three time points. Response was assessed using Response Evaluation Criteria in Solid Tumors criteria. RESULTS AND LIMITATIONS: Sunitinib-induced hypertension predicted improved response when hypertension was categorized as a discrete (p = 0.02) or continuous variable (p = 0.005 [systolic BP] and p = 0.007 [diastolic BP]). The odds ratio of response was 12.5 (95% confidence interval, 1.95-246.8) for grade 3\\/4 hypertension compared with grade 0. Response was associated with low HIF-1alpha expression in primary (p = 0.07) tissue. A nonstatistically significant trend was seen for an association between greater drug concentration and best response. A correlation between expression markers within the same pathways was identified, phosphorylated-4EBP1 and phosphorylated-S6 (p = 6.5 x 10(-9)), and vascular endothelial growth factor receptor 2 and HIF-1alpha (p = 0.008). Results are limited by small numbers. CONCLUSIONS: Clinical and molecular biomarkers of response to sunitinib may have clinical relevance and require prospective validation. There is an urgent need for predictive biomarkers to guide the management of UC.

Roles and Responsibilities, and Education and Training Requirements for Clinically Qualified Medical Physicists (Russian Edition)

International Nuclear Information System (INIS)

2014-01-01

This publication addresses the shortfall of well trained and clinically qualified medical physicists working in radiation medicine. The roles, responsibilities and clinical training requirements of medical physicists have not always been well defined or well understood by health care professionals, health authorities and regulatory agencies. To fill this gap, this publication provides recommendations for the academic education and clinical training of clinically qualified medical physicists, including recommendations for their accreditation certification and registration, along with continuous professional development. The goal is to establish criteria that support the harmonization of education and clinical training worldwide

The 20th anniversary of interleukin-2 therapy: bimodal role explaining longstanding random induction of complete clinical responses

International Nuclear Information System (INIS)

Coventry, Brendon J; Ashdown, Martin L

2012-01-01

This year marks the twentieth anniversary of the approval by the US Food and Drug Administration of interleukin-2 (IL2) for use in cancer therapy, initially for renal cell carcinoma and later for melanoma. IL2 therapy for cancer has stood the test of time, with continued widespread use in Europe, parts of Asia, and the US. Clinical complete responses are variably reported at 5%–20% for advanced malignant melanoma and renal cell carcinoma, with strong durable responses and sustained long-term 5–10-year survival being typical if complete responses are generated. The literature was reviewed for the actions and clinical effects of IL2 on subsets of T cells. The influence of IL2 on clinical efficacy was also sought. The review revealed that IL2 is capable of stimulating different populations of T cells in humans to induce either T effector or T regulatory responses. This apparent “functional paradox” has confounded a clear understanding of the mechanisms behind the clinical effects that are observed during and following administration of IL2 therapy. An average complete response rate of around 7% in small and large clinical trials using IL2 for advanced renal cell carcinoma and malignant melanoma has been shown from a recent review of the literature. This review considers the published literature concerning the actions and emerging clinical effects of IL2 therapy, spanning its 20-year period in clinical use. It further details some of the recently described “bimodal” effects of IL2 to explain the apparent functional paradox, and how IL2 might be harnessed to emerge rapidly as a much more effective and predictable clinical agent in the near future

Molecular responses during cadmium-induced stress in Daphnia magna: Integration of differential gene expression with higher-level effects

Energy Technology Data Exchange (ETDEWEB)

Soetaert, Anneleen [Department of Biology, Laboratory for Ecophysiology, Biochemistry and Toxicology, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp (Belgium)]. E-mail: anneleen.soetaert@ua.ac.be; Vandenbrouck, Tine [Department of Biology, Laboratory for Ecophysiology, Biochemistry and Toxicology, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp (Belgium); Ven, Karlijn van der [Department of Biology, Laboratory for Ecophysiology, Biochemistry and Toxicology, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp (Belgium); Maras, Marleen [Department of Biology, Laboratory for Ecophysiology, Biochemistry and Toxicology, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp (Belgium); Remortel, Piet van [Department of Mathematics and Informatics, Intelligent Systems Laboratory, University of Antwerp, Middelheimlaan 1, B-2020 Antwerp (Belgium); Blust, Ronny [Department of Biology, Laboratory for Ecophysiology, Biochemistry and Toxicology, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp (Belgium); Coen, Wim M. de [Department of Biology, Laboratory for Ecophysiology, Biochemistry and Toxicology, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp (Belgium)

2007-07-20

DNA microarrays offer great potential in revealing insight into mechanistic toxicity of contaminants. The aim of the present study was (i) to gain insight in concentration- and time-dependent cadmium-induced molecular responses by using a customized Daphnia magna microarray, and (ii) to compare the gene expression profiles with effects at higher levels of biological organization (e.g. total energy budget and growth). Daphnids were exposed to three cadmium concentrations (nominal value of 10, 50, 100 {mu}g/l) for two time intervals (48 and 96 h). In general, dynamic expression patterns were obtained with a clear increase of gene expression changes at higher concentrations and longer exposure duration. Microarray analysis revealed cadmium affected molecular pathways associated with processes such as digestion, oxygen transport, cuticula metabolism and embryo development. These effects were compared with higher-level effects (energy budgets and growth). For instance, next to reduced energy budgets due to a decline in lipid, carbohydrate and protein content, we found an up-regulated expression of genes related to digestive processes (e.g. {alpha}-esterase, cellulase, {alpha}-amylase). Furthermore, cadmium affected the expression of genes coding for proteins involved in molecular pathways associated with immune response, stress response, cell adhesion, visual perception and signal transduction in the present study.

Eosinophilic Esophagitis: Clinical Features, Endoscopic Findings and Response to Treatment

Directory of Open Access Journals (Sweden)

Robert Enns

2010-01-01

Full Text Available Eosinophilic esophagitis (EE is a motility disorder of the esophagus that typically presents with dysphagia. The objective of the present study was to explore patient characteristics, clinical and endoscopic features, and response to treatment of patients with EE. Patients were selected retrospectively based on a review of biopsy results from previous endoscopies performed between 2004 and 2008. A total of 54 patients (41 men and 13 women with biopsy-proven EE were included in the study. Further information regarding the patients’ clinical and endoscopic features, and response to treatment were obtained through chart reviews and patient telephone interviews. The mean age of the patients at symptom onset was 30 years. All patients complained of dysphagia, 81% had a history of bolus obstruction, 43% had a history of asthma and 70% had a history of environmental allergies. Thirty-three per cent had a family history of asthma, while 52% had a family history of food or seasonal allergies. The most common endoscopic findings were rings and/or corrugations, which were found in 63% of patients. Swallowed fluticasone therapy resulted in symptom resolution in 74% of patients; however, 79% of these patients relapsed after discontinuing fluticasone therapy and required repeat treatments. Esophageal dilation was complication free and resulted in improvement in 80% of patients. However, 83% of those reporting improvement relapsed within one year. The clinical and endoscopic findings were similar to those found in the literature, with most patients requiring ongoing, repeated therapies. Further studies are needed to assess the safety and efficacy of treatment modalities ideally suited to patients with EE.

Acute herpes zoster neuralgia: retrospective analysis of clinical aspects and therapeutic responsiveness.

Science.gov (United States)

Haas, N; Holle, E; Hermes, B; Henz, B M

2001-01-01

Although the efficacy of modern antiviral agents for the treatment of herpes zoster is unquestioned, their ability to affect the associated pain remains controversial. We have therefore evaluated the inpatient hospital records of 550 patients with herpes zoster with regard to pain-related clinical aspects and therapeutic responsiveness. Intensity of pain was quantified by calculating a daily pain equivalence index (PEI) on the basis of different classes of pain medication and the number of tablets used in each category. The mean age of patients was 66.7 years, cranial segments were predominantly involved (55%), 64% of patients suffered from associated diseases and 77% experienced herpes-related pain. The PEI was 0.90 in the entire patient population, with significantly higher values in women and in patients with 3 or more associated diseases. It was lower in sacral and cranial nerve involvement, and it decreased rapidly in patients prior to discharge from hospital. Although there were significant differences in hospital stay between patients who received aciclovir and those who did not (mean 20.3 vs. 23.8 days), and for high- versus low-dose oral or intravenous administration, no significant differences were noted between the two groups for initial PEI values and during the course of observation, irrespective of the route of administration or the dose of aciclovir and the individual patient's PEI value. The groups were otherwise closely similar with regard to basic demographic and clinical data. 23.3% predominantly aged female patients with more associated diseases than the total patient population had a persistently elevated PEI and stayed in hospital beyond 21 days (mean 35.1 days), representing patients who went on to postherpetic neuralgia. These data further delineate clinical aspects of acute herpes zoster neuralgia, underline the unsolved therapeutic problems associated with this condition despite otherwise effective antiviral treatment, and characterise a

Clinical features and subjective/physiological responses to emotional stimuli in the presence of emotion dysregulation in attention-deficit hyperactivity disorder.

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Taskiran, Candan; Karaismailoglu, Serkan; Cak Esen, Halime Tuna; Tuzun, Zeynep; Erdem, Aysen; Balkanci, Zeynep Dicle; Dolgun, Anil Barak; Cengel Kultur, Sadriye Ebru

2018-05-01

Emotion dysregulation (ED) has long been recognized in clinical descriptions of attention-deficit hyperactivity disorder (ADHD), but a renewed interest in ED has advanced research on the overlap between the two entities. Autonomic reactivity (AR) is a neurobiological correlate of emotion regulation; however, the association between ADHD and AR remains unclear. Our aim was to explore the clinical differences, AR, and subjective emotional responses to visual emotional stimuli in ADHD children with and without ED. School-aged ADHD children with (n = 28) and without (n = 20) ED, according to the definition of deficiency in emotional self-regulation (DESR), and healthy controls (n = 22) were interviewed by using the Schedule for Affective Disorders and Schizophrenia for School Aged Children-Present and Lifetime version (K-SADS-PL) to screen frequent psychopathologies for these ages. All subjects were evaluated with Child Behavior Checklist 6-18 (CBCL), the Strengths and Difficulties Questionnaire (SDQ), the McMaster Family Assessment Device (FAD), the School-Age Temperament Inventory (SATI), and Conners' Parent Rating Scale (CPRS-48), which were completed by parents. To evaluate emotional responses, the International Affective Picture System (IAPS) and the subjective and physiological responses (electrodermal activity and heart rate reactivity) to selected pictures were examined. Regarding clinically distinctive features, the ADHD+ED group differed from the ADHD-ED and the control groups in terms of having higher temperamental negative reactivity, more oppositional/conduct problems, and lower prosocial behaviors. In the AR measures, children in the ADHD+ED group rated unpleasant stimuli as more negative, but they still had lower heart rate reactivity (HRR) than the ADHD-ED and control groups; moreover, unlike the two other groups, the ADHD+ED group showed no differences in HRR between different emotional stimuli. The presented findings are unique in terms of their

Lens Dk/t influences the clinical response in overnight orthokeratology.

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Lum, Edward; Swarbrick, Helen A

2011-04-01

To investigate the influence of lens oxygen transmissibility (Dk/t) on the clinical response to overnight (ON) orthokeratology (OK) lens wear over 2 weeks. Eleven subjects (age, 20 to 39 years) were fitted with OK lenses (BE; Capricornia Contact Lens) in both eyes. Lenses in matched design/fitting but different materials (Boston EO and XO; nominal Dk/t: 26 and 46 ISO Fatt, respectively) were worn ON only in the two eyes over a 2-week period. Changes in logarithm of the minimum angle of resolution visual acuity, subjective refraction (spherical equivalent), corneal apical radius ro and asphericity Q (Medmont E300), and central stromal thickness (Holden-Payor optical pachometer) were measured. There were statistically significant differences in outcomes between the two lens materials (analysis of variance, p 0.05). An increase in lens Dk/t appears to increase the clinical effects of ON reverse-geometry lens wear over the medium term. This adds further support to the recommendation that high Dk materials should be used for ON OK not only to provide physiological advantages but also to optimize clinical outcomes.

Higher songs of city birds may not be an individual response to noise.

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Zollinger, Sue Anne; Slater, Peter J B; Nemeth, Erwin; Brumm, Henrik

2017-08-16

It has been observed in many songbird species that populations in noisy urban areas sing with a higher minimum frequency than do matched populations in quieter, less developed areas. However, why and how this divergence occurs is not yet understood. We experimentally tested whether chronic noise exposure during vocal learning results in songs with higher minimum frequencies in great tits ( Parus major ), the first species for which a correlation between anthropogenic noise and song frequency was observed. We also tested vocal plasticity of adult great tits in response to changing background noise levels by measuring song frequency and amplitude as we changed noise conditions. We show that noise exposure during ontogeny did not result in songs with higher minimum frequencies. In addition, we found that adult birds did not make any frequency or song usage adjustments when their background noise conditions were changed after song crystallization. These results challenge the common view of vocal adjustments by city birds, as they suggest that either noise itself is not the causal force driving the divergence of song frequency between urban and forest populations, or that noise induces population-wide changes over a time scale of several generations rather than causing changes in individual behaviour. © 2017 The Author(s).

Serial diffusion-weighted MRI correlates with clinical course and treatment response in children with intracranial pus collections

International Nuclear Information System (INIS)

Fanning, Noel F.; Laffan, Eoghan E.; Shroff, Manohar M.

2006-01-01

Accurate assessment of treatment response in children with intracranial pus collections is vital to guide appropriate therapy and reduce morbidity and mortality. To correlate serial MR-measurable changes in diffusion-weighted imaging (DWI) with clinical response to treatment. We retrospectively reviewed clinical notes, conventional MR sequences and DWI in eight children with intracranial pus collections. Trace DWI signal intensity and apparent diffusion coefficient (ADC) values were compared at three time points: at initial diagnosis (eight children, 13 collections), at follow-up during continued clinical infection (three children, sp collections), and at follow-up when clinical infection had resolved (seven children, 12 collections). At initial diagnosis all patients were septic and collections showed restricted diffusion (mean ADC 0.61±0.15 x 10 -3 mm 2 /s). Patients with persistent clinical sepsis at follow-up DWI had collections with persistent low ADC values (0.66±0.21 x 10 -3 mm 2 /s), significantly (P -3 mm 2 /s, P<0.01) compared both to patients with signs of continued sepsis and to normal gray matter values. Persistent restricted diffusion in pus collections correlates with continued sepsis. Treatment response is associated with clinical resolution of sepsis and ADC value elevation significantly above normal gray matter values. (orig.)

Clinical roles in clinical biochemistry: a national survey of practice in the UK.

Science.gov (United States)

Choudhury, Sirazum M; Williams, Emma L; Barnes, Sophie C; Alaghband-Zadeh, Jamshid; Tan, Tricia M; Cegla, Jaimini

2017-05-01

Background Using an online survey, we collected data to present a picture of how clinical authorization is performed in the UK. Methods A 21-question survey was uploaded to www.surveymonkey.com , and responses were invited via the mail base of the Association for Clinical Biochemistry and Laboratory Medicine. The questionnaire examined the intensity and function of the duty biochemist role and how different types of authorization are used to handle and release results. Results Of 70 responses received, 60 were suitable for analysis. Responses were received from every region of the UK. A typical duty biochemist shift started on average at 8:50, and finished at 17:25. The mean duration was 8 h 58 min. Clinical scientists are the most abundantly represented group on duty biochemist rotas. Higher banded clinical scientists and chemical pathologists covered out-of-hours shifts. Results were handled differently depending on the level of abnormality and the requesting area. Normal results tended to be released either directly from the analyser or after technical then autoauthorization (90%). A greater preference for clinical authorization was seen for abnormal and critical results originating from outpatients (49% and 69%, respectively) or general practice (51% and 71%) than for inpatients (33% and 53%) or A&E (25% and 37%). Conclusions The handling and authorization of biochemistry results varies greatly between laboratories. The role is clearly heterogeneous in the UK. Guidance from the Association for Clinical Biochemistry and Royal College of Pathologists may help to clarify the essential roles of the duty biochemist.

Smoking and immunomodulators do not influence the response or duration of response to infliximab in Crohn's disease.

Science.gov (United States)

Fefferman, David S; Lodhavia, Parag J; Alsahli, Mazen; Falchuk, Kenneth R; Peppercorn, Mark A; Shah, Samir A; Farrell, Richard J

2004-07-01

Clinical predictors for infliximab response are still unknown. Identifying predictors of response to infliximab in Crohn's disease may improve our selection of patients. Two hundred patients with luminal (61%) or fistulous (39%) Crohn's disease and at least 6 months of follow-up following a total of 416 infliximab infusions were evaluated. Clinical response and duration of response were the primary endpoints. Patients with fistulous disease had a higher response rate (83% versus 70%, P = 0.044) and a significantly longer duration of response compared with patients with luminal disease (17.4 versus 10.1 wks, P = 0.017). For luminal disease, nonsmokers and smokers had similar response rates (74% versus 64%, P = 0.5) and similar durations of response (9.4 wks versus 8.4 wks P = 0.6) while patients taking concurrent immunomodulators had similar response rates compared with those not taking immunomodulators (74% versus 71%, P = 0.9) and similar durations of response (10.4 wks versus 10.6 wks, P = 0.9). For fistulous disease, response rates (89% versus 83% P = 0.9) and duration of response (16.9 wks versus 10.1 wks, P = 0.10) were similar between nonsmokers and smokers and concurrent immunomodulators had no effect on response (89% versus 86%, P = 0.9) or duration of response (19.8 wks versus 15.4 wks, P = 0.46). Multivariable analysis confirmed that neither smoking, corticosteroids, immunomodulator therapy, gender, age, age of disease onset, disease duration, nor luminal disease location significantly influenced response or duration of response. Patients with fistulous disease had a higher response rate and a significantly longer duration of response compared with patients with luminal disease. However, among patients with luminal or fistulous disease, neither smoking nor immunomodulators had any effect on response or duration of response.

Cerebral venous thrombosis in Saudi Arabia. Clinical variables, response to treatment, and outcome

International Nuclear Information System (INIS)

Kajtazi, Naim I; Arulneyam, Jayanthi C; AlSenani, Fahmi M; Zimmerman, Valerie A; AlShami, Sadiq Y

2009-01-01

To investigate cerebral venous thrombosis (CVTR) clinical presentations, risk factors, and response to treatment in Saudi Arabia. Retrospective analysis of the King Farad Medical City, Riyadh, acute stroke database from April 2005 through February 2008 revealed 22 patients with CVTR. Hyper coagulable work-up and neuroimaging were performed. Sixteen patients were female (72.7%), and the median age was 35 years. Clinical presentations included: headache (77.3%), seizures (54.5%), focal neurological signs (54.5%), and decreased level of consciousness (50%). Over two-thirds (n=11; 69%) of female patients had a history of oral contraceptive use, which was the most common risk factor. Protein S deficiency (n=3), anti phospholipid antibody syndrome secondary to systemic lupus erythematosus (SLE) (n=1), rhinocerebral mucormycosis (n=1), leukemia (n=1), non-Hodgkin's lymphoma (n=1), sepsis (n=1), and unknown (n=6) were causes. Affected areas included superior sagittal (n=13), transverse (n=16), sigmoid (n=14), straight (n=6), and cavernous sinus (n=1); internal cerebral vein (n=2); vein of Galen (n=3); cortical veins (n=10); and internal jugular vein (n=12). Two patients had quadriparesis, and 2 patients died. The remainder (n=18, 81.8%) improved. Bilateral hemorrhagic presentation or venous infarction, deep venous system thrombosis, and underlying malignancy had less favorable results. Presentations in our series were similar to those in other reports, although altered consciousness and seizures were more common. Cortical vein involvement was also higher than commonly reported. Oral contraceptive use was a primary risk factor in female patients. Outcomes were favorable in 81.8% of patients. (author)

Motivation for change as a predictor of treatment response for dysthymia.

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Frías Ibáñez, Álvaro; González Vallespí, Laura; Palma Sevillano, Carol; Farriols Hernando, Núria

2016-05-01

Dysthymia constitutes a chronic, mild affective disorder characterized by heterogeneous treatment effects. Several predictors of clinical response and attendance have been postulated, although research on the role of the psychological variables involved in this mental disorder is still scarce. Fifty-four adult patients, who met criteria for dysthymia completed an ongoing naturalistic treatment based on the brief interpersonal psychotherapy (IPT-B), which was delivered bimonthly over 16 months. As potential predictor variables, the therapeutic alliance, coping strategies, perceived self-efficacy, and motivation for change were measured at baseline. Outcome variables were response to treatment (Clinical Global Impression and Beck’s Depression Inventory) and treatment attendance. Stepwise multiple linear regression analyses revealed that higher motivation for change predicted better response to treatment. Moreover, higher motivation for change also predicted treatment attendance. Therapeutic alliance was not a predictor variable of neither clinical response nor treatment attendance. These preliminary findings support the adjunctive use of motivational interviewing (MI) techniques in the treatment of dysthymia. Further research with larger sample size and follow-up assessment is warranted.

Nutritional Risk, Micronutrient Status and Clinical Outcomes: A Prospective Observational Study in an Infectious Disease Clinic

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Oguzhan Sıtkı Dizdar

2016-02-01

Full Text Available Malnutrition has been associated with increased morbidity and mortality. The objective of this study was to determine the nutritional status and micronutrient levels of hospitalized patients in an infectious disease clinic and investigate their association with adverse clinical outcomes. The nutritional status of the study participants was assessed using the Nutritional Risk Screening 2002 (NRS 2002 and micronutrient levels and routine biochemical parameters were tested within the first 24 h of the patient’s admission. The incidence of zinc, selenium, thiamine, vitamin B6, vitamin B12 deficiency were 66.7% (n = 40, 46.6% (n = 29, 39.7% (n = 27, 35.3% (n = 24, 14.1% (n = 9, respectively. Selenium levels were significantly higher in patients with urinary tract infections, but lower in soft tissue infections. Copper levels were significantly higher in patients with soft tissue infections. In the Cox regression models, lower albumin, higher serum lactate dehydrogenase levels and higher NRS-2002 scores were associated with increased death. Thiamine, selenium, zinc and vitamin B6 deficiencies but not chromium deficiencies are common in infectious disease clinics. New associations were found between micronutrient levels and infection type and their adverse clinical outcomes. Hypoalbuminemia and a high NRS-2002 score had the greatest accuracy in predicting death, systemic inflammatory response syndrome and sepsis on admission.

Responsiveness of the Ankylosing Spondylitis Disease Activity Score (ASDAS), and clinical and magnetic resonance imaging measures of disease activity in a 1 year follow-up study of patients with axial spondyloarthritis treated with TNF-{alpha} inhibitors

DEFF Research Database (Denmark)

Pedersen, Susanne J; Sørensen, Inge J; Hermann, Kay-Geert A

2010-01-01

OBJECTIVES: To investigate construct validity and responsiveness of the novel ankylosing spondylitis disease activity score (ASDAS) in patients with spondyloarthritis (SpA). METHODS: In a 46 weeks prospective, longitudinal multi-center study of 60 SpA patients (80% men, median age 40 years (range...... 21-62)) treated with tumor-necrosis-factor-alpha (TNF-alpha) inhibitors (infliximab (n=41), etanercept (n=13), adalimumab (n=6)) responsiveness of ASDAS, conventional clinical measures of disease activity and treatment response, and the Berlin magnetic resonance imaging (MRI) sacroiliac joint (SIJ......) and lumbar spine inflammation scores were compared. RESULTS: After 22 weeks, 58.3% of the patients were clinical responders (50% or 20mm reduction in BASDAI). At baseline, clinical responders had significantly higher ASDAS (median 4.15 (range 1.98-6.04), p=0.008) compared with non-responders (2.99, 2...

Treatment failure in patients with HPV 16-induced vulvar intraepithelial neoplasia: understanding different clinical responses to immunotherapy.

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van Esch, Edith M G; Welters, Marij J P; Jordanova, Ekaterina S; Trimbos, J Baptist M Z; van der Burg, Sjoerd H; van Poelgeest, Mariëtte I E

2012-07-01

Failure of the immune system to launch a strong and effective immune response to high-risk HPV is related to viral persistence and the development of anogenital (pre)malignant lesions such as vulvar intraepithelial neoplasia (VIN). Different forms of immunotherapy, aimed at overcoming the inertia of the immune system, have been developed and met with clinical success. Unfortunately these, in principal successful, therapeutic approaches also fail to induce clinical responses in a substantial number of cases. In this review, the authors summarize the traits of the immune response to HPV in healthy individuals and in patients with HPV-induced neoplasia. The potential mechanisms involved in the escape of HPV-induced lesions from the immune system indicate gaps in our knowledge. Finally, the interaction between the immune system and VIN is discussed with a special focus on the different forms of immunotherapy applied to treat VIN and the potential causes of therapy failure. The authors conclude that there are a number of pre-existing conditions that determine the patients' responsiveness to immunotherapy. An immunotherapeutic strategy in which different aspects of immune failure are attacked by complementary approaches, will improve the clinical response rate.

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

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

2015-08-01

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.

[Clinical and biological predictors of ketamine response in treatment-resistant major depression: Review].

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Romeo, B; Choucha, W; Fossati, P; Rotge, J-Y

2017-08-01

The aim of this review was to determine the clinical and biological predictors of the ketamine response. A systematic research on PubMed and PsycINFO database was performed without limits on year of publication. The main predictive factors of ketamine response, which were found in different studies, were (i) a family history of alcohol dependence, (ii) unipolar depressive disorder, and (iii) neurocognitive impairments, especially a slower processing speed. Many other predictive factors were identified, but not replicated, such as personal history of alcohol dependence, no antecedent of suicide attempt, anxiety symptoms. Some biological factors were also found such as markers of neural plasticity (slow wave activity, brain-derived neurotrophic factor Val66Met polymorphism, expression of Shank 3 protein), other neurologic factors (anterior cingulate activity, concentration of glutamine/glutamate), inflammatory factors (IL-6 concentration) or metabolic factors (concentration of B12 vitamin, D- and L-serine, alterations in the mitochondrial β-oxidation of fatty acids). This review had several limits: (i) patients had exclusively resistant major depressive episodes which represent a sub-type of depression and not all depression, (ii) response criteria were more frequently assessed than remission criteria, it was therefore difficult to conclude that these predictors were similar, and finally (iii) many studies used a very small number of patients. In conclusion, this review found that some predictors of ketamine response, like basal activity of anterior cingulate or vitamin B12 concentration, were identical to other therapeutics used in major depressive episode. These factors could be more specific to the major depressive episode and not to the ketamine response. Others, like family history of alcohol dependence, body mass index, or D- and L-serine were different from the other therapeutics. Neurocognitive impairments like slower speed processing or alterations in

Training in Using Earplugs or Using Earplugs with a Higher than Necessary Noise Reduction Rating? A Randomized Clinical Trial

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M Salmani Nodoushan

2014-09-01

Full Text Available Background: Noise-induced hearing loss (NIHL is one of the most common occupational diseases and the second most common cause of workers' claims for occupational injuries. Objective: Due to high prevalence of NIHL and several reports of improper use of hearing protective devices (HPDs, we conducted this study to compare the effect of face-to-face training in effective use of earplugs with appropriate NRR to overprotection of workers by using earplugs with higher than necessary noise reduction rating (NRR. Methods: In a randomized clinical trial, 150 workers referred to occupational medicine clinic were randomly allocated to three arms—a group wearing earplugs with an NRR of 25 with no training in appropriate use of the device; a group wearing earplugs with an NRR of 25 with training; another group wearing earplugs with an NRR of 30, with no training. Hearing threshold was measured in the study groups by real ear attenuation at threshold (REAT method. This trial is registered with Australian New Zealand clinical trials Registry, number ACTRN00363175. Results: The mean±SD age of the participants was 28±5 (range: 19–39 years. 42% of participants were female. The mean noise attenuation in the group with training was 13.88 dB, significantly higher than those observed in other groups. The highest attenuation was observed in high frequencies (4, 6, and 8 kHz in the group with training. Conclusion: Training in appropriate use of earplugs significantly affects the efficacy of earplugs—even more than using an earplug with higher NRR.

Role of ribavirin in HCV treatment response: now and in the future.

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Jain, Mamta K; Zoellner, Cindy

2010-03-01

Ribavirin is a broad spectrum antiviral agent that is used with pegylated IFN (Peg-IFN) for HCV treatment. Ribavirin does not significantly reduce HCV viral load when used alone but increases rates of sustained virologic response (SVR) when combined with Peg-IFN. HCV genotype 1 infected patients require higher doses of ribavirin administered for a longer duration of time versus HCV genotypes 2 and 3 patients who respond effectively to Peg-IFN with lower doses of ribavirin and shorter duration of therapy. Higher serum concentrations of ribavirin are associated with higher response rates but also higher rates of hemolytic anemia which is a dose limiting side effect. Alternatives to current therapy are under clinical evaluation. Systematic literature review of ribavirin use in HCV patients from 1995 to 2009 was conducted. To review the efficacy and safety of ribavirin in current HCV treatment and in new therapies in Phase III clinical trials. Ribavirin is a drug which is essential to produce higher SVR rates both with Peg-IFN and HCV protease inhibitors currently in Phase III clinical trials. Thus, ribavirin is and will remain an important drug to achieving higher SVR rates in HCV infected persons.

Prediction of clinical response to drugs in ovarian cancer using the chemotherapy resistance test (CTR-test).

Science.gov (United States)

Kischkel, Frank Christian; Meyer, Carina; Eich, Julia; Nassir, Mani; Mentze, Monika; Braicu, Ioana; Kopp-Schneider, Annette; Sehouli, Jalid

2017-10-27

In order to validate if the test result of the Chemotherapy Resistance Test (CTR-Test) is able to predict the resistances or sensitivities of tumors in ovarian cancer patients to drugs, the CTR-Test result and the corresponding clinical response of individual patients were correlated retrospectively. Results were compared to previous recorded correlations. The CTR-Test was performed on tumor samples from 52 ovarian cancer patients for specific chemotherapeutic drugs. Patients were treated with monotherapies or drug combinations. Resistances were classified as extreme (ER), medium (MR) or slight (SR) resistance in the CTR-Test. Combination treatment resistances were transformed by a scoring system into these classifications. Accurate sensitivity prediction was accomplished in 79% of the cases and accurate prediction of resistance in 100% of the cases in the total data set. The data set of single agent treatment and drug combination treatment were analyzed individually. Single agent treatment lead to an accurate sensitivity in 44% of the cases and the drug combination to 95% accuracy. The detection of resistances was in both cases to 100% correct. ROC curve analysis indicates that the CTR-Test result correlates with the clinical response, at least for the combination chemotherapy. Those values are similar or better than the values from a publication from 1990. Chemotherapy resistance testing in vitro via the CTR-Test is able to accurately detect resistances in ovarian cancer patients. These numbers confirm and even exceed results published in 1990. Better sensitivity detection might be caused by a higher percentage of drug combinations tested in 2012 compared to 1990. Our study confirms the functionality of the CTR-Test to plan an efficient chemotherapeutic treatment for ovarian cancer patients.

DNA methylation patterns of genes related to immune response in the different clinical forms of oral lichen planus.

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Cruz, Aline Fernanda; de Resende, Renata Gonçalves; de Lacerda, Júlio César Tanos; Pereira, Núbia Braga; Melo, Leonardo Augusto; Diniz, Marina Gonçalves; Gomes, Carolina Cavalieri; Gomez, Ricardo Santiago

2018-01-01

The oral lichen planus is a chronic inflammatory disease. Although its aetiology is not well understood, the role of T lymphocytes in its inflammatory events is recognised. Identifying the epigenetic mechanisms involved in the pathogenesis of this immune-mediated condition is fundamental for understanding the inflammatory reaction that occurs in the disease. The purpose of this work was to evaluate the methylation pattern of 21 immune response-related genes in the different clinical forms of oral lichen planus. A cross-sectional study was performed to analyse the DNA methylation patterns in three distinct groups of oral lichen planus: (i) reticular/plaque lesions; (ii) erosive lesions; (iii) normal oral mucosa (control group). After DNA extraction from biopsies, the samples were submitted to digestions by methylation-sensitive and methylation-dependent enzymes and double digestion. The relative percentage of methylated DNA for each gene was provided using real-time polymerase chain reaction arrays. Hypermethylation of the STAT5A gene was observed only in the control group (59.0%). A higher hypermethylation of the ELANE gene was found in reticular/plaque lesions (72.1%) compared to the erosive lesions (50.0%). Our results show variations in the methylation profile of immune response-related genes, according to the clinical type of oral lichen planus after comparing with the normal oral mucosa. Further studies are necessary to validate these findings using gene expression analysis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A quick behavioral dichotic word test is prognostic for clinical response to cognitive therapy for depression: A replication study.

Science.gov (United States)

Bruder, Gerard E; Haggerty, Agnes; Siegle, Greg J

2017-02-01

There are no commonly used clinical indicators of whether an individual will benefit from cognitive therapy (CT) for depression. A prior study found right ear (left hemisphere) advantage for perceiving dichotic words predicted CT response. This study replicates this finding at a different research center in clinical trials that included clinically representative samples and community therapists. Right-handed individuals with unipolar major depressive disorder who subsequently received 12-14 weeks of CT at the University of Pittsburgh were tested on dichotic fused words and complex tones tests. Responders to CT showed twice the mean right ear advantage in dichotic fused words performance than non-responders. Patients with a right ear advantage greater than the mean for healthy controls had an 81% response rate to CT, whereas those with performance lower than the mean for controls had a 46% response rate. Individuals with a right ear advantage, indicative of strong left hemisphere language dominance, may be better at utilizing cognitive processes and left frontotemporal cortical regions critical for success of CT for depression. Findings at two clinical research centers suggest that verbal dichotic listening may be a clinically disseminative brief, inexpensive and easily automated test prognostic for response to CT across diverse clinical settings. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Strategic response by providers to specialty hospitals, ambulatory surgery centers, and retail clinics.

Science.gov (United States)

Burns, Lawton R; David, Guy; Helmchen, Lorens A

2011-04-01

Radical innovation and disruptive technologies are frequently heralded as a solution to delivering higher quality, lower cost health care. According to the literature on disruption, local hospitals and physicians (incumbent providers) may be unable to competitively respond to such "creative destruction" and alter their business models for a host of reasons, thus threatening their future survival. However, strategic management theory and research suggest that, under certain conditions, incumbent providers may be able to weather the discontinuities posed by the disrupters. This article analyzes 3 disruptive innovations in service delivery: single-specialty hospitals, ambulatory surgical centers, and retail clinics. We first discuss the features of these innovations to assess how disruptive they are. We then draw on the literature on strategic adaptation to suggest how incumbents develop competitive responses to these disruptive innovations that assure their continued survival. These arguments are then evaluated in a field study of several urban markets based on interviews with both incumbents and entrants. The interviews indicate that entrants have failed to disrupt incumbent providers primarily as a result of strategies pursued by the incumbents. The findings cast doubt on the prospects for these disruptive innovations to transform health care.

CT in normal pressure hydrocephalus. Correlation between CT and clinical response to shunting

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Fujita, K.; Nogaki, H.; Noda, M.; Kusunoki, T.; Tamaki, N. (Kobe Univ. (Japan). School of Medicine)

1981-02-01

CT scans were obtained on 33 patients (age 73y. to 31y.) with the diagnosis of normal pressure hydrocephalus. In each case, the diagnosis was made on the basis of the symptoms, CT and cisternographic findings. Underlying diseases of normal pressure hydrocephalus are ruptured aneurysms (21 cases), arteriovenous malformations (2 cases), head trauma (1 case), cerebrovascular accidents (1 case) and idiopathie (8 cases). Sixteen of 33 patients showed marked improvement, five, moderate or minimal improvement, and twelve, no change. The results were compared with CT findings and clinical response to shunting. CT findings were classified into five types, bases on the degree of periventricular hypodensity (P.V.H.), the extent of brain damage by underlying diseases, and the degree of cortical atrophy. In 17 cases of type (I), CT shows the presence of P.V.H. with or without minimal frontal lobe damage and no cortical atrophy. The good surgical improvements were achieved in all cases of type (I) by shunting. In 4 cases of type (II), CT shows the presence of P.V.H. and severe brain damage without cortical atrophy. The fair clinical improvements were achieved in 2 cases (50%) by shunting. In one case of type (III), CT shows the absence of P.V.H. without brain damage nor cortical atrophy. No clinical improvement was obtained by shunting in this type. In 9 cases of type (IV) with mild cortical atrophy, the fair clinical improvement was achieved in two cases (22%) and no improvement in 7 cases. In 2 cases of type (V) with moderate or marked cortical atrophy, no clinical improvement was obtained by shunting. In conclusion, it appeared from the present study that there was a good correlation between the result of shunting and the type of CT, and clinical response to shunting operation might be predicted by classification of CT findings.

Prognostic value of response to external radiation in stage IIIB cancer cervix in predicting clinical outcomes: A retrospective analysis of 556 patients from India

International Nuclear Information System (INIS)

Saibishkumar, Elantholi P.; Patel, Firuza D.; Sharma, Suresh C.; Karunanidhi, Gunaseelan; Ghoshal, Sushmita; Kumar, Vinay; Kapoor, Rakesh

2006-01-01

Background and purpose: To evaluate the prognostic significance of response to external beam radiation (EBRT) in predicting the clinical outcomes in stage IIIB cancer cervix and to find out factors affecting response to EBRT. Patients and methods: This retrospective study included 556 patients of cancer cervix stage IIIB treated between 1996 and 2001 with EBRT (46 Gy/23fx/4.5 weeks) followed by intracavitary radiotherapy (ICRT). At the end of EBRT, response to EBRT was grouped as 'no gross residual tumor'(NRT) or 'gross residual tumor'(GRT). Results: Follow up ranged from 2 to 93 months with a median of 36 months. Median dose to point A was 81 Gy. At the end of EBRT, 393 patients (70.7%) attained NRT response. NRT responders had significantly better 5 year pelvic control, disease free survival (DFS) and overall survival (OS) than those who had a GRT response (75.6 vs. 54.6%; 60.6 vs. 31.9% and 62.6 vs. 33.7%, respectively; all P values <0.0001). Apart from response to EBRT, overall treatment time also has emerged as an independent factor to affect all clinical outcomes in multivariate analysis but age had significant impact on pelvic control only. Age was the only factor, which significantly influenced the response to EBRT in univariate as well as multivariate analysis (P=<0.001, OR=1.973, 95% C.I. 1.357-2.868). Patients with age more than 50 years had more NRT response (77%) than patients with age less than 50 years (63.8%). Conclusions: Patients who attain NRT response to EBRT will have an impressive long term pelvic control, DFS and OS in stage IIIB cancer cervix. Older patients (≥50 years) attain significantly higher NRT rates than younger patients

Catatonia: Etiopathological diagnoses and treatment response in a tertiary care setting: A clinical study

Directory of Open Access Journals (Sweden)

Santosh Ramdurg

2013-01-01

Full Text Available Aim: Catatonia is caused by a variety of psychiatric and organic conditions. The onset, clinical profile, and response to treatment may vary depending on the underlying cause. The study is an attempt to explore clinical profile, possible etiological correlates with neurotic/psychotic spectrum illnesses, and response to treatment and outcome in patients of catatonia. Materials and Methods: Retrospective chart analysis by using semistructured data sheet for the analysis of sociodemographic data, clinical profile, precipitating event, and response to treatment in patients with catatonic symptoms admitted to IHBAS (Institute of Human Behaviour and Allied Sciences, New Delhi, India from January 2009 to December 2010 was undertaken. Results: Catatonia was commonly observed in patients with the following profile - late twenties, female, Hindu religion, urban background, and housewives. Psychotic spectrum disorder (57%, N=35 was the most commonly entertained diagnosis and affective disorder (18%, N=11 being the second common. Thirty four percent of the subjects responded to lorazepam treatment and rest required modified electroconvulsive therapy (MECT. Conclusion: Catatonia is more likely to be associated with Schizophrenia and Other Psychotic Disorders in Indian settings. Majority of patients responded to therapy either by lorazepam alone or to its augmentation with modified ECT. The study being a retrospective one, the sample being representative of the treatment seeking group only, and unavailability of the follow up data were the limitations of the study

Bread Affects Clinical Parameters and Induces Gut Microbiome-Associated Personal Glycemic Responses.

Science.gov (United States)

Korem, Tal; Zeevi, David; Zmora, Niv; Weissbrod, Omer; Bar, Noam; Lotan-Pompan, Maya; Avnit-Sagi, Tali; Kosower, Noa; Malka, Gal; Rein, Michal; Suez, Jotham; Goldberg, Ben Z; Weinberger, Adina; Levy, Avraham A; Elinav, Eran; Segal, Eran

2017-06-06

Bread is consumed daily by billions of people, yet evidence regarding its clinical effects is contradicting. Here, we performed a randomized crossover trial of two 1-week-long dietary interventions comprising consumption of either traditionally made sourdough-leavened whole-grain bread or industrially made white bread. We found no significant differential effects of bread type on multiple clinical parameters. The gut microbiota composition remained person specific throughout this trial and was generally resilient to the intervention. We demonstrate statistically significant interpersonal variability in the glycemic response to different bread types, suggesting that the lack of phenotypic difference between the bread types stems from a person-specific effect. We further show that the type of bread that induces the lower glycemic response in each person can be predicted based solely on microbiome data prior to the intervention. Together, we present marked personalization in both bread metabolism and the gut microbiome, suggesting that understanding dietary effects requires integration of person-specific factors. Copyright © 2017 Elsevier Inc. All rights reserved.

Leadership Competency Development: A Higher Education Responsibility

Science.gov (United States)

Seemiller, Corey

2016-01-01

Moving from why, how, and what, this chapter closes with a focus on how we know the outcomes of leadership education. This final chapter provides an overview of leadership competency development as a critical component of higher education.

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

International Nuclear Information System (INIS)

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 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] 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 accuracy than

Clinical Response of Pelvic and Para-aortic Lymphadenopathy to a Radiation Boost in the Definitive Management of Locally Advanced Cervical Cancer

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Rash, Dominique L. [Department of Radiation Oncology, University of California Davis Medical Center, Sacramento, California (United States); Lee, Yongsook C. [Department of Radiation Oncology, University of Kansas School of Medicine, Kansas City, Kansas (United States); Kashefi, Amir [Division of Nuclear Medicine, Department of Radiology, University of California Davis Medical Center, Sacramento, California (United States); Durbin-Johnson, Blythe [Division of Biostatistics, Department of Public Health Sciences, University of California Davis School of Medicine, Sacramento, California (United States); Mathai, Mathew; Valicenti, Richard [Department of Radiation Oncology, University of California Davis Medical Center, Sacramento, California (United States); Mayadev, Jyoti S., E-mail: jyoti.mayadev@ucdmc.ucdavis.edu [Department of Radiation Oncology, University of California Davis Medical Center, Sacramento, California (United States)

2013-10-01

Purpose: Optimal treatment with radiation for metastatic lymphadenopathy in locally advanced cervical cancer remains controversial. We investigated the clinical dose response threshold for pelvic and para-aortic lymph node boost using radiographic imaging and clinical outcomes. Methods and Materials: Between 2007 and 2011, 68 patients were treated for locally advanced cervical cancer; 40 patients had clinically involved pelvic and/or para-aortic lymph nodes. Computed tomography (CT) or 18F-labeled fluorodeoxyglucose-positron emission tomography scans obtained pre- and postchemoradiation for 18 patients were reviewed to assess therapeutic radiographic response of individual lymph nodes. External beam boost doses to involved nodes were compared to treatment response, assessed by change in size of lymph nodes by short axis and change in standard uptake value (SUV). Patterns of failure, time to recurrence, overall survival (OS), and disease-free survival (DFS) were determined. Results: Sixty-four lymph nodes suspicious for metastatic involvement were identified. Radiation boost doses ranged from 0 to 15 Gy, with a mean total dose of 52.3 Gy. Pelvic lymph nodes were treated with a slightly higher dose than para-aortic lymph nodes: mean 55.3 Gy versus 51.7 Gy, respectively. There was no correlation between dose delivered and change in size of lymph nodes along the short axis. All lymph nodes underwent a decrease in SUV with a complete resolution of abnormal uptake observed in 68%. Decrease in SUV was significantly greater for lymph nodes treated with ≥54 Gy compared to those treated with <54 Gy (P=.006). Median follow-up was 18.7 months. At 2 years, OS and DFS for the entire cohort were 78% and 50%, respectively. Locoregional control at 2 years was 84%. Conclusions: A biologic response, as measured by the change in SUV for metastatic lymph nodes, was observed at a dose threshold of 54 Gy. We recommend that involved lymph nodes be treated to this minimum dose.

Prediction of Methotrexate Clinical Response in Portuguese Rheumatoid Arthritis Patients: Implication of MTHFR rs1801133 and ATIC rs4673993 Polymorphisms

Science.gov (United States)

Lima, Aurea; Monteiro, Joaquim; Bernardes, Miguel; Sousa, Hugo; Azevedo, Rita; Seabra, Vitor; Medeiros, Rui

2014-01-01

Objective. Methotrexate (MTX), the most used drug in rheumatoid arthritis (RA) treatment, showing variability in clinical response, is often associated with genetic polymorphisms. This study aimed to elucidate the role of methylenetetrahydrofolate reductase (MTHFR) C677T and aminoimidazole carboxamide adenosine ribonucleotide transformylase (ATIC) T675C polymorphisms and clinicopathological variables in clinical response to MTX in Portuguese RA patients. Methods. Study included 233 RA patients treated with MTX for at least six months. MTHFR C677T and ATIC T675C polymorphisms were genotyped and clinicopathological variables were collected. Statistical analyses were performed and binary logistic regression method adjusted to possible confounding variables. Results. Multivariate analyses demonstrated that MTHFR 677TT (OR = 4.63; P = 0.013) and ATIC 675T carriers (OR = 5.16; P = 0.013) were associated with over 4-fold increased risk for nonresponse. For clinicopathological variables, noncurrent smokers (OR = 7.98; P = 0.001), patients positive to anti-cyclic citrullinated peptide (OR = 3.53; P = 0.004) and antinuclear antibodies (OR = 2.28; P = 0.045), with higher health assessment questionnaire score (OR = 2.42; P = 0.007), and nonsteroidal anti-inflammatory drug users (OR = 2.77; P = 0.018) were also associated with nonresponse. Contrarily, subcutaneous administration route (OR = 0.11; P < 0.001) was associated with response. Conclusion. Our study suggests that MTHFR C677T and ATIC T675C genotyping combined with clinicopathological data may help to identify patients whom will not benefit from MTX treatment and, therefore, assist clinicians in personalizing RA treatment. PMID:24967362

Preoperative neutrophil response as a predictive marker of clinical outcome following open heart surgery and the impact of leukocyte filtration.

LENUS (Irish Health Repository)

Soo, Alan W

2010-11-01

Open heart surgery is associated with a massive systemic inflammatory response. Neutrophils, are the main mediator of this response. We hypothesised that the degree of neutrophil activation and inflammatory response to open heart surgery varies individually and correlates with clinical outcome. The aim of this study was to determine if individual clinical outcome can be predicted preoperatively through assessment of in-vitro stimulated neutrophil responses. Following that, the effects of neutrophil depletion through leukocyte filters are examined.

How Do Psychiatrists Apply the Minimum Clinically Important Difference to Assess Patient Responses to Treatment?

Directory of Open Access Journals (Sweden)

Alan J. McMichael BSc

2016-11-01

Full Text Available Symptom report scales are used in clinical practice to monitor patient outcomes. Using them permits the definition of a minimum clinically important difference (MCID beyond which a patient may be judged as having responded to treatment. Despite recommendations that clinicians routinely use MCIDs in clinical practice, statisticians disagree about how MCIDs should be used to evaluate individual patient outcomes and responses to treatment. To address this issue, we asked how clinicians actually use MCIDs to evaluate patient outcomes in response to treatment. Sixty-eight psychiatrists made judgments about whether hypothetical patients had responded to treatment based on their pre- and posttreatment change scores on the widely used Positive and Negative Syndrome Scale. Psychiatrists were provided with the scale’s MCID on which to base their judgments. Our secondary objective was to assess whether knowledge of the patient’s genotype influenced psychiatrists’ responder judgments. Thus, psychiatrists were also informed of whether patients possessed a genotype indicating hyperresponsiveness to treatment. While many psychiatrists appropriately used the MCID, others accepted a far lower posttreatment change as indicative of a response to treatment. When psychiatrists accepted a lower posttreatment change than the MCID, they were less confident in such judgments compared to when a patient’s posttreatment change exceeded the scale’s MCID. Psychiatrists were also less likely to identify patients as responders to treatment if they possessed a hyperresponsiveness genotype. Clinicians should recognize that when judging patient responses to treatment, they often tolerate lower response thresholds than warranted. At least some conflate their judgments with information, such as the patient’s genotype, that is irrelevant to a post hoc response-to-treatment assessment. Consequently, clinicians may be at risk of persisting with treatments that have failed

Inhaled corticosteroids do not influence the early inflammatory response and clinical presentation of hospitalized subjects with COPD exacerbation.

Science.gov (United States)

Crisafulli, Ernesto; Guerrero, Mónica; Menéndez, Rosario; Huerta, Arturo; Martinez, Raquel; Gimeno, Alexandra; Soler, Néstor; Torres, Antoni

2014-10-01

Inhaled corticosteroids are anti-inflammatory medications that can down-regulate the immunologic response in patients with COPD; however, their role at onset of COPD exacerbation is still not understood. The aim of this study was to assess the early inflammatory response and clinical presentation of patients with COPD exacerbation mediated by inhaled corticosteroids. Prospective data were collected on 123 hospitalized subjects with COPD exacerbation over a 30-month period at 2 Spanish university hospitals. Based on domiciliary use, comparative analyses were performed between subjects who did not use inhaled corticosteroids (n = 58) and subjects who did (n = 65). Measurements of serum biomarkers were recorded on admission to the hospital (day 1) and on day 3; clinical, physiological, microbiological, and severity data and mortality/readmission rates were also recorded. At days 1 and 3, both groups showed a similar inflammatory response; fluticasone produced lower levels of interleukin-8 compared with budesonide (P clinical features considered were similar in the 2 groups; multivariate analysis predicting clinical complications on hospitalization showed air-flow obstruction severity as the only predictive factor (odds ratio 3.13, 95% CI 1.13-8.63, P = .02). Our study demonstrates a lack of inhaled corticosteroid influence in the early systemic inflammatory response to and clinical presentation of COPD exacerbation. Copyright © 2014 by Daedalus Enterprises.

Treatment response in psychotic patients classified according to social and clinical needs, drug side effects, and previous treatment; a method to identify functional remission

DEFF Research Database (Denmark)

Alenius, Malin; Hammarlund-Udenaes, Margareta; Honoré, Per Gustaf Hartvig

2009-01-01

, fewer psychotic symptoms, and higher rate of workers than those with the worst treatment outcome. CONCLUSION: In the evaluation, CANSEPT showed validity in discriminating the patients of interest and was well tolerated by the patients. CANSEPT could secure inclusion of correct patients in the clinic......BACKGROUND: Various approaches have been made over the years to classify psychotic patients according to inadequate treatment response, using terms such as treatment resistant or treatment refractory. Existing classifications have been criticized for overestimating positive symptoms......; underestimating residual symptoms, negative symptoms, and side effects; or being to open for individual interpretation. The aim of this study was to present and evaluate a new method of classification according to treatment response and, thus, to identify patients in functional remission. METHOD: A naturalistic...

Does the use of a university lecturer as a visiting tutor support learning and assessment during physiotherapy students' clinical placements? A survey of higher education institution providers.

Science.gov (United States)

Dean, M; Levis, A

2016-12-01

To establish the rationale for using a lecturer as a visiting tutor, and to identify the activities undertaken during clinical placements to support student learning and assessment in practice. A secure electronic survey was used to incorporate qualitative and quantitative data collection procedures. Thirty-three higher education institution (HEI) providers of physiotherapy education in the UK, registered with the Chartered Society of Physiotherapy. UK HEI physiotherapy placement coordinators. A questionnaire was used to examine HEI perceptions. A pilot focus group consultation informed the questionnaire content. Surveys were analysed based on the proportion of responses to closed questions on an adapted Likert scale, with further thematic analysis of open questions. All 25 respondents (25/33, 76%) indicated their provision of support for students and clinical educators throughout their clinical placements. 'Face-to-face' engagement during the placement visit was viewed as essential to guide the clinical educator to provide a consistent approach to learning and assessment strategies; ensuring cohesion between theoretical and clinical components of the curriculum was viewed as a core objective by visiting academic tutors. However, the emergent themes highlighted key differences between HEIs' perspectives of what this support for clinical placement learning should entail. The majority of HEIs endorse the use of a lecturer as a visiting tutor to inform and maintain the standard of learning and assessment within the clinical placement. However, the value of this interaction requires confirmation via other stakeholders, and exploration of other forms of non-face-to-face support processes warrant further investigation. Copyright © 2015 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

A comparative study of therapeutic response of patients with clinical chancroid to ciprofloxacin, erythromycin, and cotrimoxazole.

Science.gov (United States)

D'Souza, P; Pandhi, R K; Khanna, N; Rattan, A; Misra, R S

1998-07-01

Cotrimoxazole has traditionally been used as first drug for treatment of chancroid in India. With reports of increasing resistance to the drug, this study was conducted to compare treatment response of clinical chancroid between ciprofloxacin, 500 mg twice daily for 3 days, erythromycin, 500 mg four times daily for 7 days, and double-strength cotrimoxazole (trimethoprim 160 mg + sulfamethoxazole 800 mg), twice daily for 7 days. Forty-six patients with a clinical diagnosis of chancroid were randomly divided into 3 groups. Sixteen patients received ciprofloxacin, whereas 15 each received erythromycin and cotrimoxazole. Patients were seen on day 7, 14, and if needed day 21. Clinical response was noted in terms of cure, improvement, or failure. Excellent response was observed to both ciprofloxacin and erythromycin therapy with cure rates of 93.7% and 93.3%, respectively. Improvement was observed in 6.7% cases in both groups. There were no failures with either ciprofloxacin or erythromycin. Poor response to cotrimoxazole therapy was observed with 53.3% cure rates and a high failure rate of 46.7%. Ciprofloxacin and erythromycin are equally effective in chancroid. Ciprofloxacin is better in terms of dosage schedule, duration of treatment, and low cost. Cotrimoxazole should be discontinued as drug of choice because of high failure rates.

Treatment response in psychotic patients classified according to social and clinical needs, drug side effects, and previous treatment; a method to identify functional remission.

Science.gov (United States)

Alenius, Malin; Hammarlund-Udenaes, Margareta; Hartvig, Per; Sundquist, Staffan; Lindström, Leif

2009-01-01

Various approaches have been made over the years to classify psychotic patients according to inadequate treatment response, using terms such as treatment resistant or treatment refractory. Existing classifications have been criticized for overestimating positive symptoms; underestimating residual symptoms, negative symptoms, and side effects; or being to open for individual interpretation. The aim of this study was to present and evaluate a new method of classification according to treatment response and, thus, to identify patients in functional remission. A naturalistic, cross-sectional study was performed using patient interviews and information from patient files. The new classification method CANSEPT, which combines the Camberwell Assessment of Need rating scale, the Udvalg for Kliniske Undersøgelser side effect rating scale (SE), and the patient's previous treatment history (PT), was used to group the patients according to treatment response. CANSEPT was evaluated by comparison of expected and observed results. In the patient population (n = 123), the patients in functional remission, as defined by CANSEPT, had higher quality of life, fewer hospitalizations, fewer psychotic symptoms, and higher rate of workers than those with the worst treatment outcome. In the evaluation, CANSEPT showed validity in discriminating the patients of interest and was well tolerated by the patients. CANSEPT could secure inclusion of correct patients in the clinic or in research.

Non-English speakers attend gastroenterology clinic appointments at higher rates than English speakers in a vulnerable patient population

Science.gov (United States)

Sewell, Justin L.; Kushel, Margot B.; Inadomi, John M.; Yee, Hal F.

2009-01-01

Goals We sought to identify factors associated with gastroenterology clinic attendance in an urban safety net healthcare system. Background Missed clinic appointments reduce the efficiency and availability of healthcare, but subspecialty clinic attendance among patients with established healthcare access has not been studied. Study We performed an observational study using secondary data from administrative sources to study patients referred to, and scheduled for an appointment in, the adult gastroenterology clinic serving the safety net healthcare system of San Francisco, California. Our dependent variable was whether subjects attended or missed a scheduled appointment. Analysis included multivariable logistic regression and classification tree analysis. 1,833 patients were referred and scheduled for an appointment between 05/2005 and 08/2006. Prisoners were excluded. All patients had a primary care provider. Results 683 patients (37.3%) missed their appointment; 1,150 (62.7%) attended. Language was highly associated with attendance in the logistic regression; non-English speakers were less likely than English speakers to miss an appointment (adjusted odds ratio 0.42 [0.28,0.63] for Spanish, 0.56 [0.38,0.82] for Asian language, p gastroenterology clinic appointment, not speaking English was most strongly associated with higher attendance rates. Patient related factors associated with not speaking English likely influence subspecialty clinic attendance rates, and these factors may differ from those affecting general healthcare access. PMID:19169147

[Good clinical practices in clinical trials: the responsibility of the researcher. A survey of 827 hospital physicians (I). Availability. Monitoring. Safety. Contract].

Science.gov (United States)

Dal-Ré, R

1993-03-06

The Law of Medicaments establishes that clinical trials (CT) with drugs must be carried out following the of Good Clinical Practice guidelines (GCP). The attitude of hospital physicians to the GCP prior to its implementation as mandatory in accordance with Spanish legislation was considered to be of interest. An anonymous survey was used with closed response questions. Questions referring to the responsibilities of the investigator included in the GCP were included. From December 1988 to February 1990 the survey was distributed among 1,706 hospital medical staff members, of any specialty, who had or had not participated in CT. In this article the results of the questions regarding the availability of the investigative team, CT monitorization, management of adverse reactions, the safety of the participants in the CT and the contract between the sponsor and the researcher are presented. A total of 827 hospital doctors replied to the survey. Fifty-nine percent had intervened in CT with drugs. At least 94% of those surveyed considered that the researcher must have the time and number of eligible patients which the CT requires. There was high acceptance (> or = 78%) of the clinical audits to be performed by the health authorities and the sponsor company of the CT. The need of urgent communication of the severe adverse reactions is admitted by a great majority (> or = 95%) of those surveyed. Eighty-five percent believe that patients should be insured against damage derived from CT with 76% considering that the investigator should sign a contract with the sponsor; 68% and 59% would hand in a copy of the same to the CT committee and the remainder of the research team, respectively. According to the Good Clinical Practice dealt with in this article, the responsibilities of the investigator have been widely accepted by the hospital physicians surveyed, therefore no problems should be expected upon the implementation of the same in this country. However, the economic

Response to combination antiretroviral therapy: variation by age

DEFF Research Database (Denmark)

Lundgren, Jens

2008-01-01

-naive individuals starting combination antiretroviral therapy from 1998 to 2006. OUTCOME MEASURES: Time from combination antiretroviral therapy initiation to HIV RNA less than 50 copies/ml (virological response), CD4 increase of more than 100 cells/microl (immunological response) and new AIDS/death were analysed...... response. The probability of virological response was lower in those aged 6-12 (adjusted hazard ratio: 0.87) and 13-17 (0.78) years, but was higher in those aged 50-54 (1.24), 55-59 (1.24) and at least 60 (1.18) years. The probability of immunological response was higher in children and younger adults...... and reduced in those 60 years or older. Those aged 55-59 and 60 years or older had poorer clinical outcomes after adjusting for the latest CD4 cell count. CONCLUSION: Better virological responses but poorer immunological responses in older individuals, together with low precombination antiretroviral therapy...

Definition of treatment response in rheumatoid arthritis based on the simplified and the clinical disease activity index.

Science.gov (United States)

Aletaha, Daniel; Martinez-Avila, Jose; Kvien, Tore K; Smolen, Josef S

2012-07-01

The simplified disease activity index (SDAI) and the clinical disease activity index (CDAI) are established instruments to measure disease activity in rheumatoid arthritis (RA). To date, no validated response definitions for the SDAI and CDAI are available. The authors aimed to define minor, moderate and major response criteria for the SDAI. The authors used data from two clinical trials on infliximab versus methotrexate in early (ASPIRE) or established (ATTRACT) RA, and identified the three SDAI cutpoints based on the best agreement (by κ statistics) with the American College of Rheumatology (ACR)20/50/70 responses. Cutpoints were then tested for different aspects of validity in the trial datasets and in a Norwegian disease modifying antirheumatic drug prescription dataset (NOR-DMARD). Based on agreement with the ACR response, the minor, moderate and major responses were identified as SDAI 50%, 70% and 85% improvement. These cutpoints had good face validity concerning the disease activity states achieved by the different response definitions. Construct validity was shown by a clear association of increasing SDAI response categories with increasing levels of functional improvement, achievement of better functional states and lower annual radiographic progression. Across SDAI 50/70/85, the sensitivities regarding a patient-perceived improvement decreased (73%/39%/22%) and the specificities increased (61%/89%/96%) in a meaningful way. Further, the cutpoints discriminated the different treatment arms in ASPIRE and ATTRACT. The same cutpoints were used for the CDAI, with similar results in the validation analyses. These new response criteria expand the usefulness of the SDAI and CDAI for their use as endpoints in clinical trials beyond the definition of disease activity categories.

Higher Education's Role in Educating for Personal and Social Responsibility: A Review of Existing Literature

Science.gov (United States)

Reason, Robert D.; Ryder, Andrew J.; Kee, Chad

2013-01-01

This chapter examines the existing literature in two major areas. A review of literature related to higher education's mission to educate for personal and social responsibility provides a rationale to refocus our collective attention on this important area of student learning and development. The chapter also reviews the current understanding…

Clinical complete response (cCR) after neoadjuvant chemoradiotherapy and conservative treatment in rectal cancer. Findings from the ACCORD 12/PRODIGE 2 randomized trial

International Nuclear Information System (INIS)

Gérard, Jean-Pierre; Chamorey, Emmanuel; Gourgou-Bourgade, Sophie; Benezery, Karène; Laroche, Guy de; Mahé, Marc-André; Boige, Valérie; Juzyna, Béata

2015-01-01

Background: During the ACCORD 12 randomized trial, an evaluation of the clinical tumor response was prospectively performed after neoadjuvant chemoradiotherapy. The correlations between clinical complete response and patient characteristics and treatment outcomes are reported. Material and methods: Between 2005 and 2008 the Accord 12 trial accrued 598 patients with locally advanced rectal cancer and compared two different neoadjuvant chemoradiotherapies (Capox 50: capecitabine + oxaliplatin + 50 Gy vs Cap 45: capecitabine + 45 Gy). An evaluation of the clinical tumor response with rectoscopy and digital rectal examination was planned before surgery. A score to classify tumor response was used adapted from the RECIST definition: complete response: no visible or palpable tumor; partial response, stable and progressive disease. Results: The clinical tumor response was evaluable in 201 patients. Score was: complete response: 8% (16 patients); partial response: 68% (137 patients); stable: 21%; progression: 3%. There was a trend toward more complete response in the Capox 50 group (9.3% vs 6.7% with Cap 45). In the whole cohort of 201 pts complete response was significantly more frequent in T2 tumors (28%; p = 0.025); tumors <4 cm in diameter (14%; p = 0.017), less than half rectal circumference and with a normal CEA level. Clinical complete response observed in 16 patients was associated with more conservative treatment (p = 0.008): 2 patients required an abdomino-perineal resection, 11 an anterior resection and 3 patients benefited from organ preservation (2 local excision, 1 “watch and wait”. A complete response was associated with more ypT0 (73%; p < 0.001); ypNO (92%); R0 circumferential margin (100%). Conclusion: These data support the hypothesis that a clinical complete response assessed using rectoscopy and digital rectal examination after neoadjuvant therapy may increase the chance of a sphincter or organ preservation in selected rectal cancers

Clinical complete response (cCR) after neoadjuvant chemoradiotherapy and conservative treatment in rectal cancer. Findings from the ACCORD 12/PRODIGE 2 randomized trial.

Science.gov (United States)

Gérard, Jean-Pierre; Chamorey, Emmanuel; Gourgou-Bourgade, Sophie; Benezery, Karène; de Laroche, Guy; Mahé, Marc-André; Boige, Valérie; Juzyna, Béata

2015-05-01

During the ACCORD 12 randomized trial, an evaluation of the clinical tumor response was prospectively performed after neoadjuvant chemoradiotherapy. The correlations between clinical complete response and patient characteristics and treatment outcomes are reported. Between 2005 and 2008 the Accord 12 trial accrued 598 patients with locally advanced rectal cancer and compared two different neoadjuvant chemoradiotherapies (Capox 50: capecitabine+oxaliplatin+50Gy vs Cap 45: capecitabine+45Gy). An evaluation of the clinical tumor response with rectoscopy and digital rectal examination was planned before surgery. A score to classify tumor response was used adapted from the RECIST definition: complete response: no visible or palpable tumor; partial response, stable and progressive disease. The clinical tumor response was evaluable in 201 patients. Score was: complete response: 8% (16 patients); partial response: 68% (137 patients); stable: 21%; progression: 3%. There was a trend toward more complete response in the Capox 50 group (9.3% vs 6.7% with Cap 45). In the whole cohort of 201 pts complete response was significantly more frequent in T2 tumors (28%; p=0.025); tumors <4cm in diameter (14%; p=0.017), less than half rectal circumference and with a normal CEA level. Clinical complete response observed in 16 patients was associated with more conservative treatment (p=0.008): 2 patients required an abdomino-perineal resection, 11 an anterior resection and 3 patients benefited from organ preservation (2 local excision, 1 "watch and wait". A complete response was associated with more ypT0 (73%; p<0.001); ypNO (92%); R0 circumferential margin (100%). These data support the hypothesis that a clinical complete response assessed using rectoscopy and digital rectal examination after neoadjuvant therapy may increase the chance of a sphincter or organ preservation in selected rectal cancers. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Clinical chemistry in higher dimensions: Machine-learning and enhanced prediction from routine clinical chemistry data.

Science.gov (United States)

Richardson, Alice; Signor, Ben M; Lidbury, Brett A; Badrick, Tony

2016-11-01

Big Data is having an impact on many areas of research, not the least of which is biomedical science. In this review paper, big data and machine learning are defined in terms accessible to the clinical chemistry community. Seven myths associated with machine learning and big data are then presented, with the aim of managing expectation of machine learning amongst clinical chemists. The myths are illustrated with four examples investigating the relationship between biomarkers in liver function tests, enhanced laboratory prediction of hepatitis virus infection, the relationship between bilirubin and white cell count, and the relationship between red cell distribution width and laboratory prediction of anaemia. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Regulation of phosphate starvation responses in higher plants.

Science.gov (United States)

Yang, Xiao Juan; Finnegan, Patrick M

2010-04-01

Phosphorus (P) is often a limiting mineral nutrient for plant growth. Many soils worldwide are deficient in soluble inorganic phosphate (P(i)), the form of P most readily absorbed and utilized by plants. A network of elaborate developmental and biochemical adaptations has evolved in plants to enhance P(i) acquisition and avoid starvation. Controlling the deployment of adaptations used by plants to avoid P(i) starvation requires a sophisticated sensing and regulatory system that can integrate external and internal information regarding P(i) availability. In this review, the current knowledge of the regulatory mechanisms that control P(i) starvation responses and the local and long-distance signals that may trigger P(i) starvation responses are discussed. Uncharacterized mutants that have P(i)-related phenotypes and their potential to give us additional insights into regulatory pathways and P(i) starvation-induced signalling are also highlighted and assessed. An impressive list of factors that regulate P(i) starvation responses is now available, as is a good deal of knowledge regarding the local and long-distance signals that allow a plant to sense and respond to P(i) availability. However, we are only beginning to understand how these factors and signals are integrated with one another in a regulatory web able to control the range of responses demonstrated by plants grown in low P(i) environments. Much more knowledge is needed in this agronomically important area before real gains can be made in improving P(i) acquisition in crop plants.

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

International Nuclear Information System (INIS)

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

1982-01-01

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

Axitinib dose titration: analyses of exposure, blood pressure and clinical response from a randomized phase II study in metastatic renal cell carcinoma.

Science.gov (United States)

Rini, B I; Melichar, B; Fishman, M N; Oya, M; Pithavala, Y K; Chen, Y; Bair, A H; Grünwald, V

2015-07-01

In a randomized, double-blind phase II trial in patients with metastatic renal cell carcinoma (mRCC), axitinib versus placebo titration yielded a significantly higher objective response rate. We evaluated pharmacokinetic and blood pressure (BP) data from this study to elucidate relationships among axitinib exposure, BP change, and efficacy. Patients received axitinib 5 mg twice daily during a lead-in period. Patients who met dose-titration criteria were randomized 1:1 to stepwise dose increases with axitinib or placebo. Patients ineligible for randomization continued without dose increases. Serial 6-h and sparse pharmacokinetic sampling were carried out; BP was measured at clinic visits and at home in all patients, and by 24-h ambulatory BP monitoring (ABPM) in a subset of patients. Area under the plasma concentration-time curve from 0 to 24 h throughout the course of treatment (AUCstudy) was higher in patients with complete or partial responses than those with stable or progressive disease in the axitinib-titration arm, but comparable between these groups in the placebo-titration and nonrandomized arms. In the overall population, AUCstudy and efficacy outcomes were not strongly correlated. Mean BP across the population was similar when measured in clinic, at home, or by 24-h ABPM. Weak correlations were observed between axitinib steady-state exposure and diastolic BP. When grouped by change in diastolic BP from baseline, patients in the ≥10 and ≥15 mmHg groups had longer progression-free survival. Optimal axitinib exposure may differ among patients with mRCC. Pharmacokinetic or BP measurements cannot be used exclusively to guide axitinib dosing. Individualization of treatment with vascular endothelial growth factor receptor tyrosine kinase inhibitors, including axitinib, is thus more complex than anticipated and cannot be limited to a single clinical factor. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical

The Localized Scleroderma Cutaneous Assessment Tool: responsiveness to change in a pediatric clinical population.

Science.gov (United States)

Kelsey, Christina E; Torok, Kathryn S

2013-08-01

Lack of agreement on how to accurately capture disease outcomes in localized scleroderma (LS) has hindered the development of efficacious treatment protocols. The LS Cutaneous Assessment Tool (LoSCAT), consisting of the modified LS Skin Severity Index (mLoSSI) and the LS Damage Index, has potential for use in clinical trials. The goal of this article is to further evaluate the clinical responsiveness of the LoSCAT. Based on the modifiable nature of disease activity versus damage, we expected the mLoSSI to be responsive to change. At 2 study visits, a physician completed the LoSCAT and Physician Global Assessment (PGA) of Disease Activity and of Disease Damage for 29 patients with LS. Spearman correlations were used to examine the relationships between the change in the LoSCAT and the PGA scores. To evaluate contrasted group validity, patients were grouped according to disease activity classification and change scores of groups were compared. Minimal clinically important differences were calculated and compared with the standard error of measurement. Change in the mLoSSI score correlated strongly with change in the PGA of Disease Activity score, whereas change in the LS Damage Index score correlated weakly with change in the PGA of Disease Damage score. The mLoSSI and PGA of Disease Activity exhibited contrasted group validity. Minimal clinically important differences for the activity measures were greater than the respective standard errors of measurement. Only 2 study visits were included in analysis. This study gives further evidence that the LoSCAT, specifically the mLoSSI, is a responsive, valid measure of activity in LS and should be used in future treatment studies. Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Cholera in pregnancy: Clinical and immunological aspects.

Science.gov (United States)

Khan, Ashraful I; Chowdhury, Fahima; Leung, Daniel T; Larocque, Regina C; Harris, Jason B; Ryan, Edward T; Calderwood, Stephen B; Qadri, Firdausi

2015-10-01

The objective of this study was to examine the clinical and immunological features of cholera in pregnancy. Women of reproductive age presenting to the icddr,b Dhaka hospital with cholera, and enrolled as part of a larger cohort study, were tested for pregnancy on admission. We compared initial clinical features and immune responses of pregnant patients with non-pregnant female patients at days 2, 7 and 21 after infection. Among reproductive age women enrolled between January 2001 and May 2006, 9.7% (14/144) were pregnant. The duration of diarrhoea prior to admission tended to be higher in pregnant compared to non-pregnant patients (p=0.08), but other clinical characteristics did not differ. Antibody responses to cholera toxin B subunit (CtxB), toxin-coregulated pilus A (TcpA), Vibrio cholerae lipopolysaccharide (LPS), and serum vibriocidal antibody responses, were comparable between pregnant and non-pregnant patients. There were no deaths among the pregnant cases or non-pregnant controls, and no adverse foetal outcomes, including stillbirths, during 21 days of follow up of pregnant cases. To our knowledge, this is the first report of immune responses in pregnant women with cholera. We found that pregnant woman early in pregnancy has comparable clinical illness and subsequent immune responses compared to non-pregnant women. These findings suggest that the evaluation of safety and immunogenicity of oral cholera vaccines in pregnancy should be an area of future investigations. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Multilevel Higher-Order Item Response Theory Models

Science.gov (United States)

Huang, Hung-Yu; Wang, Wen-Chung

2014-01-01

In the social sciences, latent traits often have a hierarchical structure, and data can be sampled from multiple levels. Both hierarchical latent traits and multilevel data can occur simultaneously. In this study, we developed a general class of item response theory models to accommodate both hierarchical latent traits and multilevel data. The…

T cell responsiveness correlates differentially with antibody isotype levels in clinical and asymptomatic filariasis

NARCIS (Netherlands)

Yazdanbakhsh, M.; Paxton, W. A.; Kruize, Y. C.; Sartono, E.; Kurniawan, A.; van het Wout, A.; Selkirk, M. E.; Partono, F.; Maizels, R. M.

1993-01-01

To establish the relationships among T and B cell responses, active infection, and clinical manifestations in lymphatic filariasis, filarial-specific lymphocyte proliferation, IgG antibody isotypes, and IgE levels were determined in an exposed population: 31 asymptomatic amicrofilaremics, 43

Value of the free light chain analysis in the clinical evaluation of response in multiple myeloma patients receiving anti-myeloma therapy

DEFF Research Database (Denmark)

Toftmann Hansen, Charlotte; Pedersen, Per T.; Jensen, Bo Amdi

Value of the free light chain analysis in the clinical evaluation of response in multiple myeloma patients receiving anti-myeloma therapy.......Value of the free light chain analysis in the clinical evaluation of response in multiple myeloma patients receiving anti-myeloma therapy....

Association of regulatory TPH2 polymorphisms with higher reduction in depressive symptoms in children and adolescents treated with fluoxetine.

Science.gov (United States)

Gassó, Patricia; Rodríguez, Natalia; Boloc, Daniel; Blázquez, Ana; Torres, Teresa; Gortat, Ana; Plana, Maria Teresa; Lafuente, Amalia; Mas, Sergi; Arnaiz, Joan Albert; Lázaro, Luisa

2017-07-03

Genetic variability related to the brain serotonergic system has a significant impact on both the susceptibility to psychiatric disorders, such as major depressive disorder (MDD), and the response to antidepressant drugs, such as fluoxetine. TPH2 is one of the most important serotonergic candidate genes in selective serotonin reuptake inhibitors (SSRIs) pharmacogenetic studies. The aim of the present study was to evaluate the influence of regulatory polymorphisms that are specifically located in human TPH2 transcription factor binding sites (TFBSs), and therefore could be functional by altering gene expression, on clinical improvement in children and adolescents treated with fluoxetine. The selection of SNPs was also based on their linkage disequilibrium with TPH2 rs4570625, a genetic variant with questionable functionality, which was previously associated with clinical response in our pediatric population. A total of 83 children and adolescents were clinically evaluated 12weeks after initiating antidepressant treatment with fluoxetine for the first time. Clinical improvement was assessed by reductions in depressive symptoms measured using the Children's Depression Inventory (CDI) scale. The polymorphisms rs11179002, rs60032326 and rs34517220 were, for the first time in the literature, significantly associated with higher clinical improvement. The strongest association was found for rs34517220. In particular, minor allele homozygotes showed higher score reductions on the CDI scale compared with the major allele carriers. Interestingly, this polymorphism is located in a human TPH2 TFBS for two relevant transcription factors in the serotoninergic neurons, Foxa1 and Foxa2, which together with the high level of significance found for this SNP, could indicate that rs34517220 is in fact the crucial functional genetic variant related to the fluoxetine response. These results provide new evidence for the role of regulatory genetic variants that could modulate human TPH2

The OnyCOE-t™ questionnaire: responsiveness and clinical meaningfulness of a patient-reported outcomes questionnaire for toenail onychomycosis

Directory of Open Access Journals (Sweden)

Kianifard Farid

2006-08-01

Full Text Available Abstract Background This research was conducted to confirm the validity and reliability and to assess the responsiveness and clinical meaningfulness of the OnyCOE-t™, a questionnaire specifically designed to measure patient-reported outcomes (PRO associated with toenail onychomycosis. Methods 504 patients with toenail onychomycosis randomized to receive 12 weeks of terbinafine 250 mg/day with or without target toenail debridement in the IRON-CLAD® trial completed the OnyCOE-t™ at baseline, weeks 6, 12, 24, and 48. The OnyCOE-t™ is composed of 6 multi-item scales and 1 single-item scale. These include a 7-item Toenail Symptom assessment, which comprises both Symptom Frequency and Symptom Bothersomeness scales; an 8-item Appearance Problems scale; a 7-item Physical Activities Problems scale; a 1-item Overall Problem scale; a 7-item Stigma scale; and a 3-item Treatment Satisfaction scale. In total, 33 toenail onychomycosis-specific items are included in the OnyCOE-t™. Clinical data, in particular the percent clearing of mycotic involvement in the target toenail, and OnyCOE-t™ responses were used to evaluate the questionnaire's reliability, validity, responsiveness, and the minimally clinical important difference (MCID. Results The OnyCOE-t™ was shown to be reliable and valid. Construct validity and known groups validity were acceptable. Internal consistency reliability of multi-item scales was demonstrated by Cronbach's alpha > .84. Responsiveness was good, with the Treatment Satisfaction, Symptom Frequency, Overall Problem, and Appearance Problem scales demonstrating the most responsiveness (Guyatt's statistic of 1.72, 1.31, 1.13, and 1.11, respectively. MCID was evaluated for three different clinical measures, and indicated that approximately an 8.5-point change (on a 0 to 100 scale was clinically meaningful based on a 25% improvement in target nail clearing. Conclusion The OnyCOE-t™ questionnaire is a unique, toenail-specific PRO

Inspiring hope-A physician's responsibility, translating the science into clinical practice.

Science.gov (United States)

Temple, Walley J

2018-03-01

Giving hope to patients is our responsibility. It is the essence of a meaningful practice in medicine. Science now allows us to understand this complex and multidimensional human dynamic, and translate it into clinical practice. Quantitative research has shown hope is strong even in terminal illness. Through qualitative methodology hope fostering strategies and hope hindering behaviors have been identified. This exciting new knowledge facilitates the challenging task of disclosure of bad news while enabling hope. © 2017 Wiley Periodicals, Inc.

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

OpenAIRE

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

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...

Clinical profile of congenital adrenal hyperplasia and short-term response to treatment

International Nuclear Information System (INIS)

Lal, S.; Lal, S.; Jamro, B.U.; Jamro, S.

2015-01-01

To determine the clinical presentation of congenital adrenal hyperplasia and short- term response to treatment. Background: Congenital adrenal hyperplasia (CAH) is a genetic disorder which usually presents with life threatening emergencies. Awareness of physicians regarding these presentations is an essential for early diagnosis and lifesaving treatment. In view of the prevalence of the condition as reported from tertiary care centers within the country and other parts of the globe, we had carried out a study in the paediatric department of Shaheed Mohtrama Benazir Bhutto Medical University Larkana. Material and Methods: The study was conducted over a period of one year from July 2012 to June 2013. All infants presenting with vomiting, dehydration, shock, failure to thrive and ambiguous genitalia were examined and investigated thoroughly. The diagnosis was based upon a raised level of serum 17 OHP in a child with suggestive clinical features. Results: A total of 40 children were diagnosed to have CAH during the study period. The major presenting features were vomiting in 13 (32.5%), ambiguous genitalia 17 (42.5%), vomiting and ambiguous genitalia 10 (25%), shock 5(12.5%) and failure to thrive in 13 (32.5%) of cases. All the patients were followed up after initiation of treatment and good response was observed to short-term treatment. Conclusion: This study highlights the importance of common clinical features like vomiting, unreasonable dehydration, shock and ambiguous genitalia being the presenting features of CAH and the effectiveness of replacement therapy in amending life threatening emergencies due to this condition. (author)

Exposure-response relationships in patients with metastatic renal cell carcinoma receiving sunitinib: maintaining optimum efficacy in clinical practice.

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Ravaud, Alain; Bello, Carlo L

2011-06-01

Targeted agents such as sunitinib, an oral, multitargeted receptor tyrosine kinase inhibitor, have greatly improved the prognosis for patients with metastatic renal cell carcinoma (mRCC). In this review we analyse data from sunitinib preclinical and clinical studies in detail and consider the key implications for the effective use of sunitinib in clinical practice. Sunitinib has shown efficacy and acceptable tolerability in patients with mRCC in phase II and III clinical studies. In a pivotal phase III study in treatment-naïve patients with mRCC, median progression-free survival for sunitinib-treated patients was double of that with interferon-α (P relationship between clinical end points and sunitinib exposure showed that increased sunitinib exposure was associated with a greater probability of objective response, longer time to tumour progression and overall survival, as well as some increased risk of specific adverse events. It is important to consider the relationship between exposure and response to maximize clinical benefit from sunitinib treatment.

Clinical response to chemotherapy in locally advanced breast cancer was not associated with several polymorphisms in detoxification enzymes and DNA repair genes.

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Saadat, Mostafa; Khalili, Maryam; Nasiri, Meysam; Rajaei, Mehrdad; Omidvari, Shahpour; Saadat, Iraj

2012-03-02

The main aim of the present study was to investigate the association between several genetic polymorphisms (in glutathione S-transferase members and DNA repair genes) and clinical response to chemotherapy in locally advanced breast cancer. A sequential series of 101 patients were prospectively included in this study. Clinical assessment of treatment was accomplished by comparing initial tumor size with preoperative tumor size using revised RECIST guideline (version 1.1). Clinical response was regarded as a response or no response. There was no difference between non-responders and responders for the prevalence of genotypes of the study polymorphisms. Copyright © 2012 Elsevier Inc. All rights reserved.

The human immune response to streptococcal extracellular antigens: clinical, diagnostic, and potential pathogenetic implications.

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Johnson, Dwight R; Kurlan, Roger; Leckman, James; Kaplan, Edward L

2010-02-15

Determination of an immune response to group A Streptococcus (GAS) antigens, frequently anti-streptolysin O and anti-DNase B, is crucial for documentation of bona fide GAS infection. Although the importance of immunologic confirmation of infection is widely accepted, the immediate and long-term immunokinetics of the human antibody response are incompletely documented and poorly understood. Pediatric study participants (n = 160) were followed during a 2-year study with monthly throat cultures (n = 3491) and blood samples (n = 1679) obtained every 13 weeks. Recovered GAS were characterized; serum anti-streptolysin O and anti-DNase B antibody titers were determined. Antibody titers and GAS culture results were temporally correlated and analyzed. The analyses clearly document, in some instances for the first time, that an increase in antibody titer more accurately defines infection than does an absolute titer (eg, "upper limit of normal"), that antibody titers can remain elevated for many months even without GAS, and that some individuals may harbor GAS continuously for months or years without symptoms of infection and without an associated immune response. Measuring 2 different antibodies is more accurate in defining infection. Single time-point cultures and single antibody titers are often misleading. Sequential samples more accurately define infection, allowing correlation of titer increases with temporal confirmation of GAS acquisition. Understanding kinetics of the immune response(s) to GAS infection is necessary in formulating accurate clinical diagnostic conclusions, to appropriate design of clinical and epidemiological studies examining the association of GAS with subsequent sequelae, and to providing insight into pathogenetic mechanisms associated with this important human pathogen.

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

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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.

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

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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.

Role perceptions of nurse clinical research coordinators

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Jones CT

2013-09-01

Full Text Available Carolynn Thomas Jones, Lynda L Wilson School of Nursing, University of Alabama at Birmingham, Birmingham, AL, USA Abstract: Nursing roles in clinical research have evolved in the last 3 decades and include diverse responsibilities and job titles. Nurse clinical research coordinators’ (NCRCs roles include study planning, implementation, participant recruitment and retention, assessment of participants’ responses to clinical protocols, data management, and evaluation. The purpose of this study was to examine NCRCs’ perceptions of 59 specific clinical research activities that have been proposed as a taxonomy of NCRC activities. Participants were asked to check whether each of the 59 activities is being performed, and whether those activities should be performed, by NCRCs. The sample included 61 NCRCs who were attending the annual meeting of the International Association of Clinical Research Nurses. The percentage of respondents who indicated that the 59 activities are being performed by NCRCs at their sites ranged from 55%–98.4%. The percentage of respondents who indicated that the 59 activities should be performed by NCRCs ranged from 61.7%–88.5%. There were eight activities that fewer than 70% of the respondents reported should be performed by NCRCs. Chi-square analyses were conducted to determine whether there was a difference in the distribution of responses to the “are performed” versus “should be performed” responses for each of the 59 activities. There were significant differences in the distributions for 49 of the activities. The percentage of nurses responding “are performed” was higher than the percentage of responses to the “should be performed” items for 41 of these 49 activities. Findings suggest that further research is needed to validate the extent to which the taxonomy of clinical research nurse (CRN roles is a valid reflection of the actual practice of NCRCs, and also to explore reasons for the

A multi-dataset time-reversal approach to clinical trial placebo response and the relationship to natural variability in epilepsy.

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Goldenholz, Daniel M; Strashny, Alex; Cook, Mark; Moss, Robert; Theodore, William H

2017-12-01

Clinical epilepsy drug trials have been measuring increasingly high placebo response rates, up to 40%. This study was designed to examine the relationship between the natural variability in epilepsy, and the placebo response seen in trials. We tested the hypothesis that 'reversing' trial direction, with the baseline period as the treatment observation phase, would reveal effects of natural variability. Clinical trial simulations were run with time running forward and in reverse. Data sources were: SeizureTracker.com (patient reported diaries), a randomized sham-controlled TMS trial, and chronically implanted intracranial EEG electrodes. Outcomes were 50%-responder rates (RR50) and median percentage change (MPC). The RR50 results showed evidence that temporal reversal does not prevent large responder rates across datasets. The MPC results negative in the TMS dataset, and positive in the other two. Typical RR50s of clinical trials can be reproduced using the natural variability of epilepsy as a substrate across multiple datasets. Therefore, the placebo response in epilepsy clinical trials may be attributable almost entirely to this variability, rather than the "placebo effect". Published by Elsevier Ltd.

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

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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.

Neutralizing antibodies explain the poor clinical response to Interferon beta in a small proportion of patients with Multiple Sclerosis: a retrospective study

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Cefaro Luca

2009-10-01

Full Text Available Abstract Background Neutralizing antibodies (NAbs against Interferon beta (IFNβ are reported to be associated with poor clinical response to therapy in multiple sclerosis (MS patients. We aimed to quantify the contribution of NAbs to the sub-optimal response of IFNβ treatment. Methods We studied the prevalence of NAbs in MS patients grouped according to their clinical response to IFNβ during the treatment period. Patients were classified as: group A, developing ≥ 1 relapse after the first 6 months of therapy; group B, exhibiting confirmed disability progression after the first 6 months of therapy, with or without superimposed relapses; group C, presenting a stable disease course during therapy. A cytopathic effect assay tested the presence of NAbs in a cohort of ambulatory MS patients treated with one of the available IFNβ formulations for at least one year. NAbs positivity was defined as NAbs titre ≥ 20 TRU. Results Seventeen patients (12.1% were NAbs positive. NAbs positivity correlated with poorer clinical response (p Conclusion The majority of patients with poor clinical response are NAbs negative suggesting that NAbs explains only partially the sub-optimal response to IFNβ.

REACTOGENITY OF TICK-BORNE ENCEPHALITIS VACCINE ENCEPUR ADULT AND IMMUNE RESPONSE

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G. N. Leonova

2005-01-01

Full Text Available Abstract. The comprehensive clinical-immunological characteristic of a tick-borne encephalitis vaccine En-cepur Adult (Germany, which was studied on a group of residents of Far East of Russia was discussed. Reactogenity in 32,4% of vaccinees was characterized by minor clinical manifestations and was due to the reaction to specific vaccine albumin. Expression of immune response (mean geometric titers was evaluated in a neutralization test. A group with the reactogenity showed higher geometric mean antibody titers (1:182 compared with a group without the reactogenity (1:97.All of vaccinees with various levels (high, middle, low of specific immune response had an increased quantity of CD20+ and CD25+ lymphocytes. We showed a difference in immunologic reactivity of people with high and low levels of specific antibody response. As compared with a low level group the group with a high level of specific response showed significantly higher quantity of lymphocytes and their subpopulations (CD3+, CD4+, CD45RA+ as well as higher levels of IgM, IgG.We conclude that vaccine Encepur Adult (Germany possesses a high immunologic activity. It is recommended to use this vaccine as a safe and effective specific preventive remedy in TBE endemic areas.

Impact of a new vaccine clinic on hepatitis B vaccine completion and immunological response rates in an HIV-positive cohort.

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Rock, Clare; de Barra, Eoghan; Sadlier, Corinna; Kelly, Sinead; Dowling, Catherine; McNally, Cora; Bergin, Colm

2013-06-01

Hepatitis B virus vaccination (HBVV) in the HIV-infected population has poor reported completion rates and immunological response rates. At our HIV clinic, we established a vaccine clinic to improve HBVV outcomes using interventions such as SMS text reminders and double-dose (DD) HBVV for standard-dose non-responders (SD NRs). A five-year (2003-2008) retrospective review of the completion rates and immunological response rates for HBVV after the establishment of the dedicated vaccine clinic was conducted. Statistical significance was assumed at presponse rate to DD HBVV among SD NRs. On-treatment analysis showed an 88% (155/176) overall immunological response to SD HBVV and DD HBVV, if required. High HBVV completion and response rates in this HIV cohort were enabled through the use of multiple interventions, including the use of SMS text message reminders and routine referral for DD vaccination. Copyright © 2012 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

Roles and Responsibilities, and Education and Training Requirements for Clinically Qualified Medical Physicists

International Nuclear Information System (INIS)

2013-01-01

The IAEA technical cooperation project Strengthening Medical Physics in Radiation Medicine was approved by the IAEA Board of Governors for the period 2009-2013 with the aim of ensuring the safe and effective diagnosis and treatment of patients. The IAEA, together with the World Health Organization and stakeholders from numerous medical physics professional societies worldwide, including the International Organization for Medical Physics (IOMP), the European Federation of Organisations for Medical Physics, the American Association of Physicists in Medicine (AAPM), the Latin American Medical Physics Association, the Asia-Oceania Federation of Organizations for Medical Physics, the European Society for Radiotherapy and Oncology, the European Commission and the International Radiation Protection Association, as well as regional counterparts from Africa, Asia, Europe and Latin America, met in Vienna in May 2009 to plan and coordinate the new project. A shortage of clinically qualified medical physicists (CQMPs), insufficient education and training (especially properly organized and coordinated clinical training), and lack of professional recognition were identified as the main problems to be addressed under this project. This publication was developed under the project framework in response to these findings. It aims, first, at defining appropriately and unequivocally the roles and responsibilities of a CQMP in specialties of medical physics related to the use of ionizing radiation, such as radiation therapy, nuclear medicine, and diagnostic and interventional radiology. Important, non-ionizing radiation imaging specialties, such as magnetic resonance and ultrasound, are also considered for completeness. On the basis of these tasks, this book provides recommended minimum requirements for the academic education and clinical training of CQMPs, including recommendations for their accreditation, certification and registration, along with continuing professional development

Roles and Responsibilities, and Education and Training Requirements for Clinically Qualified Medical Physicists

Energy Technology Data Exchange (ETDEWEB)

NONE

2013-08-15

The IAEA technical cooperation project Strengthening Medical Physics in Radiation Medicine was approved by the IAEA Board of Governors for the period 2009-2013 with the aim of ensuring the safe and effective diagnosis and treatment of patients. The IAEA, together with the World Health Organization and stakeholders from numerous medical physics professional societies worldwide, including the International Organization for Medical Physics (IOMP), the European Federation of Organisations for Medical Physics, the American Association of Physicists in Medicine (AAPM), the Latin American Medical Physics Association, the Asia-Oceania Federation of Organizations for Medical Physics, the European Society for Radiotherapy and Oncology, the European Commission and the International Radiation Protection Association, as well as regional counterparts from Africa, Asia, Europe and Latin America, met in Vienna in May 2009 to plan and coordinate the new project. A shortage of clinically qualified medical physicists (CQMPs), insufficient education and training (especially properly organized and coordinated clinical training), and lack of professional recognition were identified as the main problems to be addressed under this project. This publication was developed under the project framework in response to these findings. It aims, first, at defining appropriately and unequivocally the roles and responsibilities of a CQMP in specialties of medical physics related to the use of ionizing radiation, such as radiation therapy, nuclear medicine, and diagnostic and interventional radiology. Important, non-ionizing radiation imaging specialties, such as magnetic resonance and ultrasound, are also considered for completeness. On the basis of these tasks, this book provides recommended minimum requirements for the academic education and clinical training of CQMPs, including recommendations for their accreditation, certification and registration, along with continuing professional development

Computer-mediated communication and time pressure induce higher cardiovascular responses in the preparatory and execution phases of cooperative tasks.

Science.gov (United States)

Costa Ferrer, Raquel; Serrano Rosa, Miguel Ángel; Zornoza Abad, Ana; Salvador Fernández-Montejo, Alicia

2010-11-01

The cardiovascular (CV) response to social challenge and stress is associated with the etiology of cardiovascular diseases. New ways of communication, time pressure and different types of information are common in our society. In this study, the cardiovascular response to two different tasks (open vs. closed information) was examined employing different communication channels (computer-mediated vs. face-to-face) and with different pace control (self vs. external). Our results indicate that there was a higher CV response in the computer-mediated condition, on the closed information task and in the externally paced condition. These role of these factors should be considered when studying the consequences of social stress and their underlying mechanisms.

Response to Bile Salts in Clinical Strains of Acinetobacter baumannii Lacking the AdeABC Efflux Pump: Virulence Associated with Quorum Sensing

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Maria López

2017-05-01

Full Text Available Introduction:Acinetobacter baumannii is an opportunistic nosocomial pathogen associated with multiple infections. This pathogen usually colonizes (first stage of microbial infection host tissues that are in contact with the external environment. As one of the sites of entry in human hosts is the gastrointestinal tract, the pathogen must be capable of tolerating bile salts. However, studies analyzing the molecular characteristics involved in the response to bile salts in clinical strains of A. baumannii are scarce.Material and Methods: Microbiological and transcriptional studies (arrays and RT-PCR in the response to bile salts were carried out in isogenic (A. baumanni ΔadeB ATCC 17978 and A. baumannii ΔadeL ATCC 17978 and clinical strains from clone ST79/PFGE-HUI-1 which is characterized by lacking the AdeABC efflux pump and by overexpression the AdeFGH efflux pump.Results and Discussion: In presence of bile salts, in addition to the glutamate/aspartate transporter were found overexpressed in A. baumannii ΔadeB ATCC 17978, the virulence factors (surface motility, biofilm, and Type VI Secretion System which are associated with activation of the Quorum Sensing system. Overexpression of these factors was confirmed in clinical strains of clone ST79/PFGE-HUI-1.Conclusions: This the first study about the adaptive response to bile salts investigating the molecular and microbiological characteristics in response to bile salts of an isogenic model of A. baumannii ATCC 17978 and clinical isolates of A. baumannii (clinical strains of ST79/PFGE-HUI-1 lacking the main RND efflux pump (AdeABC. Clinical isolates of A. baumannii lacking the AdeABC efflux pump (clone ST79/PFGE-HUI-1 displayed a new clinical profile (increased invasiveness possibly associated with the response to stress conditions (such as the presence of bile salts.

Response to Bile Salts in Clinical Strains of Acinetobacter baumannii Lacking the AdeABC Efflux Pump: Virulence Associated with Quorum Sensing.

Science.gov (United States)

López, Maria; Blasco, Lucia; Gato, Eva; Perez, Astrid; Fernández-Garcia, Laura; Martínez-Martinez, Luis; Fernández-Cuenca, Felipe; Rodríguez-Baño, Jesús; Pascual, Alvaro; Bou, German; Tomás, Maria

2017-01-01

Introduction: Acinetobacter baumannii is an opportunistic nosocomial pathogen associated with multiple infections. This pathogen usually colonizes (first stage of microbial infection) host tissues that are in contact with the external environment. As one of the sites of entry in human hosts is the gastrointestinal tract, the pathogen must be capable of tolerating bile salts. However, studies analyzing the molecular characteristics involved in the response to bile salts in clinical strains of A. baumannii are scarce. Material and Methods: Microbiological and transcriptional studies (arrays and RT-PCR) in the response to bile salts were carried out in isogenic ( A. baumanni Δ adeB ATCC 17978 and A. baumannii Δ adeL ATCC 17978) and clinical strains from clone ST79/PFGE-HUI-1 which is characterized by lacking the AdeABC efflux pump and by overexpression the AdeFGH efflux pump. Results and Discussion: In presence of bile salts, in addition to the glutamate/aspartate transporter were found overexpressed in A. baumannii Δ adeB ATCC 17978, the virulence factors (surface motility, biofilm, and Type VI Secretion System) which are associated with activation of the Quorum Sensing system. Overexpression of these factors was confirmed in clinical strains of clone ST79/PFGE-HUI-1. Conclusions: This the first study about the adaptive response to bile salts investigating the molecular and microbiological characteristics in response to bile salts of an isogenic model of A. baumannii ATCC 17978 and clinical isolates of A. baumannii (clinical strains of ST79/PFGE-HUI-1) lacking the main RND efflux pump (AdeABC). Clinical isolates of A. baumannii lacking the AdeABC efflux pump (clone ST79/PFGE-HUI-1) displayed a new clinical profile (increased invasiveness) possibly associated with the response to stress conditions (such as the presence of bile salts).

Unexpected High Response Rate to Traditional Therapy after Dendritic Cell-Based Vaccine in Advanced Melanoma: Update of Clinical Outcome and Subgroup Analysis

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Laura Ridolfi

2010-01-01

Full Text Available We reviewed the clinical results of a dendritic cell-based phase II clinical vaccine trial in stage IV melanoma and analyzed a patient subgroup treated with standard therapies after stopping vaccination. From 2003 to 2009, 24 metastatic melanoma patients were treated with mature dendritic cells pulsed with autologous tumor lysate and keyhole limpet hemocyanin and low-dose interleukin-2. Overall response (OR to vaccination was 37.5% with a clinical benefit of 54.1%. All 14 responders showed delayed type hypersensitivity positivity. Median overall survival (OS was 15 months (95% CI, 8–33. Eleven patients underwent other treatments (3 surgery, 2 biotherapy, 2 radiotherapy, 2 chemotherapy, and 4 biochemotherapy after stopping vaccination. Of these, 2 patients had a complete response and 5 a partial response, with an OR of 63.6%. Median OS was 34 months (range 16–61. Our results suggest that therapeutic DC vaccination could favor clinical response in patients after more than one line of therapy.

Unexpected high response rate to traditional therapy after dendritic cell-based vaccine in advanced melanoma: update of clinical outcome and subgroup analysis.

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Ridolfi, Laura; Petrini, Massimiliano; Fiammenghi, Laura; Granato, Anna Maria; Ancarani, Valentina; Pancisi, Elena; Scarpi, Emanuela; Guidoboni, Massimo; Migliori, Giuseppe; Sanna, Stefano; Tauceri, Francesca; Verdecchia, Giorgio Maria; Riccobon, Angela; Valmorri, Linda; Ridolfi, Ruggero

2010-01-01

We reviewed the clinical results of a dendritic cell-based phase II clinical vaccine trial in stage IV melanoma and analyzed a patient subgroup treated with standard therapies after stopping vaccination. From 2003 to 2009, 24 metastatic melanoma patients were treated with mature dendritic cells pulsed with autologous tumor lysate and keyhole limpet hemocyanin and low-dose interleukin-2. Overall response (OR) to vaccination was 37.5% with a clinical benefit of 54.1%. All 14 responders showed delayed type hypersensitivity positivity. Median overall survival (OS) was 15 months (95% CI, 8-33). Eleven patients underwent other treatments (3 surgery, 2 biotherapy, 2 radiotherapy, 2 chemotherapy, and 4 biochemotherapy) after stopping vaccination. Of these, 2 patients had a complete response and 5 a partial response, with an OR of 63.6%. Median OS was 34 months (range 16-61). Our results suggest that therapeutic DC vaccination could favor clinical response in patients after more than one line of therapy.

Natural history and clinical response: "it's the virus, stupid, or is it the host?".

Science.gov (United States)

Nucara, Stefania; Caroleo, Benedetto; Guadagnino, Vincenzo; Perrotti, Nicola; Trapasso, Francesco

2012-01-01

A major goal of modern medicine is the application of personalized therapies, consisting of decisions and practices tailored to the individual patient. Information about genetic variants, either mutant or polymorphic, represents the basis for the development of this clinical approach. Recently, several independent genome-wide association studies (GWAS) have identified two single nucleotide polymorphisms (SNPs) on the IL28B locus associated with HCV containment, spontaneous clearance, treatment response, and disease progression. In this minireview we will concisely discuss some critical genetic concepts that may have possible implications for clinical decisions in the treatment of HCV infection.

Examination of a clinical teaching effectiveness instrument used for summative faculty assessment.

Science.gov (United States)

Bierer, S Beth; Hull, Alan L

2007-12-01

This study explores whether a clinical teaching effectiveness (CTE) instrument provides valid scores for summative faculty assessment. The sample included all CTE instruments (n = 10,087) that learners (N = 1,194) completed to assess clinical teachers (N = 872) during 1 academic year. The authors investigated response processes (e.g., missing data, straight-line responses, level of learner), internal structure (e.g., confirmatory and exploratory factor analysis), teaching ratings by learner group (medical student or resident), and relation to other variables (e.g., correlation with global rating). Response processes identified a high prevalence of straight-line responses (same rating across all items) and differential patterns of missing data by learner group. Medical students rated their teachers higher than residents, and CTE scores had different factor structures depending on learner group. High correlation coefficients of CTE items with a single rating of overall teaching performance suggest that learners consider global performance when assessing clinical teaching performance.

Association between IL-6 production in synovial explants from rheumatoid arthritis patients and clinical and imaging response to biologic treatment: A pilot study.

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Martin Andersen

Full Text Available The need for biomarkers which can predict disease course and treatment response in rheumatoid arthritis (RA is evident. We explored whether clinical and imaging responses to biologic disease modifying anti-rheumatic drug treatment (bDMARD were associated with the individual's mediator production in explants obtained at baseline.RA Patients were evaluated by disease activity score 28 joint C-reactive protein (DAS 28-, colour Doppler ultrasound (CDUS and 3 Tesla RA magnetic resonance imaging scores (RAMRIS. Explants were established from synovectomies from a needle arthroscopic procedure prior to initiation of bDMARD. Explants were incubated with the bDMARD in question, and the productions of interleukin-6 (IL-6, monocyte chemo-attractive protein-1 (MCP-1 and macrophage inflammatory protein-1-beta (MIP-1b were measured by multiplex immunoassays. The changes in clinical and imaging variables following a minimum of 3 months bDMARD treatment were compared to the baseline explant results. Mixed models and Spearman's rank correlations were performed. P-values below 0.05 were considered statistically significant.16 patients were included. IL-6 production in bDMARD-treated explants was significantly higher among clinical non-responders compared to responders (P = 0.04, and a lack of suppression of IL-6 by the bDMARDS correlated to a high DAS-28 (ρ = 0.57, P = 0.03, CDUS (ρ = 0.53, P = 0.04 and bone marrow oedema (ρ = 0.56, P = 0.03 at follow-up. No clinical association was found with explant MCP-1 production. MIP-1b could not be assessed due to a large number of samples below the detection limit.Synovial explants appear to deliver a disease-relevant output testing which when carried out in advance of bDMARD treatment can potentially pave the road for a more patient tailored treatment approach with better treatment effects.

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

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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. © The Author(s) 2013.

Experimental and numerical investigations of higher mode effects on seismic inelastic response of reinforced concrete shear walls

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Ghorbanirenani, Iman

This thesis presents two experimental programs together with companion numerical studies that were carried out on reinforced concrete shear walls: static tests and dynamic (shake table) tests. The first series of experiments were monotonic and cyclic quasi-static testing on ductile reinforced concrete shear wall specimens designed and detailed according to the seismic provisions of NBCC 2005 and CSA-A23.3-04 standard. The tests were carried out on full-scale and 1:2.37 reduced scale wall specimens to evaluate the seismic design provisions and similitude law and determine the appropriate scaling factor that could be applied for further studies such as dynamic tests. The second series of experiments were shake table tests conducted on two identical 1:2.33 scaled, 8-storey moderately ductile reinforced concrete shear wall specimens to investigate the effects of higher modes on the inelastic response of slender walls under high frequency ground motions expected in Eastern North America. The walls were designed and detailed according to the seismic provisions of NBCC 2005 and CSA-A23.3-04 standard. The objectives were to validate and understand the inelastic response and interaction of shear, flexure and axial loads in plastic hinge zones of the walls considering the higher mode effects and to investigate the formation of second hinge in upper part of the wall due to higher mode responses. Second mode response significantly affected the response of the walls. This caused inelastic flexural response to develop at the 6th level with approximately the same rotation ductility compared to that observed at the base. Dynamic amplification of the base shear forces was also observed in both walls. Numerical modeling of these two shake table tests was performed to evaluate the test results and validate current modeling approaches. Nonlinear time history analyses were carried out by the reinforced concrete fibre element (OpenSees program) and finite element (VecTor2 program

Variability of plasma homovanillic acid over 13 months in patients with schizophrenia; relationship with the clinical response and the Wisconsin card sort test.

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Zumárraga, Mercedes; González-Torres, Miguel A; Arrue, Aurora; Dávila, Ricardo; Dávila, Wendy; Inchausti, Lucía; Pérez-Cabeza, Lucía; Fernández-Rivas, Aránzazu; Bustamante, Sonia; Basterreche, Nieves; Guimón, José

2011-08-01

In the present study we have measured, on a monthly basis, the concentration of plasma homovanillic acid (pHVA) in schizophrenic patients during 13 months of their pharmacological treatment. The average pHVA values of each patient were within the range of 7.30-17.70 ng/ml and the coefficients of variation for each patient (CV %) were within the range of 13-33%. Half of the patients that showed higher pHVA CV% values also showed higher scores on the Brief Psychiatric Rating Scale at the beginning of the study, and improved more after 6 months, when compared to the remaining 50% with lower CV% values. There was no significant relationship between the scores of the Wisconsin Card Sort Test and the concentration or the CV% of the pHVA of each patient. A greater variability in the pHVA may be associated with a greater plasticity of the dopaminergic system and a better clinical response.

Orienting-defense responses and psychophysiological reactivity in isolated clinic versus sustained hypertension.

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García-Vera, María Paz; Sanz, Jesús; Labrador, Francisco J

2007-04-01

This study sought to determine whether patients with white-coat or isolated clinic hypertension (ICH) show, in comparison to patients with sustained hypertension (SH), a defense response pattern to novel stimuli and an enhanced psychophysiological reactivity to stress. Forty-three patients with essential hypertension were divided into two groups after 16 days of self-monitoring blood pressure (BP): ICH (24 men; self-measured BP men; self-measured BP >or= 135/85 mmHg). Defense responses were measured as the cardiac changes to phasic non-aversive auditory stimuli. Psychophysiological reactivity (heart and breath rate, blood volume pulse, electromyography, and skin conductance) was measured during mental arithmetic and video game tasks. The standard deviation of self-measured BPs and the difference between mean BPs at work and at home were used as indicators of cardiovascular reactivity to daily stress. No significant differences were seen in defense responses or psychophysiological reactivity to laboratory or naturally occurring stressors. These results do not support the hypothesis that ICH can be explained in terms of a generalized hyperreactivity to novel or stressful stimuli.

DNA damage and repair in peripheral blood lymphocytes from healthy individuals and cancer patients: a pilot study on the implications in the clinical response to chemotherapy.

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Nadin, Silvina Beatriz; Vargas-Roig, Laura M; Drago, Gisela; Ibarra, Jorge; Ciocca, Daniel R

2006-07-28

Drug resistance is considered the main impediment to successful cancer chemotherapy. The quest for a method useful to predict individual responses to chemotherapy prior to treatment is highly desired. This study was designed to determine the individual influences of doxorubicin and cisplatin on the degree of DNA damage, DNA repair and hMSH2 and the hMLH1 protein expression in peripheral blood lymphocytes (PBL) and their correlations with the clinical response. PBL were obtained from 25 cancer patients (pre- and post-chemotherapy) and from 10 healthy persons, cultured and exposed to doxorubicin or cisplatin. Cells were collected at T0 (immediately after drug treatment) and 24h after damage (T24). The alkaline comet assay was employed to assess the DNA damage and repair function, and immunocytochemistry to study hMLH1 and hMSH2 expression. Clinical response was evaluated after three cycles of chemotherapy. Pre-chemotherapy PBL from cancer patients showed significantly higher levels of basal DNA damage than healthy persons, with appreciable interindividual variations between them. The in vivo administration of antineoplasic drugs was accompanied by significant DNA damage, and an increased in the number of apoptotic cells. Cancer patients with complete response showed a high number of apoptotic cells. The DNA migration increased at T0 and at T24 in cisplatin-treated patients, reflecting a decreased rate of cisplatin adducts repair than that observed in healthy individuals. The ability to repair DNA lesions in doxorubicin-damaged cells was very similar between healthy individuals and cancer patients. Cisplatin-treated patients that died by the disease showed lower DNA migration than the mean value. The expression of hMLH1 and hMSH2 was practically identical between healthy individuals and cancer patients. Nevertheless, chemotherapy induced a depletion mostly of hMLH1. In 83% of cisplatin-treated patients with CR the hMLH1 and hMSH2 expression at T24 was higher than the

Warfarin resistance associated with genetic polymorphism of VKORC1: linking clinical response to molecular mechanism using computational modeling.

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Lewis, Benjamin C; Nair, Pramod C; Heran, Subash S; Somogyi, Andrew A; Bowden, Jeffrey J; Doogue, Matthew P; Miners, John O

2016-01-01

The variable response to warfarin treatment often has a genetic basis. A protein homology model of human vitamin K epoxide reductase, subunit 1 (VKORC1), was generated to elucidate the mechanism of warfarin resistance observed in a patient with the Val66Met mutation. The VKORC1 homology model comprises four transmembrane (TM) helical domains and a half helical lid domain. Cys132 and Cys135, located in the N-terminal end of TM-4, are linked through a disulfide bond. Two distinct binding sites for warfarin were identified. Site-1, which binds vitamin K epoxide (KO) in a catalytically favorable orientation, shows higher affinity for S-warfarin compared with R-warfarin. Site-2, positioned in the domain occupied by the hydrophobic tail of KO, binds both warfarin enantiomers with similar affinity. Displacement of Arg37 occurs in the Val66Met mutant, blocking access of warfarin (but not KO) to Site-1, consistent with clinical observation of warfarin resistance.

[Taking personal responsibility in practice: what does it mean?--Insights into daily clinical routines].

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Hansen, Leonhard

2012-01-01

In our society, taking personal responsibility is basically regarded as a key step to adopting a more active lifestyle. In health care, however, personal responsibility is primarily equated with higher levels of financial contribution from patients. Obviously, the individual's responsibility for his or her health and towards the mutually supportive community is a highly emotional and ideological issue, so the debate is usually rather heated. This is, however, at odds with the "empowered patient" concept. In the present paper "personal responsibility in practice" will be understood to include both physician and patient responsibility. Examples will be employed to demonstrate that, on an individual level, physicians are responsible for diagnosing and treating their patients as indicated and that, on a collective level, they are expected to make responsible use of the resources allocated. Here, patient responsibility will be defined as both taking care for one's own health and the individual's obligation to contribute to the maintenance of our solidarity-based health care system. The tensions between solidarity and subsidiarity and personal responsibility, respectively, will be outlined, and a readjustment of the relation between external support and individual strengths, between solidarity and personal responsibility in terms of Sect. 1 of the Social Book Code V will be advocated. Copyright © 2012. Published by Elsevier GmbH.

Clinical course and treatment response in patients with thyroid hot nodule

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Fard Esfahani, A; Aghayousefi, H.R.; Eftekhari, M.; Fallahi, B.; Saghari, M.

2002-01-01

This is a retrospective study on clinical course and treatment response of patients with thyroid hot nodule, referred to nuclear medicine department of shariaty hospital from 1360 to 1377. From the total 58 patients with average age of 43 year and incidence peak of 40 year, 81 % were female and 19 % were male. 64 % of the patients were thyrotoxic and 36 % were euthyroid at presentation. Thyrotoxic symptoms and signs increased with age (p= 0.04). 57% of patients received I-131 therapy without premedication. 7% received antithyroid drugs first and then underwent iodine therapy. From 36% of the patients who were euthyroid at presentation, 15.5 % became thyrotoxic on follow up studies and received I-131 therapy, but 20.7 % remained euthyroid without receiving andy therapy. The average of first and cumulative radioiodine doses were 16.9 mci and 21.8 mci, respectively. Treatment response during 6 and 12 month follow up were 80 % and 86.7 %, respectively. The more administered the first dose, the better was the response (p= 0.03). Men appeared to need more I-131 dosage and times of therapy as compared to women. Post radioiodine hypothyroidism incidence was 7.5 % during one year follow up. No meaningful relation was found between times of radioiodine therapy and thyroid or nodule size

Rapid response predicts 12-month post-treatment outcomes in binge-eating disorder: theoretical and clinical implications

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Grilo, C. M.; White, M. A.; Wilson, G. T.; Gueorguieva, R.; Masheb, R. M.

2011-01-01

Background We examined rapid response in obese patients with binge-eating disorder (BED) in a clinical trial testing cognitive behavioral therapy (CBT) and behavioral weight loss (BWL). Method Altogether, 90 participants were randomly assigned to CBT or BWL. Assessments were performed at baseline, throughout and post-treatment and at 6- and 12-month follow-ups. Rapid response, defined as ≥70% reduction in binge eating by week four, was determined by receiver operating characteristic curves and used to predict outcomes. Results Rapid response characterized 57% of participants (67% of CBT, 47% of BWL) and was unrelated to most baseline variables. Rapid response predicted greater improvements across outcomes but had different prognostic significance and distinct time courses for CBT versus BWL. Patients receiving CBT did comparably well regardless of rapid response in terms of reduced binge eating and eating disorder psychopathology but did not achieve weight loss. Among patients receiving BWL, those without rapid response failed to improve further. However, those with rapid response were significantly more likely to achieve binge-eating remission (62% v. 13%) and greater reductions in binge-eating frequency, eating disorder psychopathology and weight loss. Conclusions Rapid response to treatment in BED has prognostic significance through 12-month follow-up, provides evidence for treatment specificity and has clinical implications for stepped-care treatment models for BED. Rapid responders who receive BWL benefit in terms of both binge eating and short-term weight loss. Collectively, these findings suggest that BWL might be a candidate for initial intervention in stepped-care models with an evaluation of progress after 1 month to identify non-rapid responders who could be advised to consider a switch to a specialized treatment. PMID:21923964

Clinical characteristics and long-term response to mood stabilizers in patients with bipolar disorder and different age at onset

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Dell’Osso, Bernardo; Buoli, Massimiliano; Riundi, Riccardo; D’Urso, Nazario; Pozzoli, Sara; Bassetti, Roberta; Mundo, Emanuela; Altamura, A Carlo

2009-01-01

Introduction Bipolar disorder (BD) is a prevalent, comorbid, and impairing condition. Potential predictors of response to pharmacological treatment are object of continuous investigation in patients with BD. The present naturalistic study was aimed to assess clinical features and long-term response to mood stabilizers in a sample of bipolar subjects with different ages at onset. Methods The study sample included 108 euthymic patients, diagnosed as affected by BD, either type I or II, according to the DSM-IV-TR, who were started on mood stabilizer treatment. Patients were followed-up for 24 months and the occurrence of any mood episode collected. At the end of the follow-up, patients were divided in 3 subgroups according to the age at onset (early-onset ≤30 years, middle-onset >30–≤45 years, and late-onset >45 years, respectively) and the long-term response to mood stabilizers was compared between them along with other clinical features. Results The three subgroups showed significant differences in terms of clinical and demographic features and, with respect to long-term response to mood stabilizers, the early-onset subgroup showed a better outcome in terms of reduction of major depressive episodes during the 24-month follow-up compared to the other subgroups (one way ANOVA, F = 3.57, p = 0.032). Conclusions Even though further controlled studies are needed to clarify the relationship between age at onset and outcome in BD, the present follow-up study suggests clinical peculiarities and different patterns of response to mood stabilizers across distinct subgroups of patients with BD and different ages at onset. PMID:19649214

A 'joint venture' model of recontacting in clinical genomics: challenges for responsible implementation.

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Dheensa, Sandi; Carrieri, Daniele; Kelly, Susan; Clarke, Angus; Doheny, Shane; Turnpenny, Peter; Lucassen, Anneke

2017-07-01

Advances in genomics often lead healthcare professionals (HCPs) to learn new information, e.g., about reinterpreted variants that could have clinical significance for patients seen previously. A question arises of whether HCPs should recontact these former patients. We present some findings interrogating the views of patients (or parents of patients) with a rare or undiagnosed condition about how such recontacting might be organised ethically and practically. Forty-one interviews were analysed thematically. Participants suggested a 'joint venture' model in which efforts to recontact are shared with HCPs. Some proposed an ICT-approach involving an electronic health record that automatically alerts them to potentially relevant updates. The need for rigorous privacy controls and transparency about who could access their data was emphasised. Importantly, these findings highlight that the lack of clarity about recontacting is a symptom of a wider problem: the lack of necessary infrastructure to pool genomic data responsibly, to aggregate it with other health data, and to enable patients/parents to receive updates. We hope that our findings will instigate a debate about the way responsibilities for recontacting under any joint venture model could be allocated, as well as the limitations and normative implications of using ICT as a solution to this intractable problem. As a first step to delineating responsibilities in the clinical setting, we suggest HCPs should routinely discuss recontacting with patients/parents, including the new information that should trigger a HCP to initiate recontact, as part of the consent process for genetic testing. Copyright © 2017 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Assessment of the response of tumours to radiation: clinical and experimental studies

International Nuclear Information System (INIS)

Suit, H.D.; Walker, A.M.

1980-01-01

There is an important and active research programme at the laboratory and clinical level to develop indicators of the ultimate local response of tumours to radiation. In order to be of great value clinically indicators should yield a high true positivity and a low false positivity so that revisions of therapeutic strategy will be made only when there is a real need for such a change. The available data in the literature from the clinical studies, when analysed in terms of the true and false positive rates, indicate that the extent of regression at the completion of external beam therapy is not a useful prognostic indicator. This pertains to populations of tumour of a specific histopathological type, tumour size and anatomic site. Studies of laboratory animal tumour models have shown that regression patterns may be useful prognostic indicators for a tumour which is characterized by moderate immunogenicity and where there is close correlation between complete regression and permanent control. In contrast for tumours which are weakly or nonimmunogenic and which regress completely even at low tumour control probabilities, the pattern of regression has not been demonstrated to be of prognostic value. (author)

Radiation response in vitro of fibroblasts from a Fanconi anemia patient with marked clinical radiosensitivity

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Djuzenova, C.; Flentje, M. [Dept. of Radiotherapy, Univ. of Wuerzburg, Wuerzburg (Germany); Plowman, P.N. [Radiotherapy/Clinical Oncology, St. Bartholomew' s Hospital, London (United Kingdom)

2004-12-01

Background: fanconi anemia (FA) is an autosomal recessive chromosome instability disorder characterized by progressive pancytopenia and cancer susceptibility. The risks of radiation therapy in FA patients who have cancer remain to be investigated. Recently, Marcou et al. (2001) reported a case of severe clinical radiosensitivity in a female FA patient with a tonsillar squamous cell carcinoma treated by radiotherapy. By contrast, her in vitro irradiated skin fibroblasts revealed nearly normal radiosensitivity as determined by the colony survival assay. Material and methods: in view of this discrepancy, the radiation response of this particular FA fibroblast strain (designated 425BR) was further analyzed in the present study by means of the alkaline single-cell gel electrophoresis (Comet) assay, and also by the cytochalasin-blocked micronuclei (MN) test. In addition, the expression levels of DNA repair proteins, hMre11, Rad50, and Rad51, were investigated using Western blot and foci immunofluorescence staining. Results: the Comet assay revealed that the initial DNA fragmentation in irradiated FA cells was two times higher and the DNA rejoining process was three times slower than that in control (1BR3) fibroblasts. Moreover, although the baseline level of MNs was lower in FA cells than in controls, the FA fibroblasts were more prone (about two times) to MN production than control cells when irradiated with 2-4 Gy. Western blot analysis of the DNA repair proteins (hMre11, Rad50, and Rad51) did not reveal any abnormalities in protein expression levels or their migration patterns in the fibroblasts derived from an FA patient either before or after irradiation. At the same time, in vitro irradiated cells from the FA patient exhibited a significantly reduced number of nuclei with focally concentrated DNA repair Rad51 protein than in control cells. Conclusion: the increased DNA damage and MN induction in irradiated FA fibroblasts, and the reduction of the formation of DNA

Radiation response in vitro of fibroblasts from a Fanconi anemia patient with marked clinical radiosensitivity

International Nuclear Information System (INIS)

Djuzenova, C.; Flentje, M.; Plowman, P.N.

2004-01-01

Background: fanconi anemia (FA) is an autosomal recessive chromosome instability disorder characterized by progressive pancytopenia and cancer susceptibility. The risks of radiation therapy in FA patients who have cancer remain to be investigated. Recently, Marcou et al. (2001) reported a case of severe clinical radiosensitivity in a female FA patient with a tonsillar squamous cell carcinoma treated by radiotherapy. By contrast, her in vitro irradiated skin fibroblasts revealed nearly normal radiosensitivity as determined by the colony survival assay. Material and methods: in view of this discrepancy, the radiation response of this particular FA fibroblast strain (designated 425BR) was further analyzed in the present study by means of the alkaline single-cell gel electrophoresis (Comet) assay, and also by the cytochalasin-blocked micronuclei (MN) test. In addition, the expression levels of DNA repair proteins, hMre11, Rad50, and Rad51, were investigated using Western blot and foci immunofluorescence staining. Results: the Comet assay revealed that the initial DNA fragmentation in irradiated FA cells was two times higher and the DNA rejoining process was three times slower than that in control (1BR3) fibroblasts. Moreover, although the baseline level of MNs was lower in FA cells than in controls, the FA fibroblasts were more prone (about two times) to MN production than control cells when irradiated with 2-4 Gy. Western blot analysis of the DNA repair proteins (hMre11, Rad50, and Rad51) did not reveal any abnormalities in protein expression levels or their migration patterns in the fibroblasts derived from an FA patient either before or after irradiation. At the same time, in vitro irradiated cells from the FA patient exhibited a significantly reduced number of nuclei with focally concentrated DNA repair Rad51 protein than in control cells. Conclusion: the increased DNA damage and MN induction in irradiated FA fibroblasts, and the reduction of the formation of DNA

Evaluating immunologic response and clinical deterioration in treatment-naïve patients initiating first-line therapies infected with HIV-1 CRF01_AE and subtype B

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Oyomopito, Rebecca A.; Li, Patrick CK.; Sungkanuparph, Somnuek; Phanuphak, Praphan; Tee, Kok Keng; Sirisanthana, Thira; Kantipong, Pacharee; Oka, Shinichi; Lee, Chris KC.; Kamarulzaman, Adeeba; Choi, Jun Yong; Sohn, Annette H.; Law, Matthew; Chen, Yi-Ming A.

2012-01-01

Background HIV-1 group M viruses diverge 25%–35% in envelope, important for viral attachment during infection, and 10–15% in the pol region, under selection pressure from common antiretrovirals. In Asia, subtypes B and CRF01_AE are common genotypes. Our objectives were to determine whether clinical, immunologic or virologic treatment responses differed by genotype in treatment-naïve patients initiating first-line therapy. Methods Prospectively collected, longitudinal data from patients in Thailand, Hong Kong, Malaysia, Japan, Taiwan and South Korea were provided for analysis. Covariates included demographics, hepatitis B and C coinfections, baseline CD4 T lymphocyte count and plasma HIV-1 RNA levels. Clinical deterioration (a new diagnosis of CDC category B/AIDS-defining illness or death) was assessed by proportional hazards models. Surrogate endpoints were 12-month change in CD4 cell count and virologic suppression post-therapy, evaluated by linear and logistic regression, respectively. Results Of 1105 patients, 1036 (93.8%) infected with CRF01_AE or subtype B were eligible for inclusion in clinical deterioration analyses and contributed 1546.7 person-years of follow-up (median:413 days, IQR:169–672 days). Patients >40 years demonstrated smaller immunological increases (p=0.002) and higher risk of clinical deterioration (HR=2.17; p=0.008). Patients with baseline CD4 cell counts >200 cells/μL had lower risk of clinical deterioration (HR=0.373; p=0.003). A total of 532 patients (48.1% of eligible) had CD4 counts available at baseline and 12 months post-therapy for inclusion in immunolgic analyses. Patients infected with subtype B had larger increases in CD4 counts at 12 months (p=0.024). A total of 530 patients (48.0% of eligible) were included in virologic analyses with no differences in response found between genotypes. Conclusions Results suggest that patients infected with CRF01_AE have reduced immunologic response to therapy at 12 months, compared to

Understanding the Effect of Response Rate and Class Size Interaction on Students Evaluation of Teaching in a Higher Education

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Al Kuwaiti, Ahmed; AlQuraan, Mahmoud; Subbarayalu, Arun Vijay

2016-01-01

Objective: This study aims to investigate the interaction between response rate and class size and its effects on students' evaluation of instructors and the courses offered at a higher education Institution in Saudi Arabia. Study Design: A retrospective study design was chosen. Methods: One thousand four hundred and forty four different courses…

Hypertensive response to exercise: mechanisms and clinical implication.

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Kim, Darae; Ha, Jong-Won

2016-01-01

A hypertensive response to exercise (HRE) is frequently observed in individuals without hypertension or other cardiovascular disease. However, mechanisms and clinical implication of HRE is not fully elucidated. Endothelial dysfunction and increased stiffness of large artery contribute to development of HRE. From neurohormonal aspects, excess stimulation of sympathetic nervous system and augmented rise of angiotensin II seems to be important mechanism in HRE. Increasing evidences indicates that a HRE is associated with functional and structural abnormalities of left ventricle, especially when accompanied by increased central blood pressure. A HRE harbors prognostic significance in future development of hypertension and increased cardiovascular events, particularly if a HRE is documented in moderate intensity of exercise. As supported by previous studies, a HRE is not a benign phenomenon, however, currently, whether to treat a HRE is controversial with uncertain treatment strategy. Considering underlying mechanisms, angiotensin receptor blockers and beta blockers can be suggested in individuals with HRE, however, evidences for efficacy and outcomes of treatment of HRE in individuals without hypertension is scarce and therefore warrants further studies.

Cultural Perspectives on Social Responsibility in Higher Education

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Yob, Iris M.

2016-01-01

The writers of the UNESCO document, "Rethinking education: Towards a global common good?" challenge educators to address their efforts to meet the current threats to sustainable life for all who share this planet. One way that higher education has been attempting to do this is through campus-community partnerships working to solve social…

Higher specialty training in genitourinary medicine: A curriculum competencies-based approach.

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Desai, Mitesh; Davies, Olubanke; Menon-Johansson, Anatole; Sethi, Gulshan Cindy

2018-01-01

Specialty trainees in genitourinary medicine (GUM) are required to attain competencies described in the GUM higher specialty training curriculum by the end of their training, but learning opportunities available may conflict with service delivery needs. In response to poor feedback on trainee satisfaction surveys, a four-year modular training programme was developed to achieve a curriculum competencies-based approach to training. We evaluated the clinical opportunities of the new programme to determine: (1) Whether opportunity cost of training to service delivery is justifiable; (2) Which competencies are inadequately addressed by direct clinical opportunities alone and (3) Trainee satisfaction. Local faculty and trainees assessed the 'usefulness' of the new modular programme to meet each curriculum competence. The annual General Medical Council (GMC) national training survey assessed trainee satisfaction. The clinical opportunities provided by the modular training programme were sufficiently useful for attaining many competencies. Trainee satisfaction as captured by the GMC survey improved from two reds pre- to nine greens post-intervention on a background of rising clinical activity in the department. The curriculum competencies-based approach to training offers an objective way to balance training with service provision and led to an improvement in GMC survey satisfaction.

Immunohistochemical Expression of CD-10, BCL-6 and MUM-1 Antibodies and Immediate Clinical Response in Patients of Diffuse Large B-Cell Lymphomas after Six Cycles of Chemotherapy

International Nuclear Information System (INIS)

Hassan, U.; Ishtiaq, S.; Hussain, M.

2014-01-01

Objective: To determine the expression of CD-10, BCL-6 and MUM-1 in patients with diffuse large B-cell lymphoma (DLBCL) and its association with immediate clinical response after six cycles of CHOP chemotherapy. Study Design: Analytical study. Place and Duration of Study: Armed Forces Institute of Pathology (AFIP), Rawalpindi in collaboration with Nuclear medicine, Oncology and Radiotherapy Institute (NORI), Islamabad from September 2010 to September 2011. Methodology: CD-10, BCL-6 and MUM-1 antibodies were applied on cases diagnosed as DLBCL. Immediate clinical response was noted after 6 cycles of chemotherapy with the help of oncologist and divided into complete response, partial response, stable disease and relapse/ progression. Patient's age, results of expression of CD-10, BCL-6 and MUM-1 and results of immediate clinical response to chemotherapy were noted. Regarding analysis of prognostic markers (CD-10, BCL-6 and MUM-1), chi-square test was used for immediate clinical response to chemotherapy in DLBCL. Results: CD-10 was positive in 40% cases, BCL-6 in 58.7% cases and MUM-1 was positive in 46.7% cases. About 41.3% of patients showed complete response, 10.6% partial response, 17.3% stable disease and 30.8% showed relapse/progression. CD-10 expression in DLBCL was associated with better immediate clinical response (p = 0.011) whereas MUM-1 expression in DLBCL was associated with poor immediate clinical response (p < 0.0001). However, there was no statistically significant association of BCL-6 with immediate clinical response (p = 0.22). Conclusion: DLBCL shows expression of CD-10, BCL-6 and MUM-1 in nearly fifty percent of the cases. CD-10 is associated with good whereas MUM is associated with poor response. However, there was no association of BCL-6 with immediate clinical response. (author)

Comparison of Docetaxel, Doxorubicin and Cyclophosphamide (TAC with 5-Fluorouracil, Doxorubicin and Cyclophosphamide (FAC Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer: A Phase III Clinical Trial

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Mohammad Mohammadianpanah

2011-04-01

Full Text Available Background: The present study aimed to compare the rates of complete clinical and pathologic response to docetaxel, doxorubicin and cyclophosphamide (TAC vs. 5-fluorouracil, doxorubicin and cyclophosphamide (FAC as neoadjuvant chemotherapy in women with locally advanced breast cancer.Methods: One hundred women with pathologically confirmed newly diagnosed locally advanced (T3-T4 or N2-N3 breast cancer were randomly assigned to receive a median of four cycles of either 5-fluorouracil (600 mg/m2, doxorubicin (60 mg/m2 and cyclophosphamide (600 mg/m2 every three weeks or docetaxel (75 mg/m2, doxorubicin (50 mg/m2 and cyclophosphamide (500 mg/m2 every three weeks followed by modified radical mastectomy. Complete clinical and pathologic response rates and toxicity were the primary and secondary outcome measures of the study. Results: Median age for all patients was 43.4 years (range 25-63 years. Patients in the TAC arm achieved a higher clinical (16% response rate than those in the FAC arm (4%, P=0.046. The pathologic response rate was also higher in the TAC arm compared to the FAC arm [TAC (20% vs. FAC (6%, P=0.037]. Estrogen receptor-negative status correlated with a higher clinical [TAC (19% vs. FAC (4%, P=0.032]and pathologic [TAC (23% vs. FAC (4%, P=0.011] response rate in both arms. All patients generally tolerated treatment well, and treatment-related toxicities were manageable. Conclusion: Combined treatment with TAC led to higher rates of complete clinical and pathologic response with acceptable toxicity compared to FAC in patients with locally advanced breast cancer. However, further follow-up is needed to translate this response into improvements in survival.

An exploratory study on awareness towards institutional social responsibility in Indian higher education institutions

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Richa Mishra

2016-06-01

Full Text Available Institutional Social responsibility (ISR in context to a Higher Educational Institution has been defined as the ethical practice in transference of knowledge, and the active participation in betterment of quality of life in the society. It is an offshoot of the concept of Corporate Social responsibility (CSR, but unlike CSR, it is neither mandatory nor actively monitored or researched in Indian context. However, awareness towards aspects of ISR has been increasing, especially in Indian Universities. Indian Universities adopt practices related to Adoption of Villages, Awareness Drives, Environmental Care and rural Education initiatives. Critics often see ISR as an unnecessary burden; review of literature from around the world suggests that ISR practices contribute to increased accountability towards exploitation of resources by Educational Institutes as well as better reputation of Educational Institutes in the society. The purpose of this paper is to examine the perception towards the concept of ISR in Educational Institutes in India. The paper opted for a questionnaire-based exploratory survey of 50 faculty members, across Private Universities in Rajasthan. The findings suggest lacking awareness but a significant acceptance of need of ISR practices. The paper includes implications for the Universities to include ISR practices in their strategy to address its obligations to the society and simultaneously gain a competitive advantage.

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

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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…

77 FR 69631 - Draft Guidance for IRBs, Clinical Investigators, and Sponsors: IRB Responsibilities for Reviewing...

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2012-11-20

...) is needed in order to assure the protection of the rights and welfare of human subjects in clinical... responsibilities. To enhance human subject protection and reduce regulatory burden, the Department of Health and Human Services (HHS) Office for Human Research Protections (OHRP) and FDA have been actively working to...

Clinical diagnosis of polycystic ovarian syndrome and response to metformin therapy

International Nuclear Information System (INIS)

Tariq, N.; Ayub, R.; Alam, A.Y.; Raees, S.R.

2007-01-01

To determine the accuracy of diagnosing polycystic ovarian syndrome (PCOS) predominantly on clinical features and the response to metformin therapy. Women fulfilling the inclusion criteria (oligo/hypomenorrhea, infertility, weight gain, hyperandrogenism) were enrolled. Ultrasound pelvis was obtained in all women. Presence of eight or more multiple follicles in both or one ovary without presence of mature follicle was the cutoff number for positive ultrasound. Thyroid stimulating hormone levels were performed in all patients, and patients with abnormal levels were excluded from the study. Metformin was adjusted to 500 mg thrice daily. Six months later patients were again evaluated for response to metformin therapy and those who failed to conceive were given clomiphene citrate along with metformin. Fertility was re-evaluated at the end of one year. At the start of the study, 81% women had menstrual irregularity and 84% had infertility. Hirsutism was seen in 72% while history of weight gain was present in 62% of patients. Ultrasound evidence of polycystic ovaries was seen in 93% of women. After 6 months of metformin therapy, 80% patients had achieved correction in their menstrual irregularity. After 6 months on metformin alone, 51% patients conceived while an additional 20% conceived on both metformin and clomiphene citrate during next 6 months. Overall fertility rate was 71% at the end of one year. There was statistically significant change in pre-treatment and post-treatment BMI. Combination of three or more of the clinical features (irregular cycles, history of weight gain, infertility and hirsutism) provide an appropriate basis for the diagnosis of PCOS. Metformin alone was an effective treatment for PCOS in this series. (author)

Cross-talk between Clinical and Host Response Parameters of Periodontitis in Smokers

Science.gov (United States)

Nagarajan, R.; Miller, C.S.; Dawson, D.; Al-Sabbagh, M.; Ebersole, J.L.

2016-01-01

Periodontal diseases are a major public health concern leading to tooth loss and also shown to be associated with several chronic systemic diseases. Smoking is a major risk factor for developing numerous systemic diseases, as well as periodontitis. While it is clear that smokers have a significantly enhanced risk for developing periodontitis leading to tooth loss, the population varies with regards to susceptibility to disease associated with smoking. This investigation focuses on identifying differences in four broad sets of variables consisting of: (a) host response molecules, (b) periodontal clinical parameters, (c) antibody measures for periodontal pathogens and oral commensal bacteria challenge, and (d) other variables of interest in a smoking population with (n = 171) and without periodontitis (n = 117). Subsequently, Bayesian network structured learning techniques (BNSL) techniques were used to investigate potential associations and cross-talk between the four broad sets of variables. BNSL revealed two broad communities with markedly different topology between the non-periodontitis and periodontitis smoking population. Confidence of the edges in the resulting network also showed marked variations within and between the periodontitis and non-periodontitis groups. The results presented validated known associations, as well as discovered new ones with minimal precedence that may warrant further investigation and novel hypothesis generation. Cross-talk between the clinical variables and antibody profiles of bacteria were especially pronounced in the case of periodontitis and mediated by the antibody response profile to P. gingivalis. PMID:27431617

Analysis of the response of PVA-GTA Fricke-gel dosimeters with clinical magnetic resonance imaging

Science.gov (United States)

Collura, Giorgio; Gallo, Salvatore; Tranchina, Luigi; Abbate, Boris Federico; Bartolotta, Antonio; d'Errico, Francesco; Marrale, Maurizio

2018-01-01

Fricke gel dosimeters produced with a matrix of Poly-vinyl alcohol (PVA) cross-linked with glutaraldehyde (GTA) were analyzed with magnetic resonance imaging (MRI). Previous studies based on spectrophotometry showed valuable dosimetric features of these gels in terms of X-ray sensitivity and diffusion of the ferric ions produced after irradiation. In this study, MRI was performed on the gels at 1.5 T with a clinical scanner in order to optimize the acquisition parameters and obtain high contrast between irradiated and non-irradiated samples. The PVA gels were found to offer good linearity in the range of 0-10 Gy and a stable signal for several hours after irradiation. The sensitivity was about 40% higher compared to gels produced with agarose as gelling agent. The effect of xylenol orange (XO) on the MRI signal was also investigated: gel dosimeters made without XO show higher sensitivity to x-rays than those made with XO. The dosimetric accuracy of the 3D gels was investigated by comparing their MRI response to percentage depth dose and transversal dose profile measurements made with an ionization chamber in a water phantom. The comparison of PVA-GTA gels with and without XO showed that the chelating agent reduces the MRI sensitivity of the gels. Depth-dose and transversal dose profiles acquired by PVA-GTA gels without XO are more accurate and consistent with the ionization chamber data. However, diffusion effects hinder accurate measurements in the steep dose gradient regions and they should be further reduced by modifying the gel matrix and/or by minimizing the delay between irradiation and imaging.

Increased of the hepatocytes and splenocytes apoptosis accompanies clinical improvement and higher survival in mice infected with Trypanosoma cruzi and treated with highly diluted Lycopodium clavatum.

Science.gov (United States)

Falkowski-Temporini, Gislaine Janaina; Lopes, Carina Ribeiro; Massini, Paula Fernanda; Brustolin, Camila Fernanda; Ferraz, Fabiana Nabarro; Sandri, Patricia Flora; Hernandes, Luzmarina; Aleixo, Denise Lessa; Barion, Terezinha Fátima; Esper, Luiz Gilson; de Araújo, Silvana Marques

2017-09-01

Recent evidence includes apoptosis as a defense against Trypanosoma cruzi infection, which promotes an immune response in the host induced by T cells, type 1, 2 and 17. Currently, there is no medicine completely preventing the progression of this disease. We investigated the immunological and apoptotic effects, morbidity and survival of mice infected with T. cruzi and treated with dynamized homeopathic compounds 13c: Kalium causticum (GCaus), Conium maculatum, (GCon), Lycopodium clavatum (GLy) and 7% alcohol solution (control, vehicle compounds, GCI). There was significant difference in the increase of apoptosis in the treated groups, compared with GCI, which might indicate action of the compounds in these cells. Infected animals treated with Lycopodium clavatum presented better performance compared with other groups. GLy showed a higher amount of hepatocytes and splenocytes undergoing apoptosis, higher number of apoptotic bodies in the liver, predominance of Th1 response, increased TNF-α and decreased IL-6, higher survival, lower morbidity, higher water consumption, body temperature, tendency to higher feed intake and weight gain compared with GCI. Conium maculatum had worse results with increased Th2 response with increased IL-4, worsening of the infection with early mortality of the animals. Together, these data suggest that highly diluted medicines modulate the immune response and apoptosis, affecting the morbidity of animals infected with a highly virulent strain of T. cruzi, being able to minimize the course of infection, providing more alternative approaches in the treatment of Chagas disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Population Council responsible for RU486 clinical trials in USA].

Science.gov (United States)

Aguillaume, C J

1993-04-01

As a result of the sudden political change that came with the Clinton Administration, RU-486's manufacturer, Roussel-Uclaf, and the Population Council agreed on April 20, 1992, on the manufacture and distribution of RU-486 in the US. In the US, there are less than 1.6 million induced abortions annually. From now on, US women will be able to have a choice between medical and surgical abortion. The Population Council and Roussel-Uclaf have had a contract since 1982. The Council is solely responsible for the phase 2 clinical trial of RU-486 in the US and other countries. It must present to the US Food and Drug Administration (FDA) an amendment allowing it to begin phase 3 clinical trials. The Council will also lead the US medical facilities in this study. It will identify partners for future production of RU-486 and its distribution in the US. It will also submit to FDA a New Drug Application (NDA). FDA will review the scientific literature on RU-486 and evaluate all data submitted by the Population Council. There are still obstacles to be surmounted. The Population Council must demonstrate good judgment when selecting the criteria for choosing a pharmaceutical firm before a Technical Committee which will be part of a group of players promoting women's health, scientific experts, and other interested parties. It must find the necessary funds to conduct the clinical trials and prepare the NDA. Phase 3 clinical trials in the US must have at least 2000 women. They will test RU-486's efficacy, safety, and acceptability among women choosing medical abortion over surgical abortion. Since the Council operates in almost all countries in the world, has innovated contraceptive research and development activities, and has been endorsed by the UN, product approval of RU-486 in the US will affect policy in all countries concerned about abortion.

Anal sphincter responses after perianal electrical stimulation

DEFF Research Database (Denmark)

Pedersen, Ejnar; Klemar, B; Schrøder, H D

1982-01-01

By perianal electrical stimulation and EMG recording from the external anal sphincter three responses were found with latencies of 2-8, 13-18 and 30-60 ms, respectively. The two first responses were recorded in most cases. They were characterised by constant latency and uniform pattern, were...... not fatigued by repeated stimulation, were most dependent on placement of stimulating and recording electrodes, and always had a higher threshold than the third response. The third response was constantly present in normal subjects. It had the longest EMG response and the latency decreased with increasing...... stimulation to a minimum of 30-60 ms. This response represented the clinical observable spinal reflex, "the classical anal reflex". The latencies of the two first responses were so short that they probably do not represent spinal reflexes. This was further supported by the effect of epidural anaesthesia which...

Depth of Response in Multiple Myeloma: A Pooled Analysis of Three PETHEMA/GEM Clinical Trials.

Science.gov (United States)

Lahuerta, Juan-Jose; Paiva, Bruno; Vidriales, Maria-Belen; Cordón, Lourdes; Cedena, Maria-Teresa; Puig, Noemi; Martinez-Lopez, Joaquin; Rosiñol, Laura; Gutierrez, Norma C; Martín-Ramos, María-Luisa; Oriol, Albert; Teruel, Ana-Isabel; Echeveste, María-Asunción; de Paz, Raquel; de Arriba, Felipe; Hernandez, Miguel T; Palomera, Luis; Martinez, Rafael; Martin, Alejandro; Alegre, Adrian; De la Rubia, Javier; Orfao, Alberto; Mateos, María-Victoria; Blade, Joan; San-Miguel, Jesus F

2017-09-01

Purpose To perform a critical analysis on the impact of depth of response in newly diagnosed multiple myeloma (MM). Patients and Methods Data were analyzed from 609 patients who were enrolled in the GEM (Grupo Español de Mieloma) 2000 and GEM2005MENOS65 studies for transplant-eligible MM and the GEM2010MAS65 clinical trial for elderly patients with MM who had minimal residual disease (MRD) assessments 9 months after study enrollment. Median follow-up of the series was 71 months. Results Achievement of complete remission (CR) in the absence of MRD negativity was not associated with prolonged progression-free survival (PFS) and overall survival (OS) compared with near-CR or partial response (median PFS, 27, 27, and 29 months, respectively; median OS, 59, 64, and 65 months, respectively). MRD-negative status was strongly associated with prolonged PFS (median, 63 months; P < .001) and OS (median not reached; P < .001) overall and in subgroups defined by prior transplantation, disease stage, and cytogenetics, with prognostic superiority of MRD negativity versus CR particularly evident in patients with high-risk cytogenetics. Accordingly, Harrell C statistics showed higher discrimination for both PFS and OS in Cox models that included MRD (as opposed to CR) for response assessment. Superior MRD-negative rates after different induction regimens anticipated prolonged PFS. Among 34 MRD-negative patients with MM and a phenotypic pattern of bone marrow involvement similar to monoclonal gammopathy of undetermined significance at diagnosis, the probability of "operational cure" was high; median PFS was 12 years, and the 10-year OS rate was 94%. Conclusion Our results demonstrate that MRD-negative status surpasses the prognostic value of CR achievement for PFS and OS across the disease spectrum, regardless of the type of treatment or patient risk group. MRD negativity should be considered as one of the most relevant end points for transplant-eligible and elderly fit patients

Radiographic complications of biologic response modifiers

International Nuclear Information System (INIS)

Miketic, L.M.; Bahnson, R.R.; Ernstoff, M.S.; Kirkwood, J.M.; Nair, S.; Logan, T.; Downs, M.A.; Neuhart, J.A.

1989-01-01

Biologic response modifiers, such as the interferons, are increasingly used in the treatment of cancer as an adjunct to conventional chemotherapy. In certain malignancies, particularly renal cell carcinoma, they are becoming agents of choice due to higher tumor response rate. The authors have reviewed 202 patients. Protocols include interferon, interleukin, tumor necrosis factor, and monoclonal antibodies. The radiology of significant clinical complications is discussed, especially the vascular leak syndrome often seen with interleukin administration and the cardiac toxicity of interferon. Less common abnormalities include progressive splenomegaly in one interferon study and a hemorrhagic episode caused by tumor necrosis factor

A multicentre, clinical evaluation of a hydro-responsive wound dressing: the Glasgow experience.

Science.gov (United States)

Hodgson, H; Davidson, D; Duncan, A; Guthrie, J; Henderson, E; MacDiarmid, M; McGown, K; Pollard, V; Potter, R; Rodgers, A; Wilson, A; Horner, J; Doran, M; Simm, S; Taylor, R; Rogers, A; Rippon, M G; Colgrave, M

2017-11-02

Our aim was to assess the effectiveness of hydro-responsive wound dressing (HRWD) in debridement and wound bed preparation of a variety of acute and chronic wounds that presented with devitalised tissue needing removal so that healing may proceed. This was a non-comparative evaluation of acute and chronic wounds that required debridement as part of their normal treatment regimen. Clinicians recorded wound changes including a subjective assessment level of devitalised tissue and wound bed preparation, presence of pain, wound status (e.g., wound size) and periwound skin condition. Data was also collected from clinicians and patients to provide information on clinical performance of the dressing. We recruited 100 patients with a variety of wound types into the study. Over 90% of the clinicians reported removal of devitalised tissue to enable a healing response in both chronic and acute wounds. Specifically, over the course of the evaluation period, levels of devitalised tissue (necrosis and slough) reduced from 85.5% to 26.3%, and this was accompanied by an increase in wound bed granulation from 12.0% to 33.7%. Correspondingly, there was a 40% reduction in wound area, hence a clinically relevant healing response was seen upon treatment with HRWD. It is also noteworthy that this patient population included a significant proportion of chronic wounds (51.4%) that showed no signs of wound progression within debridement process (£8.05), larval therapy (£306.39) and mechanical pad debridement (£11.46). HRWD was well tolerated and was demonstrated to be an efficient debridement tool providing rapid, effective and pain free debridement in a variety of wound types.

Short-term population-based and spatiotemporal nonlinear concentration-response associations between fine particulate matter and children's respiratory clinic visits

Science.gov (United States)

Yu, Hwa-Lung; Chien, Lung-Chang

2014-05-01

Advert health impacts associated with the PM2.5 exposure have been confirmed in mortality and cardiovascular diseases; however, findings of the influence of PM2.5 on respiratory diseases investigated among previous studies are still inconsistent. We investigated the short-term population-based associations between the respiratory clinic visits of children population and the PM2.5 exposure levels with considering both the spatiotemporal distributions of the ambient pollution and clinic visit data. We applied a spatiotemporal structured additive regression model to examine the concentration-response (C-R) association between daily children's respiratory clinic visits and PM2.5 concentrations. The analysis was performed separately on the four selected respiratory disease categories of the population-based dataset, obtained from Taiwan National Health Insurance database, covering the 41 districts in Taipei area during the period of 2005 to 2007. This study reveals a strong nonlinear C-R pattern that the PM2.5 increment can significantly affect respiratory health at PM2.5 concentration ≤ 18.17µg/m3 for both preschool children and schoolchildren. The elevated risks are especially present in the category of acute respiratory infections. PM2.5 increase is mostly non-significant to the more severe respiratory diseases, e.g., COPD and pneumonia, over the ranges of 8.85-92.45µg/m3. The significantly higher relative rate of respiratory clinic visit most likely concentrated at populated areas. We highlight the nonlinearity of the respiratory health impacts of PM2.5 on children's populations from the first study, to our knowledge, to investigate this population-based association. The strong nonlinearity can possibly cause the inconsistency of PM2.5 health impact assessments with linear assumptions.

Trust, moral responsibility, the self, and well-ordered societies: the importance of basic philosophical concepts for clinical ethics.

Science.gov (United States)

Mccullough, Laurence B

2002-02-01

Although the work of clinical ethics is intensely practical, it employs and presumes philosophical concepts from the central branches of philosophy, including metaphysics, epistemology, ethics, and political philosophy. This essay introduces this issue in the Journal on clinical ethics by considering how the papers and book reviews included in it illuminate four such concepts: trust, moral responsibility, the self and well-ordered societies.

Childhood optic chiasm gliomas: radiographic response following radiotherapy and long-term clinical outcome

International Nuclear Information System (INIS)

Tao, May L.; Barnes, Patrick D.; Billett, Amy L.; Leong, Traci; Shrieve, Dennis C.; Scott, R. Michael; Tarbell, Nancy J.

1997-01-01

Purpose: In children with chiasmal gliomas, radiation therapy can arrest progressive visual and neurologic impairment. We examined the radiographic response and clinical outcomes after irradiation. Methods and Materials: Forty-two children (median age at diagnosis, 6.6 years) with chiasmal gliomas were managed as follows: 11 asymptomatic patients with neurofibromatosis-1 (NF-1) were observed only; 2 patients, less than 3 years old, underwent surgery and chemotherapy to delay irradiation; and 29 patients with progressive disease received radiation with or without prior surgery or chemotherapy. Time to radiographic response, long-term tumor control and late sequelae were reviewed for the 29 irradiated patients. Results: The probability of at least 50% radiographic response at 24 months after irradiation was 18.1% and increased to 38.2% by 48 months and 45.9% by 60 months. By actuarial analysis, the median time for such radiographic response was 62 months. For the 29 irradiated patients, the 10-year freedom from progression and overall survival rates were 100% and 89%, respectively (median follow-up for surviving patients, 108 months). Stabilization or improvement in vision occurred in 81% of 26 evaluable irradiated patients. Conclusions: Notable radiographic response may be observed years after irradiation. Radiation therapy provides excellent long-term tumor control and vision preservation or improvement in the majority of patients with progressive chiasmal gliomas

Clinical profile and response to treatment of patients with pituitary adenomas submitted to radiotherapy

International Nuclear Information System (INIS)

Moraes, Paulo Lazaro de; Freire, Geison Moreira; Dias, Rodrigo Souza; Segreto, Roberto Araujo; Segreto, Helena Regina Comodo; Abucham Filho, Julio Zaki

2008-01-01

Objective: to evaluate the clinical profile of patients with pituitary adenoma and their response to radiotherapy. Material and method: retrospective study with 22 patients with diagnosis of pituitary adenoma which were submitted to radiotherapy between March 2004 and December 2008. Patients' characteristics such as gender, age, clinical presentation, surgical approach, immunohistochemistry profile, dose of radiation and the response to therapy were analyzed using hormonal dosages and imaging exams. Results: the median age was 51 years and equally distributed in both genders. The tumors were divided according to the Hardy's classification: 27.5% had grade II, 27.5% had grade III and 45% had grade IV. The main symptoms presented by patients at diagnosis were visual impairment in 77% of cases, headache in 68%, amenorrhea and acromegaly in 27% and galactorrhoea in 4.5%. Transphenoidal surgery was performed in 21 patients and only 1 patient was submitted to transcranial approach; 91% of cases had partial resection. Concerning to immunohistochemistry, the expression of ACTH was the most frequent, being present in 41% of cases. The patients were treated in megavoltage equipment mostly with 6 MV linear accelerator. The total radiation dose was 45 Gy in 68% of patients and a dose of 50.4 Gy in 13% of cases. Three-dimensional planning was used in 20 patients. The median follow-up was 41 months. Laboratory and imaging improvement were observed in 73% of patients, stability in 22.5%, and worsening in 4.5%. Conclusion: the results show good rates of response and control of pituitary adenomas by radiation in the first four years after treatment. Considering it has a slow response to treatment, there is a high chance of improvement in results later during the follow-up. (author)

Clinical benefit response of concurrent chemoradiotherapy with protracted 5-fluorouracil infusion in patients with locally advanced pancreatic cancer

International Nuclear Information System (INIS)

Okusaka, Takuji; Okada, Shuichi; Ishii, Hiroshi

1998-01-01

Pancreatic cancer is a highly virulent disease with a poor prognosis. Although objective tumor response to chemotherapy and/or radiotherapy is low, some patients show an improvement in their symptoms after treatments, without obvious tumor regression. We assessed the clinical benefit of concurrent chemoradiotherapy with protracted 5-fluorouracil infusion in patients with locally advanced pancreatic cancer. Sixteen patients were enrolled in this study. The clinical benefit response to the chemoradiotherapy was evaluated by 2 indicators, including pain (intensity of pain and consumption of morphine) and performance status. A patient was defined to be a clinical benefit responder if 1 of these 2 variables was positive, and the other variable was positive or stable. Seven patients (44%) responded. Six patients (38%) were classified as stable, and 3 (19%) as nonresponders. The survival period in responders was significantly longer than that in nonresponders and stable patients. Concurrent external-beam radiation therapy, with protracted 5-fluorouracil infusion, may be a meaningful treatment for locally advanced pancreatic cancer. (author)

Autophagy in the immune response to tuberculosis: clinical perspectives.

LENUS (Irish Health Repository)

Ní Cheallaigh, C

2011-06-01

A growing body of evidence points to autophagy as an essential component in the immune response to tuberculosis. Autophagy is a direct mechanism of killing intracellular Mycobacterium tuberculosis and also acts as a modulator of proinflammatory cytokine secretion. In addition, autophagy plays a key role in antigen processing and presentation. Autophagy is modulated by cytokines; it is stimulated by T helper type 1 (Th1) cytokines such as tumour necrosis factor (TNF)-α and interferon (IFN)-γ, and is inhibited by the Th2 cytokines interleukin (IL)-4 and IL-13 and the anti-inflammatory cytokine IL-10. Vitamin D, via cathelicidin, can also induce autophagy, as can Toll-like receptor (TLR)-mediated signals. Autophagy-promoting agents, administered either locally to the lungs or systemically, could have a clinical application as adjunctive treatment of drug-resistant and drug-sensitive tuberculosis. Moreover, vaccines which effectively induce autophagy could be more successful in preventing acquisition or reactivation of latent tuberculosis.

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

Science.gov (United States)

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. © 2015 Society for Endocrinology.

Clinical responses after total body irradiation by over permissible dose of γ-rays in one time

International Nuclear Information System (INIS)

Jiang Benrong; Wang Guilin; Liu Huilan; Tang Xingsheng; Ai Huisheng

1990-01-01

The clinical responses of patients after total body over permissilbe dose γ-ray irradiation were observed and analysed. The results showed: when the dose was above 5 cGy, there was some immunological depression, but no significant change in hematopoietic functions. 5 cases showed some transient changes of ECG, perhaps due to vagotonia caused by psychological imbalance, One case vomitted 3-4 times after 28 cGy irradiation, this suggested that a few times of vomitting had no significance in the estimation of the irradiated dose and the whole clinical manifestations must be concretely analysed

Virus-specific immune response in HBeAg-negative chronic hepatitis B: relationship with clinical profile and HBsAg serum levels.

Directory of Open Access Journals (Sweden)

Elisabetta Loggi

Full Text Available BACKGROUND AIMS: The immune impairment characterizing chronic hepatitis B (cHBV infection is thought to be the consequence of persistent exposure to viral antigens. However, the immune correlates of different clinical stages of cHBV and their relation with different levels of HBsAg have not been investigated. The aim of the present study was to evaluate the relationship between HBV-specific T cells response and the degree of in vivo HBV control and HBsAg serum levels in HBeAg-HBeAb+ cHBV. METHODS: Peripheral blood mononuclear cells from 42 patients with different clinical profiles (treatment-suppressed, inactive carriers and active hepatitis of cHBV, 6 patients with resolved HBV infection and 10 HBV-uninfected individuals were tested with overlapping peptides spanning the entire HBV proteome. The frequency and magnitude of HBV-specific T cell responses was assessed by IFNγ ELISPOT assay. Serum HBsAg was quantified with a chemiluminescent immunoassay. RESULTS: The total breadth and magnitude of HBV-specific T cell responses did not differ significantly between the four groups. However, inactive carriers targeted preferentially the core region. In untreated patients, the breadth of the anti-core specific T cell response was inversely correlated with serum HBsAg concentrations as well as HBV-DNA and ALT levels and was significantly different in patients with HBsAg levels either above or below 1000 IU/mL. The same inverse association between anti-core T cell response and HBsAg levels was found in treated patients. CONCLUSIONS: Different clinical outcomes of cHBV infection are associated with the magnitude, breadth and specificity of the HBV-specific T cell response. Especially, robust anti-core T cell responses were found in the presence of reduced HBsAg serum levels, suggesting that core-specific T cell responses can mediate a protective effect on HBV control.

Are child and adolescent responses to placebo higher in major depression than in anxiety disorders? A systematic review of placebo-controlled trials.

Directory of Open Access Journals (Sweden)

David Cohen

Full Text Available BACKGROUND: In a previous report, we hypothesized that responses to placebo were high in child and adolescent depression because of specific psychopathological factors associated with youth major depression. The purpose of this study was to compare the placebo response rates in pharmacological trials for major depressive disorder (MDD, obsessive compulsive disorder (OCD and other anxiety disorders (AD-non-OCD. METHODOLOGY AND PRINCIPAL FINDINGS: We reviewed the literature relevant to the use of psychotropic medication in children and adolescents with internalized disorders, restricting our review to double-blind studies including a placebo arm. Placebo response rates were pooled and compared according to diagnosis (MDD vs. OCD vs. AD-non-OCD, age (adolescent vs. child, and date of publication. From 1972 to 2007, we found 23 trials that evaluated the efficacy of psychotropic medication (mainly non-tricyclic antidepressants involving youth with MDD, 7 pertaining to youth with OCD, and 10 pertaining to youth with other anxiety disorders (N = 2533 patients in placebo arms. As hypothesized, the placebo response rate was significantly higher in studies on MDD, than in those examining OCD and AD-non-OCD (49.6% [range: 17-90%] vs. 31% [range: 4-41%] vs. 39.6% [range: 9-53], respectively, ANOVA F = 7.1, p = 0.002. Children showed a higher stable placebo response within all three diagnoses than adolescents, though this difference was not significant. Finally, no significant effects were found with respect to the year of publication. CONCLUSION: MDD in children and adolescents appears to be more responsive to placebo than other internalized conditions, which highlights differential psychopathology.

(99m)Tc-Annexin A5 quantification of apoptotic tumor response: a systematic review and meta-analysis of clinical imaging trials.

Science.gov (United States)

Belhocine, Tarik Z; Blankenberg, Francis G; Kartachova, Marina S; Stitt, Larry W; Vanderheyden, Jean-Luc; Hoebers, Frank J P; Van de Wiele, Christophe

2015-12-01

(99m)Tc-Annexin A5 has been used as a molecular imaging probe for the visualization, characterization and measurement of apoptosis. In an effort to define the quantitative (99m)Tc-annexin A5 uptake criteria that best predict tumor response to treatment, we performed a systematic review and meta-analysis of the results of all clinical imaging trials found in the literature or publicly available databases. Included in this review were 17 clinical trials investigating quantitative (99m)Tc-annexin A5 (qAnx5) imaging using different parameters in cancer patients before and after the first course of chemotherapy and/or radiation therapy. Qualitative assessment of the clinical studies for diagnostic accuracy was performed using the QUADAS-2 criteria. Of these studies, five prospective single-center clinical trials (92 patients in total) were included in the meta-analysis after exclusion of one multicenter clinical trial due to heterogeneity. Pooled positive predictive values (PPV) and pooled negative predictive values (NPV) (with 95% CI) were calculated using Meta-Disc software version 1.4. Absolute quantification and/or relative quantification of (99m)Tc-annexin A5 uptake were performed at baseline and after the start of treatment. Various quantitative parameters have been used for the calculation of (99m)Tc-annexin A5 tumor uptake and delta (Δ) tumor changes post-treatment compared to baseline including: tumor-to-background ratio (TBR), ΔTBR, tumor-to-noise ratio, relative tumor ratio (TR), ΔTR, standardized tumor uptake ratio (STU), ΔSTU, maximum count per pixel within the tumor volume (Cmax), Cmax%, absolute ΔU and percentage (ΔU%), maximum ΔU counts, semiquantitative visual scoring, percent injected dose (%ID) and %ID/cm(3). Clinical trials investigating qAnx5 imaging have included patients with lung cancer, lymphoma, breast cancer, head and neck cancer and other less common tumor types. In two phase I/II single-center clinical trials, an increase of ≥25% in

Body mass index influences infliximab post-infusion levels and correlates with prospective loss of response to the drug in a cohort of inflammatory bowel disease patients under maintenance therapy with Infliximab.

Directory of Open Access Journals (Sweden)

Franco Scaldaferri

Full Text Available Infliximab is an effective treatment for inflammatory bowel disease (IBD. Studies differ regarding the influence of body mass index (BMI on the response to infliximab, with the majority of studies indicating that increased BMI may be associated with a poorer response to Infliximab. However, the pharmacokinetic mechanisms causing this have not yet been reported.Examine the correlation between BMI/immunosuppressant use with clinical response, trough and post-infusion levels of infliximab, tumour necrosis factor-α(TNF-α and anti-drug antibodies(ATI, and determine if these factors can predict future response.We collected serum from 24 patients receiving Infliximab before and 30 minutes following infusion. Clinical parameters were collected retrospectively and prospectively. ELISA measurements of infliximab, TNF-α and ATI were performed.We confirmed that patients with higher infliximab trough levels have a better response rate and that patients with an elevated BMI display a higher rate of loss of response (20%. Patients with a higher BMI had elevated post-infusion levels of infliximab. Additionally, the ratio of IFX/TNF-α trough levels correlated with clinical response to the following infusion.This study confirms that an elevated BMI is associated with a poorer response to infliximab. For the first time, we describe that a higher BMI correlates with higher post-infusion levels, however this does not correlate with a higher rate of response to the drug, suggesting that circulating drug levels do not correlate with tissue levels. Furthermore, in our small cohort of patients, we identified a possible predictive marker of future response to treatment which may be used to guide dose escalation and predict non-response to infliximab.

Responsiveness, minimal detectable change, and minimal clinically important difference of the Nottingham Extended Activities of Daily Living Scale in patients with improved performance after stroke rehabilitation.

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Wu, Ching-yi; Chuang, Li-ling; Lin, Keh-chung; Lee, Shin-da; Hong, Wei-hsien

2011-08-01

To determine the responsiveness, minimal detectable change (MDC), and minimal clinically important differences (MCIDs) of the Nottingham Extended Activities of Daily Living (NEADL) scale and to assess percentages of patients' change scores exceeding the MDC and MCID after stroke rehabilitation. Secondary analyses of patients who received stroke rehabilitation therapy. Medical centers. Patients with stroke (N=78). Secondary analyses of patients who received 1 of 4 rehabilitation interventions. Responsiveness (standardized response mean [SRM]), 90% confidence that a change score at this threshold or higher is true and reliable rather than measurement error (MDC(90)), and MCID on the NEADL score and percentages of patients exceeding the MDC(90) and MCID. The SRM of the total NEADL scale was 1.3. The MDC(90) value for the total NEADL scale was 4.9, whereas minima and maxima of the MCID for total NEADL score were 2.4 and 6.1 points, respectively. Percentages of patients exceeding the MDC(90) and MCID of the total NEADL score were 50.0%, 73.1%, and 32.1%, respectively. The NEADL is a responsive instrument relevant for measuring change in instrumental activities of daily living after stroke rehabilitation. A patient's change score has to reach 4.9 points on the total to indicate a true change. The mean change score of a stroke group on the total NEADL scale should achieve 6.1 points to be regarded as clinically important. Our findings are based on patients with improved NEADL performance after they received specific interventions. Future research with larger sample sizes is warranted to validate these estimates. Copyright © 2011 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

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

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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. Copyright © 2012 Elsevier B.V. All rights reserved.

Plasma homovanillic acid and treatment response in a large group of schizophrenic patients.

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Chang, W H; Hwu, H G; Chen, T Y; Lin, S K; Lung, F W; Chen, H; Lin, W L; Hu, W H; Lin, H N; Chien, C P

1993-10-01

Plasma levels of homovanillic acid (pHVA), a metabolite of dopamine, were measured in ninety-five Chinese schizophrenic patients free of neuroleptics for at least four weeks. These patients were treated with classical antipsychotics for six weeks. Pretreatment pHVA was positively correlated with the subsequent clinical response (r = 0.408, p or = 50%, n = 47) had higher pretreatment pHVA levels than poor responders (BPRS improvement pHVA level was associated with a more consistent clinical response to the subsequent treatment. Using a pHVA level of 12 ng/ml as a demarcation point, 72% of patients (34 of 47) who had pHVA > or = 12 responded whereas 65% (31 of 48) who had pHVA levels may predict a better clinical response to antipsychotics. Based upon the pHVA findings, two hypothetical subtypes of schizophrenia are proposed.

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

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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. (c) 2015 APA, all rights reserved).

Grooming a CAT: customizing CAT administration rules to increase response efficiency in specific research and clinical settings.

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Kallen, Michael A; Cook, Karon F; Amtmann, Dagmar; Knowlton, Elizabeth; Gershon, Richard C

2018-05-05

To evaluate the degree to which applying alternative stopping rules would reduce response burden while maintaining score precision in the context of computer adaptive testing (CAT). Analyses were conducted on secondary data comprised of CATs administered in a clinical setting at multiple time points (baseline and up to two follow ups) to 417 study participants who had back pain (51.3%) and/or depression (47.0%). Participant mean age was 51.3 years (SD = 17.2) and ranged from 18 to 86. Participants tended to be white (84.7%), relatively well educated (77% with at least some college), female (63.9%), and married or living in a committed relationship (57.4%). The unit of analysis was individual assessment histories (i.e., CAT item response histories) from the parent study. Data were first aggregated across all individuals, domains, and time points in an omnibus dataset of assessment histories and then were disaggregated by measure for domain-specific analyses. Finally, assessment histories within a "clinically relevant range" (score ≥ 1 SD from the mean in direction of poorer health) were analyzed separately to explore score level-specific findings. Two different sets of CAT administration rules were compared. The original CAT (CAT ORIG ) rules required at least four and no more than 12 items be administered. If the score standard error (SE) reached a value CAT was stopped. We simulated applying alternative stopping rules (CAT ALT ), removing the requirement that a minimum four items be administered, and stopped a CAT if responses to the first two items were both associated with best health, if the SE was CAT ORIG and CAT ALT . CAT ORIG and CAT ALT scores varied little, especially within the clinically relevant range, and response burden was substantially lower under CAT ALT (e.g., 41.2% savings in omnibus dataset). Alternate stopping rules result in substantial reductions in response burden with minimal sacrifice in score precision.

Further evidence for the validity of a response inconsistency scale for the Personality Inventory for DSM-5 in Italian community-dwelling adolescents, community-dwelling adults, and clinical adults.

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Somma, Antonella; Borroni, Serena; Kelley, Shannon E; Edens, John F; Fossati, Andrea

2018-03-22

Response inconsistency represents a major component of careless responding. Keeley, J. W., Webb, Peterson, Roussin, and Flanagan (2016) proposed a measure of response inconsistency for the Personality Inventory for DSM-5 (PID-5-VRIN). In order to evaluate the ability of the PID-5-VRIN scale to detect inconsistent responding, we examined 3 independent archival samples of Italian community-dwelling adolescents (N = 1,264), community-dwelling adults (N = 2,143), and clinical adults (N = 706) who were administered the PID-5. The impact of PID-5-VRIN scores on the associations with interview-based personality disorder (PD) scores was also assessed among clinical adults. PID-5-VRIN item pairs showed correlational values of at least medium size by conventional standards. Moreover, the PID-5-VRIN seemed to be efficient in discriminating real data from random responses in all samples. In line with Keeley and colleagues' findings, a PID-5-VRIN total score of 17 represented the best balance between sensitivity and specificity in all samples. Clinical adult participants who met this threshold for invalidity also obtained significantly higher scores on the majority of PID-5 trait scales. When the correlations between selected PID-5 trait scale scores and the corresponding interview-based ratings of DSM-5 Section II PDs were considered, appreciable differences in the magnitude and/or direction of association were observed between participants scoring below the PID-5-VRIN cutoff and those meeting the threshold for invalidity (≥17). As a whole, our data suggest that the PID-5-VRIN represents an efficient means of assessing inconsistent responding on the PID-5. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Baseline clinical predictors of antitumor response to the PARP inhibitor olaparib in germline BRCA1/2 mutated patients with advanced ovarian cancer.

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Rafii, Saeed; Gourley, Charlie; Kumar, Rajiv; Geuna, Elena; Ern Ang, Joo; Rye, Tzyvia; Chen, Lee-May; Shapira-Frommer, Ronnie; Friedlander, Michael; Matulonis, Ursula; De Greve, Jacques; Oza, Amit M; Banerjee, Susana; Molife, L Rhoda; Gore, Martin E; Kaye, Stan B; Yap, Timothy A

2017-07-18

The PARP inhibitor olaparib was recently granted Food and Drug Administration (FDA) accelerated approval in patients with advanced BRCA1/2 mutation ovarian cancer. However, antitumor responses are observed in only approximately 40% of patients and the impact of baseline clinical factors on response to treatment remains unclear. Although platinum sensitivity has been suggested as a marker of response to PARP inhibitors, patients with platinum-resistant disease still respond to olaparib. 108 patients with advanced BRCA1/2 mutation ovarian cancers were included. The interval between the end of the most recent platinum chemotherapy and PARPi (PTPI) was used to predict response to olaparib independent of conventional definition of platinum sensitivity. RECIST complete response (CR) and partial response (PR) rates were 35% in patients with platinum-sensitive versus 13% in platinum-resistant (p<0.005). Independent of platinum sensitivity status, the RECIST CR/PR rates were 42% in patients with PTPI greater than 52 weeks and 18% in patients with PTPI less than 52 weeks (p=0.016). No association was found between baseline clinical factors such as FIGO staging, debulking surgery, BRCA1 versus BRCA2 mutations, prior history of breast cancer and prior chemotherapy for breast cancer, and the response to olaparib. We conducted an international multicenter retrospective study to investigate the association between baseline clinical characteristics of patients with advanced BRCA1/2 mutation ovarian cancers from eight different cancer centers and their antitumor response to olaparib. PTPI may be used to refine the prediction of response to PARP inhibition based on the conventional categorization of platinum sensitivity.

Can a physician predict the clinical response to first-line immunomodulatory treatment in relapsing–remitting multiple sclerosis?

Directory of Open Access Journals (Sweden)

Mezei Z

2012-10-01

Full Text Available Zsolt Mezei,1 Daniel Bereczki,1,2 Lilla Racz,1 Laszlo Csiba,1 Tunde Csepany11Department of Neurology, University of Debrecen, Debrecen, Hungary; 2Department of Neurology, Semmelweis University, Budapest, HungaryBackground: Decreased relapse rate and slower disease progression have been reported with long-term use of immunomodulatory treatments (IMTs, interferon beta or glatiramer acetate in relapsing–remitting multiple sclerosis. There are, however, patients who do not respond to such treatments, and they can be potential candidates for alternative therapeutic approaches.Objective: To identify clinical factors as possible predictors of poor long-term response.Methods: A 9-year prospective, continuous follow-up at a single center in Hungary to assess clinical efficacy of IMT.Results: In a patient group of 81 subjects with mean IMT duration of 54 ± 33 months, treatment efficacy expressed as annual relapse rate and change in clinical severity from baseline did not depend on the specific IMT (any of the interferon betas or glatiramer acetate, and on mono- or multifocal features of the initial appearance of the disease. Responders had shorter disease duration and milder clinical signs at the initiation of treatment. Relapse-rate reduction in the initial 2 years of treatment predicted clinical efficacy in subsequent years.Conclusion: Based on these observations, we suggest that a 2-year trial period is sufficient to decide on the efficacy of a specific IMT. For those with insufficient relapse reduction in the first 2 years of treatment, a different IMT or other therapeutic approaches should be recommended.Keywords: multiple sclerosis, immunomodulatory, EDSS, relapse, response

Correlation between Expression of MVP, Index of p53 and AgNOR Value with Chemoradiotherapy Clinical Response of Cervical Cancer

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I. Kurnia

2014-12-01

Full Text Available Cervical cancer is the most frequent cancer found in Indonesia. The primary treatment of cervical cancer at the locally advanced stage is usually performed by using radiotherapy and chemotherapy. The combination of the two techniques is often called chemoradioherapy. The response to chemoradiotherapy is influenced by biological and physical factors. Major vault protein (MVP is a ribonucleoprotein which contributes to drug resistance in some cancers. The purposes of this research were: (1 to determine the correlation between the expression of MVP and the index of p53, including AgNOR values and index of MIB-1; and (2 between MVP and chemoradiotherapy clinical response of cervical cancer. Twenty-one microscopic slides taken from biopsy tissues of cervical cancer patients before undergoing treatment were stained to identify MVP, p53, and MIB-1 by means of immunohistochemistry techniques and AgNORs staining. After undergoing chemoradiotherapy treatment, the patients’ clinical responses were observed by pelvic control method. Experimental results showed that there was a correlation between MVP and AgNOR value (P=0.05, but no correlation between MVP and index of p53 (P=0.729, including MIB-1 LI (P=0.63, in untreated cervical cancer. In addition, there was no association between MVP and chemoradioterapy response. In conclusion, MVP expression correlates with the process of cell proliferation before the G2 phase of cell cycle in untreated cancer cells. Those have no association with clinical responses after the completion of treatment.

Correlation between expression of MVP, index of p53 and AgNOR value with chemoradiotherapy clinical response of cervical cancer

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Kurnia, I.; Tetriana, D.; Siregar, B.; Ramli, I.; Andrijono, A.; Soetopo, S.; Kurjana, T.; Hernowo, B.S.; Tobing, M.D.M.

2014-01-01

Cervical cancer is the most frequent cancer found in Indonesia. The primary treatment of cervical cancer at the locally advanced stage is usually performed by using radiotherapy and chemotherapy. The combination of the two techniques is often called chemoradiotherapy. The response to chemoradiotherapy is influenced by biological and physical factors. Major vault protein (MVP) is a ribonucleoprotein which contributes to drug resistance in some cancers. The purposes of this research were: (1) to determine the correlation between the expression of MVP and the index of p53, including AgNOR values and index of MIB-1; and (2) between MVP and chemoradiotherapy clinical response of cervical cancer. Twenty-one microscopic slides taken from biopsy tissues of cervical cancer patients before undergoing treatment were stained to identify MVP, p53, and MIB-1 by means of immunohistochemistry techniques and AgNORs staining. After undergoing chemoradiotherapy treatment, the patients’ clinical responses were observed by pelvic control method. Experimental results showed that there was a correlation between MVP and AgNOR value (P=0.05), but no correlation between MVP and index of p53 (P=0.729), including MIB-1 LI (P=0.63), in untreated cervical cancer. In addition, there was no association between MVP and chemoradiotherapy response. In conclusion, MVP expression correlates with the process of cell proliferation before the G2 phase of cell cycle in untreated cancer cells. Those have no association with clinical responses after the completion of treatment. (author)

Multi-parametric MRI in cervical cancer. Early prediction of response to concurrent chemoradiotherapy in combination with clinical prognostic factors

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Yang, Wei; Chen, Bing; Wang, Ai Jun; Zhao, Jian Guo [The General Hospital of Ningxia Medical University, Department of Radiology, Yinchuan (China); Qiang, Jin Wei [Fudan University, Department of Radiology, Jinshan Hospital, Shanghai (China); Tian, Hai Ping [The General Hospital of Ningxia Medical University, Department of Pathology, Yinchuan (China)

2018-01-15

To investigate the prediction of response to concurrent chemoradiotherapy (CCRT) through a combination of pretreatment multi-parametric magnetic resonance imaging (MRI) with clinical prognostic factors (CPF) in cervical cancer patients. Sixty-five patients underwent conventional MRI, diffusion-weighted imaging (DWI), and dynamic contrast-enhanced MRI (DCE-MRI) before CCRT. The patients were divided into non- and residual tumour groups according to post-treatment MRI. Pretreatment MRI parameters and CPF between the two groups were compared and prognostic factors, optimal thresholds, and predictive performance for post-treatment residual tumour occurrence were estimated. The residual group showed a lower maximum slope of increase (MSI{sub L}) and signal enhancement ratio (SER{sub L}) in low-perfusion subregions, a higher apparent diffusion coefficient (ADC) value, and a higher stage than the non-residual tumour group (p < 0.001, p = 0.003, p < 0.001, and p < 0.001, respectively). MSI{sub L} and ADC were independent prognostic factors. The combination of both measures improved the diagnostic performance compared with individual MRI parameters. A further combination of these two factors with CPF exhibited the highest predictive performance. Pretreatment MSI{sub L} and ADC were independent prognostic factors for cervical cancer. The predictive capacity of multi-parametric MRI was superior to individual MRI parameters. The combination of multi-parametric MRI with CPF further improved the predictive performance. (orig.)

Lymphocyte counts and responses to PHA and PPD following radiation therapy for breast cancer in patients who develop recurrent disease and those who remain clinically disease-free

International Nuclear Information System (INIS)

Blomgren, H.; Wasserman, J.; Wallgren, A.; Baral, E.; Petrini, B.; Idestroem, K.

1980-01-01

Peripheral blood lymphocyte counts and stimulations by PHA and PPD in vitro were examined before and up to four years after local pre- or post-operative radiation therapy of 99 patients with breast cancer. The patient material was divided into those who remained clinically disease-free during a follow up period of 4.5-7 years and those who relapsed. Radiation therapy reduced the lymphocyte counts and PPD response to the same levels in both groups of patients; there were no essential differences in their recoveries, with the exception of a somewhat delayed recovery of the PPD-response in the patients who relapsed. PHA responses of the lymphocytes were not decreased following radiation therapy. The data indicate that these radiation induced changes of the peripheral lymphocyte population were similar both in patients who relapsed and those who remained symptom free. A group of 47 women with breast cancer that was treated by surgery only was examined similarly as a comparison. Patients from this group who developed local recurrences had higher lymphocyte counts than those who remained disease-free; patients who developed distant metastases had somewhat decreased PHA responses

A phase I study of PRO131921, a novel anti-CD20 monoclonal antibody in patients with relapsed/refractory CD20+ indolent NHL: correlation between clinical responses and AUC pharmacokinetics.

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Casulo, Carla; Vose, Julie M; Ho, William Y; Kahl, Brad; Brunvand, Mark; Goy, Andre; Kasamon, Yvette; Cheson, Bruce; Friedberg, Jonathan W

2014-09-01

PRO131921 is a third-generation, humanized anti-CD20 monoclonal antibody with increased antibody-dependent cytotoxicity and complement-dependent cytotoxicity compared to rituximab. In this phase I study, PRO131921 was administered as a single agent to patients with CD20+, relapsed or refractory, indolent non-Hodgkin lymphoma (NHL) who had been treated with a prior rituximab-containing regimen. The primary aim of this study was safety and tolerability of PRO131921. The secondary aim of the study, and focus of this report, was to determine the pharmacokinetics (PK) profile of PRO131921 and establish a correlation between drug exposure and clinical efficacy. Patients were treated with PRO131921 by intravenous infusion weekly for 4 weeks and the dose was escalated based on safety in a 3+3 design. Twenty-four patients were treated with PRO131921 at doses from 25mg/m(2) to 800 mg/m(2). Analysis of PK data demonstrated a correlation between higher normalized drug exposure (normalized AUC) and tumor shrinkage (p = .0035). Also, normalized AUC levels were higher among responders and subjects displaying tumor shrinkage versus subjects progressing or showing no regression (p = 0.030). In conclusion, PRO131921 demonstrated clinical activity in rituximab-relapsed and refractory indolent NHL patients. The observation that higher normalized AUC may be associated with improved clinical responses has potential implications in future trials of monoclonal antibody-based therapies, and emphasizes the importance of early PK studies to optimize antibody efficacy. Copyright © 2014 Elsevier Inc. All rights reserved.

Maternal-fetal acute responses to two moderate-intensity exercise types: a randomized clinical trial

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Jousilene de Sales Tavares

2018-03-01

Full Text Available Objective:  This study aims to compare maternal and fetal responses during two physical exercise types. Design:  A randomized clinical trial compared 120 pregnant women, gestational age of 35-37 weeks, 56 exercising on a stationary bicycle (Group A and 64 on a treadmill (Group B. Methods: Participants were monitored for three 20-minute phases: resting, exercise and recovery.  Fetal heart rate (FHR and maternal heart rate (MHR were monitored.  Glucose and lactate levels were evaluated at rest and during exercise. Results:  After the beginning of exercise, maximum lactate (L levels were reached at 20 minutes and never exceeded 4 mmol/l.  FHR decreased by 22 bpm during exercise in relation to resting values, irrespective of the exercise type (p0.05, increasing at 20’ to 32% and 40.6%, respectively, (p>0.05.  The FHR decrease during exercise was accompanied by a simultaneous increase in its variability (p<0.001, nevertheless a rapid return to resting values was observed shortly after exercise end.  Glucose decreased in both groups irrespective of the exercise type (85 mg/dl at rest; 79 mg/dl during exercise and 81 mg/dl during recovery; p<0.001. There were no hypoglycemia cases. Conclusions: FHR variability increase and the rapid return to resting values after exercise suggests that the FHR fall and the presence of bradycardia during exercise is the fetal physiologic response to blood flow redistribution, with maintenance of fetal well-being. Key-words: Exercise; fetal heart rate; glucose; maternal heart rate; pregnancy Clinical Trial Registration: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01383889.

Roles and Responsibilities, and Education and Training Requirements for Clinically Qualified Medical Physicists (Spanish Edition)

International Nuclear Information System (INIS)

2014-01-01

The IAEA technical cooperation project Strengthening Medical Physics in Radiation Medicine was approved by the IAEA Board of Governors for the period 2009-2013 with the aim of ensuring the safe and effective diagnosis and treatment of patients. The IAEA, together with the World Health Organization and stakeholders from numerous medical physics professional societies worldwide, including the International Organization for Medical Physics (IOMP), the European Federation of Organisations for Medical Physics, the American Association of Physicists in Medicine (AAPM), the Latin American Medical Physics Association, the Asia-Oceania Federation of Organizations for Medical Physics, the European Society for Radiotherapy and Oncology, the European Commission and the International Radiation Protection Association, as well as regional counterparts from Africa, Asia, Europe and Latin America, met in Vienna in May 2009 to plan and coordinate the new project. A shortage of clinically qualified medical physicists (CQMPs), insufficient education and training (especially properly organized and coordinated clinical training), and lack of professional recognition were identified as the main problems to be addressed under this project. This publication was developed under the project framework in response to these findings. It aims, first, at defining appropriately and unequivocally the roles and responsibilities of a CQMP in specialties of medical physics related to the use of ionizing radiation, such as radiation therapy, nuclear medicine, and diagnostic and interventional radiology. Important, non-ionizing radiation imaging specialties, such as magnetic resonance and ultrasound, are also considered for completeness. On the basis of these tasks, this book provides recommended minimum requirements for the academic education and clinical training of CQMPs, including recommendations for their accreditation, certification and registration, along with continuing professional development

[Clinical significance of drug resistance-associated mutations in treatment of hepatitis C with direct-acting antiviral agents].

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Li, Z; Chen, Z W; Ren, H; Hu, P

2017-03-20

Direct-acting antiviral agents (DAAs) achieve a high sustained virologic response rate in the treatment of chronic hepatitis C virus infection. However, drug resistance-associated mutations play an important role in treatment failure and have attracted more and more attention. This article elaborates on the clinical significance of drug resistance-associated mutations from the aspects of their definition, association with genotype, known drug resistance-associated mutations and their prevalence rates, the impact of drug resistance-associated mutations on treatment naive and treatment-experienced patients, and the role of clinical detection, in order to provide a reference for clinical regimens with DAAs and help to achieve higher sustained virologic response rates.

A clinical trial comparing the responses of animal tumors receiving heat sensitizing drugs prior to whole body hyperthermia

International Nuclear Information System (INIS)

Klein, M.K.; Forsyth, K.; Dewhirst, M.W.; Fuller, D.J.M.

1984-01-01

Whole body hyperthermia (WBH) has rarely been found effective in inducing complete tumor responses. Recent in vitro studies showing that heat sensitizion is possible have renewed interest in this field. In this protocol, WBH is induced via a commercially available inductive device and maintained at 42 0 C for thirty minutes. The heat sensitizing drugs, difluoromethylornithine (DFMO) methylglyoxal bis (guanylhydrazone) (MGBG) are administered 48 hours before, in accordance with in vitro studies. Goals of the study include evaluation of normal tissue toxicity and tumor response. Two normal dogs were treated to study acute toxicities before inception of the clinical trial. The gastrointestinal and hematopoietic systems were used to monitor toxicities using systems review and serial bloodwork. These studies and preliminary clinical results of observed tumor regression in dogs with lymphomas are discussed. Consistent changes in all patients included elevations in liver enzymes, creatine phosphokinase (CPK), and white blood cell counts, as well as, decreases in platelet counts. All changes were transient and clinical signs were not associated with them. Tumor volume reductions from 25% to 74% have been documented

Do Family Responsibilities and a Clinical Versus Research Faculty Position Affect Satisfaction with Career and Work–Life Balance for Medical School Faculty?

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Beckett, Laurel; Nettiksimmons, Jasmine; Howell, Lydia Pleotis

2015-01-01

Abstract Background: Balancing career and family obligations poses challenges to medical school faculty and contributes to dissatisfaction and attrition from academics. We examined the relationship between family setting and responsibilities, rank, and career and work–life satisfaction for faculty in a large U.S. medical school. Methods: Baseline faculty surveys were analyzed from the first year of a 4-year National Institutes of Health–funded study to evaluate awareness, knowledge, attitudes, and use of family friendly policies and career satisfaction. The study focus was on the impact of family responsibilities and characteristics of the faculty position (rank, clinical vs. nonclinical, and academic series) in multivariate comparisons between primary predictors and outcomes of interest. Results: Both clinical and family responsibilities for children under 18 play a major and interacting role in satisfaction with career and work–life balance. Clinical faculty respondents without children at home reported significantly greater career satisfaction and better work–life balance than their nonclinical counterparts. Nonclinical faculty respondents with children reported greater satisfaction and better balance than counterparts without family responsibilities. However, the advantage in career satisfaction and work–life balance for clinical faculty respondents disappeared for those with responsibility for young children. No gender-based differences were noted in the results or across faculty rank for respondents; however, for women, reaching associate professor resulted in greater career satisfaction. Conclusion: This study suggests that both work-related factors and family responsibilities influence satisfaction with career and work–life balance, but the predictors appear to interact in complex and nuanced ways. Further research is needed to delineate more clearly these interactions and to explore other factors that may play important additional roles. PMID

Do Family Responsibilities and a Clinical Versus Research Faculty Position Affect Satisfaction with Career and Work-Life Balance for Medical School Faculty?

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Beckett, Laurel; Nettiksimmons, Jasmine; Howell, Lydia Pleotis; Villablanca, Amparo C

2015-06-01

Balancing career and family obligations poses challenges to medical school faculty and contributes to dissatisfaction and attrition from academics. We examined the relationship between family setting and responsibilities, rank, and career and work-life satisfaction for faculty in a large U.S. medical school. Baseline faculty surveys were analyzed from the first year of a 4-year National Institutes of Health-funded study to evaluate awareness, knowledge, attitudes, and use of family friendly policies and career satisfaction. The study focus was on the impact of family responsibilities and characteristics of the faculty position (rank, clinical vs. nonclinical, and academic series) in multivariate comparisons between primary predictors and outcomes of interest. Both clinical and family responsibilities for children under 18 play a major and interacting role in satisfaction with career and work-life balance. Clinical faculty respondents without children at home reported significantly greater career satisfaction and better work-life balance than their nonclinical counterparts. Nonclinical faculty respondents with children reported greater satisfaction and better balance than counterparts without family responsibilities. However, the advantage in career satisfaction and work-life balance for clinical faculty respondents disappeared for those with responsibility for young children. No gender-based differences were noted in the results or across faculty rank for respondents; however, for women, reaching associate professor resulted in greater career satisfaction. This study suggests that both work-related factors and family responsibilities influence satisfaction with career and work-life balance, but the predictors appear to interact in complex and nuanced ways. Further research is needed to delineate more clearly these interactions and to explore other factors that may play important additional roles.

DNA vaccine delivered by a needle-free injection device improves potency of priming for antibody and CD8+ T-cell responses after rAd5 boost in a randomized clinical trial.

Directory of Open Access Journals (Sweden)

Barney S Graham

Full Text Available DNA vaccine immunogenicity has been limited by inefficient delivery. Needle-free delivery of DNA using a CO2-powered Biojector® device was compared to delivery by needle and syringe and evaluated for safety and immunogenicity.Forty adults, 18-50 years, were randomly assigned to intramuscular (IM vaccinations with DNA vaccine, VRC-HIVDNA016-00-VP, (weeks 0, 4, 8 by Biojector® 2000™ or needle and syringe (N/S and boosted IM at week 24 with VRC-HIVADV014-00-VP (rAd5 with N/S at 10(10 or 10(11 particle units (PU. Equal numbers per assigned schedule had low (≤500 or high (>500 reciprocal titers of preexisting Ad5 neutralizing antibody.120 DNA and 39 rAd5 injections were given; 36 subjects completed follow-up research sample collections. IFN-γ ELISpot response rates were 17/19 (89% for Biojector® and 13/17 (76% for N/S delivery at Week 28 (4 weeks post rAd5 boost. The magnitude of ELISpot response was about 3-fold higher in Biojector® compared to N/S groups. Similar effects on response rates and magnitude were observed for CD8+, but not CD4+ T-cell responses by ICS. Env-specific antibody responses were about 10-fold higher in Biojector-primed subjects.DNA vaccination by Biojector® was well-tolerated and compared to needle injection, primed for greater IFN-γ ELISpot, CD8+ T-cell, and antibody responses after rAd5 boosting.ClinicalTrials.gov NCT00109629.

Clinical, immunological and virological response to different antiretroviral regimens in a cohort of HIV-2-infected patients

NARCIS (Netherlands)

van der Ende, Marchina E.; Prins, Jan M.; Brinkman, Kees; Keuter, Monique; Veenstra, Jan; Danner, Sven A.; Niesters, Hubert G. M.; Osterhaus, Albert D. M. E.; Schutten, Martin

2003-01-01

Objective: To assess the clinical, immunological and virological response and the emergence of resistance towards antiretroviral therapy (ART) in a cohort of HIV-2-infected patients. Design: Observational study. Patients: HIV-2-infected patients residing in the Netherlands. Results: From 1995 to

The microculture-kinetic (MiCK) assay: the role of a drug-induced apoptosis assay in drug development and clinical care.

Science.gov (United States)

Bosserman, Linda; Prendergast, Franklyn; Herbst, Roy; Fleisher, Martin; Salom, Emery; Strickland, Steven; Raptis, Anastasios; Hallquist, Allan; Perree, Mathieu; Rajurkar, Swapnil; Karimi, Misagh; Rogers, Karl; Davidson, Dirk; Willis, Carl; Penalver, Manuel; Homesley, Howard; Burrell, Matthew; Garrett, Audrey; Rutledge, James; Chernick, Michael; Presant, Cary A

2012-08-15

A drug-induced apoptosis assay, termed the microculture-kinetic (MiCK) assay, has been developed. Blinded clinical trials have shown higher response rates and longer survival in groups of patients with acute myelocytic leukemia and epithelial ovarian cancer who have been treated with drugs that show high apoptosis in the MiCK assay. Unblinded clinical trials in multiple tumor types have shown that the assay will be used frequently by clinicians to determine treatment, and when used, results in higher response rates, longer times to relapse, and longer survivals. Model economic analyses suggest possible cost savings in clinical use based on increased generic drug use and single-agent substitution for combination therapies. Two initial studies with drugs in development are promising. The assay may help reduce costs and speed time to drug approval. Correlative studies with molecular biomarkers are planned. This assay may have a role both in personalized clinical therapy and in more efficient drug development. ©2012 AACR.

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

Science.gov (United States)

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.

Assessment of clinical trial participant patient satisfaction: a call to action.

Science.gov (United States)

Pflugeisen, Bethann Mangel; Rebar, Stacie; Reedy, Anne; Pierce, Roslyn; Amoroso, Paul J

2016-10-06

As patient satisfaction scores become increasingly relevant in today's health care market, we sought to evaluate satisfaction of the unique subset of patients enrolling in clinical trials in a research facility embedded within a community hospital system. We developed and deployed a patient satisfaction survey tailored to clinical trial patients who consented to and/or completed a clinical trial in our research institute in the prior year. The survey was distributed to 222 patients. Likert scale responses were analyzed using top box and percentile rank procedures. Correlation analysis was used to evaluate associations between the clinical trial experience and intent to return to our system for routine care. Ninety surveys were returned in the 6 months following the mailing for a 41 % response rate; the bulk of these (N = 81) were returned within 6 weeks of the mailing. The questions with the highest ranking responses were related to interactions with staff (84th percentile or higher). Fifty-one point one percent of patients (64th percentile) strongly agreed that they would seek future care in our system. Patient intent to return to the provider seen during the clinical trial was most highly correlated with intent to seek future care within our system (r = 0.54, p system-based clinical trials and the relationship between clinical trial participation and perception of the healthcare system as a desirable resource for routine medical care. We argue that this work is invaluable to the research community and submit a call to action to our peers to begin systematic evaluation of clinical trial patient satisfaction.

Higher Education--The Flexible Employment Sector?

Science.gov (United States)

Scott, Jill; Ridgley, Clare; Spurgeon, Peter

2003-01-01

Explored the extent to which policies and practices promoting work-life balance (family friendly policies) have been taken up within the English higher education sector. Responses from 50 higher education institutions show that flexible working practices are more widespread than the formal policies of institutions would suggest. (SLD)

Comparing the Effectiveness of a Clinical Registry and a Clinical Data Warehouse for Supporting Clinical Trial Recruitment: A Case Study

Science.gov (United States)

Weng, Chunhua; Bigger, J Thomas; Busacca, Linda; Wilcox, Adam; Getaneh, Asqual

2010-01-01

This paper reports a case study comparing the relative efficiency of using a Diabetes Registry or a Clinical Data Warehouse to recruit participants for a diabetes clinical trial, TECOS. The Clinical Data Warehouse generated higher positive predictive accuracy (31% vs. 6.6%) and higher participant recruitment than the Registry (30 vs. 14 participants) in a shorter time period (59 vs. 74 working days). We identify important factors that increase clinical trial recruitment efficiency and lower cost. PMID:21347102

Adalimumab for Treatment of Noninfectious Uveitis: Immunogenicity and Clinical Relevance of Measuring Serum Drug Levels and Antidrug Antibodies.

Science.gov (United States)

Cordero-Coma, Miguel; Calleja-Antolín, Sara; Garzo-García, Irene; Nuñez-Garnés, Ana M; Álvarez-Castro, Carolina; Franco-Benito, Manuel; Ruiz de Morales, Jose G

2016-12-01

To evaluate the rate of immunogenicity induced by adalimumab and its relationship with drug serum levels and clinical responses in patients with noninfectious uveitis. Prospective observational study. Consecutive patients from 1 referral center who initiated treatment with adalimumab for active noninfectious uveitis resistant to conventional therapy. All patients received 40 mg adalimumab every other week. Patients were evaluated clinically and immunologically before and after 4, 8, and 24 weeks of treatment. Clinical evaluation included assessment of changes in visual acuity, degree of inflammation in the anterior chamber and vitreous cavity, central macular thickness, and retinal angiographic leakage. Immunologic evaluation included assessment of serum trough adalimumab and antibodies against adalimumab (AAA) levels and class II HLA typing. Twenty-five patients were enrolled. Overall, 18 of 25 patients (72%) showed a favorable clinical response to adalimumab therapy. Eleven patients (44%) achieved a complete response and 7 (28%) achieved a partial response. However, 7 of 25 patients (28%) were considered nonresponders. Median trough adalimumab serum levels were higher in responders than in nonresponders (P uveitis outcome was observed only in patients with permanent AAA+, which correlated with undetectable adalimumab trough levels (P = 0.014). Treatment of noninfectious uveitis with adalimumab is associated with high rates of favorable clinical response. Overall, adalimumab trough levels were higher in responder patients. Development of permanent AAA was associated with undetectable trough adalimumab levels and worse uveitis outcome. Immunogenicity was more common in patients in whom uveitis was associated with a systemic disease and was not influenced by concomitant immunosuppressors. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Glycan analysis of Fonsecaea monophora from clinical and environmental origins reveals different structural profile and human antigenic response

Directory of Open Access Journals (Sweden)

Juliana Reis Burjack

2014-10-01

Full Text Available Dematiaceous fungi constitute a large and heterogeneous group, characterized by having a dark pigment, the dihydroxynaftalen melanin - DHN, inside their cell walls. In nature they are found mainly as soil microbiota or decomposing organic matter, and are spread in tropical and subtropical regions. The fungus Fonsecaea monophora causes chromoblastomycosis in humans, and possesses essential mechanisms that may enhance pathogenicity, proliferation and dissemination inside the host. Glycoconjugates confer important properties to these pathogenic microorganisms. In this work, structural characterization of glycan structures present in two different strains of F. monophora MMHC82 and FE5p4, from clinical and environmental origins, respectively, was performed. Each one were grown on Minimal Medium (MM and Czapeck-Dox (CD medium, and the water soluble cell wall glycoconjugates and exopolysaccharides (EPS were evaluated by NMR, methylation and principal component analysis (PCA. By combining the methylation and 2D NMR analyses, it was possible to visualize the glycosidic profiles of the complex carbohydrate mixtures. Significant differences were observed in β-D-Galf-(1→5 and (1→6 linkages, α- and β-D-Glcp-(1→3, (1→4 and (1→6 units, as well as in α-D-Manp. PCA from 1H-NMR data showed that MMHC82 from CD medium showed a higher variation in the cell wall carbohydrates, mainly related to O-2 substituted β-D-Galf (δ 106.0/5.23 and δ 105.3/5.23 units. In order to investigate the antigenic response of the glycoconjugates, these were screened against serum from chromoblastomycosis patients. The antigen which contained the cell wall of MMHC82 grown in MM had β-D-Manp units that promoted higher antigenic response. The distribution of these fungal species in nature and the knowledge of how cell wall polysaccharides and glycoconjugates structure vary, may contribute to the better understanding and the elucidation of the pathology caused by this

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

Directory of Open Access Journals (Sweden)

Ye W

2014-05-01

Full Text Available Wenyu Ye,1 William Montgomery,2 Zbigniew Kadziola,3 Li Liu,4 Haibo Xue,4 Michael D Stensland,5 Tamas Treuer61Real World Analytics, Eli Lilly and Company, Indianapolis, IN, USA; 2Global Patient Outcomes and Real World Evidence, Eli Lilly Australia Pty Ltd, West Ryde, Australia; 3Real World Analytics Capabilities, Eli Lilly GmbH, Vienna, Austria; 4Lilly Suzhou Pharmaceutical Co, Ltd, Shanghai Branch, People’s Republic of China; 5Agile Outcomes Research, Inc., Rochester, MN, USA; 6Neuroscience Research, Eli Lilly and Company, Budapest, HungaryBackground: 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

Clinical trials using IFN-α as a vaccine adjuvant: new strategies for the molecular monitoring of the immune response

International Nuclear Information System (INIS)

Belardelli, F.; Arico, E.; Marincola, F.; Wang, E.

2009-01-01

The main general objective of this project was to define immunotherapy protocols based on the new concept of using IFN-a as and immune adjuvant, developing innovative methodologies suitable for predicting and monitoring the immunological and clinical responses. Specific aim of developing new micro arrays technologies particularly suitable for a molecular tracking and prediction of the response to IFN of cytokine-treated patients

Current State of the Art: Management of Higher Risk Myelodysplastic Syndromes.

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Komrokji, Rami S

2016-08-01

The higher risk myelodysplastic syndrome (MDS) patients, defined by the International Prognostic Scoring System (IPSS) as intermediate-2 or high-risk groups, compromise a third of MDS patients who have an expected survival of less than 1.5 years. Our ability to better define higher risk MDS improved with the proposal of new clinical risk models such as the revised IPSS and by integration of molecular data, including somatic gene mutations. Allogeneic hematopoietic stem-cell transplantation (AHSCT) remains the only curative option. In higher risk MDS patients, proceeding early with AHSCT is associated with maximum survival gain. The decision to pursue AHSCT is individualized according to disease risk, comorbidities, and functional status. The role of therapy before AHSCT remains controversial, and the role of post-AHSCT maintenance is evolving. Hypomethylating agents are the only medications that alter the natural history of the disease. Azacitidine is the only drug reported to improve overall survival in higher risk MDS patients. Appropriate use and assessment of response is key for assuring patients benefit of such limited options. Treatment after failure of hypomethylating agents is an unmet need. The role of detectable somatic gene mutations in prognosis and tailoring therapy continue to emerge. Copyright © 2016 Elsevier Inc. All rights reserved.

Calcium Signaling Pathway Is Associated with the Long-Term Clinical Response to Selective Serotonin Reuptake Inhibitors (SSRI and SSRI with Antipsychotics in Patients with Obsessive-Compulsive Disorder.

Directory of Open Access Journals (Sweden)

Hidehiro Umehara

Full Text Available Selective serotonin reuptake inhibitors (SSRI are established first-line pharmacological treatments for obsessive-compulsive disorder (OCD, while antipsychotics are used as an augmentation strategy for SSRI in OCD patients who have either no response or a partial response to SSRI treatment. The goal of the present study was to identify genetic variants and pathways that are associated with the long-term clinical response of OCD patients to SSRI or SSRI with antipsychotics.We first performed a genome-wide association study of 96 OCD patients to examine genetic variants contributing to the response to SSRI or SSRI with antipsychotics. Subsequently, we conducted pathway-based analyses by using Improved Gene Set Enrichment Analysis for Genome-wide Association Study (i-GSEA4GWAS to examine the combined effects of genetic variants on the clinical response in OCD.While we failed to detect specific genetic variants associated with clinical responses to SSRI or to SSRI with an atypical antipsychotic at genome-wide levels of significance, we identified 8 enriched pathways for the SSRI treatment response and 5 enriched pathways for the treatment response to SSRI with an antipsychotic medication. Notably, the calcium signaling pathway was identified in both treatment responses.Our results provide novel insight into the molecular mechanisms underlying the variability in clinical response to SSRI and SSRI with antipsychotics in OCD patients.

Prevalence of etravirine mutations and impact on response to treatment in routine clinical care: the Swiss HIV Cohort Study (SHCS).

Science.gov (United States)

Scherrer, A U; Hasse, B; von Wyl, V; Yerly, S; Böni, J; Bürgisser, P; Klimkait, T; Bucher, H C; Ledergerber, B; Günthard, H F

2009-11-01

Etravirine (ETV) is a novel nonnucleoside reverse transcriptase inhibitor (NNRTI) with reduced cross-resistance to first-generation NNRTIs, which has been primarily studied in randomized clinical trials and not in routine clinical settings. ETV resistance-associated mutations (RAMs) were investigated by analysing 6072 genotypic tests. The antiviral activity of ETV was predicted using different interpretation systems: International AIDS Society-USA (IAS-USA), Stanford, Rega and Agence Nationale de Recherches sur le Sida et les hépatites virales (ANRS). The prevalence of ETV RAMs was higher in NNRTI-exposed patients [44.9%, 95% confidence interval (CI) 41.0-48.9%] than in treatment-naïve patients (9.6%, 95% CI 8.5-10.7%). ETV RAMs in treatment-naïve patients mainly represent polymorphism, as prevalence estimates in genotypic tests for treatment-naïve patients with documented recent (IAS-USA mutations (L100I, K101E/H/P and Y181C/I/V) reduced the treatment response at week 24. Most ETV RAMs in drug-naïve patients are polymorphisms rather than transmitted RAMs. Uncertainty regarding predictions of antiviral activity for ETV in NNRTI-treated patients remains high. The lowest activity was predicted for patients harbouring extensive multidrug-resistant viruses, thus limiting ETV use in those who are most in need.

Absolute number of new lesions on 18F-FDG PET/CT is more predictive of clinical response than SUV changes in metastatic melanoma patients receiving ipilimumab.

Science.gov (United States)

Anwar, Hoda; Sachpekidis, Christos; Winkler, Julia; Kopp-Schneider, Annette; Haberkorn, Uwe; Hassel, Jessica C; Dimitrakopoulou-Strauss, Antonia

2018-03-01

Evaluation of response to immunotherapy is a matter of debate. The aim of the present study was to evaluate the response of metastatic melanoma to treatment with ipilimumab by means of 18 F-FDG PET/CT, using the patients' clinical response as reference. The final cohort included in the analyses consisted of 41 patients with metastatic melanoma who underwent 18 F-FDG PET/CT before and after administration of ipilimumab. After determination of the best clinical response, the PET/CT scans were reviewed and a separate independent analysis was performed, based on the number and functional size of newly emerged 18 F-FDG-avid lesions, as well as on the SUV changes after therapy. The median observation time of the patients after therapy was 21.4 months (range 6.3-41.9 months). Based on their clinical response, patients were dichotomized into those with clinical benefit (CB) and those without CB (No-CB). The CB group (31 patients) included those with stable disease, partial remission and complete remission, and the No-CB group (10 patients) included those with progressive disease. The application of a threshold of four newly emerged 18 F-FDG-avid lesions on the posttherapy PET/CT scan led to a sensitivity (correctly predicting CB) of 84% and a specificity (correctly predicting No-CB) of 100%. This cut-off was lower for lesions with larger functional diameters (three new lesions larger than 1.0 cm and two new lesions larger than 1.5 cm). SUV changes after therapy did not correlate with clinical response. Based on these findings, we developed criteria for predicting clinical response to immunotherapy by means of 18 F-FDG PET/CT (PET Response Evaluation Criteria for Immunotherapy, PERCIMT). Our results show that a cut-off of four newly emerged 18 F-FDG-avid lesions on posttherapy PET/CT gives a reliable indication of treatment failure in patients under ipilimumab treatment. Moreover, the functional size of the new lesions plays an important role in predicting the clinical

{sup 99m}Tc-Annexin A5 quantification of apoptotic tumor response: a systematic review and meta-analysis of clinical imaging trials

Energy Technology Data Exchange (ETDEWEB)

Belhocine, Tarik Z. [Western University, Biomedical Imaging Research Centre (BIRC), London, Ontario (Canada); Blankenberg, Francis G. [Lucile Salter Packard Children' s Hospital, Stanford, Division of Pediatric Radiology, Department of Radiology, Palo Alto, CA (United States); Kartachova, Marina S. [Medical Center Alkmaar, Department of Nuclear Medicine, Alkmaar (Netherlands); Stitt, Larry W. [LW Stitt Statistical Services, London, Ontario (Canada); Vanderheyden, Jean-Luc [JLVMI Consulting LLC, Waukesha, WI (United States); Hoebers, Frank J.P. [Maastricht University Medical Centre, Department of Radiation Oncology (MAASTRO Clinic), GROW School for Oncology and Developmental Biology, Maastricht (Netherlands); Wiele, Christophe van de [University Hospital Ghent, Department of Nuclear Medicine and Radiology, Ghent (Belgium)

2015-12-15

{sup 99m}Tc-Annexin A5 has been used as a molecular imaging probe for the visualization, characterization and measurement of apoptosis. In an effort to define the quantitative {sup 99m}Tc-annexin A5 uptake criteria that best predict tumor response to treatment, we performed a systematic review and meta-analysis of the results of all clinical imaging trials found in the literature or publicly available databases. Included in this review were 17 clinical trials investigating quantitative {sup 99m}Tc-annexin A5 (qAnx5) imaging using different parameters in cancer patients before and after the first course of chemotherapy and/or radiation therapy. Qualitative assessment of the clinical studies for diagnostic accuracy was performed using the QUADAS-2 criteria. Of these studies, five prospective single-center clinical trials (92 patients in total) were included in the meta-analysis after exclusion of one multicenter clinical trial due to heterogeneity. Pooled positive predictive values (PPV) and pooled negative predictive values (NPV) (with 95 % CI) were calculated using Meta-Disc software version 1.4. Absolute quantification and/or relative quantification of {sup 99m}Tc-annexin A5 uptake were performed at baseline and after the start of treatment. Various quantitative parameters have been used for the calculation of {sup 99m}Tc-annexin A5 tumor uptake and delta (Δ) tumor changes post-treatment compared to baseline including: tumor-to-background ratio (TBR), ΔTBR, tumor-to-noise ratio, relative tumor ratio (TR), ΔTR, standardized tumor uptake ratio (STU), ΔSTU, maximum count per pixel within the tumor volume (Cmax), Cmax%, absolute ΔU and percentage (ΔU%), maximum ΔU counts, semiquantitative visual scoring, percent injected dose (%ID) and %ID/cm{sup 3}. Clinical trials investigating qAnx5 imaging have included patients with lung cancer, lymphoma, breast cancer, head and neck cancer and other less common tumor types. In two phase I/II single-center clinical trials

Clinical and genetic predictors of response to narrowband ultraviolet B for the treatment of chronic plaque psoriasis.

LENUS (Irish Health Repository)

Ryan, C

2012-02-01

BACKGROUND: There is considerable variability in the number of exposures of narrowband ultraviolet B (NB-UVB) needed to clear psoriasis and in the duration of remission. OBJECTIVES: We assessed clinical parameters as predictors of the number of exposures needed to clear psoriasis and of the duration of remission. The influence of genetic polymorphisms of the vitamin D receptor (VDR) on treatment response was also evaluated. METHODS: This was a prospective study of 119 patients with chronic plaque psoriasis treated with NB-UVB until clearance was achieved. They were then followed for up to 1 year or until relapse occurred. The frequency of the Fok1, Apa1, Bsm1, Taq1 and rs4516035 polymorphisms of the VDR gene was assessed in 93 of the 119 patients. RESULTS: Of the 119 patients, 105 completed the course of phototherapy. Using an intention to treat analysis, 83% of the initial cohort (99 of 119 patients) achieved clearance, in a median of 26 exposures (interquartile range 19-35) with a median remission duration of 16 weeks (interquartile range 9-22). Factors significantly associated with a lower number of exposures to clearance included a lower baseline Psoriasis Area and Severity Index (P = 0.004), lower baseline Dermatology Life Quality Index (P = 0.047), female sex (P = 0.043), lower body weight (P = 0.008), and a higher number of previous courses of TL-01 (P = 0.005). The only clinical factor influencing remission duration was number of exposures (P = 0.0009), with a decreased remission duration in those who required a greater number of exposures to clear. The Taq1 VDR polymorphism (rs731236) also significantly predicted remission duration (P = 0.038). Patients homozygous for the C allele, which is associated with decreased activity of the VDR, had a shorter remission duration than those heterozygous for the allele (P = 0.026) and those homozygous for the T allele (P = 0.013). CONCLUSIONS: This study highlights the fact that both genetic and clinical parameters

Manipulation of the metabolic response in clinical practice

DEFF Research Database (Denmark)

Kehlet, H

2000-01-01

morbidity. Effective afferent neural blockade with continuous epidural local anesthetic techniques inhibits a major part of the endocrine metabolic response, leading to improved protein economy but without important effects on inflammatory or immunologic responses. In contrast, pain treatment with other...... modalities such as nonsteroidal antiinflammatory drugs (NSAIDs) and opioids has only a small inhibitory effect on endocrine metabolic responses. Preoperative high-dose glucocorticoid therapy provides additional pain relief and improves pulmonary function, but it reduces the inflammatory response (acute......-phase proteins, cytokines, hyperthermia) and immune function. Minimally invasive surgery leaves the endocrine metabolic responses largely unaltered but reduces the inflammatory response and immune suppression. Thus several techniques are available to modify the stress responses in elective surgery patients...

Responsiveness of Clinical Outcome Measures

DEFF Research Database (Denmark)

Lauridsen, Henrik Hein

Background The Oswestry Disability Index (ODI) is one of two standardised functional health measurement scales (HMS) recommended. Despite extensive psychometric testing, little is known about HMS behaviour and the minimal clinically important difference (MCID) in subgroups of LBP patients. Moreover...... obtainable by a certain treatment. Chronic LBP patients seem to have a reasonable idea of an acceptable change in pain but overestimate change in functional and psychological /affective domains....

Response to Adversity: Higher Education in a Harsh Climate. SRHE Monograph 53.

Science.gov (United States)

Williams, Gareth; Blackstone, Tessa

Issues pertaining to the prospect of decline in British higher education are considered. The following topics are addressed: The 1963 report of the Committee on Higher Education (Robbins Report), the pattern of change in higher education over the past 20 years; the basic issues of scope, diversity, access, and public service; patterns of…

The outcome of clinical parameters in adults with severe Type I Gaucher disease using very low dose enzyme replacement therapy.

Science.gov (United States)

Wilson, Callum; Spearing, Ruth; Teague, Lochie; Robertson, Patsy; Blacklock, Hilary

2007-01-01

Enzyme replacement therapy is now well established as the treatment of choice in Type I Gaucher disease. Historically higher dosage regimens have been used in preference to lower doses despite the little clinical evidence in the way of large controlled clinical trials to support this. Moreover, the extraordinary cost of therapy means that not all eligible patients are able to be treated at the higher dose. Twelve type I adult patients with relatively severe disease were commenced on a very low dose of 7.5U of alglucerase/imiglucerase per kg every two weeks (initially given thrice weekly and later weekly). Follow-up 5 year data reveal a good visceral and haematological response with outcomes consistent with recently published treatment guidelines. Satisfactory clinical and radiological skeletal improvement was also demonstrated in most patients. Three patients had an inadequate overall skeletal response to therapy. Biomarkers also steadily improved although perhaps not quite at the same rate as that seen in higher doses. Very low dose enzyme replacement therapy may be appropriate for adult type I Gaucher patients with mild-moderate skeletal disease.

Discovering biomarkers for antidepressant response: protocol from the Canadian biomarker integration network in depression (CAN-BIND) and clinical characteristics of the first patient cohort.

Science.gov (United States)

Lam, Raymond W; Milev, Roumen; Rotzinger, Susan; Andreazza, Ana C; Blier, Pierre; Brenner, Colleen; Daskalakis, Zafiris J; Dharsee, Moyez; Downar, Jonathan; Evans, Kenneth R; Farzan, Faranak; Foster, Jane A; Frey, Benicio N; Geraci, Joseph; Giacobbe, Peter; Feilotter, Harriet E; Hall, Geoffrey B; Harkness, Kate L; Hassel, Stefanie; Ismail, Zahinoor; Leri, Francesco; Liotti, Mario; MacQueen, Glenda M; McAndrews, Mary Pat; Minuzzi, Luciano; Müller, Daniel J; Parikh, Sagar V; Placenza, Franca M; Quilty, Lena C; Ravindran, Arun V; Salomons, Tim V; Soares, Claudio N; Strother, Stephen C; Turecki, Gustavo; Vaccarino, Anthony L; Vila-Rodriguez, Fidel; Kennedy, Sidney H

2016-04-16

Major Depressive Disorder (MDD) is among the most prevalent and disabling medical conditions worldwide. Identification of clinical and biological markers ("biomarkers") of treatment response could personalize clinical decisions and lead to better outcomes. This paper describes the aims, design, and methods of a discovery study of biomarkers in antidepressant treatment response, conducted by the Canadian Biomarker Integration Network in Depression (CAN-BIND). The CAN-BIND research program investigates and identifies biomarkers that help to predict outcomes in patients with MDD treated with antidepressant medication. The primary objective of this initial study (known as CAN-BIND-1) is to identify individual and integrated neuroimaging, electrophysiological, molecular, and clinical predictors of response to sequential antidepressant monotherapy and adjunctive therapy in MDD. CAN-BIND-1 is a multisite initiative involving 6 academic health centres working collaboratively with other universities and research centres. In the 16-week protocol, patients with MDD are treated with a first-line antidepressant (escitalopram 10-20 mg/d) that, if clinically warranted after eight weeks, is augmented with an evidence-based, add-on medication (aripiprazole 2-10 mg/d). Comprehensive datasets are obtained using clinical rating scales; behavioural, dimensional, and functioning/quality of life measures; neurocognitive testing; genomic, genetic, and proteomic profiling from blood samples; combined structural and functional magnetic resonance imaging; and electroencephalography. De-identified data from all sites are aggregated within a secure neuroinformatics platform for data integration, management, storage, and analyses. Statistical analyses will include multivariate and machine-learning techniques to identify predictors, moderators, and mediators of treatment response. From June 2013 to February 2015, a cohort of 134 participants (85 outpatients with MDD and 49 healthy participants

European Academy of Allergy and Clinical Immunology task force report on 'dose-response relationship in allergen-specific immunotherapy'.

Science.gov (United States)

Calderón, M A; Larenas, D; Kleine-Tebbe, J; Jacobsen, L; Passalacqua, G; Eng, P A; Varga, E M; Valovirta, E; Moreno, C; Malling, H J; Alvarez-Cuesta, E; Durham, S; Demoly, P

2011-10-01

For a century, allergen-specific immunotherapy (SIT) has proven to be an effective treatment for allergic rhinitis, asthma, and insect sting allergy. However, as allergen doses are frequently adapted to the individual patient, there are few data on dose-response relationship in SIT. Allergen products for SIT are being increasingly required to conform to regulatory requirements for human medicines, which include the need to demonstrate dose-dependent effects. This report, produced by a Task Force of the EAACI Immunotherapy Interest Group, evaluates the currently available data on dose-response relationships in SIT and aims to provide recommendations for the design of future studies. Fifteen dose-ranging studies fulfilled the inclusion criteria and twelve reported a dose-response relationship for clinical efficacy. Several studies also reported a dose-response relationship for immunological and safety endpoints. Due to the use of different reference materials and methodologies for the determination of allergen content, variations in study design, and choice of endpoints, no comparisons could be made between studies and, as a consequence, no general dosing recommendations can be made. Despite recently introduced guidelines on the standardization of allergen preparations and study design, the Task Force identified a need for universally accepted standards for the measurement of allergen content in SIT preparations, dosing protocols, and selection of clinical endpoints to enable dose-response effects to be compared across studies. © 2011 John Wiley & Sons A/S.

Biomarkers of Host Response Predict Primary End-Point Radiological Pneumonia in Tanzanian Children with Clinical Pneumonia: A Prospective Cohort Study.

Directory of Open Access Journals (Sweden)

Laura K Erdman

Full Text Available Diagnosing pediatric pneumonia is challenging in low-resource settings. The World Health Organization (WHO has defined primary end-point radiological pneumonia for use in epidemiological and vaccine studies. However, radiography requires expertise and is often inaccessible. We hypothesized that plasma biomarkers of inflammation and endothelial activation may be useful surrogates for end-point pneumonia, and may provide insight into its biological significance.We studied children with WHO-defined clinical pneumonia (n = 155 within a prospective cohort of 1,005 consecutive febrile children presenting to Tanzanian outpatient clinics. Based on x-ray findings, participants were categorized as primary end-point pneumonia (n = 30, other infiltrates (n = 31, or normal chest x-ray (n = 94. Plasma levels of 7 host response biomarkers at presentation were measured by ELISA. Associations between biomarker levels and radiological findings were assessed by Kruskal-Wallis test and multivariable logistic regression. Biomarker ability to predict radiological findings was evaluated using receiver operating characteristic curve analysis and Classification and Regression Tree analysis.Compared to children with normal x-ray, children with end-point pneumonia had significantly higher C-reactive protein, procalcitonin and Chitinase 3-like-1, while those with other infiltrates had elevated procalcitonin and von Willebrand Factor and decreased soluble Tie-2 and endoglin. Clinical variables were not predictive of radiological findings. Classification and Regression Tree analysis generated multi-marker models with improved performance over single markers for discriminating between groups. A model based on C-reactive protein and Chitinase 3-like-1 discriminated between end-point pneumonia and non-end-point pneumonia with 93.3% sensitivity (95% confidence interval 76.5-98.8, 80.8% specificity (72.6-87.1, positive likelihood ratio 4.9 (3.4-7.1, negative likelihood ratio 0

Biomarkers of Host Response Predict Primary End-Point Radiological Pneumonia in Tanzanian Children with Clinical Pneumonia: A Prospective Cohort Study

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Erdman, Laura K.; D’Acremont, Valérie; Hayford, Kyla; Kilowoko, Mary; Kyungu, Esther; Hongoa, Philipina; Alamo, Leonor; Streiner, David L.; Genton, Blaise; Kain, Kevin C.

2015-01-01

Background Diagnosing pediatric pneumonia is challenging in low-resource settings. The World Health Organization (WHO) has defined primary end-point radiological pneumonia for use in epidemiological and vaccine studies. However, radiography requires expertise and is often inaccessible. We hypothesized that plasma biomarkers of inflammation and endothelial activation may be useful surrogates for end-point pneumonia, and may provide insight into its biological significance. Methods We studied children with WHO-defined clinical pneumonia (n = 155) within a prospective cohort of 1,005 consecutive febrile children presenting to Tanzanian outpatient clinics. Based on x-ray findings, participants were categorized as primary end-point pneumonia (n = 30), other infiltrates (n = 31), or normal chest x-ray (n = 94). Plasma levels of 7 host response biomarkers at presentation were measured by ELISA. Associations between biomarker levels and radiological findings were assessed by Kruskal-Wallis test and multivariable logistic regression. Biomarker ability to predict radiological findings was evaluated using receiver operating characteristic curve analysis and Classification and Regression Tree analysis. Results Compared to children with normal x-ray, children with end-point pneumonia had significantly higher C-reactive protein, procalcitonin and Chitinase 3-like-1, while those with other infiltrates had elevated procalcitonin and von Willebrand Factor and decreased soluble Tie-2 and endoglin. Clinical variables were not predictive of radiological findings. Classification and Regression Tree analysis generated multi-marker models with improved performance over single markers for discriminating between groups. A model based on C-reactive protein and Chitinase 3-like-1 discriminated between end-point pneumonia and non-end-point pneumonia with 93.3% sensitivity (95% confidence interval 76.5–98.8), 80.8% specificity (72.6–87.1), positive likelihood ratio 4.9 (3.4–7

Workplace Bullying in Higher Education: Faculty Experiences and Responses

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Taylor, Susan K.

2012-01-01

This study examines workplace bullying in a university setting. Specifically it examines how faculty members' tenure status is related to having been targets and witnesses of bullying at work and their responses to dissatisfaction at work. The research literature reveals a correlation between being a target of workplace bullying and the target's…

Is drug-induced toxicity a good predictor of response to neo-adjuvant chemotherapy in patients with breast cancer? -A prospective clinical study

International Nuclear Information System (INIS)

Chintamani; Singhal, Vinay; Singh, JP; Lyall, Ashima; Saxena, Sunita; Bansal, Anju

2004-01-01

Neo-adjuvant chemotherapy is an integral part of multi-modality approach in the management of locally advanced breast cancer and it is vital to predict the response in order to tailor the regime for a patient. The common final pathway in the tumor cell death is believed to be apoptosis or programmed cell death and chemotherapeutic drugs like other DNA-damaging agents act on rapidly multiplying cells including both the tumor and the normal cells by following the same common final pathway. This could account for both the toxic effects and the response. Absence or decreased apoptosis has been found to be associated with chemo resistance. The change in expression of apoptotic markers (Bcl-2 and Bax proteins) brought about by various chemotherapeutic regimens is being used to identify drug resistance in the tumor cells. A prospective clinical study was conducted to assess whether chemotherapy induced toxic effects could serve as reliable predictors of apoptosis or response to neo-adjuvant chemotherapy in patients with locally advanced breast cancer. 50 cases of locally advanced breast cancer after complete routine and metastatic work up were subjected to trucut biopsy and the tissue evaluated immunohistochemically for apoptotic markers (bcl-2/bax ratio). Three cycles of Neoadjuvant Chemotherapy using FAC regime (5-fluorouracil, adriamycin, cyclophosphamide) were given at three weekly intervals and patients assessed for clinical response as well as toxicity after each cycle. Modified radical mastectomy was performed in all patients three weeks after the last cycle and the specimen were re-evaluated for any change in the bcl-2/bax ratio. The clinical response, immunohistochemical response and the drug-induced toxicity were correlated and compared. Descriptive studies were performed with SPSS version 10 and the significance of response was assessed using paired t-test. Significance of correlation between various variables was assessed using chi-square test and coefficient

Clinical correlates of sustained response to individual drugs used in naturalistic treatment of patients with bipolar disorder

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

Objective: To report use and treatment success rates of medications for bipolar disorder as a function of patients' clinical characteristics. Method: Outpatients with bipolar illness diagnosed by SCID were rated by research assistants on the NIMH-LCM and those who had an good response for at least 6

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

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Horwood, Anna; Toor, Sonia

2014-03-01

The relative efficiency of different eye exercise regimes is unclear, and in particular the influences of practice, placebo and the amount of effort required are rarely considered. This study measured conventional clinical measures following different regimes in typical young adults. A total of 156 asymptomatic young adults were directed to carry out eye exercises three times daily for 2 weeks. Exercises were directed at improving blur responses (accommodation), disparity responses (convergence), both in a naturalistic relationship, convergence in excess of accommodation, accommodation in excess of convergence, and a placebo regime. They were compared to two control groups, neither of which were given exercises, but the second of which were asked to make maximum effort during the second testing. Instruction set and participant effort were more effective than many exercises. Convergence exercises independent of accommodation were the most effective treatment, followed by accommodation exercises, and both regimes resulted in changes in both vergence and accommodation test responses. Exercises targeting convergence and accommodation working together were less effective than those where they were separated. Accommodation measures were prone to large instruction/effort effects and monocular accommodation facility was subject to large practice effects. Separating convergence and accommodation exercises seemed more effective than exercising both systems concurrently and suggests that stimulation of accommodation and convergence may act in an additive fashion to aid responses. Instruction/effort effects are large and should be carefully controlled if claims for the efficacy of any exercise regime are to be made. © 2014 The Authors Ophthalmic & Physiological Optics published by John Wiley & Sons Ltd on behalf of The College of Optometrists.

Uveitis profile and treatment response in Iranian patients with sarcoidosis.

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Mahmoudzadeh, Pouya; Tousi, Adib; Ramezani, Alireza; Soheilian, Roham; Soheilian, Masoud

2015-06-01

The aim of the study was to assess the clinical features and treatment responses in Iranian patients with sarcoid uveitis. A retrospective review of patients diagnosed with sarcoid uveitis from 1996 to 2010 was performed in a referral clinic in Tehran, Iran. Demographic and clinical features of patients, treatment modalities and therapeutic responses, and outcomes were recorded. Sixty-six eyes from 36 patients were studied. Twenty cases had biopsy-proven sarcoidosis. Mean duration of follow-up was 44.7 ± 45 months (range 3-175). Thirty-six eyes (54.5 %) had intermediate uveitis, 25 (37.9 %) panuveitis, and 5 (7.6 %) anterior uveitis. Twenty patients (55.5 %) responded to both systemic and/or topical corticosteroids, and 16 (44.4 %) required immunomodulatory drugs for control of uveitis. All of the patients finally responded to treatment in the form of inflammation reduction and/or vision improvement. The average time interval before initial clinical response following treatment was 3.2 ± 3 months (range 1-72). This study disclosed a higher predominance of females and intermediate form of uveitis in Iranian patients with sarcoid uveitis. Use of immunomodulatory drugs combined with corticosteroids resulted in good visual outcome and control of uveitis with a possible fewer corticosteroid side effects.

Genetic modulation of plasma NPY stress response is suppressed in substance abuse: association with clinical outcomes.

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Xu, Ke; Hong, Kwangik Adam; Zhou, Zhifeng; Hauger, Richard L; Goldman, David; Sinha, Rajita

2012-04-01

Neuropeptide Y (NPY) is involved in stress regulation. Genetic variations predict plasma NPY and neural correlates of emotion and stress. We examined whether the functional NPY haplotype modulates stress-induced NPY and anxiety responses, and if plasma NPY stress responses are associated with substance dependence outcomes. Thirty-seven treatment-engaged, abstinent substance dependent (SD) patients and 28 healthy controls (HCs) characterized on NPY diplotypes (HH: high expression; HLLL: intermediate/low expression) were exposed to stress, alcohol/drug cues and neutral relaxing cues, using individualized guided imagery, in a 3-session laboratory experiment. Plasma NPY, heart rate and anxiety were assessed. Patients were prospectively followed for 90-days post-treatment to assess relapse outcomes. HH individuals showed significantly lower stress-induced NPY with greater heart rate and anxiety ratings, while the HLLL group showed the reverse pattern of NPY, anxiety and heart rate responses. This differential genetic modulation of NPY stress response was suppressed in the SD group, who showed no stress-related increases in NPY and higher heart rate and greater anxiety, regardless of diplotype. Lower NPY predicted subsequent higher number of days and greater amounts of post-treatment drug use. These preliminary findings are the first to document chronic drug abuse influences on NPY diplotype expression where NPY diplotype modulation of stress-related plasma NPY, heart rate and anxiety responses was absent in the substance abuse sample. The finding that lower stress-related NPY is predictive of greater relapse severity provides support for therapeutic development of neuropeptide Y targets in the treatment of substance use disorders. Copyright © 2011 Elsevier Ltd. All rights reserved.

Predicting beneficial effects of atomoxetine and citalopram on response inhibition in Parkinson's disease with clinical and neuroimaging measures

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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

"Always Look on the Bright Side of Life!" - Higher Hypomania Scores Are Associated with Higher Mental Toughness, Increased Physical Activity, and Lower Symptoms of Depression and Lower Sleep Complaints.

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Jahangard, Leila; Rahmani, Anahita; Haghighi, Mohammad; Ahmadpanah, Mohammad; Sadeghi Bahmani, Dena; Soltanian, Ali R; Shirzadi, Shahriar; Bajoghli, Hafez; Gerber, Markus; Holsboer-Trachsler, Edith; Brand, Serge

2017-01-01

Background: In the present study, we explored the associations between hypomania, symptoms of depression, sleep complaints, physical activity and mental toughness. The latter construct has gained interest for its association with a broad variety of favorable behavior in both clinical and non-clinical samples. Subjects and Methods: The non-clinical sample consisted of 206 young adults ( M = 21.3 years; age range: 18-24 years; 57.3% males). They completed questionnaires covering hypomania, mental toughness, symptoms of depression, physical activity, and sleep quality. Results: Higher hypomania scores were associated with higher mental toughness, increased physical activity, lower symptoms of depression and lower sleep complaints. No gender differences were observed. Higher hypomania scores were predicted by higher scores of mental toughness subscales of control and challenge, and physical activity. Conclusion: The pattern of results suggests that among a non-clinical sample of young adults, self-rated hypomania scores were associated with higher scores on mental toughness and physical activity, along with lower depression and sleep complaints. The pattern of results further suggests that hypomania traits are associated with a broad range of favorable psychological, behavioral and sleep-related traits, at least among a non-clinical sample of young adults.

Medical physics in radiotherapy: The importance of preserving clinical responsibilities and expanding the profession's role in research, education, and quality control.

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Malicki, Julian

2015-01-01

Medical physicists have long had an integral role in radiotherapy. In recent decades, medical physicists have slowly but surely stepped back from direct clinical responsibilities in planning radiotherapy treatments while medical dosimetrists have assumed more responsibility. In this article, I argue against this gradual withdrawal from routine therapy planning. It is essential that physicists be involved, at least to some extent, in treatment planning and clinical dosimetry for each and every patient; otherwise, physicists can no longer be considered clinical specialists. More importantly, this withdrawal could negatively impact treatment quality and patient safety. Medical physicists must have a sound understanding of human anatomy and physiology in order to be competent partners to radiation oncologists. In addition, they must possess a thorough knowledge of the physics of radiation as it interacts with body tissues, and also understand the limitations of the algorithms used in radiotherapy. Medical physicists should also take the lead in evaluating emerging challenges in quality and safety of radiotherapy. In this sense, the input of physicists in clinical audits and risk assessment is crucial. The way forward is to proactively take the necessary steps to maintain and advance our important role in clinical medicine.

Medical physics in radiotherapy: The importance of preserving clinical responsibilities and expanding the profession's role in research, education, and quality control

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Malicki, Julian

2015-01-01

Medical physicists have long had an integral role in radiotherapy. In recent decades, medical physicists have slowly but surely stepped back from direct clinical responsibilities in planning radiotherapy treatments while medical dosimetrists have assumed more responsibility. In this article, I argue against this gradual withdrawal from routine therapy planning. It is essential that physicists be involved, at least to some extent, in treatment planning and clinical dosimetry for each and every patient; otherwise, physicists can no longer be considered clinical specialists. More importantly, this withdrawal could negatively impact treatment quality and patient safety. Medical physicists must have a sound understanding of human anatomy and physiology in order to be competent partners to radiation oncologists. In addition, they must possess a thorough knowledge of the physics of radiation as it interacts with body tissues, and also understand the limitations of the algorithms used in radiotherapy. Medical physicists should also take the lead in evaluating emerging challenges in quality and safety of radiotherapy. In this sense, the input of physicists in clinical audits and risk assessment is crucial. The way forward is to proactively take the necessary steps to maintain and advance our important role in clinical medicine. PMID:25949219

Potential Use of Classroom Response Systems (CRS, Clickers) in Foods, Nutrition, and Dietetics Higher Education.

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Gould, Susan Martin

2016-10-01

Although hundreds of articles have been published about the use of classroom response systems (CRS, clickers) in higher education, few address the use in foods, nutrition, and dietetics courses, especially upper-division, major courses. This technology has the potential to increase student engagement, motivation, assessment, and, possibly, learning. Thoughtfully designed questions may stimulate discussions, especially about challenging nutrition topics. This article presents the viability and potential benefits for the use of CRS in foods, nutrition, and dietetics classes through a brief literature summary, overview of the author's experiences, and guidance for implementing this technology. Copyright © 2016 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.

New Mexico Higher Education Department Annual Report, 2016

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New Mexico Higher Education Department, 2016

2016-01-01

The New Mexico Higher Education Department strives to bring leadership, guidance, and assistance to New Mexico's higher education stakeholders. The HED is committed to promoting best practices, institutional fiscal responsibility, and student achievement. Everything the agency does is through the lens of supporting New Mexico's higher education…

[Cryptogenic West syndrome: Clinical profile, response to treatment and prognostic factors].

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Calderón Romero, María; Arce Portillo, Elena; López Lobato, Mercedes; Muñoz Cabello, Beatriz; Blanco Martínez, Bárbara; Madruga Garrido, Marcos; Alonso Luego, Olga

2017-12-06

West syndrome (WS) is an age-dependent epileptic encephalopathy in which the prognosis varies according to the, not always identified, underlying origin. To define the profile of cryptogenic (a least studied isolated sub-group) WS, in Spain. To study its outcome, response to different treatments, and to establish prognostic factors. The study included a review of the medical records of 16 patients diagnosed with cryptogenic WS during the period, 2000-2015. The mean follow-up time was 6.6 years, with a minimum of 2 years. The large majority (11/16) were male. The mean age at onset was 6 months, and 6/16 had a family history of idiopathic epilepsy. The first line treatment with vigabatrin had an electrical-clinical response in 5/16 patients, with the remaining cases responding to adrenocorticotropic hormone (ACTH). Almost half (44%) of the patients progressed to other types of epilepsy, with no difference between those treated with vigabatrin or ACTH. A greater number of adverse effects were obtained with ACTH, with no retinal involvement being observed with vigabatrin. The aetiological cause was found in 2/16. Being female, late onset, and early control of the hypsarrhythmia, were factors of a good prognosis. The overall prognosis of cryptogenic WS was more serious than expected. Although the incidence of Lennox-Gastaut syndrome was low, the progression to focal epilepsy was the most common, with it appearing within the first 2 years of the diagnosis. The initial response to vigabatrin was lower than expected, but the long-term result was comparable to ACTH. Copyright © 2017. Publicado por Elsevier España, S.L.U.

Optical and energy dependent response of the alanine gel solution produced at IPEN to clinical photons and electrons beams

International Nuclear Information System (INIS)

Silva, Cleber F.

2011-01-01

The DL-Alanine (C 3 H 7 NO 2 ) is an amino acid tissue equivalent traditionally used as standard dosimetric material in EPR dosimetry. Recently, it has been studied to be applied in gel dosimetry, considering that the addition of Alanine in the Fricke gel solution improves the production of ferric ions radiation induced. The spectrophotometric evaluation technique can be used comparing the two spectrum wavelengths bands: 457 nm band that corresponds to ferrous ions and 588 nm band that corresponds to ferric ions concentration to evaluate the dosimetric properties of this material. The performance of the Alanine gel solution developed at IPEN has been firstly studied using the spectrophotometric technique aiming to apply this material to 3D clinical doses evaluations using MRI technique. In this work, the optical and the energy dependent response of this solution submitted to clinical photons and electrons beams were studied. Different batches of gel solutions were prepared and maintained at low temperature during 12 h to solidification. Before irradiation, the samples were maintained during 1 h at room temperature. The photons and electrons irradiations were carried out using a Varian 2100C Medical Linear Accelerator of the Radiotherapy Department of the Hospital das Clinicas of the University of Sao Paulo with absorbed doses between 1 and 40 Gy; radiation field of 10 x 10 cm 2 ; photon energies of 6 MeV and 15 MeV; and electron with energies between 6 and 15 MeV. The obtained results indicate that signal response dependence for clinical photons and electrons beams, to the same doses, for Alanine gel dosimeter is better than 3.6 % (1σ), and the energy dependence response, to the same doses, is better 3% (1σ) for both beams. These results indicate that the same calibration factor can be used and the optical response is energy independent in the studied dose range and clinical photons and electrons beams energies. (author)

Changes in thermal nociceptive responses in dairy cows following experimentally induced Escherichia coli mastitis

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Klaas Ilka C

2011-05-01

Full Text Available Abstract Background Mastitis is a high incidence disease in dairy cows. The acute stage is considered painful and inflammation can lead to hyperalgesia and thereby contribute to decreased welfare. The aim of this study was to examine changes in nociceptive responses toward cutaneous nociceptive laser stimulation (NLS in dairy cows with experimentally induced Escherichia coli mastitis, and correlate behavioral changes in nociceptive responses to clinical and paraclinical variables. Methods Seven Danish Holstein-Friesian cows were kept in tie-stalls, where the E. coli associated mastitis was induced and laser stimulations were conducted. Measurements of rectal temperature, somatic cell counts, white blood cell counts and E. coli counts were conducted. Furthermore, scores were given for anorexia, local udder inflammation and milk appearance to quantify the local and systemic disease response. In order to quantify the nociceptive threshold, behavioral responses toward cutaneous NLS applied to six skin areas at the tarsus/metatarsus and udder hind quarters were registered at evening milking on day 0 (control and days 1, 2, 3, 6 and 10 after experimental induction of mastitis. Results All clinical and paraclinical variables were affected by the induced mastitis. All cows were clinically ill on days 1 and 2. The cows responded behaviorally toward the NLS. For hind leg stimulation, the proportion of cows responding by stepping was higher on day 0 than days 3 and 6, and the frequency of leg movements after laser stimulation tended to decrease on day 1 compared to the other days. After udder stimulation, the proportion of cows responding by stepping was higher on day 1 than on all other days of testing. Significant correlations between the clinical and paraclinical variables of disease and the behavioral responses toward nociceptive stimulation were found. Conclusions Changes in behavioral responses coincide with peaks in local and systemic signs of E

Hydroxyurea responses in clinically varied beta, HbE-beta thalassaemia and sickle cell anaemia patients of Eastern India.

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Chatterjee, Tridip; Chakravarty, Amit; Chakravarty, Sudipa

2018-05-01

The haematological and clinical response to hydroxyurea was estimated in HbE-beta, beta thalassaemia and sickle cell anaemia patients of Eastern India, with variable clinical severity and transfusion requirement to determine whether hydroxyurea can help these patients to maintain their steady haemoglobin level without blood transfusions. Three hundred patients (189 HbE-beta thalassaemia, 95 beta thalassaemia and 16 other haemoglobinopathies including sickle cell anaemia) were selected for hydroxyurea therapy and were followed up for 48-60 months. Results suggest significant response to hydroxyurea therapy in 19 beta and 99 HbE-beta patients in the transfusion-dependent group (GR-I). All of them became transfusion-independent while on hydroxyurea therapy. The majority of responding patients were IVS1-5(G-C) in one of their alleles in HbE-beta cases (83 out of 119). Though IVS1-5(G-C) was found to be the commonest mutation in our selected patients, the mutational background of the patients does not found to have any significant correlation with the response category towards hydroxyurea as per the results observed in our study. But, the drug works pretty well in most of the transfusion-dependent patients, as these patients were withdrawn from regular blood transfusion. At the same time, partial or no response to the drug hydroxyurea was also recorded in our study.

Stathmin protein level, a potential predictive marker for taxane treatment response in endometrial cancer.

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Henrica M J Werner

Full Text Available Stathmin is a prognostic marker in many cancers, including endometrial cancer. Preclinical studies, predominantly in breast cancer, have suggested that stathmin may additionally be a predictive marker for response to paclitaxel. We first evaluated the response to paclitaxel in endometrial cancer cell lines before and after stathmin knock-down. Subsequently we investigated the clinical response to paclitaxel containing chemotherapy in metastatic endometrial cancer in relation to stathmin protein level in tumors. Stathmin level was also determined in metastatic lesions, analyzing changes in biomarker status on disease progression. Knock-down of stathmin improved sensitivity to paclitaxel in endometrial carcinoma cell lines with both naturally higher and lower sensitivity to paclitaxel. In clinical samples, high stathmin level was demonstrated to be associated with poor response to paclitaxel containing chemotherapy and to reduced disease specific survival only in patients treated with such combination. Stathmin level increased significantly from primary to metastatic lesions. This study suggests, supported by both preclinical and clinical data, that stathmin could be a predictive biomarker for response to paclitaxel treatment in endometrial cancer. Re-assessment of stathmin level in metastatic lesions prior to treatment start may be relevant. Also, validation in a randomized clinical trial will be important.

Absolute number of new lesions on {sup 18}F-FDG PET/CT is more predictive of clinical response than SUV changes in metastatic melanoma patients receiving ipilimumab

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Anwar, Hoda; Sachpekidis, Christos; Dimitrakopoulou-Strauss, Antonia [German Cancer Research Center, Medical PET Group-Biological Imaging, Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany); Winkler, Julia; Hassel, Jessica C. [University Hospital Heidelberg, Department of Dermatology and National Center for Tumor Diseases, Heidelberg (Germany); Kopp-Schneider, Annette [German Cancer Research Center, Department of Biostatistics, Heidelberg (Germany); Haberkorn, Uwe [German Cancer Research Center, Medical PET Group-Biological Imaging, Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany); University of Heidelberg, Division of Nuclear Medicine, Heidelberg (Germany)

2018-03-15

Evaluation of response to immunotherapy is a matter of debate. The aim of the present study was to evaluate the response of metastatic melanoma to treatment with ipilimumab by means of {sup 18}F-FDG PET/CT, using the patients' clinical response as reference. The final cohort included in the analyses consisted of 41 patients with metastatic melanoma who underwent {sup 18}F-FDG PET/CT before and after administration of ipilimumab. After determination of the best clinical response, the PET/CT scans were reviewed and a separate independent analysis was performed, based on the number and functional size of newly emerged {sup 18}F-FDG-avid lesions, as well as on the SUV changes after therapy. The median observation time of the patients after therapy was 21.4 months (range 6.3-41.9 months). Based on their clinical response, patients were dichotomized into those with clinical benefit (CB) and those without CB (No-CB). The CB group (31 patients) included those with stable disease, partial remission and complete remission, and the No-CB group (10 patients) included those with progressive disease. The application of a threshold of four newly emerged {sup 18}F-FDG-avid lesions on the posttherapy PET/CT scan led to a sensitivity (correctly predicting CB) of 84% and a specificity (correctly predicting No-CB) of 100%. This cut-off was lower for lesions with larger functional diameters (three new lesions larger than 1.0 cm and two new lesions larger than 1.5 cm). SUV changes after therapy did not correlate with clinical response. Based on these findings, we developed criteria for predicting clinical response to immunotherapy by means of {sup 18}F-FDG PET/CT (PET Response Evaluation Criteria for Immunotherapy, PERCIMT). Our results show that a cut-off of four newly emerged {sup 18}F-FDG-avid lesions on posttherapy PET/CT gives a reliable indication of treatment failure in patients under ipilimumab treatment. Moreover, the functional size of the new lesions plays an important

Higher transcription levels in ascorbic acid biosynthetic and recycling genes were associated with higher ascorbic acid accumulation in blueberry.

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Liu, Fenghong; Wang, Lei; Gu, Liang; Zhao, Wei; Su, Hongyan; Cheng, Xianhao

2015-12-01

In our preliminary study, the ripe fruits of two highbush blueberry (Vaccinium corymbosum L.) cultivars, cv 'Berkeley' and cv 'Bluecrop', were found to contain different levels of ascorbic acid. However, factors responsible for these differences are still unknown. In the present study, ascorbic acid content in fruits was compared with expression profiles of ascorbic acid biosynthetic and recycling genes between 'Bluecrop' and 'Berkeley' cultivars. The results indicated that the l-galactose pathway was the predominant route of ascorbic acid biosynthesis in blueberry fruits. Moreover, higher expression levels of the ascorbic acid biosynthetic genes GME, GGP, and GLDH, as well as the recycling genes MDHAR and DHAR, were associated with higher ascorbic acid content in 'Bluecrop' compared with 'Berkeley', which indicated that a higher efficiency ascorbic acid biosynthesis and regeneration was likely to be responsible for the higher ascorbic acid accumulation in 'Bluecrop'. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effect of nonsurgical periodontal treatment on clinical response and glycemic control in type 2 diabetic patients with periodontitis: Controlled clinical trial

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Ajitha Kanduluru

2014-01-01

Full Text Available Background: Type 2 diabetes mellitus (type 2 DM and chronic periodontitis are common chronic diseases in adults in the world population. Once periodontal disease is established, the chronic nature of this infection may contribute to worsening of diabetic status leading to more severe diabetes-related complications. It has been proposed that the relation of periodontitis and diabetes is bidirectional. Objectives: The objective was to compare the clinical response and glycemic control in type 2 DM patients with periodontitis, before and after the nonsurgical periodontal treatment with controls. Materials and Methods: A total 70 type 2 DM patients with chronic generalized moderate periodontitis was divided into 2 groups. Treatment group (35 received one stage full mouth scaling and root planning plus oral hygiene instructions; the control group (35 received only oral hygiene instructions. At baseline, 1 st month and 3 rd month, the clinical periodontal parameters (plaque index [PI], gingival index [GI], pocket depth [PD], clinical attachment loss [CAL], gingival recession [GR], and bleeding on probing [BOP] and glycemic parameters (fasting blood sugar [FBS], and postprandial blood sugar [PPBS] were recorded, whereas the glycated hemoglobin (HbA1c was recorded only at baseline and 3rd month. The collected data were subjected to statistical analysis. Results: When comparing the mean scores of clinical parameters for both the groups, there was a significant difference in all clinical parameters, that is, mean PI, GI, BOP, PD, CAL scores except mean GR, whereas for the glycemic parameters, there was a significant difference in mean FBS; PPBS values and no significant difference in mean percentage of HbA1c for treatment group at 3 rd month follow-up. Conclusion: Findings of the present study showed that nonsurgical periodontal treatment resulted in lower glycemic levels and the reduction of clinical parameters of periodontal infection, confirming the

Natural history and clinical response: “It’s the virus, stupid, or is it the host?”

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2012-01-01

Summary A major goal of modern medicine is the application of personalized therapies, consisting of decisions and practices tailored to the individual patient. Information about genetic variants, either mutant or polymorphic, represents the basis for the development of this clinical approach. Recently, several independent genome-wide association studies (GWAS) have identified two single nucleotide polymorphisms (SNPs) on the IL28B locus associated with HCV containment, spontaneous clearance, treatment response, and disease progression. In this minireview we will concisely discuss some critical genetic concepts that may have possible implications for clinical decisions in the treatment of HCV infection. PMID:23173731

Cerebral amyloid angiopathy-related inflammation presenting with steroid-responsive higher brain dysfunction: case report and review of the literature

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Maeda Yasushi

2011-09-01

Full Text Available Abstract A 56-year-old man noticed discomfort in his left lower limb, followed by convulsion and numbness in the same area. Magnetic resonance imaging (MRI showed white matter lesions in the right parietal lobe accompanied by leptomeningeal or leptomeningeal and cortical post-contrast enhancement along the parietal sulci. The patient also exhibited higher brain dysfunction corresponding with the lesions on MRI. Histological pathology disclosed β-amyloid in the blood vessels and perivascular inflammation, which highlights the diagnosis of cerebral amyloid angiopathy (CAA-related inflammation. Pulse steroid therapy was so effective that clinical and radiological findings immediately improved. CAA-related inflammation is a rare disease, defined by the deposition of amyloid proteins within the leptomeningeal and cortical arteries associated with vasculitis or perivasculitis. Here we report a patient with CAA-related inflammation who showed higher brain dysfunction that improved with steroid therapy. In cases with atypical radiological lesions like our case, cerebral biopsy with histological confirmation remains necessary for an accurate diagnosis.

Experimental results and clinical implications of the four R's in fractionated radiotherapy

International Nuclear Information System (INIS)

Trott, K.R.; Gesellschaft fuer Strahlen- und Umweltforschung m.b.H. Muenchen, Neuherberg

1982-01-01

Experimental and clinical data on the four R' in fractionated radiotherapy are reviewed. The clinical importance of redistribution has not been proven in the experiment yet. On reoxygenation no unequivocal data in human cancer exists and a lot of variability in rodent tumours. Repair and regeneration are the most important of the four R's in fractionated radiotherapy. The presented experimental and clinical evidence suggests a differential response between tumour and late responding normal tissues with regard to these two R's. Tumours appear to have, in general, a smaller capacity for repairing sublethal radiation damage but a higher capacity for repopulation than late responding normal tissues. (orig.)

Improving Publication: Advice for Busy Higher Education Academics

Science.gov (United States)

Gibbs, Anita

2016-01-01

A major challenge for higher education academics is to research and publish when faced with substantial teaching responsibilities, higher student numbers, and higher output expectations. The focus of this piece is to encourage publication more generally by educators, and to build publication capacity, which academic developers can facilitate. The…

Assessment of Responsiveness to Everyday Non-Noxious Stimuli in Pain-Free Migraineurs With Versus Without Aura.

Science.gov (United States)

Granovsky, Yelena; Shor, Merav; Shifrin, Alla; Sprecher, Elliot; Yarnitsky, David; Bar-Shalita, Tami

2018-03-27

Migraineurs with aura (MWA) express higher interictal response to non-noxious and noxious experimental sensory stimuli compared with migraineurs without aura (MWoA), but whether these differences also prevail in response to everyday non-noxious stimuli is not yet explored. This is a cross-sectional study testing 53 female migraineurs (30 MWA; 23 MWoA) who underwent a wide battery of noxious psychophysical testing at a pain-free phase, and completed a Sensory Responsiveness Questionnaire and pain-related psychological questionnaires. The MWA group showed higher questionnaire-based sensory over-responsiveness (P = .030), higher magnitude of pain temporal summation (P = .031) as well as higher monthly attack frequency (P = .027) compared with the MWoA group. Overall, 45% of migraineurs described abnormal sensory (hyper- or hypo-) responsiveness; its incidence was higher among MWA (19 of 30, 63%) versus MWoA (6 of 23, 27%, P = .012), with an odds ratio of 3.58 for MWA. Sensory responsiveness scores were positively correlated with attack frequency (r = .361, P = .008) and temporal summation magnitude (r = .390, P = .004), both regardless of migraine type. MWA express higher everyday sensory responsiveness than MWoA, in line with higher response to experimental noxious stimuli. Abnormal scores of sensory responsiveness characterize people with sensory modulation dysfunction, suggesting possible underlying mechanisms overlap, and possibly high incidence of both clinical entities. This article presents findings distinguishing MWA, showing enhanced pain amplification, monthly attack frequency, and over-responsiveness to everyday sensations, compared with MWoA. Further, migraine is characterized by a high incidence of abnormal responsiveness to everyday sensation, specifically sensory over-responsiveness, that was also found related to pain. Copyright © 2018 The American Pain Society. Published by Elsevier Inc. All rights reserved.

Exploring links between genotypes, phenotypes, and clinical predictors of response to early intensive behavioural intervention in Autism Spectrum Disorder

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Valsamma eEapen

2013-09-01

Full Text Available Autism Spectrum Disorder (ASD is amongst the most familial of psychiatric disorders. Twin and family studies have demonstrated a monozygotic concordance rate of 70–90%, dizygotic concordance of around 10% and more than a 20-fold increase in risk for first-degree relatives. Despite major advances in the genetics of autism, the relationship between different aspects of the behavioural and cognitive phenotype and their underlying genetic liability is still unclear. This is complicated by the heterogeneity of autism, which exists at both genetic and phenotypic levels. Given this heterogeneity, one method to find homogeneous entities and link these with specific genotypes would be to pursue endophenotypes. Evidence from neuroimaging, eye tracking and electrophysiology studies supports the hypothesis that, building on genetic vulnerability, ASD emerges from a developmental cascade in which a deficit in attention to social stimuli leads to impaired interactions with primary caregivers. This results in abnormal development of the neurocircuitry responsible for social cognition, which in turn adversely affects later behavioural and functional domains dependent on these early processes, such as language development. Such a model begets a heterogeneous clinical phenotype, and is also supported by studies demonstrating better clinical outcomes with earlier treatment. Treatment response following intensive early behavioural intervention in ASD is also distinctly variable; however, relatively little is known about specific elements of the clinical phenotype that may predict response to current behavioural treatments. This paper overviews the literature regarding genotypes, phenotypes and predictors of response to behavioural intervention in ASD and presents suggestions for future research to explore linkages between these that would enable better identification of, and increased treatment efficacy for, ASD.

Effect of clinical response to active drugs and placebo on antipsychotics and mood stabilizers relative efficacy for bipolar depression and mania: A meta-regression analysis.

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Bartoli, Francesco; Clerici, Massimo; Di Brita, Carmen; Riboldi, Ilaria; Crocamo, Cristina; Carrà, Giuseppe

2018-04-01

Randomised placebo-controlled trials investigating treatments for bipolar disorder have been hampered by wide variations of active drugs and placebo clinical response rates. It is important to estimate whether the active drug or placebo response has a greater influence in determining the relative efficacy of drugs for psychosis (antipsychotics) and relapse prevention (mood stabilisers) for bipolar depression and mania. We identified 53 randomised, placebo-controlled trials assessing antipsychotic or mood stabiliser monotherapy ('active drugs') for bipolar depression or mania. We carried out random-effects meta-regressions, estimating the influence of active drugs and placebo response rates on treatment relative efficacy. Meta-regressions showed that treatment relative efficacy for bipolar mania was influenced by the magnitude of clinical response to active drugs ( p=0.002), but not to placebo ( p=0.60). On the other hand, treatment relative efficacy for bipolar depression was influenced by response to placebo ( p=0.047), but not to active drugs ( p=0.98). Despite several limitations, our unexpected findings showed that antipsychotics / mood stabilisers relative efficacy for bipolar depression seems unrelated to active drugs response rates, depending only on clinical response to placebo. Future research should explore strategies to reduce placebo-related issues in randomised, placebo-controlled trials for bipolar depression.

"You Have to Know the End of the Story": Motivations to Follow Up After Transitions of Clinical Responsibility.

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Bowen, Judith L; Ilgen, Jonathan S; Irby, David M; Ten Cate, Olle; O'Brien, Bridget C

2017-11-01

Physicians routinely transition responsibility for patient care to other physicians. When transitions of responsibility occur before the clinical outcome is known, physicians may lose opportunities to learn from the consequences of their decision making. Sometimes curiosity about patients does not end with the transition and physicians continue to follow them. This study explores physicians' motivations to follow up after transitioning responsibilities. Using a constructivist grounded theory approach, the authors conducted 18 semistructured interviews in 2016 with internal medicine hospitalist and resident physicians at a single tertiary care academic medical center. Constant comparative methods guided the qualitative analysis, using motivation theories as sensitizing constructs. The authors identified themes that characterized participants' motivations to follow up. Curiosity about patients' outcomes determined whether or not follow-up occurred. Insufficient curiosity about predictable clinical problems resulted in the choice to forgo follow-up. Sufficient curiosity due to clinical uncertainty, personal attachment to patients, and/or concern for patient vulnerability motivated follow-up to fulfill goals of knowledge building and professionalism. The authors interpret these findings through the lenses of expectancy-value (EVT) and self-determination (SDT) theories of motivation. Participants' curiosity about what happened to their patients motivated them to follow up. EVT may explain how participants made choices in time-pressured work settings. SDT may help interpret how follow-up fulfills needs of relatedness. These findings add to a growing body of literature endorsing learning environments that consider task-value trade-offs and support basic psychological needs of autonomy, competency, and relatedness to motivate learning.

Clinical determinants of early parasitological response to ACTs in African patients with uncomplicated falciparum malaria

DEFF Research Database (Denmark)

Abdulla, S.; Adam, I.; Adjei, G. O.

2015-01-01

values for clearance in patients from Sub-Saharan African countries with uncomplicated malaria treated with artemisinin-based combination therapies (ACTs). Methods: A literature review in PubMed was conducted in March 2013 to identify all prospective clinical trials (uncontrolled trials, controlled...... trials and randomized controlled trials), including ACTs conducted in Sub-Saharan Africa, between 1960 and 2012. Individual patient data from these studies were shared with the WorldWide Antimalarial Resistance Network (WWARN) and pooled using an a priori statistical analytical plan. Factors affecting...... early parasitological response were investigated using logistic regression with study sites fitted as a random effect. The risk of bias in included studies was evaluated based on study design, methodology and missing data. Results: In total, 29,493 patients from 84 clinical trials were included...

Novel assessment tools to evaluate clinical and laboratory responses in a subset of patients enrolled in the Rituximab in Myositis trial.

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Rider, Lisa G; Yip, Adrienne L; Horkayne-Szakaly, Iren; Volochayev, Rita; Shrader, Joseph A; Turner, Maria L; Kong, Heidi H; Jain, Minal S; Jansen, Anna V; Oddis, Chester V; Fleisher, Thomas A; Miller, Frederick W

2014-01-01

We aimed to assess changes in myositis core set measures and ancillary clinical and laboratory data from the National Institutes of Health's subset of patients enrolled in the Rituximab in Myositis trial. Eighteen patients (5 dermatomyositis, 8 polymyositis, 5 juvenile dermatomyositis) completed more in-depth testing of muscle strength and cutaneous assessments, patient-reported outcomes, and laboratory tests before and after administration of rituximab. Percentage change in individual measures and in the definitions of improvement (DOIs) and standardized response means were examined over 44 weeks. Core set activity measures improved by 18-70% from weeks 0-44 and were sensitive to change. Fifteen patients met the DOI at week 44, 9 patients met a DOI 50% response, and 4 met a DOI 70% response. Muscle strength and function measures were more sensitive to change than cutaneous assessments. Constitutional, gastrointestinal, and pulmonary systems improved 44-70%. Patient-reported outcomes improved up to 28%. CD20+ B cells were depleted in the periphery, but B cell depletion was not associated with clinical improvement at week 16. This subset of patients had high rates of clinical response to rituximab, similar to patients in the overall trial. Most measures were responsive, and muscle strength had a greater degree of change than cutaneous assessments. Several novel assessment tools, including measures of strength and function, extra-muscular organ activity, fatigue, and health-related quality of life, are promising for use in future myositis trials. Further study of B cell-depleting therapies in myositis, particularly in treatment-naïve patients, is warranted.

Assessing the clinical outcome of Vim radiosurgery with voxel-based morphometry: visual areas are linked with tremor arrest!

Science.gov (United States)

Tuleasca, Constantin; Witjas, Tatiana; Najdenovska, Elena; Verger, Antoine; Girard, Nadine; Champoudry, Jerome; Thiran, Jean-Philippe; Van de Ville, Dimitri; Cuadra, Meritxell Bach; Levivier, Marc; Guedj, Eric; Régis, Jean

2017-11-01

Radiosurgery (RS) is an alternative to open standard stereotactic procedures (deep-brain stimulation or radiofrequency thalamotomy) for drug-resistant essential tremor (ET), aiming at the same target (ventro-intermediate nucleus, Vim). We investigated the Vim RS outcome using voxel-based morphometry by evaluating the interaction between clinical response and time. Thirty-eight patients with right-sided ET benefited from left unilateral Vim RS. Targeting was performed using 130 Gy and a single 4-mm collimator. Neurological and neuroimaging assessment was completed at baseline and 1 year. Clinical responders were considered those with at least 50% improvement in tremor score on the treated hand (TSTH). Interaction between clinical response and time showed the left temporal pole and occipital cortex (Brodmann area 19, including V4, V5 and the parahippocampal place area) as statistically significant. A decrease in gray matter density (GMD) 1 year after Vim RS correlated with higher TSTH improvement (Spearman = 0.01) for both anatomical areas. Higher baseline GMD within the left temporal pole correlated with better TSTH improvement (Spearman = 0.004). Statistically significant structural changes in the relationship to clinical response after Vim RS are present in remote areas, advocating a distant neurobiological effect. The former regions are mainly involved in locomotor monitoring toward the local and distant environment, suggesting the recruiting requirement in targeting of the specific visuomotor networks.

Clinical and ultrasound evaluation of the response to tocilizumab treatment in patients with rheumatoid arthritis: a case series.

Science.gov (United States)

Epis, Oscar; Filippucci, Emilio; Delle Sedie, Andrea; De Matthaeis, Anna; Bruschi, Eleonora

2014-05-01

This case series evaluates the clinical and ultrasound response to tocilizumab treatment in patients with rheumatoid arthritis (RA). Six patients with active RA (DAS28 ≥ 3.2) for ≥6 months, refractory to conventional DMARDs or anti-TNF agents, received tocilizumab 8 mg/kg every 4 weeks, as monotherapy or in combination with DMARDs, for 6 months. The following clinical parameters were assessed monthly: number of tender joints (28 and 44 joints), number of swollen joints (28 and 44 joints), DAS28-ESR, DAS28-CRP, VAS score, global health status, health assessment questionnaire, patient global assessment of disease activity, physician global assessment of disease activity, functional assessment of chronic illness therapy (FACIT), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). All patients also underwent a gray-scale ultrasonography (US) assessment with power Doppler evaluation at each visit. All clinical parameters improved during the study, versus baseline. This improvement was statistically significant for most parameters 2 months following tocilizumab initiation and was sustained to the end of the observation period. The number of tender joints (44-joint evaluation), the FACIT score, and ESR and CRP concentrations were significantly improved versus baseline values after the first month of tocilizumab treatment. The course of US evaluations mirrored that of clinical parameters; a faster and more evident response was observed for foot joints, with respect to hand joints. This case series suggested the rapid clinical benefit of tocilizumab. Ultrasound assessment showed that the onset of this effect was faster in the foot joints than in the hand joints.

Filariasis attenuates anemia and proinflammatory responses associated with clinical malaria: a matched prospective study in children and young adults.

Directory of Open Access Journals (Sweden)

Housseini Dolo

Full Text Available Wuchereria bancrofti (Wb and Mansonella perstans (Mp are blood-borne filarial parasites that are endemic in many countries of Africa, including Mali. The geographic distribution of Wb and Mp overlaps considerably with that of malaria, and coinfection is common. Although chronic filarial infection has been shown to alter immune responses to malaria parasites, its effect on clinical and immunologic responses in acute malaria is unknown.To address this question, 31 filaria-positive (FIL+ and 31 filaria-negative (FIL- children and young adults, matched for age, gender and hemoglobin type, were followed prospectively through a malaria transmission season. Filarial infection was defined by the presence of Wb or Mp microfilariae on calibrated thick smears performed between 10 pm and 2 am and/or by the presence of circulating filarial antigen in serum. Clinical malaria was defined as axillary temperature ≥37.5°C or another symptom or sign compatible with malaria infection plus the presence of asexual malaria parasites on a thick blood smear. Although the incidence of clinical malaria, time to first episode, clinical signs and symptoms, and malaria parasitemia were comparable between the two groups, geometric mean hemoglobin levels were significantly decreased in FIL- subjects at the height of the transmission season compared to FIL+ subjects (11.4 g/dL vs. 12.5 g/dL, p<0.01. Plasma levels of IL-1ra, IP-10 and IL-8 were significantly decreased in FIL+ subjects at the time of presentation with clinical malaria (99, 2145 and 49 pg/ml, respectively as compared to 474, 5522 and 247 pg/ml in FIL- subjects.These data suggest that pre-existent filarial infection attenuates immune responses associated with severe malaria and protects against anemia, but has little effect on susceptibility to or severity of acute malaria infection. The apparent protective effect of filarial infection against anemia is intriguing and warrants further study in a larger cohort.

Is drug-induced toxicity a good predictor of response to neo-adjuvant chemotherapy in patients with breast cancer? -A prospective clinical study

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Singh JP

2004-08-01

Full Text Available Abstract Background Neo-adjuvant chemotherapy is an integral part of multi-modality approach in the management of locally advanced breast cancer and it is vital to predict the response in order to tailor the regime for a patient. The common final pathway in the tumor cell death is believed to be apoptosis or programmed cell death and chemotherapeutic drugs like other DNA-damaging agents act on rapidly multiplying cells including both the tumor and the normal cells by following the same common final pathway. This could account for both the toxic effects and the response. Absence or decreased apoptosis has been found to be associated with chemo resistance. The change in expression of apoptotic markers (Bcl-2 and Bax proteins brought about by various chemotherapeutic regimens is being used to identify drug resistance in the tumor cells. A prospective clinical study was conducted to assess whether chemotherapy induced toxic effects could serve as reliable predictors of apoptosis or response to neo-adjuvant chemotherapy in patients with locally advanced breast cancer. Methods 50 cases of locally advanced breast cancer after complete routine and metastatic work up were subjected to trucut biopsy and the tissue evaluated immunohistochemically for apoptotic markers (bcl-2/bax ratio. Three cycles of Neoadjuvant Chemotherapy using FAC regime (5-fluorouracil, adriamycin, cyclophosphamide were given at three weekly intervals and patients assessed for clinical response as well as toxicity after each cycle. Modified radical mastectomy was performed in all patients three weeks after the last cycle and the specimen were re-evaluated for any change in the bcl-2/bax ratio. The clinical response, immunohistochemical response and the drug-induced toxicity were correlated and compared. Descriptive studies were performed with SPSS version 10 and the significance of response was assessed using paired t-test. Significance of correlation between various variables was

Acute and second-meal effects of peanuts on glycaemic response and appetite in obese women with high type 2 diabetes risk: a randomised cross-over clinical trial.

Science.gov (United States)

Reis, Caio E G; Ribeiro, Daniela N; Costa, Neuza M B; Bressan, Josefina; Alfenas, Rita C G; Mattes, Richard D

2013-06-01

Nut consumption is associated with a reduced risk of type 2 diabetes mellitus (T2DM). The aim of the present study was to assess the effects of adding peanuts (whole or peanut butter) on first (0-240 min)- and second (240-490 min)-meal glucose metabolism and selected gut satiety hormone responses, appetite ratings and food intake in obese women with high T2DM risk. A group of fifteen women participated in a randomised cross-over clinical trial in which 42·5 g of whole peanuts without skins (WP), peanut butter (PB) or no peanuts (control) were added to a 75 g available carbohydrate-matched breakfast meal. Postprandial concentrations (0-490 min) of glucose, insulin, NEFA, glucagon-like peptide-1 (GLP-1), peptide YY (PYY), cholecystokinin (CCK), appetitive sensations and food intake were assessed after breakfast treatments and a standard lunch. Postprandial NEFA incremental AUC (IAUC) (0-240 min) and glucose IAUC (240-490 min) responses were lower for the PB breakfast compared with the control breakfast. Insulin concentrations were higher at 120 and 370 min after the PB consumption than after the control consumption. Desire-to-eat ratings were lower, while PYY, GLP-1 and CCK concentrations were higher after the PB intake compared with the control intake. WP led to similar but non-significant effects. The addition of PB to breakfast moderated postprandial glucose and NEFA concentrations, enhanced gut satiety hormone secretion and reduced the desire to eat. The greater bioaccessibility of the lipid component in PB is probably responsible for the observed incremental post-ingestive responses between the nut forms. Inclusion of PB, and probably WP, to breakfast may help to moderate glucose concentrations and appetite in obese women.

Characterizing the inflammatory tissue response to acute myocardial infarction by clinical multimodality noninvasive imaging.

Science.gov (United States)

Wollenweber, Tim; Roentgen, Philipp; Schäfer, Andreas; Schatka, Imke; Zwadlo, Caroline; Brunkhorst, Thomas; Berding, Georg; Bauersachs, Johann; Bengel, Frank M

2014-09-01

Myocardial infarction (MI) triggers a systemic inflammatory response which determines subsequent healing. Experimentally, cardiac positron emission tomography and magnetic resonance imaging have been used successfully to obtain mechanistic insights. We explored the translational potential in patients early after MI. Positron emission tomography/computed tomography and cardiac magnetic resonance were performed in 15 patients sources of inflammatory cells. Positron emission tomography and cardiac magnetic resonance multimodality characterization of the acutely infarcted, inflamed myocardium may provide multiparametric end points for clinical studies aiming at support of infarct healing. © 2014 American Heart Association, Inc.

Clinical responsiveness of self-report functional assessment measures for children with juvenile idiopathic arthritis undergoing intraarticular corticosteroid injections.

Science.gov (United States)

Brown, G Ted; Wright, F Virginia; Lang, Bianca A; Birdi, Nina; Oen, Kim; Stephens, Derek; McComas, Joan; Feldman, Brian M

2005-12-15

The Childhood Health Assessment Questionnaire (CHAQ), Juvenile Arthritis Functional Assessment Report (JAFAR), and Juvenile Arthritis Functional Status Index (JASI) are widely used functional measures for juvenile idiopathic arthritis (JIA) that differ in content, format, and completion time. We compared the responsiveness and child-parent agreement of the JAFAR, CHAQ, and JASI in a prospective, multicenter study. Children and adolescents from 5 rheumatology centers were enrolled. Subjects were about to undergo therapy (intraarticular corticosteroid injections [IAS] and methotrexate or hip surgery (MTX/hip]) expected to produce a functional improvement. All subjects were studied before the intervention and at 6 weeks and 6 months posttreatment. At each study visit, the 3 measures were administered in randomized, balanced order to both parents and children. A total of 92 subjects (mean age 12.8 years) were enrolled in the study, 74 of which were in the IAS group. The responsiveness of all 3 measures was moderate to strong. The standardized response mean at 6 weeks for the IAS group on the JAFAR, CHAQ, and JASI was 0.41 (95% confidence interval [95% CI] 0.18, 0.64), 0.70 (95% CI 0.47, 0.93), and 0.36 (95% CI 0.13, 0.59), respectively. The CHAQ was somewhat more responsive to change at 6 weeks (IAS group: relative efficiency 0.34 [JAFAR], 0.27 [JASI]), but less responsive at 6 months (MTX/hip group: relative efficiency 5.1 [JAFAR], 3.9 [JASI]). All 3 questionnaires showed acceptable parent-child agreement, and overall, there were few differences between the 3 questionnaires. The functional outcome measures currently used for JIA are all adequately responsive for use in trials or in the clinic setting. The choice of which measure to use should therefore be based on the time available for completion, the intended clinical/research use, and the depth of content required.

Response to Therapeutic Plasma Exchange as a Rescue Treatment in Clinically Isolated Syndromes and Acute Worsening of Multiple Sclerosis: A Retrospective Analysis of 90 Patients.

Directory of Open Access Journals (Sweden)

Johannes Ehler

Full Text Available Experience with therapeutic plasma exchange (TPE for acute relapses in clinically isolated syndrome (CIS or multiple sclerosis (MS patients has been derived from small and inhomogeneous patient populations so far. In the present study, we retrospectively evaluated features associated with TPE response in a larger cohort of CIS and MS patients with acute worsening of disease.Ninety CIS and MS patients with acute relapses or acute worsening of symptoms were firstly treated with TPE. The population consisted of 62 women and 28 men with a median age of 38 years (range 18-69 years.Primary endpoint was the clinical response to TPE, focused on the functional improvement of the target neurologic deficit. Secondary endpoint was an improvement in expanded disability status scale (EDSS scoring.A clinical response to TPE was observed in 65 out of 90 patients (72.2%, with marked improvement in 18 (20.0% and moderate improvement in 47 out of 90 patients (52.2%. The median EDSS was reduced from 3.75 before to 3.0 after TPE (p = 0.001. Response to TPE was significantly more frequent in patients with relapsing courses of disease (CIS, RR-MS, p = 0.001, no disease modifying drugs (p = 0.017, gadolinium-positive (Gd+ MRI lesions (p = 0.001 and EDSS ≤ 5.0 before TPE (p = 0.014. In the multiple logistic regression analysis only the detection of Gd+ MRI lesions was significantly altered (p = 0.004.Clinical response to TPE was achieved in the majority of our patients. We identified clinical and diagnostic features in CIS and MS relapses that might be helpful to identify patients responding to TPE. Gd+ MRI lesions before treatment were the best predictor of the response to TPE in our cohort.

Advanced clinical practice for radiographers in Great Britain: professional roles, accountability and the educational provision

International Nuclear Information System (INIS)

Hogg, P.

2004-01-01

A change in British health care has resulted in a broadening of roles and responsibilities beyond 'traditional boundaries' for a range of health care professionals. This has occurred because of staff shortages (particularly within the medical profession) and the recognition that many 'non-doctor' health care staff can make safe, competent and effective contributions outside their 'normal' sphere of responsibilities. In the context of advanced clinical practice, this paper will explain the current arrangements for radiographers' roles and responsibilities, their accountability and the educational provision that underpins the development of competencies at these higher clinical levels. Some advanced roles that British radiographers perform, within their current normal responsibilities, will be identified and some British legislation and professional body guidance that make role advancement possible will be outlined. The article will conclude with an indication of the educational level at which the advanced competencies are learned and assessed. (author)

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

International Nuclear Information System (INIS)

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

2014-01-01

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 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 including

Partial response to biotin therapy in a patient with holocarboxylase synthetase deficiency: clinical, biochemical, and molecular genetic aspects

NARCIS (Netherlands)

Santer, R.; Muhle, H.; Suormala, T.; Baumgartner, E. R.; Duran, M.; Yang, X.; Aoki, Y.; Suzuki, Y.; Stephani, U.

2003-01-01

We report the clinical course and biochemical findings of a 10-year-old, mentally retarded girl with late-onset holocarboxylase synthetase (HCS, gene symbol HLCS) deficiency and only partial response to biotin. On treatment, even with an unusually high dose of 200mg/day, activities of the

Association of Escherichia coli J5-specific serum antibody responses with clinical mastitis outcome for J5 vaccinate and control dairy cattle.

Science.gov (United States)

Wilson, David J; Mallard, Bonnie A; Burton, Jeanne L; Schukken, Ynte H; Grohn, Yrjo T

2009-02-01

Dairy cattle in two commercial Holstein herds were randomly selected to be vaccinated twice with J5, at approximately 60 days and 28 days before the expected calving date, or to be untreated controls. Based on whether milk production changed following clinical mastitis or whether cows were culled or died within 30 days after onset, 51 mastitis cases were classified as severe or mild. J5-specific antibody responses were evaluated by enzyme-linked immunosorbent assay of all 32 severe and 19 mild cases. The amounts of J5-specific immunoglobulin M (IgM), IgG1, and IgG2 antibodies in sera from the 27 J5 vaccinates were compared with those of the 24 controls. At drying off (before J5 vaccination), all cows had similar amounts of J5-specific antibody. Immediately after calving (approximately 28 days after the second vaccination), J5 vaccinates had significantly higher production of J5-specific IgG1 and IgG2 than controls. When cows were tested following clinical mastitis, none of the three antibody classes differed significantly between the controls and the vaccinates. Vaccinates that contracted Escherichia coli mastitis had 75% less milk loss than controls. The cows that contracted clinical mastitis later in lactation, the unvaccinated controls, and those infected with E. coli had more milk loss following mastitis. The hazards of being culled for all reasons and of being culled for mastitis were significantly lower for J5 vaccinates. Vaccination with J5 was associated with protection against milk production loss and culling following clinical mastitis, and it was also significantly associated with changes in J5-specific IgM, IgG1, and IgG2 antibodies in sera of vaccinated cows.

Analysis of PSA-Specific T-Cell Responses of Prostate Cancer Patients Given a PSA-Based Vaccine on a Clinical Trial

National Research Council Canada - National Science Library

Gulley, James

2003-01-01

.... This randomized, phase II clinical trial was designed to determine if a PSA-based vaccine could induce a specific immune response when combined with radiotherapy in patients with localized prostate cancer...

On higher-spin supertranslations and superrotations

Energy Technology Data Exchange (ETDEWEB)

Campoleoni, Andrea [Université Libre de Bruxelles and International Solvay Institutes,ULB-Campus Plaine CP231, B-1050 Brussels (Belgium); Francia, Dario; Heissenberg, Carlo [Scuola Normale Superiore and INFN,Piazza dei Cavalieri 7, I-56126 Pisa (Italy)

2017-05-22

We study the large gauge transformations of massless higher-spin fields in four-dimensional Minkowski space. Upon imposing suitable fall-off conditions, providing higher-spin counterparts of the Bondi gauge, we observe the existence of an infinite-dimensional asymptotic symmetry algebra. The corresponding Ward identities can be held responsible for Weinberg’s factorisation theorem for amplitudes involving soft particles of spin greater than two.

Tocilizumab in patients with active rheumatoid arthritis and inadequate response to disease-modifying antirheumatic drugs or tumor necrosis factor inhibitors: subanalysis of Spanish results of an open-label study close to clinical practice.

Science.gov (United States)

Álvaro-Gracia, José M; Fernández-Nebro, Antonio; García-López, Alicia; Guzmán, Manuel; Blanco, Francisco J; Navarro, Francisco J; Bustabad, Sagrario; Armendáriz, Yolanda; Román-Ivorra, José A

2014-01-01

To analyze the Spanish experience in an international study which evaluated tocilizumab in patients with rheumatoid arthritis (RA) and an inadequate response to conventional disease-modifying antirheumatic drugs (DMARDs) or tumor necrosis factor inhibitors (TNFis) in a clinical practice setting. Subanalysis of 170 patients with RA from Spain who participated in a phase IIIb, open-label, international clinical trial. Patients presented inadequate response to DMARDs or TNFis. They received 8mg/kg of tocilizumab every 4 weeks in combination with a DMARD or as monotherapy during 20 weeks. Safety and efficacy of tocilizumab were analyzed. Special emphasis was placed on differences between failure to a DMARD or to a TNFi and the need to switch to tocilizumab with or without a washout period in patients who had previously received TNFi. The most common adverse events were infections (25%), increased total cholesterol (38%) and transaminases (15%). Five patients discontinued the study due to an adverse event. After six months of tocilizumab treatment, 71/50/30% of patients had ACR 20/50/70 responses, respectively. A higher proportion of TNFi-naive patients presented an ACR20 response: 76% compared to 64% in the TNFi group with previous washout and 66% in the TNFi group without previous washout. Safety results were consistent with previous results in patients with RA and an inadequate response to DMARDs or TNFis. Tocilizumab is more effective in patients who did not respond to conventional DMARDs than in patients who did not respond to TNFis. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Optical signal response pf the alanine gel solution for photons and electrons clinical beams

International Nuclear Information System (INIS)

Silva, Cleber Feijo; Campos, Leticia Lucente

2009-01-01

Alanine gel dosimeter is a new gel material developed at IPEN that presents significant improvement on previous alanine systems developed by Costa (1994). The measure technique is based on the transformation of ferrous ions (Fe 2+ ) in ferric ions (Fe 3+ ) after irradiation. The DL-Alanine (C 3 H 7 NO 2 ) is an aminoacid tissue equivalent that improves the production of ferric ions in the solution. This work aims to study the comparison of optical signal response of the alanine gel solution for photons and electrons clinical beams. It was observed that the calibration factor can be considered independent of quality of the radiation for photons and electrons clinical beams. Therefore, it can be used the same calibration factor for evaluating the absorbed dose in photons and electrons fields in the energy of 6 MeV. Alanine Gel Dosimeter presents good performance and can be useful as alternative dosimeter in the radiotherapy area using MRI technique for 3D dose distribution evaluation. (author)

The dynamic response of human subjects while seated in car seats.

OpenAIRE

Pope, M. H.; Magnusson, M.; Broman, N. H.; Hasson, T.

1998-01-01

A pendulum impact method was used to establish the dynamic response of the seated subject. Threaded K wires were placed in the L3 spinous process. The gain and phase angle between the platform and the vertebra were established. The response of the subject was observed while seated on a platform and a variety of other seats. The seats were found to be very important in the attenuation of the impulse, leading to a higher transmissibility. Clinical Relevance Skeletal impact through the lower ext...

From the Consulting Room to the Court Room? Taking the Clinical Model of Responsibility Without Blame into the Legal Realm

Science.gov (United States)

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

From the Consulting Room to the Court Room? Taking the Clinical Model of Responsibility Without Blame into the Legal Realm.

Science.gov (United States)

Lacey, Nicola; Pickard, Hanna

2013-03-01

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.

DOES CLINICAL INERTIA VARY BY PERSONALIZED A1C GOAL? A STUDY OF PREDICTORS AND PREVALENCE OF CLINICAL INERTIA IN A U.S. MANAGED-CARE SETTING.

Science.gov (United States)

Lin, Jay; Zhou, Steve; Wei, Wenhui; Pan, Chunshen; Lingohr-Smith, Melissa; Levin, Philip

2016-02-01

Clinical inertia is defined as failure to initiate or intensify therapy despite an inadequate treatment response. We assessed the prevalence and identified the predictors of clinical inertia among patients with type 2 diabetes (T2DM) based on personalized goals. Three hemoglobin A1c (A1C) targets (American Diabetes Association A1C inertia was defined as no intensification of treatment during the response period. Demographic and clinical characteristics were analyzed to identify predictors of treatment intensification. Irrespective of A1C target, the majority of patients with T2DM (70.4 to 72.8%) experienced clinical inertia in the 6 months following the index event, with 5.3 to 6.2% of patients intensifying treatment with insulin. Patients with a lower likelihood of intensification were older, used >1 oral antidiabetes drug during the baseline period, and had an above-target A1C more recently. Treatment intensification was associated with patients who had point-of-service insurance, mental illness, an endocrinologist visit in the baseline period, or higher index A1C. The prevalence of clinical inertia among patients with T2DM in a U.S. managed-care setting is high and has increased over more recent years. Factors predicting increased risk of clinical inertia may help identify "at-risk" populations and assist in developing strategies to improve their management.

Does the increasing placebo response impact outcomes of adult and pediatric ADHD clinical trials? Data from the US Food and Drug Administration 2000-2009.

Science.gov (United States)

Khan, Arif; Fahl Mar, Kaysee; Brown, Walter A

2017-11-01

In a study of recent antidepressant clinical trial data, it was found placebo response had grown significantly over time and that contrary to expectations, trial outcome measures and success rate were not impacted. The aim of this paper was to evaluate if this trend of increasing placebo response and stable outcome measures could be seen in clinical trial data for Attention-Deficit Hyperactivity Disorder, a different psychiatric condition with susceptibility to placebo response. For this reason, we evaluated efficacy data reported in the FDA Medical and Statistical reviews for 10 ADHD medication programs (4917 patients, 17 trials, 29 treatment arms). Placebo and medication response were measured as percent symptom reduction and effect sizes and drug-placebo differences were calculated for each treatment arm and analyzed in relation to year of approval. We also investigated the potential role of age and medication class on trends and outcomes. Results showed a similar pattern to antidepressants wherein the placebo response is rising significantly over time (r = 0.636, p = 0.006) and effect size (r stimulants were found to have more robust treatment effects than adult trials and non-stimulants. The results of this study suggest that like antidepressants, the relationship between placebo response and the outcomes of ADHD clinical trials is weak at best. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Delphi Decision Methods in Higher Education Administration.

Science.gov (United States)

Judd, Robert C.

This document describes and comments on the extent of use of the Delphi method in higher education decision making. Delphi is characterized by: (1) anonymity of response; (2) multiple iterations; (3) convergence of the distribution of answers; and (4) statistical group response (median, interquartile range) preserving intact a distribution that…

Rare primary headaches: clinical insights.

Science.gov (United States)

Casucci, G; d'Onofrio, F; Torelli, P

2004-10-01

So-called "rare" headaches, whose prevalence rate is lower than 1% or is not known at all and have been reported in only a few dozen cases to date, constitute a very heterogeneous group. Those that are best characterised from the clinical point of view can be classified into forms with prominent autonomic features and forms with sparse or no autonomic features. Among the former are trigeminal autonomic cephalalgias (TACs) and hemicrania continua, while the latter comprise classical trigeminal neuralgia, hypnic headache, primary thunderclap headache, and exploding head syndrome. The major clinical discriminating factor for the differential diagnosis of TACs is the relationship between duration and frequency of attacks: the forms in which pain is shorter lived are those with the higher frequency of daily attacks. Other aspects to be considered are the time pattern of symptoms, intensity and timing of attacks, the patient's behaviour during the attacks, the presence of any triggering factors and of the refractory period after an induced attack, and response to therapy, especially with indomethacin. Often these are little known clinical entities, which are not easily detected in clinical practice. For some of them, e. g., thunderclap headache, it is always necessary to perform instrumental tests to exclude the presence of underlying organic diseases.

Biomarker and Tumor Responses of Oral Cavity Squamous Cell Carcinoma to Trametinib: A Phase II Neoadjuvant Window-of-Opportunity Clinical Trial.

Science.gov (United States)

Uppaluri, Ravindra; Winkler, Ashley E; Lin, Tianxiang; Law, Jonathan H; Haughey, Bruce H; Nussenbaum, Brian; Paniello, Randal C; Rich, Jason T; Diaz, Jason A; Michel, Loren P; Wildes, Tanya; Dunn, Gavin P; Zolkind, Paul; Kallogjeri, Dorina; Piccirillo, Jay F; Dehdashti, Farrokh; Siegel, Barry A; Chernock, Rebecca D; Lewis, James S; Adkins, Douglas R

2017-05-01

Purpose: Ras/MEK/ERK pathway activation is common in oral cavity squamous cell carcinoma (OCSCC). We performed a neoadjuvant (preoperative) trial to determine the biomarker and tumor response of OCSCC to MEK inhibition with trametinib. Experimental Design: Patients with stage II-IV OCSCC received trametinib (2 mg/day, minimum 7 days) prior to surgery. Primary tumor specimens were obtained before and after trametinib to evaluate immunohistochemical staining for p-ERK1/2 and CD44, the primary endpoint. Secondary endpoints included changes in clinical tumor measurements and metabolic activity [maximum standardized uptake values (SUV max ) by F-18 fluorodeoxyglucose positron emission tomography/CT), and in tumor downstaging. Drug-related adverse events (AE) and surgical/wound complications were evaluated. Results: Of 20 enrolled patients, 17 (85%) completed the study. Three patients withdrew because of either trametinib-related ( n = 2: nausea, duodenal perforation) or unrelated ( n = 1: constipation) AEs. The most common AE was rash (9/20 patients, 45%). Seventeen patients underwent surgery. No unexpected surgical/wound complications occurred. Evaluable matched pre- and posttrametinib specimens were available in 15 (88%) of these patients. Reduction in p-ERK1/2 and CD44 expression occurred in 5 (33%) and 2 (13%) patients, respectively. Clinical tumor response by modified World Health Organization criteria was observed in 11 of 17 (65%) evaluable patients (median 46% decrease, range 14%-74%). Partial metabolic response (≥25% reduction in SUV max ) was observed in 6 of 13 (46%) evaluable patients (median 25% decrease, range 6%-52%). Clinical-to-pathologic tumor downstaging occurred in 9 of 17 (53%) evaluable patients. Conclusions: Trametinib resulted in significant reduction in Ras/MEK/ERK pathway activation and in clinical and metabolic tumor responses in patients with OCSCC. Clin Cancer Res; 23(9); 2186-94. ©2016 AACR . ©2016 American Association for Cancer

Changes in information behavior in clinical teams after introduction of a clinical librarian service

Science.gov (United States)

Urquhart, Christine; Turner, Janet; Durbin, Jane; Ryan, Jean

2007-01-01

Objectives: The eighteen-month evaluation of a clinical librarian project (October 2003–March 2005) conducted in North Wales, United Kingdom (UK) assessed the benefits of clinical librarian support to clinical teams, the impact of mediated searching services, and the effectiveness of information skills training, including journal club support. Methods: The evaluation assessed changes in teams' information-seeking behavior and their willingness to delegate searching to a clinical librarian. Baseline (n = 69 responses, 73% response rate) and final questionnaire (n = 57, 77% response rate) surveys were complemented by telephone and face-to-face interviews (n = 33) among 3 sites served. Those attending information skills training sessions (n = 130) completed evaluations at the session and were surveyed 1 month after training (n = 24 questionnaire responses, n = 12 interviews). Results: Health professionals in clinical teams reported that they were more willing to undertake their own searching, but also more willing to delegate some literature searching, than at the start of the project. The extent of change depended on the team and the type of information required. Information skills training was particularly effective when organized around journal clubs. Conclusions: Collaboration with a clinical librarian increased clinician willingness to seek information. Clinical librarian services should leverage structured training opportunities such as journal clubs. PMID:17252062

Quality of Higher Education

DEFF Research Database (Denmark)

Zou, Yihuan; Zhao, Yingsheng; Du, Xiangyun

. This transformation involves a broad scale of change at individual level, organizational level, and societal level. In this change process in higher education, staff development remains one of the key elements for university innovation and at the same time demands a systematic and holistic approach.......This paper starts with a critical approach to reflect on the current practice of quality assessment and assurance in higher education. This is followed by a proposal that in response to the global challenges for improving the quality of higher education, universities should take active actions...... of change by improving the quality of teaching and learning. From a constructivist perspective of understanding education and learning, this paper also discusses why and how universities should give more weight to learning and change the traditional role of teaching to an innovative approach of facilitation...

Clinical Predictors of Response to Cognitive-Behavioral Therapy in Pediatric Anxiety Disorders : The Genes for Treatment (GxT) Study

NARCIS (Netherlands)

Hudson, Jennifer L.; Keers, Robert; Roberts, Susanna; Coleman, Jonathan R. I.; Breen, Gerome; Arendt, Kristian; Boegels, Susan; Cooper, Peter; Creswell, Cathy; Hartman, Catharina; Heiervang, Einar R.; Hoetzel, Katrin; In-Albon, Tina; Lavallee, Kristen; Lyne-Ham, Heidi J.; Marin, Carla E.; McKinnon, Anna; Meiser-Stedman, Richard; Morris, Talia; Nauta, Maaike; Rapee, Ronald M.; Schneider, Silvia; Schneider, Sophie C.; Silverman, Wendy K.; Thastum, Mikael; Thirlwall, Kerstin; Waite, Polly; Wergeland, Gro Janne; Lester, Kathryn J.; Eley, Thalia C.

Objective: The Genes for Treatment study is an international, multisite collaboration exploring the role of genetic, demographic, and clinical predictors in response to cognitive-behavioral therapy (CBT) in pediatric anxiety disorders. The current article, the first from the study, examined

Clinical predictors of response to Cognitive-Behavioral Therapy in pediatric anxiety disorders: The genes for treatment (GxT) study

NARCIS (Netherlands)

Hudson, J.L.; Keers, R.; Roberts, S.; Coleman, J.R.I.; Breen, G.; Arendt, K.; Cooper, P.; Bögels, S.; Creswell, C.; Hartman, C.; Heiervang, E.R.; Hötzel, K.; In-Albon, T.; Lavallee, K.; Lyneham, H.J.; Marin, C.E.; McKinnon, A.; Meiser-Stedman, R.; Morris, T.; Nauta, M.

2015-01-01

Objective The Genes for Treatment study is an international, multisite collaboration exploring the role of genetic, demographic, and clinical predictors in response to cognitive-behavioral therapy (CBT) in pediatric anxiety disorders. The current article, the first from the study, examined

Development and implementation of intranasal naloxone opioid overdose response protocol at a homeless health clinic.

Science.gov (United States)

Dahlem, Chin Hwa Y; Horstman, Molly J; Williams, Brent C

2016-01-01

To describe the development, implementation, and preliminary evaluation of Opioid Overdose Response Protocol using intranasal (IN) naloxone in a homeless shelter. Opioid Overdose Response Protocol and training curriculum were developed using the Massachusetts Department of Public Health Opioid Overdose Education and Naloxone Distribution (OEND) flow chart, the American Heart Association (AHA) simplified adult basic life support algorithm, and resources through Harms Reduction Coalition. Intranasal naloxone offers a safe and effective method for opioid reversal. To combat the rising incidence of opioid overdose, IN naloxone should be made available at homeless shelters and other facilities with high frequency of opioid overdose, including the training of appropriate staff. This project has demonstrated the effective training and implementation of an Opioid Overdose Response Protocol, based on feedback received from cardiopulmonary resuscitation (CPR) trained nonhealthcare staff. Nurse practitioners (NPs), with our focus on patient care, prevention, and education, are well suited to the deployment of this life-saving protocol. NPs are in critical positions to integrate opioid overdose prevention education and provide naloxone rescue kits in clinical practices. ©2015 American Association of Nurse Practitioners.

PET-CT in Staging, Response Evaluation, and Surveillance of Lymphoma.

Science.gov (United States)

Thanarajasingam, Gita; Bennani-Baiti, Nabila; Thompson, Carrie A

2016-05-01

Lymphoma represents a broad spectrum of diseases with diverse biology, clinical behavior, and imaging features. Functional imaging with 18-F-fluorodeoxyglucose (FDG)-positron emission tomography combined with computed tomography (PET-CT) is widely recognized as the most sensitive and specific imaging modality for patients with lymphoma and is used as part of staging, response evaluation, and surveillance in patients with Hodgkin (HL) and non-Hodgkin lymphoma (NHL). Recent efforts at standardizing the conduct and consensus interpretation of PET-CT have facilitated its use in patients on clinical studies and beyond. The role of PET-CT has been affirmed in some clinical situations, such as staging and end-of-treatment evaluation in Hodgkin lymphoma and diffuse large B cell lymphoma (DLBCL), and in the evaluation of aggressive transformation of an indolent lymphoma. However, the role of functional imaging in other histologies and clinical settings is not as clear given the higher rate of false positive results and the costs inherent to PET-CT. There is little evidence to suggest its utility or impact on outcome in most indolent lymphomas, or in the setting of post-treatment surveillance. In addition, there remains controversy about the value of PET-CT in early response assessment during active therapy, particularly in DLBCL. This review will evaluate the evidence surrounding the role of PET-CT in staging, response evaluation and surveillance of Hodgkin and non-Hodgkin lymphoma.

Randomized phase 2 trial to evaluate the clinical efficacy of two high-dosage tigecycline regimens versus imipenem-cilastatin for treatment of hospital-acquired pneumonia.

Science.gov (United States)

Ramirez, Julio; Dartois, Nathalie; Gandjini, Hassan; Yan, Jean Li; Korth-Bradley, Joan; McGovern, Paul C

2013-04-01

In a previous phase 3 study, the cure rates that occurred in patients with hospital-acquired pneumonia treated with tigecycline at the approved dose were lower than those seen with patients treated with imipenem and cilastatin (imipenem/cilastatin). We hypothesized that a higher dose of tigecycline is necessary in patients with hospital-acquired pneumonia. This phase 2 study compared the safety and efficacy of two higher doses of tigecycline with imipenem/cilastatin in subjects with hospital-acquired pneumonia. Subjects with hospital-acquired pneumonia were randomized to receive one of two doses of tigecycline (150 mg followed by 75 mg every 12 h or 200 mg followed by 100 mg every 12 h) or 1 g of imipenem/cilastatin every 8 h. Empirical adjunctive therapy was administered for initial coverage of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa infection, depending on the randomization regimen. Clinical response, defined as cure, failure of treatment, or indeterminate outcome, was assessed 10 to 21 days after the last day of therapy. In the clinically evaluable population, clinical cure with tigecycline 100 mg (17/20, 85.0%) was numerically higher than with tigecycline 75 mg (16/23, 69.6%) and imipenem/cilastatin (18/24, 75.0%). No new safety signals with the high-dose tigecycline were identified. A numerically higher clinical response was observed with the 100-mg dose of tigecycline. This supports our hypothesis that a higher area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC/MIC ratio) may be necessary to achieve clinical cure in patients with hospital-acquired pneumonia. Further studies are necessary. (The ClinicalTrials.gov identifier for this clinical trial is NCT00707239.).

Soccer small-sided games in young players: rule modification to induce higher physiological responses

Science.gov (United States)

Chtourou, H; Dellal, A; Chaouachi, A; Chamari, K

2017-01-01

The aim of this study was to identify the physiological responses of 3 forms of players’ numbers during two different games rules of small-sided games (SSG: stop-ball vs. small-goals rules). Eighteen youth amateur soccer players (age 13.5±0.7 years; height 168.9±6.1cm; body mass 63.1±7.7 kg) participated in this study and performed 3 SSGs with varying players’ number (2vs.2; 3vs.3 and 4vs.4): stop-ball SSG (SB-SSG) vs. small-goals SSG (SG-SSG) in a randomized and counter-balanced order on a constant pitch dimension (20×25m). The players performed 4×4 min SSG with 2-min of passive recovery in-between. Heart rate (HR), (expressed in bpm and % HRmax), lactate ([La-]), and rating of perceived exertion (RPE) were collected during each session. SB-SSG induced the higher HR values in comparison with the SG-SSG for the 3 game formats (2vs.2; 3vs.3 and 4vs.4). Also, compared with SG-SSG, SB-SSG induced the higher HR values during 2vs.2 compared with 4vs.4 games rules (178 vs. 174 and 175 vs. 171 bpm, respectively). However, the SB-SSG was more intense compared with SG-SSG in the 2 vs. 2 game rule compared with the two others (3 vs.3 and 4 vs. 4) for [La-] and RPE (7.58 vs. 7; 7.25 vs. 6.75 and 6.5 vs. 6.16 mmol ∙ L-1, and 7.75 vs. 7.33; 7.41 vs. 7.08 and 7.16 vs. 6.83, respectively). Therefore, the use of 2 vs. 2 and 3 vs. 3 SSG with SB-SSG seems to represent an alternative to coaches to increase cardiovascular and metabolic demands in youth soccer players. PMID:28566810

Are self-report scales as effective as clinician rating scales in measuring treatment response in routine clinical practice?

Science.gov (United States)

Zimmerman, Mark; Walsh, Emily; Friedman, Michael; Boerescu, Daniela A; Attiullah, Naureen

2018-01-01

Recent treatment guidelines have suggested that outcome should be measured in routine clinical practice. In the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project, we compared three self-report scales of depressive symptoms and the two most widely used clinician administered scales in treatment studies in their sensitivity to change and evaluation of treatment response in depressed patients treated in routine practice. At baseline and 4-month follow-up 153 depressed outpatients with DSM-IV MDD completed the Clinically Useful Depression Outcome Scale (CUDOS), Quick Inventory of Depressive Symptomatology-Self-report version (QIDS-SR), and Patient Health Questionnaire (PHQ-9). The patients were rated on the 17-item Hamilton Depression Rating Scale (HAMD) and the Montgomery-Asberg Depression Rating Scale (MADRS). On each scale treatment response was defined as a 50% or greater reduction in scores from baseline. While there were some differences in the percentage of patients considered to be responders on the different scales, a large effect size was found for each scale, with little variability amongst the scales. The level of agreement between the three self-report scales and the clinician rating scales was approximately the same LIMITATIONS: The present study was conducted in a single clinical practice in which the majority of the patients were white, female, and had health insurance. When measuring outcome in clinical practice the magnitude of change in depressive symptoms is as great on self-report scales as on clinician rating scales. Copyright © 2017 Elsevier B.V. All rights reserved.

A sheeppox outbreak in Morocco: isolation and identification of virus responsible for the new clinical form of disease.

Science.gov (United States)

Zro, Khalil; Zakham, Fathiah; Melloul, Marouane; El Fahime, Elmostafa; Ennaji, Moulay Mustapha

2014-01-27

Sheeppoxvirus (SPPV) is a member of the Capripoxvirus genus of the Poxviridae family, which causes significant economic losses in Morocco. The resurgence of the sheeppox disease during 2010 was characterized by an emergence of a classical nodular form for the first time in Morocco. However, little is known about the virus strain responsible for nodular form. In this study, thirty three sheep, from the eastern region of Morocco, clinically infected were examined and dead animals were autopsied.A rapid diagnostic assay for SPPV using different type of clinical samples would be useful for outbreak management. The aim of this work was to isolate the virus strain responsible for nodular form and we identified and compared by phylogenetic analysis the field strain with Moroccan vaccine strain targeting the thymidine kinase (TK) gene and the chemokine analogue receptor of interleukin (IL8) gene. Further, it was important to investigate and validate a real-time PCR using different clinical and post-mortem samples to manage epidemic sheeppox disease. The nodular form of sheeppox disease observed in Morocco was clinically characterized by fever, depression, lacrimation, diarrhea in lambs and nodule. At necropsy, the most affected organ was the lung. The etiological strain was successfully isolated from lung nodule in a dead lamb and was identified by using real-time PCR that has been tested and validated on different types of clinical and post mortem samples from naturally infected animals. Sequence and phylogenetic analysis of TK and IL8 gene showed that there was a very close relationship between field and vaccine strain. They were clustered within other SPPV strains. In the current study, we show for the first time the nodular form of sheeppox in Morocco. We demonstrate a robust real-time PCR-based diagnostic assay to detect the sheeppox virus in multiple sample that can be implemented to efficiently manage the disease outbreak. Our study also offers the prospect for

Malignant mesothelioma clinical trial combines immunotherapy drugs.

Science.gov (United States)

Chatwal, Monica S; Tanvetyanon, Tawee

2018-04-01

Immunotherapy by checkpoint inhibitor is effective for a number of solid tumors including malignant mesothelioma. Studies utilizing single-agent PD-1 or PD-L1 inhibitor for mesothelioma have reported tumor response rates in approximately 10-20% of patients treated. Given the success of combining these agents with CTLA-4 inhibitor in melanoma, there is a strong rationale to study it in mesothelioma. Recently results from clinical trials investigating this approach have been released. Though limited by small sample size, the studies conclusively demonstrated feasibility and suggested a modestly higher tumor response rate than one would expect from treatment with single-agent PD-1 or PD-L1 inhibitor. Nevertheless, toxicity was also increased. Immunotherapy-related deaths due to encephalitis, renal failure and hepatitis were observed. Further studies are warranted.

Dependence of alanine gel dosimeter response as a function of photon clinical beams dose rate

International Nuclear Information System (INIS)

Silva, Cleber Feijo; Campos, Leticia Lucente

2013-01-01

Gel dosimetry is a new area developed by Gore, it is ery useful for application in radiotherapy because using NMR imaging as evaluation technique is possible to evaluate three dimensional absorbed dose distribution. The measure technique is based on difference of ferrous (Fe 2+ ) and ferric (Fe 3+ ) ) ions concentration that can be measured also by spectrophotometry technique. The Alanine gel dosimeter was developed at IPEN. The alanine is an amino acid and tissue equivalent material that presents significant improvement on previous alanine dosimetry systems. The addition of Alanine increases the production of ferric ions in the solution. This work aims to study the dose rate dependence of photon clinical beams radiation on the alanine gel dosimeter optical response, as well as the response repeatability and gel production reproducibility, since this property is very important for characterization and standardization of any dosimeter. (author)

What is the role of the consultant responsible for postgraduate education in the clinical department?

DEFF Research Database (Denmark)

Malling, B; Scherpbier, A J J A; Ringsted, C

2007-01-01

interviewees expressed a wish for a strong leader at the same time they did not consider the position of the CRE influential. CONCLUSION: Along with improved information about the role of the CRE, formal education, proper job-descriptions and clear leadership in the organisation concerning specialist training......BACKGROUND: The organisation of specialist training is complex and involves many clinical departments. The position of consultants responsible for education (CRE) in specialist training at department level is poorly defined in the literature. AIMS: The aim of the study was to explore expectations...... of stakeholders concerning the role and position of a CRE in specialist training. METHOD: The role and position of the CRE was explored using focus group and semi-structured individual interviews. RESULTS: Knowledge of tasks and responsibilities was limited in all stakeholders except among CREs. The expectations...

Assessing undergraduate nursing students in clinical practice: do preceptors use assessment strategies?

Science.gov (United States)

McCarthy, Bridie; Murphy, Siobhan

2008-04-01

Health care organisations such as the World Health Organisation (WHO) and An Bord Altranais (ABA, The Irish Nursing Registration Board) demand higher standards of new graduate nurses than heretofore. This is in conjunction with the implementation of degree programmes for undergraduate nurse education. These organisations stipulate that graduates must be well-educated, accountable, and can demonstrate the skills of a safe, caring and competent decision-making practitioner. The Bachelor of Science (BSc) four-year degree programme for undergraduate nurse education was introduced in Ireland in 2002, and is provided in universities and colleges of higher education throughout The Republic of Ireland. During the implementation process, each university and college of higher education developed a range of assessment strategies to clinically assess students. Preceptor nurses were subsequently assigned the responsibility of clinically assessing students, a remit previously undertaken by Clinical Ward/Unit Nurse Managers. Preceptors are qualified nurses, working in clinical units who are specially prepared to support BSc students during clinical placements. The purpose of this study was to explore to what extent preceptor nurses use the devised assessment strategies to clinically assess BSc students in one university in The Republic of Ireland. Data were collected by using a questionnaire distributed to all known preceptors in General, Psychiatric and Intellectual Disability nursing, during year four of the first cycle of the BSc programme. Findings from this descriptive study revealed that many preceptors were inexperienced, did not fully comprehend the assessment process and were not applying all of the recommended assessment strategies when assessing students in clinical practice. In light of these findings suggestions are made in the context of further research, management and education.

Clinical assessment of the response of metastatic cervical lymph nodes to radiation in patients with squamous cell carcinoma

International Nuclear Information System (INIS)

Sekiguchi, Kenji

1985-01-01

Between November 1981 to May 1985, measurements were made of the exponential regression of 69 cervical nodes from 37 patients with squamous cell carcinoma treated with radiotherapy in the division of clinical oncology, the department of Radiology at the Tokyo Women's Medical College. The volume-halving time (T 1/2(V)) which was calculated in each case was analysed. The results were as follows. 1. T 1/2(V) of oral cavity, lung, hypopharynx and esophagus seemed to be longer than those of oropharynx, uterus, larynx and epipharynx. 2. T 1/2(V) of well differentiated squamous cell carcinoma seemed to be shorter than those of moderately and poorly differentiated squamous cell carcinoma, however no significant difference was found. 3. There were two patterns of initial regression. One half of lymph nodes regressed with an initial shoulder and the other half regressed without it. And T 1/2(V) of regression curve with it was statistically shorter than that without it. 4. There was no significant correlation between T 1/2(V) and the lymph node size. 5. The response rate of lymph node to radiotherapy was higher and the regrowth rate was lower in the fast regression group, compared with those in the slow regression group. (author)

University Social Responsibility (USR): Identifying an Ethical Foundation within Higher Education Institutions

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Chen, Shu-Hsiang; Nasongkhla, Jaitip; Donaldson, J. Ana

2015-01-01

Social responsibility is a responsibility not a requirement, of an organization for the impact of its decisions and activities on society and the environment, through transparent and ethical behavior that contributes to sustainable development, health and the welfare of society; which takes into account the expectations of stakeholders, is in…

Clinical Application of {sup 18}F-FDG PET in Testicular Cancer

Energy Technology Data Exchange (ETDEWEB)

Yoon, Joon Kee [Ajou University School of Medicine, Suwon (Korea, Republic of)

2008-12-15

{sup 18}F-FDG PET has a higher diagnostic accuracy than CT in initial staging of testicular cancer. In seminoma, it can discriminate residual tumor from necrosis/fibrosis or mature teratoma. {sup 18}F-FDG PET is also useful for the response evaluation of chemotherapy. However, there's no clinical evidence for the use of {sup 18}F-FDG PET in the diagnosis and differential diagnosis of testicular cancer.

Striatal Activation Predicts Differential Therapeutic Responses to Methylphenidate and Atomoxetine.

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Schulz, Kurt P; Bédard, Anne-Claude V; Fan, Jin; Hildebrandt, Thomas B; Stein, Mark A; Ivanov, Iliyan; Halperin, Jeffrey M; Newcorn, Jeffrey H

2017-07-01

Methylphenidate has prominent effects in the dopamine-rich striatum that are absent for the selective norepinephrine transporter inhibitor atomoxetine. This study tested whether baseline striatal activation would predict differential response to the two medications in youth with attention-deficit/hyperactivity disorder (ADHD). A total of 36 youth with ADHD performed a Go/No-Go test during functional magnetic resonance imaging at baseline and were treated with methylphenidate and atomoxetine using a randomized cross-over design. Whole-brain task-related activation was regressed on clinical response. Task-related activation in right caudate nucleus was predicted by an interaction of clinical responses to methylphenidate and atomoxetine (F 1,30  = 17.00; p atomoxetine. The rate of robust response was higher for methylphenidate than for atomoxetine in youth with high (94.4% vs. 38.8%; p = .003; number needed to treat = 2, 95% CI = 1.31-3.73) but not low (33.3% vs. 50.0%; p = .375) caudate activation. Furthermore, response to atomoxetine predicted motor cortex activation (F 1,30  = 14.99; p atomoxetine in youth with ADHD, purportedly reflecting the dopaminergic effects of methylphenidate but not atomoxetine in the striatum, whereas motor cortex activation may predict response to atomoxetine. These data do not yet translate directly to the clinical setting, but the approach is potentially important for informing future research and illustrates that it may be possible to predict differential treatment response using a biomarker-driven approach. Stimulant Versus Nonstimulant Medication for Attention Deficit Hyperactivity Disorder in Children; https://clinicaltrials.gov/; NCT00183391. Copyright © 2017 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Investigation of Factors Affecting Body Temperature Changes During Routine Clinical Head Magnetic Resonance Imaging

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Kim, Myeong Seong

2016-01-01

Background Pulsed radiofrequency (RF) magnetic fields, required to produce magnetic resonance imaging (MRI) signals from tissue during the MRI procedure have been shown to heat tissues. Objectives To investigate the relationship between body temperature rise and the RF power deposited during routine clinical MRI procedures, and to determine the correlation between this effect and the body’s physiological response. Patients and Methods We investigated 69 patients from the Korean national cancer center to identify the main factors that contribute to an increase in body temperature (external factors and the body’s response) during a clinical brain MRI. A routine protocol sequence of MRI scans (1.5 T and 3.0 T) was performed. The patient’s tympanic temperature was recorded before and immediately after the MRI procedure and compared with changes in variables related to the body’s physiological response to heat. Results Our investigation of the physiological response to RF heating indicated a link between increasing age and body temperature. A higher increase in body temperature was observed in older patients after a 3.0-T MRI (r = 0.07, P = 0.29 for 1.5-T MRI; r = 0.45, P = 0.002 for 3.0-T MRI). The relationship between age and body heat was related to the heart rate (HR) and changes in HR during the MRI procedure; a higher RF power combined with a reduction in HR resulted in an increase in body temperature. Conclusion A higher magnetic field strength and a decrease in the HR resulted in an increase in body temperature during the MRI procedure. PMID:27895872

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

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Omid Asemani

2015-09-01

Full Text Available 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.

Comparative transcriptional analysis of clinically relevant heat stress response in Clostridium difficile strain 630.

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Nigel G Ternan

Full Text Available 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.

Clinical features and early treatment response of central nervous system involvement in childhood acute lymphoblastic leukemia

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Levinsen, Mette; Taskinen, Mervi; Abrahamsson, Jonas

2014-01-01

BACKGROUND: Central nervous system (CNS) involvement in childhood acute lymphoblastic leukemia (ALL) remains a therapeutic challenge. PROCEDURE: To explore leukemia characteristics of patients with CNS involvement at ALL diagnosis, we analyzed clinical features and early treatment response of 744...... leukemia and patients without such characteristics (0.50 vs. 0.61; P = 0.2). CONCLUSION: CNS involvement at diagnosis is associated with adverse prognostic features but does not indicate a less chemosensitive leukemia....

Just in Time Research: Data Breaches in Higher Education

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Grama, Joanna

2014-01-01

This "Just in Time" research is in response to recent discussions on the EDUCAUSE Higher Education Information Security Council (HEISC) discussion list about data breaches in higher education. Using data from the Privacy Rights Clearinghouse, this research analyzes data breaches attributed to higher education. The results from this…

Post-market clinical research conducted by medical device manufacturers: a cross-sectional survey.

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Ross, Joseph S; Blount, Katrina L; Ritchie, Jessica D; Hodshon, Beth; Krumholz, Harlan M

2015-01-01

In the US, once a medical device is made available for use, several requirements have been established by the US Food and Drug Administration (FDA) to ensure ongoing post-market surveillance of device safety and effectiveness. Our objective was to determine how commonly medical device manufacturers initiate post-market clinical studies or augment FDA post-market surveillance requirements for higher-risk devices that are most often approved via the FDA's pre-market approval (PMA) pathway. We conducted a cross-sectional survey of 47 manufacturers with operations in California, Minnesota, and Massachusetts who market devices approved via the PMA pathway. Among 22 respondents (response rate =47%), nearly all self-reported conducting post-market clinical research studies, commonly between 1 and 5; only 1 respondent reported never conducting post-market clinical research studies. While manufacturers most often engaged in these studies to satisfy FDA requirements, other reasons were reported, including performance monitoring and surveillance and market acceptance initiatives. Risks of conducting and not conducting post-market clinical research studies were described through open-ended response to questions. Medical device manufacturers commonly initiate post-market clinical studies at the request of the FDA. Clinical data from these studies should be integrated into national post-market surveillance initiatives.

Civic Engagement in Higher Education: Concepts and Practices

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Glenn A. Bowen

2012-04-01

Full Text Available As the new millennium dawned, it became clear that American higher education had done some serious soul-searching in light of concerns that it was losing distinctiveness in pursuit of prestige. Moreover, many institutions began returning to their roots in response to exhortations to take a new leadership role in preparing students for active, responsible citizenship. Ernest Boyer struck a responsive chord when he proposed the scholarship of engagement as a means whereby the academy would employ its considerable resources to tackle the social, civic, and ethical problems that beset our communities (Boyer, 1996. In 1999, higher education leaders across the country articulated their commitment to the civic purposes of their institutions as vital agents and architects of a flourishing democracy (Campus Compact, 2000. The present decade has witnessed a widespread renewal of higher education’s historical commitment to public engagement and the growth of service-learning as a pedagogical approach to developing civic knowledge and skills. However, much work remains to be done. Social problems persist, locally and globally; today’s youth view political involvement with skepticism; civic learning is lacking, or lagging. That is the basis of Civic Engagement in Higher Education: Concepts and Practices.

Effect of comorbid tics on a clinically meaningful response to 8-week open-label trial of fluoxetine in obsessive compulsive disorder.

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Husted, David S; Shapira, Nathan A; Murphy, Tanya K; Mann, Giselle D; Ward, Herbert E; Goodman, Wayne K

2007-01-01

Currently, there are limited published data evaluating the effects of tics on serotonin reuptake inhibitor (SRI) monotherapy responses in treating obsessive-compulsive disorder (OCD). One retrospective case-controlled analysis of OCD patients treated with SRI monotherapy showed lesser improvement in OCD symptoms in patients with tics than those without. However, more recently there were preliminary reports of OCD subjects treated with SRI monotherapy which did not demonstrate poorer response in subjects with tics or Tourette's Syndrome (TS). The specific aim of this study was to investigate whether the presence of comorbid chronic tics affected "clinically meaningful improvement" [McDougle, C.J., Goodman, W.K., Leckman, J.F., Barr, L.C., Heninger, G.R., Price, L.H., 1993. The efficacy of fluvoxamine in obsessive-compulsive disorder: effects of comorbid chronic tic disorder. Journal of Clinical Psychopharmacology 13, 354-358] of OCD in an 8-week open-label trial of fluoxetine monotherapy. Seventy-four adult subjects (13 patients with comorbid chronic tics and 61 patients without tics) with a primary DSM-IV OCD diagnosis were treated with up to 40mg fluoxetine for 8 weeks and had at least one post-baseline evaluation. The results indicate that there was a significant response by time in both fluoxetine-with-tic subjects and fluoxetine-without-tic subjects. Additionally, there were 3 (23.0%) OCD subjects with tics who had clinically meaningful improvement versus 16 (26.2%) OCD subjects without tics that demonstrated similar levels of improvement. These findings indicate that OCD patients with or without chronic tic disorders did not have a differential response to an 8-week open-label trial of fluoxetine. Limitations include the relatively low number of tic subjects and the open-label nature of the study. Additional data are needed on how comorbid tics may affect SRI treatment response in OCD.

Sputum eosinophilia can predict responsiveness to inhaled corticosteroid treatment in patients with overlap syndrome of COPD and asthma.

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Kitaguchi, Yoshiaki; Komatsu, Yoshimichi; Fujimoto, Keisaku; Hanaoka, Masayuki; Kubo, Keishi

2012-01-01

Chronic obstructive pulmonary disease (COPD) and asthma may overlap and converge in older people (overlap syndrome). It was hypothesized that patients with overlap syndrome may have different clinical characteristics such as sputum eosinophilia, and better responsiveness to treatment with inhaled corticosteroid (ICS). Sixty-three patients with stable COPD (forced expiratory volume in 1 second [FEV(1)] ≤80%) underwent pulmonary function tests, including reversibility of airflow limitation, arterial blood gas analysis, analysis of inflammatory cells in induced sputum, and chest high-resolution computed tomography. The inclusion criteria for COPD patients with asthmatic symptoms included having asthmatic symptoms such as episodic breathlessness, wheezing, cough, and chest tightness worsening at night or in the early morning (COPD with asthma group). The clinical features of COPD patients with asthmatic symptoms were compared with those of COPD patients without asthmatic symptoms (COPD without asthma group). The increases in FEV(1) in response to treatment with ICS were significantly higher in the COPD with asthma group. The peripheral eosinophil counts and sputum eosinophil counts were significantly higher. The prevalence of patients with bronchial wall thickening on chest high-resolution computed tomography was significantly higher. A significant correlation was observed between the increases in FEV(1) in response to treatment with ICS and sputum eosinophil counts, and between the increases in FEV(1) in response to treatment with ICS and the grade of bronchial wall thickening. Receiver operating characteristic curve analysis revealed 82.4% sensitivity and 84.8% specificity of sputum eosinophil count for detecting COPD with asthma, using 2.5% as the cutoff value. COPD patients with asthmatic symptoms had some clinical features. ICS should be considered earlier as a potential treatment in such patients. High sputum eosinophil counts and bronchial wall thickening on

Comparison of reliability and responsiveness of patient-reported clinical outcome measures in knee osteoarthritis rehabilitation.

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Williams, Valerie J; Piva, Sara R; Irrgang, James J; Crossley, Chad; Fitzgerald, G Kelley

2012-08-01

Secondary analysis, pretreatment-posttreatment observational study. To compare the reliability and responsiveness of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the Knee Outcome Survey activities of daily living subscale (KOS-ADL), and the Lower Extremity Functional Scale (LEFS) in individuals with knee osteoarthritis (OA). The WOMAC is the current standard in patient-reported measures of function in patients with knee OA. The KOS-ADL and LEFS were designed for potential use in patients with knee OA. If the KOS-ADL and LEFS are to be considered viable alternatives to the WOMAC for measuring patient-reported function in individuals with knee OA, they should have measurement properties comparable to the WOMAC. It would also be important to determine whether either of these instruments may be superior to the WOMAC in terms of reliability or responsiveness in this population. Data from 168 subjects with knee OA, who participated in a rehabilitation program, were used in the analyses. Reliability and responsiveness of each outcome measure were estimated at follow-ups of 2, 6, and 12 months. Reliability was estimated by calculating the intraclass correlation coefficient (ICC2,1) for subjects who were unchanged in status from baseline at each follow-up time, based on a global rating of change score. To examine responsiveness, the standard error of the measurement, minimal detectable change, minimal clinically important difference, and the Guyatt responsiveness index were calculated for each outcome measure at each follow-up time. All 3 outcome measures demonstrated reasonable reliability and responsiveness to change. Reliability and responsiveness tended to decrease somewhat with increasing follow-up time. There were no substantial differences between outcome measures for reliability or any of the 3 measures of responsiveness at any follow-up time. The results do not indicate that one outcome measure is more reliable or responsive than

[Autoimmune hepatitis in children and adolescents: clinical study, diagnosis and therapeutic response].

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Ferreira, Alexandre R; Roquete, Mariza L V; Penna, Francisco J; Toppa, Nivaldo H

2002-01-01

The aim of this study was to evaluate the clinical, laboratory and histopathological characteristics and the response to immunosuppression in children and adolescents with autoimmune hepatitis (AIH). The present research is a descriptive study consisting of 39 children and adolescents with AIH who receive care at the Department of Pediatric Gastroenterology of Hospital das Clínicas (UFMG) from 1986 to 1998. Children's age ranged from 1.6 to 17 years (mean 8.7 +/- 3.49), most of them were females (87.2%). There were three types of clinical presentations: chronic (53.9%), acute (41%), and serious hepatic failure (5.1%). The most relevant laboratory parameters were the aminotransferases and gamma-globulin increase. Antinuclear antibodies were positive in 66.7% of the patients, while smooth muscle antibodies were positive in 52.8% and anti-LKM1 in 3% of the patients. In the histopathology the most important findings were the piecemeal necrosis (93.7%), moderate to severe portal inflammation (78.1%), definitive or incomplete cirrhosis (76.9%), absence of lesion of biliary ducts (93.7%) and presence of rosettes (90.6%). During the treatment, 77.8% obtained complete resolution, associated to side effects in 27.8% of them. Seven patients died (17.9%). During the treatment there was significant z score reduction (p<0.05) for height/age. After carrying out this study, we observed that the typical characteristics of AIH were: female sex, several clinical presentations, increased aminotransferase, and hypergammaglobulinemia. Histopathology showed a predominance of incipient and/or definitive cirrhosis associated with moderate to severe portal inflammation and piecemeal necrosis. Treatment using corticosteroids and azathioprine, turned out to be effective. However, the reduction in the height/age z score probably represents an adverse effect of corticoid treatment.

High clinical and morphologic response using 90Y-DOTA-octreotate sequenced with 177Lu-DOTA-octreotate induction peptide receptor chemoradionuclide therapy (PRCRT) for bulky neuroendocrine tumours.

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Kong, Grace; Callahan, Jason; Hofman, Michael S; Pattison, David A; Akhurst, Tim; Michael, Michael; Eu, Peter; Hicks, Rodney J

2017-03-01

Bulky disease is an adverse prognostic factor for 177 Lu-DOTA-octreotate ( 177 Lu-DOTATATE) peptide receptor radionuclide therapy (PRRT). 90 Y-DOTA-octreotate ( 90 Y-DOTATATE) has theoretical advantages in this setting but may less effectively treat co-existent smaller deposits and have higher toxicity than 177 Lu-DOTATATE. The aim of this study was to assess the efficacy and safety of using these agents sequentially. We reviewed patients (pts) with at least one lesion of a transaxial diameter >4 cm who completed 1-2 cycles of 90 Y-DOTATATE followed by 2-3 cycles of 177 Lu-DOTATATE, with treatment empirically adapted to disease size and burden in individual patients. Data collected included morphological and molecular imaging response, toxicity, and progression-free and overall survival. Twenty-six pts (17 men; aged 27-74 years) received a median cumulative activity of 6.5 GBq 90 Y-DOTATATE, and 21 GBq 177 Lu-DOTATATE. All but one received radiosensitising chemotherapy. Adverse prognostic factors included ENETS grade 2 or 3 in 58 %, and FDG-avid disease in 73 %. Nineteen pts treated for progressive disease had stabilisation (37 %) or regression on CT (42 % partial response, 21 % minor response), with a mean 59 % (8-99 %) reduction in disease burden. All seven pts treated for uncontrolled symptoms reported improvement during PRRT with 4/7 having complete symptom resolution at 3 months. Eight patients had grade 3/4 lymphopaenia, and two patients grade 3/4 thrombocytopaenia without significant hepatic or renal toxicity. Median survival was not reached after a median follow-up of 35 months. Median progression-free survival was 33 months. PRCRT with 90 Y -DOTATATE followed by 177 Lu-DOTATATE in individualised regimens achieved high clinical and morphological response in patients with bulky tumours. Despite lack of a control arm, the efficacy of this treatment approach appears higher than reported results with either agent used alone or other approved

Network Mechanisms of Clinical Response to Transcranial Magnetic Stimulation in Posttraumatic Stress Disorder and Major Depressive Disorder.

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Philip, Noah S; Barredo, Jennifer; van 't Wout-Frank, Mascha; Tyrka, Audrey R; Price, Lawrence H; Carpenter, Linda L

2018-02-01

Repetitive transcranial magnetic stimulation (TMS) therapy can modulate pathological neural network functional connectivity in major depressive disorder (MDD). Posttraumatic stress disorder is often comorbid with MDD, and symptoms of both disorders can be alleviated with TMS therapy. This is the first study to evaluate TMS-associated changes in connectivity in patients with comorbid posttraumatic stress disorder and MDD. Resting-state functional connectivity magnetic resonance imaging was acquired before and after TMS therapy in 33 adult outpatients in a prospective open trial. TMS at 5 Hz was delivered, in up to 40 daily sessions, to the left dorsolateral prefrontal cortex. Analyses used a priori seeds relevant to TMS, posttraumatic stress disorder, or MDD (subgenual anterior cingulate cortex [sgACC], left dorsolateral prefrontal cortex, hippocampus, and basolateral amygdala) to identify imaging predictors of response and to evaluate clinically relevant changes in connectivity after TMS, followed by leave-one-out cross-validation. Imaging results were explored using data-driven multivoxel pattern activation. More negative pretreatment connectivity between the sgACC and the default mode network predicted clinical improvement, as did more positive amygdala-to-ventromedial prefrontal cortex connectivity. After TMS, symptom reduction was associated with reduced connectivity between the sgACC and the default mode network, left dorsolateral prefrontal cortex, and insula, and reduced connectivity between the hippocampus and the salience network. Multivoxel pattern activation confirmed seed-based predictors and correlates of treatment outcomes. These results highlight the central role of the sgACC, default mode network, and salience network as predictors of TMS response and suggest their involvement in mechanisms of action. Furthermore, this work indicates that there may be network-based biomarkers of clinical response relevant to these commonly comorbid disorders

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

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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

Indication of attenuated DHEA-s response during acute psychosocial stress in patients with clinical burnout.

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Lennartsson, Anna-Karin; Sjörs, Anna; Jonsdottir, Ingibjörg H

2015-08-01

Dehydroepiandrosterone sulphate (DHEA-s) is an anabolic protective hormone. We have previously reported that DHEA-s production capacity is attenuated in stressed individuals. The aim of the present study was to investigate the DHEA-s response during acute psychosocial stress in patients with clinical burnout. Seventeen patients with clinical burnout were compared to 13 non-chronically stressed healthy controls, aged 31-50 years (mean age 41 years, SD 6 years), as they underwent the Trier Social Stress Test (TSST). All patients fulfilled diagnostic criteria for stress-related exhaustion disorder, which is a criteria-based diagnosis that has been used in Sweden since 2005 to define patients seeking health-care for clinical burnout. Blood samples were collected before, directly after the stress test, and after 30 min of recovery. DHEA-s levels were measured and delta values (peak levels minus baseline levels) plus area under the curve with respect to increase (AUCI) were calculated. The patients had 43% smaller AUCI DHEA-s (p=0.041) during the stress test. The delta DHEA-s was 34% lower in the patients, however, this difference was not statistically significant (p=0.054). The study indicates that DHEA-s production capacity during acute stress may be attenuated in patients with clinical burnout. Reduced DHEA-s production may constitute one of the links between stress, burnout and the associated adverse health. Copyright © 2015 Elsevier Inc. All rights reserved.

Identifying clinically meaningful symptom response cut-off values on the SANS in predominant negative symptoms.

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Levine, Stephen Z; Leucht, Stefan

2013-04-01

The treatment and measurement of negative symptoms are currently at issue in schizophrenia, but the clinical meaning of symptom severity and change is unclear. To offer a clinically meaningful interpretation of severity and change scores on the Scale for the Assessment of Negative Symptoms (SANS). Patients were intention-to-treat participants (n=383) in two double-blind randomized placebo-controlled clinical trials that compared amisulpride with placebo for the treatment of predominant negative symptoms. Equipercentile linking was used to examine extrapolation from (a) CGI-S to SANS severity ratings, and (b) CGI-I to SANS percentage change (n=383). Linking was conducted at baseline, 8-14 days, 28-30 days, and 56-60 days of the trials. Across visits, CGI-S ratings of 'not ill' linked to SANS scores of 0-13, and ranged to 'extreme' ratings that linked to SANS scores of 102-105. The relationship between the CGI-S and the SANS severity scores assumed a linear trend (1=0-13, 2=15-56, 3=37-61, 4=49-66, 5=63-75, 6=79-89, 7=102-105). Similarly the relationship between CGI-I ratings and SANS percentage change followed a linear trend. For instance, CGI-I ratings of 'very much improved' were linked to SANS percent changes of -90 to -67, 'much improved' to -50 to -42, and 'minimally improved' to -21 to -13. The current results uniquely contribute to the debate surrounding negative symptoms by providing clinical meaning to SANS severity and change scores and so offer direction regarding clinically meaningful response cut-off scores to guide treatment targets of predominant negative symptoms. Copyright © 2013 Elsevier B.V. All rights reserved.

Students' approaches to learning in a clinical practicum: A psychometric evaluation based on item response theory.

Science.gov (United States)

Zhao, Yue; Kuan, Hoi Kei; Chung, Joyce O K; Chan, Cecilia K Y; Li, William H C

2018-07-01

The investigation of learning approaches in the clinical workplace context has remained an under-researched area. Despite the validation of learning approach instruments and their applications in various clinical contexts, little is known about the extent to which an individual item, that reflects a specific learning strategy and motive, effectively contributes to characterizing students' learning approaches. This study aimed to measure nursing students' approaches to learning in a clinical practicum using the Approaches to Learning at Work Questionnaire (ALWQ). Survey research design was used in the study. A sample of year 3 nursing students (n = 208) who undertook a 6-week clinical practicum course participated in the study. Factor analyses were conducted, followed by an item response theory analysis, including model assumption evaluation (unidimensionality and local independence), item calibration and goodness-of-fit assessment. Two subscales, deep and surface, were derived. Findings suggested that: (a) items measuring the deep motive from intrinsic interest and deep strategies of relating new ideas to similar situations, and that of concept mapping served as the strongest discriminating indicators; (b) the surface strategy of memorizing facts and details without an overall picture exhibited the highest discriminating power among all surface items; and, (c) both subscales appeared to be informative in assessing a broad range of the corresponding latent trait. The 21-item ALWQ derived from this study presented an efficient, internally consistent and precise measure. Findings provided a useful psychometric evaluation of the ALWQ in the clinical practicum context, added evidence to the utility of the ALWQ for nursing education practice and research, and echoed the discussions from previous studies on the role of the contextual factors in influencing student choices of different learning strategies. They provided insights for clinical educators to measure

Clinical Pharmacopsychology

DEFF Research Database (Denmark)

Fava, Giovanni A.; Tomba, Elena; Bech, Per

2017-01-01

of its most representative expressions and reference to current challenges of clinical research, with particular reference to clinimetrics. The domains of clinical pharmacopsychology encompass the clinical benefits of psychotropic drugs, the characteristics that predict responsiveness to treatment...... effects, (b) treatment-induced unwanted side effects, and (c) the patient's own personal experience of a change in terms of well-being and/or quality of life. Clinical pharmacopsychology offers a unifying framework for the understanding of clinical phenomena in medical and psychiatric settings. Research......The aim of this critical review was to outline emerging trends and perspectives of clinical pharmacopsychology, an area of clinical psychology that is concerned with the psychological effects of medications. The historical development of clinical pharmacopsychology is outlined, with discussion...

Clinical characteristics and therapeutic response in patients with Burning Mouth Syndrome: accompanying 2 years

Directory of Open Access Journals (Sweden)

Vanessa Juliana Gomes CARVALHO

Full Text Available Abstract Introduction Burning Mouth Syndrome (BMS is a condition characterized by burning symptom of the oral mucosa in the absence of clinical signs. Its etiology is still unknown and, and to date there is no effective treatment. Purpose The aim of this study was to evaluate patients with BMS profile and the therapies results in a retrospective study. Material and method Clinical and therapeutic data were collected from records of patients with BMS diagnosed between January 2013 to April 2015 at the Clinic of Stomatology Clinic, Faculdade de Odontologia of Universidade de São Paulo, according to the criteria established by the International Headache Society in 2013. The therapies used for BMS control were also evaluated. Result Twelve patients were diagnosed with BMS at this period. All of them were women with a mean age of 61.18 years and the apex of the tongue was the most common affected site and the duration of the burning sensation ranged from 6 months to 25 years. Many therapies were prescribed for BMS control, such as topical capsaicin, topical clonazepan, low level laser therapy and homeopathy. Among the established therapies, capsaicin has immediate effect in reducing symptoms. Conclusion The present study showed that the challenges towards an effective treatment for BMS are varied and are mainly related to the lack knowing of the pathogenesis of this disease. The demographic profile of patients studied here was similar to that described in the available literature, however, the variables represented by secondary symptoms (medical history, anxiety and depression levels may be modifying factors of therapeutic response and the pathogenesis of the disease itself.

Relation between N-terminal pro-brain natriuretic peptide levels and response to enhanced external counterpulsation in chronic angina pectoris.

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Sahlén, Anders; Wu, Eline; Rück, Andreas; Hagerman, Inger; Förstedt, Gunilla; Sylvén, Christer; Berglund, Margareta; Jernberg, Tomas

2014-01-01

Although enhanced external counterpulsation (EECP) provides symptom reduction in many patients with severe angina pectoris, one-quarter of patients fail to respond. Earlier reports have not clearly established whether and how EECP responders may be identified pre-hoc. We hypothesized that clinical and biochemical data may be used to predict EECP response. We explored a database of n=53 patients who had undergone clinically indicated EECP during 35 1-h sessions in our unit (65±7 years; 49 male), and sought to clarify which factors are predictive of response. Efficiency of counterpulsation was measured as the diastolic augmentation (DA) ratio, and was recorded both at beginning and end of the EECP treatment course. An increase in 6-min walk (6MW) distance of 5% was indicative of clinical response. Response occurred in 28 patients (53%; nonresponse in n=25, 47%). Responders had shorter baseline 6MW distance (377±81 vs. 445±62 m; P<0.01), lower left ventricular ejection fraction (48±9 vs. 54±8%; P<0.05), frequently had an increase in DA ratio during the EECP treatment course (23/28 vs. 5/28 with unchanged or decreased DA ratio; P<0.05), and higher levels of N-terminal pro-brain natriuretic peptide [NT-proBNP; 256 (123-547) vs. 62 (26-444) ng/l, P<0.01]. In multivariate logistic regression, response was independently predicted by baseline 6MW distance and baseline NT-proBNP levels (P<0.05 for both; model sensitivity: 82%, specificity: 72%, accuracy: 79%). There is larger clinical benefit of EECP in patients with greater functional impairment and higher levels of NT-proBNP.

Bioprinted 3D Primary Liver Tissues Allow Assessment of Organ-Level Response to Clinical Drug Induced Toxicity In Vitro.

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Deborah G Nguyen

Full Text Available 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.

“Always Look on the Bright Side of Life!” – Higher Hypomania Scores Are Associated with Higher Mental Toughness, Increased Physical Activity, and Lower Symptoms of Depression and Lower Sleep Complaints

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Leila Jahangard

2017-12-01

Full Text Available Background: In the present study, we explored the associations between hypomania, symptoms of depression, sleep complaints, physical activity and mental toughness. The latter construct has gained interest for its association with a broad variety of favorable behavior in both clinical and non-clinical samples.Subjects and Methods: The non-clinical sample consisted of 206 young adults (M = 21.3 years; age range: 18–24 years; 57.3% males. They completed questionnaires covering hypomania, mental toughness, symptoms of depression, physical activity, and sleep quality.Results: Higher hypomania scores were associated with higher mental toughness, increased physical activity, lower symptoms of depression and lower sleep complaints. No gender differences were observed. Higher hypomania scores were predicted by higher scores of mental toughness subscales of control and challenge, and physical activity.Conclusion: The pattern of results suggests that among a non-clinical sample of young adults, self-rated hypomania scores were associated with higher scores on mental toughness and physical activity, along with lower depression and sleep complaints. The pattern of results further suggests that hypomania traits are associated with a broad range of favorable psychological, behavioral and sleep-related traits, at least among a non-clinical sample of young adults.

Serum Cytokine Responses over the Entire Clinical-Immunological Spectrum of Human Leishmania (L. infantum chagasi Infection

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Patrícia Karla Ramos

2016-01-01

Full Text Available The clinical-immunological spectrum of human Leishmania (L. infantum chagasi infection in Amazonian Brazil was recently reviewed based on clinical, DTH, and IFAT (IgG evaluations that identified five profiles: three asymptomatic (asymptomatic infection, AI; subclinical resistant infection, SRI; and indeterminate initial infection, III and two symptomatic (symptomatic infection, SI; American visceral leishmaniasis, AVL; and subclinical oligosymptomatic infection, SOI. TNF-α, IL-4, IL-6, and IL-10 serum cytokines were analyzed using multiplexed Cytometric Bead Array in 161 samples from endemic areas in the Brazilian Amazon: SI [AVL] (21 cases, III (49, SRI (19, SOI (12, AI (36, and a control group [CG] (24. The highest IL-6 serum levels were observed in the SI profile (AVL; higher IL-10 serum levels were observed in SI than in SOI or CG and in AI and III than in SOI; higher TNF-α serum levels were seen in SI than in CG. Positive correlations were found between IL-6 and IL-10 serum levels in the SI and III profiles and between IL-6 and TNF-α and between IL-4 and TNF-α in the III profile. These results provide strong evidence for associating IL-6 and IL-10 with the immunopathogenesis of AVL and help clarify the role of these cytokines in the infection spectrum.

Dogs cannot bark: event-related brain responses to true and false negated statements as indicators of higher-order conscious processing.

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Herbert, Cornelia; Kübler, Andrea

2011-01-01

The present study investigated event-related brain potentials elicited by true and false negated statements to evaluate if discrimination of the truth value of negated information relies on conscious processing and requires higher-order cognitive processing in healthy subjects across different levels of stimulus complexity. The stimulus material consisted of true and false negated sentences (sentence level) and prime-target expressions (word level). Stimuli were presented acoustically and no overt behavioral response of the participants was required. Event-related brain potentials to target words preceded by true and false negated expressions were analyzed both within group and at the single subject level. Across the different processing conditions (word pairs and sentences), target words elicited a frontal negativity and a late positivity in the time window from 600-1000 msec post target word onset. Amplitudes of both brain potentials varied as a function of the truth value of the negated expressions. Results were confirmed at the single-subject level. In sum, our results support recent suggestions according to which evaluation of the truth value of a negated expression is a time- and cognitively demanding process that cannot be solved automatically, and thus requires conscious processing. Our paradigm provides insight into higher-order processing related to language comprehension and reasoning in healthy subjects. Future studies are needed to evaluate if our paradigm also proves sensitive for the detection of consciousness in non-responsive patients.

Dogs cannot bark: event-related brain responses to true and false negated statements as indicators of higher-order conscious processing.

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Cornelia Herbert

Full Text Available The present study investigated event-related brain potentials elicited by true and false negated statements to evaluate if discrimination of the truth value of negated information relies on conscious processing and requires higher-order cognitive processing in healthy subjects across different levels of stimulus complexity. The stimulus material consisted of true and false negated sentences (sentence level and prime-target expressions (word level. Stimuli were presented acoustically and no overt behavioral response of the participants was required. Event-related brain potentials to target words preceded by true and false negated expressions were analyzed both within group and at the single subject level. Across the different processing conditions (word pairs and sentences, target words elicited a frontal negativity and a late positivity in the time window from 600-1000 msec post target word onset. Amplitudes of both brain potentials varied as a function of the truth value of the negated expressions. Results were confirmed at the single-subject level. In sum, our results support recent suggestions according to which evaluation of the truth value of a negated expression is a time- and cognitively demanding process that cannot be solved automatically, and thus requires conscious processing. Our paradigm provides insight into higher-order processing related to language comprehension and reasoning in healthy subjects. Future studies are needed to evaluate if our paradigm also proves sensitive for the detection of consciousness in non-responsive patients.

Clinical Initial Response of Neoadjuvant Chemotheraphy in Triple Negative, HER-2, and Luminal Types of Breast Cancer in Denpasar (A Preliminary Study

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Kristianto Yuli Yarso

2012-01-01

Full Text Available Objectives: Triple Negative, Luminal, HER-2 subtypes of breast cancer are markers to predict behavior, aggressiveness, and response to chemotherapy. The aim of this study is to understand character and response to standard neoadjuvant chemotherapy in different subtypes of breast cancer. Method: This is a descriptive study of breast cancer subtypes. From 687 patients (2003-2010 351 patients have IHC data which divided into 3 groups, Triple negative, Luminal, and HER-2. We used 10% as a cut off point for ER, PR, while 30% & positive 3 for HER-2. We determined initial clinical response after 3 cycles of neoadjuvant chemotherapy although only 77 got standard neoadjuvant chemotherapy and had clinical response data. We used 50% diameters depreciation & no metastasis as cut off point for respond group. Results: There were 116 (33% Triple Negative, 60 (17% HER-2, and 175 (50% Luminal Subtypes. The mean of age for 351 patients are 48.32 (23-82 years. In this study, it was obtained that no significant difference of means of age (p=0.24 in these 3 groups. Triple negative group significantly more advance in grade if compared with the other two groups (p=0.02. HER-2 group had highest response with standard neoadjuvant chemotherapy (50%, Luminal group had (49%, and Triple negative group had only (15% response. One pCR in HER-2 group. There were no difference ages in subtypes. Triple negative has more advances in grade. HER-2 group has highest response to standard neoadjuvant chemotherapy and Triple negative has lowest response to standard neoadjuvant chemotherapy.

fMRI investigation of response inhibition, emotion, impulsivity, and clinical high-risk behaviour in adolescents

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Matthew R G Brown

2015-09-01

Full Text Available High-risk behaviour in adolescents is associated with injury, mental health problems, and poor outcomes in later life. Improved understanding of the neurobiology of high-risk behaviour and impulsivity shows promise for informing clinical treatment and prevention as well as policy to better address high-risk behaviour. We recruited 21 adolescents (age 14-17 with a wide range of high-risk behaviour tendencies, including medically high-risk participants recruited from psychiatric clinics. Risk tendencies were assessed using the Adolescent Risk Behaviour Screen (ARBS. ARBS risk scores correlated highly (0.78 with impulsivity scores from the Barratt Impulsivity scale (BIS. Participants underwent 4.7 Tesla functional magnetic resonance imaging (fMRI while performing an emotional Go/NoGo task. This task presented an aversive or neutral distractor image simultaneously with each Go or NoGo stimulus. Risk behaviour and impulsivity tendencies exhibited similar but not identical associations with fMRI activation patterns in prefrontal brain regions. We interpret these results as reflecting differences in response inhibition, emotional stimulus processing, and emotion regulation in relation to participant risk behaviour tendencies and impulsivity levels. The results are consistent with high impulsivity playing an important role in determining high risk tendencies in this sample containing clinically high-risk adolescents.

fMRI investigation of response inhibition, emotion, impulsivity, and clinical high-risk behavior in adolescents.

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Brown, Matthew R G; Benoit, James R A; Juhás, Michal; Dametto, Ericson; Tse, Tiffanie T; MacKay, Marnie; Sen, Bhaskar; Carroll, Alan M; Hodlevskyy, Oleksandr; Silverstone, Peter H; Dolcos, Florin; Dursun, Serdar M; Greenshaw, Andrew J

2015-01-01

High-risk behavior in adolescents is associated with injury, mental health problems, and poor outcomes in later life. Improved understanding of the neurobiology of high-risk behavior and impulsivity shows promise for informing clinical treatment and prevention as well as policy to better address high-risk behavior. We recruited 21 adolescents (age 14-17) with a wide range of high-risk behavior tendencies, including medically high-risk participants recruited from psychiatric clinics. Risk tendencies were assessed using the Adolescent Risk Behavior Screen (ARBS). ARBS risk scores correlated highly (0.78) with impulsivity scores from the Barratt Impulsivity scale (BIS). Participants underwent 4.7 Tesla functional magnetic resonance imaging (fMRI) while performing an emotional Go/NoGo task. This task presented an aversive or neutral distractor image simultaneously with each Go or NoGo stimulus. Risk behavior and impulsivity tendencies exhibited similar but not identical associations with fMRI activation patterns in prefrontal brain regions. We interpret these results as reflecting differences in response inhibition, emotional stimulus processing, and emotion regulation in relation to participant risk behavior tendencies and impulsivity levels. The results are consistent with high impulsivity playing an important role in determining high risk tendencies in this sample containing clinically high-risk adolescents.

Development of criteria for evaluating clinical response in thyroid eye disease using a modified Delphi technique

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Douglas, Raymond S; Tsirbas, Angelo; Gordon, Mark

2009-01-01

OBJECTIVE: To identify components of a provisional clinical response index for thyroid eye disease using a modified Delphi technique. METHODS: The International Thyroid Eye Disease Society conducted a structured, 3-round Delphi exercise establishing consensus for a core set of measures for clinical...... 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 8 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 because of 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. CONCLUSIONS: Using a Delphi...

Nasal nitric oxide is associated with exhaled NO, bronchial responsiveness and poor asthma control.

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Krantz, C; Janson, C; Borres, M P; Nordvall, L; Alving, K; Malinovschi, A

2014-06-01

The fraction of exhaled nitric oxide (FeNO) is an established marker of airway inflammation in asthma. Nasal nitric oxide (nNO) has initially been regarded as a promising marker of inflammation of nasal mucosa. However, due to its dual origins, paranasal sinuses and nasal mucosa, the clinical use of nNO is controversial. There is an inflammatory link between inflammation in the upper and lower airways within the united airways' paradigm, but the study of the clinical value of nNO in asthma has been limited. The objective of this study is to analyse nNO in asthmatics and its relationship to FeNO, bronchial hyperresponsiveness, allergic sensitization and asthma control. A total of 371 children and young adults from an asthma cohort were included in this study, which performed measurements of nNO (through aspiration at 5 mL s(-1)), FeNO, bronchial responsiveness to methacholine, blood eosinophil count (B-Eos) and IgE sensitization. The asthma control test (ACT) and a questionnaire regarding medical treatment, symptoms of asthma, rhinitis and chronic rhinosinusitis were completed by all subjects. An association was found between higher nNO levels and increased bronchial responsiveness (p < 0.001), FeNO (p < 0.001) and B-Eos (p = 0.002). Sensitization to furry animals related to higher levels of nNO (p < 0.001). Subjects with poorly controlled asthma (ACT < 15) had lower levels of nNO than subjects with a higher ACT score (619 ± 278 ppb, versus 807 ± 274 ppb, p = 0.002). Loss of smell showed the strongest association with lower nNO levels among the upper airway symptoms recorded. In patients with asthma, nNO was positively correlated with exhaled NO, bronchial responsiveness and asthma control. This study suggests clinical utility of nNO in subjects with asthma, but in order to get better understanding of the nNO determinants, simultaneous mapping of upper airway comorbidities by clinical examination is appropriate.

A neurocognitive comparison of cognitive flexibility and response inhibition in gamblers with varying degrees of clinical severity.

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Odlaug, B L; Chamberlain, S R; Kim, S W; Schreiber, L R N; Grant, J E

2011-10-01

As a behavioral addiction with clinical and phenomenological similarities to substance addiction, recreational and pathological gambling represent models for studying the neurobiology of addiction, without the confounding deleterious brain effects which may occur from chronic substance abuse. A community sample of individuals aged 18-65 years who gamble was solicited through newspaper advertising. Subjects were grouped a priori into three groups (no-risk, at-risk, and pathological gamblers) based on a diagnostic interview. All subjects underwent a psychiatric clinical interview and neurocognitive tests assessing motor impulsivity and cognitive flexibility. Subjects with a current axis I disorder, history of brain injury/trauma, or implementation or dose changes of psychoactive medication within 6 weeks of study enrollment were excluded. A total of 135 no-risk, 69 at-risk and 46 pathological gambling subjects were assessed. Pathological gamblers were significantly older, and exhibited significant deficiencies in motor impulse control (stop-signal reaction times), response speed (median 'go' trial response latency) and cognitive flexibility [total intra-dimensional/extra-dimensional (IDED) errors] versus controls. The finding of impaired impulse control and cognitive flexibility was robust in an age-matched subgroup analysis of pathological gamblers. The no-risk and at-risk gambling groups did not significantly differ from each other on task performance. Impaired response inhibition and cognitive flexibility exist in people with pathological gambling compared with no-risk and at-risk gamblers. The early identification of such illness in adolescence or young adulthood may aid in the prevention of addiction onset of such disabling disorders.

Non-Esterified Fatty Acids Profiling in Rheumatoid Arthritis: Associations with Clinical Features and Th1 Response.

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Javier Rodríguez-Carrio

Full Text Available Since lipid compounds are known to modulate the function of CD4+ T-cells and macrophages, we hypothesize that altered levels of serum non-esterified fatty acids (NEFA may underlie rheumatoid arthritis (RA pathogenesis.Serum levels of NEFA (palmitic, stearic, palmitoleic, oleic, linoleic, γ-linoleic, arachidonic -AA-, linolenic, eicosapentaenoic -EPA- and docosahexaenoic -DHA- were quantified by LC-MS/MS after methyl-tert-butylether (MTBE-extraction in 124 RA patients and 56 healthy controls (HC. CD4+ phenotype was studied by flow cytometry. TNFα, IL-8, VEGF, GM-CSF, IFNγ, IL-17, CCL2, CXCL10, leptin and resistin serum levels were quantified by immunoassays. The effect of FA on IFNγ production by PBMC was evaluated in vitro.Lower levels of palmitic (p<0.0001, palmitoleic (p = 0.002, oleic (p = 0.010, arachidonic (p = 0.027, EPA (p<0.0001 and DHA (p<0.0001 were found in RA patients, some NEFA being altered at onset. Cluster analysis identified a NEFA profile (hallmarked by increased stearic and decreased EPA and DHA overrepresented in RA patients compared to HC (p = 0.002, being associated with clinical features (RF, shared epitope and erosions, increased IFNγ expression in CD4+ T-cells (p = 0.002 and a Th1-enriched serum milieu (IFNγ, CCL2 and CXCL10, all p<0.005. In vitro assays demonstrated that imbalanced FA could underlie IFNγ production by CD4+ T-cells. Finally, changes on NEFA levels were associated with clinical response upon TNFα-blockade.An altered NEFA profile can be found in RA patients associated with clinical characteristics of aggressive disease and enhanced Th1 response. These results support the relevance of lipidomic studies in RA and provide a rationale for new therapeutic targets.

A Parent-Mediated Intervention to Increase Responsive Parental Behaviors and Child Communication in Children with ASD: A Randomized Clinical Trial

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Siller, Michael; Hutman, Ted; Sigman, Marian

2013-01-01

Longitudinal research has demonstrated that responsive parental behaviors reliably predict subsequent language gains in children with autism spectrum disorder. To investigate the underlying causal mechanisms, we conducted a randomized clinical trial of an experimental intervention (Focused Playtime Intervention, FPI) that aims to enhance…

Attenuation of the pressor response to exogenous angiotensin by angiotensin receptor blockers and benazepril hydrochloride in clinically normal cats.

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Jenkins, Tiffany L; Coleman, Amanda E; Schmiedt, Chad W; Brown, Scott A

2015-09-01

To compare the attenuation of the angiotensin I-induced blood pressure response by once-daily oral administration of various doses of angiotensin receptor blockers (irbesartan, telmisartan, and losartan), benazepril hydrochloride, or lactose monohydrate (placebo) for 8 days in clinically normal cats. 6 healthy cats (approx 17 months old) with surgically implanted arterial telemetric blood pressure-measuring catheters. Cats were administered orally the placebo or each of the drug treatments (benazepril [2.5 mg/cat], irbesartan [6 and 10 mg/kg], telmisartan [0.5, 1, and 3 mg/kg], and losartan [2.5 mg/kg]) once daily for 8 days in a crossover study. Approximately 90 minutes after capsule administration on day 8, each cat was anesthetized and arterial blood pressure measurements were recorded before and after IV administration of each of 4 boluses of angiotensin I (20, 100, 500, and 1,000 ng/kg). This protocol was repeated 24 hours after benazepril treatment and telmisartan (3 mg/kg) treatment. Differences in the angiotensin I-induced change in systolic arterial blood pressure (ΔSBP) among treatments were determined. At 90 minutes after capsule administration, only losartan did not significantly reduce ΔSBP in response to the 3 higher angiotensin doses, compared with placebo. Among drug treatments, telmisartan (3 mg/kg dosage) attenuated ΔSBP to a significantly greater degree than benazepril and all other treatments. At 24 hours, telmisartan was more effective than benazepril (mean ± SEM ΔSBP, 15.7 ± 1.9 mm Hg vs 55.9 ± 12.42 mm Hg, respectively). Results indicated that telmisartan administration may have advantages over benazepril administration for cats with renal or cardiovascular disease.

Does the rising placebo response impact antihypertensive clinical trial outcomes? An analysis of data from the Food and Drug Administration 1990-2016.

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Arif Khan

Full Text Available Recent studies show that placebo response has grown significantly over time in clinical trials for antidepressants, ADHD medications, antiepileptics, and antidiabetics. Contrary to expectations, trial outcome measures and success rates have not been impacted. This study aimed to see if this trend of increasing placebo response and stable efficacy outcome measures is unique to the conditions previously studied or if it occurs in trials for conditions with physiologically-measured symptoms, such as hypertension.For this reason, we evaluated the efficacy data reported in the US Food and Drug Administration Medical and Statistical reviews for 23 antihypertensive programs (32,022 patients, 63 trials, 142 treatment arms. Placebo and medication response, effect sizes, and drug-placebo differences were calculated for each treatment arm and examined over time using meta-regression. We also explored the relationship of sample size, trial duration, baseline blood pressure, and number of treatment arms to placebo/drug response and efficacy outcome measures.Like trials of other conditions, placebo response has risen significantly over time (R2 = 0.093, p = 0.018 and effect size (R2 = 0.013, p = 0.187 drug-placebo difference (R2 = 0.013, p = 0.182 and success rate (134/142, 94.4% have remained unaffected, likely due to a significant compensatory increase in antihypertensive response (R2 = 0.086, p<0.001. Treatment arms are likely overpowered with sample sizes increasing over time (R2 = 0.387, p<0.0001 and stable, large effect sizes (0.78 ±0.37. The exploratory analysis of sample size, trial duration, baseline blood pressure, and number of treatment arms yielded mixed results unlikely to explain the pattern of placebo response and efficacy outcomes over time. The magnitude of placebo response had no relationship to effect size (p = 0.877, antihypertensive-placebo differences (p = 0.752, or p-values (p = 0.963 but was correlated with antihypertensive response