Exercise Blood Pressure Guidelines: Time to Re-evaluate What is Normal and Exaggerated?

PubMed

Currie, Katharine D; Floras, John S; La Gerche, Andre; Goodman, Jack M

2018-03-24

Blood pressure responses to graded exercise testing can provide important diagnostic and prognostic information. While published guidelines outline what constitutes a "normal" and "abnormal" (i.e., exaggerated) blood pressure response to exercise testing, the widespread use of exaggerated blood pressure responses as a clinical tool is limited due to sparse and inconsistent data. A review of the original sources from these guidelines reveals an overall lack of empirical evidence to support both the normal blood pressure responses and their upper limits. In this current opinion, we critically evaluate the current exercise blood pressure guidelines including (1) the normal blood pressure responses to graded exercise testing; (2) the upper limits of this normal response; (3) the blood pressure criteria for test termination; and (4) the thresholds for exaggerated blood pressure responses. We provide evidence that exercise blood pressure responses vary according to subject characteristics, and subsequently a re-evaluation of what constitutes normal and abnormal responses is necessary to strengthen the clinical utility of this assessment.

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

PubMed Central

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

2012-01-01

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

Brain tumor response to nimotuzumab treatment evaluated on magnetic resonance imaging.

PubMed

Dalmau, Evelio Rafael González; Cabal Mirabal, Carlos; Martínez, Giselle Saurez; Dávila, Agustín Lage; Suárez, José Carlos Ugarte; Cabanas Armada, Ricardo; Rodriguez Cruz, Gretel; Darias Zayas, Daniel; Castillo, Martha Ríos; Valle Garrido, Luis; Sotolongo, Luis Quevedo; Fernández, Mercedes Monzón

2014-02-01

Nimotuzumab, a humanized monoclonal antibody anti-epidermal growth factor receptor, has been shown to improve survival and quality of life in patients with pediatric malignant brain tumor. It is necessary, however, to increase the objective response criteria to define the optimal therapeutic schedule. The aim of this study was to obtain magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) quantitative information related to dimensions and morphology, molecular mobility and metabolic activity of the lesion and surroundings in order to evaluate any changes through time. Fourteen pediatric patients treated with nimotuzumab were evaluated on MRI and MRS for >2 years. Each patient was their own control. The MRI/MRS pulse sequence parameters were standardized to ensure experimental reproducibility. A total of 71.4% of patients had stable disease; 21.4% had objective response and 7.1% had progression of disease during the >2 year evaluation period. MRI/MRS data with clinical information provide a clearer picture of treatment response and confirm once again that nimotuzumab is effective in the treatment of pediatric brain tumor. These imaging procedures can be a useful tool for the clinical evaluation of study protocol in clinical practice. © 2013 The Authors. Pediatrics International © 2013 Japan Pediatric Society.

What is the benefit of treatment with multiple lines of chemotherapy for patients with metastatic breast cancer? A retrospective cohort study.

PubMed

Bakker, J L; Wever, K; van Waesberghe, J H; Beeker, A; Meijers-Heijboer, H; Konings, I R; Verheul, H M W

2015-12-01

Despite the extensive clinical experience, it is still under debate to what extent patients with metastatic breast cancer (MBC) benefit from multiple lines of chemotherapy beyond standard first or second line treatment. Selection of patients with MBC who will benefit from treatment is crucial to improve outcome and reduce unnecessary toxicity. In this retrospective study, systemic treatment outcome for patients with metastatic MBC is being evaluated. We evaluated to what extent the clinical benefit of prior chemotherapy can predict the success of a subsequent treatment line. Ninety-one patients treated with chemotherapy for MBC between January 2005 and January 2009 were included in this study. Clinical characteristics of patients, choices of chemotherapy and response at first evaluation of every treatment line was evaluated based on radiologic and clinical data. Patients received multiple systemic cytotoxic and biological (combination) therapies. 30% of these patients received more than five consecutive systemic (combination) treatments. First line chemotherapy was mostly anthracycline-based, followed by taxanes, capecitabine and vinorelbine. The response rate (RR, complete response plus partial response according to RECIST 1.1) decreased from 20% (95% CI 11-28%) upon first line of treatment to 0% upon the fourth line. The clinical benefit rate (combining RR and stable disease) decreased from 85% (95% CI 78-93%) in the first to 54% (95% CI 26-67) upon the fourth line. 24% of the patients with clinical benefit at first evaluation did not receive a subsequent line of treatment when progressive disease occurred, while sixty-one percent of the patients with progressive disease at first evaluation of a treatment did not receive a subsequent line of chemotherapy. When applied, the efficacy of a subsequent line of treatment was similar for patients independent of previous treatment benefit. The clinical benefit at first evaluation from systemic treatment in MBC does not predict for subsequent treatment benefit in this retrospective analysis. The fact that 61% of patients did not receive subsequent treatment after previous treatment failure suggests that either clinical judgement is of critical value in selection of patients to prevent them from unnecessary toxicity or, alternatively indicates that based on the assumption that prior treatment failure predicts for lack of benefit undertreatment of patients occurs. Therefore, a more adequate clinical judgement tool or predictive biomarkers for response are urgently needed to improve treatment outcome. Copyright © 2015. Published by Elsevier Ltd.

Diagnostic medical physicists and their clinical activities.

PubMed

Cypel, Yasmin S; Sunshine, Jonathan H

2004-02-01

The primary objective of this study was to obtain basic, descriptive information about medical physicists involved in diagnostic radiology-related activities, the diagnostic-related activities that they performed, and the time spent on these activities. A survey was sent to a randomly selected sample of 1511 medical physicists from July through October 2001 using primarily e-mail methods; a total of 851 surveys was received, for a response rate of 56%. Of these, 427 were responses from physicists who do partly or only clinical diagnostic medical physics; it is this group for which results are presented. Fifty-four percent of the physicists who reported doing any clinical diagnostic medical physics performed clinical activities only in diagnostic medical physics. Fourteen percent of all those doing clinical diagnostic medical physics were women. Over 97% of the physicists doing clinical diagnostic medical physics reported having graduate degrees in physics; 53% had PhDs. The mean total weekly hours worked by physicists doing clinical diagnostic medical physics was 42. Medical physicists doing only clinical diagnostic activities reported working approximately 40 hours weekly, whereas those doing partly clinical diagnostic medical physics reported working 14 hours weekly in the field (approximately one-third of their work time). Radiography and fluoroscopy, computed tomography, nuclear medicine, and mammography are all fields in which the majority of those doing any clinical diagnostic medical physics are active. Full-time physicists working only in diagnostic medical physics were responsible for a median of 25 units of equipment, compared with a median of 10 units for those working only partly in the field. Number of units evaluated, frequency of evaluation, and hours per evaluation were reported for almost 20 types of equipment. Medical physicists performing diagnostic clinical activities typically are responsible for a large number and wide variety of imaging equipment. It would be helpful to study their work further, focusing in particular on whether there is a shortage, as is true of diagnostic radiologists, and whether the variety of responsibilities creates strain.

How to use PET/CT in the evaluation of response to radiotherapy.

PubMed

Decazes, Pierre; Thureau, Sébastien; Dubray, Bernard; Vera, Pierre

2018-06-01

Radiotherapy is a major treatment modality for many cancers. Tumor response after radiotherapy determines the subsequent steps of the patient's management (surveillance, adjuvant or salvage treatment and palliative care). Tumor response assessed during radiotherapy offers a promising opportunity to adapt the treatment plan to reduced or increased target volume, to specifically target sub-volumes with relevant biological characteristics (metabolism, hypoxia, proliferation, etc.) and to further spare the organs at risk. In addition to its role in the diagnosis and the initial staging, Positron Emission Tomography combined with a Computed Tomography (PET/CT) provides functional information and is therefore attractive to evaluate tumor response. The aim of this paper is to review the published data addressing PET/CT as an evaluation tool in irradiated tumors. Reports on PET/CT acquired at various times (during radiotherapy, after initial (chemo-) radiotherapy, after definitive radiotherapy and during posttreatment follow-up) in solid tumors (lung, head-and-neck, cervix, esophagus, prostate and rectum) were collected and reviewed. Various tracers and technical aspects are also discussed. 18F-FDG PET/CT has a well-established role in clinical routine after definitive chemo-radiotherapy for locally advanced head-and-neck cancers. 18F-choline PET/CT is indicated in prostate cancer patients with biochemical failure. 18F-FDG PET/CT is optional in many other circumstances and the clinical benefits of assessing tumor response with PET/CT remain a field of very active research. The combination of PET with Magnetic Resonance Imaging (PET/MRI) may prove to be valuable in irradiated rectal and cervix cancers. Tumor response can be evaluated by PET/CT with clinical consequences in multiple situations, notably in head and neck and prostate cancers, after radiotherapy. Further clinical evaluation for most cancers is still needed, possibly in association to MRI.

Evaluation systems for clinical governance development: a comparative study.

PubMed

Hooshmand, Elaheh; Tourani, Sogand; Ravaghi, Hamid; Ebrahimipour, Hossein

2014-01-01

Lack of scientific and confirmed researches and expert knowledge about evaluation systems for clinical governance development in Iran have made studies on different evaluation systems for clinical governance development a necessity. These studies must provide applied strategies to design criteria of implementing clinical governance for hospital's accreditation. This is a descriptive and comparative study on development of clinical governance models all over the world. Data have been gathered by reviewing related articles. Models have been studied in comprehensive review method. The evaluated models of clinical governance development were Australian, NHS, SPOCK and OPTIGOV. The final aspects extracted from these models were Responsiveness, Policies and Strategies, Organizational Structure, Allocating Resources, Education and Occupational Development, Performance Evaluation, External Evaluation, Patient Oriented Approach, Risk Management, Personnel's Participation, Information Technology, Human Resources, Research and Development, Evidence Based Medicine, Clinical Audit, Health Technology Assessment and Quality. These results are applicable for completing the present criteria which evaluating clinical governance application and provide practical framework to evaluate country's hospital on the basis of clinical governance elements.

Psychometric Properties of the Chinese Version of the Social Responsiveness Scale

ERIC Educational Resources Information Center

Gau, Susan Shur-Fen; Liu, Li-Ting; Wu, Yu-Yu; Chiu, Yen-Nan; Tsai, Wen-Che

2013-01-01

This study evaluated the psychometric properties of the Chinese version of the Social Responsiveness Scale (Chinese SRS). We assessed 1419 grade 1 to grade 8 students from northern Taiwan and 401 clinic-based participants (aged 3-20, male 90.3%). All clinic-based participants were clinically diagnosed with autism spectrum disorders (ASDs),…

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

PubMed

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 Research.

Developing education tailored to clinical roles: genetics education for haemophilia nurses.

PubMed

Burke, Sarah; Barker, Colin; Marshall, Dianne

2012-01-01

Genetics is an important component of the clinical work of haemophilia nurses, but little was known about the genetic education needs of haemophilia nurses. To develop, deliver and evaluate genetic education for haemophilia nurses, based on clinical roles. Perceived relevance of genetics to haemophilia nursing practice was explored using electronic voting (response rate 75%, 58/77). A follow-on questionnaire to a volunteer sample of participants explored educational preferences (response rate 41%, 17/41). Results informed development of a two-hour genetics workshop session, evaluated by questionnaire (response rate 67%, 47/70). Genetic competences were considered relevant to the clinical practice of haemophilia nurses, and learning needs were identified. Preference was expressed for education focused on practical skills. During the subsequent workshop, participant confidence ratings significantly increased in the four areas addressed. Planned changes to clinical care and training were reported. Within new areas of advanced nursing practice, learning needs can be addressed by: identifying relevant clinical activities and associated learning needs; creating a strategy and resources using preferred forms of delivery; implementing the strategy; and evaluating its effect. This will enable development of education that addresses the real needs of practising nurses, grounded in their daily clinical practice. Copyright © 2011 Elsevier Ltd. All rights reserved.

Tenosynovitis US scoring systems follow synovitis and clinical scoring systems in RA and are responsive to change after biologic therapy.

PubMed

Vlad, Violeta; Berghea, Florian; Micu, Mihaela; Varzaru, Luminita; Bojinca, Mihai; Milicescu, Mihaela; Ionescu, Ruxandra; Naredo, Esperanza

2015-09-01

To investigate by ultrasonography (US) in a cohort of active RA patients starting biologic therapy the responsiveness of tenosynovitis of wrist and hands compared to the responsiveness of synovitis in a 6 month period follow-up, to compare the responsiveness of finger flexor tenosynovitis with the responsiveness of wrist extensor tenosynovitis and to describe the subclinical synovitis and tenosynovitis in RA patients in clinical remission. Fifty seven patients with active RA starting biologic therapy were included. Clinical, laboratory, and US evaluations were performed at baseline, 1, and 6 months. US evaluation included wrist and MCPs 2-5 joints, bilaterally for synovitis and extensor tendons compartments 2, 4, and 6 and finger flexors 2-5 for tenosynovitis. Eighteen US scores based on semiquantitative or binary grades were calculated at each visit. Responsiveness of synovitis and tenosynovitis scores was calculated using the standardized response mean (SRM). The responsiveness of US tenosynovitis was lower comparing with the responsiveness of US synovitis but both showed large effect of therapy. Furthermore, tenosynovitis responsiveness was similar to CRP responsiveness (SRM -0.90). Finger flexors tenosynovitis showed a higher responsiveness than extensor tenosynovitis on GS (-0.94 compared to -0.63) and a lower SRM on PD (-0.56 compared to -0.85). Tenosynovitis scores remission was overlapping clinical remission according to CDAI and SDAI in 100% of cases. Overall there was less subclinical tenosynovitis than subclinical synovitis at final visit according to clinical activity indices. Tenosynovitis US scoring in RA may be as good as synovitis scoring for characterization of disease activity and responsiveness.

99mTc-sestamibi scintigraphy used to evaluate tumor response to neoadjuvant chemotherapy in locally advanced breast cancer: A quantitative analysis

PubMed Central

KOGA, KATIA HIROMOTO; MORIGUCHI, SONIA MARTA; NETO, JORGE NAHÁS; PERES, STELA VERZINHASSE; SILVA, EDUARDO TINÓIS DA; SARRI, ALMIR JOSÉ; MICHELIN, ODAIR CARLITO; MARQUES, MARIANGELA ESTHER ALENCAR; GRIVA, BEATRIZ LOTUFO

2010-01-01

To evaluate the tumor response to neoadjuvant chemotherapy, 99mTc-sestamibi breast scintigraphy was proposed as a quantitative method. Fifty-five patients with ductal carcinoma were studied. They underwent breast scintigraphy before and after neoadjuvant chemotherapy, along with clinical assessment and surgical specimen analysis. The regions of interest on the lesion and contralateral breast were identified, and the pixel counts were used to evaluate lesion uptake in relation to background radiation. The ratio of these counts before to after neoadjuvant chemotherapy was assessed. The decrease in uptake rate due to chemotherapy characterized the scintigraphy tumor response. The Kruskal-Wallis test was used to compare the mean scintigraphic tumor response and histological type. Dunn’s multiple comparison test was used to detect differences between histological types. The Mann-Whitney test was used to compare means between quantitative and qualitative variables: scintigraphic tumor response vs. clinical response and uptake before chemotherapy vs. scintigraphic tumor response. The Spearman’s test was used to correlate the quantitative variables of clinical reduction in tumor size and scintigraphic tumor response. All of the variables compared presented significant differences. The change in 99mTc-sestamibi uptake noted on breast scintigraphy, before to after neoadjuvant chemotherapy, may be used as an effective method for evaluating the response to neoadjuvant chemotherapy, since this quantification reflects the biological behavior of the tumor towards the chemotherapy regimen. Furthermore, additional analysis on the uptake rate before chemotherapy may accurately predict treatment response. PMID:22966312

Responsiveness of clinical tests for people with neck pain.

PubMed

Jørgensen, René; Ris, Inge; Juhl, Carsten; Falla, Deborah; Juul-Kristensen, Birgit

2017-12-28

Responsiveness of a clinical test is highly relevant in order to evaluate the effect of a given intervention. However, the responsiveness of clinical tests for people with neck pain has not been adequately evaluated. The objective of the present study was to examine the responsiveness of four clinical tests which are low cost and easy to perform in a clinical setting, including the craniocervical flexion test, cervical active range of movement, test for the cervical extensors and pressure pain threshold testing. This study is a secondary analysis of data collected in a previously published randomised controlled trial. Participants were randomized to either physical training, exercises and pain education combined or pain education only. Participants were tested on the clinical tests at baseline and at 4-month follow-up. An anchor-based approach using Receiver Operator Characteristics (ROC) curves was used to evaluate responsiveness of the clinical tests. The Neck Disability Index was used to discriminate between those who had improved and those who were unchanged at the 4-month follow-up. Minimum Clinically Important Difference (MCID), together with sensitivity, specificity, positive and negative predictive values, in addition to positive and negative likelihood ratios were calculated. In total, 164 participants completed the 4 month follow up. One-hundred forty four participants were classified as unchanged whereas 20 patients were considered to be improved. Twenty-six participants didn't complete all of the clinical tests, leaving a total of 138 to be included for analyses. Area Under Curve (AUC) ranged from 0.50-0.62 for the clinical tests, and were all below an acceptable level. MCID was generally large, and the corresponding sensitivity and specificity was low with sensitivity ranging from 20 to 60%, and specificity from 54 to 86%. LR+ (0.8-2.07) and LR- (0.7-1.1) showed low diagnostic value for all variables, with PPV ranging from 12.1 to 26.1 and NPV ranging from 84.7 to 89.2. Responsiveness of the included clinical tests was generally low when using change in NDI score as the anchor from baseline to the 4-month follow up. Further investigations of responsiveness are warranted, possibly using other anchors, which to a higher degree resemble similar dimensions as the clinical tests.

Treatment of painful bone metastases in prostate and breast cancer patients with the therapeutic radiopharmaceutical rhenium-188-HEDP. Clinical benefit in a real-world study.

PubMed

Lange, Rogier; Overbeek, Floor; de Klerk, John M H; Pasker-de Jong, Pieternel C M; van den Berk, Alexandra M; Ter Heine, Rob; Rodenburg, Cees J; Kooistra, Anko; Hendrikse, N Harry; Bloemendal, Haiko J

2016-09-26

Rhenium-188-HEDP ((188)Re-HEDP) is an effective radiopharmaceutical for the palliative treatment of osteoblastic bone metastases. However, only limited data on its routine use are available and its effect on quality of life (QoL) has not been studied. Therefore, we evaluated the clinical benefit of (188)Re-HEDP in routine clinical care. Prostate or breast cancer patients with painful bone metastases receiving (188)Re-HEDP as a routine clinical procedure were eligible for evaluation. Clinical benefit was assessed in terms of efficacy and toxicity. Pain palliation and QoL were monitored using the visual analogue scale (VAS), corrected for opioid intake, and the EORTC QLQ-C30 Global health status/QoL-scale. Thrombocyte and leukocyte nadirs were used to assess haematological toxicity. 45 and 47 patients were evaluable for pain palliation and QoL, respectively. After a single injection of (188)Re-HEDP, the overall pain response rate was 69% and mean VAS-scores decreased relevantly and significantly (p < 0.05). Repeated treatment resulted in similar pain response. The overall QoL response rate was 68% and mean Global health status/QoL-scores increased relevantly and significantly. Haematological side effects were mild and transient. The clinically relevant response on pain and quality of life and the limited adverse events prove clinical benefit of treatment with (188)Re-HEDP and support its use in routine clinical care. Its effectiveness appears comparable to that of external beam radiotherapy.

Evaluation of Non-Invasive Multispectral Imaging as a Tool for Measuring the Effect of Systemic Therapy in Kaposi Sarcoma

PubMed Central

Kainerstorfer, Jana M.; Polizzotto, Mark N.; Uldrick, Thomas S.; Rahman, Rafa; Hassan, Moinuddin; Najafizadeh, Laleh; Ardeshirpour, Yasaman; Wyvill, Kathleen M.; Aleman, Karen; Smith, Paul D.; Yarchoan, Robert; Gandjbakhche, Amir H.

2013-01-01

Diffuse multi-spectral imaging has been evaluated as a potential non-invasive marker of tumor response. Multi-spectral images of Kaposi sarcoma skin lesions were taken over the course of treatment, and blood volume and oxygenation concentration maps were obtained through principal component analysis (PCA) of the data. These images were compared with clinical and pathological responses determined by conventional means. We demonstrate that cutaneous lesions have increased blood volume concentration and that changes in this parameter are a reliable indicator of treatment efficacy, differentiating responders and non-responders. Blood volume decreased by at least 20% in all lesions that responded by clinical criteria and increased in the two lesions that did not respond clinically. Responses as assessed by multi-spectral imaging also generally correlated with overall patient clinical response assessment, were often detectable earlier in the course of therapy, and are less subject to observer variability than conventional clinical assessment. Tissue oxygenation was more variable, with lesions often showing decreased oxygenation in the center surrounded by a zone of increased oxygenation. This technique could potentially be a clinically useful supplement to existing response assessment in KS, providing an early, quantitative, and non-invasive marker of treatment effect. PMID:24386302

Effectiveness of adalimumab for the treatment of ulcerative colitis in clinical practice: comparison between anti-tumour necrosis factor-naïve and non-naïve patients.

PubMed

Iborra, Marisa; Pérez-Gisbert, Javier; Bosca-Watts, Marta Maia; López-García, Alicia; García-Sánchez, Valle; López-Sanromán, Antonio; Hinojosa, Esther; Márquez, Lucía; García-López, Santiago; Chaparro, María; Aceituno, Montserrat; Calafat, Margalida; Guardiola, Jordi; Belloc, Blanca; Ber, Yolanda; Bujanda, Luis; Beltrán, Belén; Rodríguez-Gutiérrez, Cristina; Barrio, Jesús; Cabriada, José Luis; Rivero, Montserrat; Camargo, Raquel; van Domselaar, Manuel; Villoria, Albert; Schuterman, Hugo Salata; Hervás, David; Nos, Pilar

2017-07-01

Ulcerative colitis (UC) treatment is focused to achieve mucosal healing, avoiding disease progression. The study aimed to evaluate the real-world effectiveness of adalimumab (ADA) in UC and to identify predictors of remission to ADA. This cohort study used data from the ENEIDA registry. Clinical response, clinical remission, endoscopic remission, adverse events (AE), colectomy, and hospitalisations were evaluated; baseline characteristics and biological parameters were compared to determine predictors of response. We included 263 patients (87 naïve and 176 previously exposed to anti-tumour necrosis factor alpha, TNF). After 12 weeks, clinical response, clinical remission, and endoscopic remission rates were 51, 26, and 14 %, respectively. The naïve group demonstrated better response to treatment than the anti-TNF-exposed group at short-term. Clinical and endoscopic remission within 1 year of treatment was better in the naïve group (65 vs. 49 and 50 vs. 35 %, respectively). The rates of AE, dose-escalation, hospitalisations, and colectomy during the first year were higher in anti-TNF-exposed patients (40, 43, and 27 % vs. 26, 21, and 11 %, respectively). Patients with primary failure and intolerance to the first anti-TNF and severe disease were associated with worse clinical response. Primary non-response to prior anti-TNF treatment and severe disease were predictive of poorer clinical remission. Low levels of C-reactive protein (CRP) and faecal calprotectin (FC) at baseline were predictors of clinical remission. In clinical practice, ADA was effective in UC, especially in anti-TNF naïve patients. FC and CRP could be predictors of treatment effectiveness.

A phase I clinical study of immunotherapy for advanced colorectal cancers using carcinoembryonic antigen-pulsed dendritic cells mixed with tetanus toxoid and subsequent IL-2 treatment.

PubMed

Liu, Ko-Jiunn; Chao, Tsu-Yi; Chang, Jang-Yang; Cheng, Ann-Lii; Ch'ang, Hui-Ju; Kao, Woei-Yau; Wu, Yu-Chen; Yu, Wei-Lan; Chung, Tsai-Rong; Whang-Peng, Jacqueline

2016-08-24

To better evaluate and improve the efficacy of dendritic cell (DC)-based cancer immunotherapy, we conducted a clinical study of patients with advanced colorectal cancer using carcinoembryonic antigen (CEA)-pulsed DCs mixed with tetanus toxoid and subsequent interleukin-2 treatment. The tetanus toxoid in the vaccine preparation serves as an adjuvant and provides a non-tumor specific immune response to enhance vaccine efficacy. The aims of this study were to (1) evaluate the toxicity of this treatment, (2) observe the clinical responses of vaccinated patients, and (3) investigate the immune responses of patients against CEA before and after treatment. Twelve patients were recruited and treated in this phase I clinical study. These patients all had metastatic colorectal cancer and failed standard chemotherapy. We first subcutaneously immunized patients with metastatic colorectal cancer with 1 × 10(6) CEA-pulsed DCs mixed with tetanus toxoid as an adjuvant. Patients received 3 successive injections with 1 × 10(6) CEA-pulsed DCs alone. Low-dose interleukin-2 was administered subcutaneously following the final DC vaccination to boost the growth of T cells. Patients were evaluated for adverse event and clinical status. Blood samples collected before, during, and after treatment were analyzed for T cell proliferation responses against CEA. No severe treatment-related side effects or toxicity was observed in patients who received the regular 4 DC vaccine injections. Two patients had stable disease and 10 patients showed disease progression. A statistically significant increase in proliferation against CEA by T cells collected after vaccination was observed in 2 of 9 patients. The results of this study indicate that it is feasible and safe to treat colorectal cancer patients using this protocol. An increase in the anti-CEA immune response and a clinical benefit was observed in a small fraction of patients. This treatment protocol should be further evaluated in additional colorectal cancer patients with modifications to enhance T cell responses. ClinicalTrials.gov (identifier NCT00154713 ), September 8, 2005.

Predicting factors of fistula healing and clinical remission after infliximab-based combined therapy for perianal fistulizing Crohn's disease.

PubMed

Tougeron, David; Savoye, Guillaume; Savoye-Collet, Céline; Koning, Edith; Michot, Francis; Lerebours, Eric

2009-08-01

Perianal fistulizing Crohn's disease (PFCD) treatment is based on fistula drainage, antibiotics, immunosuppressant (IS) drugs, and infliximab. Our aim was to study the effectiveness of combination therapy on PFCD and to search for clinical or imaging features associated with the initial complete clinical response and its stability overtime. All patients with PFCD treated in our tertiary center between 2000 and 2005 by infliximab in combination with seton placement and/or IS and evaluated by MRI before treatment were included in the study. Basal clinical and MRI characteristics were recorded. Response to treatment was evaluated after the infliximab induction regiment and at the end of the follow-up. Twenty-six patients were included and followed-up for an average 4.9 years. A complex fistula was present in 69% (18/26 patients) of cases and eight (8/26 patients) had an ano-vaginal fistula. After infliximab induction therapy, 13 patients (50%) achieved a complete clinical response. The initial clinical response was significantly associated with the absence of both, active intestinal disease (54% vs. 8%, P = 0.03) and active proctitis (77% vs. 23%, P = 0.01). No initial MRI characteristics were linked to the initial response. In multivariate analysis, only the presence of active proctitis was associated with the lack of response (P = 0.047). At the end of the follow-up, 42% of the patients remained in clinical remission. No clinical characteristics were associated to sustained response when among long-standing responders two exhibited a normal post-treatment MRI. An initial complete response of PFCD was observed in half of the patients after combined therapy including infliximab that decreased to 42% later on. Complete healing of fistulas on MRI was possible but unusual. The initial response seemed related to the absence of active intestinal disease, especially in the rectum, when the long-term response could not be predicted by the basal characteristics of patients.

Selection of response criteria for clinical trials of sarcoma treatment.

PubMed

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 tumors.

TH-E-202-03: PET for Tumor Response Evaluation

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

Lu, W.

PET/CT is a very important imaging tool in the management of oncology patients. PET/CT has been applied for treatment planning and response evaluation in radiation therapy. This educational session will discuss: Pitfalls and remedies in PET/CT imaging for RT planning The use of hypoxia PET imaging for radiotherapy PET for tumor response evaluation The first presentation will address the issue of mis-registration between the CT and PET images in the thorax and the abdomen. We will discuss the challenges of respiratory gating and introduce an average CT technique to improve the registration for dose calculation and image-guidance in radiation therapy.more » The second presentation will discuss the use of hypoxia PET Imaging for radiation therapy. We will discuss various hypoxia radiotracers, the choice of clinical acquisition protocol (in particular a single late static acquisition versus a dynamic acquisition), and the compartmental modeling with different transfer rate constants explained. We will demonstrate applications of hypoxia imaging for dose escalation/de-escalation in clinical trials. The last presentation will discuss the use of PET/CT for tumor response evaluation. We will discuss anatomic response assessment vs. metabolic response assessment, visual evaluation and semi-quantitative evaluation, and limitations of current PET/CT assessment. We will summarize clinical trials using PET response in guiding adaptive radiotherapy. Finally, we will summarize recent advancements in PET/CT radiomics and non-FDG PET tracers for response assessment. Learning Objectives: Identify the causes of mis-registration of CT and PET images in PET/CT, and review the strategies to remedy the issue. Understand the basics of PET imaging of tumor hypoxia (radiotracers, how PET measures the hypoxia selective uptake, imaging protocols, applications in chemo-radiation therapy). Understand the basics of dynamic PET imaging, compartmental modeling and parametric images. Understand the basics of using FDG PET/CT for tumor response evaluation. Learn about recent advancement in PET/CT radiomics and non-FDG PET tracers for response assessment. This work was supported in part by the National Cancer Institute Grants R01CA172638.; W. Lu, This work was supported in part by the National Cancer Institute Grants R01CA172638.« less

Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by Cetuximab plus chemotherapy

PubMed Central

Di Fiore, F; Blanchard, F; Charbonnier, F; Le Pessot, F; Lamy, A; Galais, M P; Bastit, L; Killian, A; Sesboüé, R; Tuech, J J; Queuniet, A M; Paillot, B; Sabourin, J C; Michot, F; Michel, P; Frebourg, T

2007-01-01

The predictive value of KRAS mutation in metastatic colorectal cancer (MCRC) patients treated with cetuximab plus chemotherapy has recently been suggested. In our study, 59 patients with a chemotherapy-refractory MCRC treated with cetuximab plus chemotherapy were included and clinical response was evaluated according to response evaluation criteria in solid tumours (RECIST). Tumours were screened for KRAS mutations using first direct sequencing, then two sensitive methods based on SNaPshot and PCR-ligase chain reaction (LCR) assays. Clinical response was evaluated according to gene mutations using the Fisher exact test. Times to progression (TTP) were calculated using the Kaplan–Meier method and compared with log-rank test. A KRAS mutation was detected in 22 out of 59 tumours and, in six cases, was missed by sequencing analysis but detected using the SNaPshot and PCR-LCR assays. Remarkably, no KRAS mutation was found in the 12 patients with clinical response. KRAS mutation was associated with disease progression (P=0.0005) and TTP was significantly decreased in mutated KRAS patients (3 vs 5.5 months, P=0.015). Our study confirms that KRAS mutation is highly predictive of a non-response to cetuximab plus chemotherapy in MCRC and highlights the need to use sensitive molecular methods, such as SNaPshot or PCR-LCR assays, to ensure an efficient mutation detection. PMID:17375050

Ultrasonographic Changes at 12 Weeks of Anti-TNF Drugs Predict 1-year Sonographic Response and Clinical Outcome in Crohn's Disease: A Multicenter Study.

PubMed

Ripollés, Tomás; Paredes, José M; Martínez-Pérez, María J; Rimola, Jordi; Jauregui-Amezaga, Arantza; Bouzas, Rosa; Martin, Gregorio; Moreno-Osset, Eduardo

2016-10-01

The objective was to assess the long-term effect of biological treatment on transmural lesions of Crohn's disease evaluated with ultrasound, including contrast-enhanced ultrasound. Fifty-one patients with active Crohn's disease were included in a prospective multicenter longitudinal study. All patients underwent a clinical assessment and sonographic examination at baseline, 12 weeks after treatment initiation, and after 1-year of treatment. Patients were clinically followed at least 2 years from inclusion until the end of the study. Ultrasonographic evaluation included bowel wall thickness, color Doppler grade, parietal enhancement, and presence of transmural complications or stenosis. Sonographic changes after treatment were classified as normalization, improvement, or lack of response. Improvement at 52 weeks was more frequent in patients with improvement at final of induction (12 weeks) compared with patients who did not improve (85% versus 28%; P < 0.0001). One-year sonographic evolution correlated with clinical response; 28 of the 29 (96.5%) patients with sonographic improvement at 52 weeks showed clinical remission or response. Patients without sonographic improvement at 52 weeks of treatment were more likely to have a change or intensification in medication or surgery (13/20, 65%) during the next year of follow-up than patients with improvement on the sonography (3/28, 11%). Stricturing behavior was the only sonographic feature associated to a negative predictive value of response (P = 0.0001). Sonographic response after 12 weeks of therapy is more pronounced and predicts 1-year sonographic response. Sonographic response at 1-year examination correlates with 1-year clinical response and is a predictor of further treatment's efficacy, 1-year or longer period of follow-up.

Tumor Response After Stereotactic Body Radiation Therapy to Nonspine Bone Metastases: An Evaluation of Response Criteria

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

McDonald, Rachel; Probyn, Linda; Poon, Ian

Purpose: To evaluate the applicability of the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and University of Texas MD Anderson (MDA) Cancer Center criteria in the setting of stereotactic body radiation therapy (SBRT) to nonspine bone metastases. Methods: Patients who were treated with SBRT to nonspine bone metastases were identified by retrospective chart review. An independent musculoskeletal radiologist evaluated response to treatment using computed tomography (CT) scans. Results: Thirty-three patients were treated to 42 nonspine bone metastases. The most common primary cancer cites were renal cell carcinoma (RCC) (33.3%), lung (24.2%), and prostate (18.2%). Bone metastases were either mainlymore » lytic (57.1%), mainly sclerotic (28.6%), or mixed (14.3%). When lytic and sclerotic lesions were evaluated according to RECIST 1.1, local control (LC) was 83%, 85%, 88%, and 80% for those with CT imaging between months 1 to 3, 4 to 6, 7 to 9, and 10 to 12, respectively. When evaluated by the MDA criteria by density, LC within each time period was slightly greater. Overall LC decreased considerably when evaluated by MDA in terms of size. Conclusions: Consensus definitions of response are required as they have implications on clinical trials and disease management. Without consistent response criteria, outcomes from clinical trials cannot be compared and treatment efficacy remains undetermined.« less

Accuracy of clinical swallowing evaluation for diagnosis of dysphagia in children with laryngomalacia or glossoptosis.

PubMed

Gasparin, Marisa; Schweiger, Cláudia; Manica, Denise; Maciel, Antônio Carlos; Kuhl, Gabriel; Levy, Deborah Salle; Marostica, Paulo José Cauduro

2017-01-01

To investigate the accuracy of clinical evaluation of swallowing in a sample of children with laryngomalacia or glossoptosis and describe the prevalence of dysphagia in each of these diseases, as well as characterize the swallow response to speech and language therapy interventions. Children aged 1 month to 11 years receiving care at the Department of Otolaryngology, Hospital de Clínicas de Porto Alegre, Brazil, were evaluated in a cross-sectional design. Evaluation of swallowing was performed at two time points by two blinded speech-language pathologists, one responsible for clinical evaluation and the other for videofluoroscopic study. The protocols employed were based on the instruments proposed by DeMatteo et al. (DeMatteo C, Matovich D, Hjartarson A. Comparison of clinical and videofluoroscopic evaluation of children with feeding and swallowing difficulties. Dev Med Child Neurol 2005;47:149-157.). The study sample consisted of 29 patients: 10 patients with laryngomalacia and 19 patients with glossoptosis. The sensitivity of clinical evaluation did not exceed 50% in any of the evaluations, but specificity reached 100% in some cases, using thickened liquids. The prevalence of dysphagia was 100%, and the use of thickened liquids significantly reduced tracheal aspiration. Dysphagia was highly prevalent in this sample. The sensitivity of clinical evaluation to detect laryngeal penetration and tracheal aspiration was low, as the majority of aspiration events were silent. The videofluoroscopic study is important in order to determine a safest method to feed the patient. Pediatr Pulmonol. 2017;52:41-47. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

A Pilot Trial of the Combination of Vemurafenib with Adoptive Cell Therapy in Patients with Metastatic Melanoma.

PubMed

Deniger, Drew C; Kwong, Mei Li M; Pasetto, Anna; Dudley, Mark E; Wunderlich, John R; Langhan, Michelle M; Lee, Chyi-Chia Richard; Rosenberg, Steven A

2017-01-15

This pilot feasibility clinical trial evaluated the coadministration of vemurafenib, a small-molecule antagonist of BRAF V600 mutations, and tumor-infiltrating lymphocytes (TIL) for the treatment of metastatic melanoma. A metastatic tumor was resected for growth of TILs, and patients were treated with vemurafenib for 2 weeks, followed by resection of a second lesion. Patients then received a nonmyeloablative preconditioning regimen, infusion of autologous TILs, and high-dose interleukin-2 administration. Vemurafenib was restarted at the time of TIL infusion and was continued for 2 years or until disease progression. Clinical responses were evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) 1.0. Metastases resected prior to and after 2 weeks of vemurafenib were compared using TCRB deep sequencing, immunohistochemistry, proliferation, and recognition of autologous tumor. The treatment was well tolerated and had a safety profile similar to that of TIL or vemurafenib alone. Seven of 11 patients (64%) experienced an objective clinical response, and 2 patients (18%) had a complete response for 3 years (one response is ongoing at 46 months). Proliferation and viability of infusion bag TILs and peripheral blood T cells were inhibited in vitro by research-grade vemurafenib (PLX4032) when approaching the maximum serum concentration of vemurafenib. TCRB repertoire (clonotypes numbers, clonality, and frequency) did not significantly change between pre- and post-vemurafenib lesions. Recognition of autologous tumor by T cells was similar between TILs grown from pre- and post-vemurafenib metastases. Coadministration of vemurafenib and TILs was safe and feasible and generated objective clinical responses in this small pilot clinical trial. Clin Cancer Res; 23(2); 351-62. ©2016 AACRSee related commentary by Cogdill et al., p. 327. ©2016 American Association for Cancer Research.

Clinical usefulness and feasibility of time-frequency analysis of chemosensory event-related potentials.

PubMed

Huart, C; Rombaux, Ph; Hummel, T; Mouraux, A

2013-09-01

The clinical usefulness of olfactory event-related brain potentials (OERPs) to assess olfactory function is limited by the relatively low signal-to-noise ratio of the responses identified using conventional time-domain averaging. Recently, it was shown that time-frequency analysis of the obtained EEG signals can markedly improve the signal-to-noise ratio of OERPs in healthy controls, because it enhances both phase-locked and non phase-locked EEG responses. The aim of the present study was to investigate the clinical usefulness of this approach and evaluate its feasibility in a clinical setting. We retrospectively analysed EEG recordings obtained from 45 patients (15 anosmic, 15 hyposmic and 15 normos- mic). The responses to olfactory stimulation were analysed using conventional time-domain analysis and joint time-frequency analysis. The ability of the two methods to discriminate between anosmic, hyposmic and normosmic patients was assessed using a Receiver Operating Characteristic analysis. The discrimination performance of OERPs identified using conventional time-domain averaging was poor. In contrast, the discrimination performance of the EEG response identified in the time-frequency domain was relatively high. Furthermore, we found a significant correlation between the magnitude of this response and the psychophysical olfactory score. Time-frequency analysis of the EEG responses to olfactory stimulation could be used as an effective and reliable diagnostic tool for the objective clinical evaluation of olfactory function in patients.

Outbreak!: Teaching Clinical and Diagnostic Microbiology Methodologies with an Interactive Online Game

ERIC Educational Resources Information Center

Clark, Sherri; Smith, Geoffrey Battle

2004-01-01

Outbreak! is an online, interactive educational game that helps students and teachers learn and evaluate clinical microbiology skills. When the game was used in introductory microbiology laboratories, qualitative evaluation by students showed very positive responses and increased learning. Outbreak! allows students to design diagnostic tests and…

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

ERIC Educational Resources Information Center

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

2012-01-01

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

Multimodal characterization of the semantic N400 response within a rapid evaluation brain vital sign framework.

PubMed

Ghosh Hajra, Sujoy; Liu, Careesa C; Song, Xiaowei; Fickling, Shaun D; Cheung, Teresa P L; D'Arcy, Ryan C N

2018-06-04

For nearly four decades, the N400 has been an important brainwave marker of semantic processing. It can be recorded non-invasively from the scalp using electrical and/or magnetic sensors, but largely within the restricted domain of research laboratories specialized to run specific N400 experiments. However, there is increasing evidence of significant clinical utility for the N400 in neurological evaluation, particularly at the individual level. To enable clinical applications, we recently reported a rapid evaluation framework known as "brain vital signs" that successfully incorporated the N400 response as one of the core components for cognitive function evaluation. The current study characterized the rapidly evoked N400 response to demonstrate that it shares consistent features with traditional N400 responses acquired in research laboratory settings-thereby enabling its translation into brain vital signs applications. Data were collected from 17 healthy individuals using magnetoencephalography (MEG) and electroencephalography (EEG), with analysis of sensor-level effects as well as evaluation of brain sources. Individual-level N400 responses were classified using machine learning to determine the percentage of participants in whom the response was successfully detected. The N400 response was observed in both M/EEG modalities showing significant differences to incongruent versus congruent condition in the expected time range (p < 0.05). Also as expected, N400-related brain activity was observed in the temporal and inferior frontal cortical regions, with typical left-hemispheric asymmetry. Classification robustly confirmed the N400 effect at the individual level with high accuracy (89%), sensitivity (0.88) and specificity (0.90). The brain vital sign N400 characteristics were highly consistent with features of the previously reported N400 responses acquired using traditional laboratory-based experiments. These results provide important evidence supporting clinical translation of the rapidly acquired N400 response as a potential tool for assessments of higher cognitive functions.

Clinical stage, therapy, and prognosis in canine anal sac gland carcinoma.

PubMed

Polton, Gerry A; Brearley, Malcolm J

2007-01-01

Reports of canine anal sac gland carcinoma (ASGC) describe varied clinical presentations and management and differing responses to therapy. A unifying approach to clinical stage determination and management of this disease has yet to be presented. An ordinal clinical staging scheme for canine ASGC can be devised on the basis of responses to therapy for a retrospective cohort of affected dogs. 130 dogs with naturally occurring ASGC. A simplified clinical stage system and a management algorithm for canine ASGC were derived from retrospective evaluation of a cohort of 80 dogs; applicability of both was then prospectively evaluated in a cohort of 50 dogs. Retrospective evaluation revealed 4 statistically significant negative prognostic indicators for survival: lack of therapy, presence of distant metastases, presence of lymph node metastases, and primary tumor size. Lymph node extirpation was a statistically significant positive prognostic indicator by bivariate analysis. In both retrospective and prospective analyses, the modified clinical stage scheme revealed a significant association with survival time. The clinical staging scheme permits differentiation between groups in terms of prognosis and, therefore, decisions on therapy. This will facilitate application of appropriate therapy and enhanced communication and collaboration in further investigations of ASGC.

Atypical responses in patients with advanced melanoma, lung cancer, renal-cell carcinoma and other solid tumors treated with anti-PD-1 drugs: A systematic review.

PubMed

Queirolo, Paola; Spagnolo, Francesco

2017-09-01

Anti-programmed death receptor 1 (PD-1) drugs nivolumab and pembrolizumab were recently approved for the treatment of advanced melanoma and other solid tumors. Atypical patterns of response (i.e. tumor shrinkage or stabilization after initial progression) were observed in about 10% of metastatic melanoma patients treated with anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) drug ipilimumab and were associated with improved survival; however, the rate of atypical response patterns to anti-PD-1 therapy is not clear. An electronic search was performed to identify clinical trials evaluating response to anti-PD-1 therapy with nivolumab and pembrolizumab in patients with advanced solid tumors. Thirty-eight studies were included in our analysis for a total of 7069 patients with advanced cancer treated with anti-PD-1 therapy. Responses were evaluated by unconventional response criteria in 19 trials and were observed for all cancer types but tumors with mismatch-repair deficiency and head and neck squamous cell carcinoma. Overall, 151 atypical responses were observed in 2400 patients (6%) evaluated by unconventional response criteria. The results of our systematic review highlight the clinical relevance of unconventional responses to anti-PD-1 therapy and support further investigation into the development of tools that may assist evaluation of the antitumor activity of immunotherapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Proposal of a clinical response score and predictors of clinical response to 2 years of GH replacement therapy in adult GH deficiency.

PubMed

Schneider, Harald J; Buchfelder, Michael; Wallaschofski, Henri; Luger, Anton; Johannsson, Gudmundur; Kann, Peter H; Mattsson, Anders

2015-12-01

There is no single clinical marker to reliably assess the clinical response to growth hormone replacement therapy (GHRT) in adults with growth hormone deficiency (GHD). The objective of this study was to propose a clinical response score to GHRT in adult GHD and to establish clinical factors that predict clinical response. This was a prospective observational cohort study from the international KIMS database (Pfizer International Metabolic Database). We included 3612 adult patients with GHD for proposing the response score and 844 patients for assessing predictors of response. We propose a clinical response score based on changes in total cholesterol, waist circumference and QoL-AGHDA quality of life measurements after 2 years of GHRT. A score point was added for each quintile of change in each variable, resulting in a sum score ranging from 3 to 15. For clinical response at 2 years, we analysed predictors at baseline and after 6 months using logistic regression analyses. In a baseline prediction model, IGF1, QoL-AGHDA, total cholesterol and waist circumference predicted response, with worse baseline parameters being associated with a favourable response (AUC 0.736). In a combined baseline and 6-month prediction model, baseline QoL-AGHDA, total cholesterol and waist circumference, and 6-month change in waist circumference were significant predictors of response (AUC 0.815). A simple clinical response score might be helpful in evaluating the success of GHRT. The baseline prediction model may aid in the decision to initiate GHRT and the combined prediction model may be helpful in the decision to continue GHRT. © 2015 European Society of Endocrinology.

Evaluating an Objective Structured Clinical Examination (OSCE) Adapted for Social Work

ERIC Educational Resources Information Center

Bogo, Marion; Regehr, Cheryl; Katz, Ellen; Logie, Carmen; Tufford, Lea; Litvack, Andrea

2012-01-01

Objectives: To evaluate an objective structured clinical examination (OSCE) adapted for social work in a lab course and examine the degree to which it predicts competence in the practicum. Method: 125 Masters students participated in a one-scenario OSCE and wrote responses to standardized reflection questions. OSCE performance and reflections were…

A non-pregnant woman with elevated beta-HCG: A case of para-neoplastic syndrome in ovarian cancer.

PubMed

Goldstein, Jennifer; Pandey, Prasamsa; Fleming, Nicole; Westin, Shannon; Piha-Paul, Sarina

2016-08-01

There is a broad range of possible diagnoses for an elevated beta human chorionic gonadotropin (β-hCG) in the absence of intrauterine or ectopic pregnancy. When women of child bearing potential undergo evaluation for clinical trial, it is often unclear what course of evaluation to take when a pregnancy test is positive. We describe the clinical course of a patient with widely metastatic mucinous ovarian carcinoma with metastasis to the peritoneum, lymph nodes and liver. The patient was found to have a mildly elevated β-hCG during initial evaluation for clinical trial. Extensive work up for ectopic pregnancy, trophoblastic disease, and phantom β-hCG were negative. The patient's β-hCG levels continued to rise until initiation of therapy. She was treated on a phase I protocol with restaging scans revealing a partial response. The β-hCG was retested and declined in conjunction with her response, consistent with paraneoplastic β-hCG. Here, we propose a decision making algorithm to evaluate a patient with an elevated β-hCG undergoing assessment for clinical trial.

TH-E-202-02: The Use of Hypoxia PET Imaging for Radiotherapy

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

Humm, J.

2016-06-15

PET/CT is a very important imaging tool in the management of oncology patients. PET/CT has been applied for treatment planning and response evaluation in radiation therapy. This educational session will discuss: Pitfalls and remedies in PET/CT imaging for RT planning The use of hypoxia PET imaging for radiotherapy PET for tumor response evaluation The first presentation will address the issue of mis-registration between the CT and PET images in the thorax and the abdomen. We will discuss the challenges of respiratory gating and introduce an average CT technique to improve the registration for dose calculation and image-guidance in radiation therapy.more » The second presentation will discuss the use of hypoxia PET Imaging for radiation therapy. We will discuss various hypoxia radiotracers, the choice of clinical acquisition protocol (in particular a single late static acquisition versus a dynamic acquisition), and the compartmental modeling with different transfer rate constants explained. We will demonstrate applications of hypoxia imaging for dose escalation/de-escalation in clinical trials. The last presentation will discuss the use of PET/CT for tumor response evaluation. We will discuss anatomic response assessment vs. metabolic response assessment, visual evaluation and semi-quantitative evaluation, and limitations of current PET/CT assessment. We will summarize clinical trials using PET response in guiding adaptive radiotherapy. Finally, we will summarize recent advancements in PET/CT radiomics and non-FDG PET tracers for response assessment. Learning Objectives: Identify the causes of mis-registration of CT and PET images in PET/CT, and review the strategies to remedy the issue. Understand the basics of PET imaging of tumor hypoxia (radiotracers, how PET measures the hypoxia selective uptake, imaging protocols, applications in chemo-radiation therapy). Understand the basics of dynamic PET imaging, compartmental modeling and parametric images. Understand the basics of using FDG PET/CT for tumor response evaluation. Learn about recent advancement in PET/CT radiomics and non-FDG PET tracers for response assessment. This work was supported in part by the National Cancer Institute Grants R01CA172638.; W. Lu, This work was supported in part by the National Cancer Institute Grants R01CA172638.« less

TH-E-202-00: PET for Radiation Therapy

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

NONE

PET/CT is a very important imaging tool in the management of oncology patients. PET/CT has been applied for treatment planning and response evaluation in radiation therapy. This educational session will discuss: Pitfalls and remedies in PET/CT imaging for RT planning The use of hypoxia PET imaging for radiotherapy PET for tumor response evaluation The first presentation will address the issue of mis-registration between the CT and PET images in the thorax and the abdomen. We will discuss the challenges of respiratory gating and introduce an average CT technique to improve the registration for dose calculation and image-guidance in radiation therapy.more » The second presentation will discuss the use of hypoxia PET Imaging for radiation therapy. We will discuss various hypoxia radiotracers, the choice of clinical acquisition protocol (in particular a single late static acquisition versus a dynamic acquisition), and the compartmental modeling with different transfer rate constants explained. We will demonstrate applications of hypoxia imaging for dose escalation/de-escalation in clinical trials. The last presentation will discuss the use of PET/CT for tumor response evaluation. We will discuss anatomic response assessment vs. metabolic response assessment, visual evaluation and semi-quantitative evaluation, and limitations of current PET/CT assessment. We will summarize clinical trials using PET response in guiding adaptive radiotherapy. Finally, we will summarize recent advancements in PET/CT radiomics and non-FDG PET tracers for response assessment. Learning Objectives: Identify the causes of mis-registration of CT and PET images in PET/CT, and review the strategies to remedy the issue. Understand the basics of PET imaging of tumor hypoxia (radiotracers, how PET measures the hypoxia selective uptake, imaging protocols, applications in chemo-radiation therapy). Understand the basics of dynamic PET imaging, compartmental modeling and parametric images. Understand the basics of using FDG PET/CT for tumor response evaluation. Learn about recent advancement in PET/CT radiomics and non-FDG PET tracers for response assessment. This work was supported in part by the National Cancer Institute Grants R01CA172638.; W. Lu, This work was supported in part by the National Cancer Institute Grants R01CA172638.« less

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

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

Casimiro de Deus Cardoso, Cejana; Giordani, Adelmo Jose; Borri Wolosker, Angela Maria

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 symptomsmore » 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.« less

The value of item response theory in clinical assessment: a review.

PubMed

Thomas, Michael L

2011-09-01

Item response theory (IRT) and related latent variable models represent modern psychometric theory, the successor to classical test theory in psychological assessment. Although IRT has become prevalent in the measurement of ability and achievement, its contributions to clinical domains have been less extensive. Applications of IRT to clinical assessment are reviewed to appraise its current and potential value. Benefits of IRT include comprehensive analyses and reduction of measurement error, creation of computer adaptive tests, meaningful scaling of latent variables, objective calibration and equating, evaluation of test and item bias, greater accuracy in the assessment of change due to therapeutic intervention, and evaluation of model and person fit. The theory may soon reinvent the manner in which tests are selected, developed, and scored. Although challenges remain to the widespread implementation of IRT, its application to clinical assessment holds great promise. Recommendations for research, test development, and clinical practice are provided.

Methylphenidate-Elicited Dopamine Increases in Ventral Striatum Are Associated with Long-Term Symptom Improvement in Adults with Attention Deficit Hyperactivity Disorder

PubMed Central

Volkow, Nora D.; Wang, Gene-Jack; Tomasi, Dardo; Kollins, Scott H.; Wigal, Tim L.; Newcorn, Jeffrey H.; Telang, Frank W.; Fowler, Joanna S.; Logan, Jean; Wong, Christopher T.; Swanson, James M.

2012-01-01

Stimulant medications, such as methylphenidate, which are effective treatments for attention deficit hyperactivity disorder (ADHD), enhance brain dopamine signaling. However, the relationship between regional brain dopamine enhancement and treatment response has not been evaluated. Here, we assessed whether the dopamine increases elicited by methylphenidate are associated with long-term clinical response. We used a prospective design to study 20 treatment-naive adults with ADHD who were evaluated before treatment initiation and after 12 months of clinical treatment with a titrated regimen of oral methylphenidate. Methylphenidate-induced dopamine changes were evaluated with positron emission tomography and [11C]raclopride (D2/D3 receptor radioligand sensitive to competition with endogenous dopamine). Clinical responses were assessed using the Conners' Adult ADHD Rating Scale and revealed a significant reduction in symptoms of inattention and hyperactivity with long-term methylphenidate treatment. A challenge dose of 0.5 mg/kg intravenous methylphenidate significantly increased dopamine in striatum (assessed as decreases in D2/D3 receptor availability). In the ventral striatum, these dopamine increases were associated with the reductions in ratings of symptoms of inattention with clinical treatment. Statistical parametric mapping additionally showed dopamine increases in prefrontal and temporal cortices with intravenous methylphenidate that were also associated with decreases in symptoms of inattention. Our findings indicate that dopamine enhancement in ventral striatum (the brain region involved with reward and motivation) was associated with therapeutic response to methylphenidate, further corroborating the relevance of the dopamine reward/motivation circuitry in ADHD. It also provides preliminary evidence that methylphenidate-elicited dopamine increases in prefrontal and temporal cortices may also contribute to the clinical response. PMID:22262882

Methylphenidate-Elicited Dopamine Increases in Ventral Striatum Are Associated with Long-Term Symptom Improvement in Adults with Attention Deficit Hyperactivity Disorder

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

Volkow N. D.; Wang G.; Volkow, N.D.

Stimulant medications, such as methylphenidate, which are effective treatments for attention deficit hyperactivity disorder (ADHD), enhance brain dopamine signaling. However, the relationship between regional brain dopamine enhancement and treatment response has not been evaluated. Here, we assessed whether the dopamine increases elicited by methylphenidate are associated with long-term clinical response. We used a prospective design to study 20 treatment-naive adults with ADHD who were evaluated before treatment initiation and after 12 months of clinical treatment with a titrated regimen of oral methylphenidate. Methylphenidate-induced dopamine changes were evaluated with positron emission tomography and [{sup 11}C]raclopride (D{sub 2}/D{sub 3} receptor radioligand sensitivemore » to competition with endogenous dopamine). Clinical responses were assessed using the Conners Adult ADHD Rating Scale and revealed a significant reduction in symptoms of inattention and hyperactivity with long-term methylphenidate treatment. A challenge dose of 0.5 mg/kg intravenous methylphenidate significantly increased dopamine in striatum (assessed as decreases in D{sub 2}/D{sub 3} receptor availability). In the ventral striatum, these dopamine increases were associated with the reductions in ratings of symptoms of inattention with clinical treatment. Statistical parametric mapping additionally showed dopamine increases in prefrontal and temporal cortices with intravenous methylphenidate that were also associated with decreases in symptoms of inattention. Our findings indicate that dopamine enhancement in ventral striatum (the brain region involved with reward and motivation) was associated with therapeutic response to methylphenidate, further corroborating the relevance of the dopamine reward/motivation circuitry in ADHD. It also provides preliminary evidence that methylphenidate-elicited dopamine increases in prefrontal and temporal cortices may also contribute to the clinical response.« less

Clinical reasoning and critical thinking.

PubMed

da Silva Bastos Cerullo, Josinete Aparecida; de Almeida Lopes Monteiro da Cruz, Diná

2010-01-01

This study identifies and analyzes nursing literature on clinical reasoning and critical thinking. A bibliographical search was performed in LILACS, SCIELO, PUBMED and CINAHL databases, followed by selection of abstracts and the reading of full texts. Through the review we verified that clinical reasoning develops from scientific and professional knowledge, is permeated by ethical decisions and nurses values and also that there are different personal and institutional strategies that might improve the critical thinking and clinical reasoning of nurses. Further research and evaluation of educational programs on clinical reasoning that integrate psychosocial responses to physiological responses of people cared by nurses is needed.

Job-sharing a clinical teacher's position: an evaluation.

PubMed

Williams, S; Murphy, L

1994-01-01

The aim of this study was to evaluate the effects on staff of having two teachers share one clinical teaching position in their intensive care unit (ICU). Three, six and 12 months after the job-sharing arrangement was initiated, an 11 item questionnaire was distributed to 26 students in post-registration critical care courses, 41 clinical staff in ICU and 9 RN-managers with responsibilities for the unit. The overall response rate to the three questionnaires was 58%. All groups agreed that job-sharing was a viable alternative to full-time work. Three months after the shared position was initiated, there was uncertainty about the consistency of the teachers' performance and the adequacy of communication between them. Nine months later, there was a high level of positive responses to all areas of the teachers' performance. Most respondents felt they could approach either teacher and that more diverse ideas were generated by having two people in the teaching position.

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

PubMed

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 < 0.001). We observed AAA positivity (AAA+) at least 1 time point in 8 of 25 patients (32%), including 4 with transitory AAA and 4 with permanent AAA. In all patients with permanent AAA+, trough adalimumab levels became undetectable (P < 0.001). However, in patients who demonstrated transitory AAA+, no correlation was observed between AAA titers and adalimumab trough levels (P = 0.2).Concomitant immunosuppression did not show any protective effect on adalimumab immunogenicity in our cohort. An association between the presence of AAA+ and a worse 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.

Prospective evaluation of [11C]Choline PET/CT in therapy response assessment of standardized docetaxel first-line chemotherapy in patients with advanced castration refractory prostate cancer.

PubMed

Schwarzenböck, Sarah M; Eiber, Matthias; Kundt, Günther; Retz, Margitta; Sakretz, Monique; Kurth, Jens; Treiber, Uwe; Nawroth, Roman; Rummeny, Ernst J; Gschwend, Jürgen E; Schwaiger, Markus; Thalgott, Mark; Krause, Bernd J

2016-11-01

The aim of this study was to prospectively evaluate the value of [ 11 C] Choline PET/CT in monitoring early and late response to a standardized first-line docetaxel chemotherapy in castration refractory prostate cancer (mCRPC) patients. Thirty-two patients were referred for [ 11 C] Choline PET/CT before the start of docetaxel chemotherapy, after one and ten chemotherapy cycles (or - in case of discontinuation - after the last administered cycle) for therapy response assessment. [ 11 C] Choline uptake (SUV max , SUV mean ), CT derived Houndsfield units (HU max , HU mean ), and volume of bone, lung, and nodal metastases and local recurrence were measured semi-automatically at these timepoints. Change in SUV max , SUV mean , HU max , HU mean, and volume was assessed between PET 2 and 1 (early response assessment, ERA) and PET 3 and 1 (late response assessment, LRA) on a patient and lesion basis. Results of PET/CT were compared to clinically used RECIST 1.1 and clinical criteria based therapy response assessment including PSA for defining progressive disease (PD) and non-progressive disease (nPD), respectively. Relationships between changes of SUV max and SUV mean (early and late) and changes of PSA early and PSA late were evaluated. Prognostic value of initial SUV max and SUV mean was assessed. Statistical analyses were performed using SPSS. In the patient-based ERA and LRA there were no statistically significant differences in change of choline uptake, HU, and volume between PD and nPD applying RECIST or clinical response criteria. In the lesion-based ERA, decrease in choline uptake of bone metastases was even higher in PD (applying RECIST criteria), whereas in LRA the decrease was higher in nPD (applying clinical criteria). There were only significant correlations between change in choline uptake and PSA in ERA in PD, in LRA no significant correlations were discovered. Initial SUV max and SUV mean were statistically significantly higher in nPD (applying clinical criteria). There is no significant correlation between change in choline uptake in [ 11 C] Choline PET/CT and clinically routinely used objective response assessment during the early and late course of docetaxel chemotherapy. Therefore, [ 11 C] Choline PET/CT seems to be of limited use in therapy response assessment in standardized first-line chemotherapy in mCRPC patients.

Teachers' Perceptions of and Responses to Student Evaluation of Teaching: Purposes and Uses in Clinical Education

ERIC Educational Resources Information Center

Wong, Wai Yee; Moni, Karen

2014-01-01

Student evaluation of teaching (SET) only becomes an effective tool for improving teaching and learning when the relevant stakeholders seriously consider and plan appropriate actions according to student feedback. It is common practice in medical education to provide clinical teachers with student feedback. However, there is limited evidence about…

The responsiveness and correlation between Fugl-Meyer Assessment, Motor Status Scale, and the Action Research Arm Test in chronic stroke with upper-extremity rehabilitation robotic training.

PubMed

Wei, Xi-Jun; Tong, Kai-Yu; Hu, Xiao-Ling

2011-12-01

Responsiveness of clinical assessments is an important element in the report of clinical effectiveness after rehabilitation. The correlation could reflect the validity of assessments as an indication of clinical performance before and after interventions. This study investigated the correlation and responsiveness of Fugl-Meyer Assessment (FMA), Motor Status Scale (MSS), Action Research Arm Test (ARAT) and the Modified Ashworth Scale (MAS), which are used frequently in effectiveness studies of robotic upper-extremity training in stroke rehabilitation. Twenty-seven chronic stroke patients were recruited for a 20-session upper-extremity rehabilitation robotic training program. This was a rater-blinded randomized controlled trial. All participants were evaluated with FMA, MSS, ARAT, MAS, and Functional Independent Measure before and after robotic training. Spearman's rank correlation coefficient was applied for the analysis of correlation. The standardized response mean (SRM) and Guyatt's responsiveness index (GRI) were used to analyze responsiveness. Spearman's correlation coefficient showed a significantly high correlation (ρ=0.91-0.96) among FMA, MSS, and ARAT and a fair-to-moderate correlation (ρ=0.40-0.62) between MAS and the other assessments. FMA, MSS, and MAS on the wrist showed higher responsiveness (SRM=0.85-0.98, GRI=1.59-3.62), whereas ARAT showed relatively less responsiveness (SRM=0.22, GRI=0.81). The results showed that FMA or MSS would be the best choice for evaluating the functional improvement in stroke studies on robotic upper-extremity training with high responsiveness and good correlation with ARAT. MAS could be used separately to evaluate the spasticity changes after intervention in terms of high responsiveness.

Quantifying learning in medical students during a critical care medicine elective: a comparison of three evaluation instruments.

PubMed

Rogers, P L; Jacob, H; Rashwan, A S; Pinsky, M R

2001-06-01

To compare three different evaluative instruments and determine which is able to measure different aspects of medical student learning. Student learning was evaluated by using written examinations, objective structured clinical examination, and patient simulator that used two clinical scenarios before and after a structured critical care elective, by using a crossover design. Twenty-four 4th-yr students enrolled in the critical care medicine elective. All students took a multiple-choice written examination; evaluated a live simulated critically ill patient, requested data from a nurse, and intervened as appropriate at different stations (objective structured clinical examination); and evaluated the computer-controlled patient simulator and intervened as appropriate. Students' knowledge was assessed by using a multiple-choice examination containing the same data incorporated into the other examinations. Student performance on the objective structured clinical examination was evaluated at five stations. Both objective structured clinical examination and simulator tests were videotaped for subsequent scores of responses, quality of responses, and response time. The videotapes were reviewed for specific behaviors by faculty masked to time of examination. Students were expected to perform the following: a) assess airway, breathing, and circulation; b) prepare a mannequin for intubation; c) provide appropriate ventilator settings; d) manage hypotension; and e) request, interpret, and provide appropriate intervention for pulmonary artery catheter data. Students were expected to perform identical behaviors during the simulator examination; however, the entire examination was performed on the whole-body computer-controlled mannequin. The primary outcome measure was the difference in examination scores before and after the rotation. The mean preelective scores were 77 +/- 16%, 47 +/- 15%, and 41 +/- 14% for the written examination, objective structured clinical examination, and simulator, respectively, compared with 89 +/- 11%, 76 +/- 12%, and 62 +/- 15% after the elective (p <.0001). Prerotation scores for the written examination were significantly higher than the objective structured clinical examination or the simulator; postrotation scores were highest for the written examination and lowest for the simulator. Written examinations measure acquisition of knowledge but fail to predict if students can apply knowledge to problem solving, whereas both the objective structured clinical examination and the computer-controlled patient simulator can be used as effective performance evaluation tools.

Exploring the scope of oncology specialist nurses' practice in the UK.

PubMed

Farrell, Carole; Molassiotis, Alexander; Beaver, Kinta; Heaven, Cathy

2011-04-01

Revolutionary changes have taken place to nurses' roles and clinical responsibilities over the past decade, leading to new ways of working and higher levels of nursing practice. However, despite the development of nurse-led clinics and services within oncology there has been little formal evaluation. A survey of 103 UK oncology specialist nurses was undertaken to explore their scope of practice, with emphasis on nurse-led services. The survey highlighted significant developments within nurses' roles and nurse-led services, although there was a distinct lack of clarity between nurses' titles and their roles/responsibilities. Most nurses had extended their role. However there were significant differences in the nature of clinical practice, such as clinical examination and nurse prescribing. Overall, new roles were greatly valued by the multidisciplinary team, reducing waiting times and providing benefits for patients. However other nurses felt frustrated by deficiencies in infrastructure and support, which often overshadowed potential benefits. There is a great diversity in oncology specialist nurses' roles; however lack of clarity in titles, training, competencies and responsibilities is creating confusion. Role developments and nurse-led clinics have been ad hoc and poorly evaluated. The introduction of a competency framework, national standards and a system of clinical appraisals seems key to providing increased transparency and vital safeguards for both nurses and patients. Without further exploration and evaluation of nurse-led initiatives it is difficult to fully appreciate their impact on patients, staff and service delivery. Copyright © 2010 Elsevier Ltd. All rights reserved.

A Parent-Mediated Intervention that Targets Responsive Parental Behaviors Increases Attachment Behaviors in Children with ASD: Results from a Randomized Clinical Trial

ERIC Educational Resources Information Center

Siller, Michael; Swanson, Meghan; Gerber, Alan; Hutman, Ted; Sigman, Marian

2014-01-01

The current study is a randomized clinical trial evaluating the efficacy of Focused Playtime Intervention (FPI) in a sample of 70 children with Autism Spectrum Disorder. This parent-mediated intervention has previously been shown to significantly increase responsive parental communication (Siller et al. in "J Autism Dev Disord"…

Qualitative radiology assessment of tumor response: does it measure up?

PubMed

Gottlieb, Ronald H; Litwin, Alan; Gupta, Bhavna; Taylor, John; Raczyk, Cheryl; Mashtare, Terry; Wilding, Gregory; Fakih, Marwan

2008-01-01

Our purpose was to assess whether a simpler qualitative evaluation of tumor response by computed tomography is as reproducible and predictive of clinical outcome as the Response Evaluation Criteria in Solid Tumors (RECIST) and World Health Organization (WHO) methods. This study was a two-reader retrospective evaluation in which qualitative assessment resulted in agreement in 21 of 23 patients with metastatic colorectal carcinoma (91.3%, kappa=0.78; 95% CI, 0.51-1.00). Hepatic metastases were classified as increased, decreased, or unchanged, compared with agreement in 20 of 23 patients (87.0%) for RECIST (kappa=0.62; 95% CI, 0.23-1.00) and WHO (kappa=0.67; 95% CI, 0.34-1.00) methods. Patients were placed into partial response, stable disease, and disease progression categories. Time to progression of disease was better predicted qualitatively than by RECIST or WHO. Our pilot data suggest that our qualitative scoring system is more reproducible and predictive of patient clinical outcome than the RECIST and WHO methods.

A prospective pilot study of genome-wide exome and transcriptome profiling in patients with small cell lung cancer progressing after first-line therapy.

PubMed

Weiss, Glen J; Byron, Sara A; Aldrich, Jessica; Sangal, Ashish; Barilla, Heather; Kiefer, Jeffrey A; Carpten, John D; Craig, David W; Whitsett, Timothy G

2017-01-01

Small cell lung cancer (SCLC) that has progressed after first-line therapy is an aggressive disease with few effective therapeutic strategies. In this prospective study, we employed next-generation sequencing (NGS) to identify therapeutically actionable alterations to guide treatment for advanced SCLC patients. Twelve patients with SCLC were enrolled after failing platinum-based chemotherapy. Following informed consent, genome-wide exome and RNA-sequencing was performed in a CLIA-certified, CAP-accredited environment. Actionable targets were identified and therapeutic recommendations made from a pharmacopeia of FDA-approved drugs. Clinical response to genomically-guided treatment was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The study completed its accrual goal of 12 evaluable patients. The minimum tumor content for successful NGS was 20%, with a median turnaround time from sample collection to genomics-based treatment recommendation of 27 days. At least two clinically actionable targets were identified in each patient, and six patients (50%) received treatment identified by NGS. Two had partial responses by RECIST 1.1 on a clinical trial involving a PD-1 inhibitor + irinotecan (indicated by MLH1 alteration). The remaining patients had clinical deterioration before NGS recommended therapy could be initiated. Comprehensive genomic profiling using NGS identified clinically-actionable alterations in SCLC patients who progressed on initial therapy. Recommended PD-1 therapy generated partial responses in two patients. Earlier access to NGS guided therapy, along with improved understanding of those SCLC patients likely to respond to immune-based therapies, should help to extend survival in these cases with poor outcomes.

Alcohol- and light-induced electro-oculographic responses: variability and clinical utility.

PubMed

Marmor, Michael F; Wu, Kathy H C

2005-01-01

The alcohol-induced electro-oculographic (EOG) response has been proposed by Arden as an indicator of retinal pigment epithelial (RPE) integrity. We have evaluated the consistency of the alcohol-EOG with respect to clinical applicability and compared this response to the ISCEV-standard EOG. We recorded, in a group of normal subjects (n=29, 14 men with mean age 42+/-11 years and 15 women with mean age 36+/-13 years), the alcohol response to a single oral dose of ethanol at 160 mg/kg (as 40 proof vodka, drunk in 15 s after 12 h of fasting), followed by an ISCEV-standard EOG 90 min after alcohol administration. Blood alcohol levels were monitored at regular intervals with a breath analyzer. We found a wide range of amplitudes in both light and alcohol responses among participants, from minimal to large values. Subjects had a wide range of blood alcohol concentrations from 0.02 to 0.10%; near the time of the response peak, but there was no relationship between alcohol levels and peak/baseline ratios. In addition, there was no relationship between alcohol peak/baseline ratio and the Arden ratio. Neither the alcohol nor the light response parameters showed any relationship with age or gender. Some of the inter-individual variability in the EOG response to alcohol may reflect variable absorption of oral alcohol. The alcohol-induced EOG has too broad a range of responses to be useful clinically for the one-time evaluation of individual patients. We have similar concerns regarding clinical applications of the standard light-induced EOG.

INVITED REVIEW – NEUROIMAGING RESPONSE ASSESSMENT CRITERIA FOR BRAIN TUMORS IN VETERINARY PATIENTS

PubMed Central

Rossmeisl, John H.; Garcia, Paulo A.; Daniel, Gregory B.; Bourland, John Daniel; Debinski, Waldemar; Dervisis, Nikolaos; Klahn, Shawna

2013-01-01

The evaluation of therapeutic response using cross-sectional imaging techniques, particularly gadolinium-enhanced MRI, is an integral part of the clinical management of brain tumors in veterinary patients. Spontaneous canine brain tumors are increasingly recognized and utilized as a translational model for the study of human brain tumors. However, no standardized neuroimaging response assessment criteria have been formulated for use in veterinary clinical trials. Previous studies have found that the pathophysiologic features inherent to brain tumors and the surrounding brain complicate the use of the Response Evaluation Criteria in Solid Tumors (RECIST) assessment system. Objectives of this review are to describe strengths and limitations of published imaging-based brain tumor response criteria and propose a system for use in veterinary patients. The widely used human Macdonald and Response Assessment in Neuro-oncology (RANO) criteria are reviewed and described as to how they can be applied to veterinary brain tumors. Discussion points will include current challenges associated with the interpretation of brain tumor therapeutic responses such as imaging pseudophenomena and treatment-induced necrosis, and how advancements in perfusion imaging, positron emission tomography, and magnetic resonance spectroscopy have shown promise in differentiating tumor progression from therapy-induced changes. Finally, although objective endpoints such as MR-imaging and survival estimates will likely continue to comprise the foundations for outcome measures in veterinary brain tumor clinical trials, we propose that in order to provide a more relevant therapeutic response metric for veterinary patients, composite response systems should be formulated and validated that combine imaging and clinical assessment criteria. PMID:24219161

User acceptance of observation and response charts with a track and trigger system: a multisite staff survey.

PubMed

Elliott, Doug; Allen, Emily; McKinley, Sharon; Perry, Lin; Duffield, Christine; Fry, Margaret; Gallagher, Robyn; Iedema, Rick; Roche, Michael

2016-08-01

To examine user acceptance with a new format of charts for recording observations and as a prompt for responding to episodes of clinical deterioration in adult medical-surgical patients. Improving recognition and response to clinical deterioration remains a challenge for acute healthcare institutions globally. Five chart templates were developed in Australia, combining human factors design principles with a track and trigger system for escalation of care. Two chart templates were previously tested in simulations, but none had been evaluated in clinical practice. Prospective multisite survey of user acceptance of the charts in practice. New observation and response charts were trialled in parallel with existing charts for 24 hours across 36 adult acute medical-surgical wards, covering 108 shifts, in five Australian states. Surveys were completed by 477 staff respondents, with open-ended comments and narrative from short informal feedback groups providing elaboration and context of user experiences. Respondents were broadly supportive of the chart format and content for monitoring patients, and as a prompt for escalating care. Some concerns were noted for chart size and style, use of ranges to graph vital signs and with specific human factors design features. Information and training issues were identified to improve usability and adherence to chart guidelines and to support improved detection and response for patients with clinical deterioration. This initial evaluation demonstrated that the charts were perceived as appropriate for documenting observations and as a prompt to detect clinical deterioration. Further evaluation after some minor modifications to the chart is recommended. Explicit training on the principles and rationale of human factors chart design, use of embedded change management strategies and addressing practical issues will improve authentic engagement, staff acceptance and adoption by all clinical users when implementing a similar observation and response chart into practice. © 2016 John Wiley & Sons Ltd.

Exploring the measurement properties of the osteopathy clinical teaching questionnaire using Rasch analysis.

PubMed

Vaughan, Brett

2018-01-01

Clinical teaching evaluations are common in health profession education programs to ensure students are receiving a quality clinical education experience. Questionnaires students use to evaluate their clinical teachers have been developed in professions such as medicine and nursing. The development of a questionnaire that is specifically for the osteopathy on-campus, student-led clinic environment is warranted. Previous work developed the 30-item Osteopathy Clinical Teaching Questionnaire. The current study utilised Rasch analysis to investigate the construct validity of the Osteopathy Clinical Teaching Questionnaire and provide evidence for the validity argument through fit to the Rasch model. Senior osteopathy students at four institutions in Australia, New Zealand and the United Kingdom rated their clinical teachers using the Osteopathy Clinical Teaching Questionnaire. Three hundred and ninety-nine valid responses were received and the data were evaluated for fit to the Rasch model. Reliability estimations (Cronbach's alpha and McDonald's omega) were also evaluated for the final model. The initial analysis demonstrated the data did not fit the Rasch model. Accordingly, modifications to the questionnaire were made including removing items, removing person responses, and rescoring one item. The final model contained 12 items and fit to the Rasch model was adequate. Support for unidimensionality was demonstrated through both the Principal Components Analysis/t-test, and the Cronbach's alpha and McDonald's omega reliability estimates. Analysis of the questionnaire using McDonald's omega hierarchical supported a general factor (quality of clinical teaching in osteopathy). The evidence for unidimensionality and the presence of a general factor support the calculation of a total score for the questionnaire as a sufficient statistic. Further work is now required to investigate the reliability of the 12-item Osteopathy Clinical Teaching Questionnaire to provide evidence for the validity argument.

Electromyographic evaluation of the 'vertical' dimension: the Learreta TMJ decompression test.

PubMed

Freire Matos, Marcelo; Durst, Andreas C; Freire Matos, Jane Luzia; Learreta, Jorge Alfonso

2011-10-01

The clinical observation of the incisors overbite is the most common form used to evaluate the occlusal vertical dimension (OVD); however, this technique offers poor information about the compression state of the TMJ. In order to obtain such information, it is necessary to evaluate the electrical activity of the elevator muscles using surface electromyography (EMG). In case of a compressive irritation of the joint receptors, the trigeminal nucleus returns an inhibitory motor response of the elevator muscles that can be measured. The Learreta's EMG decompression test is done by measuring the EMG response of the masticatory muscles at maximal occlusion in four different OVD positions in such a way that the reduction of the TMJ pressure, and subsequently, relief of the inhibitory motor response can be studied. The aim of this study is to illustrate this technique, its clinical use and its limitations.

Improving the clinical instruction of student technologists.

PubMed

Steves, Ann M

2005-12-01

Many nuclear medicine technologists (NMTs) are employed in departments affiliated with programs that prepare individuals to become NMTs. These departments are sites where students receive hands-on clinical experience. The NMTs who staff these departments serve as clinical instructors whose responsibilities include teaching students the skills, attitudes, and knowledge necessary to become competent technologists. Clinical instructors often have no formal preparation in teaching or evaluating students. The purpose of this article is to review some principles related to teaching and critiquing clinical performance that will help clinical instructors support and foster the professional development of student technologists. After reading this article, the reader should be able to (a) identify the qualities of an effective clinical instructor, (b) identify the characteristics of constructive feedback, (c) identify appropriate times for evaluation and feedback, and (d) use facilitation skills when providing feedback and evaluating student performance.

Partial clinical response to anakinra in severe palmoplantar pustular psoriasis.

PubMed

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.

Development and Implementation of an Electronic Clinical Formative Assessment: Dental Faculty and Student Perspectives.

PubMed

Kirkup, Michele L; Adams, Brooke N; Meadows, Melinda L; Jackson, Richard

2016-06-01

A traditional summative grading structure, used at Indiana University School of Dentistry (IUSD) for more than 30 years, was identified by faculty as outdated for assessing students' clinical performance. In an effort to change the status quo, a feedback-driven assessment was implemented in 2012 to provide a constructive assessment tool acceptable to both faculty and students. Building on the successful non-graded clinical evaluation employed at Baylor College of Dentistry, IUSD implemented a streamlined electronic formative feedback model (FFM) to assess students' daily clinical performance. An important addition to this evaluation tool was the inclusion of routine student self-assessment opportunities. The aim of this study was to determine faculty and student response to the new assessment instrument. Following training sessions, anonymous satisfaction surveys were examined for the three user groups: clinical faculty (60% response rate), third-year (D3) students (72% response rate), and fourth-year (D4) students (57% response rate). In the results, 70% of the responding faculty members preferred the FFM over the summative model; however, 61.8% of the D4 respondents preferred the summative model, reporting insufficient assessment time and low faculty participation. The two groups of students had different responses to the self-assessment component: 70.2% of the D4 respondents appreciated clinical self-assessment compared to 46% of the D3 respondents. Overall, while some components of the FFM assessment were well received, a phased approach to implementation may have facilitated a transition more acceptable to both faculty and students. Improvements are being made in an attempt to increase overall satisfaction.

Clinical End Points and Response Criteria in Mycosis Fungoides and Sézary Syndrome: A Consensus Statement of the International Society for Cutaneous Lymphomas, the United States Cutaneous Lymphoma Consortium, and the Cutaneous Lymphoma Task Force of the European Organisation for Research and Treatment of Cancer

PubMed Central

Olsen, Elise A.; Whittaker, Sean; Kim, Youn H.; Duvic, Madeleine; Prince, H. Miles; Lessin, Stuart R.; Wood, Gary S.; Willemze, Rein; Demierre, Marie-France; Pimpinelli, Nicola; Bernengo, Maria Grazia; Ortiz-Romero, Pablo L.; Bagot, Martine; Estrach, Teresa; Guitart, Joan; Knobler, Robert; Sanches, José Antonio; Iwatsuki, Keiji; Sugaya, Makoto; Dummer, Reinhard; Pittelkow, Mark; Hoppe, Richard; Parker, Sareeta; Geskin, Larisa; Pinter-Brown, Lauren; Girardi, Michael; Burg, Günter; Ranki, Annamari; Vermeer, Maartan; Horwitz, Steven; Heald, Peter; Rosen, Steve; Cerroni, Lorenzo; Dreno, Brigette; Vonderheid, Eric C.

2011-01-01

Mycosis fungoides (MF) and Sézary syndrome (SS), the major forms of cutaneous T-cell lymphoma, have unique characteristics that distinguish them from other types of non-Hodgkin's lymphomas. Clinical trials in MF/SS have suffered from a lack of standardization in evaluation, staging, assessment, end points, and response criteria. Recently defined criteria for the diagnosis of early MF, guidelines for initial evaluation, and revised staging and classification criteria for MF and SS now offer the potential for uniform staging of patients enrolled in clinical trials for MF/SS. This article presents consensus recommendations for the general conduct of clinical trials of patients with MF/SS as well as methods for standardized assessment of potential disease manifestations in skin, lymph nodes, blood, and visceral organs, and definition of end points and response criteria. These guidelines should facilitate collaboration among investigators and collation of data from sponsor-generated or investigator-initiated clinical trials involving patients with MF or SS. PMID:21576639

Prediction of therapeutic response in steroid-treated pulmonary sarcoidosis. Evaluation of clinical parameters, bronchoalveolar lavage, gallium-67 lung scanning, and serum angiotensin-converting enzyme levels

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

Hollinger, W.M.; Staton, G.W. Jr.; Fajman, W.A.

1985-07-01

To find a pretreatment predictor of steroid responsiveness in pulmonary sarcoidosis the authors studied 21 patients before and after steroid treatment by clinical evaluation, pulmonary function tests, bronchoalveolar lavage (BAL), gallium-67 lung scan, and serum angiotensin-converting enzyme (SACE) level. Although clinical score, forced vital capacity (FVC), BAL percent lymphocytes (% lymphs), quantitated gallium-67 lung uptake, and SACE levels all improved with therapy, only the pretreatment BAL % lymphs correlated with the improvement in FVC (r = 0.47, p less than 0.05). Pretreatment BAL % lymphs of greater than or equal to 35% predicted improvement in FVC of 10/11 patients, whereasmore » among 10 patients with BAL % lymphs less than 35%, 5 patients improved and 5 deteriorated. Clinical score, pulmonary function parameters, quantitated gallium-67 lung uptake, and SACE level used alone, in combination with BAL % lymphs or in combination with each other, did not improve this predictive value. The authors conclude that steroid therapy improves a number of clinical and laboratory parameters in sarcoidosis, but only the pretreatment BAL % lymphs are useful in predicting therapeutic responsiveness.« less

IgG sera levels against a subset of periodontopathogens and severity of disease in aggressive periodontitis patients: a cross-sectional study of selected pocket sites.

PubMed

Saraiva, Luciana; Rebeis, Estela S; Martins, Eder de S; Sekiguchi, Ricardo T; Ando-Suguimoto, Ellen S; Mafra, Carlos Eduardo S; Holzhausen, Marinella; Romito, Giuseppe A; Mayer, Marcia P A

2014-10-01

To evaluate the association among serum immunoglobulin G (IgG) responses to Aggregatibacter actinomycetemcomitans (Aa) serotypes a, b and c, Porphyromonas gingivalis (Pg), Tannerella forsythia (Tf) and clinical parameters in Aggressive Periodontitis (AP) subjects. Associations between periodontal pathogens and clinical and immunological parameters were also evaluated. Thirty-eight subjects diagnosed with generalized AP (GAP) and localized AP (LAP) were included. Ten healthy controls were also evaluated. Clinical parameters were assessed and percentages of subgingival levels of Aa, Pg and Tf (beyond bacterial load), were determined by quantitative real-time polymerase chain reaction. Serum IgG antibody levels against Aa, Pg and Tf were evaluated by enzyme-linked immunosorbent assay. Percentages of Aa, Pg and Tf were significantly higher in AP than in controls. The response to Aa serotype c was higher in LAP subjects than in controls. There were no differences in microbial composition or antibodies responses between GAP and LAP, except for IgG response to Tf. Pg levels were correlated with probing depth (PD), BoP and CAL in GAP but not in LAP subjects. Tf levels correlated with PD and CAL in GAP subjects. In GAP, the infection levels of Aa and Pg correlated with the corresponding IgG levels to Aa serotype c and Pg. Given the evidences that IgG response in AP patients correlated with bacterial infection level in GAP, but not in LAP, and that LAP patients lack a response to Tf, despite harbouring this species, our data suggest a difference in host immune defence between these two forms of aggressive periodontitis. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

NASA Astrophysics Data System (ADS)

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

2004-08-01

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

TH-E-202-01: Pitfalls and Remedies in PET/CT Imaging for RT Planning

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

Pan, T.

2016-06-15

PET/CT is a very important imaging tool in the management of oncology patients. PET/CT has been applied for treatment planning and response evaluation in radiation therapy. This educational session will discuss: Pitfalls and remedies in PET/CT imaging for RT planning The use of hypoxia PET imaging for radiotherapy PET for tumor response evaluation The first presentation will address the issue of mis-registration between the CT and PET images in the thorax and the abdomen. We will discuss the challenges of respiratory gating and introduce an average CT technique to improve the registration for dose calculation and image-guidance in radiation therapy.more » The second presentation will discuss the use of hypoxia PET Imaging for radiation therapy. We will discuss various hypoxia radiotracers, the choice of clinical acquisition protocol (in particular a single late static acquisition versus a dynamic acquisition), and the compartmental modeling with different transfer rate constants explained. We will demonstrate applications of hypoxia imaging for dose escalation/de-escalation in clinical trials. The last presentation will discuss the use of PET/CT for tumor response evaluation. We will discuss anatomic response assessment vs. metabolic response assessment, visual evaluation and semi-quantitative evaluation, and limitations of current PET/CT assessment. We will summarize clinical trials using PET response in guiding adaptive radiotherapy. Finally, we will summarize recent advancements in PET/CT radiomics and non-FDG PET tracers for response assessment. Learning Objectives: Identify the causes of mis-registration of CT and PET images in PET/CT, and review the strategies to remedy the issue. Understand the basics of PET imaging of tumor hypoxia (radiotracers, how PET measures the hypoxia selective uptake, imaging protocols, applications in chemo-radiation therapy). Understand the basics of dynamic PET imaging, compartmental modeling and parametric images. Understand the basics of using FDG PET/CT for tumor response evaluation. Learn about recent advancement in PET/CT radiomics and non-FDG PET tracers for response assessment. This work was supported in part by the National Cancer Institute Grants R01CA172638.; W. Lu, This work was supported in part by the National Cancer Institute Grants R01CA172638.« less

Clinical efficacy and safety following dose tapering of ciclosporin in cats with hypersensitivity dermatitis.

PubMed

Roberts, Elizabeth S; Tapp, Tiffany; Trimmer, Ann; Roycroft, Linda; King, Stephen

2016-11-01

Objectives This study was designed to evaluate the efficacy and safety of reducing ciclosporin (CsA) dosing frequency from daily to every other day (EOD) or twice a week (TW) according to clinical response in cats with hypersensitivity dermatitis (HD) and treated with CsA. Methods One hundred and ninety-one cats with HD were given 7 mg/kg CsA daily for at least 4 weeks. Depending on clinical response, the dosing frequency was tapered from daily to EOD over the next 4 weeks and further to TW for an additional 4 weeks. Safety was evaluated through physical examinations, clinical pathology and the monitoring of adverse events (AEs). Results The majority of cats were able to have their dose of CsA tapered to either EOD (15.5%) or TW (62.9%) according to the clinical response. Observed AEs were most frequently mild and self-limiting vomiting and diarrhea. A higher percentage of AEs occurred with daily administration (73%) compared with other dosing regimens (27%). Conclusions and relevance Following 4 weeks of daily dosing at 7 mg/kg, CsA may be tapered to EOD or TW while maintaining the desired therapeutic response in cats with HD. Additionally, CsA appears to be well tolerated with fewer AEs at EOD or TW dosing. Establishing the lowest effective dosing frequency of CsA improves the drug's safety profile.

Recommendations on risk-based strategies for detection and characterization of antibodies against biotechnology products.

PubMed

Koren, Eugen; Smith, Holly W; Shores, Elizabeth; Shankar, Gopi; Finco-Kent, Deborah; Rup, Bonita; Barrett, Yu-Chen; Devanarayan, Viswanath; Gorovits, Boris; Gupta, Shalini; Parish, Thomas; Quarmby, Valerie; Moxness, Michael; Swanson, Steven J; Taniguchi, Gary; Zuckerman, Linda A; Stebbins, Christopher C; Mire-Sluis, Anthony

2008-04-20

The appropriate evaluation of the immunogenicity of biopharmaceuticals is of major importance for their successful development and licensure. Antibodies elicited by these products in many cases cause no detectable clinical effects in humans. However, antibodies to some therapeutic proteins have been shown to cause a variety of clinical consequences ranging from relatively mild to serious adverse events. In addition, antibodies can affect drug efficacy. In non-clinical studies, anti-drug antibodies (ADA) can complicate interpretation of the toxicity, pharmacokinetic (PK) and pharmacodynamic (PD) data. Therefore, it is important to develop testing strategies that provide valid assessments of antibody responses in both non-clinical and clinical studies. This document provides recommendations for antibody testing strategies stemming from the experience of contributing authors. The recommendations are intended to foster a more unified approach to antibody testing across the biopharmaceutical industry. The strategies proposed are also expected to contribute to better understanding of antibody responses and to further advance immunogenicity evaluation.

Phase-II trials in osteosarcoma recurrences: A systematic review of past experience.

PubMed

Omer, Natacha; Le Deley, Marie-Cécile; Piperno-Neumann, Sophie; Marec-Berard, Perrine; Italiano, Antoine; Corradini, Nadège; Bellera, Carine; Brugières, Laurence; Gaspar, Nathalie

2017-04-01

The most appropriate design of Phase-II trials evaluating new therapies in osteosarcoma remains poorly defined. To study consistency in phase-II clinical trials evaluating new therapies for osteosarcoma recurrences with respect to eligibility criteria, response assessment, end-points, statistical design and reported results. Systematic review of clinical trials registered on clinicaltrials.gov, clinicaltrialsregister.eu and French National Cancer Institute website or referenced in PubMed and American Society of Clinical Oncology websites, between 2003 and 2016, using the following criteria: (osteosarcoma OR bone sarcoma) AND (Phase-II). Among the 99 trials identified, 80 were Phase-II, 17 I/II and 2 II/III, evaluating mostly targeted therapy (n = 40), and chemotherapy alone (n = 26). Results were fully (n = 28) or partially (abstract, n = 6) published. Twenty-four trials were dedicated to osteosarcoma, 22 had an osteosarcoma stratum. Twenty-eight out of 99 trials refer to the age range observed at recurrence (28%). Overall, 65 trials were run in multicentre settings, including 17 international trials. Only 9 trials were randomised. The primary end-point was tumour response in 71 trials (response rate, n = 40 or best response, n = 31), with various definitions (complete + partial ± minor response and stable disease), mainly evaluated with RECIST criteria (n = 69); it was progression-free survival in 24 trials and OS in 3. In single-arm trials evaluating response rate, the null hypothesis tested (when available, n = 12) varied from 5% to 25%. No robust historical data can currently be derived from past efficacy Phase-II trials. There is an urgent need to develop international randomised Phase-II trials across all age ranges with standardised primary end-point. Copyright © 2017 Elsevier Ltd. All rights reserved.

Implementation of an audio computer-assisted self-interview (ACASI) system in a general medicine clinic: patient response burden.

PubMed

Trick, W E; Deamant, C; Smith, J; Garcia, D; Angulo, F

2015-01-01

Routine implementation of instruments to capture patient-reported outcomes could guide clinical practice and facilitate health services research. Audio interviews facilitate self-interviews across literacy levels. To evaluate time burden for patients, and factors associated with response times for an audio computer-assisted self interview (ACASI) system integrated into the clinical workflow. We developed an ACASI system, integrated with a research data warehouse. Instruments for symptom burden, self-reported health, depression screening, tobacco use, and patient satisfaction were administered through touch-screen monitors in the general medicine clinic at the Cook County Health & Hospitals System during April 8, 2011-July 27, 2012. We performed a cross-sectional study to evaluate the mean time burden per item and for each module of instruments; we evaluated factors associated with longer response latency. Among 1,670 interviews, the mean per-question response time was 18.4 [SD, 6.1] seconds. By multivariable analysis, age was most strongly associated with prolonged response time and increased per decade compared to < 50 years as follows (additional seconds per question; 95% CI): 50-59 years (1.4; 0.7 to 2.1 seconds); 60-69 (3.4; 2.6 to 4.1); 70-79 (5.1; 4.0 to 6.1); and 80-89 (5.5; 4.1 to 7.0). Response times also were longer for Spanish language (3.9; 2.9 to 4.9); no home computer use (3.3; 2.8 to 3.9); and, low mental self-reported health (0.6; 0.0 to 1.1). However, most interviews were completed within 10 minutes. An ACASI software system can be included in a patient visit and adds minimal time burden. The burden was greatest for older patients, interviews in Spanish, and for those with less computer exposure. A patient's self-reported health had minimal impact on response times.

A prospective pilot study of genome-wide exome and transcriptome profiling in patients with small cell lung cancer progressing after first-line therapy

PubMed Central

Byron, Sara A.; Aldrich, Jessica; Sangal, Ashish; Barilla, Heather; Kiefer, Jeffrey A.; Carpten, John D.; Craig, David W.; Whitsett, Timothy G.

2017-01-01

Background Small cell lung cancer (SCLC) that has progressed after first-line therapy is an aggressive disease with few effective therapeutic strategies. In this prospective study, we employed next-generation sequencing (NGS) to identify therapeutically actionable alterations to guide treatment for advanced SCLC patients. Methods Twelve patients with SCLC were enrolled after failing platinum-based chemotherapy. Following informed consent, genome-wide exome and RNA-sequencing was performed in a CLIA-certified, CAP-accredited environment. Actionable targets were identified and therapeutic recommendations made from a pharmacopeia of FDA-approved drugs. Clinical response to genomically-guided treatment was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Results The study completed its accrual goal of 12 evaluable patients. The minimum tumor content for successful NGS was 20%, with a median turnaround time from sample collection to genomics-based treatment recommendation of 27 days. At least two clinically actionable targets were identified in each patient, and six patients (50%) received treatment identified by NGS. Two had partial responses by RECIST 1.1 on a clinical trial involving a PD-1 inhibitor + irinotecan (indicated by MLH1 alteration). The remaining patients had clinical deterioration before NGS recommended therapy could be initiated. Conclusions Comprehensive genomic profiling using NGS identified clinically-actionable alterations in SCLC patients who progressed on initial therapy. Recommended PD-1 therapy generated partial responses in two patients. Earlier access to NGS guided therapy, along with improved understanding of those SCLC patients likely to respond to immune-based therapies, should help to extend survival in these cases with poor outcomes. PMID:28586388

High Familial Correlation in Methylphenidate Response and Side Effect Profile.

PubMed

Gazer-Snitovsky, Michal; Brand-Gothelf, Ayelet; Dubnov-Raz, Gal; Weizman, Abraham; Gothelf, Doron

2015-04-21

To examine whether a familial tendency exists in clinical response to methylphenidate. Nineteen pairs of siblings or parent-child stimulant-naive individuals with ADHD were prescribed methylphenidate-immediate release, and were comprehensively evaluated at baseline, Week 2, and Week 4, using the ADHD Rating Scale IV, Clinical Global Impression Scale, and the Barkley Side Effects Rating Scale. We found significant intraclass correlations in family member response to methylphenidate-immediate release and side effect profile, including emotional symptoms and loss of appetite and weight. Family history of response to methylphenidate should be taken into account when treating ADHD. © 2015 SAGE Publications.

Evaluation of a respiratory symptom diary for clinical studies of idiopathic pulmonary fibrosis.

PubMed

Bacci, Elizabeth Dansie; O'Quinn, Sean; Leidy, Nancy Kline; Murray, Lindsey; Vernon, Margaret

2018-01-01

There are no validated patient diaries for evaluating respiratory symptoms in idiopathic pulmonary fibrosis (IPF). To evaluate the performance properties of the chronic obstructive pulmonary disease (COPD) Evaluating Respiratory Symptoms™ (E-RS™: COPD) measure in patients with IPF. Concept elicitation and cognitive interviews were conducted with IPF patients to evaluate content validity, including comprehensiveness, relevance, and interpretability of E-RS™ items in this patient population. Secondary analyses of IPF clinical study data were performed to evaluate the scoring structure of the tool. With modifications, reliability, validity, and responsiveness of the instrument (E-RS™: IPF) were evaluated. Qualitative interviews (n = 30) were conducted. During the elicitation interviews (n = 20), concept saturation for IPF respiratory symptoms was achieved; all respiratory symptoms covered by the E-RS™ were endorsed by ≥ 30% of the sample. During cognitive interviews (n = 10), all participants found the items interpretable and relevant. Factor analyses conducted via secondary analysis of IPF clinical study data identified no total score and four symptom scales: Chest, Breathlessness, Cough, and Sputum. Reliability of each scale was high (internal consistency [α] >0.85); 2-day reproducibility (ICC >0.88). Validity was supported through significant (P < 0.0001) relationships with the St. George's Respiratory Questionnaire (SGRQ), the University of California, San Diego Shortness of Breath Questionnaire (UCSD-SOBQ), and other variables. The scales were responsive to change when evaluated using SGRQ Symptoms, UCSD-SOBQ, and Patient Global Impression of Change as anchors (P < 0.01 to P < 0.0001). The E-RS™: IPF is a valid, reliable, and responsive tool for evaluating respiratory symptoms in patients with IPF. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Update: Interim Guidance for the Diagnosis, Evaluation, and Management of Infants with Possible Congenital Zika Virus Infection - United States, October 2017.

PubMed

Adebanjo, Tolulope; Godfred-Cato, Shana; Viens, Laura; Fischer, Marc; Staples, J Erin; Kuhnert-Tallman, Wendi; Walke, Henry; Oduyebo, Titilope; Polen, Kara; Peacock, Georgina; Meaney-Delman, Dana; Honein, Margaret A; Rasmussen, Sonja A; Moore, Cynthia A

2017-10-20

CDC has updated its interim guidance for U.S. health care providers caring for infants with possible congenital Zika virus infection (1) in response to recently published updated guidance for health care providers caring for pregnant women with possible Zika virus exposure (2), unknown sensitivity and specificity of currently available diagnostic tests for congenital Zika virus infection, and recognition of additional clinical findings associated with congenital Zika virus infection. All infants born to mothers with possible Zika virus exposure* during pregnancy should receive a standard evaluation at birth and at each subsequent well-child visit including a comprehensive physical examination, age-appropriate vision screening and developmental monitoring and screening using validated tools (3-5), and newborn hearing screen at birth, preferably using auditory brainstem response (ABR) methodology (6). Specific guidance for laboratory testing and clinical evaluation are provided for three clinical scenarios in the setting of possible maternal Zika virus exposure: 1) infants with clinical findings consistent with congenital Zika syndrome regardless of maternal testing results, 2) infants without clinical findings consistent with congenital Zika syndrome who were born to mothers with laboratory evidence of possible Zika virus infection, † and 3) infants without clinical findings consistent with congenital Zika syndrome who were born to mothers without laboratory evidence of possible Zika virus infection. Infants in the first two scenarios should receive further testing and evaluation for Zika virus, whereas for the third group, further testing and clinical evaluation for Zika virus are not recommended. Health care providers should remain alert for abnormal findings (e.g., postnatal-onset microcephaly and eye abnormalities without microcephaly) in infants with possible congenital Zika virus exposure without apparent abnormalities at birth.

76 FR 49776 - The Development and Evaluation of Next-Generation Smallpox Vaccines; Public Workshop

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-11

... antibodies and cell- mediated immune responses, with both clinical and immunological outcomes similar to... appropriate, and to comparative human immune response data. As for any biologic product, licensure of new...

The 6 "ws" of rapid response systems: best practices for improving development, implementation, and evaluation.

PubMed

Lazzara, Elizabeth H; Benishek, Lauren E; Sonesh, Shirley C; Patzer, Brady; Robinson, Patricia; Wallace, Ruth; Salas, Eduardo

2014-01-01

Delays in care have been cited as one of the primary contributors of preventable mortality; thus, quality patient safety is often contingent upon the delivery of timely clinical care. Rapid response systems (RRSs) have been touted as one mechanism to improve the ability of suitable staff to respond to deteriorating patients quickly and appropriately. Rapid response systems are defined as highly skilled individual(s) who mobilize quickly to provide medical care in response to clinical deterioration. While there is mounting evidence that RRSs are a valid strategy for managing obstetric emergencies, reducing adverse events, and improving patient safety, there remains limited insight into the practices underlying the development and execution of these systems. Therefore, the purpose of this article was to synthesize the literature and answer the primary questions necessary for successfully developing, implementing, and evaluating RRSs within inpatient settings-the Who, What, When, Where, Why, and How of RRSs.

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

PubMed

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

2004-02-01

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

Change in plasma lactate concentration during arctigenin administration in a phase I clinical trial in patients with gemcitabine-refractory pancreatic cancer

PubMed Central

Fujioka, Rumi; Mochizuki, Nobuo; Ikeda, Masafumi; Sato, Akihiro; Nomura, Shogo; Owada, Satoshi; Yomoda, Satoshi; Tsuchihara, Katsuya; Kishino, Satoshi

2018-01-01

Arctigenin is evaluated for antitumor efficacy in patients with pancreatic cancer. It has an inhibitory activity on mitochondrial complex I.Therefore, plasma lactate level of patients after arctigenin administration was evaluated for biomarker of clinical response and/or adverse effect. Plasma lactate level in 15 patients enrolled in a Phase I clinical trial of GBS-01 rich in arctigenin was analyzed by colorimetric assay. Statistical analyses for association of plasma lactate and clinical responses, pharmacokinetics of arctigenin, and background factors of each patient by multivariate and univariate analyses.In about half of the patients, transient increase of lactate was observed. Correlation between plasma lactate level and pharmacokinetic parameters of arctigenin and its glucuronide conjugate, and clinical outcome was not detected. Regarding to the determinant of lactate level, only slight association with liver function test was detected. Plasma lactate level is primary determined by reutilization rather than production for antitumor effect and dose not serve as a biomarker. Arctigenin, inhibition of mitochondrial complex I, plasma lactate concentration, phase I clinical trial of GBS-01, Cori cycle. PMID:29856804

Change in plasma lactate concentration during arctigenin administration in a phase I clinical trial in patients with gemcitabine-refractory pancreatic cancer.

PubMed

Fujioka, Rumi; Mochizuki, Nobuo; Ikeda, Masafumi; Sato, Akihiro; Nomura, Shogo; Owada, Satoshi; Yomoda, Satoshi; Tsuchihara, Katsuya; Kishino, Satoshi; Esumi, Hiroyasu

2018-01-01

Arctigenin is evaluated for antitumor efficacy in patients with pancreatic cancer. It has an inhibitory activity on mitochondrial complex I.Therefore, plasma lactate level of patients after arctigenin administration was evaluated for biomarker of clinical response and/or adverse effect. Plasma lactate level in 15 patients enrolled in a Phase I clinical trial of GBS-01 rich in arctigenin was analyzed by colorimetric assay. Statistical analyses for association of plasma lactate and clinical responses, pharmacokinetics of arctigenin, and background factors of each patient by multivariate and univariate analyses.In about half of the patients, transient increase of lactate was observed. Correlation between plasma lactate level and pharmacokinetic parameters of arctigenin and its glucuronide conjugate, and clinical outcome was not detected. Regarding to the determinant of lactate level, only slight association with liver function test was detected. Plasma lactate level is primary determined by reutilization rather than production for antitumor effect and dose not serve as a biomarker. Arctigenin, inhibition of mitochondrial complex I, plasma lactate concentration, phase I clinical trial of GBS-01, Cori cycle.

Evaluation of in-hospital NT-proBNP changes in heart failure patients to identify the six-month clinical response following cardiac resynchronization therapy.

PubMed

Davoodi, Gholamreza; Bagheri, Ahmadreza; Yamini-Sharif, Ahmad; Boroumand, Mohammadali; Saroukhani, Sepideh; Sahebjam, Mohammad

2014-01-01

N-terminal pro β-type natriuretic peptide (NT-proBNP) is a valuable marker for monitoring the response to treatment in patients with heart failure. Based on the clinically observed improvement of heart failure symptoms early after cardiac resynchronization therapy (CRT), we sought to investigate whether CRT induce any significant reduction in the plasma level of NT-proBNP in three days after implantation and whether it is correlated with patients' response at six months. In this prospective study, 21 consecutive patients with severe heart failure (New York Heart Association class 3.19±0.40) who underwent CRT were enrolled. Being alive, no hospitalization due to decompensated heart failure, and improvement of at least one NYHA functional class at six months were classified as clinical responsiveness. The plasma level of NT-proBNP was measured before, three days, and six months after CRT. Clinical evaluation, echocardiographic study, and six-minute walking test were performed before and six months after the procedure. At six months' follow-up, 16 (76.2%) patients were responders. The plasma level of NT-proBNP at three days after CRT increased almost equally in both responder and non-responder groups of patients (∆NT-proBNP was 40.94±135.74 vs. 54.80±88.98); however, at six months' follow-up, the NT-proBNP changes statistically differed across the two groups of patients (P=0.005). According to our findings, NT-proBNP percent deviation from baseline to three days after CRT appears to be not correlated with the patients' clinical response after six months, which was incongruent to the patients' clinical improvement after CRT.

Predicting Response to Histone Deacetylase Inhibitors Using High-Throughput Genomics.

PubMed

Geeleher, Paul; Loboda, Andrey; Lenkala, Divya; Wang, Fan; LaCroix, Bonnie; Karovic, Sanja; Wang, Jacqueline; Nebozhyn, Michael; Chisamore, Michael; Hardwick, James; Maitland, Michael L; Huang, R Stephanie

2015-11-01

Many disparate biomarkers have been proposed as predictors of response to histone deacetylase inhibitors (HDI); however, all have failed when applied clinically. Rather than this being entirely an issue of reproducibility, response to the HDI vorinostat may be determined by the additive effect of multiple molecular factors, many of which have previously been demonstrated. We conducted a large-scale gene expression analysis using the Cancer Genome Project for discovery and generated another large independent cancer cell line dataset across different cancers for validation. We compared different approaches in terms of how accurately vorinostat response can be predicted on an independent out-of-batch set of samples and applied the polygenic marker prediction principles in a clinical trial. Using machine learning, the small effects that aggregate, resulting in sensitivity or resistance, can be recovered from gene expression data in a large panel of cancer cell lines.This approach can predict vorinostat response accurately, whereas single gene or pathway markers cannot. Our analyses recapitulated and contextualized many previous findings and suggest an important role for processes such as chromatin remodeling, autophagy, and apoptosis. As a proof of concept, we also discovered a novel causative role for CHD4, a helicase involved in the histone deacetylase complex that is associated with poor clinical outcome. As a clinical validation, we demonstrated that a common dose-limiting toxicity of vorinostat, thrombocytopenia, can be predicted (r = 0.55, P = .004) several days before it is detected clinically. Our work suggests a paradigm shift from single-gene/pathway evaluation to simultaneously evaluating multiple independent high-throughput gene expression datasets, which can be easily extended to other investigational compounds where similar issues are hampering clinical adoption. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Efficacy and Safety of the Biosimilar Infliximab CT-P13 Treatment in Inflammatory Bowel Diseases: A Prospective, Multicentre, Nationwide Cohort.

PubMed

Gecse, Krisztina B; Lovász, Barbara D; Farkas, Klaudia; Banai, János; Bene, László; Gasztonyi, Beáta; Golovics, Petra Anna; Kristóf, Tünde; Lakatos, László; Csontos, Ágnes Anna; Juhász, Márk; Nagy, Ferenc; Palatka, Károly; Papp, Mária; Patai, Árpád; Lakner, Lilla; Salamon, Ágnes; Szamosi, Tamás; Szepes, Zoltán; Tóth, Gábor T; Vincze, Áron; Szalay, Balázs; Molnár, Tamás; Lakatos, Péter L

2016-02-01

Biosimilar infliximab CT-P13 is approved for all indications of the originator product in Europe. Prospective data on its efficacy, safety, and immunogenicity in inflammatory bowel diseases are lacking. A prospective, nationwide, multicentre, observational cohort was designed to examine the efficacy, safety, and immunogenicity of CT-P13 infliximab biosimilar in the induction treatment of Crohn's disease [CD] and ulcerative colitis [UC]. Demographic data were collected and a harmonised monitoring strategy was applied. Early clinical remission, response, and early biochemical response were evaluated at Week 14, steroid-free clinical remission was evaluated at Week 30. Therapeutic drug level was monitored using a conventional enzyme-linked immunosorbent assay. In all, 210 consecutive inflammatory bowel disease [126 CD and 84 UC] patients were included in the present cohort. At Week 14, 81.4% of CD and 77.6% of UC patients showed clinical response and 53.6% of CD and 58.6% of UC patients were in clinical remission. Clinical remission rates at Week 14 were significantly higher in CD and UC patients who were infliximab naïve, compared with those with previous exposure to the originator compound [p < 0.05]. Until Week 30, adverse events were experienced in 17.1% of all patients. Infusion reactions and infectious adverse events occurred in 6.6% and 5.7% of all patients, respectively. This prospective multicentre cohort shows that CT-P13 is safe and effective in the induction of clinical remission and response in both CD and UC. Patients with previous infliximab exposure exhibited decreased response rates and were more likely to develop allergic reactions. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

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

PubMed

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.

Automating Collection of Pain-Related Patient-Reported Outcomes to Enhance Clinical Care and Research.

PubMed

Owen-Smith, Ashli; Mayhew, Meghan; Leo, Michael C; Varga, Alexandra; Benes, Lindsay; Bonifay, Allison; DeBar, Lynn

2018-05-01

Chronic pain is highly prevalent, and the ability to routinely measure patients' pain and treatment response using validated patient-reported outcome (PRO) assessments is important to clinical care. Despite this recognition, systematic use in everyday clinical care is rare. The aims of this study were to (1) describe infrastructure designed to automate PRO data collection, (2) compare study-enhanced PRO completion rates to those in clinical care, and (3) evaluate patient response rates by method of PRO administration and sociodemographic and/or clinical characteristics. The Pain Program for Active Coping and Training (PPACT) is a pragmatic clinical trial conducted within three regions of the Kaiser Permanente health care system. PPACT evaluates the effect of integrative primary care-based pain management services on outcomes for chronic pain patients on long-term opioid treatment. We implemented a tiered process for quarterly assessment of PROs to supplement clinical collection and ensure adequate trial data using three methods: web-based personal health records (PHR), automated interactive voice response (IVR) calls, and live outreach. Among a subset of PPACT participants examined (n = 632), the tiered study-enhanced PRO completion rates were higher than in clinical care: 96% completed ≥ 1 study-administered PRO with mean of 3.46 (SD = 0.85) vs. 74% completed in clinical care with a mean of 2.43 (SD = 2.08). Among all PPACT participants at 3 months (n = 831), PRO completion was 86% and analyses of response by key characteristics found only that participant age predicted an increased likelihood of responding to PHR and IVR outreach. Adherence to pain-related PRO data collection using our enhanced tiered approach was high. No demographic or clinical identifiers other than age were associated with differential response by modality. Successful ancillary support should employ multimodal electronic health record functionalities for PRO administration. Using automated modalities is feasible and may facilitate better sustainability for regular PRO administration within health care systems. Clinical Trials Registration Number: NCT02113592.

A comparison of dentifrices for clinical relief from dentin hypersensitivity using the Jay Sensitivity Sensor Probe.

PubMed

Hegde, Shashikanth; Rao, B H Sripathi; Kakar, Ravish Chander; Kakar, Ashish

2013-05-01

To evaluate the clinical relief from dentin hypersensitivity among subjects provided with a dentifrice formulated with 8% arginine, calcium carbonate and 1,000 ppm fluoride [sodium monofluorophosphate (MFP)] in comparison to those issued a commercially available dentifrice containing 1,000 ppm fluoride [as sodium monofluorophosphate (MFP)]. Clinical evaluations for hypersensitivity were performed with a novel tactile hypersensitivity measuring instrument--the Jay Sensitivity Sensor (Jay) Probe--in conjunction with evaporative triggers by air blast (Schiff scale) and Visual Analog Scores (VAS). Qualified adults from the Mangalore, India area who presented two teeth with dentin hypersensitivity were enrolled for this double-blind, randomized, parallel, controlled clinical trial conducted in an outpatient clinical setting. At baseline, dentin hypersensitivity was evaluated by the Jay Probe (tactile), air blast and VAS methods. Subjects were randomly issued a study dentifrice and instructed to brush their teeth for 1 minute twice daily with the provided dentifrice. Clinical evaluations for hypersensitivity were repeated after 2, 4 and 8 weeks of product use. 86 subjects (35 males and 51 females) complied with the study protocol and completed the entire study. At each recall visit, both treatment groups demonstrated significant reductions in dentin hypersensitivity from their corresponding baselines (P < 0.05). Subjects assigned the 8% arginine, calcium carbonate and 1,000 ppm fluoride dentifrice demonstrated statistically significant reductions in responses to tactile stimuli, air blast, and VAS responses in comparison to those using the dentifrice containing 1,000 ppm fluoride after 2, 4, and 8 weeks, respectively.

Standardization of pathologic evaluation and reporting of postneoadjuvant specimens in clinical trials of breast cancer: recommendations from an international working group.

PubMed

Provenzano, Elena; Bossuyt, Veerle; Viale, Giuseppe; Cameron, David; Badve, Sunil; Denkert, Carsten; MacGrogan, Gaëtan; Penault-Llorca, Frédérique; Boughey, Judy; Curigliano, Giuseppe; Dixon, J Michael; Esserman, Laura; Fastner, Gerd; Kuehn, Thorsten; Peintinger, Florentia; von Minckwitz, Gunter; White, Julia; Yang, Wei; Symmans, W Fraser

2015-09-01

Neoadjuvant systemic therapy is being used increasingly in the treatment of early-stage breast cancer. Response, in the form of pathological complete response, is a validated and evaluable surrogate end point of survival after neoadjuvant therapy. Thus, pathological complete response has become a primary end point for clinical trials. However, there is a current lack of uniformity in the definition of pathological complete response. A review of standard operating procedures used by 28 major neoadjuvant breast cancer trials and/or 25 sites involved in such trials identified marked variability in specimen handling and histologic reporting. An international working group was convened to develop practical recommendations for the pathologic assessment of residual disease in neoadjuvant clinical trials of breast cancer and information expected from pathology reports. Systematic sampling of areas identified by informed mapping of the specimen and close correlation with radiological findings is preferable to overly exhaustive sampling, and permits taking tissue samples for translational research. Controversial areas are discussed, including measurement of lesion size, reporting of lymphovascular space invasion and the presence of isolated tumor cells in lymph nodes after neoadjuvant therapy, and retesting of markers after treatment. If there has been a pathological complete response, this must be clearly stated, and the presence/absence of residual ductal carcinoma in situ must be described. When there is residual invasive carcinoma, a comment must be made as to the presence/absence of chemotherapy effect in the breast and lymph nodes. The Residual Cancer Burden is the preferred method for quantifying residual disease in neoadjuvant clinical trials in breast cancer; other methods can be included per trial protocols and regional preference. Posttreatment tumor staging using the Tumor-Node-Metastasis system should be included. These recommendations for standardized pathological evaluation and reporting of neoadjuvant breast cancer specimens should improve prognostication for individual patients and allow comparison of treatment outcomes within and across clinical trials.

Implementing novel imaging methods for improved diagnosis of disorder of consciousness patients.

PubMed

Bick, Atira S; Leker, Ronen R; Ben-Hur, Tamir; Levin, Netta

2013-11-15

The clinical evaluation of consciousness in disorder of consciousness (DOC) patients based on their exhibited behavior is difficult and remains erroneous in many cases. Recent studies demonstrated different levels of stimulus processing as well as evidence of some level of awareness in sub-groups of these patients. The aim of the current study was to examine the plausibility and challenges of implementing a clinical service for evaluation of consciousness level in DOC patients. Eleven Patients (ages 11-67) diagnosed as being in vegetative or minimal conscious states were included. Functional MRI evaluations included auditory, language, voice familiarity, imagery, and visual tests. In 9 patients auditory-related activation was found, however only in 5 of the subjects was differential activation found for language. Six patients exhibited differential response to their own name. In three patients a response to visual stimuli was identified. In one patient the auditory and linguistic systems were clearly activated in a hierarchical pattern, and moreover willful modulation of brain activity was identified in the imagery test. We discuss the importance of using a wide battery of tests, the difference between our clinical cohort and previous publications, as well as the challenges of clinically implementing this method. Translating novel imaging methods into the clinical evaluation of DOC patients is essential for better diagnosis and may encourage treatment development. © 2013 Elsevier B.V. All rights reserved.

Real-world Efficacy and Safety of Nivolumab for Advanced Non-Small-cell Lung Cancer: A Retrospective Multicenter Analysis.

PubMed

Kobayashi, Keigo; Nakachi, Ichiro; Naoki, Katsuhiko; Satomi, Ryosuke; Nakamura, Morio; Inoue, Takashi; Tateno, Hiroki; Sakamaki, Fumio; Sayama, Koichi; Terashima, Takeshi; Koh, Hidefumi; Abe, Takayuki; Nishino, Makoto; Arai, Daisuke; Yasuda, Hiroyuki; Kawada, Ichiro; Soejima, Kenzo; Betsuyaku, Tomoko

2018-05-01

Nivolumab, an immune checkpoint inhibitor, is now a standard treatment for previously treated advanced non-small-cell lung cancer based on the results from phase III clinical trials. We evaluated the real-world efficacy and safety of nivolumab in a nonselected population and identified the clinical characteristics that influence efficacy. A total of 142 patients with advanced non-small-cell lung cancer who were administered nivolumab at Keio University and affiliated hospitals in Japan from January to July 2016 were enrolled. The treatment efficacy and adverse events were retrospectively reviewed, and the clinical characteristics associated with the nivolumab response were evaluated using univariate and stratified analyses and the Cochran-Mantel-Haenszel test. The objective response rate was 17.0% (95% confidence interval [CI], 12.0%-24.0%), the median progression-free survival (PFS) was 58 days (95% CI, 50-67 days), and the proportion of patients with adverse events of any grade was 45.0%. EGFR/ALK mutation status was inversely associated with the treatment response (P < .05), and the difference in PFS for the mutation-positive versus mutation-negative patients was statistically significant (49 vs. 63 days; hazard ratio, 1.9; 95% CI, 1.1-5.2; P = .029). Previous radiotherapy also had a positive association with the treatment response (P = .012). The objective response rate, PFS, and adverse event profiles were comparable to those observed in previous clinical trials. EGFR/ALK mutation-negative status and previous radiotherapy might be key clinical characteristics associated with a positive treatment response. Our findings could aid in the efficient immunotherapeutic management of lung cancer. Copyright © 2018 Elsevier Inc. All rights reserved.

Clinical Usefulness of Response Profiles to Rapidly Incremental Cardiopulmonary Exercise Testing

PubMed Central

Ramos, Roberta P.; Alencar, Maria Clara N.; Treptow, Erika; Arbex, Flávio; Ferreira, Eloara M. V.; Neder, J. Alberto

2013-01-01

The advent of microprocessed “metabolic carts” and rapidly incremental protocols greatly expanded the clinical applications of cardiopulmonary exercise testing (CPET). The response normalcy to CPET is more commonly appreciated at discrete time points, for example, at the estimated lactate threshold and at peak exercise. Analysis of the response profiles of cardiopulmonary responses at submaximal exercise and recovery, however, might show abnormal physiologic functioning which would not be otherwise unraveled. Although this approach has long been advocated as a key element of the investigational strategy, it remains largely neglected in practice. The purpose of this paper, therefore, is to highlight the usefulness of selected submaximal metabolic, ventilatory, and cardiovascular variables in different clinical scenarios and patient populations. Special care is taken to physiologically justify their use to answer pertinent clinical questions and to the technical aspects that should be observed to improve responses' reproducibility and reliability. The most recent evidence in favor of (and against) these variables for diagnosis, impairment evaluation, and prognosis in systemic diseases is also critically discussed. PMID:23766901

The headache under-response to treatment (HURT) questionnaire, an outcome measure to guide follow-up in primary care: development, psychometric evaluation and assessment of utility.

PubMed

Steiner, T J; Buse, D C; Al Jumah, M; Westergaard, M L; Jensen, R H; Reed, M L; Prilipko, L; Mennini, F S; Láinez, M J A; Ravishankar, K; Sakai, F; Yu, S-Y; Fontebasso, M; Al Khathami, A; MacGregor, E A; Antonaci, F; Tassorelli, C; Lipton, R B

2018-02-14

Headache disorders are both common and burdensome but, given the many people affected, provision of health care to all is challenging. Structured headache services based in primary care are the most efficient, equitable and cost-effective solution but place responsibility for managing most patients on health-care providers with limited training in headache care. The development of practical management aids for primary care is therefore a purpose of the Global Campaign against Headache. This manuscript presents an outcome measure, the Headache Under-Response to Treatment (HURT) questionnaire, describing its purpose, development, psychometric evaluation and assessment for clinical utility. The objective was a simple-to-use instrument that would both assess outcome and provide guidance to improving outcome, having utility across the range of headache disorders, across clinical settings and across countries and cultures. After literature review, an expert consensus group drawn from all six world regions formulated HURT through item development and item reduction using item-response theory. Using the American Migraine Prevalence and Prevention Study's general-population respondent panel, two mailed surveys assessed the psychometric properties of HURT, comparing it with other instruments as external validators. Reliability was assessed in patients in two culturally-contrasting clinical settings: headache specialist centres in Europe (n = 159) and primary-care centres in Saudi Arabia (n = 40). Clinical utility was assessed in similar settings (Europe n = 201; Saudi Arabia n = 342). The final instrument, an 8-item self-administered questionnaire, addressed headache frequency, disability, medication use and effect, patients' perceptions of headache "control" and their understanding of their diagnoses. Psychometric evaluation revealed a two-factor model (headache frequency, disability and medication use; and medication efficacy and headache control), with scale properties apparently stable across disorders and correlating well and in the expected directions with external validators. The literature review found few instruments linking assessment to clinical advice or suggested actions: HURT appeared to fill this gap. In European specialist care, it showed utility as an outcome measure across headache disorders. In Saudi Arabian primary care, HURT (translated into Arabic) was reliable and responsive to clinical change. With demonstrated validity and clinical utility across disorders, cultures and settings, HURT is available for clinical and research purposes.

Evaluation of a Statewide HIV-HCV-STD Online Clinical Education Program by Healthcare Providers - A Comparison of Nursing and Other Disciplines.

PubMed

Wang, Dongwen; Luque, Amneris E

2016-01-01

The New York State HIV-HCV-STD Clinical Education Initiative (CEI) has developed a large repository of online resources and disseminated them to a wide range of healthcare providers. To evaluate the CEI online education program and in particular to compare the self-reported measures by clinicians from different disciplines, we analyzed the data from 1,558 course completions in a study period of three months. The results have shown that the overall evaluations by the clinicians were very positive. Meanwhile, there were significant differences across the clinical disciplines. In particular, physicians and nurse practitioners were the most satisfied. In contrast, pharmacists and case/care managers recorded lower than average responses. Nurses and counselors had mixed results. Nurse practitioners' responses were very similar to physicians on most measures, but significantly different from nurses in many aspects. For more effective knowledge dissemination, online education programs should consider the unique needs by clinicians from specific disciplines.

Improved clinical, functional and work outcomes in spondyloarthritides during real-life adalimumab treatment in central-eastern Europe.

PubMed

Szántó, Sándor; Poór, Gyula; Opris, Daniela; Iaremenko, Oleg; Procházková, Leona; Kuuse, Reet; Nagy, Orsolya; Chernyshov, Valentyn; Géher, Pál

2016-08-01

Adalimumab effectiveness on clinical, functional and work-related outcomes was evaluated in patients with active ankylosing spondylitis or psoriatic arthritis treated in routine clinical practice in central-eastern Europe. Patients (n = 555) were followed for 12 months. Primary end point was percentage of patients with a treatment response (≥50% decrease from baseline in Bath Ankylosing Spondylitis Disease Activity Index or ≥1.2 point decrease from baseline in Disease Activity Index-28 joint for axial or peripheral symptoms, respectively). Functional status was evaluated by the Bath Ankylosing Spondylitis Functional Index and Health Assessment Questionnaire Disability Index. Working ability was evaluated by the Work Productivity and Activity Impairment Questionnaire - Specific Health Problem. 76.1% of patients with axial symptoms and 83.5% with peripheral symptoms achieved a treatment response. Frequency of extra-articular manifestations decreased. Improvements were observed in functional status and workability. No new safety signals were observed. Adalimumab was effective and well tolerated during real-world use in central-eastern Europe.

Safety assessment of adjuvanted vaccines: Methodological considerations

PubMed Central

Da Silva, Fernanda Tavares; Di Pasquale, Alberta; Yarzabal, Juan P; Garçon, Nathalie

2015-01-01

Adjuvants mainly interact with the innate immune response and are used to enhance the quantity and quality of the downstream adaptive immune response to vaccine antigens. Establishing the safety of a new adjuvant-antigen combination is achieved through rigorous evaluation that begins in the laboratory, and that continues throughout the vaccine life-cycle. The strategy for the evaluation of safety pre-licensure is guided by the disease profile, vaccine indication, and target population, and it is also influenced by available regulatory guidelines. In order to allow meaningful interpretation of clinical data, clinical program methodology should be optimized and standardized, making best use of all available data sources. Post-licensure safety activities are directed by field experience accumulated pre- and post-licensure clinical trial data and spontaneous adverse event reports. Continued evolution of safety evaluation processes that keep pace with advances in vaccine technology and updated communication of the benefit-risk profile is necessary to maintain public confidence in vaccines. PMID:26029975

A Pilot Trial of the Combination of Vemurafenib with Adoptive Cell Therapy in Patients with Metastatic Melanoma

PubMed Central

Deniger, Drew C.; Kwong, Mei Li M.; Pasetto, Anna; Dudley, Mark E.; Wunderlich, John R.; Langhan, Michelle M.; Lee, Chyi-Chia Richard; Rosenberg, Steven A.

2016-01-01

Purpose This pilot feasibility clinical trial evaluated the co-administration of vemurafenib, a small molecule antagonist of BRAFV600 mutations, and tumor infiltrating lymphocytes (TIL) for the treatment of metastatic melanoma. Experimental Design A metastatic tumor was resected for growth of TIL and patients were treated with vemurafenib for 2 weeks followed by resection of a second lesion. Patients then received a non-myeloablative pre-conditioning regimen, infusion of autologous TIL and high-dose interleukin-2 administration. Vemurafenib was restarted at the time of TIL infusion and was continued for 2 years or until disease progression. Clinical responses were evaluated by RECIST 1.0. Metastases resected prior to and after two weeks of vemurafenib were compared using TCRB deep sequencing, immunohistochemistry, proliferation and recognition of autologous tumor. Results The treatment was well tolerated and had a safety profile similar to that of TIL or vemurafenib alone. Seven of 11 patients (64%) experienced an objective clinical response and 2 patients (18%) had a complete response for 3 years (one response is ongoing at 46 months). Proliferation and viability of infusion bag TIL and peripheral blood T cells were inhibited in vitro by vemurafenib (PLX4032) when approaching the maximum serum concentration of vemurafenib. TCRB repertoire (clonotypes numbers, clonality and frequency) did not significantly change between pre- and post-vemurafenib lesions. Recognition of autologous tumor by T cells was similar between TIL grown from pre- and post-vemurafenib metastases. Conclusions Co-administration of vemurafenib and TIL was safe, feasible and generated objective clinical responses in this small pilot clinical trial. PMID:28093487

Evaluation of DNA Repair Function as a Predictor of Response in a Clinical Trial of PARP Inhibitor Monotherapy for Recurrent Ovarian Carcinoma

DTIC Science & Technology

2016-12-01

no specifi c biomarkers were tested in a trial of a PARP inhibitor in patients with ovarian carcinoma with measurable disease . There is currently no... disease that was measurable with the Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST) and amenable to biopsy at trial entry. Patients...have measurable disease treated with a PARP inhibitor, thereby testing the assay as a biomarker for PARP inhibitor response. Other prospective

CONSORT to community: translation of an RCT to a large-scale community intervention and learnings from evaluation of the upscaled program.

PubMed

Moores, Carly Jane; Miller, Jacqueline; Perry, Rebecca Anne; Chan, Lily Lai Hang; Daniels, Lynne Allison; Vidgen, Helen Anna; Magarey, Anthea Margaret

2017-11-29

Translation encompasses the continuum from clinical efficacy to widespread adoption within the healthcare service and ultimately routine clinical practice. The Parenting, Eating and Activity for Child Health (PEACH™) program has previously demonstrated clinical effectiveness in the management of child obesity, and has been recently implemented as a large-scale community intervention in Queensland, Australia. This paper aims to describe the translation of the evaluation framework from a randomised controlled trial (RCT) to large-scale community intervention (PEACH™ QLD). Tensions between RCT paradigm and implementation research will be discussed along with lived evaluation challenges, responses to overcome these, and key learnings for future evaluation conducted at scale. The translation of evaluation from PEACH™ RCT to the large-scale community intervention PEACH™ QLD is described. While the CONSORT Statement was used to report findings from two previous RCTs, the REAIM framework was more suitable for the evaluation of upscaled delivery of the PEACH™ program. Evaluation of PEACH™ QLD was undertaken during the project delivery period from 2013 to 2016. Experiential learnings from conducting the evaluation of PEACH™ QLD to the described evaluation framework are presented for the purposes of informing the future evaluation of upscaled programs. Evaluation changes in response to real-time changes in the delivery of the PEACH™ QLD Project were necessary at stages during the project term. Key evaluation challenges encountered included the collection of complete evaluation data from a diverse and geographically dispersed workforce and the systematic collection of process evaluation data in real time to support program changes during the project. Evaluation of large-scale community interventions in the real world is challenging and divergent from RCTs which are rigourously evaluated within a more tightly-controlled clinical research setting. Constructs explored in an RCT are inadequate in describing the enablers and barriers of upscaled community program implementation. Methods for data collection, analysis and reporting also require consideration. We present a number of experiential reflections and suggestions for the successful evaluation of future upscaled community programs which are scarcely reported in the literature. PEACH™ QLD was retrospectively registered with the Australian New Zealand Clinical Trials Registry on 28 February 2017 (ACTRN12617000315314).

Blood Pressure Response to Exercise and Cardiovascular Disease.

PubMed

Schultz, Martin G; La Gerche, Andre; Sharman, James E

2017-10-18

This review aimed to provide a clinical update on exercise blood pressure (BP) and its relationship to cardiovascular disease (CVD), outlining key determinants of abnormal exercise BP responses. We also highlight current evidence gaps that need addressing in order to optimise the relevance of exercise BP as clinical CVD risk factor. Abnormal exercise BP manifests as either exercise hypotension (low BP response) or as exaggerated exercise BP (high BP response). Exercise hypotension is an established sign of existing and likely severe CVD, but exaggerated exercise BP also carries elevated CVD risk due to its association with sub-clinical hypertension. Although exaggerated exercise BP is related to heightened CVD risk at any exercise intensity, recent data suggest that the BP response to submaximal intensity exercise holds greater prognostic and clinical significance than BP achieved at peak/maximal intensity exercise. Cardiorespiratory fitness is a strong modifier of the exercise BP response, and should be taken into consideration when assessing the association with CVD. Both exercise hypotension and exaggerated exercise BP serve as markers that should prompt evaluation for potential underlying CVD. However, the clinical utility of these markers is currently inhibited by the lack of consensus informing the definitions and thresholds for abnormalities in exercise BP.

Challenges of teacher-based clinical evaluation from nursing students' point of view: Qualitative content analysis.

PubMed

Sadeghi, Tabandeh; Seyed Bagheri, Seyed Hamid

2017-01-01

Clinical evaluation is very important in the educational system of nursing. One of the most common methods of clinical evaluation is evaluation by the teacher, but the challenges that students would face in this evaluation method, have not been mentioned. Thus, this study aimed to explore the experiences and views of nursing students about the challenges of teacher-based clinical evaluation. This study was a descriptive qualitative study with a qualitative content analysis approach. Data were gathered through semi-structured focused group sessions with undergraduate nursing students who were passing their 8 th semester at Rafsanjan University of Medical Sciences. Date were analyzed using Graneheim and Lundman's proposed method. Data collection and analysis were concurrent. According to the findings, "factitious evaluation" was the main theme of study that consisted of three categories: "Personal preferences," "unfairness" and "shirking responsibility." These categories are explained using quotes derived from the data. According to the results of this study, teacher-based clinical evaluation would lead to factitious evaluation. Thus, changing this approach of evaluation toward modern methods of evaluation is suggested. The finding can help nursing instructors to get a better understanding of the nursing students' point of view toward this evaluation approach and as a result could be planning for changing of this approach.

Clinical evaluation of GEM 21S® and a collagen membrane with a coronally advanced flap as a root coverage procedure in the treatment of gingival recession defects: A comparative study

PubMed Central

Singh, Preetinder; Suresh, D. K.

2012-01-01

Aim: Clinical evaluation of efficacy of rhPDGF-BB plus beta tricalcium phosphate (GEM 21S®) along with a collagen membrane in root coverage using a coronally advanced flap. Materials and Methods: This human case series evaluated the clinical outcome of rhPDGF-BB with beta-tricalcium phosphate (GEM 21S®) and a collagen membrane in the treatment of recession defects using a coronally advanced flap. Patients were followed postoperatively, and healing was evaluated at 1, 3, and 6 months, with recession depth as the primary outcome measure. Results: This pioneer case series revealed a favorable tissue response to GEM 21S® and collagen membrane from both clinical and esthetic point of view in regenerative periodontal surgery. PMID:23493720

Defining Clinical Response Criteria and Early Response Criteria for Precision Oncology: Current State-of-the-Art and Future Perspectives.

PubMed

Subbiah, Vivek; Chuang, Hubert H; Gambhire, Dhiraj; Kairemo, Kalevi

2017-02-15

In this era of precision oncology, there has been an exponential growth in the armamentarium of genomically targeted therapies and immunotherapies. Evaluating early responses to precision therapy is essential for "go" versus "no go" decisions for these molecularly targeted drugs and agents that arm the immune system. Many different response assessment criteria exist for use in solid tumors and lymphomas. We reviewed the literature using the Medline/PubMed database for keywords "response assessment" and various known response assessment criteria published up to 2016. In this article we review the commonly used response assessment criteria. We present a decision tree to facilitate selection of appropriate criteria. We also suggest methods for standardization of various response assessment criteria. The relevant response assessment criteria were further studied for rational of development, key features, proposed use and acceptance by various entities. We also discuss early response evaluation and provide specific case studies of early response to targeted therapy. With high-throughput, advanced computing programs and digital data-mining it is now possible to acquire vast amount of high quality imaging data opening up a new field of "omics in radiology"-radiomics that complements genomics for personalized medicine. Radiomics is rapidly evolving and is still in the research arena. This cutting-edge technology is poised to move soon to the mainstream clinical arena. Novel agents with new mechanisms of action require advanced molecular imaging as imaging biomarkers. There is an urgent need for development of standardized early response assessment criteria for evaluation of response to precision therapy.

In Silico Investigations of the Anti-Catabolic Effects of Pamidronate and Denosumab on Multiple Myeloma-Induced Bone Disease

PubMed Central

Wang, Yan; Lin, Bo

2012-01-01

It is unclear whether the new anti-catabolic agent denosumab represents a viable alternative to the widely used anti-catabolic agent pamidronate in the treatment of Multiple Myeloma (MM)-induced bone disease. This lack of clarity primarily stems from the lack of sufficient clinical investigations, which are costly and time consuming. However, in silico investigations require less time and expense, suggesting that they may be a useful complement to traditional clinical investigations. In this paper, we aim to (i) develop integrated computational models that are suitable for investigating the effects of pamidronate and denosumab on MM-induced bone disease and (ii) evaluate the responses to pamidronate and denosumab treatments using these integrated models. To achieve these goals, pharmacokinetic models of pamidronate and denosumab are first developed and then calibrated and validated using different clinical datasets. Next, the integrated computational models are developed by incorporating the simulated transient concentrations of pamidronate and denosumab and simulations of their actions on the MM-bone compartment into the previously proposed MM-bone model. These integrated models are further calibrated and validated by different clinical datasets so that they are suitable to be applied to investigate the responses to the pamidronate and denosumab treatments. Finally, these responses are evaluated by quantifying the bone volume, bone turnover, and MM-cell density. This evaluation identifies four denosumab regimes that potentially produce an overall improved bone-related response compared with the recommended pamidronate regime. This in silico investigation supports the idea that denosumab represents an appropriate alternative to pamidronate in the treatment of MM-induced bone disease. PMID:23028650

Evaluating the Responsiveness to Therapeutic Change with Routine Outcome Monitoring: A Comparison of the Symptom Questionnaire-48 (SQ-48) with the Brief Symptom Inventory (BSI) and the Outcome Questionnaire-45 (OQ-45).

PubMed

Carlier, Ingrid V E; Kovács, Viktória; van Noorden, Martijn S; van der Feltz-Cornelis, Christina; Mooij, Nanda; Schulte-van Maaren, Yvonne W M; van Hemert, Albert M; Zitman, Frans G; Giltay, Erik J

2017-01-01

Assessment of psychological distress is important, because it may help to monitor treatment effects and predict treatment outcomes. We previously developed the 48-item Symptom Questionnaire (SQ-48) as a public domain self-report psychological distress instrument and showed good internal consistency as well as good convergent and divergent validity among clinical and non-clinical samples. The present study, conducted among psychiatric outpatients in a routine clinical setting, describes additional psychometric properties of the SQ-48. The primary focus is on responsiveness to therapeutic change, which to date has been rarely examined within psychiatry or clinical psychology. Since a questionnaire should also be stable when no clinically important change occurs, we also examined test-retest reliability within a test-retest design before treatment (n = 43). A pre-treatment/post-treatment design was used for responsiveness to therapeutic change, comparing the SQ-48 with two internationally widely used instruments: the Brief Symptom Inventory (n = 97) and the Outcome Questionnaire-45 (n = 109). The results showed that the SQ-48 has excellent test-retest reliability and good responsiveness to therapeutic change, without significant differences between the questionnaires in terms of responsiveness. In sum, the SQ-48 is a psychometrically sound public domain self-report instrument that can be used for routine outcome monitoring, as a benchmark tool or for research purposes. Copyright © 2015 John Wiley & Sons, Ltd. Key Practitioner Message The SQ-48 is developed as a public domain self-report questionnaire, in line with growing efforts to develop clinical instruments that are free of charge. The SQ-48 has excellent test-retest reliability and good responsiveness to therapeutic change or patient progress. There were no significant differences in terms of responsiveness between the SQ-48 and BSI or OQ-45. The SQ-48 can be used as a routine evaluation outcome measure for quality assurance in clinical practice. Providing feedback on patient progress via outcome measures could contribute to the enhancement of treatment outcomes. Copyright © 2015 John Wiley & Sons, Ltd.

Facial Angiofibroma Severity Index (FASI): reliability assessment of a new tool developed to measure severity and responsiveness to therapy in tuberous sclerosis-associated facial angiofibroma.

PubMed

Salido-Vallejo, R; Ruano, J; Garnacho-Saucedo, G; Godoy-Gijón, E; Llorca, D; Gómez-Fernández, C; Moreno-Giménez, J C

2014-12-01

Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous disorder characterized by the development of multisystem hamartomatous tumours. Topical sirolimus has recently been suggested as a potential treatment for TSC-associated facial angiofibroma (FA). To validate a reproducible scale created for the assessment of clinical severity and treatment response in these patients. We developed a new tool, the Facial Angiofibroma Severity Index (FASI) to evaluate the grade of erythema and the size and extent of FAs. In total, 30 different photographs of patients with TSC were shown to 56 dermatologists at each evaluation. Three evaluations using the same photographs but in a different random order were performed 1 week apart. Test and retest reliability and interobserver reproducibility were determined. There was good agreement between the investigators. Inter-rater reliability showed strong correlations (> 0.98; range 0.97-0.99) with inter-rater correlation coefficients (ICCs) for the FASI. The global estimated kappa coefficient for the degree of intra-rater agreement (test-retest) was 0.94 (range 0.91-0.97). The FASI is a valid and reliable tool for measuring the clinical severity of TSC-associated FAs, which can be applied in clinical practice to evaluate the response to treatment in these patients. © 2014 British Association of Dermatologists.

Implementation of an Audio Computer-Assisted Self-Interview (ACASI) System in a General Medicine Clinic

PubMed Central

Deamant, C.; Smith, J.; Garcia, D.; Angulo, F.

2015-01-01

Summary Background Routine implementation of instruments to capture patient-reported outcomes could guide clinical practice and facilitate health services research. Audio interviews facilitate self-interviews across literacy levels. Objectives To evaluate time burden for patients, and factors associated with response times for an audio computer-assisted self interview (ACASI) system integrated into the clinical workflow. Methods We developed an ACASI system, integrated with a research data warehouse. Instruments for symptom burden, self-reported health, depression screening, tobacco use, and patient satisfaction were administered through touch-screen monitors in the general medicine clinic at the Cook County Health & Hospitals System during April 8, 2011-July 27, 2012. We performed a cross-sectional study to evaluate the mean time burden per item and for each module of instruments; we evaluated factors associated with longer response latency. Results Among 1,670 interviews, the mean per-question response time was 18.4 [SD, 6.1] seconds. By multivariable analysis, age was most strongly associated with prolonged response time and increased per decade compared to < 50 years as follows (additional seconds per question; 95% CI): 50–59 years (1.4; 0.7 to 2.1 seconds); 60–69 (3.4; 2.6 to 4.1); 70–79 (5.1; 4.0 to 6.1); and 80–89 (5.5; 4.1 to 7.0). Response times also were longer for Spanish language (3.9; 2.9 to 4.9); no home computer use (3.3; 2.8 to 3.9); and, low mental self-reported health (0.6; 0.0 to 1.1). However, most interviews were completed within 10 minutes. Conclusions An ACASI software system can be included in a patient visit and adds minimal time burden. The burden was greatest for older patients, interviews in Spanish, and for those with less computer exposure. A patient’s self-reported health had minimal impact on response times. PMID:25848420

Exploring the validity and reliability of a questionnaire for evaluating veterinary clinical teachers' supervisory skills during clinical rotations.

PubMed

Boerboom, T B B; Dolmans, D H J M; Jaarsma, A D C; Muijtjens, A M M; Van Beukelen, P; Scherpbier, A J J A

2011-01-01

Feedback to aid teachers in improving their teaching requires validated evaluation instruments. When implementing an evaluation instrument in a different context, it is important to collect validity evidence from multiple sources. We examined the validity and reliability of the Maastricht Clinical Teaching Questionnaire (MCTQ) as an instrument to evaluate individual clinical teachers during short clinical rotations in veterinary education. We examined four sources of validity evidence: (1) Content was examined based on theory of effective learning. (2) Response process was explored in a pilot study. (3) Internal structure was assessed by confirmatory factor analysis using 1086 student evaluations and reliability was examined utilizing generalizability analysis. (4) Relations with other relevant variables were examined by comparing factor scores with other outcomes. Content validity was supported by theory underlying the cognitive apprenticeship model on which the instrument is based. The pilot study resulted in an additional question about supervision time. A five-factor model showed a good fit with the data. Acceptable reliability was achievable with 10-12 questionnaires per teacher. Correlations between the factors and overall teacher judgement were strong. The MCTQ appears to be a valid and reliable instrument to evaluate clinical teachers' performance during short rotations.

The perceived value of clinical pharmacy service provision by pharmacists and physicians: an initial assessment of family medicine and internal medicine providers.

PubMed

Wietholter, Jon P; Ponte, Charles D; Long, Dustin M

2017-10-01

Few publications have addressed the perceptions of pharmacists and physicians regarding the value of clinical pharmacist services. A survey-based study was conducted to determine whether Internal Medicine (IM) and Family Medicine (FM) pharmacists and physicians differed in their attitudes regarding the benefits of collaboration in an acute care setting. The primary objective was to evaluate perceived differences regarding self-assessment of value between IM and FM pharmacists. The secondary objective was to evaluate perceived differences of clinical pharmacist benefit between IM and FM physicians. An eight-item questionnaire assessed the attitudes and beliefs of pharmacists and physicians regarding the value of clinical pharmacy services. Surveys were emailed and participants marked their responses using a 7-point Likert scale for each item. Demographic data and overall comments were collected from each participant. Overall, 167 surveys were completed. When comparing cumulative physician and pharmacist responses, none of the eight questions showed significant differences. Statistically significant differences were noted when comparing IM and FM clinical pharmacists on five of the eight survey items; for each of these items, FM pharmacists had more favourable perceptions than their IM counterparts. No statistically significant differences were noted when comparing responses of IM and FM physicians. This study found that FM pharmacists perceived a greater benefit regarding participation in inpatient acute care rounds when compared to their IM pharmacist counterparts. Future studies are necessary to determine if other medical specialties' perceptions of clinical pharmacy provision differ from our findings and to evaluate the rationale behind specific attitudes and behaviours. © 2016 Royal Pharmaceutical Society.

Performance of Crohn's disease Clinical Trial Endpoints based upon Different Cutoffs for Patient Reported Outcomes or Endoscopic Activity: Analysis of EXTEND Data.

PubMed

Feagan, Brian; Sandborn, William J; Rutgeerts, Paul; Levesque, Barrett G; Khanna, Reena; Huang, Bidan; Zhou, Qian; Maa, Jen-Fue; Wallace, Kori; Lacerda, Ana; Thakkar, Roopal B; Robinson, Anne M

2018-04-23

Clinical trial endpoints for Crohn's disease (CD) activity correlate poorly with mucosal inflammation; to assess treatment efficacy, patient-reported outcomes and endoscopic assessments are preferred. This study assessed the impact on treatment efficacy estimations of using different definitions of clinical and endoscopic remission and endoscopic response, and of using site- or central-based endoscopy evaluation. This post hoc analysis of data fromEXTEND (extend the safety and efficacy of adalimumab through endoscopic healing), a placebo (PBO)-controlled, randomized trial of adalimumab (ADA) for mucosal healing, included adults with moderate-to-severe CD. Subsets of patients meeting specified Simplified Endoscopic Score for CD (SES-CD) inclusion criteria, according to site or central reading, and baseline stool frequency (SF) and/or abdominal pain score (AP) thresholds were evaluated. Various endpoint definitions based on the Crohn's Disease Activity Index (CDAI), its SF and AP components, SES-CD, and composite endpoints were compared between treatment groups. Increased stringency of Week 12 clinical endpoints compared to CDAI<150 to SF≤3.0/1.5&AP≤1.0 reduced PBO response rates by ≥12% and increased treatment effects by ≤10%. Amending the SES-CD endpoint from ≤4 to ≤2 reduced the treatment effect from 24% to 8%. Composite endpoints further diminished response rates and effect sizes. Site-based evaluation was associated with lower remission rates versus central reading in the PBO group and, thus, greater ADA-related treatment effects. This analysis is the first to demonstrate that increasing the stringency of clinical and endoscopic endpoint definitions in CD trials, especially lowering SF or SES-CD definitions, reduces the ability to detect treatment-related change in CD activity; focus on endpoints that reflect clinical change is warranted.

An evaluation of learning clinical decision-making for early rehabilitation in the ICU via interactive education with audience response system.

PubMed

Toonstra, Amy L; Nelliot, Archana; Aronson Friedman, Lisa; Zanni, Jennifer M; Hodgson, Carol; Needham, Dale M

2017-06-01

Knowledge-related barriers to safely implement early rehabilitation programs in intensive care units (ICUs) may be overcome via targeted education. The purpose of this study was to evaluate the effectiveness of an interactive educational session on short-term knowledge of clinical decision-making for safe rehabilitation of patients in ICUs. A case-based teaching approach, drawing from published safety recommendations for initiation of rehabilitation in ICUs, was used with a multidisciplinary audience. An audience response system was incorporated to promote interaction and evaluate knowledge before vs. after the educational session. Up to 175 audience members, of 271 in attendance (129 (48%) physical therapists, 51 (19%) occupational therapists, 31 (11%) nursing, 14 (5%) physician, 46 (17%) other), completed both the pre- and post-test questions for each of the six unique patient cases. In four of six patient cases, there was a significant (p< 0.001) increase in identifying the correct answer regarding initiation of rehabilitation activities. This learning effect was similar irrespective of participants' years of experience and clinical discipline. An interactive, case-based, educational session may be effective for increasing short-term knowledge, and identifying knowledge gaps, regarding clinical decision-making for safe rehabilitation of patients in ICUs. Implications for Rehabilitation Lack of knowledge regarding the safety considerations for early rehabilitation of ICU patients is a barrier to implementing early rehabilitation. Interactive educational formats, such as the use of audience response systems, offer a new method of teaching and instantly assessing learning of clinically important information. In a small study, we have shown that an interactive, case-based educational format may be used to effectively teach clinical decision-making for the safe rehabilitation of ICU patients to a diverse audience of clinicians.

Responsiveness of pain and disability measures for chronic whiplash.

PubMed

Stewart, Mark; Maher, Christopher G; Refshauge, Kathryn M; Bogduk, Nikolai; Nicholas, Michael

2007-03-01

Cohort study. To evaluate the responsiveness of common pain and disability measures in a cohort of patients with chronic whiplash. Pain and disability are routinely measured in clinical practice and clinical research. However, to date, a head-to-head comparison of competing measures for whiplash patients has not been performed. Pain (pain intensity, bothersomeness, and SF-36 bodily pain score) and disability (Patient Specific Functional Scale, Neck Disability Index, Functional Rating Index, Copenhagen Scale, and SF-36 physical summary) measures were completed by 132 patients with chronic whiplash at baseline and then again after 6 weeks together with an 11-point global perceived effect scale. Internal responsiveness was evaluated by calculating effect sizes and standardized response means, and external responsiveness by correlating change scores with global perceived effect scores and by ROC curves. The ranking of responsiveness was consistent across the different analyses. Pain bothersomeness was more responsive than pain intensity, which was more responsive than the SF-36 pain measure. The Patient Specific Functional Scale was the most responsive disability measure, followed by the spine-specific measures, with the SF-36 physical summary measure the least responsive. Pain bothersomeness and the Patient Specific Functional Scale provide the most responsive measures of pain and disability, respectively, in patients with chronic whiplash.

Enhancing Clinical Evaluation Skills: Palpation as the Principal Skill

ERIC Educational Resources Information Center

Eberman, Lindsey E.; Finn, Megan E.

2010-01-01

Context: Recognition and evaluation of injuries/illnesses accounts for the greatest percentage (24%) of an athletic trainer's responsibilities as a clinician. When teaching orthopedic evaluation, we often emphasize history taking and special/ligamentous tests to achieve a diagnosis. Because of its complexity and variability, palpation becomes an…

Use of an Objective Structured Clinical Examination in Clinical Nurse Specialist Education.

PubMed

Cuevas, Heather E; Timmerman, Gayle M

2016-01-01

Helping patients maximize their potential using expert coaching to facilitate lifestyle change is an important practice area for clinical nurse specialists (CNSs). The purpose is to determine the usefulness of objective structured clinical examinations (OSCEs) for evaluating CNS students' coaching competencies in the context of facilitating lifestyle change. Despite the use of OSCEs to assess competencies in clinical skills (eg, performance of procedures, decision making), its potential for evaluating coaching competencies for lifestyle change has not been demonstrated. We developed 4 OSCEs dealing with coaching patients in exercise, weight loss, stress reduction, or nonpharmacologic management of hyperlipidemia. Evaluation criteria included (1) approach to the patient, (2) information gathering, (3) motivational interviewing, and (4) management (medical and behavioral strategies). Student performance ranged from highly organized with proficient coaching skills to disorganized and focused solely on clinical management and prescriptive communication. Student responses were positive. Objective structured clinical examinations were highly useful for evaluating CNS students' coaching competencies for lifestyle change. Using OSCEs early in the semester to provide students feedback on their performance and again at the end to determine improvement optimizes use of this teaching strategy.

Characterization of OSL dosimeters for use in dose assessment in Computed Tomography procedures.

PubMed

Giansante, Louise; Santos, Josilene C; Umisedo, Nancy K; Terini, Ricardo A; Costa, Paulo R

2018-03-01

This study describes the characterization of an Al 2 O 3 :C OSLD (Landauer's Luxel™ tape) for dose evaluation in Computed Tomography. The irradiations were conducted using both a constant potential X-ray equipment and a 64-slice clinical CT scanner, and the readouts were performed using a Risø TL/OSL reader. The following aspects were studied: batch homogeneity, energy response, linearity of dose response, reproducibility, reusability, and effect of uncertainties with the normalization of OSL signals per their response to beta radiation. A group of 330 dosimeters from the 452 irradiated with the same dose presented OSL signals within the interval of 4.7% from the average. The dosimeters presented energy-dependent response in good agreement with results found in the literature. The air kerma response of the OSL signal showed a linear trend for both the constant potential X-ray device and the clinical CT scanner, with differences in their slopes of approximately 10%. Reproducibility, reusability, and effect of beta normalization were analyzed by separating 72 dosimeters in 3 groups. The results obtained in this study together with those of previous works indicate that this type of dosimeter is adequate for dose evaluation in CT clinical applications. Copyright © 2018 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Development of criteria for evaluating clinical response in thyroid eye disease using a modified Delphi technique.

PubMed

Douglas, Raymond S; Tsirbas, Angelo; Gordon, Mark; Lee, Diana; Khadavi, Nicole; Garneau, Helene Chokron; Goldberg, Robert A; Cahill, Kenneth; Dolman, Peter J; Elner, Victor; Feldon, Steve; Lucarelli, Mark; Uddin, Jimmy; Kazim, Michael; Smith, Terry J; Khanna, Dinesh

2009-09-01

To identify components of a provisional clinical response index for thyroid eye disease using a modified Delphi technique. The International Thyroid Eye Disease Society conducted a structured, 3-round Delphi exercise establishing consensus for a core set of measures for clinical trials in thyroid eye disease. The steering committee discussed the results in a face-to-face meeting (nominal group technique) and evaluated each criterion with respect to its feasibility, reliability, redundancy, and validity. Redundant measures were consolidated or excluded. Criteria were parsed into 11 domains for the Delphi surveys. Eighty-four respondents participated in the Delphi 1 survey, providing 220 unique items. Ninety-two members (100% of the respondents from Delphi 1 plus 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. Using a Delphi exercise, we developed provisional core measures for assessing disease activity and severity in clinical trials of therapies for thyroid eye disease. These measures will be iteratively refined for use in multicenter clinical trials.

Development of criteria for evaluating clinical response in thyroid eye disease (CRI-TED) using a modified Delphi technique

PubMed Central

Douglas, Raymond S.; Tsirbas, Angelo; Gordon, Mark; Lee, Diana; Khadavi, Nicole; Garneau, Helene Chokron; Goldberg, Robert A.; Cahill, Kenneth; Dolman, Peter J.; Elner, Victor; Feldon, Steve; Lucarelli, Mark; Uddin, Jimmy; Kazim, Michael; Smith, Terry J.; Khanna, Dinesh

2014-01-01

To identify components of a provisional clinical response index for thyroid eye disease (CRI-TED) using a modified Delphi technique. The International Thyroid Eye Disease Society (ITEDS) conducted a structured, 3-round Delphi exercise establishing consensus for a core set of measures for clinical trials in TED. The steering committee discussed the results in a face-to-face meeting (nominal group technique) and evaluated each criterion with respect to its feasibility, reliability, redundancy, and validity. Redundant measures were consolidated or excluded. Criteria were parsed into 11 domains for the Delphi surveys. Eighty four respondents participated in the Delphi-1 survey, providing 220 unique items. Ninety- two members (100% of the respondents from Delphi 1 plus eight new participants) responded in Delphi-2 and rated the same 220 items. Sixty-four members (76% of participants) rated 153 criteria in Delphi-3 (67 criteria were excluded due to redundancy). Criteria with a mean greater than 6 (1 least appropriate to 9 most appropriate) were further evaluated by the nominal group technique and provisional core measures were chosen. Using a Delphi exercise, we developed provisional core measures for assessing disease activity and severity in clinical trials of therapies for TED. These measures will be iteratively refined for use in multicenter clinical trials. PMID:19752424

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

PubMed

Naito, Takafumi; Kawakami, Junichi

2015-01-01

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

Comparative oncology evaluation of intravenous recombinant oncolytic Vesicular Stomatitis Virus therapy in spontaneous canine cancer

PubMed Central

Naik, Shruthi; Galyon, Gina D.; Jenks, Nathan J.; Steele, Michael B.; Miller, Amber C.; Allstadt, Sara D.; Suksanpaisan, Lukkana; Peng, Kah Whye; Federspiel, Mark J.; Russell, Stephen J.; LeBlanc, Amy K.

2017-01-01

Clinical translation of intravenous therapies to treat disseminated or metastatic cancer is imperative. Comparative oncology, the evaluation of novel cancer therapies in animals with spontaneous cancer, can be utilized to inform and accelerate clinical translation. Preclinical murine studies demonstrate that single shot systemic therapy with a VSV-IFNβ-NIS, a novel recombinant oncolytic Vesicular stomatitis virus (VSV), can induce curative remission in tumor bearing mice. Clinical translation of VSV-IFNβ-NIS therapy is dependent on comprehensive assessment of clinical toxicities, virus shedding, pharmacokinetics, and efficacy in clinically relevant models. Dogs spontaneously develop cancer with comparable etiology, clinical progression and response to therapy as human malignancies. A comparative oncology study was carried out to investigate feasibility and tolerability of intravenous oncolytic VSV-IFNβ-NIS therapy in pet dogs with spontaneous cancer. Nine dogs with various malignancies were treated with a single intravenous dose of VSV-IFNβ-NIS. Two dogs with high-grade peripheral T-cell lymphoma had rapid but transient remission of disseminated disease and transient hepatotoxicity that resolved spontaneously. There was no shedding of infectious virus. Correlative pharmacokinetic studies revealed elevated levels of VSV RNA in blood in dogs with measurable disease remission. This is the first evaluation of intravenous oncolytic virus therapy for spontaneous canine cancer, demonstrating that VSV-IFNβ-NIS is well-tolerated and safe in dogs with advanced or metastatic disease. This approach has informed clinical translation, including dose and target indication selection, leading to a clinical investigation of intravenous VSV-IFNβ-NIS therapy, and provided preliminary evidence of clinical efficacy, and potential biomarkers that correlate with therapeutic response. PMID:29158470

Application of a responsive evaluation approach in medical education.

PubMed

Curran, Vernon; Christopher, Jeanette; Lemire, Francine; Collins, Alice; Barrett, Brendan

2003-03-01

This paper reports on the usefulness of a responsive evaluation model in evaluating the clinical skills assessment and training (CSAT) programme at the Faculty of Medicine, Memorial University of Newfoundland, Canada. The purpose of this paper is to introduce the responsive evaluation approach, ascertain its utility, feasibility, propriety and accuracy in a medical education context, and discuss its applicability as a model for medical education programme evaluation. Robert Stake's original 12-step responsive evaluation model was modified and reduced to five steps, including: (1) stakeholder audience identification, consultation and issues exploration; (2) stakeholder concerns and issues analysis; (3) identification of evaluative standards and criteria; (4) design and implementation of evaluation methodology; and (5) data analysis and reporting. This modified responsive evaluation process was applied to the CSAT programme and a meta-evaluation was conducted to evaluate the effectiveness of the approach. The responsive evaluation approach was useful in identifying the concerns and issues of programme stakeholders, solidifying the standards and criteria for measuring the success of the CSAT programme, and gathering rich and descriptive evaluative information about educational processes. The evaluation was perceived to be human resource dependent in nature, yet was deemed to have been practical, efficient and effective in uncovering meaningful and useful information for stakeholder decision-making. Responsive evaluation is derived from the naturalistic paradigm and concentrates on examining the educational process rather than predefined outcomes of the process. Responsive evaluation results are perceived as having more relevance to stakeholder concerns and issues, and therefore more likely to be acted upon. Conducting an evaluation that is responsive to the needs of these groups will ensure that evaluative information is meaningful and more likely to be used for programme enhancement and improvement.

Clinical evaluation of CpG oligonucleotides as adjuvants for vaccines targeting infectious diseases and cancer

PubMed Central

Scheiermann, Julia; Klinman, Dennis M.

2014-01-01

Synthetic oligonucleotides (ODN) that express unmethylated “CpG motifs” trigger cells that express Toll-like receptor 9. In humans this includes plasmacytoid dendritic cells and B cells. CpG ODN induce an innate immune response characterized by the production of Th1 and pro-inflammatory cytokines. Their utility as vaccine adjuvants was evaluated in a number of clinical trials. Results indicate that CpG ODN improve antigen presentation and the generation of vaccine-specific cellular and humoral responses. This work provides an up-to-date overview of the utility of CpG ODN as adjuvants for vaccines targeting infectious agents and cancer. PMID:24975812

Phase II Investigator-Initiated Study of Brentuximab Vedotin in Mycosis Fungoides and Sézary Syndrome With Variable CD30 Expression Level: A Multi-Institution Collaborative Project

PubMed Central

Kim, Youn H.; Tavallaee, Mahkam; Sundram, Uma; Salva, Katrin A.; Wood, Gary S.; Li, Shufeng; Rozati, Sima; Nagpal, Seema; Krathen, Michael; Reddy, Sunil; Hoppe, Richard T.; Nguyen-Lin, Annie; Weng, Wen-Kai; Armstrong, Randall; Pulitzer, Melissa; Advani, Ranjana H.; Horwitz, Steven M.

2015-01-01

Purpose In contrast to Hodgkin lymphoma and systemic anaplastic large-cell lymphoma, CD30 expression of malignant lymphocytes in mycosis fungoides (MF) and Sézary syndrome (SS) is quite variable. Clinical activity and safety of brentuximab vedotin, a CD30 targeting antibody-drug conjugate, was evaluated in MF and SS. Tissue and blood biomarkers of clinical response were explored. Patients and Methods In this phase II study, patients with MF or SS with negligible to 100% CD30 expression levels were treated with brentuximab vedotin (1.8 mg/kg) every 3 weeks for a maximum of sixteen doses. The primary end point was overall global response rate. Secondary end points included correlation of tissue CD30 expression level with clinical response, time to response, duration of response, progression-free and event-free survivals, and safety. Results Of the 32 patients enrolled and treated, 30 patients had available efficacy evaluations. Objective global response was observed in 21 (70%) of 30 patients (90% CI, 53% to 83%). CD30 expression assessed by immunohistochemistry was highly variable, with a median CD30max of 13% (range, 0% to 100%). Those with <5% CD30 expression had a lower likelihood of global response than did those with 5% or greater CD30 expression (P < .005). CD163 positive tumor-associated macrophages, many of which coexpress CD30, were abundant in tissue. Peripheral neuropathy was the most common adverse event. Conclusion Brentuximab vedotin demonstrated significant clinical activity in treatment-refractory or advanced MF or SS with a wide range of CD30 expression levels. Additional biomarker studies may help optimize rational design of combination therapies with brentuximab vedotin. PMID:26195720

Cooperative learning as applied to resident instruction in radiology reporting.

PubMed

Mueller, Donald; Georges, Alexandra; Vaslow, Dale

2007-12-01

The study is designed to evaluate the effectiveness of an active form of resident instruction, cooperative learning, and the residents' response to that form of instruction. The residents dictated three sets of reports both before and after instruction in radiology reporting using the cooperative learning method. The reports were evaluated for word count, Flesch-Kincaid grade level, advancement on clinical spectrum, clarity, and comparison to prior reports. The reports were evaluated for changes in performance characteristics between the pre- and postinstruction dictations. The residents' response to this form of instruction was evaluated by means of a questionnaire. The instruction was effective in changing the resident dictations. The results became shorter (P<.035), more complex (P<.0126), and demonstrated increased advancement on clinical spectrum (P<.0204). The resident response to this form of instruction was positive. One hundred percent or respondents indicated enjoyment working with their groups. Seventy-five percent stated they would like to participate in more cooperative learning activities. The least positive responses related to the amount of time devoted to the project. Sixty-three percent of respondents stated that the time devoted to the project was appropriate. Cooperative learning can be an effective tool in the setting of the radiology residency. Instructional time requirements must be strongly considered in designing a cooperative learning program.

Collaborative learning in pre-clinical dental hygiene education.

PubMed

Mueller-Joseph, Laura J; Nappo-Dattoma, Luisa

2013-04-01

Dental hygiene education continues to move beyond mastery of content material and skill development to learning concepts that promote critical-thinking and problem-solving skills. The purpose of this research was to evaluate the effectiveness of collaborative learning and determine the growth in intellectual development of 54 first-year dental hygiene students. The control group used traditional pre-clinical teaching and the experimental group used collaborative pedagogy for instrument introduction. All students were subjected to a post-test evaluating their ability to apply the principles of instrumentation. Intellectual development was determined using pre- and post-tests based on the Perry Scheme of Intellectual Development. Student attitudes were assessed using daily Classroom Assessment Activities and an end-of-semester departmental course evaluation. Findings indicated no significant difference between collaborative learning and traditional learning in achieving pre-clinical competence as evidenced by the students' ability to apply the principles of instrumentation. Advancement in intellectual development did not differ significantly between groups. Value added benefits of a collaborative learning environment as identified by the evaluation of student attitudes included decreased student reliance on authority, recognition of peers as legitimate sources of learning and increased self-confidence. A significant difference in student responses to daily classroom assessments was evident on the 5 days a collaborative learning environment was employed. Dental hygiene students involved in a pre-clinical collaborative learning environment are more responsible for their own learning and tend to have a more positive attitude toward the subject matter. Future studies evaluating collaborative learning in clinical dental hygiene education need to investigate the cost/benefit ratio of the value added outcomes of collaborative learning.

Drug development in neuropsychopharmacology.

PubMed

Fritze, Jürgen

2008-03-01

Personalized medicine is still in its infancy concerning drug development in neuropsychopharmacology. Adequate biomarkers with clinical relevance to drug response and/or tolerability and safety largely remain to be identified. Possibly, this kind of personalized medicine will first gain clinical relevance in the dementias. The clinical relevance of the genotyping of drug-metabolizing enzymes as suggested by drug licensing authorities for the pharmacokinetic evaluation of medicinal products needs to be proven in sound clinical trials.

Prediction of Short- and Medium-term Efficacy of Biosimilar Infliximab Therapy. Do Trough Levels and Antidrug Antibody Levels or Clinical And Biochemical Markers Play the More Important Role?

PubMed

Gonczi, Lorant; Vegh, Zsuzsanna; Golovics, Petra Anna; Rutka, Mariann; Gecse, Krisztina Barbara; Bor, Renata; Farkas, Klaudia; Szamosi, Tamás; Bene, László; Gasztonyi, Beáta; Kristóf, Tünde; Lakatos, László; Miheller, Pál; Palatka, Károly; Papp, Mária; Patai, Árpád; Salamon, Ágnes; Tóth, Gábor Tamás; Vincze, Áron; Biro, Edina; Lovasz, Barbara Dorottya; Kurti, Zsuzsanna; Szepes, Zoltan; Molnár, Tamás; Lakatos, Péter L

2017-06-01

Biosimilar infliximab CT-P13 received European Medicines Agency [EMA] approval in June 2013 for all indications of the originator product. In the present study, we aimed to evaluate the predictors of short- and medium-term clinical outcome in patients treated with the biosimilar infliximab at the participating inflammatory bowel disease [IBD] centres in Hungary. Demographic data were collected and a harmonised monitoring strategy was applied. Clinical and biochemical activities were evaluated at Weeks 14, 30, and 54. Trough level [TL] and anti-drug antibody [ADA] concentrations were measured by enzyme-linked immunosorbent assay [ELISA] [LT-005, Theradiag, France] at baseline at 14, 30 and 54 weeks and in two centres at Weeks 2 and 6. A total of 291 consecutive IBD patients (184 Crohn's disease [CD] and 107 ulcerative colitis [UC]) were included. In UC, TLs at Week 2 predicted both clinical response and remission at Weeks 14 and 30 (clinical response/remission at Week 14: area under the curve [AUC] = 0.81, p < 0.001, cut-off: 11.5 μg/ml/AUC = 0.79, p < 0.001, cut-off: 15.3μg/ml; clinical response/remission at Week 30: AUC = 0.79, p = 0.002, cut-off: 11.5 μg/ml/AUC = 0.74, p = 0.006, cut-off: 14.5 μg/ml), whereas ADA positivity at Week 14 was inversely associated with clinical response at Week 30 [58.3% vs 84.8% ,p = 0.04]. Previous anti-tumour necrosis factor [TNF] exposure was inversely associated with short-term clinical remission [Week 2: 18.8% vs 47.8%, p = 0.03, at Week 6: 38.9% vs 69.7%, p = 0.013, at Week 14: 37.5% vs 2.5%, p = 0.06]. In CD, TLs at Week 2 predicted short-term [Week 14 response/remission, AUCTLweek2 = 0.715-0.721, p = 0.05/0.005] but not medium-term clinical efficacy. In addition, early ADA status by Week 14 [p = 0.04-0.05 for Weeks 14 and 30], early clinical response [p < 0.001 for Weeks 30/54] and normal C-reactive protein [CRP] at Week 14 [p = 0.005-0.0001] and previous anti-TNF exposure [p = 0.03-0.0001 for Weeks 14, 30, and 54] were associated with short-and medium-term clinical response and remission. In UC, early TLs were predictive for short- and medium-term clinical efficacy, whereas in CD, Week 2 TLs were associated only with short-term clinical outcomes. Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com

Association between dynamic features of breast DCE-MR imaging and clinical response of neoadjuvant chemotherapy: a preliminary analysis

NASA Astrophysics Data System (ADS)

Huang, Lijuan; Fan, Ming; Li, Lihua; Zhang, Juan; Shao, Guoliang; Zheng, Bin

2016-03-01

Neoadjuvant chemotherapy (NACT) is being used increasingly in the management of patients with breast cancer for systemically reducing the size of primary tumor before surgery in order to improve survival. The clinical response of patients to NACT is correlated with reduced or abolished of their primary tumor, which is important for treatment in the next stage. Recently, the dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is used for evaluation of the response of patients to NACT. To measure this correlation, we extracted the dynamic features from the DCE- MRI and performed association analysis between these features and the clinical response to NACT. In this study, 59 patients are screened before NATC, of which 47 are complete or partial response, and 12 are no response. We segmented the breast areas depicted on each MR image by a computer-aided diagnosis (CAD) scheme, registered images acquired from the sequential MR image scan series, and calculated eighteen features extracted from DCE-MRI. We performed SVM with the 18 features for classification between patients of response and no response. Furthermore, 6 of the 18 features are selected to refine the classification by using Genetic Algorithm. The accuracy, sensitivity and specificity are 87%, 95.74% and 50%, respectively. The calculated area under a receiver operating characteristic (ROC) curve is 0.79+/-0.04. This study indicates that the features of DCE-MRI of breast cancer are associated with the response of NACT. Therefore, our method could be helpful for evaluation of NACT in treatment of breast cancer.

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

PubMed

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 education effectiveness, although simulation can be effective. No study shows any type of intervention results in sustained improvement. There are workload implications in education and the matching of load, number and type of alarms with nurse demographics which should be evaluated. There also needs to be a connection between education and the clinical setting to contribute to clinical alarm awareness for undergraduate nurses and practicing nurses. Education solely supported by employers is insufficient. Patient safety and long-term effects must be further explored. © 2016 John Wiley & Sons Ltd.

Validity and Responsiveness of the Two-Minute Walk Test for Measuring Functional Recovery After Total Knee Arthroplasty.

PubMed

Unnanuntana, Aasis; Ruangsomboon, Pakpoom; Keesukpunt, Worawut

2018-06-01

The 2-minute walk test (2mwt) is a performance-based test that evaluates functional recovery after total knee arthroplasty (TKA). This study evaluated its validity compared with the modified Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Oxford Knee Score (OKS), modified Knee Score, Numerical Pain Rating Scale, and Timed Up and Go test, and its responsiveness in assessing functional recovery in TKA patients. This prospective cohort study included 162 patients undergoing primary TKA between 2013 and 2015. We used patient-reported outcome measures (modified WOMAC, OKS, modified Knee Score, Numerical Pain Rating Scale) and performance-based tests (2mwt and Timed Up and Go test) at baseline and 3, 6, and 12 months postoperatively. The construct validity of 2mwt was determined between the 2mwt distances walked and other outcome measurements. To assess responsiveness, effect size and standardized response mean were analyzed. Minimal clinically important difference of 2mwt at 12 months after TKA was also calculated. All outcome measurements improved significantly from baseline to 3, 6, and 12 months postoperatively. Bivariate analysis revealed mild to moderate associations between the 2mwt and modified WOMAC function subscales, and moderate to strong associations with OKS. Mild to moderate correlations were found for pain and stiffness between 2mwt and other outcome measurements. The effect size and standardized response mean at 12 months were large, with a minimal clinically important difference of 12.7 m. 2mwt is a validated performance-based test with responsiveness properties. Being simple and easy to perform, it can be used routinely in clinical practice to evaluate functional recovery after TKA. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

A pilot study: sequential gemcitabine/cisplatin and icotinib as induction therapy for stage IIB to IIIA non-small-cell lung adenocarcinoma

PubMed Central

2013-01-01

Background A phase II clinical trial previously evaluated the sequential administration of erlotinib after chemotherapy for advanced non-small-cell lung cancer (NSCLC). This current pilot study assessed the feasibility of sequential induction therapy in patients with stage IIB to IIIA NSCLC adenocarcinoma. Methods Patients received gemcitabine 1,250 mg/m2 on days 1 and 8 and cisplatin 75 mg/m2 on day 1, followed by oral icotinib (125 mg, three times a day) on days 15 to 28. A repeatcomputed tomography(CT) scan evaluated the response to the induction treatment after two 4-week cycles and eligible patients underwent surgical resection. The primary objective was to assess the objective response rate (ORR), while EGFR and KRAS mutations and mRNA and protein expression levels of ERCC1 and RRM1 were analyzed in tumor tissues and blood samples. Results Eleven patients, most with stage IIIA disease, completed preoperative treatment. Five patients achieved partial response according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria (ORR=45%) and six patients underwent resection. Common toxicities included neutropenia, alanine transaminase (ALT) elevation, fatigue, dry skin, rash, nausea, alopecia and anorexia. No serious complications were recorded perioperatively. Three patients had exon 19 deletions and those with EGFR mutations were more likely to achieve a clinical response (P= 0.083). Furthermore, most cases who achieved a clinical response had low levels of ERCC1 expression and high levels of RRM1. Conclusions Two cycles of sequentially administered gemcitabine/cisplatin with icotinib as an induction treatment is a feasible and efficacious approach for stage IIB to IIIA NSCLC adenocarcinoma, which provides evidence for the further investigation of these chemotherapeutic and molecularly targeted therapies. PMID:23621919

SLC6A3 polymorphism and response to methylphenidate in children with ADHD: A systematic review and meta-analysis.

PubMed

Soleimani, Robabeh; Salehi, Zivar; Soltanipour, Soheil; Hasandokht, Tolou; Jalali, Mir Mohammad

2018-04-01

Methylphenidate (MPH) is the most commonly used treatment for attention-deficit hyperactivity disorder (ADHD) in children. However, the response to MPH is not similar in all patients. This meta-analysis investigated the potential role of SLC6A3 polymorphisms in response to MPH in children with ADHD. Clinical trials or naturalistic studies were selected from electronic databases. A meta-analysis was conducted using a random-effects model. Cohen's d effect size and 95% confidence intervals (CIs) were determined. Sensitivity analysis and meta-regression were performed. Q-statistic and Egger's tests were conducted to evaluate heterogeneity and publication bias, respectively. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to assess the quality of evidence. Sixteen studies with follow-up periods of 1-28 weeks were eligible. The mean treatment acceptability of MPH was 97.2%. In contrast to clinical trials, the meta-analysis of naturalistic studies indicated that children without 10/10 repeat carriers had better response to MPH (Cohen's d: -0.09 and 0.44, respectively). The 9/9 repeat polymorphism had no effect on the response rate (Cohen's d: -0.43). In the meta-regression, a significant association was observed between baseline severity of ADHD, MPH dosage, and combined type of ADHD in some genetic models. Sensitivity analysis indicated the robustness of our findings. No publication bias was observed in our meta-analysis. The GRADE evaluations revealed very low levels of confidence for each outcome of response to MPH. The results of clinical trials and naturalistic studies regarding the effect size between different polymorphisms of SLC6A3 were contradictory. Therefore, further research is recommended. © 2017 Wiley Periodicals, Inc.

[Immunological surrogate endpoints to evaluate vaccine efficacy].

PubMed

Jin, Pengfei; Li, Jingxin; Zhou, Yang; Zhu, Fengcai

2015-12-01

An immunological surrogate endpoints is a vaccine-induced immune response (either humoral or cellular immune) that predicts protection against clinical endpoints (infection or disease), and can be used to evaluate vaccine efficacy in clinical vaccine trials. Compared with field efficacy trials observing clinical endpoints, immunological vaccine trials could reduce the sample size or shorten the duration of a trial, which promote the license and development of new candidate vaccines. For these reasons, establishing immunological surrogate endpoints is one of 14 Grand Challenges of Global Health of the National Institutes of Health (NIH) and the Bill and Melinda Gates Foundation. From two parts of definition and statistical methods for evaluation of surrogate endpoints, this review provides a more comprehensive description.

[Implementation of the new clinical practice training model in Andalusia: a qualitative evaluation of the Nursing and Physiotherapy degrees].

PubMed

Fernández-Sola, Cayetano; Granero-Molina, José; Márquez-Membrive, Josefa; Aguilera-Manrique, Gabriel; Castro-Sánchez, Adelaida M

2014-01-01

The design of new Bachelor degree courses, together with the agreement reached between the Regional Government of Andalusia and Andalusian universities shape the new clinical training model for Health Science students. The aim of this project is to present a qualitative evaluation of the implementation of the new model in Nursing and Physiotherapy degrees at the University of Almeria and the Andalusian Public Health System. An exploratory qualitative study using document content analysis techniques, by analyzing 12 reports from teachers and those responsible for Practicum in Nursing and Physiotherapy degrees at the University of Almeria. The reports included opinions and proposals from university and clinical placement teachers, healthcare professionals or clinical placement tutors, students, and those in positions of responsibility as regards clinical placements. Three categories emerged in the data analysis: Health system organization, with sub-categories of disparity between shifts, difficulties with supervisor coordination, feelings of a lack of control, disparities in evaluation criteria and geographic distribution; academic organization, with sub-categories of short rotations, a lack of information received by the clinical placement tutor, and carrying out placements without studying the theory; and management of the work agreement, with sub-categories of being discouraged by what is received in return, extra work for those in charge, and delays in evaluations. The study suggests a need to support and guide clinical tutors, to increase coordination between the university and health services, to organize the students' theoretical and practical training and to provide the management of the model with flexibility and transparency. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Is It Important to Adapt Neoadjuvant Chemotherapy to the Visible Clinical Response? An Open Randomized Phase II Study Comparing Response-Guided and Standard Treatments in HER2-Negative Operable Breast Cancer

PubMed Central

Mouret-Reynier, Marie-Ange; Savoye, Aude-Marie; Abrial, Catherine; Kwiatkowski, Fabrice; Garbar, Christian; DuBray-Longeras, Pascale; Eymard, Jean-Christophe; Lebouedec, Guillaume; Vanpraagh, Isabelle; Penault-Llorca, Frederique; Chollet, Philippe; Cure, Hervé

2015-01-01

Background. Neoadjuvant treatment provides a unique opportunity to evaluate individual tumor sensitivity. This study evaluated whether a response-guided strategy could improve clinical outcome compared with a standard treatment. Methods. Overall, 264 previously untreated stage II–III operable breast cancer patients were randomized to receive either standard treatment (arm A, n = 131), consisting of fluorouracil, epirubicin, and cyclophosphamide (FEC100: 500, 100, and 500 mg/m2, respectively, for 3 cycles) followed by docetaxel (100 mg/m2 for 3 cycles), or adapted treatment (arm B, n = 133), beginning with 2 cycles of FEC100 and switching to docetaxel if tumor size decreased by <30% after 2 cycles or <50% after 4 cycles of FEC100 (ultrasound assessments according to World Health Organization criteria). Otherwise, FEC100 was given for six cycles before surgery. Intent-to-treat analysis was performed. Results. Similar results were observed for clinical response (objective response was 54% vs 56%, p = .18), breast conservation surgery (BCS; 67% vs 68%, p = .97), and pathological complete response rate (Chevallier classification: 14% vs 11%, p = .68; Statloff classification: 16% vs 13%, p = .82) between arms A and B. Similar toxicities were observed, even with unbalanced numbers of FEC100 and docetaxel courses. Conclusion. Adapted and standard treatments had similar results in terms of tumor response, BCS rate, and tolerability. Further survival outcome data are expected. PMID:25637380

Clinical utility of measures of breathlessness.

PubMed

Cullen, Deborah L; Rodak, Bernadette

2002-09-01

The clinical utility of measures of dyspnea has been debated in the health care community. Although breathlessness can be evaluated with various instruments, the most effective dyspnea measurement tool for patients with chronic lung disease or for measuring treatment effectiveness remains uncertain. Understanding the evidence for the validity and reliability of these instruments may provide a basis for appropriate clinical application. Evaluate instruments designed to measure breathlessness, either as single-symptom or multidimensional instruments, based on psychometrics foundations such as validity, reliability, and discriminative and evaluative properties. Classification of each dyspnea measurement instrument will recommend clinical application in terms of exercise, benchmarking patients, activities of daily living, patient outcomes, clinical trials, and responsiveness to treatment. Eleven dyspnea measurement instruments were selected. Each instrument was assessed as discriminative or evaluative and then analyzed as to its psychometric properties and purpose of design. Descriptive data from all studies were described according to their primary patient application (ie, chronic obstructive pulmonary disease, asthma, or other patient populations). The Borg Scale and the Visual Analogue Scale are applicable to exertion and thus can be applied to any cardiopulmonary patient to determine dyspnea. All other measures were determined appropriate for chronic obstructive pulmonary disease, whereas the Shortness of Breath Questionnaire can be applied to cystic fibrosis and lung transplant patients. The most appropriate utility for all instruments was measuring the effects on activities of daily living and for benchmarking patient progress. Instruments that quantify function and health-related quality of life have great utility for documenting outcomes but may be limited as to documenting treatment responsiveness in terms of clinically important changes. The dyspnea measurement instruments we studied meet important standards of validity and reliability. Discriminative measures have limited clinical utility and, when used for populations or conditions for which they are not designed or validated, the data collected may not be clinically relevant. Evaluative measures have greater clinical utility and can be applied for outcome purposes. Measures should be applied to the populations and conditions for which they were designed. The relationship between clinical therapies and the measurement of dyspnea as an outcome can develop as respiratory therapists become more comfortable with implementing dyspnea measurement instruments and use the data to improve patient treatment. Dyspnea evaluation should be considered for all clinical practice guidelines and care pathways.

Two-year efficacy of tocilizumab in patients with active rheumatoid arthritis in clinical practice.

PubMed

Notario Ferreira, Irene; Ferrer González, Miguel Angel; Morales Garrido, Pilar; González Utrilla, Alfonso; García Sanchez, Antonio; Soto Pino, María José; Suero Rosario, Evelyn; Caro Hernández, Cristina; Añón Oñate, Isabel; Pérez Albaladejo, Lorena; Cáliz Cáliz, Rafael

To evaluate the efficacy of tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) in clinical practice, retention rates of the drug and predictors of response. We performed a descriptive, prospective, longitudinal, open-label study in patients receiving TCZ (8mg/kg/4 weeks) in a clinical practice setting. The clinical responses were evaluated using the European League Against Rheumatism (EULAR) response criteria, and the low activity and remission rates according to the Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) and the Clinical Disease Activity Index (CDAI). The EULAR response rate was 86.63% and the DAS28 remission rate was 53.7% after 6 months of treatment; rates of low disease activity were 52.9% on CDAI and 47.1% on DAS28 at month 24. There were no statistically significant differences in EULAR response, rates of low activity and remission on DAS28 between patients receiving TCZ alone and those receiving TCZ in combination therapy, or between patients positive or negative for rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide (anti-CCP) antibodies. The naïve biological therapy patients showed better remission and low activity rates after 6 months of treatment. The retention rate was 61% at month 24. Adverse events were among the most frequent causes of discontinuation. Tocilizumab is effective in RA, has a similar efficacy when used alone or in combination with synthetic disease-modifying antirheumatic drugs (DMARDs) and shows high retention rates. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

A randomized phase II trial comparing two different sequence combinations of autologous vaccine and human recombinant interferon gamma and human recombinant interferon alpha2B therapy in patients with metastatic renal cell carcinoma: clinical outcome and analysis of immunological parameters.

PubMed

Schwaab, T; Heaney, J A; Schned, A R; Harris, R D; Cole, B F; Noelle, R J; Phillips, D M; Stempkowski, L; Ernstoff, M S

2000-04-01

The clinical observation of spontaneous regression in patients with renal cell carcinoma (RCC) and the response to various immunotherapeutic therapies strongly suggest a role for the host immune system in this disease. Prior studies showed that sequential administration of interferon (IFN) gamma and IFN alpha to RCC patients was safe. Clinical responses as well as immune changes in the peripheral blood mononuclear cell compartment were observed. Autologous tumor cell vaccines (AV) have also demonstrated activity in renal cell carcinoma. We hypothesize that the addition of AV to sequential IFN gamma and a therapy might improve the tumor-specific immune response by providing an appropriate source of antigen in the appropriate cytokine environment. To our knowledge, this is the first trial using AV combined with IFN alpha and IFN gamma. The purpose of this study was to evaluate the feasibility of manufacturing and administering (AV) from resected tumor samples, and administration of AV with combination IFN gamma and IFN alpha therapy. Finally, the impact on immunological parameters of these treatment options was assessed. Patients with metastatic RCC were randomly assigned to receive AV plus bCG along with a sequential administration of IFN gamma and a either together or after initiation of vaccine. Toxicity and clinical responses were evaluated. Modulations of the immune system were investigated by analyzing phenotype, cytokine mRNA expression, T cell proliferation and cytotoxicity in the peripheral blood mononuclear cell compartment. Fourteen patients with metastatic renal cell carcinoma were enrolled in this study; 9 were available for response evaluation. In a 70 day period, 3 (33%) showed mixed responses, 5 (56%) stable disease and 1 (11%) progression of disease. Toxicities were consistent with previous clinical reports. In the flow-cytometry phenotype analysis, stimulation of distinct subsets of circulating T-lymphocytes and a decrease of CD8+ T cell subsets was demonstrated. T-cell proliferation to allogeneic tumor cell stimulation improved following treatment. IL-4 and IL-5 mRNA levels were reduced in all patients after treatment. Patients who responded to treatment did not produce any IL-4 mRNA at all, before or after treatment. AV with IFNgamma and IFNalpha therapy might induce a MHC class-mediated cytotoxic T lymphocyte (CTL) response. We suggest that adequate therapy might direct T cell response toward a Th1 type response. We hypothesize a state of improved immune readiness in patients who might eventually respond to immunotherapy.

Evaluating cardiac risk: exposure response analysis in early clinical drug development.

PubMed

Grenier, Julie; Paglialunga, Sabina; Morimoto, Bruce H; Lester, Robert M

2018-01-01

The assessment of a drug's cardiac liability has undergone considerable metamorphosis by regulators since International Council for Harmonization of Technical Requirement for Pharmaceuticals for Human Use E14 guideline was introduced in 2005. Drug developers now have a choice in how proarrhythmia risk can be evaluated; the options include a dedicated thorough QT (TQT) study or exposure response (ER) modeling of intensive electrocardiogram (ECG) captured in early clinical development. The alternative approach of ER modeling was incorporated into a guidance document in 2015 as a primary analysis tool which could be utilized in early phase dose escalation studies as an option to perform a dedicated TQT trial. This review will describe the current state of ER modeling of intensive ECG data collected during early clinical drug development; the requirements with regard to the use of a positive control; and address the challenges and opportunities of this alternative approach to assessing QT liability.

Personalized Drug Therapy in Cystic Fibrosis: From Fiction to Reality.

PubMed

de Lima Marson, Fernando Augusto; Bertuzzo, Carmen Silvia; Ribeiro, Jose Dirceu

2015-01-01

Personalized drug therapy for cystic fibrosis (CF) is a long-term dream for CF patients, caregivers, physicians and researchers. After years of study, the fiction of personalized treatment has turned to hope. Basic information about CFTR mutations classes and new treatments is needed if we are to deal properly with the new CF era. The problems involved in this issue, however, should be evaluated with greater care and attention. VX-770 is a new drug available to treat CF patients with some class III CFTR mutations and other drugs are being studied regarding other classes. The scientific literature has constantly given information about each therapy, both in vitro and in vivo. The hope is increasing. Nevertheless the "scientific world" still lacks information about patients' reality and daily health related practical needs. Clinical trials have showed good evaluation of some drugs so far, but clinical response is a wide spectrum yet to be analyzed: CFTR mutations spectrum, costs related to the treatment with new drugs (for VX-770 therapy), variability of CF clinical expression, limitations to test in vitro drugs, absence of good clinical markers to evaluate drug response, absence of long-term studies and with patients below six years old, multidrug treatment used to improve the expression response, and finally, the most important problem, who will benefit from the new drugs therapy, are issues that constitute a barrier that should be overcome. Personalized drug therapy may not be a fiction anymore, but it is not yet a reality for all CF patients.

Retrospective clinical study on the notable efficacy and related factors of infliximab therapy in a rheumatoid arthritis management group in Japan: one-year clinical outcomes (RECONFIRM-2)

PubMed Central

Takeuchi, Tsutomu; Inoue, Eisuke; Saito, Kazuyoshi; Sekiguchi, Naoya; Sato, Eri; Nawata, Masao; Kameda, Hideto; Iwata, Shigeru; Amano, Kouichi; Yamanaka, Hisashi

2008-01-01

Biologics targeting TNF have brought about a paradigm shift in the treatment of rheumatoid arthritis (RA) and infliximab, anti-TNF-α chimeric monoclonal antibody, was marketed in 2003 in Japan. We previously reported on the RECONFIRM study, a retrospective clinical study on the efficacy of infliximab therapy in a RA management group in Japan, where we evaluated the clinical response after 22 weeks of the therapy in 258 patients. The study reported here was aimed at reconfirming the clinical efficacy of the infliximab therapy and demographic factors related to the efficacy over a 54-week study period in 410 RA patients in the same study group. Infliximab was infused according to the domestically approved method, and the clinical response was evaluated following 54 weeks of infliximab therapy using the European League Against Rheumatism (EULAR) response criteria. Disease activity was assessed by DAS28-CRP (Disease Activity Score including a 28-joint count/C-reactive protein). Infliximab was discontinued in 24.4% of the 410 patients at 54 weeks and 9.3% and 8.1% discontinued the therapy due to adverse events and inefficiency, respectively. Average DAS28-CRP decreased from 5.5 at week 0 to 3.1 at week 54 after the therapy. Patients in remission and those showing low-, moderate-, and high-disease activity changed from 0.0, 1.0, 9.0 and 90.0%, respectively, at the start of the study to 27.6, 11.7, 34.4 and 26.3%, respectively, at week 54. Younger age, RF-negativity and low scores of DAS28-CRP showed significant correlations with remission at week 54. EULAR response criteria—good, moderate, and no response to infliximab—were 37.0, 41.7 and 21.2%, respectively. In conclusion, we reconfirmed the clinical efficacy of infliximab and demographic factors related to the efficacy over a 54-week study period in 410 Japanese patients with RA using DAS28-CRP and EULAR response criteria. PMID:18283523

Larval Zebrafish Model for FDA-Approved Drug Repositioning for Tobacco Dependence Treatment

PubMed Central

Cousin, Margot A.; Ebbert, Jon O.; Wiinamaki, Amanda R.; Urban, Mark D.; Argue, David P.; Ekker, Stephen C.; Klee, Eric W.

2014-01-01

Cigarette smoking remains the most preventable cause of death and excess health care costs in the United States, and is a leading cause of death among alcoholics. Long-term tobacco abstinence rates are low, and pharmacotherapeutic options are limited. Repositioning medications approved by the U.S. Food and Drug Administration (FDA) may efficiently provide clinicians with new treatment options. We developed a drug-repositioning paradigm using larval zebrafish locomotion and established predictive clinical validity using FDA-approved smoking cessation therapeutics. We evaluated 39 physician-vetted medications for nicotine-induced locomotor activation blockade. We further evaluated candidate medications for altered ethanol response, as well as in combination with varenicline for nicotine-response attenuation. Six medications specifically inhibited the nicotine response. Among this set, apomorphine and topiramate blocked both nicotine and ethanol responses. Both positively interact with varenicline in the Bliss Independence test, indicating potential synergistic interactions suggesting these are candidates for translation into Phase II clinical trials for smoking cessation. PMID:24658307

[Diagnosis and treatment of the most frequent vestibular syndromes].

PubMed

Kanashiro, Aline Mizuta Kozoroski; Pereira, Cristiana Borges; Melo, Antonio Carlos de Paiva; Scaff, Milberto

2005-03-01

The aims of this study were to identify the most common vestibular syndromes in a dizziness unit, and to observe their clinical aspects and response to treatment. Five hundred and fifteen patients were studied retrospectively in two institutions. Aspects of anamnesis, physical examination and the response to treatment were evaluated. The most frequent syndromes were: benign paroxysmal positioning vertigo (VPPB) (28.5%), phobic postural vertigo (11.5%), central vertigo (10.1%), vestibular neuritis (9.7%), Meniere disease (8.5%), and migraine (6.4%). A good response to treatment was observed in most patients with migraine (78.8%), VPPB (64%), vestibular neuritis (62%), Meniere disease (54.5%) and vestibular paroxismia (54.5%). On the other hand, patients with downbeat nystagmus and bilateral vestibulopathy had poor response (52.6% and 42.8%, respectively). The diagnosis of these most frequent vestibular syndromes were established through anamnesis and physical examination (with specific clinical tests for evaluation of the vestibular function). The correct diagnosis and adequate treatment are important since these syndromes may have a good prognosis.

The Transplantation of hBM-MSCs Increases Bone Neo-Formation and Preserves Hearing Function in the Treatment of Temporal Bone Defects - on the Experience of Two Month Follow Up.

PubMed

Školoudík, Lukáš; Chrobok, Viktor; Kočí, Zuzana; Popelář, Jiří; Syka, Josef; Laco, Jan; Filipová, Alžběta; Syková, Eva; Filip, Stanislav

2018-06-03

Temporal bone reconstruction is a persisting problem following middle ear cholesteatoma surgery. Seeking to advance the clinical transfer of stem cell therapy we attempted the reconstruction of temporal bone using a composite bioartificial graft based on a hydroxyapatite bone scaffold combined with human bone marrow-derived mesenchymal stromal cells (hBM-MSCs). The aim of this study was to evaluate the effect of the combined biomaterial on the healing of postoperative temporal bone defects and the preservation of physiological hearing functions in a guinea pig model. The treatment's effect could be observed at 1 and 2 months after implantation of the biomaterial, as opposed to the control group. The clinical evaluation of our results included animal survival, clinical signs of an inflammatory response, and exploration of the tympanic bulla. Osteogenesis, angiogenesis, and inflammation were evaluated by histopathological analyses, whereas hBM-MSCs survival was evaluated by immunofluorescence assays. Hearing capacity was evaluated by objective audiometric methods, i.e. auditory brainstem responses and otoacoustic emission. Our study shows that hBM-MSCs, in combination with hydroxyapatite scaffolds, improves the repair of bone defects providing a safe and effective alternative in their treatment following middle ear surgery due to cholesteatoma.

Implementing a pilot leadership course for internal medicine residents: design considerations, participant impressions, and lessons learned.

PubMed

Blumenthal, Daniel M; Bernard, Ken; Fraser, Traci N; Bohnen, Jordan; Zeidman, Jessica; Stone, Valerie E

2014-11-30

Effective clinical leadership is associated with better patient care. We implemented and evaluated a pilot clinical leadership course for second year internal medicine residents at a large United States Academic Medical Center that is part of a multi-hospital health system. The course met weekly for two to three hours during July, 2013. Sessions included large group discussions and small group reflection meetings. Topics included leadership styles, emotional intelligence, and leading clinical teams. Course materials were designed internally and featured "business school style" case studies about everyday clinical medicine which explore how leadership skills impact care delivery. Participants evaluated the course's impact and quality using a post-course survey. Questions were structured in five point likert scale and free text format. Likert scale responses were converted to a 1-5 scale (1 = strongly disagree; 3 = neither agree nor disagree; 5 = strongly agree), and means were compared to the value 3 using one-way T-tests. Responses to free text questions were analyzed using the constant comparative method. All sixteen pilot course participants completed the survey. Participants overwhelmingly agreed that the course provided content and skills relevant to their clinical responsibilities and leadership roles. Most participants also acknowledged that taking the course improved their understanding of their strengths and weaknesses as leaders, different leadership styles, and how to manage interpersonal conflict on clinical teams. 88% also reported that the course increased their interest in pursuing additional leadership training. A clinical leadership course for internal medicine residents designed by colleagues, and utilizing case studies about clinical medicine, resulted in significant self-reported improvements in clinical leadership competencies.

Corticosteroid therapy in ulcerative colitis: Clinical response and predictors

PubMed Central

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

2015-01-01

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

Ratio of urine and blood urea nitrogen concentration predicts the response of tolvaptan in congestive heart failure.

PubMed

Shimizu, Keisuke; Doi, Kent; Imamura, Teruhiko; Noiri, Eisei; Yahagi, Naoki; Nangaku, Masaomi; Kinugawa, Koichiro

2015-06-01

This study was conducted to evaluate the performance of the ratio of urine and blood urea nitrogen concentration (UUN/BUN) as a new predictive factor for the response of an arginine vasopressin receptor 2 antagonist tolvaptan (TLV) in decompensated heart failure patients. This study enrolled 70 decompensated heart failure patients who were administered TLV at University of Tokyo Hospital. We collected the data of clinical parameters including UUN/BUN before administering TLV. Two different outcomes were defined as follows: having over 300 mL increase in urine volume on the first day (immediate urine output response) and having any decrease in body weight within one week after starting TLV treatment (subsequent clinical response). Among the 70 enrolled patients, 37 patients (52.9%) showed immediate urine output response; 51 patients (72.9%) showed a subsequent clinical response of body weight decrease. Receiver operating characteristics (ROC) analysis showed good prediction by UUN/BUN for the immediate response (AUC-ROC 0.86 [0.75-0.93]) and a significantly better prediction by UUN/BUN for the subsequent clinical response compared with urinary osmolality (AUC-ROC 0.78 [0.63-0.88] vs. 0.68 [0.52-0.80], P < 0.05). We demonstrated that a clinical parameter of UUN/BUN can predict the response of TLV even when measured before TLV administration. UUN/BUN might enable identification of good responders for this new drug. © 2015 Asian Pacific Society of Nephrology.

A novel approach to assess the treatment response using Gaussian random field in PET

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

Wang, Mengdie; Guo, Ning; Hu, Guangshu

2016-02-15

Purpose: The assessment of early therapeutic response to anticancer therapy is vital for treatment planning and patient management in clinic. With the development of personal treatment plan, the early treatment response, especially before any anatomically apparent changes after treatment, becomes urgent need in clinic. Positron emission tomography (PET) imaging serves an important role in clinical oncology for tumor detection, staging, and therapy response assessment. Many studies on therapy response involve interpretation of differences between two PET images, usually in terms of standardized uptake values (SUVs). However, the quantitative accuracy of this measurement is limited. This work proposes a statistically robustmore » approach for therapy response assessment based on Gaussian random field (GRF) to provide a statistically more meaningful scale to evaluate therapy effects. Methods: The authors propose a new criterion for therapeutic assessment by incorporating image noise into traditional SUV method. An analytical method based on the approximate expressions of the Fisher information matrix was applied to model the variance of individual pixels in reconstructed images. A zero mean unit variance GRF under the null hypothesis (no response to therapy) was obtained by normalizing each pixel of the post-therapy image with the mean and standard deviation of the pretherapy image. The performance of the proposed method was evaluated by Monte Carlo simulation, where XCAT phantoms (128{sup 2} pixels) with lesions of various diameters (2–6 mm), multiple tumor-to-background contrasts (3–10), and different changes in intensity (6.25%–30%) were used. The receiver operating characteristic curves and the corresponding areas under the curve were computed for both the proposed method and the traditional methods whose figure of merit is the percentage change of SUVs. The formula for the false positive rate (FPR) estimation was developed for the proposed therapy response assessment utilizing local average method based on random field. The accuracy of the estimation was validated in terms of Euler distance and correlation coefficient. Results: It is shown that the performance of therapy response assessment is significantly improved by the introduction of variance with a higher area under the curve (97.3%) than SUVmean (91.4%) and SUVmax (82.0%). In addition, the FPR estimation serves as a good prediction for the specificity of the proposed method, consistent with simulation outcome with ∼1 correlation coefficient. Conclusions: In this work, the authors developed a method to evaluate therapy response from PET images, which were modeled as Gaussian random field. The digital phantom simulations demonstrated that the proposed method achieved a large reduction in statistical variability through incorporating knowledge of the variance of the original Gaussian random field. The proposed method has the potential to enable prediction of early treatment response and shows promise for application to clinical practice. In future work, the authors will report on the robustness of the estimation theory for application to clinical practice of therapy response evaluation, which pertains to binary discrimination tasks at a fixed location in the image such as detection of small and weak lesion.« less

Atezolizumab, an Anti-Programmed Death-Ligand 1 Antibody, in Metastatic Renal Cell Carcinoma: Long-Term Safety, Clinical Activity, and Immune Correlates From a Phase Ia Study.

PubMed

McDermott, David F; Sosman, Jeffrey A; Sznol, Mario; Massard, Christophe; Gordon, Michael S; Hamid, Omid; Powderly, John D; Infante, Jeffrey R; Fassò, Marcella; Wang, Yan V; Zou, Wei; Hegde, Priti S; Fine, Gregg D; Powles, Thomas

2016-03-10

The objective was to determine the safety and clinical activity of atezolizumab (MPDL3280A), a humanized programmed death-ligand 1 (PD-L1) antibody, in renal cell carcinoma (RCC). Exploratory biomarkers were analyzed and associated with outcomes. Seventy patients with metastatic RCC, including clear cell (ccRCC; n = 63) and non-clear cell (ncc; n = 7) histologies, received atezolizumab intravenously every 3 weeks. PD-L1 expression was scored at four diagnostic levels (0/1/2/3) that were based on PD-L1 staining on tumor cells and tumor-infiltrating immune cells (IC) with the SP142 assay. Primary end points were safety and toxicity; secondary end points assessed clinical activity per Response Evaluation Criteria in Solid Tumors version 1.1 and immune-related response criteria. Plasma and tissue were analyzed for potential biomarkers of atezolizumab response. Grade 3 treatment-related and immune-mediated adverse events occurred in 17% and 4% of patients, respectively, and there were no grade 4 or 5 events. Sixty-three patients with ccRCC were evaluable for overall survival (median, 28.9 months; 95% CI, 20.0 months to not reached) and progression-free survival (median, 5.6 months; 95% CI, 3.9 to 8.2 months), and 62 patients were evaluable for objective response rate (ORR; 15%; 95% CI, 7% to 26%). ORR was evaluated on the basis of PD-L1 IC expression (IC1/2/3: n = 33; 18%; 95% CI, 7% to 35%; and IC0: n = 22; 9%; 95% CI, 1% to 29%). The ORR for patients with Fuhrman grade 4 and/or sarcomatoid histology was 22% (n = 18; 95% CI, 6% to 48%). Decreases in circulating plasma markers and acute-phase proteins and an increased baseline effector T-cell-to-regulatory T-cell gene expression ratio correlated with response to atezolizumab. Atezolizumab demonstrated a manageable safety profile and promising antitumor activity in patients with metastatic RCC. Correlative studies identified potential predictive and pharmacodynamic biomarkers. These results have guided ongoing studies and combinations with atezolizumab in RCC. © 2016 by American Society of Clinical Oncology.

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

PubMed

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

2016-04-01

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

Evaluation of the tip-bending response in clinically used endoscopes

PubMed Central

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

2016-01-01

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

Assessing Health Status in Inflammatory Bowel Disease using a Novel Single-Item Numeric Rating Scale

PubMed Central

Surti, Bijal; Spiegel, Brennan; Ippoliti, Andrew; Vasiliauskas, Eric; Simpson, Peter; Shih, David; Targan, Stephan; McGovern, Dermot; Melmed, Gil Y.

2014-01-01

Background Current instruments used to measure disease activity and health-related quality of life (HRQOL) in patients with Crohn’s disease (CD) and ulcerative colitis (UC) are often cumbersome, time-consuming, and expensive; although used in clinical trials, they are not convenient for clinical practice. A numeric rating scale (NRS) is a quick, inexpensive, and convenient patient-reported outcome (PRO) that can capture the patient’s overall perception of health. Aims To assess the validity, reliability, and responsiveness of an NRS and evaluate its use in clinical practice in patients with CD and UC. Methods We prospectively evaluated patient-reported NRS scores and measured correlations between NRS and a range of severity measures, including physician-reported NRS, Crohn’s disease activity index (CDAI), Harvey-Bradshaw index (HBI), inflammatory bowel disease questionnaire (IBDQ), and C-reactive protein (CRP) in patients with CD. Subsequently, we evaluated the correlation between the NRS and standard measures of health status (HBI or simple colitis clinical activity index [SCCAI]) and laboratory tests (sedimentation rate [ESR], CRP, and fecal calprotectin) in patients with CD and UC. Results The patient-reported NRS showed excellent correlation with CDAI (R2=0.59, p<0.0001), IBDQ (R2=0.66, p<0.0001), and HBI (R2=0.32, p<0.0001) in patients with CD. The NRS showed poor, but statistically significant correlation with SCCAI (R2=0.25, p<0.0001) in patients with UC. The NRS did not correlate with CRP, ESR, or calprotectin. The NRS was reliable and responsive to change. Conclusions The NRS is a valid, reliable, and responsive measure that may be useful to evaluate patients with CD and possibly UC. PMID:23250673

Assessing health status in inflammatory bowel disease using a novel single-item numeric rating scale.

PubMed

Surti, Bijal; Spiegel, Brennan; Ippoliti, Andrew; Vasiliauskas, Eric A; Simpson, Peter; Shih, David Q; Targan, Stephan R; McGovern, Dermot P B; Melmed, Gil Y

2013-05-01

Current instruments used to measure disease activity and health-related quality of life in patients with Crohn's disease (CD) and ulcerative colitis (UC) are often cumbersome, time-consuming, and expensive; although used in clinical trials, they are not convenient for clinical practice. A numeric rating scale (NRS) is a quick, inexpensive, and convenient patient-reported outcome that can capture the patient's overall perception of health. The aim of this study was to assess the validity, reliability, and responsiveness of an NRS and evaluate its use in clinical practice in patients with CD and UC. We prospectively evaluated patient-reported NRS scores and measured correlations between NRS and a range of severity measures, including physician-reported NRS, Crohn's disease activity index (CDAI), Harvey-Bradshaw index (HBI), inflammatory bowel disease questionnaire (IBDQ), and C-reactive protein (CRP) in patients with CD. Subsequently, we evaluated the correlation between the NRS and standard measures of health status (HBI or simple colitis clinical activity index [SCCAI]) and laboratory tests (sedimentation rate [ESR], CRP, and fecal calprotectin) in patients with CD and UC. The patient-reported NRS showed excellent correlation with CDAI (R (2) = 0.59, p < 0.0001), IBDQ (R (2) = 0.66, p < 0.0001), and HBI (R (2) = 0.32, p < 0.0001) in patients with CD. The NRS showed poor, but statistically significant correlation with SCCAI (R (2) = 0.25, p < 0.0001) in patients with UC. The NRS did not correlate with CRP, ESR, or calprotectin. The NRS was reliable and responsive to change. The NRS is a valid, reliable, and responsive measure that may be useful to evaluate patients with CD and possibly UC.

Telomerase inhibition improves tumor response to radiotherapy in a murine orthotopic model of human glioblastoma.

PubMed

Ferrandon, Sylvain; Malleval, Céline; El Hamdani, Badia; Battiston-Montagne, Priscillia; Bolbos, Radu; Langlois, Jean-Baptiste; Manas, Patrick; Gryaznov, Sergei M; Alphonse, Gersende; Honnorat, Jérôme; Rodriguez-Lafrasse, Claire; Poncet, Delphine

2015-07-17

Glioblastoma (GBM) is the most frequent and aggressive type of adult brain tumor. Most GBMs express telomerase; a high level of intra-tumoral telomerase activity (TA) is predictive of poor prognosis. Thus, telomerase inhibitors are promising options to treat GBM. These inhibitors increase the response to radiotherapy (RT), in vitro as well as in vivo. Since typical treatments for GBM include RT, our objective was to evaluate the efficiency of Imetelstat (TA inhibitor) combined with RT. We used a murine orthotopic model of human GBM (N = 8 to11 mice per group) and μMRI imaging to evaluate the efficacy of Imetelstat (delivered by intra-peritoneal injection) alone and combined with RT. Using a clinically established protocol, we demonstrated that Imetelstat significantly: (i) inhibited the TA in the very center of the tumor, (ii) reduced tumor volume as a proportion of TA inhibition, and (iii) increased the response to RT, in terms of tumor volume regression and survival increase. Imetelstat is currently evaluated in refractory brain tumors in young patients (without RT). Our results support its clinical evaluation combined with RT to treat GBM.

The role of interim 18F-FDG PET/CT in prediction of response to ipilimumab treatment in metastatic melanoma.

PubMed

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

2018-07-01

The aim of the present study was to assess the value of interim 18 F-FDG PET/CT performed after the first two cycles of ipilimumab treatment in the prediction of the final clinical response to this type of immunotherapy. The study group comprised 41 patients with unresectable metastatic melanoma scheduled for ipilimumab therapy. Whole-body 18 F-FDG PET/CT was performed before the start of ipilimumab treatment (baseline PET/CT) and after the initial two cycles of ipilimumab treatment (interim PET/CT). Evaluation of patient response to treatment was based on the European Organization for Research and Treatment of Cancer (EORTC) 1999 criteria for PET as well as the recently proposed PET Response Evaluation Criteria for Immunotherapy (PERCIMT). The patients' best clinical response, assessed at a median of 21.4 months (range 6.3-41.9 months) was used as reference. According to their best clinical response, the patients were divided into two groups: those showing clinical benefit (CB) including stable disease, partial response and complete response (31 patients), and those showing no clinical benefit (no-CB including progressive disease (10 patients). According to the EORTC criteria, interim PET/CT demonstrated progressive metabolic disease (PMD) in 20 patients, stable metabolic disease (SMD) in 11 patients, partial metabolic response (PMR) in 8 patients, and complete metabolic response (CMR) in 2 patients. According to the PERCIMT, interim PET/CT demonstrated PMD in 9 patients, SMD in 24 patients, PMR in 6 patients and CMR in 2 patients. On the basis of the interim PET, the patients were divided in a similar manner to the division according to clinical response into those showing metabolic benefit (MB) including SMD, PMR and CMR, and those showing no metabolic benefit (no-MB) including PMD. According to this dichotomization, the EORTC criteria showed a sensitivity (correctly predicting CB) of 64.5%, a specificity (correctly predicting no-CB) of 90.0%, a positive predictive value (PPV) of 95.2%, a negative predictive value (NPV) of 45.0% and an accuracy of 70.7% in predicting best clinical response. The PERCIMT showed a sensitivity of 93.6%, a specificity of 70.0%, a PPV of 90.6%, a NPV of 77.8% and an accuracy of 87.8%. The McNemar test showed that the PERCIMT had a significantly higher sensitivity than EORTC criteria (p = 0.004), while there was no significant difference in specificity (p = 0.5). The agreement between the two sets of criteria was poor (McNemar test p = 0.001, and accordingly kappa = 0.46). The application of the recently proposed PERCIMT to interim 18 F-FDG PET/CT provides a more sensitive predictor of final clinical response to immunotherapy than the application of the EORTC criteria in patients with metastatic melanoma.

Conclusions and future directions for the REiNS International Collaboration

PubMed Central

Blakeley, Jaishri O.; Dombi, Eva; Fisher, Michael J.; Hanemann, Clemens O.; Walsh, Karin S.; Wolters, Pamela L.; Plotkin, Scott R.

2013-01-01

The Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration was established with the goal to develop consensus recommendations for the use of endpoints in neurofibromatosis (NF) clinical trials. This supplement includes the first series of REiNS recommendations for the use of patient-reported, functional, and visual outcomes, and for the evaluation of imaging response in NF clinical trials. Recommendations for neurocognitive outcome measures, the use of whole-body MRI in NF, the evaluation of potential biomarkers of disease, and the comprehensive evaluation of functional and patient-reported outcomes in NF are in development. The REiNS recommendations are made based on current knowledge. Experience with the use of the recommended endpoints in clinical trials, development of new tools and technologies, new knowledge of the natural history of NF, and advances in the methods used to analyze endpoints will likely lead to modifications of the currently proposed guidelines, which will be shared with the NF research community through the REiNS Web site www.reinscollaboration.org. Due to the clinical complexity of NF, there is a need to seek expertise from multiple medical disciplines, regulatory agencies, and industry to develop trial endpoints and designs, which will lead to the identification and approval of effective treatments for NF tumor and nontumor manifestations. The REiNS Collaboration welcomes anyone interested in providing his or her expertise toward this effort. PMID:24249805

Computer-Simulated Psychotherapy as an Aid in Teaching Clinical Psychology.

ERIC Educational Resources Information Center

Suler, John R.

1987-01-01

Describes how Elisa, a widely known computer program which simulates the responses of a psychotherapist, can be used as a teaching aid in undergraduate clinical psychology classes. Provides information on conducting the exercise, integrating it into the course syllabus, and evaluating its impact on students. (JDH)

Problems Related to the Use of Human Subjects in Clinical Evaluation/Responsibility for Follow-up Care.

ERIC Educational Resources Information Center

Buchanan, Richard N.

1991-01-01

This presentation on licensing and credentialing in dentistry denounces the use of human subjects for entry level clinical examinations in dentistry as contrary to the values of the profession that the patient's welfare is paramount. Recommended, instead, are various forms of simulation. (DB)

Concurrence of benign edematous polysynovitis in the elderly (RS3PE syndrome) and endometrial adenocarcinoma.

PubMed

Olivo, D; Mattace, R

1997-01-01

RS3PE Syndrome is an inflammatory disease which affects mainly males and responds, rapidly, to low dose steroids. We describe the concurrence of RS3PE, poorly responsive to low dose steroids, and endometrial adenocarcinoma. In this patient, clinical and laboratory signs of RS3PE disappeared after total hysterectomy. Patients with RS3PE, poorly responsive to low dose steroids, need an accurate clinical and laboratory evaluation before considering the disease as idiopathic.

Effects of BRAF mutations and BRAF inhibition on immune responses to melanoma

PubMed Central

Ilieva, Kristina M.; Correa, Isabel; Josephs, Debra H.; Karagiannis, Panagiotis; Egbuniwe, Isioma U.; Cafferkey, Michiala J.; Spicer, James F.; Harries, Mark; Nestle, Frank O.; Lacy, Katie E.; Karagiannis, Sophia N.

2014-01-01

Malignant melanoma is associated with poor clinical prognosis; however, novel molecular and immune therapies are now improving patient outcomes. Almost 50% of melanomas harbor targetable activating mutations of BRAF which promote RAS-RAF-MEK-ERK pathway activation and melanoma proliferation. Recent evidence also indicates that melanomas bearing mutant BRAF may also have altered immune responses, suggesting additional avenues for treatment of this patient group. The small molecule inhibitors selective for mutant BRAF induce significant but short-lived clinical responses in a proportion of patients, but also lead to immune stimulatory bystander events, which then subside with the emergence of resistance to inhibition. Simultaneous BRAF and MEK inhibition, and especially combination of BRAF inhibitors with new immunotherapies such as checkpoint blockade antibodies, may further enhance immune activation, or counteract immunosuppressive signals. Pre-clinical evaluation and ongoing clinical trials should provide novel insights into the role of immunity in the therapy of BRAF-mutant melanoma. PMID:25385327

Melaleuca alternifolia and its application against dental plaque and periodontal diseases: A systematic review.

PubMed

Casarin, Maísa; Pazinatto, Josiele; Santos, Roberto Christ Vianna; Zanatta, Fabricio Batistin

2018-02-01

This is a systematic review of clinical and laboratory studies evaluating the effect of Melaleuca alternifolia on periodontopathogens, dental plaque, gingivitis, periodontitis, and inflammatory responses. The PubMed, Cochrane, Web of science, Bireme, Lilacs, Prospero, Open Grey, and Clinical Trials databases were searched to identify potentially eligible studies through October 2016. Of 1,654 potentially eligible studies, 25 were included in the systematic review. Their methodology was evaluated through the Cochrane Handbook for clinical studies and the GRADE system for in vivo/in vitro studies. Although clinical studies must be interpreted with caution due to methodological limitations, laboratory studies have found promising results. In vitro evidences showed that M. alternifolia has bactericidal and bacteriostatic effects against the most prevalent periodontopathogens. Clinical studies found comparable effects to chlorhexidine 0.12% in reducing gingival inflammation, although the antiplaque effect was lower. M. alternifolia also showed antioxidant properties, which are beneficial to the host, allied to the reduction on immune-inflammatory responses to pathogens. This systematic review suggests that the M. alternifolia has potential anti-inflammatory and antimicrobial properties, which can be easily applied to the periodontal tissues. However, further clinical trials are needed to elucidate the clinical relevance of its application. Copyright © 2017 John Wiley & Sons, Ltd.

Use of reflectance spectrophotometry to predict the response of port wine stains to pulsed dye laser.

PubMed

Halachmi, Shlomit; Azaria, Ron; Inbar, Roy; Ad-El, Dean; Lapidoth, Moshe

2014-01-01

Reflectance spectroscopy can be used to quantitate subtle differences in color. We applied a portable reflectance spectrometer to determine its utility in the evaluation of pulsed dye laser treatment of port wine stains (PWS) and in prediction of clinical outcome, in a prospective study. Forty-eight patients with PWS underwent one to nine pulsed dye laser treatments. Patient age and skin color as well as PWS surface area, anatomic location, and color were recorded. Pretreatment spectrophotometric measurements were performed. The subjective clinical results of treatment and the quantitative spectrophotometry results were evaluated by two independent teams, and the findings were correlated. The impact of the clinical characteristics on the response to treatment was assessed as well. Patients with excellent to good clinical results of laser treatments had pretreatment spectrophotometric measurements which differed by more than 10%, whereas patients with fair to poor results had spectrophotometric measurements with a difference of of less than 10%. The correlation between the spectrophotometric results and the clinical outcome was 73% (p < 0.01). The impact of the other clinical variables on outcome agreed with the findings in the literature. Spectrophotometry has a higher correlation with clinical outcome and a better predictive value than other nonmeasurable, nonquantitative, dependent variables.

Efficacy of vedolizumab for induction of clinical response and remission in patients with moderate to severe inflammatory bowel disease who failed at least two TNF antagonists.

PubMed

De Vos, Martine; Dhooghe, Barbara; Vermeire, Severine; Louis, Edouard; Mana, Fazia; Elewaut, Ann; Bossuyt, Peter; Baert, Filip; Reenaers, Catherine; Van Gossum, Marc; Macken, Elisabeth; Ferrante, Marc; Hindryckx, Pieter; Dewit, Olivier; Holvoet, Tom; Franchimont, Denis

2018-04-01

Vedolizumab is a recently available monoclonal antibody targeting α4β7 integrin for the treatment of ulcerative colitis (UC) and Crohn's disease (CD). The objective of this article is to evaluate the efficacy of vedolizumab induction therapy in anti-TNF-refractory/intolerant UC and CD patients in real life. A cohort of 149 moderately to severely active UC and CD patients who failed or showed intolerance to at least two TNF antagonists participated in a medical need program and received vedolizumab in 37 Belgian centers (April-September 2015). Rates of clinical response and remission were retrospectively evaluated at Week 10 for UC and Week 14 for CD using the physician's global assessment (PGA), Mayo score and Harvey Bradshaw index (HBI) or Crohn's disease activity score (CDAI) scores. Eighty-four patients (29 UC, 55 CD) had sufficient data for analysis. For UC patients, clinical response was observed in 76% based on PGA and 59% based on the Mayo score. The corresponding percentages for CD patients were 80% for PGA and 65% for HBI/CDAI. Clinical remission rates were 10% and 40% for UC and CD, respectively. Steroid-free remission was observed in respectively 10% and 35%. Globally, corticosteroids were stopped in 14 out of 48 patients (29%). No new safety signals were reported. Up to 70% TNF-refractory/intolerant UC and CD patients achieved a clinical response after 10 to 14 weeks of vedolizumab treatment in this real-life cohort.

Visual evoked potentials in the horse.

PubMed

Ström, L; Ekesten, B

2016-06-21

Electrical potentials generated in the central nervous system in response to brief visual stimuli, flash visual evoked potentials (FVEPs), can be recorded non-invasively over the occipital cortex. FVEPs are used clinically in human medicine and also experimentally in a number of animal species, but the method has not yet been evaluated in the horse. The method would potentially allow the ophthalmologist and equine clinician to evaluate visual impairment caused by disorders affecting post-retinal visual pathways. The aim was to establish a method for recording of FVEPs in horses in a clinical setting and to evaluate the waveform morphology in the normal horse. Ten horses were sedated with a continuous detomidine infusion. Responses were recorded from electrodes placed on the scalp. Several positions were evaluated to determine suitable electrode placement. Flash electroretinograms (FERGs) were recorded simultaneously. To evaluate potential contamination of the FVEP from retinal potentials, a retrobulbar nerve block was performed in two horses and transection of the optic nerve was performed in one horse as a terminal procedure. A series of positive (P) and negative (N) peaks in response to light stimuli was recorded in all horses. Reproducible wavelets with mean times-to-peaks of 26 (N1), 55 (P2), 141 (N2) and 216 ms (P4) were seen in all horses in all recordings. Reproducible results were obtained when the active electrode was placed in the midline rostral to the nuchal crest. Recording at lateral positions gave more variable results, possibly due to ear muscle artifacts. Averaging ≥100 responses reduced the impact of noise and artifacts. FVEPs were reproducible in the same horse during the same recording session and between sessions, but were more variable between horses. Retrobulbar nerve block caused a transient loss of the VEP whereas transection of the optic nerve caused an irreversible loss. We describe the waveform of the equine FVEP and our results show that it is possible to record FVEPs in sedated horses in a clinical setting. The potentials recorded were shown to be of post-retinal origin. Further studies are needed to provide normative data and assess potential clinical use.

The clinical syndrome of specific antibody deficiency in children.

PubMed

Boyle, R J; Le, C; Balloch, A; Tang, M L-K

2006-12-01

Specific antibody deficiency (SAD) is an immune deficiency which has been reported in adults and children with recurrent respiratory tract infections; however, the clinical features of SAD are not well described. This study evaluated formally the clinical syndrome of SAD, by comparing the clinical features of children with SAD and those of children with recurrent infection but normal immune function tests. SAD was defined as an adequate IgG antibody response to less than 50% of 12 pneumococcal serotypes tested following 23-valent unconjugated pneumococcal immunization. An adequate IgG antibody response was defined as a post-immunization titre of >or= 1.3 microg/ml or >or= four times the preimmunization value. Seventy-four children with recurrent infection were evaluated where immune deficiencies other than SAD had been excluded. Eleven (14.9%) of these children had SAD. Clinical features differed between the group with SAD and the group with normal antibody responses. A history of otitis media, particularly in association with chronic otorrhoea was associated with SAD [relative risk (RR) of SAD in those with chronic otorrhoea 4.64 (P = 0.02)]. SAD was associated with allergic disease, particularly allergic rhinitis [RR of SAD in those with allergic rhinitis 3.77 (P = 0.04)]. These two clinical associations of SAD were independent in this study [RR of chronic otorrhoea in those with allergic rhinitis 0.85 (P = 0.28)]. SAD was not an age-related phenomenon in this population. SAD has a distinct clinical phenotype, presenting as recurrent infection associated with chronic otorrhoea and/or allergic disease, and the condition should be sought in children with these features.

Predictors of Clinical Response and Remission at One year among a Multicenter Cohort of Patients with Inflammatory Bowel Disease Treated with Vedolizumab

PubMed Central

Allegretti, Jessica R.; Barnes, Edward L.; Stevens, Betsey; Storm, Margaret; Ananthakrishnan, Ashwin; Yajnik, Vijay; Korzenik, Joshua

2017-01-01

Background Vedolizumab (VDZ) has demonstrated long term efficacy in Crohn’s disease (CD) and ulcerative colitis (UC) in phase III trials. Aims Our aim was to evaluate the efficacy of VDZ at week 54 in inflammatory bowel disease (IBD) in a multicenter cohort of patients. Methods Adult patients completing induction therapy with VDZ were eligible for this study. Clinical response and remission was assessed using the Harvey Bradshaw index (HBI) for CD, the simple clinical colitis activity index (SCCAI) for UC and physician assessment. Results Among 136 total patients (96 CD and 40 UC), 76 (56%) demonstrated clinical response or remission at week 54. In univariate analysis, for patients with CD concomitant initiation of immunomodulator therapy (2.71, 95% CI 1.11 – 6.57), the addition of an immunomodulator (OR 11.49, 3.16 – 41.75) and CRP <3 (4.92, 95% CI 1.99 – 12.15) were associated with increased odds of clinical response or remission at week 54. For UC patients hospitalization after VDZ induction was associated with decreased odds of response or remission at week 54 ( OR 0.22, 95%CI 0.05–0.88). On multivariate analysis in CD, addition of an immunomodulator (OR 8.33, 95% CI 2.15–32.26) remained significant predictors of clinical response or remission at week 54. Conclusions Among a multicenter cohort of patients with IBD demonstrating primary response to VDZ, the addition of combination therapy with an immunomodulator is a significant predictor of clinical response or remission at week 54 in patients with CD. PMID:28357697

Pancreatic adenocarcinoma response to chemotherapy enhanced with non-invasive radio frequency evaluated via an integrated experimental/computational approach.

PubMed

Ware, Matthew J; Curtis, Louis T; Wu, Min; Ho, Jason C; Corr, Stuart J; Curley, Steven A; Godin, Biana; Frieboes, Hermann B

2017-06-13

Although chemotherapy combined with radiofrequency exposure has shown promise in cancer treatment by coupling drug cytotoxicity with thermal ablation or thermally-induced cytotoxicity, limited access of the drug to tumor loci in hypo-vascularized lesions has hampered clinical application. We recently showed that high-intensity short-wave capacitively coupled radiofrequency (RF) electric-fields may reach inaccessible targets in vivo. This non-invasive RF combined with gemcitabine (Gem) chemotherapy enhanced drug uptake and effect in pancreatic adenocarcinoma (PDAC), notorious for having poor response and limited therapeutic options, but without inducing thermal injury. We hypothesize that the enhanced cytotoxicity derives from RF-facilitated drug transport in the tumor microenvironment. We propose an integrated experimental/computational approach to evaluate chemotherapeutic response combined with RF-induced phenotypic changes in tissue with impaired transport. Results show that RF facilitates diffusive transport in 3D cell cultures representing hypo-vascularized lesions, enhancing drug uptake and effect. Computational modeling evaluates drug vascular extravasation and diffusive transport as key RF-modulated parameters, with transport being dominant. Assessment of hypothetical schedules following current clinical protocol for Stage-IV PDAC suggests that unresponsive lesions may be growth-restrained when exposed to Gem plus RF. Comparison of these projections to experiments in vivo indicates that synergy may result from RF-induced cell phenotypic changes enhancing drug transport and cytotoxicity, thus providing a potential baseline for clinically-focused evaluation.

Biomarkers in sarcoidosis.

PubMed

Chopra, Amit; Kalkanis, Alexandros; Judson, Marc A

2016-11-01

Numerous biomarkers have been evaluated for the diagnosis, assessment of disease activity, prognosis, and response to treatment in sarcoidosis. In this report, we discuss the clinical and research utility of several biomarkers used to evaluate sarcoidosis. Areas covered: The sarcoidosis biomarkers discussed include serologic tests, imaging studies, identification of inflammatory cells and genetic analyses. Literature was obtained from medical databases including PubMed and Web of Science. Expert commentary: Most of the biomarkers examined in sarcoidosis are not adequately specific or sensitive to be used in isolation to make clinical decisions. However, several sarcoidosis biomarkers have an important role in the clinical management of sarcoidosis when they are coupled with clinical data including the results of other biomarkers.

Evaluation of agreement among dermatologists in the assessment of the color of port wine stains and their clearance after treatment with the flashlamp-pumped dye laser.

PubMed

Pérez, B; Abraira, V; Núñez, M; Boixeda, P; Perez Corral, F; Ledo, A

1997-01-01

Color classification and its subjective clearance evaluation in response to treatment are essential in the management of patients with port wine stains (PWS). But color perception by physicians is not an objective measurement so that it can change among observers. Agreement among physicians is essential for the reliability of the color classification and the clinical assessment of the response to laser treatment. The purpose of our study was to determine the reliability of the clinical color classification of port wine stains and of their color change or clearance in response to laser treatment. The study was not designed to evaluate the outcome of laser treatment in PWS or the factors that could predict the final response. We used the kappa index to evaluate the proportion of agreement in color and clearance perception among dermatologists. Six dermatologists classified the initial color of PWS in 80 patients. Three of them also assessed the amount of clearance achieved after treatment with the flashlamp-pumped dye laser. These three dermatologists were usually dedicated to treat patients with PWS, while the other three were not. The kappa index showed a substantial agreement in both cases. No difference in the initial color perception was observed between the group of dermatologists specialized in PWS and the other three dermatologists. These results favor the reliability of the clinical method in the assessment of PWS before and after laser treatment. So, although subjective, color perception by physicians can be used in the study of laser treatment outcome in PWS and its related factors, and the results of different authors can be compared.

Metabolic and clinical assessment of efficacy of cryoablation therapy on skeletal masses by 18F-FDG positron emission tomography/computed tomography (PET/CT) and visual analogue scale (VAS): initial experience.

PubMed

Masala, Salvatore; Schillaci, Orazio; Bartolucci, Alberto D; Calabria, Ferdinando; Mammucari, Matteo; Simonetti, Giovanni

2011-02-01

Various therapy modalities have been proposed as standard treatments in management of bone metastases. Radiation therapy remains the standard of care for patients with localized bone pain, but up to 30% of them do not experience notable pain relief. Percutaneous cryoablation is a minimally invasive technique that induces necrosis by alternately freezing and thawing a target tissue. This technique is successfully used to treat a variety of malignant and benign diseases in different sites. (18)F-FDG positron emission tomography/computed tomography ((18)F-FDG PET/CT) is a single technique of imaging that provides in a "single step" both morphological and metabolic features of neoplastic lesions of the bone. The aim of this study was to evaluate the efficacy of the cryosurgical technique on secondary musculoskeletal masses according to semi-quantitative PET analysis and clinical-test evaluation with the visual analogue scale (VAS). We enrolled 20 patients with painful bone lesions (score pain that exceeded 4 on the VAS) that were non-responsive to treatment; one lesion per patient was treated. All patients underwent a PET-CT evaluation before and 8 weeks after cryotherapy; maximum standardized uptake value (SUV(max)) was measured before and after treatment for metabolic assessment of response to therapy. After treatment, 18 patients (90%) showed considerable reduction in SUV(max) value (>50%) suggestive of response to treatment; only 2 patients did not show meaningful reduction in metabolic activity. Our preliminary study demonstrates that quantitative analysis provided by PET correlates with response to cryoablation therapy as assessed by CT data and clinical VAS evaluation.

Novel Applications of Metabolomics in Personalized Medicine: A Mini-Review.

PubMed

Li, Bingbing; He, Xuyun; Jia, Wei; Li, Houkai

2017-07-13

Interindividual variability in drug responses and disease susceptibility is common in the clinic. Currently, personalized medicine is highly valued, the idea being to prescribe the right medicine to the right patient. Metabolomics has been increasingly applied in evaluating the therapeutic outcomes of clinical drugs by correlating the baseline metabolic profiles of patients with their responses, i.e., pharmacometabonomics, as well as prediction of disease susceptibility among population in advance, i.e., patient stratification. The accelerated advance in metabolomics technology pinpoints the huge potential of its application in personalized medicine. In current review, we discussed the novel applications of metabolomics with typical examples in evaluating drug therapy and patient stratification, and underlined the potential of metabolomics in personalized medicine in the future.

[Evaluation of the radiofrequency ablation effectiveness in patients with the Wolff-Parkinson-White syndrome].

PubMed

Ushakov, I B; Ardashev, A V; Ardashev, V N; Voronkov, Iu I; Sharoĭko, M V; Akimova, O S

2012-01-01

A one-year prospective study involved 22 patients with the Wolff-Parkinson-White syndrome (WPW) and 20 healthy people. Means age of patients was 34.3 +/- 16.3 years. All 22 patients were successfully treated with radiofrequency ablation (RFA) of additional pathways. RFA effectiveness was evaluated with the help of clinical questionnaire, data of ECG, EchoCG, heart rate variability (HRV), frequency response and nonlinear dynamics. Cardiac rhythm disturbances were verified using Holter monitoring applied to all patients. Positive clinical effect was achieved in all the WPW patients, as RFA arrested cardiac arrhythmias completely. Holter monitoring did not register cardiac disturbances which points to high RFA effectiveness in WPW patients. HRV, frequency response and nonlinear dynamics reassumed their normal patterns.

Monitoring the response of patients with cutaneous leishmaniasis to treatment with pentamidine isethionate by quantitative real-time PCR, and identification of Leishmania parasites not responding to therapy.

PubMed

Mans, D R A; Kent, A D; Hu, R V; Lai A Fat, E J; Schoone, G J; Adams, E R; Rood, E J; Alba, S; Sabajo, L O A; Lai A Fat, R F; de Vries, H J C; Schallig, H D F H

2016-08-01

Leishmania (Viannia) guyanensis is believed to be the principal cause of cutaneous leishmaniasis (CL) in Suriname. This disease is treated with pentamidine isethionate (PI), but treatment failure has increasingly been reported. To evaluate PI for its clinical efficacy, to compare parasite load, and to assess the possibility of treatment failure due to other infecting Leishmania species. Parasite load of patients with CL was determined in skin biopsies using real-time quantitative PCR before treatment and 6 and 12 weeks after treatment. Clinical responses were evaluated at week 12 and compared with parasite load. In parallel, molecular species differentiation was performed. L. (V.) guyanensis was the main infecting species in 129 of 143 patients (about 90%). PI treatment led to a significant decrease (P < 0.001) in parasite counts, and cured about 75% of these patients. Treatment failure was attributable to infections with Leishmania (Viannia) braziliensis, Leishmania (Leishmania) amazonensis and L. (V.) guyanensis (1/92, 1/92 and 22/92 evaluable cases, respectively). There was substantial agreement beyond chance between the parasite load at week 6 and the clinical outcome at week 12, as indicated by the κ value of 0.61. L. (V.) guyanensis is the main infecting species of CL in Suriname, followed by L. (V.) braziliensis and L. (L.) amazonensis. Furthermore, patient response to PI can be better anticipated based on the parasite load 6 weeks after the treatment rather than on parasite load before treatment. © 2015 The Authors Clinical and Experimental Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists, North American Clinical Dermatologic Society and St Johns Dermatological Society.

Metabolic monitoring of advanced uterine cervical cancer neoadjuvant chemotherapy by using [F-18]-Fluorodeoxyglucose positron emission tomography: preliminary results in three patients.

PubMed

Yoshida, Yoshio; Kurokawa, Tetsuji; Kawahara, Kazumi; Yagihara, Akira; Tsuchida, Tatsuro; Okazawa, Hidehiko; Fujibayashi, Yasuhisa; Yonekura, Yoshiharu; Kotsuji, Fumikazu

2004-12-01

The aim of this report is to describe the potential clinical utility of tracer [F-18]-Fluorodeoxyglucose (FDG) uptake, quantitated as a standardized uptake value (SUV) by positron emission tomography (PET), to evaluate treatment response to neoadjuvant chemotherapy (NAC) in advanced uterine cervical cancer. We briefly describe the clinical courses of three women with advanced cervical cancer who were treated with neoadjuvant chemotherapy (NAC) prior to radical hysterectomy and who were analyzed for correlation with the decrease in tumor volume by magnetic resonance imaging (MRI), in SUV by FDG-PET, and by histologic response. In these individuals, tumor volume and SUV were decreased by NAC. The decrease in SUV by FDG-PET was better correlated to histologic response for NAC than MRI was in advanced cervical cancer. Measurement of SUV by FDG-PET has clinical utility in evaluating treatment response for NAC in advanced cervical cancer. Although work in this field is still in the early stages, this report demonstrates that SUV by FDG-PET has the potential to become the new standard for monitoring the treatment response of NAC in cervical cancer. This monitoring approach must be proven in a larger number of patients for both primary and secondary lesions and should be further explored in another gynecologic cancer.

Benchmarking Treatment Response in Tourette's Disorder: A Psychometric Evaluation and Signal Detection Analysis of the Parent Tic Questionnaire.

PubMed

Ricketts, Emily J; McGuire, Joseph F; Chang, Susanna; Bose, Deepika; Rasch, Madeline M; Woods, Douglas W; Specht, Matthew W; Walkup, John T; Scahill, Lawrence; Wilhelm, Sabine; Peterson, Alan L; Piacentini, John

2018-01-01

This study assessed the psychometric properties of a parent-reported tic severity measure, the Parent Tic Questionnaire (PTQ), and used the scale to establish guidelines for delineating clinically significant tic treatment response. Participants were 126 children ages 9 to 17 who participated in a randomized controlled trial of Comprehensive Behavioral Intervention for Tics (CBIT). Tic severity was assessed using the Yale Global Tic Severity Scale (YGTSS), Hopkins Motor/Vocal Tic Scale (HMVTS) and PTQ; positive treatment response was defined by a score of 1 (very much improved) or 2 (much improved) on the Clinical Global Impressions - Improvement (CGI-I) scale. Cronbach's alpha and intraclass correlations (ICC) assessed internal consistency and test-retest reliability, with correlations evaluating validity. Receiver- and Quality-Receiver Operating Characteristic analyses assessed the efficiency of percent and raw-reduction cutoffs associated with positive treatment response. The PTQ demonstrated good internal consistency (α = 0.80 to 0.86), excellent test-retest reliability (ICC = .84 to .89), good convergent validity with the YGTSS and HM/VTS, and good discriminant validity from hyperactive, obsessive-compulsive, and externalizing (i.e., aggression and rule-breaking) symptoms. A 55% reduction and 10-point decrease in PTQ Total score were optimal for defining positive treatment response. Findings help standardize tic assessment and provide clinicians with greater clarity in determining clinically meaningful tic symptom change during treatment. Copyright © 2017. Published by Elsevier Ltd.

Detection of residual disease after neoadjuvant chemoradiotherapy for oesophageal cancer (preSANO): a prospective multicentre, diagnostic cohort study.

PubMed

Noordman, Bo Jan; Spaander, Manon C W; Valkema, Roelf; Wijnhoven, Bas P L; van Berge Henegouwen, Mark I; Shapiro, Joël; Biermann, Katharina; van der Gaast, Ate; van Hillegersberg, Richard; Hulshof, Maarten C C M; Krishnadath, Kausilia K; Lagarde, Sjoerd M; Nieuwenhuijzen, Grard A P; Oostenbrug, Liekele E; Siersema, Peter D; Schoon, Erik J; Sosef, Meindert N; Steyerberg, Ewout W; van Lanschot, J Jan B

2018-05-31

After neoadjuvant chemoradiotherapy for oesophageal cancer, roughly half of the patients with squamous cell carcinoma and a quarter of those with adenocarcinoma have a pathological complete response of the primary tumour before surgery. Thus, the necessity of standard oesophagectomy after neoadjuvant chemoradiotherapy should be reconsidered for patients who respond sufficiently to neoadjuvant treatment. In this study, we aimed to establish the accuracy of detection of residual disease after neoadjuvant chemoradiotherapy with different diagnostic approaches, and the optimal combination of diagnostic techniques for clinical response evaluations. The preSANO trial was a prospective, multicentre, diagnostic cohort study at six centres in the Netherlands. Eligible patients were aged 18 years or older, had histologically proven, resectable, squamous cell carcinoma or adenocarcinoma of the oesophagus or oesophagogastric junction, and were eligible for potential curative therapy with neoadjuvant chemoradiotherapy (five weekly cycles of carboplatin [area under the curve 2 mg/mL per min] plus paclitaxel [50 mg/m 2 of body-surface area] combined with 41·4 Gy radiotherapy in 23 fractions) followed by oesophagectomy. 4-6 weeks after completion of neoadjuvant chemoradiotherapy, patients had oesophagogastroduodenoscopy with biopsies and endoscopic ultrasonography with measurement of maximum tumour thickness. Patients with histologically proven locoregional residual disease or no-pass during endoscopy and without distant metastases underwent immediate surgical resection. In the remaining patients a second clinical response evaluation was done (PET-CT, oesophagogastroduodenoscopy with biopsies, endoscopic ultrasonography with measurement of maximum tumour thickness, and fine-needle aspiration of suspicious lymph nodes), followed by surgery 12-14 weeks after completion of neoadjuvant chemoradiotherapy. The primary endpoint was the correlation between clinical response during clinical response evaluations and the final pathological response in resection specimens, as shown by the proportion of tumour regression grade (TRG) 3 or 4 (>10% residual carcinoma in the resection specimen) residual tumours that was missed during clinical response evaluations. This study was registered with the Netherlands Trial Register (NTR4834), and has been completed. Between July 22, 2013, and Dec 28, 2016, 219 patients were included, 207 of whom were included in the analyses. Eight of 26 TRG3 or TRG4 tumours (31% [95% CI 17-50]) were missed by endoscopy with regular biopsies and fine-needle aspiration. Four of 41 TRG3 or TRG4 tumours (10% [95% CI 4-23]) were missed with bite-on-bite biopsies and fine-needle aspiration. Endoscopic ultrasonography with maximum tumour thickness measurement missed TRG3 or TRG4 residual tumours in 11 of 39 patients (28% [95% CI 17-44]). PET-CT missed six of 41 TRG3 or TRG4 tumours (15% [95% CI 7-28]). PET-CT detected interval distant histologically proven metastases in 18 (9%) of 190 patients (one squamous cell carcinoma, 17 adenocarcinomas). After neoadjuvant chemoradiotherapy for oesophageal cancer, clinical response evaluation with endoscopic ultrasonography, bite-on-bite biopsies, and fine-needle aspiration of suspicious lymph nodes was adequate for detection of locoregional residual disease, with PET-CT for detection of interval metastases. Active surveillance with this combination of diagnostic modalities is now being assessed in a phase 3 randomised controlled trial (SANO trial; Netherlands Trial Register NTR6803). Dutch Cancer Society. Copyright © 2018 Elsevier Ltd. All rights reserved.

Adoptive immunotherapy for cancer.

PubMed

Ruella, Marco; Kalos, Michael

2014-01-01

Recent clinical success has underscored the potential for immunotherapy based on the adoptive cell transfer (ACT) of engineered T lymphocytes to mediate dramatic, potent, and durable clinical responses. This success has led to the broader evaluation of engineered T-lymphocyte-based adoptive cell therapy to treat a broad range of malignancies. In this review, we summarize concepts, successes, and challenges for the broader development of this promising field, focusing principally on lessons gleaned from immunological principles and clinical thought. We present ACT in the context of integrating T-cell and tumor biology and the broader systemic immune response. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Prospective analysis of adoptive TIL therapy in patients with metastatic melanoma: response, impact of anti-CTLA4, and biomarkers to predict clinical outcome.

PubMed

Forget, Marie-Andrée; Haymaker, Cara; Hess, Kenneth R; Meng, Yuzhong Jeff; Creasy, Caitlin; Karpinets, Tatiana V; Fulbright, Orenthial J; Roszik, Jason; Woodman, Scott E; Kim, Young Uk; Sakellariou-Thompson, Donastas; Bhatta, Ankit; Wahl, Arely; Flores, Esteban; Thorsen, Shawne T; Tavera, Rene J; Ramachandran, Renjith; Gonzalez, Audrey M; Toth, Christopher; Wardell, Seth; Mansaray, Rahmatu; Patel, Vruti; Carpio, Destiny Joy; Vaughn, Carol S; Farinas, Chantell M; Velasquez, Portia G; Hwu, Wen-Jen; Patel, Sapna P; Davies, Michael A; Diab, Adi; Glitza, Isabella C; Tawbi, Hussein; Wong, Michael K K; Cain, Suzanne; Ross, Merrick I; Lee, Jeffrey E; Gershenwald, Jeffrey E; Lucci, Anthony; Royal, Richard; Cormier, J N; Wargo, Jennifer A; Radvanyi, Laszlo G; Torres Cabala, Carlos A; Beroukhim, Rameen; Hwu, Patrick; Amaria, Rodabe N; Bernatchez, Chantale

2018-05-30

Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TIL) has consistently demonstrated clinical efficacy in metastatic melanoma. Recent widespread use of checkpoint blockade has shifted the treatment landscape, raising questions regarding impact of these therapies on response to TIL and appropriate immunotherapy sequence. Seventy-four metastatic melanoma patients were treated with autologous TIL and evaluated for clinical response according to irRC, overall survival and progression free survival. Immunologic factors associated with response were also evaluated. Best overall response for the entire cohort was 42%; 47% in 43 checkpoint naïve patients, 38% when patients were exposed to anti-CTLA4 alone (21 patients) and 33% if also exposed to anti-PD1 (9 patients) prior to TIL ACT. Median overall survival was 17.3 months; 24.6 months in CTLA4 naïve patients and 8.6 months in patients with prior CTLA4 blockade. The latter patients were infused with fewer TIL and experienced a shorter duration of response. Infusion of higher numbers of TIL with CD8 predominance and expression of BTLA correlated with improved response in anti-CTLA-4 naive patients, but not in anti-CTLA-4 refractory patients. Baseline serum levels of IL-9 predicted response to TIL ACT, while TIL persistence, tumor recognition and mutation burden did not correlate with outcome. This study demonstrates the deleterious effects of prior exposure to anti-CTLA4 on TIL ACT response and shows that baseline IL-9 levels can potentially serve as a predictive tool to appropriately select sequence for immunotherapies. Copyright ©2018, American Association for Cancer Research.

Matrix metalloproteinase-9 expression correlated with tumor response in patients with locally advanced rectal cancer undergoing preoperative chemoradiotherapy

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

Unsal, Diclehan; Uner, Aytug; Akyurek, Nalan

2007-01-01

Purpose: To analyze whether the expression of matrix metalloproteinases (MMPs) and their tissue inhibitors are associated with tumor response to preoperative chemoradiotherapy in rectal cancer patients. Methods and Materials: Forty-four patients who had undergone preoperative chemoradiotherapy were evaluated retrospectively. Treatment consisted of pelvic radiotherapy and two cycles of 5-fluorouracil plus leucovorin. Surgery was performed 6-8 weeks later. MMP-2, MMP-9, and tissue inhibitors of metalloproteinase-1 and -2 expression was analyzed by immunohistochemistry of the preradiation biopsy and surgical specimens. The intensity and extent of staining were evaluated separately, and a final score was calculated by multiplying the two scores. The primarymore » endpoint was the correlation of expression with tumor response, with the secondary endpoint the effect of chemoradiotherapy on the expression. Results: Preoperative treatment resulted in downstaging in 20 patients (45%) and no clinical response in 24 (55%). The pathologic tumor response was complete in 11 patients (25%), partial in 23 (52%), and none in 10 (23%). Positive MMP-9 staining was observed in 20 tumors (45%) and was associated with the clinical nodal stage (p = 0.035) and the pathologic and clinical response (p < 0.0001). The staining status of the other markers was associated with neither stage nor response. The overall pathologic response rate was 25% in MMP-9-positive patients vs. 52% in MMP-9-negative patients (p = 0.001). None of the 11 patients with pathologic complete remission was MMP-9 positive. Conclusions: Matrix metalloproteinase-9 expression correlated with a poor tumor response to preoperative chemoradiotherapy in rectal carcinoma patients.« less

An Evaluation of Preference for Mode of Instruction Following Variations in Response Effort

ERIC Educational Resources Information Center

Romani, Patrick W.; McCoy, Thomasin E.; Wacker, David P.; Padilla-Dalmau, Yaniz C.

2014-01-01

The current study evaluated preference for mode of instruction (i.e., visual or vocal) for four children diagnosed with a language-based learning disability. Each participant was an elementary student who was initially referred to a neuropsychology clinic specializing in learning disabilities. As a part of the evaluation, measures of each…

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

PubMed

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 < 0.0001, p = 1.0), drug-placebo difference (r = -0.238, p = 0.214), and success rate (28/29 97%) have remained unaffected, likely due to a parallel, although not statistically significant increase in medication response (r = 0.326, p = 0.085). Age and medication class did not alter these observed time trends but pediatric trials and 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.

[Introduction of a Clinical Research Experience Program in Hospital Practical Training for Pharmacy Students and Its Evaluation].

PubMed

Takahashi, Katsuyuki; Suda, Yasuki; Kawaguchi, Hiroshi; Nakamura, Yasutaka; Kawabata, Shiho; Kawakami, Noriko; Nishikawa, Takeshi; Nagayama, Katsuya

2015-01-01

Long-term clinical training based on a model core curriculum was conducted to nurture highly competent pharmacists in the clinical field. Pharmacists' responsibilities are expanding, and a system has been developed to help pharmacists gain accreditation, identify specialties, and improve their training. However, this system requires research competency. Therefore clinical research should be considered a part of clinical training to encourage high competency among pharmacists. Because the model core curriculum does not include a section on clinical research. Osaka City University Hospital introduced a hands-on clinical research experience program and evaluated its usefulness. A significant improvement in the level of knowledge and awareness of clinical research was seen among students who underwent the clinical research experience program. In addition, the level of student satisfaction was higher. These findings suggest that a clinical research experience program may be useful to nurture a greater awareness of clinical research and knowledge acquisition among pharmacists.

Effectiveness of a Web-Based Simulation in Improving Nurses' Workplace Practice With Deteriorating Ward Patients: A Pre- and Postintervention Study.

PubMed

Liaw, Sok Ying; Wong, Lai Fun; Lim, Eunice Ya Ping; Ang, Sophia Bee Leng; Mujumdar, Sandhya; Ho, Jasmine Tze Yin; Mordiffi, Siti Zubaidah; Ang, Emily Neo Kim

2016-02-19

Nurses play an important role in detecting patients with clinical deterioration. However, the problem of nurses failing to trigger deteriorating ward patients still persists despite the implementation of a patient safety initiative, the Rapid Response System. A Web-based simulation was developed to enhance nurses' role in recognizing and responding to deteriorating patients. While studies have evaluated the effectiveness of the Web-based simulation on nurses' clinical performance in a simulated environment, no study has examined its impact on nurses' actual practice in the clinical setting. The objective of this study was to evaluate the impact of Web-based simulation on nurses' recognition of and response to deteriorating patients in clinical settings. The outcomes were measured across all levels of Kirkpatrick's 4-level evaluation model with clinical outcome on triggering rates of deteriorating patients as the primary outcome measure. A before-and-after study was conducted on two general wards at an acute care tertiary hospital over a 14-month period. All nurses from the two study wards who undertook the Web-based simulation as part of their continuing nursing education were invited to complete questionnaires at various time points to measure their motivational reaction, knowledge, and perceived transfer of learning. Clinical records on cases triggered by ward nurses from the two study wards were evaluated for frequency and types of triggers over a period of 6 months pre- and 6 months postintervention. The number of deteriorating patients triggered by ward nurses in a medical general ward increased significantly (P<.001) from pre- (84/937, 8.96%) to postintervention (91/624, 14.58%). The nurses reported positively on the transfer of learning (mean 3.89, SD 0.49) from the Web-based simulation to clinical practice. A significant increase (P<.001) on knowledge posttest score from pretest score was also reported. The nurses also perceived positively their motivation (mean 3.78, SD 0.56) to engage in the Web-based simulation. This study provides evidence on the effectiveness of Web-based simulation in improving nursing practice when recognizing and responding to deteriorating patients. This educational tool could be implemented by nurse educators worldwide to address the educational needs of a large group of hospital nurses responsible for patients in clinical deterioration.

How do stimulant treatments for ADHD work? Evidence for mediation by improved cognition.

PubMed

Hawk, Larry W; Fosco, Whitney D; Colder, Craig R; Waxmonsky, James G; Pelham, William E; Rosch, Keri S

2018-05-07

Stimulant medications such as methylphenidate (MPH) are the frontline treatment for Attention-Deficit/Hyperactivity Disorder (ADHD). Despite their well-documented efficacy, the mechanisms by which stimulants improve clinical outcomes are not clear. The current study evaluated whether MPH effects on classroom behavior were mediated by improved cognitive functioning. Children with ADHD (n = 82; 9-12 years old) participated in a week-long summer research camp, consisting of cognitive testing, classroom periods, and recreational activities. After a baseline day, participants completed a 3-day randomized, double-blind, placebo-controlled trial of MPH (at doses approximating 0.3 and 0.6 mg/kg of immediate-release MPH dosed TID). Cognitive domains included inhibitory control (Stop Signal Task and prepulse inhibition of startle), attention (Continuous Performance Task and reaction time variability), and working memory (forward and backward spatial span). Clinical outcomes included math seatwork productivity and teacher-rated classroom behavior. A within-subjects path-analytic approach was used to test mediation. MPH-placebo and dose-response contrasts were used to evaluate drug effects. Methylphenidate improved seatwork productivity and teacher ratings (ds = 1.4 and 1.1) and all domains of cognition (ds = 0.3-1.1). Inhibitory control (Stop Signal Task, SST) and working memory backward uniquely mediated the effect of MPH (vs. placebo) on productivity. Only working memory backward mediated the impact of MPH on teacher-rated behavior. The dose-response (0.6 vs. 0.3 mg/kg) effects were more modest for clinical outcomes (ds = 0.4 and 0.2) and cognition (ds = 0-0.3); there was no evidence of cognitive mediation of the clinical dose-response effects. These findings are novel in demonstrating that specific cognitive processes mediate clinical improvement with stimulant treatment for ADHD. They converge with work on ADHD theory, neurobiology, and treatment development in suggesting that inhibitory control and working memory may be mechanisms of stimulant treatment response in ADHD. More work is necessary to evaluate the degree to which these findings generalize to chronic treatment, a broader array of clinical outcomes, and nonstimulant treatments. © 2018 Association for Child and Adolescent Mental Health.

Evaluation of DNA Repair Function as a Predictor of Response in a Clinical Trial of PARP Inhibitor Monotherapy for Recurrent Ovarian Carcinoma

DTIC Science & Technology

2015-10-01

Monotherapy for Recurrent Ovarian Carcinoma PRINCIPAL INVESTIGATOR: Scott H. Kaufmann CONTRACTING ORGANIZATION: Mayo Clinic Rochester, MN 55905...UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Mayo Clinic and Foundation AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT...NUMBER 200 First St., S.W. Rochester, MN 55905 9. SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) Mayo Clinic Rochester, MN 55905 10. SPONSOR

A single mothers' group for mothers of children attending an outpatient psychiatric clinic: preliminary results.

PubMed

McNamee, J E; Lipman, E L; Hicks, F

1995-09-01

To provide a preliminary report of data from 2 support groups for single mothers, all of whom were mothers of children attending a child outpatient psychiatric clinic. The groups' 2 purposes were: 1. to assess the feasibility of adding structured evaluation to a common clinical intervention; 2. to improve single mothers' parenting skills through raised levels of self-esteem, increased capacity for family functioning and reduced levels of depression. Three structured evaluation instruments were used to measure the domains of self-esteem, family functioning and depression. These instruments were given to both groups of women on 3 occasions: 1. before the group; 2. after the group; 3. at a follow-up session 4 months after group termination. Open-ended questions were also asked at group termination. The questionnaire response rate was 100%; overall response rate for the 3 open-ended questions was 89%. Comparisons of pre-group and post-group scores showed that there was a significant increase in self-esteem (p < 0.01) and significant improvements in family functioning (p < 0.05) and depression (p < 0.01). It is possible to introduce a structured evaluation component into a common clinical intervention, and this support group seemed to assist single mothers' parenting skills. Methodologic concerns and future directions are discussed.

The CRF1 Antagonist Verucerfont in Anxious Alcohol-Dependent Women: Translation of Neuroendocrine, But not of Anti-Craving Effects

PubMed Central

Schwandt, Melanie L; Cortes, Carlos R; Kwako, Laura E; George, David T; Momenan, Reza; Sinha, Rajita; Grigoriadis, Dimitri E; Pich, Emilio Merlo; Leggio, Lorenzo; Heilig, Markus

2016-01-01

Blockade of corticotropin-releasing factor receptor 1 (CRF1) suppresses stress-induced alcohol seeking in rodents, but clinical translation remains. Here, we first showed that the CRF1 antagonist verucerfont potently blocks hypothalamic-pituitary adrenal (HPA) axis activation in adrenalectomized rats. We then evaluated verucerfont for its ability to block HPA axis activation and reduce stress-induced alcohol craving in alcohol-dependent patients. Anxious, alcohol-dependent women (age 21–65 years, n=39) were admitted to the NIH Clinical Center and completed withdrawal treatment before enrollment if needed. One-week single-blind placebo was followed by randomized double-blind verucerfont (350 mg per day) or placebo for 3 weeks. Verucerfont effects on the HPA axis were evaluated using the dexamethasone-CRF test. Craving was evaluated using two established protocols, one that combines a social stressor with physical alcohol cue exposure, and one that uses guided imagery to present personalized stress, alcohol, or neutral stimuli. An fMRI session examined brain responses to negative affective stimuli and alcohol cues. In contrast to our recent observations with another CRF1 antagonist, pexacerfont, verucerfont potently blocked the HPA axis response to the dexamethasone-CRF test, but left alcohol craving unaffected. Right amygdala responses to negative affective stimuli were significantly attenuated by verucerfont, but responses to alcohol-associated stimuli were increased in some brain regions, including left insula. Discontinuation rates were significantly higher in the verucerfont group. Our findings provide the first translational evidence that CRF1 antagonists with slow receptor dissociation kinetics may have increased efficacy to dampen HPA axis responses. The findings do not support a clinical efficacy of CRF1 blockade in stress-induced alcohol craving and relapse. PMID:27109623

Measurement properties of existing clinical assessment methods evaluating scapular positioning and function. A systematic review.

PubMed

Larsen, Camilla Marie; Juul-Kristensen, Birgit; Lund, Hans; Søgaard, Karen

2014-10-01

The aims were to compile a schematic overview of clinical scapular assessment methods and critically appraise the methodological quality of the involved studies. A systematic, computer-assisted literature search using Medline, CINAHL, SportDiscus and EMBASE was performed from inception to October 2013. Reference lists in articles were also screened for publications. From 50 articles, 54 method names were identified and categorized into three groups: (1) Static positioning assessment (n = 19); (2) Semi-dynamic (n = 13); and (3) Dynamic functional assessment (n = 22). Fifteen studies were excluded for evaluation due to no/few clinimetric results, leaving 35 studies for evaluation. Graded according to the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN checklist), the methodological quality in the reliability and validity domains was "fair" (57%) to "poor" (43%), with only one study rated as "good". The reliability domain was most often investigated. Few of the assessment methods in the included studies that had "fair" or "good" measurement property ratings demonstrated acceptable results for both reliability and validity. We found a substantially larger number of clinical scapular assessment methods than previously reported. Using the COSMIN checklist the methodological quality of the included measurement properties in the reliability and validity domains were in general "fair" to "poor". None were examined for all three domains: (1) reliability; (2) validity; and (3) responsiveness. Observational evaluation systems and assessment of scapular upward rotation seem suitably evidence-based for clinical use. Future studies should test and improve the clinimetric properties, and especially diagnostic accuracy and responsiveness, to increase utility for clinical practice.

Implementations of clinical functional magnetic resonance imaging using character-based paradigms for the prediction of Chinese language dominance.

PubMed

Liu, Ho-Ling; Wu, Chien-Te; Chen, Jian-Chuan; Hsu, Yuan-Yu; Wai, Yau-Yau; Wan, Yung-Liang

2003-01-01

Recently, functional MRI (fMRI) using word generation (WG) tasks has been shown to be effective for mapping the Chinese language-related brain areas. In clinical applications, however, patients' performance cannot be easily monitored during WG tasks. In this study, we evaluated the feasibility of a word choice (WC) paradigm in the clinical setting and compared the results with those from WG tasks. Intrasubject comparisons of fMRI with both WG and WC paradigms were performed on six normal human subjects and two tumor patients. Subject responses in the WC paradigm, based on semantic judgments, were recorded. Activation strength, extent, and laterality were evaluated and compared. Our results showed that fMRI with the WC paradigm evoked weaker neuronal activation than that with the WG paradigm in Chinese language-related brain areas. It was sufficient to reveal language laterality for clinical use, however. In addition, it resulted in less nonlanguage-specific brain activation. Results from the patient data demonstrated strong evidence for the necessity of incorporating response monitoring during fMRI studies, which suggested that fMRI with the WC paradigm is more appropriate to be implemented for the prediction of Chinese language dominance in clinical environments.

[Strategics of medical centers and regional hospitals in response to new labour insurance fee schedule].

PubMed

Wang, S C; Sheen, P C; Ko, Y C

1993-02-01

The purpose of this paper is to evaluate the medical centers and regional hospitals, strategic response to the implementation of new labour insurance fee schedule. This survey selects fifty-one medical centers and regional hospitals, with the response rate of 92.73%. This questionnaire was developed and evaluated by the authors and mailed to the questionnaire response by hospital's director or relative department director. We have selected Shortell et al. (1985) theory as the framework for evaluating and explaining hospital response to regulation environment (ex: change in the reimbursement system) at institutional-level response (ex: hospital association activity aimed at influencing regulation), managerial-level response (ex: increased physician participation in hospital-wide decision making; starting or expanding a planning department) and technical-level response (ex: shared clinical services such as lab., X-ray, pharmacy). The result found that hospitals with the characteristics as non-public ownership, medical centers, bigger size, and more administrative staff are more inclined to adopt institutional-level response. And a technical-level response occurs to hospital when market competibility becomes more intense which leads to higher reimbursement resource dependency.

Systemic inflammatory response syndrome (SIRS)

PubMed Central

Balk, Robert A

2014-01-01

The concept of a systemic inflammatory response syndrome (SIRS) to describe the complex pathophysiologic response to an insult such as infection, trauma, burns, pancreatitis, or a variety of other injuries came from a 1991 consensus conference charged with the task of developing an easy-to-apply set of clinical parameters to aid in the early identification of potential candidates to enter into clinical trials to evaluate new treatments for sepsis. There was recognition that a diverse group of injuries produced a common inflammatory response in the host and provided attractive targets for new anti-inflammatory molecules designed to prevent further propagation and/or provide specific treatment. Effective application of these new anti-inflammatory strategies necessitated identification of early clinical markers that could be assessed in real-time and were likely to define a population of patients that would have a beneficial response to the targeted intervention. It was felt that early clinical manifestations might be more readily available to clinicians than more sophisticated and specific assays for inflammatory substances that were systemically released by the network of injurious inflammatory events. Therefore, the early definition of a systemic inflammatory response syndrome (SIRS) was built upon a foundation of basic clinical and laboratory abnormalities that were readily available in almost all clinical settings. With further refinement, it was hoped, that this definition would have a high degree of sensitivity, coupled with a reasonable degree of specificity. This manuscript reviews the derivation, application, utilization, potential benefits, and speculation regarding the future of the SIRS definition. PMID:24280933

Proportionate Responses to Life Events Influence Clinicians' Judgments of Psychological Abnormality

ERIC Educational Resources Information Center

Kim, Nancy S.; Paulus, Daniel J.; Gonzalez, Jeffrey S.; Khalife, Danielle

2012-01-01

Psychological abnormality is a fundamental concept in the "Diagnostic and Statistical Manual of Mental Disorders" ("DSM-IV-TR"; American Psychiatric Association, 2000) and in all clinical evaluations. How do practicing clinical psychologists use the context of life events to judge the abnormality of a person's current behaviors? The appropriate…

LesionTracker: Extensible Open-Source Zero-Footprint Web Viewer for Cancer Imaging Research and Clinical Trials.

PubMed

Urban, Trinity; Ziegler, Erik; Lewis, Rob; Hafey, Chris; Sadow, Cheryl; Van den Abbeele, Annick D; Harris, Gordon J

2017-11-01

Oncology clinical trials have become increasingly dependent upon image-based surrogate endpoints for determining patient eligibility and treatment efficacy. As therapeutics have evolved and multiplied in number, the tumor metrics criteria used to characterize therapeutic response have become progressively more varied and complex. The growing intricacies of image-based response evaluation, together with rising expectations for rapid and consistent results reporting, make it difficult for site radiologists to adequately address local and multicenter imaging demands. These challenges demonstrate the need for advanced cancer imaging informatics tools that can help ensure protocol-compliant image evaluation while simultaneously promoting reviewer efficiency. LesionTracker is a quantitative imaging package optimized for oncology clinical trial workflows. The goal of the project is to create an open source zero-footprint viewer for image analysis that is designed to be extensible as well as capable of being integrated into third-party systems for advanced imaging tools and clinical trials informatics platforms. Cancer Res; 77(21); e119-22. ©2017 AACR . ©2017 American Association for Cancer Research.

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

NASA Astrophysics Data System (ADS)

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.

Integrating service development with evaluation in telehealthcare: an ethnographic study.

PubMed

Finch, Tracy; May, Carl; Mair, Frances; Mort, Maggie; Gask, Linda

2003-11-22

To identify issues that facilitate the successful integration of evaluation and development of telehealthcare services. Ethnographic study using various qualitative research techniques to obtain data from several sources, including in-depth semistructured interviews, project steering group meetings, and public telehealthcare meetings. Seven telehealthcare evaluation projects (four randomised controlled trials and three pragmatic service evaluations) in the United Kingdom, studied over two years. Projects spanned a range of specialties-dermatology, psychiatry, respiratory medicine, cardiology, and oncology. Clinicians, managers, technical experts, and researchers involved in the projects. Key problems in successfully integrating evaluation and service development in telehealthcare are, firstly, defining existing clinical practices (and anticipating changes) in ways that permit measurement; secondly, managing additional workload and conflicting responsibilities brought about by combining clinical and research responsibilities (including managing risk); and, thirdly, understanding various perspectives on effectiveness and the limitations of evaluation results beyond the context of the research study. Combined implementation and evaluation of telehealthcare systems is complex, and is often underestimated. The distinction between quantitative outcomes and the workability of the system is important for producing evaluative knowledge that is of practical value. More pragmatic approaches to evaluation, that permit both quantitative and qualitative methods, are required to improve the quality of such research and its relevance for service provision in the NHS.

Thymidine phosphorylase and hypoxia-inducible factor 1-α expression in clinical stage II/III rectal cancer: association with response to neoadjuvant chemoradiation therapy and prognosis.

PubMed

Lin, Shuhan; Lai, Hao; Qin, Yuzhou; Chen, Jiansi; Lin, Yuan

2015-01-01

The aim of this study was to determine whether pretreatment status of thymidine phosphorylase (TP), and hypoxia-inducible factor alpha (HIF-1α) could predict pathologic response to neoadjuvant chemoradiation therapy with oxaliplatin and capecitabine (XELOXART) and outcomes for clinical stage II/III rectal cancer patients. A total of 180 patients diagnosed with clinical stage II/III rectal cancer received XELOXART. The status of TP, and HIF-1α were determined in pretreatment biopsies by immunohistochemistry (IHC). Tumor response was assessed in resected regimens using the tumor regression grade system and TNM staging system. 5-year disease free survival (DFS) and 5-year overall survival (OS) were evaluated with the Kaplan-Meier method and were compared by the log-rank test. Over expression of TP and low expression of HIF-1α were associated with pathologic response to XELOXART and better outcomes (DFS and OS) in clinical stage II/III rectal cancer patients (P < 0.05). Our result suggested that pretreatment status of TP and HIF-1α were found to predict pathologic response and outcomes in clinical stage II/III rectal cancer received XELOXART. Additional well-designed, large sample, multicenter, prospective studies are needed to confirm the result of this study.

Usefulness of Interim FDG-PET After Induction Chemotherapy in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck Receiving Sequential Induction Chemotherapy Followed by Concurrent Chemoradiotherapy

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

Yoon, Dok Hyun; Cho, Yoojin; Kim, Sang Yoon

2011-09-01

Purpose: Induction chemotherapy (ICT) has been used to select patients for organ preservation and determine subsequent treatments in patients with locally advanced squamous cell carcinoma of the head and neck (LASCCHN). Still, the clinical outcomes of LASCCHN patients who showed response to ICT are heterogeneous. We evaluated the efficacy of interim 18-fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) after ICT in this specific subgroup of LASCCHN patients who achieved partial response (PR) after ICT to predict clinical outcomes after concurrent chemoradiotherapy (CCRT). Methods and Materials: Twenty-one patients with LASCCHN who showed PR to ICT by Response Evaluation Criteria In Solid Tumors beforemore » definitive CCRT were chosen in this retrospective analysis. FDG-PET was performed before and 2-4 weeks after ICT to assess the extent of disease at baseline and the metabolic response to ICT, respectively. We examined the correlation of the metabolic response by the percentage decrease of maximum standardized uptake value (SUVmax) on the primary tumor or lymph node after ICT or a specific threshold of SUVmax on interim FDG-PET with clinical outcomes including complete response (CR) rate to CCRT, progression-free survival (PFS), and overall survival (OS). Results: A SUVmax of 4.8 on interim FDG-PET could predict clinical CR after CCRT (100% vs. 20%, p = 0.001), PFS (median, not reached vs. 8.5 mo, p < 0.001), and OS (median, not reached vs. 12.0 months, p = 0.001) with a median follow-up of 20.3 months in surviving patients. A 65% decrease in SUVmax after ICT from baseline also could predict clinical CR after CCRT (100% vs. 33.3%, p = 0.003), PFS (median, not reached vs. 8.9 months, p < 0.001) and OS (median, not reached vs. 24.4 months, p = 0.001) of the patients. Conclusion: These data suggest that interim FDG-PET after ICT might be a useful determinant to predict clinical outcomes in patients with LASCCHN receiving sequential ICT followed by CCRT.« less

Effect of antipyretic analgesics on immune responses to vaccination.

PubMed

Saleh, Ezzeldin; Moody, M Anthony; Walter, Emmanuel B

2016-09-01

While antipyretic analgesics are widely used to ameliorate vaccine adverse reactions, their use has been associated with blunted vaccine immune responses. Our objective was to review literature evaluating the effect of antipyretic analgesics on vaccine immune responses and to highlight potential underlying mechanisms. Observational studies reporting on antipyretic use around the time of immunization concluded that their use did not affect antibody responses. Only few randomized clinical trials demonstrated blunted antibody response of unknown clinical significance. This effect has only been noted following primary vaccination with novel antigens and disappears following booster immunization. The mechanism by which antipyretic analgesics reduce antibody response remains unclear and not fully explained by COX enzyme inhibition. Recent work has focused on the involvement of nuclear and subcellular signaling pathways. More detailed immunological investigations and a systems biology approach are needed to precisely define the impact and mechanism of antipyretic effects on vaccine immune responses.

Effect of antipyretic analgesics on immune responses to vaccination

PubMed Central

Saleh, Ezzeldin; Moody, M. Anthony; Walter, Emmanuel B.

2016-01-01

ABSTRACT While antipyretic analgesics are widely used to ameliorate vaccine adverse reactions, their use has been associated with blunted vaccine immune responses. Our objective was to review literature evaluating the effect of antipyretic analgesics on vaccine immune responses and to highlight potential underlying mechanisms. Observational studies reporting on antipyretic use around the time of immunization concluded that their use did not affect antibody responses. Only few randomized clinical trials demonstrated blunted antibody response of unknown clinical significance. This effect has only been noted following primary vaccination with novel antigens and disappears following booster immunization. The mechanism by which antipyretic analgesics reduce antibody response remains unclear and not fully explained by COX enzyme inhibition. Recent work has focused on the involvement of nuclear and subcellular signaling pathways. More detailed immunological investigations and a systems biology approach are needed to precisely define the impact and mechanism of antipyretic effects on vaccine immune responses. PMID:27246296

Predictive factors in the evaluation of treatment response to neoadjuvant chemoradiotherapy in patients with advanced esophageal squamous cell cancer

PubMed Central

Wong, Claudia

2017-01-01

Neoadjuvant therapy before esophagectomy is evidence-based, and is a standard-of-care for locally advanced and operable esophageal cancer. However response to such treatment varies in individual patients, from no clinical response to pathological complete response. It has been consistently shown that a good pathological responses is of prognostic value, but perhaps in the expense of those who do not. It is important to identify suitable predictive factors for response, so that patients are not exposed to potentially harmful chemotherapy and/or radiotherapy without benefits. Alternative management strategies can be devised. Various clinical, radiological, serological and potential molecular markers have been studied. None has been shown to be sufficiently reliable to be used in daily practice. Certainly more understanding of the molecular basis for response to chemotherapy/radiotherapy is needed, so that patient treatment can be tailored and individualized. PMID:28815073

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2015-06-16

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. 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. 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. 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.

Information needs for the rapid response team electronic clinical tool.

PubMed

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.

Multiple Vaccinations: Friend or Foe

PubMed Central

Church, Sarah E.; Jensen, Shawn M.; Twitty, Chris; Bahjat, Keith; Hu, Hong-Ming; Urba, Walter J.; Fox, Bernard A.

2013-01-01

Few immunotherapists would accept the concept of a single vaccination inducing a therapeutic anti-cancer immune response in a patient with advanced cancer. But what is the evidence to support the “more-is-better” approach of multiple vaccinations? Since we are unaware of trials comparing the effect of a single vaccine versus multiple vaccinations on patient outcome, we considered that an anti-cancer immune response might provide a surrogate measure of the effectiveness of vaccination strategies. Since few large trials include immunological monitoring, the majority of information is gleaned from smaller trials in which an evaluation of immune responses to vaccine or tumor, before and at one or more times following the first vaccine was performed. In some studies there is convincing evidence that repeated administration of a specific vaccine can augment the immune response to antigens contained in the vaccine. In other settings multiple vaccinations can significantly reduce the immune response to one or more targets. Results from three large adjuvant vaccine studies support the potential detrimental effect of multiple vaccinations as clinical outcomes in the control arms were significantly better than that for treatment groups. Recent research has provided insights into mechanisms that are likely responsible for the reduced responses in the studies noted above, but supporting evidence from clinical specimens is generally lacking. Interpretation of these results is further complicated by the possibility that the dominant immune response may evolve to recognize epitopes not present in the vaccine. Nonetheless, the FDA-approval of the first therapeutic cancer vaccine and recent developments from preclinical models and clinical trials provide a substantial basis for optimism and a critical evaluation of cancer vaccine strategies. PMID:21952289

Modeling Efficacy of Bevacizumab Treatment for Metastatic Colon Cancer

PubMed Central

Islam, Rezwan; Chyou, Po-Huang; Burmester, James K

2013-01-01

Purpose: Bevacizumab, an FDA-approved adjuvant treatment for metastatic colon cancer, has extended survival for many patients. However, factors predicting response to treatment remain undefined. Patients and Methods: Relevant clinical and environmental data were abstracted from medical records of 149 evaluable patients treated with bevacizumab for metastatic colon cancer at a multi-specialty clinic. Tumor response was calculated from radiologic reports using Response Evaluation Criteria in Solid Tumors (RECIST) criteria and verified by oncologist review. Patients with at least one occurrence of complete or partial response or stable disease were classified as responders; those exhibiting progressive disease were classified as non-responders. Results: Univariate analysis demonstrated that blood in stool (P<0.05), unexplained weight loss (P<0.05), primary colon cancer site (P<0.05), chemotherapy treatment of primary tumor site (P<0.05), and adenocarcinoma versus adenoma subtype (P<0.05) was associated with tumor responsiveness. Factors remaining statistically significant following multivariate modeling included adenocarcinoma as tumor cell type versus other adenocarcinoma subtypes (OR=6.35, 95% CI: 1.08-37.18), chemotherapy treatment applied to primary tumor (OR= 0.07, 95% CI: 0.0-0.76,), tumor localization to cecal/ascending colon (OR=0.061, 95% CI: 0.006-0.588,), and unexplained weight loss (OR=0.1, 95% CI: 0.02-0.56,). Chemotherapy treatment of primary tumor, unexplained weight loss, and cecal/ascending localization of the tumor were associated with poorer outcomes. Adenocarcinoma as cell type compared to other adenocarcinoma subtypes was associated with better response to bevacizumab treatment. Conclusion: Results suggest that response to bevacizumab therapy may be predicted by modeling clinical factors including symptomology on presentation, tumor location and type, and initial response to chemotherapy. PMID:23678369

[PK/PD breakpoints and clinical/bacteriological effects of cefcapene pivoxil fine granules for children at free drug concentrations in pediatric patients with respiratory infection].

PubMed

Toyonaga, Yoshikiyo; Iwai, Naoichi; Motohiro, Takashi; Sunakawa, Keisuke; Fujii, Ryochi

2008-06-01

A post-marketing clinical study was previously conducted in pediatric patients with respiratory infection to evaluate the pharmacokinetics, efficacy and safety of cefcapene pivoxil (CFPN-PI) fine granules for children. Based on the results from this study, we evaluated PK/PD breakpoints and clinical/bacteriological effects of CFPN-PI at free drug concentrations in pediatric patients with respiratory infection to determine an effective and safe dosage regimen of CFPN-PI. The following results were obtained from 61 pediatric patients evaluated in our research. 1) The response rate of pediatric respiratory infection to CFPN-PI was 100% for laryngopharyngitis, 84.6% for acute bronchitis, 100% for tonsillitis, 100% for pneumonia and 95.8% for all. 2) The bacteriological response (eradication rate of Haemophilus influenzae, Streptococcus pyogenes, Moraxella catarrhalis, Streptococcus pneumoniae, etc.) of pediatric respiratory infection to CFPN-PI was 87.5% for laryngopharyngitis, 66.7% for acute bronchitis, 75.0% for tonsillitis, 63.6% for pneumonia and 73.8% for all. 3) The blood concentration simulation demonstrated that the PK/PD breakpoint exceeding the time above MIC (TAM) of 40% after administration of CFPN-PI 3 mg/kg three times daily was 0.27 microg/mL. 4) The pediatric patients with respiratory infection were stratified by the TAM (%) of CFPN-PI into 40% to 100% (TAM > or = 40% group) and 0% to 40% (TAM < 40% group) to compare the clinical and bacteriological effects of CFPN-PI. The clinical and bacteriological response rates, respectively, were 97.4% and 77.8% in the TAM > or = 40% group, and 88.9% and 62.5% in the TAM < 40% group. There was no difference in the clinical effect between the two TAM-stratified groups. On the other hand, the bacteriological effect, i.e., eradication rate, tended to be higher in the TAM > or = 40% group than in the TAM < 40% group, although the between-group difference was not statistically significant.

Outcome Measures in Myasthenia Gravis: Incorporation Into Clinical Practice.

PubMed

Muppidi, Srikanth

2017-03-01

The development of validated assessment tools for evaluating disease status and response to interventions in patients with myasthenia gravis (MG) has been driven by clinical studies of emerging MG therapies. However, only a small proportion of MG-focused neurology practices have adopted these assessment tools for routine clinical use. This article reviews the suitability of 5 assessment instruments for incorporation into clinical practice, which should be driven by their ability to contribute to improved patient outcomes, and to be implemented within practice personnel and resource constraints. It is recommended that assessments based on both physician-evaluated and patient-reported outcomes be selected, to adequately evaluate both point-in-time symptom load and functional impact of MG symptoms over time. Provider resource allocation and reimbursement issues may be the most significant roadblocks to successful ongoing use of these tools; to that end, the addition of regular assessments to MG standards of care is recommended.

A novel cosmetic antifungal/anti-inflammatory topical gel for the treatment of mild to moderate seborrheic dermatitis of the face: an open-label trial utilizing clinical evaluation and erythema-directed digital photography.

PubMed

Dall' Oglio, Federica; Tedeschi, Aurora; Fusto, Carmelinda M; Lacarrubba, Francesco; Dinotta, Franco; Micali, Giuseppe

2017-10-01

Topical cosmetic agents may play a role in the management of facial seborrheic dermatitis by reducing inflammation and scale production. Advanced digital photography, equipped with technology able to provide a detailed evaluation of red skin components corresponding to vascular flare (erythema-directed digital photography), is a useful tool for evaluation of erythema in patients affected by inflammatory dermatoses. The aim of this study was to assess the efficacy and safety of a new cosmetic topical gel containing piroctone olamine, lactoferrin, glycero-phospho-inositol, and Aloe vera for the treatment of facial seborrheic dermatitis by clinical and advanced digital photography evaluation. An open-label, prospective, clinical trial was conducted on 25 patients with mild to moderate facial seborrheic dermatitis. Subjects were instructed to apply the gel twice daily for 45 days. The clinical efficacy was evaluated by measuring at baseline, at day 15 and 45 the degree of desquamation (by clinical examination) and erythema (by digital photography technology via VISIA-CR™ system equipped with RBX™), using a 5-point severity scale, and pruritus (by subject-completed Visual Analogue Scale; scale from 0 to 100 mm). Finally, at baseline and at the end of the study, IGA (Investigator Global Assessment) was performed using a 5-point severity scale (from 0 = worsening to 4 = excellent response). At the end of treatment, a significant reduction (P<0.001) of all considered parameters was observed. Moreover, an excellent response (>80% improvement) was recorded in 47.9% of patients, with no case of worsening. No signs of local intolerance were documented. The tested cosmetic topical gel was effective in treating mild to moderate seborrheic dermatitis of the face. Erythema-directed digital photography may represent a noteworthy tool for the therapeutic monitoring of facial seborrheic dermatitis and an important adjunct aid in the dermatologic clinical practice.

Clinical findings associated with cardiovascular autonomic dysfunction in adult sickle cell anaemia patients.

PubMed

Oguanobi, Nelson I; Onwubere, Basden J C; Anisiuba, Benedict C; Ike, Samuel O; Ejim, Emmanuel C; Ibegbulam, Obike G

2012-04-01

Involvement of the cardiovascular autonomic nervous system in various diseases is often associated with increased morbidity and mortality. The objective of this study was to examine the clinical features associated with cardiovascular autonomic neuropathy (CAN) in adult Nigerians with sickle cell anaemia. A cross-sectional study was carried out on 62 steady state sickle cell anaemia patients recruited from the adult out-patient clinic. Cardiovascular autonomic dysfunction was determined based on abnormal values in at least two of five non-invasive tests: Valsalva manoeuvre, heart rate variation during deep breathing, heart rate response to standing, blood pressure response to sustained handgrip, and blood pressure response to standing. All the subjects were initially evaluated in the clinic for symptoms of cardiovascular disease and peripheral vascular disease, and then clinically examined to assess their cardiovascular and neurological status at rest. Out of the 44 patients with cardiovascular autonomic neuropathy 23 were males, while 21 were females. The mean ages were 28.3 +/- 5.8 y for patients with CAN and 28.0 +/- 5.0 y for patients without CAN (P = 0.817). Sickle cell anaemia patients with CAN had significantly lower ankle systolic blood pressure, reduced ankle brachial blood pressure index, mean arterial blood pressure and haematocrit than patients without CAN. Of all the variables evaluated leg ulcers, postural dizziness, erectile dysfunction in men, and history of recurrent acute chest syndromes were found significantly more in patients with CAN than without. Clinical abnormalities tend to worsen with increasing degree of cardiovascular autonomic dysfunction. Significant cardiac morbidity is associated with abnormal cardiovascular autonomic function in sickle cell anaemia.

Evaluation of Clostridium novyi–NT spores in dogs with naturally occurring tumors

PubMed Central

Krick, Erika L.; Sorenmo, Karin U.; Rankin, Shelley C.; Cheong, Ian; Kobrin, Barry; Thornton, Katherine; Kinzler, Kenneth W.; Vogelstein, Bert; Zhou, Shibin; Diaz, Luis A.

2015-01-01

Objective To establish the maximum tolerated dose of Clostridium novyi–NT spores in tumor-bearing dogs and evaluate spore germination within tumors and tumor response. Animals 6 client-owned dogs. Procedures A standard dose-escalation study was planned, with maximum tolerated dose defined as the highest dose at which 0 or 1 of 6 dogs had dose-limiting toxicoses (DLT). Dogs received 1 dose of C novyi–NT spores IV. Toxicoses were graded and interventions performed according to specific guidelines. Grade 3 or higher toxicosis or any toxicosis combination that substantially affected patient status was considered DLT. Clinical response was measured by use of response evaluation criteria in solid tumors at 28 days. Results The first 2 dogs had DLT. The dose was decreased. Two of the next 4 dogs had DLT; therefore, dose administration was stopped because the study endpoint had been reached. The most common toxicosis was fever (n = 6 dogs). Two dogs developed abscesses (1 within a nasal carcinoma and 1 splenic abscess) attributable to C novyi–NT infection; both required surgical intervention. Clostridium novyi–NT was cultured from 1 of 6 tumors. Five dogs were available for response assessment (4 had stable disease; 1 had progressive disease). Conclusions and Clinical Relevance Results indicated that C novyi–NT can germinate within tumors of dogs. Toxicosis, although common and sometimes severe, was manageable with treatment. Further studies in dogs with superficial tumors may allow for continued dose escalation and provide information for use in clinical trials in veterinary and human oncology. PMID:22204296

Use of 64-channel electroencephalography to study neural otolith-evoked responses.

PubMed

McNerney, Kathleen M; Lockwood, Alan H; Coad, Mary Lou; Wack, David S; Burkard, Robert F

2011-03-01

The vestibular evoked myogenic potential (VEMP) is a myogenic response that can be used clinically to evaluate the function of the saccule. However, to date, little is known about the thalamo-cortical representation of saccular activation. It is important to understand all aspects of the VEMP, as this test is currently used clinically in the evaluation of saccular function. To identify the areas of the brain that are activated in response to stimuli used clinically to evoke the VEMP. Electroencephalography (EEG) recordings combined with current density analyses were used to identify the areas of the brain that are activated in response to stimuli presented above VEMP threshold (500 Hz, 120 dB peak SPL [pSPL] tone bursts), as compared to stimuli presented below VEMP threshold (90 dB pSPL, 500 Hz tone bursts). Ten subjects without any history of balance or hearing impairment participated in the study. The neural otolith-evoked responses (NOERs) recorded in response to stimuli presented below VEMP threshold were absent or smaller than NOERs that were recorded in response to stimuli presented above VEMP threshold. Subsequent analyses with source localization techniques, followed by statistical analysis with SPM5 (Statistical Parametric Mapping), revealed several areas that were activated in response to the 120 dB pSPL tone bursts. These areas included the primary visual cortex, the precuneus, the precentral gyrus, the medial temporal gyrus, and the superior temporal gyrus. The present study found a number of specific brain areas that may be activated by otolith stimulation. Given the findings and source localization techniques (which required limited input from the investigator as to where the sources are believed to be located in the brain) used in the present study as well as the similarity in findings between studies employing galvanic stimuli, fMRI (functional magnetic resonance imaging), and scalp-recorded potentials in response to VEMP-eliciting stimuli, our study provides additional evidence that these brain regions are activated in response to stimuli that can be used clinically to evoke the VEMP. American Academy of Audiology.

Oral Azathioprine for Recalcitrant Pediatric Atopic Dermatitis: Clinical Response and Thiopurine Monitoring

PubMed Central

Caufield, Maura; Tom, Wynnis L.

2012-01-01

Background Azathioprine is prescribed as a corticosteroid-sparing agent for many inflammatory conditions, including refractory atopic dermatitis (AD). There is limited prospective data on its appropriate use and monitoring for children with AD. Objectives This study was designed to assess clinical response to azathioprine, determine the necessity for repeat measurement of thiopurine methyltransferase (TPMT) activity during treatment, and test the utility of measuring levels of the metabolites 6-thioguanine nucleotide (6-TGN) and 6-methylmercaptopurine (6-MMP). Methods Twelve children with severe, recalcitrant AD were treated with oral azathioprine and followed prospectively. Disease severity was determined by the SCORing Atopic Dermatitis Index. Baseline TPMT activity was measured and this was repeated along with 6-TGN and 6-MMP measurement at times of stable improvement, inadequate response, or change in response. Results Azathioprine therapy was associated with clinical improvement in all but one subject. There were few adverse effects. Three subjects showed a significant change in TPMT activity during treatment: two had a mild decrease and one demonstrated enzyme inducibility with an increase from the intermediate to the normal activity range. These changes, but not 6-TGN or 6-MMP levels, inversely correlated with the clinical response to therapy. Limitations Small sample size Conclusions Azathioprine can be of benefit in the treatment of recalcitrant pediatric AD. Repeat assessment of TPMT activity may be helpful for evaluation of non–response or change in response and warrants further study. In contrast, measurement of thiopurine metabolites during treatment was not clinically useful. PMID:22892285

A Brief Review of OPT101 Sensor Application in Near-Infrared Spectroscopy Instrumentation for Intensive Care Unit Clinics

PubMed Central

Li, Ting; Zhong, Fulin; Pan, Boan; Li, Zebin; Huang, Chong; Deng, Zishan

2017-01-01

The optoelectronic sensor OPT101 have merits in advanced optoelectronic response characteristics at wavelength range for medical near-infrared spectroscopy and small-size chip design with build-in trans-impedance amplifier. Our lab is devoted to developing a series of portable near-infrared spectroscopy (NIRS) devices embedded with OPT101 for applications in intensive care unit clinics, based on NIRS principle. Here we review the characteristics and advantages of OPT101 relative to clinical NIRS instrumentation, and the most recent achievements, including early-diagnosis and therapeutic effect evaluation of thrombus, noninvasive monitoring of patients' shock severity, and fatigue evaluation. The future prospect on OPT101 improvements in noninvasive clinical applications is also discussed. PMID:28757564

Evaluation and comparison of predictive individual-level general surrogates.

PubMed

Gabriel, Erin E; Sachs, Michael C; Halloran, M Elizabeth

2018-07-01

An intermediate response measure that accurately predicts efficacy in a new setting at the individual level could be used both for prediction and personalized medical decisions. In this article, we define a predictive individual-level general surrogate (PIGS), which is an individual-level intermediate response that can be used to accurately predict individual efficacy in a new setting. While methods for evaluating trial-level general surrogates, which are predictors of trial-level efficacy, have been developed previously, few, if any, methods have been developed to evaluate individual-level general surrogates, and no methods have formalized the use of cross-validation to quantify the expected prediction error. Our proposed method uses existing methods of individual-level surrogate evaluation within a given clinical trial setting in combination with cross-validation over a set of clinical trials to evaluate surrogate quality and to estimate the absolute prediction error that is expected in a new trial setting when using a PIGS. Simulations show that our method performs well across a variety of scenarios. We use our method to evaluate and to compare candidate individual-level general surrogates over a set of multi-national trials of a pentavalent rotavirus vaccine.

[Pharmacogenomics of the first-line treatment for gastric cancer: advances in the identification of genomic biomarkers for clinical response to chemotherapy].

PubMed

Castro-Rojas, Carlos; Ortiz-Lópezj, Rocío; Rojas-Martínez, Augusto

2014-06-01

Gastric cancer (GC) is often diagnosed at later stages due to the lack of specificity of symptoms associated with the neoplasm, causing high mortality rates worldwide. The first line of adjuvant and neoadjuvant treatment includes cytotoxic fluoropyrimidines and platin-containing compounds which cause the formation of DNA adducts. The clinical outcome with these antineoplastic agents depends mainly on tumor sensitivity, which is conditioned by the expression level of the drug targets and the DNA-repair system enzymes. In addition, some germ line polymorphisms, in genes linked to drug metabolism and response to chemotherapy, have been associated with poor responses and the development of adverse effects, even with fatal outcomes in GC patients. The identification of genomic biomarkers, such as individual gene polymorphisms or differential expression patterns of specific genes, in a patient-by-patient context with potential clinical application is the main focus of current pharmacogenomic research, which aims at developing a rational and personalized therapy (i.e., a therapy that ensures maximum efficacy with no predictable side effects). However, because of the future application of genomic technologies in the clinical setting, it is necessary to establish the prognostic value of these genomic biomarkers with genotype-phenotype association studies and to evaluate their prevalence in the population under treatment. These issues are important for their cost-effectiveness evaluation, which determines the feasibility of using these medical genomic research products for GC treatment in the clinical setting.

Fear-avoidance beliefs and temporal summation of evoked thermal pain influence self-report of disability in patients with chronic low back pain.

PubMed

George, Steven Z; Wittmer, Virgil T; Fillingim, Roger B; Robinson, Michael E

2006-03-01

Quantitative sensory testing has demonstrated a promising link between experimentally determined pain sensitivity and clinical pain. However, previous studies of quantitative sensory testing have not routinely considered the important influence of psychological factors on clinical pain. This study investigated whether measures of thermal pain sensitivity (temporal summation, first pulse response, and tolerance) contributed to clinical pain reports for patients with chronic low back pain, after controlling for depression or fear-avoidance beliefs about work. Consecutive patients (n=27) with chronic low back pain were recruited from an interdisciplinary pain rehabilitation program in Jacksonville, FL. Patients completed validated self-report questionnaires for depression, fear-avoidance beliefs, clinical pain intensity, and clinical pain related disability. Patients also underwent quantitative sensory testing from previously described protocols to determine thermal pain sensitivity (temporal summation, first pulse response, and tolerance). Hierarchical regression models investigated the contribution of depression and thermal pain sensitivity to clinical pain intensity, and fear-avoidance beliefs and thermal pain sensitivity to clinical pain related disability. None of the measures of thermal pain sensitivity contributed to clinical pain intensity after controlling for depression. Temporal summation of evoked thermal pain significantly contributed to clinical pain disability after controlling for fear-avoidance beliefs about work. Measures of thermal pain sensitivity did not contribute to pain intensity, after controlling for depression. Fear-avoidance beliefs about work and temporal summation of evoked thermal pain significantly influenced pain related disability. These factors should be considered as potential outcome predictors for patients with work-related low back pain. This study supported the neuromatrix theory of pain for patients with CLBP, as cognitive-evaluative factor contributed to pain perception, and cognitive-evaluative and sensory-discriminative factors uniquely contributed to an action program in response to chronic pain. Future research will determine if a predictive model consisting of fear-avoidance beliefs and temporal summation of evoked thermal pain has predictive validity for determining clinical outcome in rehabilitation or vocational settings.

Comparison of the prognostic value of pretreatment measurements of systemic inflammatory response in patients undergoing curative resection of clear cell renal cell carcinoma.

PubMed

Lucca, Ilaria; de Martino, Michela; Hofbauer, Sebastian L; Zamani, Nura; Shariat, Shahrokh F; Klatte, Tobias

2015-12-01

Pretreatment measurements of systemic inflammatory response, including the Glasgow prognostic score (GPS), the neutrophil-to-lymphocyte ratio (NLR), the monocyte-to-lymphocyte ratio (MLR), the platelet-to-lymphocyte ratio (PLR) and the prognostic nutritional index (PNI) have been recognized as prognostic factors in clear cell renal cell carcinoma (CCRCC), but there is at present no study that compared these markers. We evaluated the pretreatment GPS, NLR, MLR, PLR and PNI in 430 patients, who underwent surgery for clinically localized CCRCC (pT1-3N0M0). Associations with disease-free survival were assessed with Cox models. Discrimination was measured with the C-index, and a decision curve analysis was used to evaluate the clinical net benefit. On multivariable analyses, all measures of systemic inflammatory response were significant prognostic factors. The increase in discrimination compared with the stage, size, grade and necrosis (SSIGN) score alone was 5.8 % for the GPS, 1.1-1.4 % for the NLR, 2.9-3.4 % for the MLR, 2.0-3.3 % for the PLR and 1.4-3.0 % for the PNI. On the simultaneous multivariable analysis of all candidate measures, the final multivariable model contained the SSIGN score (HR 1.40, P < 0.001), the GPS (HR 2.32, P < 0.001) and the MLR (HR 5.78, P = 0.003) as significant variables. Adding both the GPS and the MLR increased the discrimination of the SSIGN score by 6.2 % and improved the clinical net benefit. In patients with clinically localized CCRCC, the GPS and the MLR appear to be the most relevant prognostic measures of systemic inflammatory response. They may be used as an adjunct for patient counseling, tailoring management and clinical trial design.

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

PubMed

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.

Combination of paclitaxel and carboplatin as second-line therapy for patients with metastatic melanoma.

PubMed

Rao, Ravi D; Holtan, Shernan G; Ingle, James N; Croghan, Gary A; Kottschade, Lisa A; Creagan, Edward T; Kaur, Judith S; Pitot, Henry C; Markovic, Svetomir N

2006-01-15

Patients with metastatic melanoma (MM) have very few therapy options. Based on reports of responses to paclitaxel and carboplatin (PC), 31 patients with MM were treated with PC. Data regarding patients treated with PC were abstracted from medical records. Clinical outcomes as determined by the treating oncologist were used for this analysis. Response determination was retrospectively confirmed using Response Evaluation Criteria in Solid Tumors (RECIST). Thirty-one patients with MM were treated with PC. Patients had a median of 2 previous therapies, with the majority (29; 94%) having failed prior temozolomide (TMZ) or dacarbazine (DTIC) therapy. The most commonly used regimen was weekly paclitaxel (at a dose of 100 mg/m(2)) and carboplatin (area under the curve 2) administered on Days 1, 8, and 15 of a 28-day cycle. An objective partial response was noted in 8 patients (26%) with an additional 6 patients (19%) having stable disease; therefore, a clinical benefit was noted in 45% of those patients treated. The median time to disease progression for the entire group was 3 months (range, 0-7 mos), with a median overall survival of 7.8 months (range, 1-14 mos). The clinical benefit derived by the 14 patients, which lasted for a median of 5.7 months (range, 2.5-7.3 mos), was considered to be clinically significant. At the time of last follow-up, eight patients continued to receive PC therapy. The PC combination appears to have definite and clinically meaningful activity when used as second-line therapy after TMZ or DTIC. Further evaluation of this regimen, alone or as a 'backbone' for other agents, needs to be considered.

How do chiropractors manage clinical risk? A questionnaire study.

PubMed

Wangler, Martin; Peterson, Cynthia; Zaugg, Beatrice; Thiel, Haymo; Finch, Rob

2013-06-08

The literature on chiropractic safety tends to focus on adverse events and little is known about how chiropractors ensure safety and manage risk in the course of their daily practice. The purpose of this study was to investigate how chiropractors manage potentially risky clinical scenarios. We also sought to establish how chiropractors perceive the safety climate in their workplace and thus whether there is an observable culture of safety within the profession. An online questionnaire was designed to determine which of nine management options would be chosen by the respondent in response to four defined clinical case scenarios. Safety climate within the respondent's practice setting was measured by seeking the level of agreement with 23 statements relating to six different safety dimensions. 260 licensed chiropractors in Switzerland and 1258 UK members of The Royal College of Chiropractors were invited to complete the questionnaire. Questionnaire responses were analysed quantitatively in respect of the four clinical scenarios and the nine management options to determine the likelihood of each option being undertaken, with results recorded in terms of % likelihood. Gender differences in response to the management options for each scenario were evaluated using the Mann-Whitney U (MWU) test. Positive agreement with elements comprising each of the six safety dimensions contributed to a composite '% positive agreement' score calculated for each dimension. Questionnaire responses were received from 76% (200/260) of Swiss participants and 31% (393/1258) of UK members of The Royal College of Chiropractors. There was a general trend for Swiss and UK chiropractors to manage clinical scenarios where treatment appears not to be successful, not indicated, possibly harmful or where a patient is apparently getting worse, by re-evaluating their care. Stopping treatment and/or incident reporting to a safety incident reporting and learning system were generally found to be unlikely courses of action. Gender differences were observed with female chiropractors appearing to be more risk averse. Swiss and UK chiropractors tend to manage potentially risky clinical scenarios by re-evaluating the case. The unlikeliness of safety incident reporting is probably due to a range of recognised barriers, although Swiss and UK chiropractors are positive about local communication and openness which are important tenets for safety incident reporting. The observed positivity towards key aspects of clinic safety indicates a developing safety culture within the Swiss and UK chiropractic professions.

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

PubMed Central

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

2014-01-01

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

Comparison of Noninvasive High-Intensity Focused Ultrasound with Radiofrequency Ablation of Osteoid Osteoma.

PubMed

Sharma, Karun V; Yarmolenko, Pavel S; Celik, Haydar; Eranki, Avinash; Partanen, Ari; Smitthimedhin, Anilawan; Kim, Aerang; Oetgen, Matthew; Santos, Domiciano; Patel, Janish; Kim, Peter

2017-11-01

To evaluate clinical feasibility and safety of magnetic resonance imaging-guided high-intensity focused ultrasound (MR-HIFU) treatment of symptomatic osteoid osteoma and to compare clinical response with standard of care treatment. Nine subjects with radiologically confirmed, symptomatic osteoid osteoma were treated with MR-HIFU in an institutional review board-approved clinical trial. Treatment feasibility and safety were assessed. Clinical response was evaluated in terms of analgesic requirement, visual analog scale pain score, and sleep quality. Anesthesia, procedure, and recovery times were recorded. This MR-HIFU group was compared with a historical control group of 9 consecutive patients treated with radiofrequency ablation. Nine subjects (7 male, 2 female; 16 ± 6 years) were treated with MR-HIFU without technical difficulties or any serious adverse events. There was significant decrease in their median pain scores 4 weeks within treatment (6 vs 0, P < .01). Total pain resolution and cessation of analgesics were achieved in 8 of 9 patients after 4 weeks. In the radiofrequency ablation group, 9 patients (8 male, 1 female; 10 ± 6 years) were treated in routine clinical practice. All 9 demonstrated complete pain resolution and cessation of medications by 4 weeks with a significant decrease in median pain scores (9 vs 0, P < .001). One developed a second-degree skin burn, but there were no other adverse events. Procedure times and treatment charges were comparable between the 2 groups. This pilot study shows that MR-HIFU treatment of osteoid osteoma refractory to medical therapy is feasible and can be performed safely in pediatric patients. Clinical response is comparable with standard of care treatment but without any incisions or exposure to ionizing radiation. ClinicalTrials.govNCT02349971. Copyright © 2017 Elsevier Inc. All rights reserved.

Reporting Items for Updated Clinical Guidelines: Checklist for the Reporting of Updated Guidelines (CheckUp)

PubMed Central

Vernooij, Robin W. M.; Alonso-Coello, Pablo; Brouwers, Melissa

2017-01-01

Background Scientific knowledge is in constant development. Consequently, regular review to assure the trustworthiness of clinical guidelines is required. However, there is still a lack of preferred reporting items of the updating process in updated clinical guidelines. The present article describes the development process of the Checklist for the Reporting of Updated Guidelines (CheckUp). Methods and Findings We developed an initial list of items based on an overview of research evidence on clinical guideline updating, the Appraisal of Guidelines for Research and Evaluation (AGREE) II Instrument, and the advice of the CheckUp panel (n = 33 professionals). A multistep process was used to refine this list, including an assessment of ten existing updated clinical guidelines, interviews with key informants (response rate: 54.2%; 13/24), a three-round Delphi consensus survey with the CheckUp panel (33 participants), and an external review with clinical guideline methodologists (response rate: 90%; 53/59) and users (response rate: 55.6%; 10/18). CheckUp includes 16 items that address (1) the presentation of an updated guideline, (2) editorial independence, and (3) the methodology of the updating process. In this article, we present the methodology to develop CheckUp and include as a supplementary file an explanation and elaboration document. Conclusions CheckUp can be used to evaluate the completeness of reporting in updated guidelines and as a tool to inform guideline developers about reporting requirements. Editors may request its completion from guideline authors when submitting updated guidelines for publication. Adherence to CheckUp will likely enhance the comprehensiveness and transparency of clinical guideline updating for the benefit of patients and the public, health care professionals, and other relevant stakeholders. PMID:28072838

Evaluation of health alerts from an early illness warning system in independent living.

PubMed

Rantz, Marilyn J; Scott, Susan D; Miller, Steven J; Skubic, Marjorie; Phillips, Lorraine; Alexander, Greg; Koopman, Richelle J; Musterman, Katy; Back, Jessica

2013-06-01

Passive sensor networks were deployed in independent living apartments to monitor older adults in their home environments to detect signs of impending illness and alert clinicians so they can intervene and prevent or delay significant changes in health or functional status. A retrospective qualitative deductive content analysis was undertaken to refine health alerts to improve clinical relevance to clinicians as they use alerts in their normal workflow of routine care delivery to older adults. Clinicians completed written free-text boxes to describe actions taken (or not) as a result of each alert; they also rated the clinical significance (relevance) of each health alert on a scale of 1 to 5. Two samples of the clinician's written responses to the health alerts were analyzed after alert algorithms had been adjusted based on results of a pilot study using health alerts to enhance clinical decision-making. In the first sample, a total of 663 comments were generated by seven clinicians in response to 385 unique alerts; there are more comments than alerts because more than one clinician rated the same alert. The second sample had a total of 142 comments produced by three clinicians in response to 88 distinct alerts. The overall clinical relevance of the alerts, as judged by the content of the qualitative comments by clinicians for each alert, improved from 33.3% of the alerts in the first sample classified as clinically relevant to 43.2% in the second. The goal is to produce clinically relevant alerts that clinicians find useful in daily practice. The evaluation methods used are described to assist others as they consider building and iteratively refining health alerts to enhance clinical decision making.

The development and evaluation of online stories to enhance clinical learning experiences across health professions in rural Australia.

PubMed

Paliadelis, Penny Susan; Stupans, Leva; Parker, Vicki; Piper, Donella; Gillan, Pauline; Lea, Jackie; Jarrott, Helen Mary; Wilson, Rhonda; Hudson, Judith N; Fagan, Anthea

2015-01-01

Clinical placement learning experiences are integral to all health and medical curricula as a means of integrating theory into practice and preparing graduates to deliver safe, high-quality care to health consumers. A growing challenge for education providers is to access sufficient clinical placements with experienced supervisors who are skilled at maximising learning opportunities for students. This paper reports on the development and evaluation of an innovative online learning program aimed at enhancing student and clinical supervisors' preparedness for effective workplace-based learning. The evidence-based learning program used 'story-telling' as the learning framework. The stories, which were supported by a range of resources, aimed to engage the learners in understanding student and supervisor responsibilities, as well as the expectations and competencies needed to support effective learning in the clinical environment. Evaluation of this program by the learners and stakeholders clearly indicated that they felt authentically 'connected' with the characters in the stories and developed insights that suggested effective learning had occurred.

Association of fecal calprotectin concentrations with disease severity, response to treatment, and other biomarkers in dogs with chronic inflammatory enteropathies

PubMed Central

Berghoff, Nora; Mansell, Joanne; Grützner, Niels; Parnell, Nolie K.; Gurtner, Corinne; Suchodolski, Jan S.; Steiner, Jörg M.

2018-01-01

Background Calprotectin is a marker of inflammation, but its clinical utility in dogs with chronic inflammatory enteropathies (CIE) is unknown. Objective Evaluation of fecal calprotectin in dogs with biopsy‐confirmed CIE. Animals 127 dogs. Methods Prospective case‐control study. Dogs were assigned a canine chronic enteropathy clinical activity index (CCECAI) score, and histologic lesions severity was assessed. Fecal calprotectin, fecal S100A12, and serum C‐reactive protein (CRP) were measured. Food‐ or antibiotic‐responsive cases (FRE/ARE, n = 13) were distinguished from steroid‐/immunosuppressant‐responsive or ‐refractory cases (SRE/IRE, n = 20). Clinical response to treatment in SRE/IRE dogs was classified as complete remission (CR), partial response (PR), or no response (NR). Results Fecal calprotectin correlated with CCECAI (ρ = 0.27, P = .0065) and fecal S100A12 (ρ = 0.90, P < .0001), some inflammatory criteria, and cumulative inflammation scores, but not serum CRP (ρ = 0.16, P = .12). Dogs with SRE/IRE had higher fecal calprotectin concentrations (median: 2.0 μg/g) than FRE/ARE dogs (median: 1.4 μg/g), and within the SRE/IRE group, dogs with PR/NR had higher fecal calprotectin (median: 37.0 μg/g) than dogs with CR (median: 1.6 μg/g). However, both differences did not reach statistical significance (both P = .10). A fecal calprotectin ≥15.2 μg/g separated both groups with 80% sensitivity (95% confidence interval [95%CI]: 28%‐100%) and 75% specificity (95%CI: 43%‐95%). Conclusions and Clinical Importance Fecal calprotectin could be a useful surrogate marker of disease severity in dogs with CIE, but larger longitudinal studies are needed to evaluate its utility in predicting the response to treatment. PMID:29460444

Invited commentary: Evaluating epidemiologic research methods--the importance of response rate calculation.

PubMed

Harris, M Anne

2010-09-15

Epidemiologic research that uses administrative records (rather than registries or clinical surveys) to identify cases for study has been increasingly restricted because of concerns about privacy, making unbiased population-based research less practicable. In their article, Nattinger et al. (Am J Epidemiol. 2010;172(6):637-644) present a method for using administrative data to contact participants that has been well received. However, the methods employed for calculating and reporting response rates require further consideration, particularly the classification of untraceable cases as ineligible. Depending on whether response rates are used to evaluate the potential for bias to influence study results or to evaluate the acceptability of the method of contact, different fractions may be considered. To improve the future study of epidemiologic research methods, a consensus on the calculation and reporting of study response rates should be sought.

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

PubMed Central

Qi, Xing-Shun

2017-01-01

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

Clinical Decision Support Alert Appropriateness: A Review and Proposal for Improvement

PubMed Central

McCoy, Allison B.; Thomas, Eric J.; Krousel-Wood, Marie; Sittig, Dean F.

2014-01-01

Background Many healthcare providers are adopting clinical decision support (CDS) systems to improve patient safety and meet meaningful use requirements. Computerized alerts that prompt clinicians about drug-allergy, drug-drug, and drug-disease warnings or provide dosing guidance are most commonly implemented. Alert overrides, which occur when clinicians do not follow the guidance presented by the alert, can hinder improved patient outcomes. Methods We present a review of CDS alerts and describe a proposal to develop novel methods for evaluating and improving CDS alerts that builds upon traditional informatics approaches. Our proposal incorporates previously described models for predicting alert overrides that utilize retrospective chart review to determine which alerts are clinically relevant and which overrides are justifiable. Results Despite increasing implementations of CDS alerts, detailed evaluations rarely occur because of the extensive labor involved in manual chart reviews to determine alert and response appropriateness. Further, most studies have solely evaluated alert overrides that are appropriate or justifiable. Our proposal expands the use of web-based monitoring tools with an interactive dashboard for evaluating CDS alert and response appropriateness that incorporates the predictive models. The dashboard provides 2 views, an alert detail view and a patient detail view, to provide a full history of alerts and help put the patient's events in context. Conclusion The proposed research introduces several innovations to address the challenges and gaps in alert evaluations. This research can transform alert evaluation processes across healthcare settings, leading to improved CDS, reduced alert fatigue, and increased patient safety. PMID:24940129

Basophil responsiveness and clinical picture of acetylsalicylic acid intolerance.

PubMed

Korosec, Peter; Mavsar, Nusa; Bajrovic, Nissera; Silar, Mira; Mrhar, Ales; Kosnik, Mitja

2011-01-01

Exposure to acetylsalicylic acid (ASA) may exacerbate respiratory or skin diseases or induce anaphylactoid reactions in apparently healthy individuals. We wanted to evaluate specific responsiveness of basophils to ASA in correlation with the clinical picture. We performed a prospective single-blind study of 59 subjects involved in clinical evaluation and/or ASA provocation testing. Whole blood basophils were stained with anti-CD63/CD123/HLA-DR mAbs after stimulation with 0.25 or 1 mg/ml ASA. We found that 40 subjects were ASA tolerant and 19 were ASA intolerant. Both groups had comparable manifestations of asthma and/or rhinitis (13 in the tolerant and 9 in the intolerant group). Intolerant subjects showed significantly higher basophil responsiveness to ASA in comparison to tolerant subjects, which was concentration-dependent in both groups. The ratio between responses at 1 mg/ml of ASA and at baseline (activation index) was analyzed according to the clinical picture. We demonstrate that the activation index was higher only in the intolerant subjects with anaphylactoid reactions, but not in a subgroup of subjects with asthma/rhinitis. The ROC calculations show that the optimal threshold activation index was more than 2.18. The sensitivity was 80% and the specificity was 83% in the subgroup with anaphylactoid reactions. In the asthma/rhinitis subgroup, the sensitivity was 78% and the specificity was 50%. Our study demonstrates that there is a significantly higher in vitro basophil response to ASA in intolerant as compared to tolerant subjects. ROC analyses suggest that this measurement might only have a diagnostic value in subjects without asthma and/or rhinitis. Copyright © 2011 S. Karger AG, Basel.

Critical features and challenges associated with imaging in patients undergoing cancer immunotherapy.

PubMed

Solinas, Cinzia; Porcu, Michele; Hlavata, Zuzana; De Silva, Pushpamali; Puzzoni, Marco; Willard-Gallo, Karen; Scartozzi, Mario; Saba, Luca

2017-12-01

Manipulating an individual's immune system through immune checkpoint blockade is revolutionizing the paradigms of cancer treatment. Peculiar patterns and kinetics of response have been observed with these new drugs, rendering the assessment of tumor burden particularly challenging in cancer immunotherapy. The mechanisms of action for immune checkpoint blockade, based upon engagement of the adaptive immune system, can generate unusual response patterns, including pseudoprogression, hyperprogression, atypical and delayed responses. In patients treated with immune checkpoint blockade and radiotherapy, a reduction in tumor burden at metastatic sites distant from the irradiation field (abscopal effect) has been observed, with synergistic systemic immune effects provoked by this combination. New toxicities have also been observed, due to excessive immune activity in several organs, including lung, colon, liver and endocrine glands. Efforts to standardize assessment of cancer immunotherapy responses include novel consensus guidelines derived by modifying World Health Organization (WHO) and Response Evaluation Criteria In Solid Tumors (RECIST) criteria. The aim of this review is to evaluate imaging techniques currently used routinely in the clinic and those being used as investigational tools in immunotherapy clinical trials. Copyright © 2017 Elsevier B.V. All rights reserved.

Evaluation of a continual compliance monitoring program for dapsone in an outpatient Hansen's disease clinic.

PubMed

Fischer, J H; West, D P; Worobec, S M

1986-12-01

Guidelines for the assessment of patient compliance to dapsone were developed and evaluated. The urinary dapsone-to-creatinine (D/C) ratio following standardization by dose, ideal body weight, and time since last dose was used for assessment of compliance. Compliance standards were established in 12 patients of known compliance and confirmed prospectively in nine inpatients on 14 occasions. Compliance increased significantly among outpatients (N = 30) attending the University of Illinois Hansen's Disease Clinic from 47% at base line to 73% at 6 months and 80% at 18 months after establishing the monitoring program. In a subgroup of 18 patients, a similar increase in compliance was observed from 50% to 80%. A good therapeutic response was seen in the subgroup patients who were compliant. A poor therapeutic response was seen in the consistently noncompliant patients. These results demonstrate that use of a continual compliance monitoring program can improve patient drug compliance in an outpatient Hansen's disease clinic.

Evaluation of embolization for periuterine varices involving chronic pelvic pain secondary to pelvic congestion syndrome.

PubMed

Siqueira, Flavio Meirelles; Monsignore, Lucas Moretti; Rosa-E-Silva, Julio Cesar; Poli-Neto, Omero Benedicto; Castro-Afonso, Luis Henrique de; Nakiri, Guilherme Seizem; Muglia, Valdair Francisco; Abud, Daniel Giansante

2016-12-01

To evaluate the clinical response and success rate after periuterine varices embolization in patients with chronic pelvic pain secondary to pelvic congestion syndrome and to report the safety of endovascular treatment and its rate of complications. Retrospective cohort of patients undergoing endovascular treatment of pelvic congestion syndrome in our department from January 2012 to November 2015. Data were analyzed based on patient background, imaging findings, embolized veins, rate of complications, and clinical response as indicated by the visual analog pain scale. We performed periuterine varices embolization in 22 patients during the study, four of which required a second embolization. Seventeen patients reported a reduction in pelvic pain after the first embolization and three patients reported a reduction in pelvic pain after the second embolization. Minor complications were observed in our patients, such as postural hypotension, postoperative pain, and venous perforation during the procedure, without clinical repercussion. Periuterine varices embolization in patients with chronic pelvic pain secondary to pelvic congestion syndrome appears to be an effective and safe technique.

Efficacy and Biological Correlates of Response in a Phase II Study of Venetoclax Monotherapy in Patients with Acute Myelogenous Leukemia.

PubMed

Konopleva, Marina; Pollyea, Daniel A; Potluri, Jalaja; Chyla, Brenda; Hogdal, Leah; Busman, Todd; McKeegan, Evelyn; Salem, Ahmed Hamed; Zhu, Ming; Ricker, Justin L; Blum, William; DiNardo, Courtney D; Kadia, Tapan; Dunbar, Martin; Kirby, Rachel; Falotico, Nancy; Leverson, Joel; Humerickhouse, Rod; Mabry, Mack; Stone, Richard; Kantarjian, Hagop; Letai, Anthony

2016-10-01

We present a phase II, single-arm study evaluating 800 mg daily venetoclax, a highly selective, oral small-molecule B-cell leukemia/lymphoma-2 (BCL2) inhibitor in patients with high-risk relapsed/refractory acute myelogenous leukemia (AML) or unfit for intensive chemotherapy. Responses were evaluated following revised International Working Group (IWG) criteria. The overall response rate was 19%; an additional 19% of patients demonstrated antileukemic activity not meeting IWG criteria (partial bone marrow response and incomplete hematologic recovery). Twelve (38%) patients had isocitrate dehydrogenase 1/2 mutations, of whom 4 (33%) achieved complete response or complete response with incomplete blood count recovery. Six (19%) patients had BCL2-sensitive protein index at screening, which correlated with time on study. BH3 profiling was consistent with on-target BCL2 inhibition and identified potential resistance mechanisms. Common adverse events included nausea, diarrhea and vomiting (all grades), and febrile neutropenia and hypokalemia (grade 3/4). Venetoclax demonstrated activity and acceptable tolerability in patients with AML and adverse features. Venetoclax monotherapy demonstrated clinical activity in patients with AML (relapsed/refractory or unfit for intensive chemotherapy) with a tolerable safety profile in this phase II study. Predictive markers of response consistent with BCL2 dependence were identified. Clinical and preclinical findings provide a compelling rationale to evaluate venetoclax combined with other agents in AML. Cancer Discov; 6(10); 1106-17. ©2016 AACRSee related commentary by Pullarkat and Newman, p. 1082This article is highlighted in the In This Issue feature, p. 1069. ©2016 American Association for Cancer Research.

Clinical and biological effects of demethylating agents on solid tumours - A systematic review.

PubMed

Linnekamp, J F; Butter, R; Spijker, R; Medema, J P; van Laarhoven, H W M

2017-03-01

It is assumed that DNA methylation plays a key role in both tumour development and therapy resistance. Demethylating agents have been shown to be effective in the treatment of haematological malignancies. Based on encouraging preclinical results, demethylating agents may also be effective in solid tumours. This systematic review summarizes the evidence of the effect of demethylating agents on clinical response, methylation and the immune system in solid tumours. We conducted a systematic literature search from 1949 to December 2016, according to the PRISMA guidelines. Studies which evaluated treatment with azacitidine, decitabine, guadecitabine, hydralazine, procaine, MG98 and/or zebularine in patients with solid tumours were included. Data on clinical response, effects on methylation and immune response were extracted. Fifty-eight studies were included: in 13 studies complete responses (CR) were observed, 35 studies showed partial responses (PR), 47 studies stable disease (SD) and all studies except two showed progressive disease (PD). Effects on global methylation were observed in 11/15 studies and demethylation/re-expression of tumour specific genes was seen in 15/17 studies. No clear correlation between (de)methylation and clinical response was observed. In 14 studies immune-related responses were reported, such as re-expression of cancer-testis antigens and upregulation of interferon genes. Demethylating agents are able to improve clinical outcome and alter methylation status in patients with solid tumours. Although beneficial effect has been shown in individual patients, overall response is limited. Further research on biomarker predicting therapy efficacy is indicated, particularly in earlier stage and highly methylated tumours. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Predicting clinical outcomes in chordoma patients receiving immunotherapy: a comparison between volumetric segmentation and RECIST.

PubMed

Fenerty, Kathleen E; Folio, Les R; Patronas, Nicholas J; Marté, Jennifer L; Gulley, James L; Heery, Christopher R

2016-08-23

The Response Evaluation Criteria in Solid Tumors (RECIST) are the current standard for evaluating disease progression or therapy response in patients with solid tumors. RECIST 1.1 calls for axial, longest-diameter (or perpendicular short axis of lymph nodes) measurements of a maximum of five tumors, which limits clinicians' ability to adequately measure disease burden, especially in patients with irregularly shaped tumors. This is especially problematic in chordoma, a disease for which RECIST does not always adequately capture disease burden because chordoma tumors are typically irregularly shaped and slow-growing. Furthermore, primary chordoma tumors tend to be adjacent to vital structures in the skull or sacrum that, when compressed, lead to significant clinical consequences. Volumetric segmentation is a newer technology that allows tumor burden to be measured in three dimensions on either MR or CT. Here, we compared the ability of RECIST measurements and tumor volumes to predict clinical outcomes in a cohort of 21 chordoma patients receiving immunotherapy. There was a significant difference in radiologic time to progression Kaplan-Meier curves between clinical outcome groups using volumetric segmentation (P = 0.012) but not RECIST (P = 0.38). In several cases, changes in volume were earlier and more sensitive reflections of clinical status. RECIST is a useful evaluation method when obvious changes are occurring in patients with chordoma. However, in many cases, RECIST does not detect small changes, and volumetric assessment was capable of detecting changes and predicting clinical outcome earlier than RECIST. Although this study was small and retrospective, we believe our results warrant further research in this area.

Voltage-Gated Potassium Channel Autoimmunity Mimicking Creutzfeldt-Jakob Disease

PubMed Central

Geschwind, Michael D.; Tan, K. Meng; Lennon, Vanda A.; Barajas, Ramon F.; Haman, Aissa; Klein, Christopher J.; Josephson, S. Andrew; Pittock, Sean J.

2009-01-01

Background Rapidly progressive dementia has a variety of causes, including Creutzfeldt-Jakob disease (CJD) and neuronal voltage-gated potassium channel (VGKC) autoantibody–associated encephalopathy. Objective To describe patients thought initially to have CJD but found subsequently to have immunotherapy-responsive VGKC autoimmunity. Design Observational, prospective case series. Setting Department of Neurology, Mayo Clinic, and the Memory and Aging Center, University of California, San Francisco. Patients A clinical serologic cohort of 15 patients referred for paraneoplastic autoantibody evaluation. Seven patients were evaluated clinically by at least one of us. Clinical information for the remaining patients was obtained by physician interview or medical record review. Main Outcome Measures Clinical features, magnetic resonance imaging abnormalities, electroencephalographic patterns, cerebrospinal fluid analyses, and responses to immunomodulatory therapy. Results All the patients presented subacutely with neurologic manifestations, including rapidly progressive dementia, myoclonus, extrapyramidal dysfunction, visual hallucinations, psychiatric disturbance, and seizures; most (60%) satisfied World Health Organization diagnostic criteria for CJD. Magnetic resonance imaging abnormalities included cerebral cortical diffusion-weighted imaging hyperintensities. Electroencephalographic abnormalities included diffuse slowing, frontal intermittent rhythmic delta activity, and focal epileptogenic activity but not periodic sharp wave complexes. Cerebrospinal fluid 14-3-3 protein or neuron-specific enolase levels were elevated in 5 of 8 patients. Hyponatremia was common (60%). Neoplasia was confirmed histologically in 5 patients (33%) and was suspected in another 5. Most patients’ conditions (92%) improved after immunomodulatory therapy. Conclusions Clinical, radiologic, electrophysiologic, and laboratory findings in VGKC autoantibody–associated encephalopathy may be confused with those of CJD. Serologic evaluation for markers of neurologic autoimmunity, including VGKC autoantibodies, may be warranted in suspected CJD cases. PMID:18852349

Prevalence of periodontopathogens and Candida spp. in smokers after nonsurgical periodontal therapy - a pilot study.

PubMed

Camargo, Gabriela Alessandra da Cruz Galhardo; Abreu, Mariana Gouvêa Latini; Cordeiro, Renata Dos Santos; Wenderoscky, Letícia de Farias; Duque, Cristiane

2016-08-22

This pilot study aimed to evaluate the influence of smoking on clinical and microbiological parameters after nonsurgical periodontal therapy. Forty-eight subjects were grouped into smokers (SM, n = 24) and nonsmokers (NS, n = 24) and paired according to gender, age, ethnicity, and periodontal status. Both groups received oral hygiene education and scaling and root planing. Clinical evaluation was performed using plaque index (PI), bleeding on probing (BOP), pocket probing depth (PPD), gingival recession (GR), and clinical attachment level (CAL) before instrumentation (baseline) and at 3 and 6 months. The prevalence of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Candida albicans, Candida glabrata, Candida tropicalis, and Candida dubliniensis in subgingival biofilm was determined by polymerase chain reaction. The data were statistically analyzed considering p < 0.05. Clinical conditions improved between baseline and 3 months after periodontal treatment. However, NS had a better clinical response, presenting greater PPD reduction and CAL increase in comparison to SM. Periodontal treatment reduced the levels of P. gingivalis, A. actinomycetemcomitans, and T. forsythia individually after 3 months for the NS group and after 6 months for both groups. The prevalence of Candida species was markedly higher in SM than in NS at all time points evaluated. Periodontopathogens associated or not with C. albicans or C. dubliniensis were more prevalent in SM than in NS at baseline and after 3 months. It was concluded that smoking impairs clinical and microbiological responses to periodontal therapy. Periodontopathogens combined or not with some Candida species are resistant to short-term periodontal therapy in SM.

[Experiences and recommendations of the German Federal Institute for Drugs and Medical Devices (BfArM) concerning clinical investigation of medical devices and the evaluation of serious adverse events (SAE)].

PubMed

Renisch, B; Lauer, W

2014-12-01

An integral part of the conformity assessment process for medical devices is a clinical evaluation based on clinical data. Particularly in the case of implantable devices and products of risk class III clinical trials must be performed. Since March 2010 applications for the authorization of clinical trials as well as for the waiver of the authorization requirement must be submitted centrally in Germany to the appropriate federal authority, the Federal Institute for Drugs and Medical Devices (BfArM) or the Paul Ehrlich Institute (PEI). In addition to authorization, approval by the responsible ethics committee is also required under law in order to begin clinical testing of medical devices in Germany. In this paper, the legal framework for the clinical testing of medical devices as well as those involved and possible procedures including evaluation criteria for the initial application of a trial and subsequent amendments are presented in detail. In addition, the reporting requirements for serious adverse events (SAEs) are explained and possible consequences of the evaluation are presented. Finally, a summary of application and registration numbers for all areas of extensive experience of the BfArM as well as requests and guidance for applicants are presented.

Surrogacy in antiviral drug development

PubMed Central

Shaunak, Sunil; Davies, Donald S

2002-01-01

The coming of age of molecular biology has resulted in an explosion in our understanding of the pathogenesis of virus related diseases. New pathogens have been identified and characterized as being responsible for old diseases. Empirical clinical evaluation of morbidity and mortality as outcome measures after a therapeutic intervention have started to give way to the use of an increasing number of surrogate markers. Using a combination of these markers, it is now possible to measure and monitor the pathogen as well as the host's response. Nowhere is this better exemplified in virology than in the field of AIDS. We have utilized the advances in pathogenesis and new antiretroviral drug development to: develop a new class of drugs which block the entry of HIV-1 into cells.develop a new approach for effectively delivering these drugs to those tissues in which most viral replication takes place. Over the last 10 years, our work has progressed from concept to clinical trial. Our laboratory based evaluation of the new molecules developed as well as our clinical evaluation of their safety and efficacy have had to respond and adapt to the rapid changes taking place in AIDS research. This paper discusses the problems encountered and the lessons learnt. PMID:12100230

Practice-based learning experience to develop residents as clinical faculty members.

PubMed

Slazak, Erin M; Zurick, Gina M

2009-07-01

A practice-based learning experience designed to expose postgraduate year 1 (PGY1) and 2 (PGY2) residents to and prepare them for a career as clinical faculty is described. A practice-based learning experience was designed to give PGY1 and PGY2 residents exposure to the responsibilities of a clinical faculty member, integrating clinical practice, preceptor duties, and other academia-related responsibilities. The learning experience is a four-week, elective rotation for PGY1 and PGY2 residents. The rotation is designed to correspond to a four-week advanced pharmacy practice experience (APPE) rotation, allowing the resident to work continuously with the same one or two APPE students for the entire rotation. The resident is required to design and implement a rotation for the students and provide clinical services while integrating students into daily tasks, facilitating topic and patient discussions, evaluating assignments, providing constructive feedback, and assigning a final rotation grade. The resident also attends all academic and committee meetings and teaching obligations with his or her residency director, if applicable. The resident is mentored by the residency director throughout all phases of the rotation and is evaluated using goals and objectives tailored to this experience. The development of a formal, structured rotation to give postgraduate residents experience as a preceptor provided an opportunity for residents to further explore their interests in academia and allowed them to serve as a primary preceptor while being guided and evaluated by a mentor.

A novel 3D human glioblastoma cell culture system for modeling drug and radiation responses

PubMed Central

Stevenson, Katrina; Gilmour, Lesley; Hamilton, Graham; Chalmers, Anthony J

2017-01-01

Abstract Background. Glioblastoma (GBM) is the most common primary brain tumor, with dismal prognosis. The failure of drug–radiation combinations with promising preclinical data to translate into effective clinical treatments may relate to the use of simplified 2-dimensional in vitro GBM cultures. Methods. We developed a customized 3D GBM culture system based on a polystyrene scaffold (Alvetex) that recapitulates key histological features of GBM and compared it with conventional 2D cultures with respect to their response to radiation and to molecular targeted agents for which clinical data are available. Results. In 3 patient-derived GBM lines, no difference in radiation sensitivity was observed between 2D and 3D cultures, as measured by clonogenic survival. Three different molecular targeted agents, for which robust clinical data are available were evaluated in 2D and 3D conditions: (i) temozolomide, which improves overall survival and is standard of care for GBM, exhibited statistically significant effects on clonogenic survival in both patient-derived cell lines when evaluated in the 3D model compared with only one cell line in 2D cells; (ii) bevacizumab, which has been shown to increase progression-free survival when added to standard chemoradiation in phase III clinical trials, exhibited marked radiosensitizing activity in our 3D model but had no effect on 2D cells; and (iii) erlotinib, which had no efficacy in clinical trials, displayed no activity in our 3D GBM model, but radiosensitized 2D cells. Conclusions. Our 3D model reliably predicted clinical efficacy, strongly supporting its clinical relevance and potential value in preclinical evaluation of drug–radiation combinations for GBM. PMID:27576873

Response to Placebo in Clinical Epilepsy Trials - Old Ideas and New Insights

PubMed Central

Goldenholz, Daniel M.; Goldenholz, Shira R

2016-01-01

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

Hemodynamic characterization of geometric cerebral aneurysm templates.

PubMed

Nair, Priya; Chong, Brian W; Indahlastari, Aprinda; Lindsay, James; DeJeu, David; Parthasarathy, Varsha; Ryan, Justin; Babiker, Haithem; Workman, Christopher; Gonzalez, L Fernando; Frakes, David

2016-07-26

Hemodynamics are currently considered to a lesser degree than geometry in clinical practices for evaluating cerebral aneurysm (CA) risk and planning CA treatment. This study establishes fundamental relationships between three clinically recognized CA geometric factors and four clinically relevant hemodynamic responses. The goal of the study is to develop a more combined geometric/hemodynamic basis for informing clinical decisions. Flows within eight idealized template geometries were simulated using computational fluid dynamics and measured using particle image velocimetry under both steady and pulsatile flow conditions. The geometric factor main effects were then analyzed to quantify contributions made by the geometric factors (aneurysmal dome size (DS), dome-to-neck ratio (DNR), and parent-vessel contact angle (PV-CA)) to effects on the hemodynamic responses (aneurysmal and neck-plane root-mean-square velocity magnitude (Vrms), aneurysmal wall shear stress (WSS), and cross-neck flow (CNF)). Two anatomical aneurysm models were also examined to investigate how well the idealized findings would translate to more realistic CA geometries. DNR made the greatest contributions to effects on hemodynamics including a 75.05% contribution to aneurysmal Vrms and greater than 35% contributions to all responses. DS made the next greatest contributions, including a 43.94% contribution to CNF and greater than 20% contributions to all responses. PV-CA and several factor interactions also made contributions of greater than 10%. The anatomical aneurysm models and the most similar idealized templates demonstrated consistent hemodynamic response patterns. This study demonstrates how individual geometric factors, and combinations thereof, influence CA hemodynamics. Bridging the gap between geometry and flow in this quantitative yet practical way may have potential to improve CA evaluation and treatment criteria. Agreement among results from idealized and anatomical models further supports the potential for a template-based approach to play a useful role in clinical practice. Copyright © 2015 Elsevier Ltd. All rights reserved.

Neurophysiology of the pelvic floor in clinical practice: a systematic literature review

PubMed Central

Bianchi, Francesca; Squintani, Giovanna Maddalena; Osio, Maurizio; Morini, Alberto; Bana, Cristina; Ardolino, Gianluca; Barbieri, Sergio; Bertolasi, Laura; Caramelli, Riccardo; Cogiamanian, Filippo; Currà, Antonio; de Scisciolo, Giuseppe; Foresti, Camillo; Frasca, Vittorio; Frasson, Emma; Inghilleri, Maurizio; Maderna, Luca; Motti, Luisa; Onesti, Emanuela; Romano, Marcello Calogero; Del Carro, Ubaldo

2017-01-01

Summary Neurophysiological testing of the pelvic floor is recognized as an essential tool to identify pathophysiological mechanisms of pelvic floor disorders, support clinical diagnosis, and aid in therapeutic decisions. Nevertheless, the diagnostic value of these tests in specific neurological diseases of the pelvic floor is not completely clarified. Seeking to fill this gap, the members of the Neurophysiology of the Pelvic Floor Study Group of the Italian Clinical Neurophysiology Society performed a systematic review of the literature to gather available evidence for and against the utility of neurophysiological tests. Our findings confirm the utility of some tests in specific clinical conditions [e.g. concentric needle electromyography, evaluation of sacral reflexes and of pudendal somatosensory evoked potentials (pSEPs) in cauda equina and conus medullaris lesions, and evaluation of pSEPs and perineal sympathetic skin response in spinal cord lesions], and support their use in clinical practice. Other tests, particularly those not currently supported by high-level evidence, when employed in individual patients, should be evaluated in the overall clinical context, or otherwise used for research purposes.

21 CFR 862.3080 - Breath nitric oxide test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... fractional nitric oxide concentration in expired breath aids in evaluating an asthma patient's response to anti-inflammatory therapy, as an adjunct to established clinical and laboratory assessments of asthma...

Systematic Analysis of Icotinib Treatment for Patients with Non-Small Cell Lung Cancer.

PubMed

Shi, Bing; Zhang, Xiu-Bing; Xu, Jian; Huang, Xin-En

2015-01-01

This analysis was conducted to evaluate the efficacy and safety of icotinib based regimens in treating patients with non-small cell lung cancer (NSCLC). Clinical studies evaluating the efficacy and safety of icotinib-based regimens with regard to response and safety for patients with NSCLC were identified using a predefined search strategy. Pooled response rates of treatment were calculated. With icotinib-based regimens, 7 clinical studies which including 5,985 Chinese patients with NSCLC were considered eligible for inclusion. The pooled analysis suggested that, in all patients, the positive reponse rate was 30.1% (1,803/5,985) with icotinib-based regimens. Mild skin itching, rashes and diarrhea were the main side effects. No grade III or IV renal or liver toxicity was observed. No treatment-related death occurred in patients treated with icotinib-based regimens. This evidence based analysis suggests that icotinib based regimens are associated with mild response rate and acceptable toxicity for treating Chinese patients with NSCLC.

Ultrasound disease activity of bilateral wrist and finger joints at three months reflects the clinical response at six months of patients with rheumatoid arthritis treated with biologic disease-modifying anti-rheumatic drugs.

PubMed

Kawashiri, Shin-Ya; Nishino, Ayako; Shimizu, Toshimasa; Umeda, Masataka; Fukui, Shoichi; Nakashima, Yoshikazu; Suzuki, Takahisa; Koga, Tomohiro; Iwamoto, Naoki; Ichinose, Kunihiro; Tamai, Mami; Nakamura, Hideki; Origuchi, Tomoki; Aoyagi, Kiyoshi; Kawakami, Atsushi

2017-03-01

We evaluated whether the early responsiveness of ultrasound synovitis can predict the clinical response in rheumatoid arthritis (RA) patients treated with biologic disease-modifying anti-rheumatic drugs (bDMARDs). Articular synovitis was assessed by ultrasound at 22 bilateral wrist and finger joints in 39 RA patients treated with bDMARDs. Each joint was assigned a gray-scale (GS) and power Doppler (PD) score from 0 to 3, and the sum of the GS or PD scores was considered to represent the ultrasound disease activity. We investigated the correlation of the change in ultrasound disease activity at three months with the EULAR response criteria at six months. GS and PD scores were significantly decreased at three months (p < 0.0001). The % changes of the GS and PD scores at three months were significantly higher at six months in moderate and good responders compared with non-responders (p < 0.05). These tendencies were numerically more prominent if clinical response was set as good responder or Disease Activity Score 28 remission. Poor improvement of ultrasound synovitis scores had good predictive value for non-responders at six months. The responsiveness of ultrasound disease activity is considered to predict further clinical response in RA patients treated with bDMARDs.

Evaluation of the end user (dentist) experience of undertaking clinical audit in the post April 2001 general dental services (GDS) scheme.

PubMed

Cannell, P J

2012-09-01

A mandatory scheme for clinical audit in the general dental services (GDS) was launched in April 2001. No evaluation of this mandatory scheme exists in the literature. This study provides an evaluation of this scheme. More recently a new dental contract was introduced in the general dental services (GDS) in April 2006. Responsibility for clinical audit activities was devolved to primary care trusts (PCTs) as part of their clinical governance remit. All GDPs within Essex were contacted by letter and invited to participate in the research. A qualitative research method was selected for this evaluation, utilising audio-taped semi-structured research interviews with eight general dental practitioners (GDPs) who had taken part in the GDS clinical audit scheme and who fitted the sampling criteria and strategy. The evaluation focused on dentists' experiences of the scheme. The main findings from the analysis of the GDS scheme data suggest that there is clear evidence of change following audit activities occurring within practices and for the benefit of patients. However, often it is the dentist only that undertakes a clinical audit project rather than the dental team, there is a lack of dissemination of project findings beyond the individual participating practices, very little useful feedback provided to participants who have completed a project and very limited use of formal re-auditing of a particular topic. This study provides evaluation of the GDS clinical audit scheme. Organisations who propose to undertake clinical audit activities in conjunction with dentistry in the future may benefit from incorporating and/or developing some findings from this evaluation into their project design and avoiding others.

The Glasgow Prognostic Score Predicts Response to Chemotherapy in Patients with Metastatic Breast Cancer.

PubMed

Wang, Dexing; Duan, Li; Tu, Zhiquan; Yan, Fei; Zhang, Cuicui; Li, Xu; Cao, Yuzhu; Wen, Hongsheng

2016-01-01

Breast cancer is one of the most common causes of cancer death in women worldwide. The Glasgow Prognostic Score (GPS), a cumulative prognostic score based on C-reactive protein and albumin, indicates the presence of a systemic inflammatory response. The GPS has been adopted as a powerful prognostic tool for patients with various types of malignant tumors, including breast cancer. The aim of this study was to assess the value of the GPS in predicting the response and toxicity in breast cancer patients treated with chemotherapy. Patients with metastatic breast cancers in a progressive stage for consideration of chemotherapy were eligible. The clinical characteristics and demographics were recorded. The GPS was calculated before the onset of chemotherapy. Data on the response to chemotherapy and progression-free survival (PFS) were also collected. Objective tumor responses were evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST). Toxicities were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTC) version 3.0 throughout therapy. In total, 106 breast cancer patients were recruited. The GPS was associated with the response rate (p = 0.05), the clinical benefit rate (p = 0.03), and PFS (p = 0.005). The GPS was the only independent predictor of PFS (p = 0.005). The GPS was significantly associated with neutropenia, thrombocytopenia, anorexia, nausea and vomiting, fatigue, and mucositis (p = 0.05-0.001). Our data demonstrate that GPS assessment is associated with poor clinical outcomes and severe chemotherapy-related toxicities in patients with metastatic breast cancer who have undergone chemotherapy, without any specific indication regarding the type of chemotherapy applied. © 2016 S. Karger AG, Basel.

Validity and reliability of a novel measure of activity performance and participation.

PubMed

Murgatroyd, Phil; Karimi, Leila

2016-01-01

To develop and evaluate an innovative clinician-rated measure, which produces global numerical ratings of activity performance and participation. Repeated measures study with 48 community-dwelling participants investigating clinical sensibility, comprehensiveness, practicality, inter-rater reliability, responsiveness, sensitivity and concurrent validity with Barthel Index. Important clinimetric characteristics including comprehensiveness and ease of use were rated >8/10 by clinicians. Inter-rater reliability was excellent on the summary scores (intraclass correlation of 0.95-0.98). There was good evidence that the new outcome measure distinguished between known high and low functional scoring groups, including both responsiveness to change and sensitivity at the same time point in numerous tests. Concurrent validity with the Barthel Index was fair to high (Spearman Rank Order Correlation 0.32-0.85, p > 0.05). The new measure's summary scores were nearly twice as responsive to change compared with the Barthel Index. Other more detailed data could also be generated by the new measure. The Activity Performance Measure is an innovative outcome instrument that showed good clinimetric qualities in this initial study. Some of the results were strong, given the sample size, and further trial and evaluation is appropriate. Implications for Rehabilitation The Activity Performance Measure is an innovative outcome measure covering activity performance and participation. In an initial evaluation, it showed good clinimetric qualities including responsiveness to change, sensitivity, practicality, clinical sensibility, item coverage, inter-rater reliability and concurrent validity with the Barthel Index. Further trial and evaluation is appropriate.

Association between new-onset hypothyroidism and clinical response in patients treated with tyrosine kinase inhibitor therapy in phase I clinical trials.

PubMed

Bilen, Mehmet Asim; Patel, Amy; Hess, Kenneth R; Munoz, Javier; Busaidy, Naifa L; Wheler, Jennifer J; Janku, Filip; Falchook, Gerald S; Hong, David S; Meric-Bernstam, Funda; Habra, Mouhammed Amir; Naing, Aung

2016-07-01

Tyrosine kinase inhibitor (TKI)-induced thyroid dysfunction has been identified as an important but manageable adverse effect of targeted therapy. Several studies have suggested that patients who develop hypothyroidism respond better to TKIs, but this relationship is not well elucidated. We evaluated the relationship between new-onset hypothyroidism and clinical response in patients with advanced cancers treated with TKIs at our institution. We retrospectively reviewed records for patients from four clinical trials that included at least one TKI  therapy between January 2006 and December 2011. Patients with preexisting thyroid disease, including thyroid cancer, hypothyroidism, or hyperthyroidism, were excluded. Analysis of 197 patients was performed. Response was determined using RECIST 1.0. Clinical benefit was described as complete response, partial response, or stable disease greater than 4 months. Multivariable logistic regression analysis was performed to correlate patient characteristics with clinical response. The median age for the 197 patients was 58 years (range, 13-85 years), and 56 % were female. Of the 197 patients, 52 (26 %) developed hypothyroidism after therapy. Clinical benefit rates were 50 % in patients with new-onset hypothyroidism versus 34 % in patients without hypothyroidism. In the univariate model, the odds ratio (OR) for new-onset hypothyroidism was 1.9 [95 % confidence interval (CI) (1.0, 3.6) and p = 0.05]. We grouped tumor types into six categories (breast, colorectal carcinoma, melanoma, non-small cell lung cancer, pancreas, and other). When adjusted for tumor type, age (>50 years) and sex, the OR was 2.9 [95 % CI (1.3, 6.5) and p = 0.012] for new-onset hypothyroidism. New-onset hypothyroidism was associated with favorable clinical response in patients who received TKI treatment.

Dissociation predicts treatment response in eye-movement desensitization and reprocessing for posttraumatic stress disorder.

PubMed

Bae, Hwallip; Kim, Daeho; Park, Yong Chon

2016-01-01

Using clinical data from a specialized trauma clinic, this study investigated pretreatment clinical factors predicting response to eye-movement desensitization and reprocessing (EMDR) among adult patients diagnosed with posttraumatic stress disorder (PTSD). Participants were evaluated using the Clinician-Administered PTSD Scale (CAPS), the Symptom Checklist-90-Revised, the Beck Depression Inventory, and the Dissociative Experiences Scale before treatment and were reassessed using the CAPS after treatment and at 6-month follow-up. A total of 69 patients underwent an average of 4 sessions of EMDR, and 60 (87%) completed the posttreatment evaluation, including 8 participants who terminated treatment prematurely. Intent-to-treat analysis revealed that 39 (65%) of the 60 patients were classified as responders and 21 (35%) as nonresponders when response was defined as more than a 30% decrease in total CAPS score. The nonresponders had higher levels of dissociation (depersonalization and derealization) and numbing symptoms, but other PTSD symptoms, such as avoidance, hyperarousal, and intrusion, were not significantly different. The number of psychiatric comorbidities was also associated with treatment nonresponse. The final logistic regression model yielded 2 significant variables: dissociation (p < .001) and more than 2 comorbidities compared to none (p < .05). These results indicate that complex symptom patterns in PTSD may predict treatment response and support the inclusion of the dissociative subtype of PTSD in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition.

Usability Evaluation of Electronic Health Record System around Clinical Notes Usage-An Ethnographic Study.

PubMed

Rizvi, Rubina F; Marquard, Jenna L; Hultman, Gretchen M; Adam, Terrence J; Harder, Kathleen A; Melton, Genevieve B

2017-10-01

Background A substantial gap exists between current Electronic Health Record (EHR) usability and potential optimal usability. One of the fundamental reasons for this discrepancy is poor incorporation of a User-Centered Design (UCD) approach during the Graphical User Interface (GUI) development process. Objective To evaluate usability strengths and weaknesses of two widely implemented EHR GUIs for critical clinical notes usage tasks. Methods Twelve Internal Medicine resident physicians interacting with one of the two EHR systems (System-1 at Location-A and System-2 at Location-B) were observed by two usability evaluators employing an ethnographic approach. User comments and observer findings were analyzed for two critical tasks: (1) clinical notes entry and (2) related information-seeking tasks. Data were analyzed from two standpoints: (1) usability references categorized by usability evaluators as positive, negative, or equivocal and (2) usability impact of each feature measured through a 7-point severity rating scale. Findings were also validated by user responses to a post observation questionnaire. Results For clinical notes entry, System-1 surpassed System-2 with more positive (26% vs. 12%) than negative (12% vs. 34%) usability references. Greatest impact features on EHR usability (severity score pertaining to each feature) for clinical notes entry were: autopopulation (6), screen options (5.5), communication (5), copy pasting (4.5), error prevention (4.5), edit ability (4), and dictation and transcription (3.5). Both systems performed equally well on information-seeking tasks and features with greatest impacts on EHR usability were navigation for notes (7) and others (e.g., looking for ancillary data; 5.5). Ethnographic observations were supported by follow-up questionnaire responses. Conclusion This study provides usability-specific insights to inform future, improved, EHR interface that is better aligned with UCD approach.

The effect of pneumatic dilation in management of postfundoplication dysphagia.

PubMed

Sunjaya, D; Podboy, A; Blackmon, S H; Katzka, D; Halland, M

2017-06-01

Fundoplication surgery is a commonly performed procedure for gastro-esophageal reflux disease or hiatal hernia repair. Up to 10% of patients develop persistent postoperative dysphagia after surgery. Data on the effectiveness of pneumatic dilation for treatment are limited. The aim of this study was to evaluate clinical outcomes and identify clinical factors associated with successful response to pneumatic dilation among patients with persistent postfundoplication dysphagia (PPFD). We retrospectively evaluated patients who had undergone pneumatic dilation for PPFD between 1999 and 2016. Patients with dysphagia or achalasia prior to fundoplication were excluded. Demographic information, surgical history, severity of dysphagia, and clinical outcomes were collected. Data pertaining to esophagram, manometry, endoscopy, and pneumatic dilation were also collected. We identified 38 patients (82% female, 95% Caucasian, and median age 59 years) with PPFD who completed pneumatic dilation. The median postfundoplication dysphagia score was 2. Eleven patients had abnormal peristalsis on manometry. Seventeen patients reported response (seven complete) with an average decrease of 1 in their dysphagia score. Fifteen patients underwent reoperation due to PPFD. Hiatal hernia repair was the only factor that predicts a higher response rate to pneumatic dilation. Only one patient in our study developed complication (pneumoperitoneum) from pneumatic dilation. We found that pneumatic dilation to be a safe treatment option for PPFD with moderate efficacy. Patients who developed PPFD after a hiatal hernia repair may gain the greatest benefit after pneumatic dilation. We were not able to identify additional clinical, radiological, endoscopic, or manometric parameters that were predictive of response. © 2017 John Wiley & Sons Ltd.

Posaconazole exposure-response relationship: evaluating the utility of therapeutic drug monitoring.

PubMed

Dolton, Michael J; Ray, John E; Marriott, Deborah; McLachlan, Andrew J

2012-06-01

Posaconazole has become an important part of the antifungal armamentarium in the prophylaxis and salvage treatment of invasive fungal infections (IFIs). Structurally related to itraconazole, posaconazole displays low oral bioavailability due to poor solubility, with significant drug interactions and gastrointestinal disease also contributing to the generally low posaconazole plasma concentrations observed in patients. While therapeutic drug monitoring (TDM) of plasma concentrations is widely accepted for other triazole antifungal agents such as voriconazole, the utility of TDM for posaconazole is controversial due to debate over the relationship between posaconazole exposure in plasma and clinical response to therapy. This review examines the available evidence for a relationship between plasma concentration and clinical efficacy for posaconazole, as well as evaluating the utility of TDM and providing provisional target concentrations for posaconazole therapy. Increasing evidence supports an exposure-response relationship for plasma posaconazole concentrations for prophylaxis and treatment of IFIs; a clear relationship has not been identified between posaconazole concentration and toxicity. Intracellular and intrapulmonary concentrations have been studied for posaconazole but have not been correlated to clinical outcomes. In view of the high mortality and cost associated with the treatment of IFIs, increasing evidence of an exposure-response relationship for posaconazole efficacy in the prevention and treatment of IFIs, and the common finding of low posaconazole concentrations in patients, TDM for posaconazole is likely to be of significant clinical utility. In patients with subtherapeutic posaconazole concentrations, increased dose frequency, administration with high-fat meals, and withdrawal of interacting medications from therapy are useful strategies to improve systemic absorption.

Malignant pleural mesothelioma: a phase II trial with docetaxel.

PubMed

Vorobiof, D A; Rapoport, B L; Chasen, M R; Abratt, R P; Cronje, N; Fourie, L; McMichael, G; Hacking, D

2002-03-01

Current cytotoxic therapy has been of limited benefit to patients with malignant pleural mesothelioma. Single agent chemotherapy has been extensively evaluated in small series of phase II clinical trials, with disappointing responses. Docetaxel, an effective taxane in the treatment of advanced breast cancer and non-small-cell lung cancer, was administered intravenously at a dose of 100 mg/m2 every 3 weeks to 30 chemotherapy naive patients with malignant pleural mesothelioma in a prospective multi-institutional phase II clinical trial. An objective response rate (partial responses) of 10% was documented. Additionally, 21% of the patients had minor responses (intention-to-treat analysis). Three patients died within 2 weeks post-first cycle of therapy, although only one patient's death was directly attributed to the investigational drug, whilst in the majority of the patients, manageable and treatable toxicities were encountered. In this phase II clinical trial, docetaxel proved to be mildly effective in the treatment of patients with malignant pleural mesothelioma.

Psychometric evaluation of a daily gastro-oesophageal reflux disease symptom measure.

PubMed

Bytzer, Peter; Reimer, Christina; Smith, Gary; Anatchkova, Milena D; Hsieh, Ray; Wilkinson, Joanne; Thomas, S Jane; Lenderking, William R

2017-03-01

The objective of this study was to evaluate the validity of the Heartburn Reflux Dyspepsia Questionnaire (HRDQ), a newly developed measure of gastro-oesophageal reflux disease (GORD) symptoms. Specifically, the HRDQ was developed for patients, who still experience symptoms with proton pump inhibitor (PPI) treatment. The psychometric properties of HRDQ were evaluated based on data from two clinical trials of patients with GORD with a partial response to PPIs, one from the UK and one from Denmark and Germany. The HRDQ had good internal consistency (Cronbach's alpha range .83-.88) and test-retest reliability (intraclass correlation coefficient range .71-.90). Convergent and discriminant validity were supported by high correlations with ReQuest™ and ability to differentiate between groups based on ReQuest™ cut-off values. Responsiveness of HRDQ was demonstrated by moderate to high correlations with ReQuest™ change scores and time with symptoms. An HRDQ cut-off value of 0.70 for definition of 'bad day' was also evaluated. Based on existing evidence, the HRDQ is a valid and reliable measure of GORD symptoms that can be used as a study outcome in clinical trials.

Peficitinib, an Oral Janus Kinase Inhibitor, in Moderate-to-Severe Ulcerative Colitis: Results From a Randomized, Phase 2 Study.

PubMed

Sands, Bruce E; Sandborn, William J; Feagan, Brian G; Lichtenstein, Gary R; Zhang, Hongyan; Strauss, Richard; Szapary, Philippe; Johanns, Jewel; Panes, Julian; Vermeire, Severine; O'Brien, Christopher D; Yang, Zijiang; Bertelsen, Kirk; Marano, Colleen

2018-06-15

Janus kinase (JAK) inhibitors have shown efficacy in ulcerative colitis (UC). We studied the dose-response, efficacy, and safety of peficitinib, an oral JAK inhibitor, in patients with moderate-to-severe UC. In this Phase 2b, dose-ranging trial, we evaluated peficitinib at 25mg once daily (qd), 75mg qd, 150mg qd, and 75mg twice daily versus placebo for efficacy and safety in 219 patients with moderate-to-severe UC. The primary outcome was peficitinib dose-response at Week 8 with response assessed using Mayo score change from baseline. Secondary endpoints were clinical response, clinical remission, mucosal healing, change from baseline in Inflammatory Bowel Disease Questionnaire (IBDQ), and normalization of inflammatory biomarkers at Week 8; other secondary endpoints were treatment response through Week 16 and through Week 32 for patients in clinical response at Week 8. Safety was assessed through Week 36 or 4 weeks after the last dose. A statistically significant peficitinib dose-response was not demonstrated at Week 8, although a numerically greater proportion of patients receiving peficitinib ≥75mg qd achieved clinical response, remission, and mucosal healing at Week 8, supported by IBDQ improvement and inflammatory biomarker normalization. Treatment-emergent adverse event (TEAE) rates reported through Week 8 and the final safety visit were higher in the combined peficitinib group than placebo; patients receiving doses of ≥75mg qd peficitinib reported TEAEs more frequently. While no dose-response in patients with moderate-to-severe UC was demonstrated with peficitinib, evidence of efficacy was suggested at doses ≥75mg qd. The safety profile of peficitinib was consistent with current information. ClinicalTrials.gov NCT01959282.

Electrochemotherapy efficacy evaluation for treatment of locally advanced stage III cutaneous squamous cell carcinoma: a 22-cases retrospective analysis.

PubMed

Di Monta, Gianluca; Caracò, Corrado; Simeone, Ester; Grimaldi, Antonio Maria; Marone, Ugo; Di Marzo, Massimiliano; Vanella, Vito; Festino, Lucia; Palla, Marco; Mori, Stefano; Mozzillo, Nicola; Ascierto, Paolo Antonio

2017-04-26

Extensive squamous cell carcinoma has few therapeutic options. In such cases, electrochemotherapy involving electroporation combined with antineoplastic drug appears to be a new potential option and may be considered as an alternative treatment. The aim of this retrospective single-center study was to evaluate electrochemotherapy efficacy in treatment of locally advanced stage III squamous cell carcinoma, in which surgical procedures would have entailed wide tissue sacrifice. Clinical features, treatment response, and adverse effects were evaluated in 22 patients treated with electrochemotherapy with intravenous injection of bleomycin for extensive stage III cutaneous squamous cell carcinoma. Treatment of cutaneous lesions were performed according to the European Standard Operating Procedures of Electrochemotherapy. Overall response to electrochemotherapy treatment was observed in 18 (81.8%) patients. Clinical response with necrosis of tumor mass was observed from the first session and lasted for all follow up period that ranged between 5 and 48 months with a median of 34 months. Overall the treatment was well tolerated with a very low complication rate. Electrochemotherapy represents a safe and effective therapeutic approach, associated with a good tolerability.

Periodontitis in pregnancy: clinical and serum antibody observations from a baboon model of ligature-induced disease.

PubMed

Cappelli, D; Steffen, M J; Holt, S C; Ebersole, J L

2009-07-01

Chronic oral infections that elicit host responses leading to periodontal disease are linked with various sequelae of systemic diseases. This report provides seminal information on the clinical and adaptive immunologic characteristics of a baboon model of ligature-induced periodontitis during pregnancy. Female Papio anubis were evaluated for periodontal health at baseline. Ligatures were tied around selected teeth to initiate oral inflammation and periodontitis. Then the animals were bred. At midpregnancy ( approximately 90 days), a clinical evaluation was performed, and additional ligatures were tied on teeth in the contralateral quadrants to maintain progressing periodontitis throughout pregnancy. A final clinical evaluation was done for all experimental teeth after delivery, and ligatures were removed. Serum was collected at all sampling intervals for the determination of antibody levels to a group of 20 oral bacteria. Unligated animals served as controls. At baseline, 16% of animals exhibited minimal plaque and gingival inflammation without periodontal disease. The remaining baboons demonstrated varying levels of inflammation/bleeding, and approximately 20% of the population had periodontal pocketing (>3 mm). Ligated animals expressed increased levels of inflammation and increased probing depths and clinical attachment loss (AL) and could be stratified into multiple subsets postligation based upon changes in clinical parameters at midpregnancy and at delivery. Baboons were categorized into disease susceptibility groups (periodontal disease susceptibility 1 through 4) that described the extent/severity of induced disease during pregnancy. Control animals showed minimal periodontal changes during gestation. Significant differences in serum antibody to multiple oral bacteria were found in animals presenting with periodontitis at baseline and during the 6 months of ligature-induced disease. A significant correlation to antibody to P. gingivalis, which was sustained throughout ligation and pregnancy, was observed with disease presentation. The clinical presentation at baseline, reflecting the natural history of oral disease in these animals, suggests individual variation that is reflected in the characteristics of the adaptive immune responses to oral bacteria. The variability in the response to ligation with resulting periodontal disease provides a model to document prospectively the relationship between oral and systemic health outcomes.

Effectiveness Study of Paromomycin IM Injection (PMIM) for the Treatment of Visceral Leishmaniasis (VL) in Bangladesh.

PubMed

Jamil, Kazi M; Haque, Rashidul; Rahman, Ridwanur; Faiz, M Abul; Bhuiyan, Abu Toha Md Rezwanul Haque; Kumar, Amresh; Hassan, Syed Misbah; Kelly, Heather; Dhalaria, Pritu; Kochhar, Sonali; Desjeux, Philippe; Bhuiyan, Mohammad A A; Khan, Mohammed M; Ghosh, Raj Shankar

2015-01-01

This study was conducted in Bangladeshi patients in an outpatient setting to support registration of Paromomycin Intramuscular Injection (PMIM) as a low-cost treatment option in Bangladesh. This Phase IIIb, open-label, multi-center, single-arm trial assessed the efficacy and safety of PMIM administered at 11 mg/kg (paromomycin base) intramuscularly once daily for 21 consecutive days to children and adults with VL in a rural outpatient setting in Bangladesh. Patients ≥5 and ≤55 years were eligible if they had signs and symptoms of VL (intermittent fever, weight loss/decreased appetite, and enlarged spleen), positive rK39 test, and were living in VL-endemic areas. Compliance was the percentage of enrolled patients who received 21 daily injections over no more than 22 days. Efficacy was evaluated by initial clinical response, defined as resolution of fever and reduction of splenomegaly at end of treatment, and final clinical response, defined as the absence of new clinical signs and symptoms of VL 6 months after end of treatment. Safety was assessed by evaluation of adverse events. A total of 120 subjects (49% pediatric) were enrolled. Treatment compliance was 98.3%. Initial clinical response in the Intent-to-Treat population was 98.3%, and final clinical response 6 months after end of treatment was 94.2%. Of the 119 subjects who received ≥1 dose of PMIM, 28.6% reported at least one adverse event. Injection site pain was the most commonly reported adverse event. Reversible renal impairment and/or hearing loss were reported in 2 subjects. PMIM was an effective and safe treatment for VL in Bangladesh. The short treatment duration and lower cost of PMIM compared with other treatment options may make this drug a preferred treatment to be investigated as part of a combination therapy regimen. This study supports the registration of PMIM for use in government health facilities in Bangladesh. ClinicalTrials.gov identifier: NCT01328457.

Role of Nonsteroidal Anti-inflammatory Drug in Treatment of Extra-abdominal Desmoid Tumors.

PubMed

Cho, Ja Young; Gupta, Sanjay; Cho, Hwan Seong; Park, Min Suk; Mok, Su Jung; Han, Ilkyu; Kim, Han-Soo

2018-06-01

We retrospectively reviewed the outcomes of patients who had been treated with meloxicam for the extra-abdominal desmoid tumors and evaluated the correlation between clinical outcome and clinic pathological variables. Twenty patients treated with meloxicam were followed up every 3 to 6 months. Meloxicam administration was planned at 15 mg/day orally for 6 months. Of the 20 patients evaluated, according to Response Evaluation Criteria in Solid Tumors criteria, there were five patients with partial response (25.0%), eight with stable disease (40.0%), and seven with tumor progression (35.0%). The cumulative probability of dropping out from our nonsurgical strategy using meloxicam was 35.0% at 1 year and 35.0% at 5 years. The present study suggests that conservative treatment would be a primary treatment option for this perplexing disease even though we were not able to determine that the use of a cyclooxygenase-2 inhibitor would have an additional influence on the natural course of a desmoid tumor.

Integrating service development with evaluation in telehealthcare: an ethnographic study

PubMed Central

Finch, Tracy; May, Carl; Mair, Frances; Mort, Maggie; Gask, Linda

2003-01-01

Objectives To identify issues that facilitate the successful integration of evaluation and development of telehealthcare services. Design Ethnographic study using various qualitative research techniques to obtain data from several sources, including in-depth semistructured interviews, project steering group meetings, and public telehealthcare meetings. Setting Seven telehealthcare evaluation projects (four randomised controlled trials and three pragmatic service evaluations) in the United Kingdom, studied over two years. Projects spanned a range of specialties—dermatology, psychiatry, respiratory medicine, cardiology, and oncology. Participants Clinicians, managers, technical experts, and researchers involved in the projects. Results and discussion Key problems in successfully integrating evaluation and service development in telehealthcare are, firstly, defining existing clinical practices (and anticipating changes) in ways that permit measurement; secondly, managing additional workload and conflicting responsibilities brought about by combining clinical and research responsibilities (including managing risk); and, thirdly, understanding various perspectives on effectiveness and the limitations of evaluation results beyond the context of the research study. Conclusions Combined implementation and evaluation of telehealthcare systems is complex, and is often underestimated. The distinction between quantitative outcomes and the workability of the system is important for producing evaluative knowledge that is of practical value. More pragmatic approaches to evaluation, that permit both quantitative and qualitative methods, are required to improve the quality of such research and its relevance for service provision in the NHS. PMID:14630758

[Multifocal visual electrophysiology in visual function evaluation].

PubMed

Peng, Shu-Ya; Chen, Jie-Min; Liu, Rui-Jue; Zhou, Shu; Liu, Dong-Mei; Xia, Wen-Tao

2013-08-01

Multifocal visual electrophysiology, consisting of multifocal electroretinography (mfERG) and multifocal visual evoked potential (mfVEP), can objectively evaluate retina function and retina-cortical conduction pathway status by stimulating many local retinal regions and obtaining each local response simultaneously. Having many advantages such as short testing time and high sensitivity, it has been widely used in clinical ophthalmology, especially in the diagnosis of retinal disease and glaucoma. It is a new objective technique in clinical forensic medicine involving visual function evaluation of ocular trauma in particular. This article summarizes the way of stimulation, the position of electrodes, the way of analysis, the visual function evaluation of mfERG and mfVEP, and discussed the value of multifocal visual electrophysiology in forensic medicine.

Quantitative EEG features selection in the classification of attention and response control in the children and adolescents with attention deficit hyperactivity disorder.

PubMed

Bashiri, Azadeh; Shahmoradi, Leila; Beigy, Hamid; Savareh, Behrouz A; Nosratabadi, Masood; N Kalhori, Sharareh R; Ghazisaeedi, Marjan

2018-06-01

Quantitative EEG gives valuable information in the clinical evaluation of psychological disorders. The purpose of the present study is to identify the most prominent features of quantitative electroencephalography (QEEG) that affect attention and response control parameters in children with attention deficit hyperactivity disorder. The QEEG features and the Integrated Visual and Auditory-Continuous Performance Test ( IVA-CPT) of 95 attention deficit hyperactivity disorder subjects were preprocessed by Independent Evaluation Criterion for Binary Classification. Then, the importance of selected features in the classification of desired outputs was evaluated using the artificial neural network. Findings uncovered the highest rank of QEEG features in each IVA-CPT parameters related to attention and response control. Using the designed model could help therapists to determine the existence or absence of defects in attention and response control relying on QEEG.

Very Early PSA Response to Abiraterone in mCRPC Patients: A Novel Prognostic Factor Predicting Overall Survival.

PubMed

Facchini, Gaetano; Caffo, Orazio; Ortega, Cinzia; D'Aniello, Carmine; Di Napoli, Marilena; Cecere, Sabrina C; Della Pepa, Chiara; Crispo, Anna; Maines, Francesca; Ruatta, Fiorella; Iovane, Gelsomina; Pisconti, Salvatore; Montella, Maurizio; Berretta, Massimiliano; Pignata, Sandro; Cavaliere, Carla

2016-01-01

Abiraterone Acetate (AA) is approved for the treatment of mCRPC after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated and for treatment of mCRPC progressed during or after docetaxel-based chemotherapy regimen. The aim of this study is to evaluate the role of early PSA decline for detection of therapy success or failure in mCRPC patients treated with AA in post chemotherapy setting. We retrospectively evaluated 87 patients with mCRPC treated with AA. Serum PSA levels were evaluated after 15, 90 days and then monthly. The PSA flare phenomenon was evaluated, according to a confirmation value at least 1 week apart. The primary endpoint was to demonstrate that an early PSA decline correlates with a longer progression free survival (PFS) and overall survival (OS). The secondary endpoind was to demonstrate a correlation between better outcome and demographic and clinical patient characteristics. We have collected data of 87 patients between Sep 2011 and Sep 2014. Early PSA response (≥50% from baseline at 15 days) was found in 56% evaluated patients and confirmed in 29 patients after 90 days. The median PFS was 5.5 months (4.6-6.5) and the median OS was 17.1 months (8.8-25.2). In early responders patients (PSA RR ≥ 50% at 15 days), we found a significant statistical advantage in terms of PFS at 1 year, HR 0.28, 95%CI 0.12-0.65, p = 0.003, and OS, HR 0.21 95% CI 0.06-0.72, p = 0.01. The results in PFS at 1 years and OS reached statistical significance also in the evaluation at 90 days. A significant proportion (78.6%) of patients achieved a rapid response in terms of PSA decline. Early PSA RR (≥50% at 15 days after start of AA) can provide clinically meaningful information and can be considered a surrogate of longer PFS and OS.

First clinical evaluation of a new long-term subconjunctival glucose sensor.

PubMed

Müller, Achim Josef; Knuth, Monika; Nikolaus, Katharina Sibylle; Herbrechtsmeier, Peter

2012-07-01

To evaluate the feasibility of an implantable subconjunctival glucose monitoring system (SGMS) for glucose monitoring in humans, we investigated the in vivo performance of the sensor in a clinical trial with five patients. The new SGMS consists of an implantable ocular mini implant (OMI) and a hand-held fluorescence photometer. The implantable subconjunctival glucose sensor is composed of a fluorescence resonance energy transfer system based on Concanavalin A chemistry, embedded in a nelfilcon polymer hydrogel disk. Blood glucose changes in humans were induced by oral glucose intake and insulin injections. The in vivo response of the new SGMS was tested in a first human clinical study with five diabetes patients. The OMI was well tolerated in the eyes of the patients. The SGMS exhibited high correlation coefficients (>0.88) with blood glucose changes and a good stability of the sensor response to glucose for the study period of 2 weeks. Lag times were in the range of 5-10 min. A total of 98% of all data pairs was in the clinical acceptable ranges A and B of the consensus error grid. For the first time, the possibility to measure glucose in vivo in the subconjunctival interstitial fluid for a period of 2 weeks was demonstrated in a human clinical trial. © 2012 Diabetes Technology Society.

Developing a multi-component immune model for evaluating the risk of respiratory illness in athletes.

PubMed

Gleeson, Maree; Pyne, David B; Elkington, Lisa J; Hall, Sharron T; Attia, John R; Oldmeadow, Christopher; Wood, Lisa G; Callister, Robin

2017-01-01

Clinical and laboratory identification of the underlying risk of respiratory illness in athletes has proved problematic. The aim of this study was to determine whether clinical data, combined with immune responses to standardised exercise protocols and genetic cytokine polymorphism status, could identify the risk of respiratory illness (symptoms) in a cohort of highly-trained athletes. Male endurance athletes (n=16; VO2max 66.5 ± 5.1 mL.kg-1.min-1) underwent a clinical evaluation of known risk factors by a physician and comprehensive laboratory analysis of immune responses both at rest and after two cycling ergometer tests: 60 min at 65% VO2max (LONG); and 6 x 3 min intervals at 90% VO2max (INTENSE). Blood tests were performed to determine Epstein Barr virus (EBV) status and DNA was genotyped for a panel of cytokine gene polymorphisms. Saliva was collected for measurement of IgA and detection of EBV DNA. Athletes were then followed for 9 months for self-reported episodes of respiratory illness, with confirmation of the underlying cause by a sports physician. There were no associations with risk of respiratory illness identified for any parameter assessed in the clinical evaluations. The laboratory parameters associated with an increased risk of respiratory illnesses in highly-trained athletes were cytokine gene polymorphisms for the high expression of IL-6 and IFN-ɣ; expression of EBV-DNA in saliva; and low levels of salivary IgA concentration. A genetic risk score was developed for the cumulative number of minor alleles for the cytokines evaluated. Athletes prone to recurrent respiratory illness were more likely to have immune disturbances that allow viral reactivation, and a genetic predisposition to pro-inflammatory cytokine responses to intense exercise. Copyright © 2016 International Society of Exercise and Immunology. All rights reserved.

Therapeutic efficacy of sulfadoxine-pyrimethamine, amodiaquine and the sulfadoxine-pyrimethamine-amodiaquine combination against uncomplicated Plasmodium falciparum malaria in young children in Cameroon.

PubMed Central

Basco, Leonardo K.; Same-Ekobo, Albert; Ngane, Vincent Foumane; Ndounga, Mathieu; Metoh, Theresia; Ringwald, Pascal; Soula, Georges

2002-01-01

OBJECTIVE: To evaluate the therapeutic efficacy of sulfadoxine-pyrimethamine, amodiaquine, and the sulfadoxine-pyrimethamine-amodiaquine combination for the treatment of uncomplicated Plasmodium falciparum malaria in young children in Cameroon. METHODS: In a randomized study we evaluated the effectiveness and tolerance of (i) sulfadoxine-pyrimethamine (SP) (25 mg/kg body weight of sulfadoxine and 1.25 mg/kg of pyrimethamine in a single oral dose), (ii) amodiaquine (AQ) (30 mg/kg body weight in three divided daily doses), and (iii) the sulfadoxine-pyrimethamine-amodiaquine combination (SP+AQ) (same doses as in the other two treatment groups, given simultaneously on day 0) in young children in southern Cameroon. The parasitological and clinical responses were studied until day 28 in accordance with the modified 1996 WHO protocol for the evaluation of the therapeutic efficacy of antimalarial drugs. FINDINGS: Of 191 enrolled patients, 6 and 8 were excluded or lost to follow-up before day 14 and between day 14 and day 28, respectively. For the AQ-treated patients, parasitological and clinical evaluation on day 14 showed late treatment failure in 2 of 61 (3.3%) and adequate clinical response with parasitological failure in one (1.6%). There was an adequate clinical response in all patients treated with SP or SP+AQ. Therapeutic failure rates on day 28 were 13.6%, 10.2% and 0% in the SP, AQ, and SP+AQ groups, respectively. Anaemia improved in all three regimens. AQ produced faster fever clearance but was associated with more transient minor side-effects than SP. SP+AQ reduced the risk of recrudescence between day 14 and day 28 but increased the incidence of minor side-effects. CONCLUSION: SP+AQ can be recommended as a temporary means of slowing the spread of multidrug resistance in Plasmodium falciparum in Africa while the introduction of other combinations, including artemisinin derivatives, is awaited. PMID:12163917

Simulation-Based Dysphagia Training: Teaching Interprofessional Clinical Reasoning in a Hospital Environment.

PubMed

Miles, Anna; Friary, Philippa; Jackson, Bianca; Sekula, Julia; Braakhuis, Andrea

2016-06-01

This study evaluated hospital readiness and interprofessional clinical reasoning in speech-language pathology and dietetics students following a simulation-based teaching package. Thirty-one students participated in two half-day simulation workshops. The training included orientation to the hospital setting, part-task skill learning and immersive simulated cases. Students completed workshop evaluation forms. They filled in a 10-question survey regarding confidence, knowledge and preparedness for working in a hospital environment before and immediately after the workshops. Students completed written 15-min clinical vignettes at 1 month prior to training, immediately prior to training and immediately after training. A marking rubric was devised to evaluate the responses to the clinical vignettes within a framework of interprofessional education. The simulation workshops were well received by all students. There was a significant increase in students' self-ratings of confidence, preparedness and knowledge following the study day (p < .001). There was a significant increase in student overall scores in clinical vignettes after training with the greatest increase in clinical reasoning (p < .001). Interprofessional simulation-based training has benefits in developing hospital readiness and clinical reasoning in allied health students.

Passing the baton: a grounded practical theory of handoff communication between multidisciplinary providers in two Department of Veterans Affairs outpatient settings.

PubMed

Koenig, Christopher J; Maguen, Shira; Daley, Aaron; Cohen, Greg; Seal, Karen H

2013-01-01

Handoffs are communication processes that enact the transfer of responsibility between providers across clinical settings. Prior research on handoff communication has focused on inpatient settings between provider teams and has emphasized patient safety. This study examines handoff communication within multidisciplinary provider teams in two outpatient settings. To conduct an exploratory study that describes handoff communication among multidisciplinary providers, to develop a theory-driven descriptive framework for outpatient handoffs, and to evaluate the strengths and weaknesses of different handoff types. Qualitative, in-depth, semi-structured interviews with 31 primary care, mental health, and social work providers in two Department of Veterans Affairs (VA) Medical Center outpatient clinics. Audio-recorded interviews were transcribed and analyzed using Grounded Practical Theory to develop a theoretical model of and a descriptive framework for handoff communication among multidisciplinary providers. Multidisciplinary providers reported that handoff decisions across settings were made spontaneously and without clear guidelines. Two situated values, clinic efficiency and patient-centeredness, shaped multidisciplinary providers' handoff decisions. Providers reported three handoff techniques along a continuum: the electronic handoff, which was the most clinically efficient; the provider-to-provider handoff, which balanced clinic efficiency and patient-centeredness; and the collaborative handoff, which was the most patient-centered. Providers described handoff choice as a practical response to manage constituent features of clinic efficiency (time, space, medium of communication) and patient-centeredness (information continuity, management continuity, relational continuity, and social interaction). We present a theoretical and descriptive framework to help providers evaluate differential handoff use, reflect on situated values guiding clinic communication, and guide future research. Handoff communication reflected multidisciplinary providers' efforts to balance clinic efficiency with patient-centeredness within the constraints of day-to-day clinical practice. Evaluating the strengths and weaknesses among alternative handoff options may enhance multidisciplinary provider handoff decision-making and may contribute to increased coordination and continuity of care across outpatient settings.

Rating the raters: assessing the quality of Hamilton rating scale for depression clinical interviews in two industry-sponsored clinical drug trials.

PubMed

Engelhardt, Nina; Feiger, Alan D; Cogger, Kenneth O; Sikich, Dawn; DeBrota, David J; Lipsitz, Joshua D; Kobak, Kenneth A; Evans, Kenneth R; Potter, William Z

2006-02-01

The quality of clinical interviews conducted in industry-sponsored clinical drug trials is an important but frequently overlooked variable that may influence the outcome of a study. We evaluated the quality of Hamilton Rating Scale for Depression (HAM-D) clinical interviews performed at baseline in 2 similar multicenter, randomized, placebo-controlled depression trials sponsored by 2 pharmaceutical companies. A total of 104 audiotaped HAM-D clinical interviews were evaluated by a blinded expert reviewer for interview quality using the Rater Applied Performance Scale (RAPS). The RAPS assesses adherence to a structured interview guide, clarification of and follow-up to patient responses, neutrality, rapport, and adequacy of information obtained. HAM-D interviews were brief and cursory and the quality of interviews was below what would be expected in a clinical drug trial. Thirty-nine percent of the interviews were conducted in 10 minutes or less, and most interviews were rated fair or unsatisfactory on most RAPS dimensions. Results from our small sample illustrate that the clinical interview skills of raters who administered the HAM-D were below what many would consider acceptable. Evaluation and training of clinical interview skills should be considered as part of a rater training program.

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

PubMed

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.

Effect of comorbid tics on a clinically meaningful response to 8-week open-label trial of fluoxetine in obsessive compulsive disorder.

PubMed

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.

High serum soluble tumor necrosis factor receptor 1 predicts poor treatment response in acute-stage schizophrenia.

PubMed

Nishimon, Shohei; Ohnuma, Tohru; Takebayashi, Yuto; Katsuta, Narimasa; Takeda, Mayu; Nakamura, Toru; Sannohe, Takahiro; Higashiyama, Ryoko; Kimoto, Ayako; Shibata, Nobuto; Gohda, Tomohito; Suzuki, Yusuke; Yamagishi, Sho-Ichi; Tomino, Yasuhiko; Arai, Heii

2017-06-02

Inflammation may be involved in the pathophysiology of schizophrenia. However, few cross-sectional or longitudinal studies have examined changes in biomarker expression to evaluate diagnostic and prognostic efficacy in acute-stage schizophrenia. We compared serum inflammatory biomarker concentrations in 87 patients with acute-stage schizophrenia on admission to 105 age-, sex-, and body mass index (BMI)-matched healthy controls. The measured biomarkers were soluble tumor necrosis factor receptor 1 (sTNFR1) and adiponectin, which are associated with inflammatory responses, and pigment epithelium-derived factor (PEDF), which has anti-inflammatory properties. We then investigated biomarker concentrations and associations with clinical factors in 213 patients (including 42 medication-free patients) and 110 unmatched healthy controls to model conditions typical of clinical practice. Clinical symptoms were assessed using the Brief Psychiatric Rating Scale and Global Assessment of Function. In 121 patients, biomarker levels and clinical status were evaluated at both admission and discharge. Serum sTNFR1 was significantly higher in patients with acute-stage schizophrenia compared to matched controls while no significant group differences were observed for the other markers. Serum sTNFR1 was also significantly higher in the 213 patients compared to unmatched controls. The 42 unmedicated patients had significantly lower PEDF levels compared to controls. Between admission and discharge, sTNFR1 levels decreased significantly; however, biomarker changes did not correlate with clinical symptoms. The discriminant accuracy of sTNFR1 was 93.2% between controls and patients, showing no symptom improvement during care. Inflammation and a low-level anti-inflammatory state may be involved in both schizophrenia pathogenesis and acute-stage onset. High serum sTNFR1 in the acute stage could be a useful prognostic biomarker for treatment response in clinical practice. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaluation of a spontaneous canine model of immunoglobulin E-mediated food hypersensitivity: dynamic changes in serum and fecal allergen-specific immunoglobulin E values relative to dietary change.

PubMed

Jackson, Hilary A; Hammerberg, Bruce

2002-08-01

The purpose of the pilot study reported here was to evaluate serum and fecal total and allergen-specific immunoglobulin E (IgE) responses to dietary change in five Maltese x beagle dogs with suspected food hypersensitivity, compared with those of five clinically normal dogs. Clinical parameters (pruritus, otitis, and diarrhea) improved in the Maltese x beagle dogs during feeding of a novel diet, and signs were exacerbated by oral allergen provocation. Relative concentrations of serum and fecal wheat-, corn-, and milk-specific IgE were determined by use of an ELISA. The onset of clinical signs of disease was accompanied by an increase in serum allergen-specific IgE concentrations. In contrast, changes in clinical signs of disease or allergen-specific IgE values were not seen in the control group undergoing the same regimen. Total serum IgE concentration was measured by use of the ELISA, and comparison with known quantities of a monoclonal IgE allowed absolute values to be reported. Values were high in the Maltese x beagle colony (7 to 34 microg/ml), compared with those in the control dogs (0.7 to 6 microg/ml). Total serum and total fecal IgE concentrations did not change in either group during the study. Although allergen-specific IgE was detected in the feces of both groups, significant interassay variability made interpretation of the results difficult. The authors concluded that these Maltese x beagle dogs satisfied the currently recognized clinical criteria for the diagnosis of canine food hypersensitivity. Furthermore, the clinical and serologic responses seen in these dogs in response to oral allergen provocation suggest that this may be a useful model for the study of spontaneous food hypersensitivity.

Predicting the Naturalistic Course of Major Depressive Disorder Using Clinical and Multimodal Neuroimaging Information: A Multivariate Pattern Recognition Study.

PubMed

Schmaal, Lianne; Marquand, Andre F; Rhebergen, Didi; van Tol, Marie-José; Ruhé, Henricus G; van der Wee, Nic J A; Veltman, Dick J; Penninx, Brenda W J H

2015-08-15

A chronic course of major depressive disorder (MDD) is associated with profound alterations in brain volumes and emotional and cognitive processing. However, no neurobiological markers have been identified that prospectively predict MDD course trajectories. This study evaluated the prognostic value of different neuroimaging modalities, clinical characteristics, and their combination to classify MDD course trajectories. One hundred eighteen MDD patients underwent structural and functional magnetic resonance imaging (MRI) (emotional facial expressions and executive functioning) and were clinically followed-up at 2 years. Three MDD trajectories (chronic n = 23, gradual improving n = 36, and fast remission n = 59) were identified based on Life Chart Interview measuring the presence of symptoms each month. Gaussian process classifiers were employed to evaluate prognostic value of neuroimaging data and clinical characteristics (including baseline severity, duration, and comorbidity). Chronic patients could be discriminated from patients with more favorable trajectories from neural responses to various emotional faces (up to 73% accuracy) but not from structural MRI and functional MRI related to executive functioning. Chronic patients could also be discriminated from remitted patients based on clinical characteristics (accuracy 69%) but not when age differences between the groups were taken into account. Combining different task contrasts or data sources increased prediction accuracies in some but not all cases. Our findings provide evidence that the prediction of naturalistic course of depression over 2 years is improved by considering neuroimaging data especially derived from neural responses to emotional facial expressions. Neural responses to emotional salient faces more accurately predicted outcome than clinical data. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Treatment with DAV for advanced-stage hemangiosarcoma in dogs.

PubMed

Dervisis, Nikolaos G; Dominguez, Pedro A; Newman, Rebecca G; Cadile, Casey D; Kitchell, Barbara E

2011-01-01

Hemangiosarcoma (HSA) is an aggressive disease that is fairly common in the dog. The authors evaluated a doxorubicin, dacarbazine, and vincristine (DAV) combination protocol in dogs with nonresectable stage II and stage III HSA. Twenty-four dogs were enrolled in this prospective, phase 2 study. Doxorubicin and dacarbazine were administered on day 1 while vincristine was administered on days 8 and 15. The protocol was repeated every 21 days for a maximum of six cycles or until disease progression. Toxicity and efficacy were assessed by clinical and laboratory evaluation and by questionnaires completed by the owners. Of the 24 included dogs, 19 were evaluable for response. The response rate (including five complete responses and four partial responses) was 47.4%. Median time to tumor progression was 101 days and median overall survival was 125 days. Significant toxicities were noted, including 41 high-grade hematologic and 12 high-grade gastrointestinal toxic events. Five dogs discontinued treatment due to chemotherapy-related toxicities, but no treatment-related deaths occurred. Multivariate analysis identified patient age (relative risk [RR], 2.3, P=0.049) to be negatively associated with time to progression whereas dacarbazine dose reductions (RR, 0.06, P=0.031) were positively associated with time to progression. Dacarbazine dose reduction was the sole factor positively associated with overall survival (RR, 0.28, P=0.015). In conclusion, the DAV combination appears to offer clinical responses and may prolong survival in dogs with advanced-stage HSA.

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

PubMed

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.

Clinical comparison and complete cure rates of Terbinafine efficacy in affected onychomycotic toenails.

PubMed

Shemer, A; Sakka, N; Baran, R; Scher, R; Amichai, B; Norman, L; Farhi, R; Magun, R; Brazilai, A; Daniel, R

2015-03-01

Clinical studies regarding complete cure rate of onychomycosis using oral Terbinafine have a very broad range (14-90%) based solely on response to treatment on the big toenail. To evaluate the efficacy of Terbinafine in all affected onychomycotic toenails and, furthermore, to evaluate differences in mycological, clinical and complete cure rate between affected onychomycotic toenails. Inclusion criteria are as follows: distolateralsubungual onychomycotic involvement of the hallux and additional involvement of at least two more toenails of the same foot. Exclusion criteria are as follows: patients with nail traumata and hypersensitivity to Terbinafine. Patients were treated with oral Terbinafine 250 mg/day for 16 weeks. Mycological analysis was performed using direct microscopy and culture. Clinical improvement was assessed using digital photography. Statistically significant difference was found in clinical improvement between the great toenail and all other involved toenails. The rate of complete cure (100% clinical cure and mycological cure) of the big toenail was lower (23%) as compared to the second (65%), third (51%) and the fourth toenail (67%). This is a case series study that was based on a single-centre cohort. Our results support findings that efficacy of Terbinafine should be based on all involved onychomycotic toenails; the big toenail is not superior in response compared to other affected toenails. © 2014 European Academy of Dermatology and Venereology.

An Argument-Based Approach to the Validation of UHTRUST: Can We Measure How Recent Graduates Can Be Trusted with Unfamiliar Tasks?

ERIC Educational Resources Information Center

Wijnen-Meijer, M.; Van der Schaaf, M.; Booij, E.; Harendza, S.; Boscardin, C.; Wijngaarden, J. Van; Ten Cate, Th. J.

2013-01-01

There is a need for valid methods to assess the readiness for clinical practice of medical graduates. This study evaluates the validity of Utrecht Hamburg Trainee Responsibility for Unfamiliar Situations Test (UHTRUST), an authentic simulation procedure to assess whether medical trainees are ready to be entrusted with unfamiliar clinical tasks…

Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification

PubMed Central

Cheson, Bruce D.; Fisher, Richard I.; Barrington, Sally F.; Cavalli, Franco; Schwartz, Lawrence H.; Zucca, Emanuele; Lister, T. Andrew

2014-01-01

The purpose of this work was to modernize recommendations for evaluation, staging, and response assessment of patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). A workshop was held at the 11th International Conference on Malignant Lymphoma in Lugano, Switzerland, in June 2011, that included leading hematologists, oncologists, radiation oncologists, pathologists, radiologists, and nuclear medicine physicians, representing major international lymphoma clinical trials groups and cancer centers. Clinical and imaging subcommittees presented their conclusions at a subsequent workshop at the 12th International Conference on Malignant Lymphoma, leading to revised criteria for staging and of the International Working Group Guidelines of 2007 for response. As a result, fluorodeoxyglucose (FDG) positron emission tomography (PET)–computed tomography (CT) was formally incorporated into standard staging for FDG-avid lymphomas. A modification of the Ann Arbor descriptive terminology will be used for anatomic distribution of disease extent, but the suffixes A or B for symptoms will only be included for HL. A bone marrow biopsy is no longer indicated for the routine staging of HL and most diffuse large B-cell lymphomas. However, regardless of stage, general practice is to treat patients based on limited (stages I and II, nonbulky) or advanced (stage III or IV) disease, with stage II bulky disease considered as limited or advanced disease based on histology and a number of prognostic factors. PET-CT will be used to assess response in FDG-avid histologies using the 5-point scale. The product of the perpendicular diameters of a single node can be used to identify progressive disease. Routine surveillance scans are discouraged. These recommendations should improve evaluation of patients with lymphoma and enhance the ability to compare outcomes of clinical trials. PMID:25113753

Clinical evaluation of postpartum vaginal mucus reflects uterine bacterial infection and the immune response in cattle.

PubMed

Williams, Erin J; Fischer, Deborah P; Pfeiffer, Dirk U; England, Gary C W; Noakes, David E; Dobson, Hilary; Sheldon, I Martin

2005-01-01

Bacteria contaminate the uterus of most dairy cattle after parturition and endometritis causes infertility. An endometritis score can be ascribed based on the vaginal mucus character and odour but it is not clear if the clinical score reflects the number of uterine bacteria or the inflammatory response. The present study tested the hypothesis that clinical evaluation of endometritis reflects the number of bacteria present in the uterus, and the acute phase protein response. Swabs (n = 328) were collected from the uterine lumen of dairy cattle, 21 and 28 days postpartum, vaginal mucus was scored for character and odour, and blood samples collected for acute phase protein measurement. Bacteria were identified following aerobic and anaerobic culture, and the bacterial growth density was scored semi-quantitatively. When bacteria were categorised by their expected pathogenic potential in the uterus, purulent or fetid odour vaginal mucus was associated with the growth density of pathogenic bacteria but not opportunist contaminants. When bacteria were analysed independently, Arcanobacterium pyogenes, Proteus and Fusobacterium necrophorum growth densities were associated with mucopurulent or purulent vaginal mucus. The bacterial growth densities for A. pyogenes, Escherichia coli, non-hemolytic Streptococci, and Mannheimia haemolytica were associated with a fetid mucus odour. Peripheral plasma concentrations of alpha(1)-acid glycoprotein were higher if there was a fetid compared with a normal vaginal mucus odour (1.50 +/- 0.09 mg/mL versus 1.05 +/- 0.02 mg/mL, P < 0.001), but did not differ significantly between vaginal mucus character scores. The evaluation of the character and odour of vaginal mucus reflects the number of bacteria in the uterus, and the acute phase protein response.

Commissioning and comprehensive evaluation of the ArcCHECK cylindrical diode array for VMAT pretreatment delivery QA.

PubMed

Chaswal, Vibha; Weldon, Michael; Gupta, Nilendu; Chakravarti, Arnab; Rong, Yi

2014-07-08

We present commissioning and comprehensive evaluation for ArcCHECK as a QA equipment for volumetric-modulated arc therapy (VMAT), using the 6 MV photon beam with and without the flattening filter, and the SNC patient software (version 6.2). In addition to commissioning involving absolute dose calibration, array calibration, and PMMA density verification, ArcCHECK was evaluated for its response dependency on linac dose rate, instantaneous dose rate, radiation field size, beam angle, and couch insertion. Scatter dose characterization, consistency and symmetry of response, and dosimetry accuracy evaluation for fixed aperture arcs and clinical VMAT patient plans were also investigated. All the evaluation tests were performed with the central plug inserted and the homogeneous PMMA density value. Results of gamma analysis demonstrated an overall agreement between ArcCHECK-measured and TPS-calculated reference doses. The diode based field size dependency was found to be within 0.5% of the reference. The dose rate-based dependency was well within 1% of the TPS reference, and the angular dependency was found to be ± 3% of the reference, as tested for BEV angles, for both beams. Dosimetry of fixed arcs, using both narrow and wide field widths, resulted in clinically acceptable global gamma passing rates on the 3%/3mm level and 10% threshold. Dosimetry of narrow arcs showed an improvement over published literature. The clinical VMAT cases demonstrated high level of dosimetry accuracy in gamma passing rates.

Magnetic resonance imaging in the evaluation of clinical treatment of otospongiosis: a pilot study.

PubMed

de Oliveira Vicente, Andy; Chandrasekhar, Sujana S; Yamashita, Helio K; Cruz, Oswaldo Laercio M; Barros, Flavia A; Penido, Norma O

2015-06-01

To evaluate the applicability of magnetic resonance imaging (MRI) as a method for monitoring the activity of otospongiotic lesions before and after clinical treatment. Prospective, randomized, controlled, double-blind study. One single tertiary care institution in a large, cosmopolitan city. Twenty-six patients (n = 42 ears) with clinical, audiometric, and tomographic diagnosis of otosclerosis were enrolled. If computed tomography (CT) demonstrated active lesions, these patients underwent MRI to detect otospongiotic foci, seen as areas of gadolinium enhancement. Patients were divided into 3 groups and received treatment with placebo, sodium alendronate, or sodium fluoride for 6 months. After this period, clinical and audiometric evaluations and a second MRI were performed. Each MRI was evaluated by both a neuroradiologist and an otolaryngologist in a subjective (visual) and objective (using specific eFilm Workstation software) manner. Otospongiosis was most predominantly identified in the region anterior to the oval window, and this site was reliable for comparing pre- and posttreatment scans. The patients in the alendronate and sodium fluoride groups had MRI findings that suggested a decrease in activity of otospongiotic lesions, more relevant in the alendronate group. These findings were statistically significant for both subjective and objective MRI evaluations. MRI shows higher sensitivity than clinical or audiometric assessment for detecting reduction in activity of otospongiosis. The objective MRI evaluation based on software analysis was the most accurate method of monitoring clinical treatment response in otospongiosis. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.

Clinical evaluation of multiple inflammation biomarkers for diagnosis and prognosis for patients with systemic inflammatory response syndrome.

PubMed

Reichsoellner, M; Raggam, R B; Wagner, J; Krause, R; Hoenigl, M

2014-11-01

A multiplexed biomarker bundle consisting of nine different inflammation markers was evaluated regarding their diagnostic and prognostic performances in 159 adult systemic inflammatory response syndrome (SIRS) patients enrolled at the emergency department. Fibronectin, interleukin-8 (IL-8), biotin, and neutrophil gelatinase-associated lipocalin (NGAL) were the most robust markers but were not superior to the already established markers IL-6, C-reactive protein (CRP), procalcitonin (PCT), and soluble urokinase plasminogen activator receptor (suPAR). Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Response and Remission After Cognitive and Exposure Therapy for Hypochondriasis.

PubMed

Weck, Florian; Neng, Julia M B

2015-11-01

Cognitive behavioral therapy has demonstrated large effect sizes for the treatment of hypochondriasis. However, response and remission rates, which provide important additional information about clinically significant improvements, have seldom been reported. In the current study, rates of response and remission after cognitive therapy and exposure therapy were evaluated. The study was based on a randomized controlled trial that treated patients with hypochondriasis (N = 75). The primary outcome measure was a clinician-administered structured interview for hypochondriasis. At posttreatment, response was found for 72.0% and remission for 45.3% of the patients. At 12-month follow-up, the response rate was 68.0%, and the remission rate was 54.7%. No significant differences in the frequency of response/remission were found between the cognitive therapy and the exposure therapy groups. Patients' and therapists' perspectives of clinical improvement corresponded with remission rather than response rates. Improvement rates were compared with those of other mental disorders, and implications for the treatment of hypochondriasis were discussed.

Pharmacoepigenomic responses of antipsychotic drugs on pharmacogenes are likely to be modulated by miRNAs.

PubMed

Swathy, Babu; Saradalekshmi, Koramannil R; Nair, Indu V; Nair, Chandrasekharan; Banerjee, Moinak

2017-06-01

It is imperative to differentiate the role of host epigenetics from pharmacoepigenetics in resolving therapeutic response. Therefore, the objective was to identify how antipsychotic drugs influence epigenetic response on pharmacogenes. The study design was based on in vitro evaluation of pharmacoepigenetic response of haloperidol, clozapine and olanzapine. Post antipsychotic treatment, the alterations in expression of ABCB1, CYP1A2 and CYP3A4 were monitored, and followed up by promoter methylation and their target miRNA expression studies. Critical observations were followed up in a restrictive clinical setting. Under in vitro conditions increased expression of ABCB1, CYP1A2 and CYP3A4 was observed which seems to be regulated by miR-27a and miR-128a and not by methylation. A similar pattern was observed in clinical setting with ABCB1, which was reflective of good therapeutic response. The study demonstrates that antipsychotic drugs can influence miRNA-mediated epigenetic response in pharmacogenes resulting in modulating therapeutic response.

Clinical descriptors for the recognition of central sensitization pain in patients with knee osteoarthritis.

PubMed

Lluch, Enrique; Nijs, Jo; Courtney, Carol A; Rebbeck, Trudy; Wylde, Vikki; Baert, Isabel; Wideman, Timothy H; Howells, Nick; Skou, Søren T

2017-08-02

Despite growing awareness of the contribution of central pain mechanisms to knee osteoarthritis pain in a subgroup of patients, routine evaluation of central sensitization is yet to be incorporated into clinical practice. The objective of this perspective is to design a set of clinical descriptors for the recognition of central sensitization in patients with knee osteoarthritis that can be implemented in clinical practice. A narrative review of original research papers was conducted by nine clinicians and researchers from seven different countries to reach agreement on clinically relevant descriptors. It is proposed that identification of a dominance of central sensitization pain is based on descriptors derived from the subjective assessment and the physical examination. In the former, clinicians are recommended to inquire about intensity and duration of pain and its association with structural joint changes, pain distribution, behavior of knee pain, presence of neuropathic-like or centrally mediated symptoms and responsiveness to previous treatment. The latter includes assessment of response to clinical test, mechanical hyperalgesia and allodynia, thermal hyperalgesia, hypoesthesia and reduced vibration sense. This article describes a set of clinically relevant descriptors that might indicate the presence of central sensitization in patients with knee osteoarthritis in clinical practice. Although based on research data, the descriptors proposed in this review require experimental testing in future studies. Implications for Rehabilitation Laboratory evaluation of central sensitization for people with knee osteoarthritis is yet to be incorporated into clinical practice. A set of clinical indicators for the recognition of central sensitization in patients with knee osteoarthritis is proposed. Although based on research data, the clinical indicators proposed require further experimental testing of psychometric properties.

Clinical Oversight: Conceptualizing the Relationship Between Supervision and Safety

PubMed Central

Lingard, Lorelei; Baker, G. Ross; Kitchen, Lisa; Regehr, Glenn

2007-01-01

Background Concern about the link between clinical supervision and safe, quality health care has led to widespread increases in the supervision of medical trainees. The effects of increased supervision on patient care and trainee education are not known, primarily because the current multifacted and poorly operationalized concept of clinical supervision limits the potential for evaluation. Objective To develop a conceptual model of clinical supervision to inform and guide policy and research. Design, Setting, and Participants Observational fieldwork and interviews were conducted in the Emergency Department and General Internal Medicine in-patient teaching wards of two academic health sciences centers associated with an urban Canadian medical school. Members of 12 Internal Medicine and Emergency Medicine teaching teams (n = 88) were observed during regular clinical activities (216 hours). Sixty-five participants (12 physicians, 28 residents, 17 medical students, 8 nurses) also completed interviews about supervision. Field notes and interview transcripts were analyzed for emergent themes using grounded theory methodology. Results The term “clinical oversight” was developed to describe patient care activities performed by supervisors to ensure quality of care. “Routine oversight” (preplanned monitoring of trainees’ clinical work) can expose supervisors to concerns that trigger “responsive oversight” (a double-check or elaboration of trainees’ clinical work). Supervisors sometimes engage in “backstage oversight” (oversight of which the trainee is not directly aware). When supervisors encounter a situation that exceeds a trainee’s competence, they move beyond clinical oversight to “direct patient care”. Conclusions This study elaborates a typology of clinical oversight activities including routine, responsive, and backstage oversight. This new typology provides a framework for clinical supervision policy and for research to evaluate the relationship between supervision and safety. PMID:17557190

Approaches to veterinary education--tracking versus a final year broad clinical experience. Part one: effects on career outcome.

PubMed

Klosterman, E S; Kass, P H; Walsh, D A

2009-08-01

This is the first of two papers that provide extensive data and analysis on the two major approaches to clinical veterinary education, which either provide students with experience of a broad range of species (often defined as omni/general clinical competence), or just a few species (sometimes just one), usually termed 'tracking'. Together the two papers provide a detailed analysis of these two approaches for the first time. The responsibilities of veterinary medicine and veterinary education are rapidly increasing throughoutthe globe. It is critical for all in veterinary education to reassess the approaches that have been used, and evaluate on a school-by-school basis which may best meet its expanding and ever-deepening responsibilities.

Childhood asthma clusters and response to therapy in clinical trials.

PubMed

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.

Evaluation of Patient Satisfaction Surveys in Pediatric Orthopaedics.

PubMed

Segal, Lee S; Plantikow, Carla; Hall, Randon; Wilson, Kristina; Shrader, M Wade

2015-01-01

Patient satisfaction survey scores are increasingly being tied to incentive compensation, impact how we practice medicine, influence decisions on where patients seek care, and in the future may be required for accreditation. The goal of this study is to compare the results of an internal distribution of patient satisfaction surveys at the point of care to responses received by mail in a hospital-based, high-volume pediatric orthopaedic practice. A pediatric outpatient survey is used at our institution to evaluate patient satisfaction. Surveys are randomly mailed out to families seen in our clinic by the survey vendor, and the results are determined on a quarterly basis. We distributed the same survey in a similar manner in our clinic. The results of the surveys, external/mailed (EXM) versus internal/point of care (INP) over the same 3-month time period (second quarter 2013) were compared. The survey questions are dichotomized from an ordinal scale into either excellent (9 to 10) or not excellent (0 to 8) commonly used in patient satisfaction methodology. We evaluated the raw data from the INP surveys for the question on provider rating by evaluating the mean score, the standard excellent response (9 to 10), and an expanded excellent response (8 to 10). Response rate was 72/469 (15.4%) for EXM, and 231/333 (69.4%) for INP. An excellent response for the "rating your provider" question was 72.2% (EXM) versus 84.8% (INP) (P=0.015). Our analysis of the raw data (INP) has a mean rating of 9.42. The expanded scale (8 to 10) for an excellent response increased the provider rating to 94.4% (P=0.001). Waiting time response within 15 minutes was the only item that correlated with rating of provider (P=0.02). For the majority of the items, the INP responses were consistently higher than the EXM responses, including 6/7 responses that were statistically significant (P<0.05). As mandated by the Centers for Medicare and Medicaid Services, patient satisfaction surveys will be important in determining health care outcomes. Properly designed and administered surveys provide robust measures of quality. Our study reinforces methodological concerns about patient satisfaction surveys distributed in a high-volume pediatric subspecialty practice. Further research is needed to evaluate the patients' health care experience and true quality of care in pediatric subspecialty ambulatory settings.

Development and clinical study of mobile 12-lead electrocardiography based on cloud computing for cardiac emergency.

PubMed

Fujita, Hideo; Uchimura, Yuji; Waki, Kayo; Omae, Koji; Takeuchi, Ichiro; Ohe, Kazuhiko

2013-01-01

To improve emergency services for accurate diagnosis of cardiac emergency, we developed a low-cost new mobile electrocardiography system "Cloud Cardiology®" based upon cloud computing for prehospital diagnosis. This comprises a compact 12-lead ECG unit equipped with Bluetooth and Android Smartphone with an application for transmission. Cloud server enables us to share ECG simultaneously inside and outside the hospital. We evaluated the clinical effectiveness by conducting a clinical trial with historical comparison to evaluate this system in a rapid response car in the real emergency service settings. We found that this system has an ability to shorten the onset to balloon time of patients with acute myocardial infarction, resulting in better clinical outcome. Here we propose that cloud-computing based simultaneous data sharing could be powerful solution for emergency service for cardiology, along with its significant clinical outcome.

Influence of the Co-Administration of Heptavalent Conjugate Vaccine PCV7-TT on the Immunological Response Elicited by VA-MENGOC-BC® and Heberpenta®-L in Rabbits.

PubMed

Espinosa-Viñals, Carlos; García-Rivera, Dagmar; Rodríguez Noda, Laura; Amador Gómez, Aylín; Nicot, Milagros; Valle, Orialys; Núñez, Juan F; Martin, Yanet; Santana, Darielys; Valdés, Yury; Vérez Bencomo, Vicente

2017-05-01

Finlay Vaccine Institute is developing a new heptavalent conjugate vaccine against Streptococcus pneumoniae. As infants are the target population, PCV7-TT will be necessarily co-administered with other vaccines, and then, the interactions represent a concern. The aim of this work is to evaluate the possible immunological interferences in rabbits as animal experimental model. Rabbits were immunized with Heberpenta®-L, VA-MENGOC-BC®, and PCV7-TT. Blood samples were taken fourteen days after final immunization for obtaining sera. Antibody responses to all antigens were evaluated by indirect ELISA. Functional responses against diphtheria and tetanus toxoid were done by in vivo seroneutralization assay. No interference was observed by PCV7-TT over the humoral response against diphtheria toxoid and meningococcal antigens (p > 0.05). A nonstatistically significant reduction (p > 0.05) was observed in the case of the humoral response against Haemophilus influenzae type b oligosaccharide. Concomitant administration of Heberpenta®-L and PCV7-TT increased twice the antibody titers as well as the protective activity against tetanus toxoid, but no statistical differences were found. The co-administration did not induce a reduction in the percent of responders against pneumococcal polysaccharides contained in PCV7-TT vaccine. Concomitant administration of PCV7-TT did not induce interferences over the evaluated antigens of Heberpenta®-L and VA-MENGOC-BC®. Also, no interference was observed on the immune response elicited by PCV7-TT. These preclinical results suggest that PCV7-TT will not result in a serious problem over the immune response elicited by the licensed vaccines Heberpenta®-L and VA-MENGOC-BC®. However, the clinical interference could be strictly studied during clinical trials in infants.

Social support and responsiveness in online patient communities: impact on service quality perceptions.

PubMed

Nambisan, Priya; Gustafson, David H; Hawkins, Robert; Pingree, Suzanne

2016-02-01

Hospitals frequently evaluate their service quality based on the care and services provided to patients by their clinical and non-clinical staff.(1,2) However, such evaluations do not take into consideration the many interactions that patients have in online patient communities with the health-care organization (HCO) as well as with peer patients. Patients' interactions in these online communities could impact their perceptions regarding the HCO's service quality. The objective of this pilot study was to evaluate the impact of social support and responsiveness that patients experience in an HCO's online community on patients' perceptions regarding the HCO's service quality. The study data are collected from CHESS, a health-care programme (Comprehensive Health Enhancement Support System) run by the Centre for Health Enhancement System Studies at the University of Wisconsin-Madison. Findings show that the social support and the responsiveness received from peer patients in the online patient communities will impact patients' perceptions regarding the service quality of the HCO even when the organizational members themselves do not participate in the online discussions. The results indicate that interactions in such HCO-provided online patient communities should not be ignored as they could translate into patients' perceptions regarding HCOs' service quality. Ways to improve responsiveness and social support in an HCO's online patient community are discussed. © 2014 John Wiley & Sons Ltd.

Positron emission tomography using [18F]fluorotamoxifen to evaluate therapeutic responses in patients with breast cancer: preliminary study.

PubMed

Inoue, T; Kim, E E; Wallace, S; Yang, D J; Wong, F C; Bassa, P; Cherif, A; Delpassand, E; Buzdar, A; Podoloff, D A

1996-08-01

Positron emission tomography (PET) was used to assess the biodistribution and clinical usefulness of [18F]fluorotamoxifen (FTX) in 10 patients with estrogen-receptor(ER)-positive breast tumors. Ten patients with ER-positive breast cancer were prospectively studied, and the consecutive PET imagings (each takes 15 or 20 min) were obtained for 60 or 80 min after the injection of 88.8-392.2 MBq (2.4-10.6 mCi) of [18F]FTX. Twenty three suspected primary or metastatic lesions in 10 patients were evaluated and the tumor uptakes of [18F]FTX in nineteen tumor lesions were correlated to the response of tamoxifen therapy. Three lesions in three patients were considered to be truly negative for breast cancer on the bases of biopsy specimens and/or clinical course. Five (71.4%) of seven patients and 16 (80.0%) of 20 lesions were interpreted to be truly positive for breast cancer. The mean standardized uptake value (SUV) of the radiotracer in tumor was 3.0 on delayed images. There was no significant correlation between the standardized uptake values of [18F]FTX and the ER concentrations in primary lesions. Nineteen tumor lesions in six patients were evaluable to compare the [18F]FTX uptake with responses to tamoxifen therapy after the PET study. Three patients who had a good response to tamoxifen therapy showed positive lesions on PET images, whereas two of three patients who had a poor response showed negative lesions and one showed mixed results. There was no significant difference of [18F]FTX uptake in bone lesions between good and poor responders. However, when bone lesions were excluded, [18F]FTX uptakes in tumors with good responses were significantly higher than those with poor responses (mean and standard deviation of SUV: 2.46 +/- 0.62 vs 1.37 +/- 0.59, P < 0.05). PET imaging using [18F]FTX provides useful information in predicting the effect of tamoxifen therapy in patients with ER-positive breast cancer. Further study is warranted to confirm the clinical utility of PET using [18F]FTX in breast cancer patients.

Palliation of clinical signs in 48 dogs with nasal carcinomas treated with coarse-fraction radiation therapy.

PubMed

Gieger, Tracy; Rassnick, Kenneth; Siegel, Sheri; Proulx, David; Bergman, Philip; Anderson, Christine; LaDue, Tracy; Smith, Annette; Northrup, Nicole; Roberts, Royce

2008-01-01

Data from 48 dogs with nasal carcinomas treated with palliative radiation therapy (PRT) were retrospectively reviewed. Factors potentially influencing resolution of clinical signs and survival after PRT were evaluated. Clinical signs completely resolved in 66% of dogs for a median of 120 days. The overall median survival time was 146 days. Duration of response to PRT was shorter in dogs that had clinical signs for <90 days before PRT. Survival times were shorter in dogs that had partial or no resolution of clinical signs after PRT than in dogs that had complete resolution of clinical signs.

The clinical impact of the novel tumor marker DR-70 in unresectable gastric cancer patients.

PubMed

Hung, Yi-Ping; Chen, Ming-Huang; Lin, June-Seng; Hsiao, Chin-Fu; Shan, Yan-Shen; Chen, Yeu-Chin; Chen, Li-Tzong; Liu, Tsang-Wu; Li, Chung-Pin; Chao, Yee

2018-07-01

Gastric cancer tumor markers, such as carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA 19-9), have been applied in clinical practice to screen or monitor treatment responses. However, their sensitivity and specificity are unsatisfactory. Therefore, we assessed the novel tumor marker DR-70 and evaluated its performance in screening and response monitoring. The study included newly diagnosed patients with advanced gastric cancer from March 2012 to October 2015. We measured the DR-70, CEA, and CA 19-9 levels at the time of enrollment. The patients subsequently underwent chemotherapy. We followed-up the patients every 3 months; DR-70 levels and abdominal computed tomography scans were re-evaluated and repeated, respectively, at each follow-up. The correlation between treatment response and DR-70 level after chemotherapy was analyzed. The overall survival and progression-free survival rates were also evaluated. A total of 51 patients with gastric cancer were enrolled. Most (82.4%) had metastatic disease. At enrollment, the sensitivity of DR-70 in our study group was 78.4%, compared with 52.9% and 43.1% for CEA and CA 19-9, respectively. When we used the three tumor markers together, the sensitivity increased to 80.4%. We observed a correlation between treatment response and DR-70 level after chemotherapy. No difference in either overall survival or progression-free survival was observed between the DR-70 positive and negative groups. However, a trend toward poorer overall survival was observed for the high DR-70 group, although this was not statistically significant. DR-70 is a powerful tool not only for screening unresectable gastric cancer but also for treatment response evaluation. Copyright © 2018. Published by Elsevier Taiwan LLC.

Evaluative measurement properties of the patient-specific functional scale for primary shoulder complaints in physical therapy practice.

PubMed

Koehorst, Marije L S; van Trijffel, Emiel; Lindeboom, Robert

2014-08-01

Clinical measurement, longitudinal. To assess the test-retest reliability, construct validity, and responsiveness of the Patient-Specific Functional Scale (PSFS) in patients with a primary shoulder complaint. Health measurement outcomes have become increasingly important for evaluating treatment. Patient-specific questionnaires are useful tools for determining treatment goals and evaluating treatment in individual patients. These questionnaires have not yet been validated in patients with nonspecific shoulder pain. Patients completed the PSFS, the numeric pain rating scale, and the Shoulder Pain and Disability Index at baseline, and after 1 week and 4 to 6 weeks. Test-retest reliability was determined using intraclass correlation coefficients. To assess convergent validity, change scores of the PSFS were correlated with the numeric pain rating scale and Shoulder Pain and Disability Index change scores. Responsiveness was assessed by calculating the area under the curve, the minimal clinically important change, and minimal detectable change, using the global rating of change as an external criterion. Fifty patients (37 men; mean age, 47.7 years) participated in the study. Reliability was high (intraclass correlation coefficient = 0.87; 95% confidence interval [CI]: 0.72, 0.94). The correlations between the change scores of the PSFS and those of the Shoulder Pain and Disability Index and numeric pain rating scale were 0.45 (95% CI: 0.17, 0.80) and 0.55 (95% CI: 0.29, 0.73), respectively. The area under the curve for the PSFS was 0.67 (95% CI: 0.51, 0.83). The minimal detectable change and minimal clinically important change were 0.97 and 1.29 points, respectively. These results suggest that the PSFS is a reliable, valid, and responsive instrument that can be used as an evaluative instrument in patients with a primary shoulder complaint.

Study design of PANGAEA 2.0, a non-interventional study on RRMS patients to be switched to fingolimod.

PubMed

Ziemssen, Tjalf; Kern, Raimar; Cornelissen, Christian

2016-08-08

The therapeutic options for patients with Multiple Sclerosis (MS) have steadily increased due to the approval of new substances that now supplement traditional first-line agents, demanding a paradigm shift in the assessment of disease activity and treatment response in clinical routine. Here, we report the study design of PANGAEA 2.0 (Post-Authorization Non-interventional GermAn treatment benefit study of GilEnyA in MS patients), a non-interventional study in patients with relapsing-remitting MS (RRMS) identify patients with disease activity and monitor their disease course after treatment switch to fingolimod (Gilenya®), an oral medication approved for patients with highly active RRMS. In the first phase of the PANGAEA 2.0 study the disease activity status of patients receiving a disease-modifying therapy (DMT) is evaluated in order to identify patients at risk of disease progression. This evaluation is based on outcome parameters for both clinical disease activity and magnetic resonance imaging (MRI), and subclinical measures, describing disease activity from the physician's and the patient's perspective. In the second phase of the study, 1500 RRMS patients identified as being non-responders and switched to fingolimod (oral, 0.5 mg/daily) are followed-up for 3 years. Data on relapse activity, disability progression, MRI lesions, and brain volume loss will be assessed in accordance to 'no evidence of disease activity-4' (NEDA-4). The modified Rio score, currently validated for the evaluation of treatment response to interferons, will be used to evaluate the treatment response to fingolimod. The MS management software MSDS3D will guide physicians through the complex processes of diagnosis and treatment. A sub-study further analyzes the benefits of a standardized quantitative evaluation of routine MRI scans by a central reading facility. PANGAEA 2.0 is being conducted between June 2015 and December 2019 in 350 neurological practices and centers in Germany, including 100 centers participating in the sub-study. PANGAEA 2.0 will not only evaluate the long-term benefit of a treatment change to fingolimod but also the applicability of new concepts of data acquisition, assessment of MS disease activity and evaluation of treatment response for the in clinical routine. BfArM6532; Trial Registration Date: 20/05/2015.

Patient phenotyping in clinical trials of chronic pain treatments: IMMPACT recommendations

PubMed Central

Edwards, Robert R.; Dworkin, Robert H.; Turk, Dennis C.; Angst, Martin S.; Dionne, Raymond; Freeman, Roy; Hansson, Per; Haroutounian, Simon; Arendt-Nielsen, Lars; Attal, Nadine; Baron, Ralf; Brell, Joanna; Bujanover, Shay; Burke, Laurie B.; Carr, Daniel; Chappell, Amy S.; Cowan, Penney; Etropolski, Mila; Fillingim, Roger B.; Gewandter, Jennifer S.; Katz, Nathaniel P.; Kopecky, Ernest A.; Markman, John D.; Nomikos, George; Porter, Linda; Rappaport, Bob A.; Rice, Andrew S.C.; Scavone, Joseph M.; Scholz, Joachim; Simon, Lee S.; Smith, Shannon M.; Tobias, Jeffrey; Tockarshewsky, Tina; Veasley, Christine; Versavel, Mark; Wasan, Ajay D.; Wen, Warren; Yarnitsky, David

2018-01-01

There is tremendous inter-patient variability in the response to analgesic therapy (even for efficacious treatments), which can be the source of great frustration in clinical practice. This has led to calls for “precision medicine”, or personalized pain therapeutics (i.e., empirically-based algorithms that determine the optimal treatments, or treatment combinations, for individual patients) that would presumably improve both the clinical care of patients with pain, and the success rates for putative analgesic drugs in Phase 2 and 3 clinical trials. However, before implementing this approach, the characteristics of individual patients or subgroups of patients that increase or decrease the response to a specific treatment need to be identified. The challenge is to identify the measurable phenotypic characteristics of patients that are most predictive of individual variation in analgesic treatment outcomes, and the measurement tools that are best suited to evaluate these characteristics. In this article, we present evidence on the most promising of these phenotypic characteristics for use in future research, including psychosocial factors, symptom characteristics, sleep patterns, responses to noxious stimulation, endogenous pain-modulatory processes, and response to pharmacologic challenge. We provide evidence-based recommendations for core phenotyping domains and recommend measures of each domain. PMID:27152687

Clinical evaluation of a nutraceutical diet as an adjuvant to pharmacological treatment in dogs affected by Keratoconjunctivitis sicca.

PubMed

Destefanis, Simona; Giretto, Daniela; Muscolo, Maria Cristina; Di Cerbo, Alessandro; Guidetti, Gianandrea; Canello, Sergio; Giovazzino, Angela; Centenaro, Sara; Terrazzano, Giuseppe

2016-09-22

Canine keratoconjunctivitis sicca (cKCS) is an inflammatory eye condition related to a deficiency in the tear aqueous fraction. Etiopathogenesis of such disease is substantially multifactorial, combining the individual genetic background with environmental factors that contribute to the process of immunological tolerance disruption and, as a consequence, to the emergence of autoimmunity disease. In this occurrence, it is of relevance the role of the physiological immune-dysregulation that results in immune-mediated processes at the basis of cKCS. Current therapies for this ocular disease rely on immunosuppressive treatments. Clinical response to treatment frequently varies from poor to good, depending on the clinical-pathological status of eyes at diagnosis and on individual response to therapy. In the light of the variability of clinical response to therapies, we evaluated the use of an anti-inflammatory/antioxidant nutraceutical diet with potential immune-modulating activity as a therapeutical adjuvant in cKCS pharmacological treatment. Such combination was administered to a cohort of dogs affected by cKCS in which the only immunosuppressive treatment resulted poorly responsive or ineffective in controlling the ocular symptoms. Fifty dogs of different breeds affected by immune-mediated cKCS were equally distributed and randomly assigned to receive either a standard diet (control, n = 25) or the nutraceutical diet (treatment group, n = 25) both combined with standard immunosuppressive therapy over a 60 days period. An overall significant improvement of all clinical parameters (tear production, conjunctival inflammation, corneal keratinization, corneal pigment density and mucus discharge) and the lack of food-related adverse reactions were observed in the treatment group (p < 0.0001). Our results showed that the association of traditional immune-suppressive therapy with the antioxidant/anti-inflammatory properties of the nutraceutical diet resulted in a significant amelioration of clinical signs and symptoms in cKCS. The beneficial effects, likely due to the presence of supplemented nutraceuticals in the diet, appeared to specifically reduce the immune-mediated ocular symptoms in those cKCS-affected dogs that were poorly responsive or unresponsive to classical immunosuppressive drugs. These data suggest that metabolic changes could affect the immune response orchestration in a model of immune-mediated ocular disease, as represented by cKCS.

Improving access to clinical practice guidelines with an interactive graphical interface using an iconic language

PubMed Central

2014-01-01

Background Clinical practice guidelines are useful for physicians, and guidelines are available on the Internet from various websites such as Vidal Recos. However, these guidelines are long and difficult to read, especially during consultation. Similar difficulties have been encountered with drug summaries of product characteristics. In a previous work, we have proposed an iconic language (called VCM, for Visualization of Concepts in Medicine) for representing patient conditions, treatments and laboratory tests, and we have used these icons to design a user interface that graphically indexes summaries of product characteristics. In the current study, our objective was to design and evaluate an iconic user interface for the consultation of clinical practice guidelines by physicians. Methods Focus groups of physicians were set up to identify the difficulties encountered when reading guidelines. Icons were integrated into Vidal Recos, taking human factors into account. The resulting interface includes a graphical summary and an iconic indexation of the guideline. The new interface was evaluated. We compared the response times and the number of errors recorded when physicians answered questions about two clinical scenarios using the interactive iconic interface or a textual interface. Users’ perceived usability was evaluated with the System Usability Scale. Results The main difficulties encountered by physicians when reading guidelines were obtaining an overview and finding recommendations for patients corresponding to “particular cases”. We designed a graphical interface for guideline consultation, using icons to identify particular cases and providing a graphical summary of the icons organized by anatomy and etiology. The evaluation showed that physicians gave clinical responses more rapidly with the iconic interface than the textual interface (25.2 seconds versus 45.6, p < 0.05). The physicians appreciated the new interface, and the System Usability Scale score value was 75 (between good and excellent). Conclusion An interactive iconic interface can provide physicians with an overview of clinical practice guidelines, and can decrease the time required to access the content of such guidelines. PMID:25158762

Improving access to clinical practice guidelines with an interactive graphical interface using an iconic language.

PubMed

Pereira, Suzanne; Hassler, Sylvain; Hamek, Saliha; Boog, César; Leroy, Nicolas; Beuscart-Zéphir, Marie-Catherine; Favre, Madeleine; Venot, Alain; Duclos, Catherine; Lamy, Jean-Baptiste

2014-08-26

Clinical practice guidelines are useful for physicians, and guidelines are available on the Internet from various websites such as Vidal Recos. However, these guidelines are long and difficult to read, especially during consultation. Similar difficulties have been encountered with drug summaries of product characteristics. In a previous work, we have proposed an iconic language (called VCM, for Visualization of Concepts in Medicine) for representing patient conditions, treatments and laboratory tests, and we have used these icons to design a user interface that graphically indexes summaries of product characteristics. In the current study, our objective was to design and evaluate an iconic user interface for the consultation of clinical practice guidelines by physicians. Focus groups of physicians were set up to identify the difficulties encountered when reading guidelines. Icons were integrated into Vidal Recos, taking human factors into account. The resulting interface includes a graphical summary and an iconic indexation of the guideline. The new interface was evaluated. We compared the response times and the number of errors recorded when physicians answered questions about two clinical scenarios using the interactive iconic interface or a textual interface. Users' perceived usability was evaluated with the System Usability Scale. The main difficulties encountered by physicians when reading guidelines were obtaining an overview and finding recommendations for patients corresponding to "particular cases". We designed a graphical interface for guideline consultation, using icons to identify particular cases and providing a graphical summary of the icons organized by anatomy and etiology. The evaluation showed that physicians gave clinical responses more rapidly with the iconic interface than the textual interface (25.2 seconds versus 45.6, p < 0.05). The physicians appreciated the new interface, and the System Usability Scale score value was 75 (between good and excellent). An interactive iconic interface can provide physicians with an overview of clinical practice guidelines, and can decrease the time required to access the content of such guidelines.

Justify Your Answer: The Role of Written Think Aloud in Script Concordance Testing.

PubMed

Power, Alyssa; Lemay, Jean-Francois; Cooke, Suzette

2017-01-01

Construct: Clinical reasoning assessment is a growing area of interest in the medical education literature. Script concordance testing (SCT) evaluates clinical reasoning in conditions of uncertainty and has emerged as an innovative tool in the domain of clinical reasoning assessment. SCT quantifies the degree of concordance between a learner and an experienced clinician and attempts to capture the breadth of responses of expert clinicians, acknowledging the significant yet acceptable variation in practice under situations of uncertainty. SCT has been shown to be a valid and reliable clinical reasoning assessment tool. However, as SCT provides only quantitative information, it may not provide a complete assessment of clinical reasoning. Think aloud (TA) is a qualitative research tool used in clinical reasoning assessment in which learners verbalize their thought process around an assigned task. This study explores the use of TA, in the form of written reflection, in SCT to assess resident clinical reasoning, hypothesizing that the information obtained from the written TA would enrich the quantitative data obtained through SCT. Ninety-one pediatric postgraduate trainees and 21 pediatricians from 4 Canadian training centers completed an online test consisting of 24 SCT cases immediately followed by retrospective written TA. Six of 24 cases were selected to gather TA data. These cases were chosen to allow all phases of clinical decision making (diagnosis, investigation, and treatment) to be represented in the TA data. Inductive thematic analysis was employed when systematically reviewing TA responses. Three main benefits of adding written TA to SCT were identified: (a) uncovering instances of incorrect clinical reasoning despite a correct SCT response, (b) revealing sound clinical reasoning in the context of a suboptimal SCT response, and (c) detecting question misinterpretation. Written TA can optimize SCT by demonstrating when correct examinee responses are based on guessing or uncertainty rather than robust clinical rationale. TA can also enhance SCT by allowing examinees to provide justification for responses that otherwise would have been considered incorrect and by identifying questions that are frequently misinterpreted to avoid including them in future examinations. TA also has significant value in differentiating between acceptable variations in expert clinician responses and deviance associated with faulty rationale or question misinterpretation; this could improve SCT reliability. A written TA protocol appears to be a valuable tool to assess trainees' clinical reasoning and can strengthen the quantitative assessment provided by SCT.

Violence among Family Members of Children and Adolescents Evaluated for Sexual Abuse

ERIC Educational Resources Information Center

Kellogg, Nancy D.; Menard, Shirley W.

2003-01-01

Objectives: The two aims of this study were to: (1) describe the prevalence and characteristics of domestic adult and child physical violence in the homes of children and adolescents evaluated in a specialized sexual abuse clinic and (2) describe parent or caretaker responses to domestic adult and child violence and child sexual abuse, including…

Unilateral Laryngoscopic Findings Associated With Response to Gabapentin in Patients With Chronic Cough.

PubMed

Giliberto, John Paul; Dibildox, Daniel; Merati, Albert

2017-11-01

Chronic cough is a debilitating, often multifactorial problem. Vagal neuropathy has been proposed as a cause for a fraction of these cases. There are certain features that support the clinical diagnosis of vagal neuropathy. It is hypothesized that patients with neurogenic cough who have vocal fold motion asymmetry (VFMA) on laryngoscopy will be more likely to respond to gabapentin. To evaluate the association between the history, physical and videostroboscopic examinations, and clinical response to gabapentin. In a retrospective cohort study, patients with chronic cough visiting an academic tertiary laryngology clinic from January 1, 2013, to September 1, 2015, were identified through International Classification of Diseases, Ninth Revision. Of those who had a chronic cough (>8 weeks), 27 patients who received a prescription for gabapentin were included. Patients without videostroboscopy, who did not complete voice therapy, or those without a follow-up examination more than 1 month from the initial evaluation were excluded. Initial history, physical and videostroboscopic examinations, and follow-up evaluations, were performed in a multidisciplinary laryngology clinic including a speech-language pathologist. Documented VFMA by a multidisciplinary team was decided by consensus after review of videostroboscopy recording at the time of the visit. Response to gabapentin was defined by physician-documented subjective patient report of improvement in cough symptoms. Follow-up data were available on 25 of the 27 patients (15 [60%] women; mean [SD] age, 57 [11.8] years). Therapy was initiated in patients with chronic cough with gabapentin, 100 mg twice daily, which was titrated to response or adverse effects. The maximum daily dose was 1800 mg. Partial or complete response to gabapentin was noted in 16 (64%) patients. Vocal fold motion asymmetry was noted in 20 (80%) patients. Fifteen of 16 (94%) responders had VFMA compared with 5 of 9 (56%) nonresponders. The difference in the frequency of VFMA between responders and nonresponders was 38% (95% CI, 18%-58%). Adverse effects limited the gabapentin dose in 4 of 9 (44%) nonresponders and 4 of 16 (25%) responders (odds ratio, 2.5; 95% CI, 0.42-13.6). In patients with chronic cough suspected to be related to vagal neuropathy, the odds of response to gabapentin are higher with the presence of VFMA noted on videostroboscopy.

Kinematic measures for upper limb motor assessment during robot-mediated training in patients with severe sub-acute stroke.

PubMed

Duret, Christophe; Courtial, Ophélie; Grosmaire, Anne Gaelle

2016-01-01

Kinematic assessments are increasingly used as motor outcome measures during upper limb robot-assisted training, in addition to clinical scales. However, their relevance has not been evaluated much. Thirty-eight patients with severe sub-acute stroke (age 56 ± 17 [19-87] years; time since stroke, 55 ± 22 days) carried out 16 sessions (average 3/week, 35 ± 15 days) of upper limb robot-assisted training combined with standard therapy. Pre/post motor performance was evaluated using the Fugl-Meyer Assessment scale, Motor Status Scale (MSS) and kinematic measures. Motor outcomes were compared and relationships between clinical and kinematic outcomes were analyzed. All clinical and kinematic outcomes improved after training (p <  0.01). FM score increased from 17.7 ± 10.0 to 28.6 ± 15.4. All baseline kinematic measures were strongly correlated with clinical scores. Correlations between clinical and kinematic changes were moderate (r = -0.65 for change in FM Proximal score and change in accuracy measure). However, smoothness and accuracy indicators were shown to be responsive measures. This study demonstrated that baseline kinematic measures and their pre/post training changes were significantly correlated with clinical motor outcome measures. However, even if kinematic measures are valid for the evaluation of motor impairment we cannot propose to substitute common clinical measures of motor function which also evaluate functional abilities of the upper limb.

A qualitative evaluation of a pilot leadership programme for dentists.

PubMed

Walsh, Jonathan; Taylor, Nicholas; Hough, Donna; Brocklehurst, Paul

2015-07-06

The purpose of this paper was to evaluate a pilot training programme run by Health Education North West to promote clinical leadership amongst general dental practitioners (GDPs). New powers and responsibilities for clinicians have caused a fundamental shift in the way that local services are planned and delivered in England. GDPs are being appointed onto the boards of local professional networks (LPNs) to influence the way that services are delivered at a local level. Analogous to clinical commissioning groups in medicine, the role of LPNs is to ensure that GDPs lead change and drive up the quality of service provision. Clinical leadership has been argued to be fundamentally important in these new structures, but has received little attention in the dental literature. Semi-structured interviews and a focus group were held with participants of the pilot to explore their understanding and experience of clinical leadership. These were recorded, transcribed verbatim and underwent thematic analysis. Nineteen codes were identified and organized into four themes: nature of clinical leadership, challenges for clinical leaders in dentistry, Leadership Exploration and Discovery programme evaluation and future direction. The research provides an understanding of how GDPs conceptualise clinical leadership and provides recommendations for future leadership training programmes. This is the first evaluation of a leadership programme for GDPs and so helps address the paucity of evidence in the dental literature.

Evaluating Random Error in Clinician-Administered Surveys: Theoretical Considerations and Clinical Applications of Interobserver Reliability and Agreement.

PubMed

Bennett, Rebecca J; Taljaard, Dunay S; Olaithe, Michelle; Brennan-Jones, Chris; Eikelboom, Robert H

2017-09-18

The purpose of this study is to raise awareness of interobserver concordance and the differences between interobserver reliability and agreement when evaluating the responsiveness of a clinician-administered survey and, specifically, to demonstrate the clinical implications of data types (nominal/categorical, ordinal, interval, or ratio) and statistical index selection (for example, Cohen's kappa, Krippendorff's alpha, or interclass correlation). In this prospective cohort study, 3 clinical audiologists, who were masked to each other's scores, administered the Practical Hearing Aid Skills Test-Revised to 18 adult owners of hearing aids. Interobserver concordance was examined using a range of reliability and agreement statistical indices. The importance of selecting statistical measures of concordance was demonstrated with a worked example, wherein the level of interobserver concordance achieved varied from "no agreement" to "almost perfect agreement" depending on data types and statistical index selected. This study demonstrates that the methodology used to evaluate survey score concordance can influence the statistical results obtained and thus affect clinical interpretations.

An item response theory evaluation of the young mania rating scale and the montgomery-asberg depression rating scale in the systematic treatment enhancement program for bipolar disorder (STEP-BD).

PubMed

Prisciandaro, James J; Tolliver, Bryan K

2016-11-15

The Young Mania Rating Scale (YMRS) and Montgomery-Asberg Depression Rating Scale (MADRS) are among the most widely used outcome measures for clinical trials of medications for Bipolar Disorder (BD). Nonetheless, very few studies have examined the measurement characteristics of the YMRS and MADRS in individuals with BD using modern psychometric methods. The present study evaluated the YMRS and MADRS in the Systematic Treatment Enhancement Program for BD (STEP-BD) study using Item Response Theory (IRT). Baseline data from 3716 STEP-BD participants were available for the present analysis. The Graded Response Model (GRM) was fit separately to YMRS and MADRS item responses. Differential item functioning (DIF) was examined by regressing a variety of clinically relevant covariates (e.g., sex, substance dependence) on all test items and on the latent symptom severity dimension, within each scale. Both scales: 1) contained several items that provided little or no psychometric information, 2) were inefficient, in that the majority of item response categories did not provide incremental psychometric information, 3) poorly measured participants outside of a narrow band of severity, 4) evidenced DIF for nearly all items, suggesting that item responses were, in part, determined by factors other than symptom severity. Limited to outpatients; DIF analysis only sensitive to certain forms of DIF. The present study provides evidence for significant measurement problems involving the YMRS and MADRS. More work is needed to refine these measures and/or develop suitable alternative measures of BD symptomatology for clinical trials research. Copyright © 2016 Elsevier B.V. All rights reserved.

Crizotinib therapy for advanced lung adenocarcinoma and a ROS1 rearrangement: results from the EUROS1 cohort.

PubMed

Mazières, Julien; Zalcman, Gérard; Crinò, Lucio; Biondani, Pamela; Barlesi, Fabrice; Filleron, Thomas; Dingemans, Anne-Marie C; Léna, Hervé; Monnet, Isabelle; Rothschild, Sacha I; Cappuzzo, Federico; Besse, Benjamin; Thiberville, Luc; Rouvière, Damien; Dziadziuszko, Rafal; Smit, Egbert F; Wolf, Jurgen; Spirig, Christian; Pecuchet, Nicolas; Leenders, Frauke; Heuckmann, Johannes M; Diebold, Joachim; Milia, Julie D; Thomas, Roman K; Gautschi, Oliver

2015-03-20

Approximately 1% of lung adenocarcinomas are driven by oncogenic ROS1 rearrangement. Crizotinib is a potent inhibitor of both ROS1 and ALK kinase domains. In the absence of a prospective clinical trial in Europe, we conducted a retrospective study in centers that tested for ROS1 rearrangement. Eligible patients had stage IV lung adenocarcinoma, had ROS1 rearrangement according to fluorescent in situ hybridization, and had received crizotinib therapy through an individual off-label use. Best response was assessed locally using RECIST (version 1.1). All other data were analyzed centrally. We identified 32 eligible patients. One patient was excluded because next-generation sequencing was negative for ROS1 fusion. Median age was 50.5 years, 64.5% of patients were women, and 67.7% were never-smokers. Thirty patients were evaluable for progression-free survival (PFS), and 29 patients were evaluable for best response. We observed four patients with disease progression, two patients with stable disease, and objective response in 24 patients, including five complete responses (overall response rate, 80%; disease control rate, 86.7%). Median PFS was 9.1 months, and the PFS rate at 12 months was 44%. No unexpected adverse effects were observed. Twenty-six patients received pemetrexed (either alone or in combination with platinum and either before or after crizotinib) and had a response rate of 57.7% and a median PFS of 7.2 months. Crizotinib was highly active at treating lung cancer in patients with a ROS1 rearrangement, suggesting that patients with lung adenocarcinomas should be tested for ROS1. Prospective clinical trials with crizotinib and other ROS1 inhibitors are ongoing or planned. © 2015 by American Society of Clinical Oncology.

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

Igidbashian, Levon, E-mail: levonig@hotmail.co; Fortin, Bernard; Guertin, Louis

Purpose: To evaluate the role of neck dissection (ND) after chemoradiation therapy (CRT) for head and neck squamous cell carcinoma (HNSCC) with N3 disease. Methods and Materials: From March 1998 to September 2006, 70 patients with HNSCC and N3 neck disease were treated with concomitant CRT as primary therapy. Response to treatment was assessed using clinical examination and computed tomography 6 to 8 weeks posttreatment. Neck dissection was not routinely performed and considered for those with less than complete response. Of the patients, 26 (37.1%) achieved clinical complete response (cCR) after CRT. A total of 31 (44.3%) underwent ND aftermore » partial response (cPR-ND). Thirteen patients (29.5%) did not achieve cCR and did not undergo ND for the following reasons: incomplete response/progression at primary site, refusal/contraindication to surgery, metastatic progression, or death. These patients were excluded from the analysis. Outcomes were computed using Kaplan-Meier curves and were compared with log rank tests. Results: Comparing the cCR and cPR-ND groups at 2 years, the disease-free survival was respectively 62.7% and 84.9% (p = 0.048); overall survival was 63.0% and 79.4% (p = 0.26), regional relapse-free survival was 87.8% and 96.0% (p = 0.21); and distant disease-free survival was 67.1% and 92.6% (p = 0.059). In the cPR-ND group, 71.0% had no pathologic evidence of disease (PPV of 29.0%). Conclusions: Patients with N3 disease achieving regional cPR and primary cCR who underwent ND seemed to have better outcomes than patients achieving global cCR without ND. Clinical assessment with computed tomography is not adequate for evaluating response to treatment. Because of the inherent limitations of our study, further confirmatory studies are warranted.« less

Safety and Immunogenicity of a Quadrivalent Meningococcal Conjugate Vaccine and Commonly Administered Vaccines After Coadministration.

PubMed

Gasparini, Roberto; Tregnaghi, Miguel; Keshavan, Pavitra; Ypma, Ellen; Han, Linda; Smolenov, Igor

2016-01-01

Given the broad age range across which the quadrivalent meningococcal conjugate vaccine MenACWY-CRM is used, coadministration with routine vaccines should be evaluated across age groups for possible immunologic interference and impact on vaccine reactogenicity and safety. We summarize data from a large population of infants, adolescents and international travelers from 10 phase 3 or 4 clinical studies to evaluate coadministration of MenACWY-CRM with commonly administered vaccines. Noninferiority analyses of immune responses were performed across studies and age groups for each vaccine. Reactogenicity and safety were also assessed. In infants, MenACWY-CRM coadministered with routine vaccines did not reduce immune responses to diphtheria, tetanus, poliovirus, hepatitis B, Haemophilus influenzae type b, pneumococcal conjugate, measles-mumps-rubella, varicella or pertussis antigens. Noninferiority criteria were not met for some pneumococcal conjugate serotypes at 7 months of age, but no consistent trends were observed. In adolescents, coadministration did not reduce immune responses to tetanus, diphtheria and human papilloma virus vaccine antigens. Noninferiority criteria for pertussis antigens were not uniformly met in infant and adolescent studies, although the clinical relevance is unclear. In adults, coadministration did not reduce immune responses to hepatitis A/B, typhoid fever, yellow fever, Japanese encephalitis and rabies antigens. Immune responses to MenACWY-CRM were not impacted by coadministration of commonly administered vaccines. Coadministration did not increase frequencies of postvaccination adverse events in any age group. With no clinically relevant vaccine interactions or impact on vaccine reactogenicity or safety, these results support the coadministration of MenACWY-CRM with routine vaccines in all age groups.

Down-regulation of heat-shock protein 70 (HSP-70) correlated with responsiveness to neoadjuvant aromatase inhibitor therapy in breast cancer patients.

PubMed

Yiu, Christopher C P; Chanplakorn, Niramol; Chan, Monica S M; Loo, Wings T Y; Chow, Louis W C; Toi, Masakazu; Sasano, Hironobu

2010-09-01

Aromatase inhibitor (AI) has been established as an effective endocrine therapy in estrogen receptor (ER)-positive postmenopausal breast cancer patients. Our recent proteomic analysis demonstrated that ten proteins were significantly altered in their expression levels before and after the therapy in the patients receiving neoadjuvant AI. Among these newly identified proteins, heat-shock protein 70 (HSP-70) was the most significantly correlated with both clinical and pathological responses. Therefore, in this study, we further evaluated the significance of this HSP-70 alteration using immunohistochemistry. A total of 32 patients treated with neoadjuvant exemestane or letrozole in whom pre- and post-treatment tumor tissues were available were included. Immunohistochemical evaluation of ER, progesterone receptor (PgR), Her-2, Ki-67 and HSP-70 was performed. Results obtained were compared to both clinical and biological responses of the patients. The majority of the patients responded to treatment (16 patients with partial response, 14 with stable disease and 2 with progressive disease). The means of ER, Ki-67 and HSP-70 were significantly different between treatment responders and non-responders. Decrement of HSP-70 and Ki-67 after AI treatment and pretreatment Ki-67 labeling index of >10% tumor cells were significantly associated with clinical responsiveness to AI treatment (p<0.0001). There was a significant positive correlation between changes of HSP-70 and Ki-67 before and after the therapy. Decrement of HSP-70 in breast carcinoma cells plays important roles in therapeutic mechanisms of AIs through suppressing tumor cell proliferation in breast cancer patients.

EFFICACY OF TACROLIMUS FOR INDUCTION OF REMISSION IN PATIENTS WITH MODERATE-TO-SEVERE ULCERATIVE COLITIS: A SYSTEMATIC REVIEW AND META-ANALYSIS.

PubMed

Lasa, Juan; Olivera, Pablo

2017-01-01

There is evidence that shows that calcineurin inhibitors may be useful for the treatment of severe ulcerative colitis. However, evidence regarding the efficacy of tacrolimus for remission induction in this setting is scarce. To develop a systematic review on the existing evidence regarding the clinical efficacy of tacrolimus for the induction of remission in patients with moderate-to-severe ulcerative colitis. A literature search was undertaken from 1966 to August 2016 using MEDLINE, Embase, LILACS and the Cochrane Library. The following MeSH terms were used: "Inflammatory Bowel Diseases" or "Ulcerative Colitis" and "Calcineurin Inhibitors" or "Tacrolimus" or "FK506". Studies performed in adult ulcerative colitis patients that evaluated the clinical efficacy of tacrolimus for the induction of remission were considered for revision. A meta-analysis was performed with those included studies that were also placebo-controlled and randomized. Clinical response as well as clinical remission and mucosal healing were evaluated. Overall, 755 references were identified, from which 22 studies were finally included. Only two of them were randomized, placebo-controlled trials. A total of 172 patients were evaluated. A significantly lower risk of failure in clinical response was found for tacrolimus versus placebo [RR 0.58 (0.45-0.73)]; moreover, a lower risk of failure in the induction of remission was also found versus placebo [RR 0.91 (0.82-1)]. Tacrolimus seems to be a valid therapeutic alternative for the induction of remission in patients with moderate-to-severe ulcerative colitis.

Survival distributions impact the power of randomized placebo-phase design and parallel groups randomized clinical trials.

PubMed

Abrahamyan, Lusine; Li, Chuan Silvia; Beyene, Joseph; Willan, Andrew R; Feldman, Brian M

2011-03-01

The study evaluated the power of the randomized placebo-phase design (RPPD)-a new design of randomized clinical trials (RCTs), compared with the traditional parallel groups design, assuming various response time distributions. In the RPPD, at some point, all subjects receive the experimental therapy, and the exposure to placebo is for only a short fixed period of time. For the study, an object-oriented simulation program was written in R. The power of the simulated trials was evaluated using six scenarios, where the treatment response times followed the exponential, Weibull, or lognormal distributions. The median response time was assumed to be 355 days for the placebo and 42 days for the experimental drug. Based on the simulation results, the sample size requirements to achieve the same level of power were different under different response time to treatment distributions. The scenario where the response times followed the exponential distribution had the highest sample size requirement. In most scenarios, the parallel groups RCT had higher power compared with the RPPD. The sample size requirement varies depending on the underlying hazard distribution. The RPPD requires more subjects to achieve a similar power to the parallel groups design. Copyright © 2011 Elsevier Inc. All rights reserved.

Psychosocial screening at paediatric BEEC clinics: a pilot evaluation study.

PubMed

Hurrell, Ruth A; Fullwood, Catherine; Keys, Joni; Dickson, Alan P; Fishwick, Janet; Whitnall, Beverley; Cervellione, Raimondo M

2015-04-01

Bladder Exstrophy and Epispadias Complex (BEEC) is associated with an increased risk of impaired mental health, quality of life, and psychosocial functioning. Therefore, screening patients to help identify and evaluate potential psychosocial difficulty is arguably an important consideration for BEEC Services. To screen paediatric BEEC patients for a range of general psychosocial difficulties in a multi-disciplinary out-patient clinic setting. This cross-sectional evaluation was conducted between April 2012 and July 2013. Families attending BEEC multi-disciplinary out-patient clinics were asked to complete a range of standardised psychosocial questionnaires, including the Paediatric Quality of Life Inventory (PedsQL 4.0 Generic Core and Family Impact Module), the Strengths and Difficulties Questionnaire (SDQ), the Paediatric Index of Emotional Distress (PI-ED), and the Hospital Anxiety and Depression Scale (HADS). 108 children attended clinic of which 80 (74.1%) patients and their parents/carers completed some or all of the questionnaires. The mean patient age was 8.41 years (SD = 4.46, range = 1-18 years). There were more boys (N = 50, 62.5%) and the majority had a diagnosis of classic bladder exstrophy (N = 51, 63.8%), followed by primary epispadias (N = 22, 27.5%) and cloacal exstrophy (N = 7, 8.7%). Mean total scores fell within the average/normal range on all questionnaires used (See table below). However, variation around these means was high. Age, gender and diagnosis were found to significantly influence certain questionnaire responses with older-age groups, males, and those with classic bladder exstrophy particularly at risk across some domains. The children/adolescents self-reported better health related quality of life (HRQoL) scores than published results for a range of paediatric chronic health conditions. Differences between parent and child responses on both the PedsQL and SDQ favoured a more positive response on the child self-report questionnaire but were not statistically significant. Mean scores on the measures used suggest a relatively optimistic picture of general psychosocial well-being, especially for HRQoL, in the BEEC population studied. Positive HRQoL outcomes have recently been reported for BEEC paediatric populations. Our results reflect this trend with better mean HRQoL scores than paediatric patients with a range of other chronic health conditions. However, this optimism is cautious given the limitations of this evaluation study and the high variation around the means. Limitations included the small sample size (especially for patients with cloacal exstrophy), the lack of a control group, the limited sensitivity of generic questionnaires in respect of BEEC-specific issues, and the low mean age of patients in the study. Future screening programmes may wish to consider measuring BEEC-specific variables (e.g. satisfaction with genital appearance/function); collecting information on medical aspects, such as continence, pubertal stage and frequency/timing of medical intervention; and asking both parents/carers (where possible) to complete the questionnaires. Screening questionnaire responses were used in conjunction with clinical psychology consultations to evaluate a range of psychosocial aspects in BEEC paediatric patients. Whilst mean scores on the measures used suggest a relatively optimistic picture, certain individual scores did fall within the clinical ranges, highlighting the potential need for further assessment. Developmentally tailored consultations with a clinical psychologist can provide detailed information around questionnaire responses and further assess BEEC specific aspects. Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Students' approaches to learning in a clinical practicum: A psychometric evaluation based on item response theory.

PubMed

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 nursing students' approaches to learning and facilitate their learning in the clinical practicum setting. Copyright © 2018. Published by Elsevier Ltd.

The tinnitus functional index: development of a new clinical measure for chronic, intrusive tinnitus.

PubMed

Meikle, Mary B; Henry, James A; Griest, Susan E; Stewart, Barbara J; Abrams, Harvey B; McArdle, Rachel; Myers, Paula J; Newman, Craig W; Sandridge, Sharon; Turk, Dennis C; Folmer, Robert L; Frederick, Eric J; House, John W; Jacobson, Gary P; Kinney, Sam E; Martin, William H; Nagler, Stephen M; Reich, Gloria E; Searchfield, Grant; Sweetow, Robert; Vernon, Jack A

2012-01-01

Chronic subjective tinnitus is a prevalent condition that causes significant distress to millions of Americans. Effective tinnitus treatments are urgently needed, but evaluating them is hampered by the lack of standardized measures that are validated for both intake assessment and evaluation of treatment outcomes. This work was designed to develop a new self-report questionnaire, the Tinnitus Functional Index (TFI), that would have documented validity both for scaling the severity and negative impact of tinnitus for use in intake assessment and for measuring treatment-related changes in tinnitus (responsiveness) and that would provide comprehensive coverage of multiple tinnitus severity domains. To use preexisting knowledge concerning tinnitus-related problems, an Item Selection Panel (17 expert judges) surveyed the content (175 items) of nine widely used tinnitus questionnaires. From those items, the Panel identified 13 separate domains of tinnitus distress and selected 70 items most likely to be responsive to treatment effects. Eliminating redundant items while retaining good content validity and adding new items to achieve the recommended minimum of 3 to 4 items per domain yielded 43 items, which were then used for constructing TFI Prototype 1.Prototype 1 was tested at five clinics. The 326 participants included consecutive patients receiving tinnitus treatment who provided informed consent-constituting a convenience sample. Construct validity of Prototype 1 as an outcome measure was evaluated by measuring responsiveness of the overall scale and its individual items at 3 and 6 mo follow-up with 65 and 42 participants, respectively. Using a predetermined list of criteria, the 30 best-functioning items were selected for constructing TFI Prototype 2.Prototype 2 was tested at four clinics with 347 participants, including 155 and 86 who provided 3 and 6 mo follow-up data, respectively. Analyses were the same as for Prototype 1. Results were used to select the 25 best-functioning items for the final TFI. Both prototypes and the final TFI displayed strong measurement properties, with few missing data, high validity for scaling of tinnitus severity, and good reliability. All TFI versions exhibited the same eight factors characterizing tinnitus severity and negative impact. Responsiveness, evaluated by computing effect sizes for responses at follow-up, was satisfactory in all TFI versions.In the final TFI, Cronbach's alpha was 0.97 and test-retest reliability 0.78. Convergent validity (r = 0.86 with Tinnitus Handicap Inventory [THI]; r = 0.75 with Visual Analog Scale [VAS]) and discriminant validity (r = 0.56 with Beck Depression Inventory-Primary Care [BDI-PC]) were good. The final TFI was successful at detecting improvement from the initial clinic visit to 3 mo with moderate to large effect sizes and from initial to 6 mo with large effect sizes. Effect sizes for the TFI were generally larger than those obtained for the VAS and THI. After careful evaluation, a 13-point reduction was considered a preliminary criterion for meaningful reduction in TFI outcome scores. The TFI should be useful in both clinical and research settings because of its responsiveness to treatment-related change, validity for scaling the overall severity of tinnitus, and comprehensive coverage of multiple domains of tinnitus severity.

Latin American and Caribbean countries' baseline clinical and policy guidelines for responding to intimate partner violence and sexual violence against women.

PubMed

Stewart, Donna E; Aviles, Raquel; Guedes, Alessandra; Riazantseva, Ekaterina; MacMillan, Harriet

2015-07-15

Violence against women is a global public health problem with negative effects on physical, mental, and reproductive health. The World Health Organization (WHO) has identified intimate partner violence (IPV) and sexual violence (SV) as major targets for prevention and amelioration and recently developed clinical and policy guidelines to assist healthcare providers. This project was undertaken to determine the 2013 baseline national policies and clinical guidelines on IPV and SV within the Latin American and Caribbean (LAC) region to identify strengths and gaps requiring action. Each Pan American Health Organization/World Health Organization Regional Office for the Americas (PAHO/WHO) country focal point was contacted to request their current national policy and clinical guidelines (protocol) on IPV/SV. We augmented this by searching the internet and the United Nations Women website. Each country's policy and clinical guideline (where available) was reviewed and entered into a scoring matrix based on WHO Clinical and Policy Guidelines. A total score for each heading and subheading was developed by adding positive responses to identify LAC regional strengths and gaps. We obtained 15 national policies and 12 national clinical guidelines (protocols) from a total of 18 countries ("response" rate 66.7%). National policies were comprehensive in terms of physical, emotional, and sexual violence and recommended good intersectoral collaboration. The greatest gap was in the training of health-care providers. National Guidelines for women-centered care for IPV/SV survivors were strong in the vital areas of privacy, confidentiality, danger assessment, safety planning, and supportive reactions to disclosure. The largest gaps noted were again in training healthcare professionals and strengthening monitoring and evaluation of services. Baseline measurement of policy and clinical guidelines for IPV/SV in LAC PAHO/WHO member countries at the time of issuing the 2013 WHO Clinical and Policy Guidelines reveals some important strengths, but also serious gaps that need to be addressed. The most pressing needs are for concerted training initiatives for healthcare providers and strengthening multisectoral monitoring and evaluation of services. A future evaluation of national policies, clinical guidelines, monitoring and evaluation will need to be conducted to measure the progress of the required scaling-up process.

Towards personalized therapy for multiple sclerosis: prediction of individual treatment response.

PubMed

Kalincik, Tomas; Manouchehrinia, Ali; Sobisek, Lukas; Jokubaitis, Vilija; Spelman, Tim; Horakova, Dana; Havrdova, Eva; Trojano, Maria; Izquierdo, Guillermo; Lugaresi, Alessandra; Girard, Marc; Prat, Alexandre; Duquette, Pierre; Grammond, Pierre; Sola, Patrizia; Hupperts, Raymond; Grand'Maison, Francois; Pucci, Eugenio; Boz, Cavit; Alroughani, Raed; Van Pesch, Vincent; Lechner-Scott, Jeannette; Terzi, Murat; Bergamaschi, Roberto; Iuliano, Gerardo; Granella, Franco; Spitaleri, Daniele; Shaygannejad, Vahid; Oreja-Guevara, Celia; Slee, Mark; Ampapa, Radek; Verheul, Freek; McCombe, Pamela; Olascoaga, Javier; Amato, Maria Pia; Vucic, Steve; Hodgkinson, Suzanne; Ramo-Tello, Cristina; Flechter, Shlomo; Cristiano, Edgardo; Rozsa, Csilla; Moore, Fraser; Luis Sanchez-Menoyo, Jose; Laura Saladino, Maria; Barnett, Michael; Hillert, Jan; Butzkueven, Helmut

2017-09-01

Timely initiation of effective therapy is crucial for preventing disability in multiple sclerosis; however, treatment response varies greatly among patients. Comprehensive predictive models of individual treatment response are lacking. Our aims were: (i) to develop predictive algorithms for individual treatment response using demographic, clinical and paraclinical predictors in patients with multiple sclerosis; and (ii) to evaluate accuracy, and internal and external validity of these algorithms. This study evaluated 27 demographic, clinical and paraclinical predictors of individual response to seven disease-modifying therapies in MSBase, a large global cohort study. Treatment response was analysed separately for disability progression, disability regression, relapse frequency, conversion to secondary progressive disease, change in the cumulative disease burden, and the probability of treatment discontinuation. Multivariable survival and generalized linear models were used, together with the principal component analysis to reduce model dimensionality and prevent overparameterization. Accuracy of the individual prediction was tested and its internal validity was evaluated in a separate, non-overlapping cohort. External validity was evaluated in a geographically distinct cohort, the Swedish Multiple Sclerosis Registry. In the training cohort (n = 8513), the most prominent modifiers of treatment response comprised age, disease duration, disease course, previous relapse activity, disability, predominant relapse phenotype and previous therapy. Importantly, the magnitude and direction of the associations varied among therapies and disease outcomes. Higher probability of disability progression during treatment with injectable therapies was predominantly associated with a greater disability at treatment start and the previous therapy. For fingolimod, natalizumab or mitoxantrone, it was mainly associated with lower pretreatment relapse activity. The probability of disability regression was predominantly associated with pre-baseline disability, therapy and relapse activity. Relapse incidence was associated with pretreatment relapse activity, age and relapsing disease course, with the strength of these associations varying among therapies. Accuracy and internal validity (n = 1196) of the resulting predictive models was high (>80%) for relapse incidence during the first year and for disability outcomes, moderate for relapse incidence in Years 2-4 and for the change in the cumulative disease burden, and low for conversion to secondary progressive disease and treatment discontinuation. External validation showed similar results, demonstrating high external validity for disability and relapse outcomes, moderate external validity for cumulative disease burden and low external validity for conversion to secondary progressive disease and treatment discontinuation. We conclude that demographic, clinical and paraclinical information helps predict individual response to disease-modifying therapies at the time of their commencement. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Checkpoint inhibition for advanced mucosal melanoma.

PubMed

Thierauf, Julia; Veit, Johannes A; Hess, Jochen; Treiber, Nicolai; Lisson, Catharina; Weissinger, Stephanie E; Bommer, Martin; Hoffmann, Thomas K

2017-04-01

Whereas anti-PD-1 therapy has demonstrated a significant and durable response against advanced cutaneous melanoma, conventional chemotherapies have shown only minor benefit against advanced mucosal melanoma. To investigate the efficacy of anti-PD-1 therapy in a small cohort of patients with mucosal melanoma of the head and neck. We analysed five patients with mucosal melanoma of the head and neck who received nivolumab or pembrolizumab, at an advanced stage. Expression of PD-L1 and PD-1 in all tumour samples was evaluated immunohistochemically. All patients received at least two cycles of nivolumab or pembrolizumab. The most severe adverse events were categorised as CTCAE (common terminology criteria for adverse events) Grade 2. All patients showed progressive disease after restaging at three and six months, and no partial or complete response was observed. Immunohistochemical staining demonstrated PD-L1 expression in less than 5% of tumour cells. Systemic therapy with either nivolumab or pembrolizumab showed no clinical response, however, tumour progression was identified in all patients using Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 and immune-related response criteria (irRC) to evaluate tumour response.

Student Evaluation of Faculty Physicians: Gender Differences in Teaching Evaluations.

PubMed

Morgan, Helen K; Purkiss, Joel A; Porter, Annie C; Lypson, Monica L; Santen, Sally A; Christner, Jennifer G; Grum, Cyril M; Hammoud, Maya M

2016-05-01

To investigate whether there is a difference in medical student teaching evaluations for male and female clinical physician faculty. The authors examined all teaching evaluations completed by clinical students at one North American medical school in the surgery, obstetrics and gynecology, pediatrics, and internal medicine clinical rotations from 2008 to 2012. The authors focused on how students rated physician faculty on their "overall quality of teaching" using a 5-point response scale (1 = Poor to 5 = Excellent). Linear mixed-effects models provided estimated mean differences in evaluation outcomes by faculty gender. There were 14,107 teaching evaluations of 965 physician faculty. Of these evaluations, 7688 (54%) were for male physician faculty and 6419 (46%) were for female physician faculty. Female physicians received significantly lower mean evaluation scores in all four rotations. The discrepancy was largest in the surgery rotation (males = 4.23, females = 4.01, p = 0.003). Pediatrics showed the next greatest difference (males = 4.44, females = 4.29, p = 0.009), followed by obstetrics and gynecology (males = 4.38, females = 4.26, p = 0.026), and internal medicine (males = 4.35, females = 4.27, p = 0.043). Female physicians received lower teaching evaluations in all four core clinical rotations. This comprehensive examination adds to the medical literature by illuminating subtle differences in evaluations based on physician gender, and provides further evidence of disparities for women in academic medicine.

Network Mechanisms of Clinical Response to Transcranial Magnetic Stimulation in Posttraumatic Stress Disorder and Major Depressive Disorder.

PubMed

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. Published by Elsevier Inc.

Defining competency-based evaluation objectives in family medicine

PubMed Central

Allen, Tim; Brailovsky, Carlos; Rainsberry, Paul; Lawrence, Katherine; Crichton, Tom; Carpentier, Marie-Pierre; Visser, Shaun

2011-01-01

Abstract Objective To develop a definition of competence in family medicine sufficient to guide a review of Certification examinations by the Board of Examiners of the College of Family Physicians of Canada. Design Delphi analysis of responses to a 4-question postal survey. Setting Canadian family practice. Participants A total of 302 family physicians who have served as examiners for the College of Family Physicians of Canada’s Certification examination. Methods A survey comprising 4 short-answer questions was mailed to the 302 participating family physicians asking them to list elements that define competence in family medicine among newly certified family physicians beginning independent practice. Two expert groups used a modified Delphi consensus process to analyze responses and generate 2 basic components of this definition of competence: first, the problems that a newly practising family physician should be competent to handle; second, the qualities, behaviour, and skills that characterize competence at the start of independent practice. Main findings Response rate was 54%; total number of elements among all responses was 5077, for an average 31 per respondent. Of the elements, 2676 were topics or clinical situations to be dealt with; the other 2401 were skills, behaviour patterns, or qualities, without reference to a specific clinical problem. The expert groups identified 6 essential skills, the phases of the clinical encounter, and 99 priority topics as the descriptors used by the respondents. More than 20% of respondents cited 30 of the topics. Conclusion Family physicians define the domain of competence in family medicine in terms of 6 essential skills, the phases of the clinical encounter, and priority topics. This survey represents the first level of definition of evaluation objectives in family medicine. Definition of the interactions among these elements will permit these objectives to become detailed enough to effectively guide assessment. PMID:21918130

Incorporating prognostic imaging biomarkers into clinical practice

PubMed Central

Miles, Kenneth A.

2013-01-01

Abstract A prognostic imaging biomarker can be defined as an imaging characteristic that is objectively measurable and provides information on the likely outcome of the cancer disease in an untreated individual and should be distinguished from predictive imaging biomarkers and imaging markers of response. A range of tumour characteristics of potential prognostic value can be measured using a variety imaging modalities. However, none has currently been adopted into routine clinical practice. This article considers key examples of emerging prognostic imaging biomarkers and proposes an evaluation framework that aims to demonstrate clinical efficacy and so support their introduction into the clinical arena. With appropriate validation within an established evaluation framework, prognostic imaging biomarkers have the potential to contribute to individualized cancer care, in some cases reducing the financial burden of expensive cancer treatments by facilitating their more rational use. PMID:24060808

Dorsal midbrain syndrome associated with persistent neck extension: Clinical and diagnostic imaging findings in 2 dogs

PubMed Central

Canal, Sara; Baroni, Massimo; Falzone, Cristian; De Benedictis, Giulia M.; Bernardini, Marco

2015-01-01

Two young dogs were evaluated for an acute onset of abnormal head posture and eye movement. Neurological examination was characterized mostly by permanent neck extension, abnormalities of pupils, and eye movement. A mesencephalic mass lesion was detected on magnetic resonance imaging in both cases. Neurophysiological pathways likely responsible for this peculiar clinical presentation are discussed. PMID:26663922

A Comparative Analysis of Drug-Induced Hepatotoxicity in Clinically Relevant Situations

PubMed Central

Thiel, Christoph; Cordes, Henrik; Fabbri, Lorenzo; Aschmann, Hélène Eloise; Baier, Vanessa; Atkinson, Francis; Blank, Lars Mathias; Kuepfer, Lars

2017-01-01

Drug-induced toxicity is a significant problem in clinical care. A key problem here is a general understanding of the molecular mechanisms accompanying the transition from desired drug effects to adverse events following administration of either therapeutic or toxic doses, in particular within a patient context. Here, a comparative toxicity analysis was performed for fifteen hepatotoxic drugs by evaluating toxic changes reflecting the transition from therapeutic drug responses to toxic reactions at the cellular level. By use of physiologically-based pharmacokinetic modeling, in vitro toxicity data were first contextualized to quantitatively describe time-resolved drug responses within a patient context. Comparatively studying toxic changes across the considered hepatotoxicants allowed the identification of subsets of drugs sharing similar perturbations on key cellular processes, functional classes of genes, and individual genes. The identified subsets of drugs were next analyzed with regard to drug-related characteristics and their physicochemical properties. Toxic changes were finally evaluated to predict both molecular biomarkers and potential drug-drug interactions. The results may facilitate the early diagnosis of adverse drug events in clinical application. PMID:28151932

The Physiological Basis and Clinical Use of the Binaural Interaction Component of the Auditory Brainstem Response

PubMed Central

Klump, Georg M.; Tollin, Daniel J.

2016-01-01

The auditory brainstem response (ABR) is a sound-evoked non-invasively measured electrical potential representing the sum of neuronal activity in the auditory brainstem and midbrain. ABR peak amplitudes and latencies are widely used in human and animal auditory research and for clinical screening. The binaural interaction component (BIC) of the ABR stands for the difference between the sum of the monaural ABRs and the ABR obtained with binaural stimulation. The BIC comprises a series of distinct waves, the largest of which (DN1) has been used for evaluating binaural hearing in both normal hearing and hearing-impaired listeners. Based on data from animal and human studies, we discuss the possible anatomical and physiological bases of the BIC (DN1 in particular). The effects of electrode placement and stimulus characteristics on the binaurally evoked ABR are evaluated. We review how inter-aural time and intensity differences affect the BIC and, analyzing these dependencies, draw conclusion about the mechanism underlying the generation of the BIC. Finally, the utility of the BIC for clinical diagnoses are summarized. PMID:27232077

“Glowing Head” Mice: A Genetic Tool Enabling Reliable Preclinical Image-Based Evaluation of Cancers in Immunocompetent Allografts

PubMed Central

Day, Chi-Ping; Carter, John; Ohler, Zoe Weaver; Bonomi, Carrie; El Meskini, Rajaa; Martin, Philip; Graff-Cherry, Cari; Feigenbaum, Lionel; Tüting, Thomas; Van Dyke, Terry; Hollingshead, Melinda; Merlino, Glenn

2014-01-01

Preclinical therapeutic assessment currently relies on the growth response of established human cell lines xenografted into immunocompromised mice, a strategy that is generally not predictive of clinical outcomes. Immunocompetent genetically engineered mouse (GEM)-derived tumor allograft models offer highly tractable preclinical alternatives and facilitate analysis of clinically promising immunomodulatory agents. Imageable reporters are essential for accurately tracking tumor growth and response, particularly for metastases. Unfortunately, reporters such as luciferase and GFP are foreign antigens in immunocompetent mice, potentially hindering tumor growth and confounding therapeutic responses. Here we assessed the value of reporter-tolerized GEMs as allograft recipients by targeting minimal expression of a luciferase-GFP fusion reporter to the anterior pituitary gland (dubbed the “Glowing Head” or GH mouse). The luciferase-GFP reporter expressed in tumor cells induced adverse immune responses in wildtype mouse, but not in GH mouse, as transplantation hosts. The antigenicity of optical reporters resulted in a decrease in both the growth and metastatic potential of the labeled tumor in wildtype mice as compared to the GH mice. Moreover, reporter expression can also alter the tumor response to chemotherapy or targeted therapy in a context-dependent manner. Thus the GH mice and experimental approaches vetted herein provide concept validation and a strategy for effective, reproducible preclinical evaluation of growth and response kinetics for traceable tumors. PMID:25369133

Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017)

PubMed Central

Huang, Hongyun; Young, Wise; Chen, Lin; Feng, Shiqing; Zoubi, Ziad M. Al; Sharma, Hari Shanker; Saberi, Hooshang; Moviglia, Gustavo A.; He, Xijing; Muresanu, Dafin F.; Sharma, Alok; Otom, Ali; Andrews, Russell J.; Al-Zoubi, Adeeb; Bryukhovetskiy, Andrey S.; Chernykh, Elena R.; Domańska-Janik, Krystyna; Jafar, Emad; Johnson, W. Eustace; Li, Ying; Li, Daqing; Luan, Zuo; Mao, Gengsheng; Shetty, Ashok K.; Siniscalco, Dario; Skaper, Stephen; Sun, Tiansheng; Wang, Yunliang; Wiklund, Lars; Xue, Qun; You, Si-Wei; Zheng, Zuncheng; Dimitrijevic, Milan R.; Masri, W. S. El; Sanberg, Paul R.; Xu, Qunyuan; Luan, Guoming; Chopp, Michael; Cho, Kyoung-Suok; Zhou, Xin-Fu; Wu, Ping; Liu, Kai; Mobasheri, Hamid; Ohtori, Seiji; Tanaka, Hiroyuki; Han, Fabin; Feng, Yaping; Zhang, Shaocheng; Lu, Yingjie; Zhang, Zhicheng; Rao, Yaojian; Tang, Zhouping; Xi, Haitao; Wu, Liang; Shen, Shunji; Xue, Mengzhou; Xiang, Guanghong; Guo, Xiaoling; Yang, Xiaofeng; Hao, Yujun; Hu, Yong; Li, Jinfeng; AO, Qiang; Wang, Bin; Zhang, Zhiwen; Lu, Ming; Li, Tong

2018-01-01

Cell therapy has been shown to be a key clinical therapeutic option for central nervous system diseases or damage. Standardization of clinical cell therapy procedures is an important task for professional associations devoted to cell therapy. The Chinese Branch of the International Association of Neurorestoratology (IANR) completed the first set of guidelines governing the clinical application of neurorestoration in 2011. The IANR and the Chinese Association of Neurorestoratology (CANR) collaborated to propose the current version “Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017)”. The IANR council board members and CANR committee members approved this proposal on September 1, 2016, and recommend it to clinical practitioners of cellular therapy. These guidelines include items of cell type nomenclature, cell quality control, minimal suggested cell doses, patient-informed consent, indications for undergoing cell therapy, contraindications for undergoing cell therapy, documentation of procedure and therapy, safety evaluation, efficacy evaluation, policy of repeated treatments, do not charge patients for unproven therapies, basic principles of cell therapy, and publishing responsibility. PMID:29637817

Recommendations for standardized pathological characterization of residual disease for neoadjuvant clinical trials of breast cancer by the BIG-NABCG collaboration

PubMed Central

Bossuyt, V.; Provenzano, E.; Symmans, W. F.; Boughey, J. C.; Coles, C.; Curigliano, G.; Dixon, J. M.; Esserman, L. J.; Fastner, G.; Kuehn, T.; Peintinger, F.; von Minckwitz, G.; White, J.; Yang, W.; Badve, S.; Denkert, C.; MacGrogan, G.; Penault-Llorca, F.; Viale, G.; Cameron, D.; Earl, Helena; Alba, Emilio; Lluch, Ana; Albanell, Joan; Amos, Keith; Biernat, Wojciech; Bonnefoi, Hervé; Buzdar, Aman; Cane, Paul; Pinder, Sarah; Carson, Lesley; Dickson-Witmer, Diana; Gong, Gyungyub; Green, Jimmy; Hsu, Chih-Yi; Tseng, Ling-Ming; Kroep, Judith; Leitch, A. Marilyn; Sarode, Venetia; Mamounas, Eleftherios; Marcom, Paul Kelly; Nuciforo, Paolo; Paik, Soonmyung; Peg, Vicente; Peston, David; Pierga, Jean-Yves; Quintela-Fandino, Miguel; Salgado, Roberto; Sikov, William; Thomas, Jeremy; Unzeitig, Gary; Wesseling, Jelle

2015-01-01

Neoadjuvant systemic therapy (NAST) provides the unique opportunity to assess response to treatment after months rather than years of follow-up. However, significant variability exists in methods of pathologic assessment of response to NAST, and thus its interpretation for subsequent clinical decisions. Our international multidisciplinary working group was convened by the Breast International Group-North American Breast Cancer Group (BIG-NABCG) collaboration and tasked to recommend practical methods for standardized evaluation of the post-NAST surgical breast cancer specimen for clinical trials that promote accurate and reliable designation of pathologic complete response (pCR) and meaningful characterization of residual disease. Recommendations include multidisciplinary communication; clinical marking of the tumor site (clips); and radiologic, photographic, or pictorial imaging of the sliced specimen, to map the tissue sections and reconcile macroscopic and microscopic findings. The information required to define pCR (ypT0/is ypN0 or ypT0 yp N0), residual ypT and ypN stage using the current AJCC/UICC system, and the Residual Cancer Burden system were recommended for quantification of residual disease in clinical trials. PMID:26019189

Targeted Proteomics Predicts a Sustained Complete-Response after Transarterial Chemoembolization and Clinical Outcomes in Patients with Hepatocellular Carcinoma: A Prospective Cohort Study.

PubMed

Yu, Su Jong; Kim, Hyunsoo; Min, Hophil; Sohn, Areum; Cho, Young Youn; Yoo, Jeong-Ju; Lee, Dong Hyeon; Cho, Eun Ju; Lee, Jeong-Hoon; Gim, Jungsoo; Park, Taesung; Kim, Yoon Jun; Kim, Chung Yong; Yoon, Jung-Hwan; Kim, Youngsoo

2017-03-03

This study was aimed to identify blood-based biomarkers to predict a sustained complete response (CR) after transarterial chemoembolization (TACE) using targeted proteomics. Consecutive patients with HCC who had undergone TACE were prospectively enrolled (training (n = 100) and validation set (n = 80)). Serum samples were obtained before and 6 months after TACE. Treatment responses were evaluated using the modified Response Evaluation Criteria in Solid Tumors (mRECIST). In the training set, the MRM-MS assay identified five marker candidate proteins (LRG1, APCS, BCHE, C7, and FCN3). When this five-marker panel was combined with the best-performing clinical variables (tumor number, baseline PIVKA, and baseline AFP), the resulting ensemble model had the highest area under the receiver operating curve (AUROC) value in predicting a sustained CR after TACE in the training and validation sets (0.881 and 0.813, respectively). Furthermore, the ensemble model was an independent predictor of rapid progression (hazard ratio (HR), 2.889; 95% confidence interval (CI), 1.612-5.178; P value < 0.001) and overall an unfavorable survival rate (HR, 1.985; 95% CI, 1.024-3.848; P value = 0.042) in the entire population by multivariate analysis. Targeted proteomics-based ensemble model can predict clinical outcomes after TACE. Therefore, this model can aid in determining the best candidates for TACE and the need for adjuvant therapy.

Analysis of the psychometric properties of the Multiple Sclerosis Impact Scale-29 (MSIS-29) in relapsing–remitting multiple sclerosis using classical and modern test theory

PubMed Central

Wyrwich, KW; Phillips, GA; Vollmer, T; Guo, S

2016-01-01

Background Investigations using classical test theory support the psychometric properties of the original version of the Multiple Sclerosis Impact Scale (MSIS-29v1), a disease-specific measure of multiple sclerosis (MS) impact (physical and psychological subscales). Later, assessments of the MSIS-29v1 in an MS community-based sample using Rasch analysis led to revisions of the instrument’s response options (MSIS-29v2). Objective The objective of this paper is to evaluate the psychometric properties of the MSIS-29v1 in a clinical trial cohort of relapsing–remitting MS patients (RRMS). Methods Data from 600 patients with RRMS enrolled in the SELECT clinical trial were used. Assessments were performed at baseline and at Weeks 12, 24, and 52. In addition to traditional psychometric analyses, Item Response Theory (IRT) and Rasch analysis were used to evaluate the measurement properties of the MSIS-29v1. Results Both MSIS-29v1 subscales demonstrated strong reliability, construct validity, and responsiveness. The IRT and Rasch analysis showed overall support for response category threshold ordering, person-item fit, and item fit for both subscales. Conclusions Both MSIS-29v1 subscales demonstrated robust measurement properties using classical, IRT, and Rasch techniques. Unlike previous research using a community-based sample, the MSIS-29v1 was found to be psychometrically sound to assess physical and psychological impairments in a clinical trial sample of patients with RRMS. PMID:28607741

Analysis of the psychometric properties of the Multiple Sclerosis Impact Scale-29 (MSIS-29) in relapsing-remitting multiple sclerosis using classical and modern test theory.

PubMed

Bacci, E D; Wyrwich, K W; Phillips, G A; Vollmer, T; Guo, S

2016-01-01

Investigations using classical test theory support the psychometric properties of the original version of the Multiple Sclerosis Impact Scale (MSIS-29v1), a disease-specific measure of multiple sclerosis (MS) impact (physical and psychological subscales). Later, assessments of the MSIS-29v1 in an MS community-based sample using Rasch analysis led to revisions of the instrument's response options (MSIS-29v2). The objective of this paper is to evaluate the psychometric properties of the MSIS-29v1 in a clinical trial cohort of relapsing-remitting MS patients (RRMS). Data from 600 patients with RRMS enrolled in the SELECT clinical trial were used. Assessments were performed at baseline and at Weeks 12, 24, and 52. In addition to traditional psychometric analyses, Item Response Theory (IRT) and Rasch analysis were used to evaluate the measurement properties of the MSIS-29v1. Both MSIS-29v1 subscales demonstrated strong reliability, construct validity, and responsiveness. The IRT and Rasch analysis showed overall support for response category threshold ordering, person-item fit, and item fit for both subscales. Both MSIS-29v1 subscales demonstrated robust measurement properties using classical, IRT, and Rasch techniques. Unlike previous research using a community-based sample, the MSIS-29v1 was found to be psychometrically sound to assess physical and psychological impairments in a clinical trial sample of patients with RRMS.

Further consideration of the clonal nature of Salmonella typhi: evaluation of molecular and clinical characteristics of strains from Indonesia and Peru.

PubMed Central

Franco, A; Gonzalez, C; Levine, O S; Lagos, R; Hall, R H; Hoffman, S L; Moechtar, M A; Gotuzzo, E; Levine, M M; Hone, D M

1992-01-01

We examined envelope protein profiles, chromosomal restriction endonuclease digest patterns, and immune responses to envelope proteins for collections of Salmonella typhi strains isolated in Peru and Indonesia. Only minor differences in envelope protein patterns were apparent among strains. Strains from 7 of 20 Indonesian patients had a distinct chromosomal digest pattern compared with patterns of Peruvian and other Indonesian strains. Strains with this pattern carried the gene for the j flagellar antigen (H1-j); differences in response to envelope proteins of j and d strains were noted on immunoblot analysis. Our data suggest that there are genotypic and phenotypic differences among S. typhi strains. The clinical importance of these differences remains to be fully evaluated; however, in this study it was not possible to show a clear correlation between strain characteristics and disease severity. Images PMID:1500532

Evaluation of several ultrasonography scoring systems for synovitis and comparison to clinical examination: results from a prospective multicentre study of rheumatoid arthritis.

PubMed

Dougados, Maxime; Jousse-Joulin, Sandrine; Mistretta, Frederic; d'Agostino, Maria-Antonietta; Backhaus, Marina; Bentin, Jacques; Chalès, Gérard; Chary-Valckenaere, Isabelle; Conaghan, Philip; Etchepare, Fabien; Gaudin, Philippe; Grassi, Walter; van der Heijde, Désirée; Sellam, Jérémie; Naredo, Esperanza; Szkudlarek, Marcin; Wakefield, Richard; Saraux, Alain

2010-05-01

To evaluate different global ultrasonographic (US) synovitis scoring systems as potential outcome measures of rheumatoid arthritis (RA) according to the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) filter. To study selected global scoring systems, for the clinical, B mode and power Doppler techniques, the following joints were evaluated: 28 joints (28-joint Disease Activity Score (DAS28)), 20 joints (metacarpophalangeals (MCPs) + metatarsophalangeals (MTPs)) and 38 joints (28 joints + MTPs) using either a binary (yes/no) or a 0-3 grade. The study was a prospective, 4-month duration follow-up of 76 patients with RA requiring anti-tumour necrosis factor (TNF) therapy (complete follow-up data: 66 patients). Intraobserver reliability was evaluated using the intraclass correlation coefficient (ICC), construct validity was evaluated using the Cronbach alpha test and external validity was evaluated using level of correlation between scoring system and C reactive protein (CRP). Sensitivity to change was evaluated using the standardised response mean. Discriminating capacity was evaluated using the standardised mean differences in patients considered by the doctor as significantly improved or not at the end of the study. Different clinimetric properties of various US scoring systems were at least as good as the clinical scores with, for example, intraobserver reliability ranging from 0.61 to 0.97 versus from 0.53 to 0.82, construct validity ranging from 0.76 to 0.89 versus from 0.76 to 0.88, correlation with CRP ranging from 0.28 to 0.34 versus from 0.28 to 0.35 and sensitivity to change ranging from 0.60 to 1.21 versus from 0.96 to 1.36 for US versus clinical scoring systems, respectively. This study suggests that US evaluation of synovitis is an outcome measure at least as relevant as physical examination. Further studies are required in order to achieve optimal US scoring systems for monitoring patients with RA in clinical trials and in clinical practice.

Immune response to Sarcocystis neurona infection in naturally infected horses with equine protozoal myeloencephalitis.

PubMed

Yang, Jibing; Ellison, Siobhan; Gogal, Robert; Norton, Heather; Lindsay, David S; Andrews, Frank; Ward, Daniel; Witonsky, Sharon

2006-06-15

Equine protozoal myeloencephalitis (EPM) is one of the most common neurologic diseases of horses in the United States. The primary etiologic agent is Sarcocystis neurona. Currently, there is limited knowledge regarding the protective or pathophysiologic immune response to S. neurona infection or the subsequent development of EPM. The objectives of this study were to determine whether S. neurona infected horses with clinical signs of EPM had altered or suppressed immune responses compared to neurologically normal horses and if blood sample storage would influence these findings. Twenty clinically normal horses and 22 horses with EPM, diagnosed by the presence of S. neurona specific antibodies in the serum and/or cerebrospinal (CSF) and clinical signs, were evaluated for differences in the immune cell subsets and function. Our results demonstrated that naturally infected horses had significantly (P<0.05) higher percentages of CD4 T-lymphocytes and neutrophils (PMN) in separated peripheral blood leukocytes than clinically normal horses. Leukocytes from naturally infected EPM horses had significantly lower proliferation responses, as measured by thymidine incorporation, to a non-antigen specific mitogen than did clinically normal horses (P<0.05). Currently, studies are in progress to determine the role of CD4 T cells in disease and protection against S. neurona in horses, as well as to determine the mechanism associated with suppressed in vitro proliferation responses. Finally, overnight storage of blood samples appears to alter T lymphocyte phenotypes and viability among leukocytes.

Cholera in pregnancy: Clinical and immunological aspects.

PubMed

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.

Validation study of a web-based assessment of functional recovery after radical prostatectomy.

PubMed

Vickers, Andrew J; Savage, Caroline J; Shouery, Marwan; Eastham, James A; Scardino, Peter T; Basch, Ethan M

2010-08-05

Good clinical care of prostate cancer patients after radical prostatectomy depends on careful assessment of post-operative morbidities, yet physicians do not always judge patient symptoms accurately. Logistical problems associated with using paper questionnaire limit their use in the clinic. We have implemented a web-interface ("STAR") for patient-reported outcomes after radical prostatectomy. We analyzed data on the first 9 months of clinical implementation to evaluate the validity of the STAR questionnaire to assess functional outcomes following radical prostatectomy. We assessed response rate, internal consistency within domains, and the association between survey responses and known predictors of sexual and urinary function, including age, time from surgery, nerve sparing status and co-morbidities. Of 1581 men sent an invitation to complete the instrument online, 1235 responded for a response rate of 78%. Cronbach's alpha was 0.84, 0.86 and 0.97 for bowel, urinary and sexual function respectively. All known predictors of sexual and urinary function were significantly associated with survey responses in the hypothesized direction. We have found that web-based assessment of functional recovery after radical prostatectomy is practical and feasible. The instrument demonstrated excellent psychometric properties, suggested that validity is maintained when questions are transferred from paper to electronic format and when patients give responses that they know will be seen by their doctor and added to their clinic record. As such, our system allows ready implementation of patient-reported outcomes into routine clinical practice.

Validation study of a web-based assessment of functional recovery after radical prostatectomy

PubMed Central

2010-01-01

Background Good clinical care of prostate cancer patients after radical prostatectomy depends on careful assessment of post-operative morbidities, yet physicians do not always judge patient symptoms accurately. Logistical problems associated with using paper questionnaire limit their use in the clinic. We have implemented a web-interface ("STAR") for patient-reported outcomes after radical prostatectomy. Methods We analyzed data on the first 9 months of clinical implementation to evaluate the validity of the STAR questionnaire to assess functional outcomes following radical prostatectomy. We assessed response rate, internal consistency within domains, and the association between survey responses and known predictors of sexual and urinary function, including age, time from surgery, nerve sparing status and co-morbidities. Results Of 1581 men sent an invitation to complete the instrument online, 1235 responded for a response rate of 78%. Cronbach's alpha was 0.84, 0.86 and 0.97 for bowel, urinary and sexual function respectively. All known predictors of sexual and urinary function were significantly associated with survey responses in the hypothesized direction. Conclusions We have found that web-based assessment of functional recovery after radical prostatectomy is practical and feasible. The instrument demonstrated excellent psychometric properties, suggested that validity is maintained when questions are transferred from paper to electronic format and when patients give responses that they know will be seen by their doctor and added to their clinic record. As such, our system allows ready implementation of patient-reported outcomes into routine clinical practice. PMID:20687938

Influence of vestibulovaginal stenosis, pelvic bladder, and recessed vulva on response to treatment for clinical signs of lower urinary tract disease in dogs: 38 cases (1990-1999).

PubMed

Crawford, Jason T; Adams, William M

2002-10-01

To determine influence of vestibulovaginal stenosis, pelvic bladder, and recessed vulva on response to treatment for clinical signs of lower urinary tract disease in dogs. Retrospective study. 38 spayed female dogs. Medical records and client follow-up were reviewed for dogs evaluated via excretory urography because of clinical signs of lower urinary tract disease. Clinical signs, results of radiography, and response to surgical or medical treatment were analyzed. Clinical signs included urinary tract infection (n = 24), urinary incontinence (20), vaginitis (11), pollakiuria or stranguria (10), and perivulvar dermatitis (4). Vaginocystourethrographic findings included vestibulovaginal stenosis (n = 28), pelvic bladder (17), and ureteritis or pyelonephritis (4). Ten dogs had a vestibulovaginal ratio of < 0.20 (severe stenosis), 9 dogs had a ratio of 0.20 to 0.25 (moderate stenosis), 9 dogs had a ratio of 0.26 to 0.35 (mild stenosis), and 10 dogs had a ratio of > 0.35 (anatomically normal). Lower urinary tract infection, incontinence, and pelvic bladder were not associated with response to treatment for recessed vulva. Vestibulovaginal stenosis with a ratio < 0.20 was significantly associated negatively with response to treatment. Dogs without severe vestibulovaginal stenosis that received vulvoplasty for a recessed vulva responded well to treatment. Vestibulovaginal stenosis is likely an important factor in dogs with vestibulovaginal ratio < 0.20. Vaginectomy or resection and anastomosis should be considered in dogs with severe vestibulovaginal stenosis and signs of lower urinary tract disease.

Using Chinese Version of MYMOP in Chinese Medicine Evaluation: Validity, Responsiveness and Minimally Important Change

PubMed Central

2010-01-01

Background Measure Yourself Medical Outcome Profile (MYMOP) is a patient generated outcome instrument applicable in the evaluation of both allopathic and complementary medicine treatment. This study aims to adapt MYMOP into Chinese, and to assess its validity, responsiveness and minimally important change values in a sample of patients using Chinese medicine (CM) services. Methods A Chinese version of MYMOP (CMYMOP) is developed by forward-backward-forward translation strategy, expert panel assessment and pilot testing amongst patients. 272 patients aged 18 or above with subjective symptoms in the past 2 weeks were recruited at a CM clinic, and were invited to complete a set of questionnaire containing CMYMOP and SF-36. Follow ups were performed at 2nd and 4th week after consultation, using the same set of questionnaire plus a global rating of change question. Criterion validity of CMYMOP was assessed by its correlation with SF-36 at baseline, and responsiveness was evaluated by calculating the Cohen effect size (ES) of change at two follow ups. Minimally important difference (MID) values were estimated via anchor based method, while minimally detectable difference (MDC) figures were calculated by distribution based method. Results Criterion validity of CMYMOP was demonstrated by negative correlation between CMYMOP Profile scores and all SF-36 domain and summary scores at baseline. For responsiveness between baseline and 4th week follow up, ES of CMYMOP Symptom 1, Activity and Profile reached the moderate change threshold (ES>0.5), while Symptom 2 and Wellbeing reached the weak change threshold (ES>0.2). None of the SF-36 scores reached the moderate change threshold, implying CMYMOP's stronger responsiveness in CM setting. At 2nd week follow up, MID values for Symptom 1, Symptom 2, Wellbeing and Profile items were 0.894, 0.580, 0.263 and 0.516 respectively. For Activity item, MDC figure of 0.808 was adopted to estimate MID. Conclusions The findings support the validity and responsiveness of CMYMOP for capturing patient centred clinical changes within 2 weeks in a CM clinical setting. Further researches are warranted (1) to estimate Activity item MID, (2) to assess the test-retest reliability of CMYMOP, and (3) to perform further MID evaluation using multiple, item specific anchor questions. PMID:20920284

Time-dependent transition of the immunoglobulin G subclass and immunoglobulin E response in cancer patients vaccinated with cholesteryl pullulan-melanoma antigen gene-A4 nanogel

PubMed Central

Kyogoku, Noriaki; Ikeda, Hiroaki; Tsuchikawa, Takahiro; Abiko, Takehiro; Fujiwara, Aki; Maki, Takehiro; Yamamura, Yoshiyuki; Ichinokawa, Masaomi; Tanaka, Kimitaka; Imai, Naoko; Miyahara, Yoshihiro; Kageyama, Shinichi; Shiku, Hiroshi; Hirano, Satoshi

2016-01-01

A phase I+II clinical trial of vaccination with MAGE-A4 protein complexed with cholesteryl pullulan melanoma antigen gene-A4 nanogel (CHP-MAGE-A4) is currently underway in patients with MAGE-A4-expressing cancer. In the present study, the primary phase I endpoint was to test the safety of the administration of 300 µg CHP-MAGE-A4 with and without OK-432. Another aim of the study was to clarify the details of the specific humoral immune response to vaccination. The 9 patients enrolled for phase I were vaccinated 6 times, once every 2 weeks: 3 patients with 100 µg and 3 patients with 300 µg CHP-MAGE-A4, and 3 patients with 300 µg CHP-MAGE-A4 plus 0.5 clinical units of OK-432. Toxicities were assessed using Common Terminology Criteria for Adverse Events v3.0. Clinical response was evaluated by modified Response Evaluation Criteria in Solid Tumours. Immunological monitoring of anti-MAGE-A4-specific antibodies was performed by ELISA of pre- and post-vaccination patient sera. The 6 vaccinations produced no severe adverse events. Stable disease was assessed in 4/9 patients. Anti-MAGE-A4 total immunoglobulin (Ig)G titers increased in 7/9 patients. Efficacious anti-MAGE-A4 IgG1, 2 and 3 antibody responses were observed in 7/9 patients. Among them, positive conversions to T helper 2 (Th2)-type antibody responses (IgG4 and IgE) were observed after frequent vaccination in 4/7 patients. The Th2 conversion was possibly associated with undesirable clinical observations, including progressive disease and the appearance of a new relapse lesion. The present study suggested that frequent vaccinations activated a Th2-dominant status in the cancer patients. The identification of a time-dependent IgG subclass and IgE antibody production during vaccination protocols may be a useful surrogate marker indicating a potentially undesirable change of the immunological environment for an effective antitumor immune response in cancer patients. PMID:28105158

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

PubMed

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.

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

PubMed Central

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:26070036

Construction of an efficient evaluative instrument for myasthenia gravis: the MG composite.

PubMed

Burns, Ted M; Conaway, Mark R; Cutter, Gary R; Sanders, Donald B

2008-12-01

We assessed the performance of items from the Quantitative Myasthenia Gravis (QMG), MMT (Manual Muscle Test), and MG-ADL (Myasthenia Gravis - Activities of Daily Living) scales, using data from two recently completed treatment trials of generalized MG. Items were selected that were relevant to manifestations of MG, meaningful to both the physician and the patient, and responsive to clinical change. After the 10 items were chosen, they were weighted based on input from MG experts from around the world, considering factors such as quality of life, disease severity, risk, prognosis, validity, and reliability. The MG Composite is easy to administer, takes less than 5 minutes to complete, and requires no equipment. Weighting of the response options of the 10 items should result in ordinal scores that better represent MG status and are more responsive to meaningful clinical change. To better determine its suitability for clinical use and for treatment trials, the MG Composite will be tested prospectively at several academic medical centers and will be used as a secondary measure of efficacy in pending clinical trials of MG.

Efficacy of infliximab rescue therapy in patients with chronic refractory pouchitis: a multicenter study.

PubMed

Barreiro-de Acosta, M; García-Bosch, O; Souto, R; Mañosa, M; Miranda, J; García-Sanchez, V; Gordillo, J; Chacon, S; Loras, C; Carpio, D; Maroto, N; Menchén, L; Rojas-Feria, M; Sierra, M; Villoria, A; Marin-Jimenez, I

2012-05-01

Despite medical therapy, 30% of patients with ulcerative colitis (UC) need to undergo surgery. Around 50% of patients with proctocolectomy with ileal pouch-anal anastomosis (IPAA) develop complications of the pouch. Clinical evidence for the use of infliximab (IFX) in refractory pouchitis is limited. The aim of this study was to report efficacy of IFX in these patients. A retrospective, multicenter study was designed. Patients older than 18 years with chronic refractory pouchitis treated with IFX (5 mg/kg) were included. Short-term IFX efficacy was evaluated at week 8 and mid-term efficacy at weeks 26 and 52. Complete response was defined as cessation of diarrhea and urgency and partial response as marked clinical improvement but persisting symptoms. The modified Pouchitis Disease Activity Index (mPDAI) without endoscopy was calculated when available. Thirty-three consecutive UC patients with chronic refractory pouchitis were included (18 male, mean age 45 years, range 21-67). At week 8, 21% patients achieved complete response and 63% showed partial clinical response. At weeks 26 and 52, 33% and 27% achieved complete response and 33% and 18% showed partial clinical response, respectively. Thirteen patients (39%) withdrew treatment (four for lack of efficacy, four for loss of response and five for adverse events). None of the potential factors analyzed had an influence on response to IFX. IFX was effective in the short- and mid-term in patients with chronic refractory pouchitis. However, medication had to be discontinued in a high number of patients. Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.

Biological evaluation of silver nanoparticles incorporated into chitosan-based membranes.

PubMed

Shao, Jinlong; Yu, Na; Kolwijck, Eva; Wang, Bing; Tan, Ke Wei; Jansen, John A; Walboomers, X Frank; Yang, Fang

2017-11-01

To evaluate the antibacterial potential and biological performance of silver nanoparticles in chitosan-based membranes. Electrospun chitosan/poly(ethylene oxide) membranes with different amounts of silver nanoparticles were evaluated for antibacterial properties and cytotoxicity in vitro and for tissue response in a rabbit subcutaneous model. The nanoparticles displayed dose-dependent antibacterial properties against Porphyromonas gingivalis and Fusobacterium nucleatum, without showing noticeable cytotoxicity. The membranes with silver nanoparticles evoked a similar inflammatory response compared with the membranes without silver nanoparticles. The antibacterial effect, combined with the findings on cyto- and biocompatibility warrants further investigation to the usefulness of chitosan/poly(ethylene oxide) membranes with silver nanoparticles, for clinical applications like guided tissue regeneration.

["Re-evaluation upon suspected event" is an approach for post-marketing clinical study: lessons from adverse drug events related to Bupleuri Radix preparations].

PubMed

Wu, Shu-Xin; Sun, Hong-Feng; Yang, Xiao-Hui; Long, Hong-Zhu; Ye, Zu-Guang; Ji, Shao-Liang; Zhang, Li

2014-08-01

We revisited the "Xiao Chaihu Decoction event (XCHDE)" occurred in late 1980s in Japan and the Bupleuri Radix related adverse drug reaction (ADR) reports in China After careful review, comparison, analysis and evaluation, we think the interstitial pneumonitis, drug induced Liver injury (DILI) and other severe adverse drug envents (ADEs) including death happened in Japan is probably results from multiple factors, including combinatory use of XCHDE with interferon, Kampo usage under modern medicine theory guidance, and use of XCHD on the basis of disease diagnosis instead of traditional Chinese syndrome complex differentiation. There are less ADE case reports related to XCHD preparation in China compared to Japan, mostly manifest with hypersensitivity responses of skin and perfuse perspiration. The symptoms of Radix Bupleuri injection related ADEs mainly manifest hypersensitivity-like response, 2 cases of intravenous infusion instead of intramuscular injection developed hypokalemia and renal failure. One case died from severe hypersensitivity shock. In Chinese literatures, there is no report of the interstitial pneumonitis and DILI associated with XCHDG in Japan. So far, there is no voluntary monitoring data and large sample clinical research data available. The author elaborated the classification of "reevaluation" and clarified "re-evaluation upon events" included the reaction to the suspected safety and efficacy events. Based on the current status of the clinical research on the Radix Bupleuri preparations, the author points out that post-marketing "re-evaluation upon suspected event" is not only a necessity of continuous evaluation of the safety, efficacy of drugs, it is also a necessity for providing objective clinical research data to share with the international and domestic drug administrations in the risk-benefit evaluation. It is also the unavoidable pathway to culture and push the excellent species and famous brands of TCM to the international market, in that it enhances the pharmaceutical manufactures the ability to control enterprise risk and eliminate the negative impact on traditional Chinese medicine. With the widely used and ADR report concentrated Radix Bupleuri injection as an example, the author provide a new approach to post-marketing clinical research.

Improved CD4⁺ T cell responses to Mycobacterium tuberculosis in PPD-negative adults by M72/AS01 as compared to the M72/AS02 and Mtb72F/AS02 tuberculosis candidate vaccine formulations: a randomized trial.

PubMed

Leroux-Roels, Isabel; Forgus, Sheron; De Boever, Fien; Clement, Frédéric; Demoitié, Marie-Ange; Mettens, Pascal; Moris, Philippe; Ledent, Edouard; Leroux-Roels, Geert; Ofori-Anyinam, Opokua

2013-04-19

The Bacille Calmette-Guérin (BCG) tuberculosis (TB) vaccine provides incomplete protection, necessitating development of an effective vaccine against TB disease. The Mtb72F/AS02 candidate vaccine was previously shown to be clinically well tolerated and immunogenic in Purified Protein Derivative (PPD)-negative adults. To improve the stability of Mtb72F, a point mutation was introduced into a putative serine protease site to give the final M72 construct. AS01 is an Adjuvant System that can potentially improve both humoral and cellular immune responses compared to the AS02 Adjuvant System or unadjuvanted vaccine. This study evaluated the safety and immunogenicity in Mtb-naïve adults of vaccines containing 40 μg of the M72 antigen with AS02 or AS01 and compared the results with Mtb72F/AS02 vaccine (40 μg dose), M72 in saline (40 μg dose) and AS01 alone. In this Phase I/II observer-blind controlled trial, 110 participants were randomized (4:4:1:1:1) to receive M72/AS01, M72/AS02, Mtb72F/AS02, M72/saline or AS01, following a 0, 1-month schedule. Subjects receiving the adjuvanted M72 vaccines were followed up until 3 years post vaccination. Evaluation of the immune response and safety/reactogenicity was performed. For all vaccines, solicited adverse events (AEs) were predominantly mild to moderate and transient. No vaccine-related serious AEs occurred and no subject withdrew due to an AE. Immune responses induced by Mtb72F and M72 antigens combined with AS02 were similar. M72/AS01 and M72/AS02 induced robust polyfunctional M72-specific CD4(+) T cell and antibody responses persisting at 3 years, with the highest CD4(+) T cell responses found with M72/AS01. This first clinical study with M72/AS01 and M72/AS02 showed that both vaccines were clinically well tolerated and induced high magnitude and persistent cell-mediated and humoral immune responses. The Mtb72F/AS02 and M72/AS02 vaccines were comparably immunogenic with significantly higher immune responses compared to the M72/saline control. Of the formulations tested, M72/AS01 demonstrated significantly higher vaccine specific Th1 CD4(+) T cell responses supporting its further clinical evaluation. Copyright © 2012 Elsevier Ltd. All rights reserved.

Evaluation of Viewpoints of Health Care Professionals on the Role of Ethics Committees and Hospitals in the Resolution of Clinical Ethical Dilemmas Based on Practice Environment.

PubMed

Marcus, Brian S; Carlson, Jestin N; Hegde, Gajanan G; Shang, Jennifer; Venkat, Arvind

2016-03-01

We sought to evaluate whether health care professionals' viewpoints differed on the role of ethics committees and hospitals in the resolution of clinical ethical dilemmas based on practice location. We conducted a survey study from December 21, 2013 to March 15, 2014 of health care professionals at six hospitals (one tertiary care academic medical center, three large community hospitals and two small community hospitals). The survey consisted of eight clinical ethics cases followed by statements on whether there was a role for the ethics committee or hospital in their resolution, what that role might be and case specific queries. Respondents used a 5-point Likert scale to express their degree of agreement with the premises posed. We used the ANOVA test to evaluate whether respondent views significantly varied based on practice location. 240 health care professionals (108-tertiary care center, 92-large community hospitals, 40-small community hospitals) completed the survey (response rate: 63.6 %). Only three individual queries of 32 showed any significant response variations across practice locations. Overall, viewpoints did not vary across practice locations within question categories on whether the ethics committee or hospital had a role in case resolution, what that role might be and case specific queries. In this multicenter survey study, the viewpoints of health care professionals on the role of ethics committees or hospitals in the resolution of clinical ethics cases varied little based on practice location.

Monitoring multiple myeloma patients treated with daratumumab: teasing out monoclonal antibody interference.

PubMed

McCudden, Christopher; Axel, Amy E; Slaets, Dominique; Dejoie, Thomas; Clemens, Pamela L; Frans, Sandy; Bald, Jaime; Plesner, Torben; Jacobs, Joannes F M; van de Donk, Niels W C J; Moreau, Philippe; Schecter, Jordan M; Ahmadi, Tahamtan; Sasser, A Kate

2016-06-01

Monoclonal antibodies are promising anti-myeloma treatments. As immunoglobulins, monoclonal antibodies have the potential to be identified by serum protein electrophoresis (SPE) and immunofixation electrophoresis (IFE). Therapeutic antibody interference with standard clinical SPE and IFE can confound the use of these tests for response assessment in clinical trials and disease monitoring. To discriminate between endogenous myeloma protein and daratumumab, a daratumumab-specific immunofixation electrophoresis reflex assay (DIRA) was developed using a mouse anti-daratumumab antibody. To evaluate whether anti-daratumumab bound to and shifted the migration pattern of daratumumab, it was spiked into daratumumab-containing serum and resolved by IFE/SPE. The presence (DIRA positive) or absence (DIRA negative) of residual M-protein in daratumumab-treated patient samples was evaluated using predetermined assessment criteria. DIRA was evaluated for specificity, limit of sensitivity, and reproducibility. In all of the tested samples, DIRA distinguished between daratumumab and residual M-protein in commercial serum samples spiked with daratumumab and in daratumumab-treated patient samples. The DIRA limit of sensitivity was 0.2 g/L daratumumab, using spiking experiments. Results from DIRA were reproducible over multiple days, operators, and assays. The anti-daratumumab antibody was highly specific for daratumumab and did not shift endogenous M-protein. As the treatment of myeloma evolves to incorporate novel monoclonal antibodies, additional solutions will be needed for clinical monitoring of patient responses to therapeutic regimens. In the interim, assays such as DIRA can inform clinical outcomes by distinguishing daratumumab from endogenous M-protein by IFE.

Pre-clinical toxicity and immunogenicity evaluation of a MUC1-MBP/BCG anti-tumor vaccine.

PubMed

Hu, Boqi; Wang, Juan; Guo, Yingying; Chen, Tanxiu; Ni, Weihua; Yuan, Hongyan; Zhang, Nannan; Xie, Fei; Tai, Guixiang

2016-04-01

Mucin 1 (MUC1), as an oncogene, plays a key role in the progression and tumorigenesis of many human adenocarcinomas and is an attractive target in tumor immunotherapy. Our previous study showed that the MUC1-MBP/BCG anti-tumor vaccine induced a MUC1-specific Th1-dominant immune response, simulated MUC1-specific cytotoxic T lymphocyte killing activity, and could significantly inhibit MUC1-expression B16 cells' growth in mice. To help move the vaccine into a Phase I clinical trial, in the current study, a pre-clinical toxicity and immunogenicity evaluation of the vaccine was conducted. The evaluation was comprised of a single-dose acute toxicity study in mice, repeat-dose chronic toxicity and immunogenicity studies in rats, and pilot toxicity and immunogenicity studies in cynomolgus monkeys. The results showed that treatment with the MUC1-MBP/BCG anti-tumor vaccine did not cause any organ toxicity, except for arthritis or local nodules induced by BCG in several rats. Furthermore, the vaccine significantly increased the levels of IFN-γ in rats, indicating that Th1 cells were activated. In addition, the results showed that the MUC1-MBP/BCG anti-tumor vaccine induced a MUC1-specific IgG antibody response both in rats and cynomolgus monkeys. Collectively, these data are beneficial to move the MUC1-MBP/BCG anti-tumor vaccine into a Phase I clinical trial. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluation of the functional performance and technical quality of an Electronic Documentation System of the Nursing Process.

PubMed

de Oliveira, Neurilene Batista; Peres, Heloisa Helena Ciqueto

2015-01-01

To evaluate the functional performance and the technical quality of the Electronic Documentation System of the Nursing Process of the Teaching Hospital of the University of São Paulo. exploratory-descriptive study. The Quality Model of regulatory standard 25010 and the Evaluation Process defined under regulatory standard 25040, both of the International Organization for Standardization/International Electrotechnical Commission. The quality characteristics evaluated were: functional suitability, reliability, usability, performance efficiency, compatibility, security, maintainability and portability. The sample was made up of 37 evaluators. in the evaluation of the specialists in information technology, only the characteristic of usability obtained a rate of positive responses of less than 70%. For the nurse lecturers, all the quality characteristics obtained a rate of positive responses of over 70%. The staff nurses of the medical and surgical clinics with experience in using the system) and staff nurses from other units of the hospital and from other health institutions (without experience in using the system) obtained rates of positive responses of more than 70% referent to the functional suitability, usability, and security. However, performance efficiency, reliability and compatibility all obtained rates below the parameter established. the software achieved rates of positive responses of over 70% for the majority of the quality characteristics evaluated.

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

PubMed Central

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

Clinically led performance management in secondary healthcare: evaluating the attitudes of medical and non-clinical managers.

PubMed

Trebble, Timothy M; Paul, Maureen; Hockey, Peter M; Heyworth, Nicola; Humphrey, Rachael; Powell, Timothy; Clarke, Nicholas

2015-03-01

Improving the quality and activity of clinicians' practice improves patient care. Performance-related human resource management (HRM) is an established approach to improving individual practice but with limited use among clinicians. A framework for performance-related HRM was developed from successful practice in non-healthcare organisations centred on distributive leadership and locally provided, validated and interpreted performance measurement. This study evaluated the response of medical and non-clinical managers to its implementation into a large secondary healthcare organisation. A semistructured qualitative questionnaire was developed from themes identified during framework implementation and included attitudes to previous approaches to measuring doctors' performance, and the structure and response to implementation of the performance-related HRM framework. Responses were analysed through a process of data summarising and categorising. A total of 29, from an invited cohort of 31, medical and non-clinical managers from departmental to executive level were interviewed. Three themes were identified: (1) previous systems of managing clinical performance were considered to be ineffective due to insufficient empowerment of medical managers and poor quality of available performance data; (2) the implemented framework was considered to address these needs and was positively received by medical and non-clinical managers; (3) introduction of performance-related HRM required the involvement of the whole organisation to executive level and inclusion within organisational strategy, structure and training. This study suggests that a performance-related HRM framework may facilitate the management of clinical performance in secondary healthcare, but is dependent on the design and methods of application used. Such approaches contrast with those currently proposed for clinicians in secondary healthcare in the UK and suggest that alternative strategies should be considered. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Volumetric modulated arc therapy with flattening filter free beams for isolated abdominal/pelvic lymph nodes: report of dosimetric and early clinical results in oligometastatic patients

PubMed Central

2012-01-01

Background SBRT is a safe and efficient strategy to locally control multiple metastatic sites. While research in the physics domain for Flattening Filter Free Beams (FFF) beams is increasing, there are few clinical data of FFF beams in clinical practice. Here we reported dosimentric and early clinical data of SBRT and FFF delivery in isolated lymph node oligometastatic patients. Methods Between October 2010 and March 2012, 34 patients were treated with SBRT for oligometastatic lymph node metastasis on a Varian TrueBeamTM treatment machine using Volumetric Modulated Arc Therapy (RapidArc). We retrospectively evaluated a total of 25 patients for isolated lymph node metastases in abdomen and/or pelvis treated with SBRT and FFF (28 treatments). Acute toxicity was recorded. Local control evaluation was scored by means of CT scan and/or PET scan. Results All dosimetric results are in line with what published for the same type of stereotactic abdominal lymph node metastases treatments and fractionation, using RapidArc. All 25 FFF SBRT patients completed the treatment. Acute gastrointestinal toxicity was minimal: one patient showed Grade 1 gastrointestinal toxicity. Three other patients presented Grade 2 toxicity. No Grade 3 or higher was recorded. All toxicities were recovered within one week. The preliminary clinical results at the median follow up of 195 days are: complete response in 12 cases, partial response in 11, stable disease in 5, with an overall response rate of 82%; no local progression was recorded. Conclusions Data of dosimetrical findings and acute toxicity are excellent for patients treated with SBRT with VMAT using FFF beams. Preliminary clinical results showed a high rate of local control in irradiated lesion. Further data and longer follow up are needed to assess late toxicity and definitive clinical outcomes. PMID:23216821

VEGFA and VEGFR2 gene polymorphisms and response to anti-vascular endothelial growth factor therapy: comparison of age-related macular degeneration treatments trials (CATT).

PubMed

Hagstrom, Stephanie A; Ying, Gui-shuang; Pauer, Gayle J T; Sturgill-Short, Gwen M; Huang, Jiayan; Maguire, Maureen G; Martin, Daniel F

2014-05-01

Individual variation in response and duration of anti-vascular endothelial growth factor (VEGF) therapy is seen among patients with neovascular age-related macular degeneration. Identification of genetic markers that affect clinical response may result in optimization of anti-VEGF therapy. To evaluate the pharmacogenetic relationship between genotypes of single-nucleotide polymorphisms (SNPs) in the VEGF signaling pathway and response to treatment with ranibizumab or bevacizumab for neovascular age-related macular degeneration. In total, 835 of 1149 patients (72.7%) participating in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT) at 43 CATT clinical centers. Each patient was genotyped for 7 SNPs in VEGFA (rs699946, rs699947, rs833069, rs833070, rs1413711, rs2010963, and rs2146323) and 1 SNP in VEGFR2 (rs2071559) using TaqMan SNP genotyping assays. Genotypic frequencies were compared with clinical measures of response to therapy at 1 year, including the mean visual acuity, mean change in visual acuity, at least a 15-letter increase, retinal thickness, mean change in total foveal thickness, presence of fluid on optical coherence tomography, presence of leakage on fluorescein angiography, mean change in lesion size, and mean number of injections administered. Differences in response by genotype were evaluated with tests of linear trend calculated from logistic regression models for categorical outcomes and linear regression models for continuous outcomes. The method of controlling the false discovery rate was used to adjust for multiple comparisons. For each of the measures of visual acuity evaluated, no association was observed with any of the genotypes or with the number of risk alleles. Four VEGFA SNPs demonstrated an association with retinal thickness: rs699947 (P = .03), rs833070 (P = .04), rs1413711 (P = .045), and rs2146323 (P = .006). However, adjusted P values for these associations were all statistically nonsignificant (range, P = .24 to P = .45). Among the participants in 2 as-needed groups, no association was found in the number of injections among the different genotypes or for the total number of risk alleles. The effect of risk alleles on each clinical measure did not differ by treatment group, drug, or dosing regimen (P > .01 for all). This study provides evidence that no pharmacogenetic associations exist between the studied VEGFA and VEGFR2 SNPs and response to anti-VEGF therapy. clinicaltrials.gov Identifier: NCT00593450.

Response assessment challenges in clinical trials of gliomas.

PubMed

Wen, Patrick Y; Norden, Andrew D; Drappatz, Jan; Quant, Eudocia

2010-01-01

Accurate, reproducible criteria for determining tumor response and progression after therapy are critical for optimal patient care and effective evaluation of novel therapeutic agents. Currently, the most widely used criteria for determining treatment response in gliomas is based on two-dimensional tumor measurements using neuroimaging studies (Macdonald criteria). In recent years, the limitation of these criteria, which only address the contrast-enhancing component of the tumor, have become increasingly apparent. This review discusses challenges that have emerged in assessing response in patients with gliomas and approaches being introduced to address them.

A Pooled Analysis on Crizotinib in Treating Chinese Patients with EML4-ALK Positive Non-small-cell Lung Cancer.

PubMed

Li, Yang; Huang, Xin-En

2015-01-01

This analysis was conducted to evaluate the efficacy and safety of crizotinib based regimens in treating Chinese patients with EML4-ALK positive non-small-cell lung cancer. Clinical studies evaluating the efficacy and safety of crizotinib based regimens on response and safety for Chinese patients with EML4-ALK positive non-small-cell lung cancer were identified by using a predefined search strategy. Pooled response rate (RR) of treatment were calculated. In crizotinib based regimens, 3 clinical studies which including 128 Chinese patients with EML4-ALK positive non-small-cell lung cancer and treated with crizotinib based regimen were considered eligible for inclusion. Pooled analysis suggested that, in all patients, the pooled RR was 59.3% (76/128) in crizotinib based regimens. ALT/AST mild visual disturbances, nausea, and vomiting were the main side effects. No treatment related death occurred in these crizotinib based treatments. This pooled analysis suggests that crizotinib based regimens are associated with good response rate and accepted toxicities in treating Chinese patients with EML4-ALK positive non-small-cell lung cancer.

Evaluating the effect of distractions in the operating room on clinical decision-making and patient safety.

PubMed

Murji, Ally; Luketic, Lea; Sobel, Mara L; Kulasegaram, Kulamakan Mahan; Leyland, Nicholas; Posner, Glenn

2016-10-01

Answering telephone calls and pagers is common distraction in the operating room. We sought to evaluate the impact of distractions on patient care by (1) assessing the accuracy and safety of responses to clinical questions posed to a surgeon while operating and (2) determining whether pager distractions affect simulation-based surgical performance. We conducted a randomized crossover study of obstetrics and gynecology residents. After studying a patient sign-out list, subjects performed a virtual salpingectomy. They were randomized to a distraction phase followed by quiet phase or vice versa. In the distraction phase, a pager beeped and subjects were asked questions based on the sign-out list. Accuracy of responses and the number of unsafe responses were recorded. In the quiet phase, trainees performed the task uninterrupted. Measures of surgical performance were successful task completion, time to task completion and operative blood loss. The mean score for correct responses to clinical questions during the distracted phase was 80 % (SD ±14 %). Nineteen residents (63 %) made at least 1 unsafe clinical decision while operating on the simulator (range 0-3). Subjects were more likely to successfully complete the surgical task in the allotted time under the quiet compared to distraction condition (OR 11.3, p = 0.03). There was no difference between the conditions in paired analysis for mean time (seconds) to task completion [426 (SD 133) vs. 440 (SD 186), p = 0.61] and mean operative blood loss (mL) [73.14 (SD 106) vs. 112.70 (SD 358), p = 0.47]. Distractions in the operating room may have a profound impact on patient safety on the wards. While multitasking in a simulated setting, the majority of residents made at least one unsafe clinical decision. Pager distractions also hindered surgical residents' ability to complete a simulated laparoscopic task in the allotted time without affecting other variables of surgical performance.

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

PubMed

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 ability to clinically and physiologically differentiate between ADHD children with and without ED.

Development of guidance on the timeliness in response to acute kidney injury warning stage test results for adults in primary care: an appropriateness ratings evaluation

PubMed Central

Blakeman, Tom; Griffith, Kathryn; Lasserson, Dan; Lopez, Berenice; Tsang, Jung Y; Campbell, Stephen; Tomson, Charles

2016-01-01

Objectives Tackling the harm associated with acute kidney injury (AKI) is a global priority. In England, a national computerised AKI algorithm is being introduced across the National Health Service (NHS) to drive this change. The study sought to maximise its clinical utility and minimise the potential for burden on clinicians and patients in primary care. Design An appropriateness ratings evaluation using the RAND/UCLA Appropriateness Method. Setting Clinical scenarios were developed to test the timeliness in (1) communication of AKI warning stage test results from clinical pathology services to primary care, and (2) primary care clinician response to an AKI warning stage test result. Participants A 10-person panel was purposively sampled with representation from clinical biochemistry, acute and emergency medicine and general practice. General practitioners (GPs) represented typical practice in relation to rural and urban practice, out of hours care, GP commissioning and those interested in reducing the impact of medicalisation and ‘overdiagnosis’. Results There was agreement that delivery of AKI warning stage test results through interruptive methods of communication (ie, telephone) from laboratories to primary care was the appropriate next step for patients with an AKI warning stage 3 test result. In the context of acute illness, waiting up to 72 hours to respond to an AKI warning stage test result was deemed an inappropriate action in 62 out of the 65 (94.5%) cases. There was agreement that a clinician response was required within 6 hours, or less, in 39 out of 40 (97.5%) clinical cases relating AKI warning stage test results in the presence of moderate hyperkalaemia. Conclusions The study has informed national guidance to support a timely and calibrated response to AKI warning stage test results for adults in primary care. Further research is needed to support effective implementation, with a view to examine the effect on health outcomes and costs. PMID:27729353

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

PubMed

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 expression in the SSRI antidepressant response. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaluating the Well-Being of Public Library Workers

ERIC Educational Resources Information Center

Juniper, Bridget; Bellamy, Pat; White, Nicola

2012-01-01

This study aimed to develop and pilot a questionnaire to determine the ways in which working in a UK public library system can impact the well-being of those deployed in the sector. The methodological framework was based on an approach used to evaluate the well-being of patients in a clinical setting. Based on the responses of 466 employees, the…

Obtaining Self-Report Data from Cognitively Impaired Elders: Methodological Issues and Clinical Implications for Nursing Home Pain Assessment

ERIC Educational Resources Information Center

Fisher, Susan E.; Burgio, Louis D.; Thorn, Beverly E.; Hardin, J. Michael

2006-01-01

Purpose: We developed and evaluated an explicit procedure for obtaining self-report pain data from nursing home residents across a broad range of cognitive status, and we evaluated the consistency, stability, and concurrent validity of resident responses. Design and Methods: Using a modification of the Geriatric Pain Measure (GPM-M2), we…

Item Bank Development for a Revised Pediatric Evaluation of Disability Inventory (PEDI)

ERIC Educational Resources Information Center

Dumas, Helene; Fragala-Pinkham, Maria; Haley, Stephen; Coster, Wendy; Kramer, Jessica; Kao, Ying-Chia; Moed, Richard

2010-01-01

The Pediatric Evaluation of Disability Inventory (PEDI) is a useful clinical and research assessment, but it has limitations in content, age range, and efficiency. The purpose of this article is to describe the development of the item bank for a new computer adaptive testing version of the PEDI (PEDI-CAT). An expanded item set and response options…

Live and Web-based orientations are comparable for a required rotation.

PubMed

Prunuske, Jacob

2010-03-01

Studies show equivalency in knowledge when measured following Web-based learning and live lecture. However, the effectiveness of a Web-based orientation for a required clinical rotation is unknown. Medical students viewed a Web-based orientation and completed a 13-item evaluation before beginning a required 6-week community medicine rotation. Evaluation data from 2007-2008 live orientation sessions were compared to responses from 2008-2009 Web-based orientation sessions. Data were analyzed by two-sample tests of proportion. A total of 169 students completed surveys during the study period--78 following the live and 91 following the Web-based orientation. Response rates were equal in the two groups. The survey tool had a high level of reliability (Cronbach's alpha=0.96). There was no statistical difference in student evaluations for 12 of 13 orientation evaluation items. Live and Web-based formats are comparable for presenting orientation materials to a required clinical rotation. Students felt the purpose of the rotation, educational goals, course structure, and requirements were clearly presented regardless of format. Transition from a live to Web-based format reduced faculty time required to present at rotation orientations.

models of congenital heart disease.

PubMed

Biglino, Giovanni; Capelli, Claudio; Leaver, Lindsay-Kay; Schievano, Silvia; Taylor, Andrew M; Wray, Jo

2015-01-01

To develop a participatory approach in the evaluation of 3D printed patient-specific models of congenital heart disease (CHD) with different stakeholders who would potentially benefit from the technology (patients, parents, clinicians and nurses). Workshops, focus groups and teaching sessions were organised, targeting different stakeholders. Sessions involved displaying and discussing different 3D models of CHD. Model evaluation involved response counts from questionnaires and thematic analysis of audio-recorded discussions and written feedback. Stakeholders’ responses indicated the scope and potential for clinical translation of 3D models. As tangible, three-dimensional artefacts, these can have a role in communicative processes. Their patient-specific quality is also important in relation to individual characteristics of CHD. Patients indicated that 3D models can help them visualise ‘what’s going on inside’. Parents agreed that models can spark curiosity in young people. Clinicians indicated that teaching might be the most relevant application. Nurses agreed that 3D models improved their learning experience during a CHD course. Engagement of different stakeholders to evaluate 3D printing technology for CHD identified the potential of the models for improving patient– doctor communication, patient empowerment and training. A participatory approach could benefit the clinical evaluation and translation of 3D printing technology.

Transepidermal drug delivery: a new treatment option for areata alopecia?

PubMed

Issa, Maria Claudia Almeida; Pires, Marianna; Silveira, Priscilla; Xavier de Brito, Esther; Sasajima, Cristiane

2015-02-01

Transepidermal drug delivery (TED) is a new potential method in dermatology. Permeability alterations induced by ablative fractional resurfacing have been described with the aim to increasing the delivery of different substances into the skin. To evaluate clinical response and side effects of TED in areata alopecia (AA) treatment using ablative fractional methods associated with acoustic pressure ultrasound (US) to deliver triamcinolone solution into the skin. Five cases of AA underwent treatment which comprised of 3 steps: 1) Ablative fractioned RF or CO2 laser 2) topical application of triamcinolone 3) acoustic pressure wave US. The number of sessions varied according to the clinical response, ranging from one to six sessions. All patients had complete recovery of the area treated. Two of them treated with ablative fractional RF + triamcinolone + US had complete response after three and six sessions. The other two treated with ablative fractional CO2 + triamcinolone + US had complete response after one session. Fractioned ablative resurfacing associated with acoustic pressure wave US is a new option to areata alopecia treatment with good clinical result and low incidence of side effects.

Clinical outcome of high-dose-rate interstitial brachytherapy in vulvar cancer: A single institutional experience.

PubMed

Mahantshetty, Umesh; Naga, Pushpa; Engineer, Reena; Sastri, Supriya; Ghadi, Yogesh; Upreti, Udita; Somesan, Vijaya; Kadam, Sudarshan; Kohle, Satish; Deshpande, Deepak; Shrivastava, Shyam Kishore

With an aim to evaluate and report high dose date interstitial brachytherapy (HDR-ISBT) in vulvar cancers, we undertook this retrospective analysis. Histologically proven vulvar cancers treated with HDR-ISBT between 2001 and 2016 were analyzed. Radiotherapy details, clinical outcome in terms of local control rates, survivals, and toxicities were evaluated. A total of 38 patients received HDR-ISBT, with definitive radiation in 29 (76.3%), adjuvant postoperative in six (15.8%) and salvage radiation in three (7.9%) patients. Of them, 29 patients received brachytherapy boost and nine patients ISBT alone. BT procedure included freehand plastic tube technique in 23 (single [n = 5] or multiple plane [n = 18]), 13 patients with template based and two patients combined approach. Patients with brachytherapy alone received median EQD2 of 38.4 Gy 10 (35.5-46.7 Gy 10 ), as boost received median 23.3 Gy 10 (13-37.3 Gy 10 ). At 3-month post-treatment response evaluation, 30 patients achieved clinically complete response, two patients partial response and six maintained postoperative status. With a median follow-up of 30 months, 29 (76.3%) were disease free, and 9 (23.7%) patients had relapsed disease with four patients expired due to disease and two died of other causes. The 5-year overall survival, disease free survival, and local control rates were 82%, 51%, and 77%, respectively. HDR-ISBT in vulvar cancer is a feasible and a viable option with acceptable and comparable outcomes. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Development and Validation of the PROMIS Pediatric Sleep Disturbance and Sleep-Related Impairment Item Banks.

PubMed

Forrest, Christopher B; Meltzer, Lisa J; Marcus, Carole L; de la Motte, Anna; Kratchman, Amy; Buysse, Daniel J; Pilkonis, Paul A; Becker, Brandon D; Bevans, Katherine B

2018-03-13

To develop and evaluate the measurement properties of child-report and parent-proxy versions of the PROMIS ® Pediatric Sleep Disturbance and Sleep-Related Impairment item banks. A national sample of 1,104 children (8-17 years-old) and 1,477 parents of children 5-17 years-old was recruited from an internet panel to evaluate the psychometric properties of 43 sleep health items. A convenience sample of children and parents recruited from a pediatric sleep clinic was obtained to provide evidence of the measures' validity; polysomnography data were collected from a subgroup of these children. Factor analyses suggested two dimensions: sleep disturbance and daytime sleep-related impairment. The final item banks included 15 items for Sleep Disturbance and 13 for Sleep-Related Impairment. Items were calibrated using the graded response model from item response theory. Of the 28 items, 16 are included in the parallel PROMIS adult sleep health measures. Reliability of the measures exceeded 0.90. Validity was supported by correlations with existing measures of pediatric sleep health and higher sleep disturbance and sleep-related impairment scores for children with sleep problems and those with chronic and neurodevelopmental disorders. The sleep health measures were not correlated with results from polysomnography. The PROMIS Pediatric Sleep Disturbance and Sleep-Related Impairment item banks provide subjective assessments of a child's difficulties falling and staying asleep as well as daytime sleepiness and its impact on functioning. They may prove useful in the future for clinical research and practice. Future research should evaluate their responsiveness to clinical change in diverse patient populations.

Clinical effects of laser immunotherapy on metastatic cancer patients

NASA Astrophysics Data System (ADS)

Naylor, Mark F.; Lam, Anh K.; Bahavar, Cody F.; Nordquist, Robert E.; Chen, Wei R.

2016-03-01

Clinical trials of late-stage breast cancer patients and late-stage melanoma patients treated by laser immunotherapy (LIT) have shown promising results. In a 2010 study of Li et al, eleven late-stage melanoma patients received LIT in one or multiple 6-week treatment cycles applied to a 200-cm2 treatment site, which usually contained multiple cutaneous metastases. Long-term, positive response was observed in six patients. All lesions in the treatment area of the patients responded to LIT, eight of which achieved complete local response (CLR). CLR was observed in the non-treatment site (regional) lesions in four patients. Five patients were still alive at the time of last follow-up. The probability of 12-month overall survival was 70%.2 In 2011, Li et al, treated ten late stage breast cancer patients with LIT.1 In 8 patients available for evaluation, the objective response rate was 62.5% and the clinical beneficial response rate was 75%.1 This review demonstrates that LIT is safe and well tolerated, so it can be easily applied on an outpatient basis and can be combined with other pharmaceutical modalities to improve the therapeutic response of metastatic cancers.

Diffusion MRI in early cancer therapeutic response assessment

PubMed Central

Galbán, C. J.; Hoff, B. A.; Chenevert, T. L.; Ross, B. D.

2016-01-01

Imaging biomarkers for the predictive assessment of treatment response in patients with cancer earlier than standard tumor volumetric metrics would provide new opportunities to individualize therapy. Diffusion-weighted MRI (DW-MRI), highly sensitive to microenvironmental alterations at the cellular level, has been evaluated extensively as a technique for the generation of quantitative and early imaging biomarkers of therapeutic response and clinical outcome. First demonstrated in a rodent tumor model, subsequent studies have shown that DW-MRI can be applied to many different solid tumors for the detection of changes in cellularity as measured indirectly by an increase in the apparent diffusion coefficient (ADC) of water molecules within the lesion. The introduction of quantitative DW-MRI into the treatment management of patients with cancer may aid physicians to individualize therapy, thereby minimizing unnecessary systemic toxicity associated with ineffective therapies, saving valuable time, reducing patient care costs and ultimately improving clinical outcome. This review covers the theoretical basis behind the application of DW-MRI to monitor therapeutic response in cancer, the analytical techniques used and the results obtained from various clinical studies that have demonstrated the efficacy of DW-MRI for the prediction of cancer treatment response. PMID:26773848

A Multiinstitutional Phase 2 Trial of Pazopanib Monotherapy in Advanced Anaplastic Thyroid Cancer

PubMed Central

Suman, Vera J.; Menefee, Michael E.; Smallridge, Robert C.; Molina, Julian R.; Maples, William J.; Karlin, Nina J.; Traynor, Anne M.; Kumar, Priya; Goh, Boon Cher; Lim, Wan-Teck; Bossou, Ayoko R.; Isham, Crescent R.; Webster, Kevin P.; Kukla, Andrea K.; Bieber, Carolyn; Burton, Jill K.; Harris, Pamela; Erlichman, Charles

2012-01-01

Context/Objectives: Pazopanib, an inhibitor of kinases including vascular endothelial growth factor receptor, demonstrated impressive activity in progressive metastatic differentiated thyroid cancer, prompting its evaluation in anaplastic thyroid cancer (ATC). Design/Setting/Patients/Interventions/Outcome Measures: Preclinical studies, followed by a multicenter single arm phase 2 trial of continuously administered 800 mg pazopanib daily by mouth (designed to provide 90% chance of detecting a response rate of >20% at the 0.10 significance level when the true response rate is >5%), were undertaken. The primary trial end point was Response Evaluation Criteria in Solid Tumors (RECIST) response. Results: Pazopanib displayed activity in the KTC2 ATC xenograft model, prompting clinical evaluation. Sixteen trial patients were enrolled; 15 were treated: 66.7% were female, median age was 66 yr (range 45–77 yr), and 11 of 15 had progressed through prior systemic therapy. Enrollment was halted, triggered by a stopping rule requiring more than one confirmed RECIST response among the first 14 of 33 potential patients. Four patients required one to two dose reductions; severe toxicities (National Cancer Institute Common Toxicity Criteria-Adverse Events version 3.0 grades >3) were hypertension (13%) and pharyngolaryngeal pain (13%). Treatment was discontinued because of the following: disease progression (12 patients), death due to a possibly treatment-related tumor hemorrhage (one patient), and intolerability (radiation recall tracheitis and uncontrolled hypertension, one patient each). Although transient disease regression was observed in several patients, there were no confirmed RECIST responses. Median time to progression was 62 d; median survival time was 111 d. Two patients are alive with disease 9.9 and 35 months after the registration; 13 died of disease. Conclusions: Despite preclinical in vivo activity in ATC, pazopanib has minimal single-agent clinical activity in advanced ATC. PMID:22774206

Preclinical Efficacy of the Anti-Hepatocyte Growth Factor Antibody Ficlatuzumab in a Mouse Brain Orthotopic Glioma Model Evaluated by Bioluminescence, PET, and MRI

PubMed Central

Mittra, Erik S.; Fan-Minogue, Hua; Lin, Frank I.; Karamchandani, Jason; Sriram, Venkataraman; Han, May; Gambhir, Sanjiv S.

2016-01-01

Purpose Ficlatuzumab is a novel therapeutic agent targeting the hepatocyte growth factor (HGF)/c-MET pathway. We summarize extensive preclinical work using this agent in a mouse brain orthotopic model of glioblastoma. Experimental Design Sequential experiments were done using eight- to nine-week-old nude mice injected with 3 × 105 U87 MG (glioblastoma) cells into the brain. Evaluation of ficlatuzumab dose response for this brain tumor model and comparison of its response to ficlatuzumab and to temozolamide were conducted first. Subsequently, various small-animal imaging modalities, including bioluminescence imaging (BLI), positron emission tomography (PET), and MRI, were used with a U87 MG-Luc 2 stable cell line, with and without the use of ficlatuzumab, to evaluate the ability to non-invasively assess tumor growth and response to therapy. ANOVA was conducted to evaluate for significant differences in the response. Results There was a survival benefit with ficlatuzumab alone or in combination with temozolamide. BLI was more sensitive than PET in detecting tumor cells. Fluoro-D-thymidine (FLT) PET provided a better signal-to-background ratio than 2[18F]fluoro-2-deoxy-D-glucose (FDG) PET. In addition, both BLI and FLT PET showed significant changes over time in the control group as well as with response to therapy. MRI does not disclose any time-dependent change. Also, the MRI results showed a temporal delay in comparison to the BLI and FLT PET findings, showing similar results one drug cycle later. Conclusions Targeting the HGF/c-MET pathway with the novel agent ficlatuzumab appears promising for the treatment of glioblastoma. Various clinically applicable imaging modalities including FLT, PET, and MRI provide reliable ways of assessing tumor growth and response to therapy. Given the clinical applicability of these findings, future studies on patients with glioblastoma may be appropriate. PMID:23983258

Medical student responses to clinical procedure teaching in the anatomy lab.

PubMed

Wilson, Donald R; Nava, Pedro B

2010-03-01

the teaching of gross anatomy to first-year medical students has progressed from a 'stand-alone' discipline to one with much clinical emphasis. The curriculum at Loma Linda University School of Medicine has had increasing clinical correlates in recent years. We decided to supplement this with procedure demonstrations early in the course, and measure the student response. clinical procedures were performed on cadavers in the anatomy lab. For example, pleural and pericardial effusions were simulated by placing bags of intravenous fluid in the pleural and pericardial cavities; pneumothorax and tension pneumothorax were simulated using an inflatable rubber bladder. Videos were made and then presented in sequence with gross anatomy lectures. The student response was evaluated with a survey sheet. the Student response was overwhelmingly positive, with all students stating that the presentations made anatomy more relevant, and most indicating that anatomy also became easier to learn. Feedback confirmed that first-year medical students have a strong clinical orientation, which can facilitate both the teaching and learning of gross anatomy. advantages of having clinicians present simulated procedures in the anatomy lab include: heightened student interest; mentoring and modelling for students; introduction to clinical concepts now encountered in basic science examinations; supplementation of the thinning ranks of qualified gross anatomy teachers. The use of intravenous fluid bags and distensible bladders to simulate abnormal collections of fluid and air in body cavities is simple, inexpensive, and can be replicated in any anatomy lab. Blackwell Publishing Ltd 2010.

Trauma associated sleep disorder: a proposed parasomnia encompassing disruptive nocturnal behaviors, nightmares, and REM without atonia in trauma survivors.

PubMed

Mysliwiec, Vincent; O'Reilly, Brian; Polchinski, Jason; Kwon, Herbert P; Germain, Anne; Roth, Bernard J

2014-10-15

To characterize the clinical, polysomnographic and treatment responses of patients with disruptive nocturnal behaviors (DNB) and nightmares following traumatic experiences. A case series of four young male, active duty U.S. Army Soldiers who presented with DNB and trauma related nightmares. Patients underwent a clinical evaluation in a sleep medicine clinic, attended overnight polysomnogram (PSG) and received treatment. We report pertinent clinical and PSG findings from our patients and review prior literature on sleep disturbances in trauma survivors. DNB ranged from vocalizations, somnambulism to combative behaviors that injured bed partners. Nightmares were replays of the patient's traumatic experiences. All patients had REM without atonia during polysomnography; one patient had DNB and a nightmare captured during REM sleep. Prazosin improved DNB and nightmares in all patients. We propose Trauma associated Sleep Disorder (TSD) as a unique sleep disorder encompassing the clinical features, PSG findings, and treatment responses of patients with DNB, nightmares, and REM without atonia after trauma.

A Prediction Algorithm for Drug Response in Patients with Mesial Temporal Lobe Epilepsy Based on Clinical and Genetic Information

PubMed Central

Carvalho, Benilton S.; Bilevicius, Elizabeth; Alvim, Marina K. M.; Lopes-Cendes, Iscia

2017-01-01

Mesial temporal lobe epilepsy is the most common form of adult epilepsy in surgical series. Currently, the only characteristic used to predict poor response to clinical treatment in this syndrome is the presence of hippocampal sclerosis. Single nucleotide polymorphisms (SNPs) located in genes encoding drug transporter and metabolism proteins could influence response to therapy. Therefore, we aimed to evaluate whether combining information from clinical variables as well as SNPs in candidate genes could improve the accuracy of predicting response to drug therapy in patients with mesial temporal lobe epilepsy. For this, we divided 237 patients into two groups: 75 responsive and 162 refractory to antiepileptic drug therapy. We genotyped 119 SNPs in ABCB1, ABCC2, CYP1A1, CYP1A2, CYP1B1, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, and CYP3A5 genes. We used 98 additional SNPs to evaluate population stratification. We assessed a first scenario using only clinical variables and a second one including SNP information. The random forests algorithm combined with leave-one-out cross-validation was used to identify the best predictive model in each scenario and compared their accuracies using the area under the curve statistic. Additionally, we built a variable importance plot to present the set of most relevant predictors on the best model. The selected best model included the presence of hippocampal sclerosis and 56 SNPs. Furthermore, including SNPs in the model improved accuracy from 0.4568 to 0.8177. Our findings suggest that adding genetic information provided by SNPs, located on drug transport and metabolism genes, can improve the accuracy for predicting which patients with mesial temporal lobe epilepsy are likely to be refractory to drug treatment, making it possible to identify patients who may benefit from epilepsy surgery sooner. PMID:28052106

Cetuximab in the treatment of head and neck cancer: preliminary results outside clinical trials

PubMed Central

Dequanter, Didier; Shahla, Mohammad; Paulus, Pascal; Lothaire, Phillippe

2010-01-01

Introduction: The purpose of this study was to evaluate the clinical efficacy in our daily practice, outside clinical trials, of cetuximab plus radiotherapy in a majority of treatment-naive patients with locoregionally advanced head and neck squamous cell carcinomas. Methods: A retrospective study was performed to evaluate outcomes in patients who were treated definitively with cetuximab and radiotherapy (ExRT). Patients with stage III or IV, nonmetastatic, measurable squamous cell carcinoma of the head and neck (SCCHN) were eligible. Results: There were 18 males and two females. The median age was 61 years (range from 49 to 87 years old). Concurrent radiotherapy and cetuximab was used, in first line, in 17 patients with locally advanced disease; two patients with recurrent SCCHN, who were intolerant of Cisplatin-based regimens, were treated with radiotherapy combined with weekly cetuximab; and 1 patient received cetuximab and radiotherapy postoperatively. The median time of response was 10 months (range from 2 to 24 months). A partial response was observed in 11 cases; a complete response in nine cases. The occurrence of grade 2–3 skin toxicity was observed in 11 cases. Skin toxicity was clearly correlated with a better response and the duration of the response to the treatment. The use of cetuximab in combination with radiotherapy does not increase the side effects of radiotherapy. At the end of the follow-up, 17 patients died. Conclusion: Cetuximab, with its highly targeted mechanism of action and synergistic activity with current treatment modalities, is a valuable treatment option in head and neck patients. The effect of the epidermal growth factor receptor antagonist occurs without any change in the pattern and the severity of toxicity usually associated with head and neck radiation. Cetuximab seems not to provide the most benefit for patients with oropharyngeal cancers but will in patients with T4 tumors. However, the median duration of local control was less as described in the clinical trials. PMID:21188107

Mental health and learning disability nursing students' perceptions of the usefulness of the objective structured clinical examination to assess their competence in medicine administration.

PubMed

Hemingway, Steve; Stephenson, John; Roberts, Bronwyn; McCann, Terence

2014-08-01

The aim of this study was to evaluate mental health and learning disability nursing students' perceptions of the usefulness of the objective structured clinical examination (OSCE) in assessing their administration of medicine competence. Learning disability (n = 24) and mental health (n = 46) students from a single cohort were invited to evaluate their experience of the OSCE. A 10-item survey questionnaire was used, comprising open- and closed-response questions. Twelve (50%) learning disability and 32 (69.6%) mental health nursing students participated. The OSCE was rated highly compared to other theoretical assessments; it was also reported as clinically real and as a motivational learning strategy. However, it did not rate as well as clinical practice. Content analysis of written responses identified four themes: (i) benefits of the OSCE; (ii) suggestions to improve the OSCE; (iii) concern about the lack of clinical reality of the OSCE; and (iv) OSCE-induced stress. The themes, although repeating some of the positive statistical findings, showed that participants were critical of the university setting as a place to conduct clinical assessment, highlighted OSCE-related stress, and questioned the validity of the OSCE as a real-world assessment. The OSCE has an important role in the development of student nurses' administration of medicine skills. However, it might hinder their performance as a result of the stress of being assessed in a simulated environment.

Clinical, serological, and parasitological analysis of snakes naturally infected with Cryptosporidium serpentis.

PubMed

Paiva, Philipp Ricardo S O; Grego, Kathleen F; Lima, Valéria M F; Nakamura, Alex A; da Silva, Deuvânia C; Meireles, Marcelo V

2013-11-15

Infection by Cryptosporidium serpentis is one of the most important diseases in reptiles and is characterized by chronic clinical or subclinical infection and the presence of hypertrophic gastritis, food regurgitation, progressive weight loss, mortality, and intermittent or continuous shedding of oocysts in the feces. The objectives of this study were to standardize an indirect enzyme-linked immunosorbent assay (ELISA) to detect antibodies against C. serpentis and to evaluate the clinical, parasitological, and humoral immune response in snakes naturally infected with C. serpentis. Twenty-one snakes naturally infected with C. serpentis and housed at the Butantan Institute, São Paulo, Brazil, underwent clinical and parasitological analyses for C. serpentis infection through daily records of clinical signs and a monthly survey of fecal shedding of oocysts using the Kinyoun's acid-fast staining. The serological evaluation was performed monthly by indirect ELISA using crude total antigen from oocysts of C. serpentis to detect anti-C. serpentis antibodies. Clinical symptoms consisted of food regurgitation, inappetence, and progressive weight loss. The parasitological analysis revealed intermittent fecal shedding of a variable number of oocysts in all snakes, with positivity in 85.32% (157/184) of the samples. The indirect ELISA was positive in 68.25% (86/126) of the samples. A humoral immune response was observed in most animals; however, fluctuating antibodies levels, leading to alternating positive and negative results, were observed in most snakes. Copyright © 2013 Elsevier B.V. All rights reserved.

Psychometric Evaluation of the Hypogonadism Impact of Symptoms Questionnaire Short Form (HIS-Q-SF).

PubMed

Gelhorn, Heather L; Roberts, Laurie J; Khandelwal, Nikhil; Revicki, Dennis A; DeRogatis, Leonard R; Dobs, Adrian; Hepp, Zsolt; Miller, Michael G

2017-08-01

The Hypogonadism Impact of Symptoms Questionnaire Short Form (HIS-Q-SF) is a patient-reported outcome measurement designed to evaluate the symptoms of hypogonadism. The HIS-Q-SF is an abbreviated version including17 items from the original 28-item HIS-Q. To conduct item analyses and reduction, evaluate the psychometric properties of the HIS-Q-SF, and provide guidance on score interpretation. A 12-week observational longitudinal study of hypogonadal men was conducted as part of the original HIS-Q psychometric evaluation. Participants completed the original HIS-Q every 2 weeks. Blood samples were collected to evaluate testosterone levels. Participants completed the Aging Male's Symptoms Scale, the International Index of Erectile Function, the Short Form-12, and the PROMIS Sexual Activity, Satisfaction with Sex Life, Sleep Disturbance, and Applied Cognition Scales (baseline and weeks 6 and 12). Clinicians completed the Clinical Global Impression of Severity and Change scales and a clinical form. Item performance was evaluated using descriptive statistics and Rasch analyses. Reliability (internal consistency and test-retest), validity (concurrent and know groups), and responsiveness were assessed. One hundred seventy-seven men participated (mean age = 54.1 years, range = 23-83). Similar to the full HIS-Q, the final abbreviated HIS-Q-SF instrument includes five domains (sexual, energy, sleep, cognition, and mood) with two sexual subdomains (libido and sexual function). For key domains, test-retest reliability was very good, and construct validity was good for all domains. Known-groups validity was demonstrated for all domain scores, subdomain scores, and total score based on the Clinical Global Impression-Severity. All domains and subdomains were responsive to change based on patient-rated anchor questions. The HIS-Q-SF could be a useful tool in clinical practice, epidemiologic studies, and other academic research settings. Careful consideration was given to the selection of the final HIS-Q-SF items based on quantitative data and clinical expert feedback. Overall, the reduced set of items demonstrated strong psychometric properties. Testosterone levels for the participating men were not as low as anticipated, which could have limited the ability to examine the relations between the HIS-Q-SF and testosterone levels. Further, the analyses used data collected through administration of the full HIS-Q, and future studies should administer the standalone HIS-Q-SF to replicate the psychometric analyses reported in the present study. Similar to the original HIS-Q, the HIS-Q-SF has evidence supporting reliability, validity, and responsiveness. The short form includes a smaller set of items that might be more suitable for use in clinical practice or academic research settings. Gelhorn HL, Roberts LJ, Khandelwal N, et al. Psychometric Evaluation of the Hypogonadism Impact of Symptoms Questionnaire Short Form (HIS-Q-SF). J Sex Med 2017;14:1046-1058. Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Early Effects of Responsivity Education/Prelinguistic Milieu Teaching for Children with Developmental Delays and Their Parents

ERIC Educational Resources Information Center

Fey, Marc E.; Warren, Steven F.; Brady, Nancy; Finestack, Lizbeth H.; Bredin-Oja, Shelley L.; Fairchild, Martha; Sokol, Shari; Yoder, Paul J.

2006-01-01

Purpose: To evaluate the efficacy of a 6-month course of responsivity education/prelinguistic milieu teaching (RE/PMT) for children with developmental delay and RE/PMT's effects on parenting stress in a randomized clinical trial. Method: Fifty-one children, age 24-33 months, with no more than 10 expressive words or signs, were randomly assigned to…

Gaze Response to Dyadic Bids at 2 Years Related to Outcomes at 3 Years in Autism Spectrum Disorders: A Subtyping Analysis

ERIC Educational Resources Information Center

Campbell, Daniel J.; Shic, Frederick; Macari, Suzanne; Chawarska, Katarzyna

2014-01-01

Variability in attention towards direct gaze and child-directed speech may contribute to heterogeneity of clinical presentation in toddlers with autism spectrum disorders (ASD). To evaluate this hypothesis, we clustered sixty-five 20-month-old toddlers with ASD based on their visual responses to dyadic cues for engagement, identifying three…

Commissioning and comprehensive evaluation of the ArcCHECK cylindrical diode array for VMAT pretreatment delivery QA

PubMed Central

Chaswal, Vibha; Weldon, Michael; Gupta, Nilendu; Chakravarti, Arnab

2014-01-01

We present commissioning and comprehensive evaluation for ArcCHECK as a QA equipment for volumetric‐modulated arc therapy (VMAT), using the 6 MV photon beam with and without the flattening filter, and the SNC patient software (version 6.2). In addition to commissioning involving absolute dose calibration, array calibration, and PMMA density verification, ArcCHECK was evaluated for its response dependency on linac dose rate, instantaneous dose rate, radiation field size, beam angle, and couch insertion. Scatter dose characterization, consistency and symmetry of response, and dosimetry accuracy evaluation for fixed aperture arcs and clinical VMAT patient plans were also investigated. All the evaluation tests were performed with the central plug inserted and the homogeneous PMMA density value. Results of gamma analysis demonstrated an overall agreement between ArcCHECK‐measured and TPS‐calculated reference doses. The diode based field size dependency was found to be within 0.5% of the reference. The dose rate‐based dependency was well within 1% of the TPS reference, and the angular dependency was found to be ± 3% of the reference, as tested for BEV angles, for both beams. Dosimetry of fixed arcs, using both narrow and wide field widths, resulted in clinically acceptable global gamma passing rates on the 3%/3 mm level and 10% threshold. Dosimetry of narrow arcs showed an improvement over published literature. The clinical VMAT cases demonstrated high level of dosimetry accuracy in gamma passing rates. PACS numbers: 87.56.Fc, 87.55.kh, 87.55.Qr PMID:25207411

Social Cognition Psychometric Evaluation: Results of the Final Validation Study.

PubMed

Pinkham, Amy E; Harvey, Philip D; Penn, David L

2018-06-06

Social cognition is increasingly recognized as an important treatment target in schizophrenia; however, the dearth of well-validated measures that are suitable for use in clinical trials remains a significant limitation. The Social Cognition Psychometric Evaluation (SCOPE) study addresses this need by systematically evaluating the psychometric properties of promising measures. In this final phase of SCOPE, eight new or modified tasks were evaluated. Stable outpatients with schizophrenia (n = 218) and healthy controls (n = 154) completed the battery at baseline and 2-4 weeks later across three sites. Tasks included the Bell Lysaker Emotion Recognition Task (BLERT), Penn Emotion Recognition Task (ER-40), Reading the Mind in the Eyes Task (Eyes), The Awareness of Social Inferences Test (TASIT), Hinting Task, Mini Profile of Nonverbal Sensitivity (MiniPONS), Social Attribution Task-Multiple Choice (SAT-MC), and Intentionality Bias Task (IBT). BLERT and ER-40 modifications included response time and confidence ratings. The Eyes task was modified to include definitions of terms and TASIT to include response time. Hinting was scored with more stringent criteria. MiniPONS, SAT-MC, and IBT were new to this phase. Tasks were evaluated on (1) test-retest reliability, (2) utility as a repeated measure, (3) relationship to functional outcome, (4) practicality and tolerability, (5) sensitivity to group differences, and (6) internal consistency. Hinting, BLERT, and ER-40 showed the strongest psychometric properties and are recommended for use in clinical trials. Eyes, TASIT, and IBT showed somewhat weaker psychometric properties and require further study. MiniPONS and SAT-MC showed poorer psychometric properties that suggest caution for their use in clinical trials.

Psychometrics evaluation of Charcot-Marie-Tooth Neuropathy Score (CMTNSv2) second version, using Rasch analysis.

PubMed

Sadjadi, Reza; Reilly, Mary M; Shy, Michael E; Pareyson, Davide; Laura, Matilde; Murphy, Sinead; Feely, Shawna M E; Grider, Tiffany; Bacon, Chelsea; Piscosquito, Giuseppe; Calabrese, Daniela; Burns, Ted M

2014-09-01

Charcot-Marie-Tooth Neuropathy Score second version (CMTNSv2) is a validated clinical outcome measure developed for use in clinical trials to monitor disease impairment and progression in affected CMT patients. Currently, all items of CMTNSv2 have identical contribution to the total score. We used Rasch analysis to further explore psychometric properties of CMTNSv2, and in particular, category response functioning, and their weight on the overall disease progression. Weighted category responses represent a more accurate estimate of actual values measuring disease severity and therefore could potentially be used in improving the current version. © 2014 Peripheral Nerve Society.

Body Mass Index and Phenotype in Mild-to-Moderate Persistent Asthma

PubMed Central

Sutherland, E. Rand; Lehman, Erik B.; Teodorescu, Mihaela; Wechsler, Michael E.

2009-01-01

Background While obesity has been hypothesized to worsen asthma, data from studies of well-characterized asthmatics are lacking. Objective Evaluate the relationship between body mass index (BMI), asthma impairment and response to therapy. Methods BMI (kg/m2) and asthma phenotypic and treatment response data were extracted from Asthma Clinical Research Network (ACRN) studies. The cross-sectional relationship between BMI and asthma impairment was analyzed, as was the longitudinal relationship between BMI and response to asthma controller therapies. Results 1,265 subjects with mild-to-moderate persistent asthma were evaluated. Analyses of lean vs. overweight/obese asthmatics demonstrated small differences in FEV1 (3.05 vs. 2.91 L, p=0.001), FEV1/FVC (mean 83.5% vs. 82.4%, p=0.01), rescue albuterol use (1.1 vs. 1.2 puffs/day, p=0.03) and asthma-related quality of life (5.77 vs. 5.59, p=0.0004). Overweight/obese asthmatics demonstrated a smaller improvement in exhaled nitric oxide with inhaled corticosteroid (ICS) treatment than did lean asthmatics (3.6 vs. 6.5ppb, p=0.04). With ICS/long-acting beta agonist treatment, overweight/obese asthmatics demonstrated smaller improvements in lung function than lean asthmatics, with an 80mL (p=0.04) and 1.7% (p=0.02) lesser improvement in FEV1 and FEV1/FVC ratio, respectively. Significant differences in therapeutic response to leukotriene modifiers between BMI categories were not observed. Conclusions Elevated BMI is not associated with clinically-significant worsening of impairment in patients with mild-to-moderate persistent asthma. There is a modest association between elevated BMI and reduced therapeutic effect of ICS-containing regimens in this patient population. Prospective studies evaluating the impact of overweight and obesity on treatment response in asthma are warranted. Clinical Implications In individuals with mild to moderate persistent asthma, being overweight or obese does not appear to modify indices of asthma-related impairment. Elevated body mass index may reduce response to inhaled corticosteroid-containing treatment regimens. PMID:19501235

Trial watch

PubMed Central

Galluzzi, Lorenzo; Senovilla, Laura; Vacchelli, Erika; Eggermont, Alexander; Fridman, Wolf Hervé; Galon, Jerome; Sautès-Fridman, Catherine; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido

2012-01-01

Dendritic cells (DCs) occupy a central position in the immune system, orchestrating a wide repertoire of responses that span from the development of self-tolerance to the elicitation of potent cellular and humoral immunity. Accordingly, DCs are involved in the etiology of conditions as diverse as infectious diseases, allergic and autoimmune disorders, graft rejection and cancer. During the last decade, several methods have been developed to load DCs with tumor-associated antigens, ex vivo or in vivo, in the attempt to use them as therapeutic anticancer vaccines that would elicit clinically relevant immune responses. While this has not always been the case, several clinical studies have demonstrated that DC-based anticancer vaccines are capable of activating tumor-specific immune responses that increase overall survival, at least in a subset of patients. In 2010, this branch of clinical research has culminated with the approval by FDA of a DC-based therapeutic vaccine (sipuleucel-T, Provenge®) for use in patients with asymptomatic or minimally symptomatic metastatic hormone-refractory prostate cancer. Intense research efforts are currently dedicated to the identification of the immunological features of patients that best respond to DC-based anticancer vaccines. This knowledge may indeed lead to personalized combination strategies that would extend the benefit of DC-based immunotherapy to a larger patient population. In addition, widespread enthusiasm has been generated by the results of the first clinical trials based on in vivo DC targeting, an approach that holds great promises for the future of DC-based immunotherapy. In this Trial Watch, we will summarize the results of recently completed clinical trials and discuss the progress of ongoing studies that have evaluated/are evaluating DC-based interventions for cancer therapy. PMID:23170259

Alumni-based evaluation of a novel veterinary curriculum: are Nottingham graduates prepared for clinical practice?

PubMed Central

Cobb, K. A.; Brown, G. A.; Hammond, R. H.; Mossop, L. H.

2015-01-01

Introduction Outcomes-based education has been the core of the curriculum strategy of the Nottingham School of Veterinary Medicine and Science (SVMS) since its inception in 2006. As part of the ongoing curriculum evaluation, the first two graduating cohorts were invited to provide an appraisal of their preparation by the SVMS curriculum for their role in clinical practice. This paper provides brief accounts of the SVMS curriculum model, the development of the evaluation instrument and the findings of the alumni survey. Materials and Methods The evaluation instrument contained 25 attributes expected of SVMS graduates. Alumni rated their preparation for practice in relation to each attribute. Results The four highest rated characteristics were compassion for animals and the application of ethics to animal welfare; communication skills; recognising own limitations and seeking help and advice where needed and clinical examination skills. The four lowest rated were clinical case management and therapeutic strategies; dealing with veterinary public health and zoonotic issues; knowledge of current veterinary legislation and dealing with emergency and critical care cases. Free text responses were in line with these quantitative findings. Conclusion The results indicate that this sample of SVMS graduates were satisfied with their undergraduate education and felt well prepared for their role in clinical practice. PMID:26392910

Evaluation of the dosimetric properties of a synthetic single crystal diamond detector in high energy clinical proton beams.

PubMed

Mandapaka, A K; Ghebremedhin, A; Patyal, B; Marinelli, Marco; Prestopino, G; Verona, C; Verona-Rinati, G

2013-12-01

To investigate the dosimetric properties of a synthetic single crystal diamond Schottky diode for accurate relative dose measurements in large and small field high-energy clinical proton beams. The dosimetric properties of a synthetic single crystal diamond detector were assessed by comparison with a reference Markus parallel plate ionization chamber, an Exradin A16 microionization chamber, and Exradin T1a ion chamber. The diamond detector was operated at zero bias voltage at all times. Comparative dose distribution measurements were performed by means of Fractional depth dose curves and lateral beam profiles in clinical proton beams of energies 155 and 250 MeV for a 14 cm square cerrobend aperture and 126 MeV for 3, 2, and 1 cm diameter circular brass collimators. ICRU Report No. 78 recommended beam parameters were used to compare fractional depth dose curves and beam profiles obtained using the diamond detector and the reference ionization chamber. Warm-up∕stability of the detector response and linearity with dose were evaluated in a 250 MeV proton beam and dose rate dependence was evaluated in a 126 MeV proton beam. Stem effect and the azimuthal angle dependence of the diode response were also evaluated. A maximum deviation in diamond detector signal from the average reading of less than 0.5% was found during the warm-up irradiation procedure. The detector response showed a good linear behavior as a function of dose with observed deviations below 0.5% over a dose range from 50 to 500 cGy. The detector response was dose rate independent, with deviations below 0.5% in the investigated dose rates ranging from 85 to 300 cGy∕min. Stem effect and azimuthal angle dependence of the diode signal were within 0.5%. Fractional depth dose curves and lateral beam profiles obtained with the diamond detector were in good agreement with those measured using reference dosimeters. The observed dosimetric properties of the synthetic single crystal diamond detector indicate that its behavior is proton energy independent and dose rate independent in the investigated energy and dose rate range and it is suitable for accurate relative dosimetric measurements in large as well as in small field high energy clinical proton beams.

Immunoregulatory mechanisms in Chagas disease: modulation of apoptosis in T-cell mediated immune responses.

PubMed

Chaves, Ana Thereza; de Assis Silva Gomes Estanislau, Juliana; Fiuza, Jacqueline Araújo; Carvalho, Andréa Teixeira; Ferreira, Karine Silvestre; Fares, Rafaelle Christine Gomes; Guimarães, Pedro Henrique Gazzinelli; de Souza Fagundes, Elaine Maria; Morato, Maria José; Fujiwara, Ricardo Toshio; da Costa Rocha, Manoel Otávio; Correa-Oliveira, Rodrigo

2016-04-30

Chronic Chagas disease presents different clinical manifestations ranging from asymptomatic (namely indeterminate) to severe cardiac and/or digestive. Previous results have shown that the immune response plays an important role, although no all mechanisms are understood. Immunoregulatory mechanisms such as apoptosis are important for the control of Chagas disease, possibly affecting the morbidity in chronic clinical forms. Apoptosis has been suggested to be an important mechanism of cellular response during T. cruzi infection. We aimed to further understand the putative role of apoptosis in Chagas disease and its relation to the clinical forms of the disease. Apoptosis of lymphocytes, under antigenic stimuli (soluble T. cruzi antigens - TcAg) where compared to that of non-stimulated cells. Apoptosis was evaluated using the expression of annexin and caspase 3(+) by T cells and the percentage of cells positive evaluated by flow cytometry. In addition activation and T cell markers were used for the identification of TCD4(+) and TCD8(+) subpopulations. The presence of intracellular and plasma cytokines were also evaluated. Analysis of the activation status of the peripheral blood cells showed that patients with Chagas disease presented higher levels of activation determined by the expression of activation markers, after TcAg stimulation. PCR array were used to evaluate the contribution of this mechanism in specific cell populations from patients with different clinical forms of human Chagas disease. Our results showed a reduced proliferative response associated a high expression of T CD4(+)CD62L(-) cells in CARD patients when compared with IND group and NI individuals. We also observed that both groups of patients presented a significant increase of CD4(+) and CD8(+) T cell subsets in undergoing apoptosis after in vitro stimulation with T. cruzi antigens. In CARD patients, both CD4(+) and CD8(+) T cells expressing TNF-α were highly susceptible to undergo apoptosis after in vitro stimulation. Interestingly, the in vitro TcAg stimulation increased considerably the expression of cell death TNF/TNFR superfamily and Caspase family receptors genes in CARD patients. Taken together, our results suggest that apoptosis may be an important mechanism for the control of morbidity in T. cruzi infection by modulating the expression of apoptosis genes, the cytokine environment and/or killing of effector cells.

Treatment of female pattern hair loss with oral antiandrogens.

PubMed

Sinclair, R; Wewerinke, M; Jolley, D

2005-03-01

It has not been conclusively established that female pattern hair loss (FPHL) is either due to androgens or responsive to oral antiandrogen therapy. To evaluate the efficacy of oral antiandrogen therapy in the management of women with FPHL using standardized photographic techniques (Canfield Scientific), and to identify clinical and histological parameters predictive of clinical response. For this single-centre, before-after, open intervention study, 80 women aged between 12 and 79 years, with FPHL and biopsy-confirmed hair follicle miniaturization [terminal/vellus (T/V) hair ratio < or = 4 : 1] were photographed at baseline and again after receiving a minimum of 12 months of oral antiandrogen therapy. Forty women received spironolactone 200 mg daily and 40 women received cyproterone acetate, either 50 mg daily or 100 mg for 10 days per month if premenopausal. Women using topical minoxidil were excluded. Standardized photographs of the midfrontal and vertex scalp were taken with the head positioned in a stereotactic device. Images were evaluated by a panel of three clinicians experienced in the assessment of FPHL, blinded to patient details and treatment and using a three-point scale. As there was no significant difference in the results or the trend between spironolactone and cyproterone acetate the results were combined. Thirty-five (44%) women had hair regrowth, 35 (44%) had no clear change in hair density before and after treatment, and 10 (12%) experienced continuing hair loss during the treatment period. Ordinal logistic regression analysis to identify predictors of response revealed no influence of patient age, menopause status, serum ferritin, serum hormone levels, clinical stage (Ludwig) or histological parameters such as T/V ratio or fibrosis. The only significant predictor was midscalp clinical grade, with higher-scale values associated with a greater response (P = 0.013). Eighty-eight percent of women receiving oral antiandrogens could expect to see no progression of their FPHL or improvement. High midscalp clinical grade was the only predictor of response identified. A placebo-controlled study is required to compare this outcome to the natural history of FPHL.

The Script Concordance Test: a new tool assessing clinical judgement in neurology.

PubMed

Lubarsky, Stuart; Chalk, Colin; Kazitani, Driss; Gagnon, Robert; Charlin, Bernard

2009-05-01

Clinical judgment, the ability to make appropriate decisions in uncertain situations, is central to neurological practice, but objective measures of clinical judgment in neurology trainees are lacking. The Script Concordance Test (SCT), based on script theory from cognitive psychology, uses authentic clinical scenarios to compare a trainee's judgment skills with those of experts. The SCT has been validated in several medical disciplines, but has not been investigated in neurology. We developed an Internet-based neurology SCT (NSCT) comprising 24 clinical scenarios with three to four questions each. The scenarios were designed to reflect the uncertainty of real-life clinical encounters in adult neurology. The questions explored aspects of the scenario in which several responses might be acceptable; trainees were asked to judge which response they considered to be best. Forty-one PGY1-PGY5 neurology residents and eight medical students from three North American neurology programs (McGill, Calgary, and Mayo Clinic) completed the NSCT. The responses of trainees to each question were compared with the aggregate responses of an expert panel of 16 attending neurologists. The NSCT demonstrated good reliability (Cronbach alpha = 0.79). Neurology residents scored higher than medical students and lower than attending neurologists, supporting the test's construct validity. Furthermore, NSCT scores discriminated between senior (PGY3-5) and junior residents (PGY1-2). Our NSCT is a practical and reliable instrument, and our findings support its construct validity for assessing judgment in neurology trainees. The NSCT has potentially widespread applications as an evaluation tool, both in neurology training and for licensing examinations.

A Comparison of Two Electric Taste Stimulation Devices

PubMed Central

McClure, Scott T.; Lawless, Harry T.

2016-01-01

Electrical stimulation of the tongue, commonly used in clinical evaluations of taste dysfunction, can produce a variety of sensations including reports of metallic taste. Two studies compared responses to a fabricated electrical stimulator (a 1.6 V battery, anode side exposed) and a clinical electrogustometer (Rion TR-06). Batteries placed on the anterior dorsal tongue surface produced sensations similar in intensity and quality to those produced by the clinical electrogustometer, with equal intensity on the tongue tip for the 1.6 V battery in the range of 33 – 56 µA from the electrogustometer. A second study examined responses on three areas of the tongue on each side. Responses declined for areas lower in fungiform papillae for both devices, but at different rates. Higher current levels were required to match the battery in lower density areas, indicating spatial summation for the larger battery surface area. A consistent pattern of lateral differences was seen in only one subject. Quality descriptions were similar in frequency whether or not a word list was provided, with metallic, sour, pain and bitter being the most frequently mentioned words for both electric stimuli. Similarities in response to the battery device and electrogustometer were evident in intensity, qualities evoked, lack of a laterality effect and decreasing response in areas with lower fungiform papillae density. The battery device may provide an inexpensive portable alternative to an electrogustometer for use in clinical testing of taste. PMID:17573078

Using Instructive Feedback to Increase Response Variability During Intraverbal Training for Children with Autism Spectrum Disorder.

PubMed

Carroll, Regina A; Kodak, Tiffany

2015-10-01

We evaluated the effects of instructive feedback on the variability of intraverbal responses for two children with autism spectrum disorder. Specifically, we used an adapted alternating treatments design to compare participants' novel responses and response combinations during an intraverbal category program across conditions with and without instructive feedback. During instructive feedback, secondary targets were presented during the consequence event of the learning trial and consisted of a therapist's model of response variability. The results showed that participants engaged in more novel response combinations during instructive feedback conditions. We discussed the clinical implications of these results as well as areas for future research.

Update on metabolism and nutrition therapy in critically ill burn patients.

PubMed

Moreira, E; Burghi, G; Manzanares, W

Major burn injury triggers severe oxidative stress, a systemic inflammatory response, and a persistent hypermetabolic and hypercatabolic state with secondary sarcopenia, multiorgan dysfunction, sepsis and an increased mortality risk. Calorie deficit, negative protein balance and antioxidant micronutrient deficiency after thermal injury have been associated to poor clinical outcomes. In this context, personalized nutrition therapy with early enteral feeding from the start of resuscitation are indicated. Over the last four decades, different nutritional and pharmacological interventions aimed at modulating the immune and metabolic responses have been evaluated. These strategies have been shown to be able to minimize acute malnutrition, as well as modulate the immunoinflammatory response, and improve relevant clinical outcomes in this patient population. The purpose of this updating review is to summarize the most current evidence on metabolic response and nutrition therapy in critically ill burn patients. Copyright © 2017 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

Irradiation-hyperthermia in canine hemangiopericytomas: large-animal model for therapeutic response.

PubMed

Richardson, R C; Anderson, V L; Voorhees, W D; Blevins, W E; Inskeep, T K; Janas, W; Shupe, R E; Babbs, C F

1984-11-01

Results of irradiation-hyperthermia treatment in 11 dogs with naturally occurring hemangiopericytoma were reported. Similarities of canine and human hemangiopericytomas were described. Orthovoltage X-irradiation followed by microwave-induced hyperthermia resulted in a 91% objective response rate. A statistical procedure was given to evaluate quantitatively the clinical behavior of locally invasive, nonmetastatic tumors in dogs that were undergoing therapy for control of local disease. The procedure used a small sample size and demonstrated distribution of the data on a scaled response as well as transformation of the data through classical parametric and nonparametric statistical methods. These statistical methods set confidence limits on the population mean and placed tolerance limits on a population percentage. Application of the statistical methods to human and animal clinical trials was apparent.

Can we predict the blood pressure response to renal denervation?

PubMed Central

Fink, Gregory D.; Phelps, Jeremiah T.

2016-01-01

Renal denervation (RDN) is a new therapy used to treat drug-resistant hypertension in the clinical setting. Published human trials show substantial inter-individual variability in the blood pressure (BP) response to RDN, even when technical aspects of the treatment are standardized as much as possible between patients. Widespread acceptance of RDN for treating hypertension will require accurate identification of patients likely to respond to RDN with a fall in BP that is clinically significant in magnitude, well-maintained over time and does not cause adverse consequences. In this paper we review and evaluate clinical studies that address possible predictors of the BP response to RDN. We conclude that only one generally reliable predictor has been identified to date, namely pre-RDN BP level, although there is some evidence for a few other factors. Experimental interventions in laboratory animals provide the opportunity to explore potential predictors that are difficult to investigate in human patients. Therefore we also describe results (from our lab and others) with RDN in spontaneously hypertensive rats. Since virtually all patients receiving RDN are taking three or more antihypertensive drugs, a particular focus of our work was on how ongoing antihypertensive drug treatment might alter the BP response to RDN. We conclude that patient age (or duration of hypertension) and concomitant treatment with certain drugs can affect the blood pressure response to RDN and that this information could help predict a favorable clinical response. PMID:27530600

Return to Play after Cervical Spine Injuries: A Consensus of Opinion

PubMed Central

France, John C.; Karsy, Michael; Harrop, James S.; Dailey, Andrew T.

2016-01-01

Study Design Survey. Objective Sports-related spinal cord injury (SCI) represents a growing proportion of total SCIs but lacks evidence or guidelines to guide clinical decision-making on return to play (RTP). Our objective is to offer the treating physician a consensus analysis of expert opinion regarding RTP that can be incorporated with the unique factors of a case for clinical decision-making. Methods Ten common clinical scenarios involving neurapraxia and stenosis, atlantoaxial injury, subaxial injury, and general cervical spine injury were presented to 25 spine surgeons from level 1 trauma centers for whom spine trauma is a significant component of their practice. We evaluated responses to questions about patient RTP, level of contact, imaging required for a clinical decision, and time to return for each scenario. The chi-square test was used for statistical analysis, with p < 0.05 considered significant. Results Evaluation of the surgeons' responses to these cases showed significant consensus regarding return to high-contact sports in cases of cervical cord neurapraxia without symptoms or stenosis, surgically repaired herniated disks, and nonoperatively healed C1 ring or C2 hangman's fractures. Greater variability was found in recommendations for patients showing persistent clinical symptomatology. Conclusion This survey suggests a consensus among surgeons for allowing patients with relatively normal imaging and resolution of symptoms to return to high-contact activities; however, patients with cervical stenosis or clinical symptoms continue to be a challenge for management. This survey may serve as a basis for future clinical trials and consensus guidelines. PMID:27853664

Autoimmune Disease with Cardiac Valves Involvement: Libman-Sacks Endocarditis.

PubMed

Ginanjar, Eka; Yulianto, Yulianto

2017-04-01

This case study aim to evaluate the response of steroid treatment for autoimmune endocarditis. Valvular heart disease is relatively rising in both congenital and acquired cases, but the autoimmune endocarditis remains rare. In this case, a 34 year old woman with clinical manifestation resembling systemic lupus erythematosus (SLE) is diagnosed with Libman-sacks Endocarditis. After six months of steroid treatment, her clinical manifestations and heart structure improved.

Location of injected polymethylmethacrylate microspheres influences the onset of late adverse effects: an experimental and histopathologic study

PubMed Central

de Jesus, Luciano Henrique; de Campos Hildebrand, Laura; Martins, Manoela Domingues; da Rosa, Francinne Miranda; Danilevicz, Chris Krebs; Sant’Ana Filho, Manoel

2015-01-01

Polymethylmethacrylate (PMMA) has been widely used in the correction of wrinkles because of its long-lasting cosmetic improvements. However, side effects and complications may occur, and its clinical appearance on the oral mucosa can be similar to that of inflammatory or neoplastic disease. The aim of this research was to compare the clinical and histopathologic responses to PMMA injected by two different methods. Twenty-two rats received an injection of PMMA using the tunneling technique (gold standard), with subcutaneous deposition of the filler in the face, or a variation of the technique with transcutaneous submucosal deposition of the filler in the cheek. The tissue reaction was analyzed clinically every 24 hours during the first week, then once a week for the following 3 months. Histologic evaluation was based on the local inflammatory response to the filler. No clinical changes were observed during the initial evaluation period (0–14 days). After 14 days, only the submucosal group showed extra-oral enlargement (n=4, 18.2%). Histopathologic analysis revealed nodule formation in four animals (18.2%) in the submucosal group, with no nodules observed in the subcutaneous group. The data obtained in this study demonstrate that the technique used to deliver the filler may influence the risk of adverse reactions. PMID:26346665

Can probiotics enhance vaccine-specific immunity in children and adults?

PubMed

Kwak, J Y; Lamousé-Smith, E S N

2017-10-13

The growing use of probiotics by the general public has heightened the interest in understanding the role of probiotics in promoting health and preventing disease. General practitioners and specialists often receive inquiries from their patients regarding probiotic products and their use to ward off systemic infection or intestinal maladies. Enhanced immune function is among the touted health benefits conferred by probiotics but has not yet been fully established. Results from recent clinical trials in adults suggest a potential role for probiotics in enhancing vaccine-specific immunity. Although almost all vaccinations are given during infancy and childhood, the numbers of and results from studies using probiotics in pediatric subjects are limited. This review evaluates recent clinical trials of probiotics used to enhance vaccine-specific immune responses in adults and infants. We highlight meaningful results and the implications of these findings for designing translational and clinical studies that will evaluate the potential clinical role for probiotics. We conclude that the touted health claims of probiotics for use in children to augment immunity warrant further investigation. In order to achieve this goal, a consensus should be reached on common study designs that apply similar treatment timelines, compare well-characterised probiotic strains and monitor effective responses against different classes of vaccines.

Nurses' evaluation of physicians' non-clinical performance in emergency departments: advantages, disadvantages and lessons learned.

PubMed

Alameddine, Mohamad; Mufarrij, Afif; Saliba, Miriam; Mourad, Yara; Jabbour, Rima; Hitti, Eveline

2015-02-27

Peer evaluation is increasingly used as a method to assess physicians' interpersonal and communication skills. We report on experience with soliciting registered nurses' feedback on physicians' non-clinical performance in the ED of a large academic medical center in Lebanon. We utilized a secondary analysis of a de-identified database of ED nurses' assessment of physicians' non-clinical performance coupled with an evaluation of interventions carried out as a result of this evaluation. The database was compiled as part of quality/performance improvement initiatives using a cross-sectional design to survey registered nurses working at the ED. The survey instrument included open ended and closed ended questions assessing physicians' communication, professionalism and leadership skills. Three episodes of evaluation were carried out over an 18 month period. Physicians were provided with a communication training carried out after the first cycle of evaluation and a detailed feedback on their assessment by nurses after each evaluation cycle. A paired t-test was carried out to compare mean evaluation scores between the three cycles of evaluation. Thematic analysis of nurses' qualitative comments was carried out. A statistically significant increase in the averages of skills was observed between the first and second evaluations, followed by a significant decrease in the averages of the three skills between the second and third evaluations. Personalized feedback to ED physicians and communication training initially contributed to a significant positive impact on improving ED physicians' non-clinical skills as perceived by the ED nurses. Yet, gains achieved were lost upon reaching the third cycle of evaluation. However, the thematic analysis of the nurses' qualitative responses portrays a decrease in concerns across the various dimensions of non-clinical performance. Nurses' evaluation of the non-clinical performance of physicians has the potential of improving communication, professionalism and leadership skills amongst physicians. For improvement to be realized in a sustainable manner, such programs may need to be offered in a staged and incremental manner over a long period of time with proper dedication of resources and timely monitoring and evaluation of outcomes. Department directors need to be trained on providing peer evaluation feedback in a constructive manner.

Consumer response to a report card comparing healthcare systems.

PubMed

Braun, Barbara L; Kind, Elizabeth A; Fowles, Jinnet B; Suarez, Walter G

2002-06-01

Report cards to date have focused on quality of care in health plans rather than within healthcare delivery systems. The purpose of this study was to evaluate consumer response to the first healthcare system-level report card. Qualitative assessment of consumer response. We conducted 5 focus groups of community members to evaluate consumer response to the report card; 2 included community club members, 3 included community-dwelling retired persons. Discussions were audiotaped and transcribed; comments were categorized by topic area from the script, and common themes identified. Focus group participants, in general, were unaware of the current emphasis on medical quality improvement initiatives. However, they believed that the opinion that the descriptive clinic information and patient survey data contained in the report card would be most useful mainly for choosing a healthcare system if they were dissatisfied with current medical care, if their healthcare options changed, or if they were in poor health. Personal experience was considered a more trustworthy measure of healthcare quality than were patient survey results. Trustworthiness was perceived to be higher if the report card sponsor was not affiliated with the healthcare systems being evaluated. Participants also believed care system administrators should use the data to enact positive clinic-level and physician-level changes. Healthcare consumers appreciated the attention to patient experiences and supported healthcare quality improvement initiatives. Report cards were considered important for choosing a healthcare system in certain circumstances and for guiding quality improvement efforts at all levels.

Evaluation of Clostridium novyi-NT spores in dogs with naturally occurring tumors.

PubMed

Krick, Erika L; Sorenmo, Karin U; Rankin, Shelley C; Cheong, Ian; Kobrin, Barry; Thornton, Katherine; Kinzler, Kenneth W; Vogelstein, Bert; Zhou, Shibin; Diaz, Luis A

2012-01-01

To establish the maximum tolerated dose of Clostridium novyi-NT spores in tumor-bearing dogs and evaluate spore germination within tumors and tumor response. 6 client-owned dogs. A standard dose-escalation study was planned, with maximum tolerated dose defined as the highest dose at which 0 or 1 of 6 dogs had dose-limiting toxicoses (DLT). Dogs received 1 dose of C. novyi-NT spores i.v.. Toxicoses were graded and interventions performed according to specific guidelines. Grade 3 or higher toxicosis or any toxicosis combination that substantially affected patient status was considered DLT. Clinical response was measured by use of response evaluation criteria in solid tumors at 28 days. The first 2 dogs had DLT. The dose was decreased. Two of the next 4 dogs had DLT; therefore, dose administration was stopped because the study endpoint had been reached. The most common toxicosis was fever (n = 6 dogs). Two dogs developed abscesses (1 within a nasal carcinoma and 1 splenic abscess) attributable to C. novyi-NT infection; both required surgical intervention. Clostridium novyi-NT was cultured from 1 of 6 tumors. Five dogs were available for response assessment (4 had stable disease; 1 had progressive disease). Results indicated that C. novyi-NT can germinate within tumors of dogs. Toxicosis, although common and sometimes severe, was manageable with treatment. Further studies in dogs with superficial tumors may allow for continued dose escalation and provide information for use in clinical trials in veterinary and human oncology.

Cognitive Analysis of Decision Support for Antibiotic Prescribing at the Point of Ordering in a Neonatal Intensive Care Unit

PubMed Central

Sheehan, Barbara; Kaufman, David; Stetson, Peter; Currie, Leanne M.

2009-01-01

Computerized decision support systems have been used to help ensure safe medication prescribing. However, the acceptance of these types of decision support has been reported to be low. It has been suggested that decreased acceptance may be due to lack of clinical relevance. Additionally, cognitive fit between the user interface and clinical task may impact the response of clinicians as they interact with the system. In order to better understand clinician responses to such decision support, we used cognitive task analysis methods to evaluate clinical alerts for antibiotic prescribing in a neonatal intensive care unit. Two methods were used: 1) a cognitive walkthrough; and 2) usability testing with a ‘think-aloud’ protocol. Data were analyzed for impact on cognitive effort according to categories of cognitive distance. We found that responses to alerts may be context specific and that lack of screen cues often increases cognitive effort required to use a system. PMID:20351922

Model‐Informed Development and Registration of a Once‐Daily Regimen of Extended‐Release Tofacitinib

PubMed Central

Lamba, M; Hutmacher, MM; Furst, DE; Dikranian, A; Dowty, ME; Conrado, D; Stock, T; Nduaka, C; Cook, J

2017-01-01

Extended‐release (XR) formulations enable less frequent dosing vs. conventional (e.g., immediate release (IR)) formulations. Regulatory registration of such formulations typically requires pharmacokinetic (PK) and clinical efficacy data. Here we illustrate a model‐informed, exposure–response (E‐R) approach to translate controlled trial data from one formulation to another without a phase III trial, using a tofacitinib case study. Tofacitinib is an oral Janus kinase (JAK) inhibitor for the treatment of rheumatoid arthritis (RA). E‐R analyses were conducted using validated clinical endpoints from phase II dose–response and nonclinical dose fractionation studies of the IR formulation. Consistent with the delay in clinical response dynamics relative to PK, average concentration was established as the relevant PK parameter for tofacitinib efficacy and supported pharmacodynamic similarity. These evaluations, alongside demonstrated equivalence in total systemic exposure between IR and XR formulations, provided the basis for the regulatory approval of tofacitinib XR once daily by the US Food and Drug Administration. PMID:27859030

The anti-CD6 antibody itolizumab provides clinical benefit without lymphopenia in rheumatoid arthritis patients: results from a 6-month, open-label Phase I clinical trial.

PubMed

Rodríguez, P C; Prada, D M; Moreno, E; Aira, L E; Molinero, C; López, A M; Gómez, J A; Hernández, I M; Martínez, J P; Reyes, Y; Milera, J M; Hernández, M V; Torres, R; Avila, Y; Barrese, Y; Viada, C; Montero, E; Hernández, P

2018-02-01

Itolizumab is a humanized anti-CD6 monoclonal antibody (mAb) that has previously shown encouraging results, in terms of safety and positive clinical effects, in a 6-week monotherapy clinical trial conducted in rheumatoid arthritis (RA) patients. The current Phase I study evaluated the safety and clinical response for a longer treatment of 12 itolizumab intravenous doses in subjects with active RA despite previous disease-modifying anti-rheumatic drug (DMARD) therapy. Twenty-one subjects were enrolled into four dosage groups (0·1, 0·2, 0·4 and 0·8 mg/kg). Efficacy end-points including American College of Rheumatology (ACR)20, ACR50 and ACR70 response rates and disease activity score in 28 joints (DAS28) were monitored at baseline and at specific time-points during a 10-week follow-up period. Itolizumab was well tolerated up to the highest tested dose. No related serious adverse events were reported and most adverse events were mild. Remarkably, itolizumab treatment did not produce lymphopenia and, therefore, was not associated with infections. All patients achieved a clinical response (ACR20) at least once during the study. Eleven subjects (55%) achieved at least a 20% improvement in ACR just 1 week after the first itolizumab administration. The clinical response was observed from the beginning of the treatment and was sustained during 24 weeks. The efficacy profile of this 12-week treatment was similar to that of the previous study (6-week treatment). These results reinforce the safety profile of itolizumab and provide further evidence on the clinical benefit from the use of this anti-CD6 mAb in RA patients. © 2017 British Society for Immunology.

Outcomes assessment of dental hygiene clinical teaching workshops.

PubMed

Wallace, Juanita S; Infante, Taline D

2008-10-01

Faculty development courses related to acquiring clinical teaching skills in the health professions are limited. Consequently, the Department of Dental Hygiene at the University of Texas Health Science Center at San Antonio conducted a series of clinical teaching workshops to address clinical teaching methodology. The goal of these workshops was to promote a problem-solving learning atmosphere for dental hygiene faculty to acquire and share sound clinical teaching strategies. To determine the value of the annual workshops on clinical teaching and evaluation, a web-based qualitative program assessment was developed using software by Survey Tracker. Four open-ended questions were designed to elicit perceptions regarding what significant changes in teaching strategies were achieved, what barriers or challenges were encountered in making these changes, and what strategies were used to overcome the barriers. The assessment was sent to dental hygiene educators representing thirty-eight dental hygiene programs who had participated in two or more of these workshops. Twenty-eight programs provided collective responses to the questions, and the narrative data were analyzed, using a qualitative methodology. Responses revealed that programs had made productive changes to their clinical education curricula and the information gained from the workshops had a positive effect on clinical teaching.

Adalimumab for Moderately to Severely Active Ulcerative Colitis: A Systematic Review and Meta-Analysis.

PubMed

Chen, Xinlin; Hou, Jiangtao; Yuan, Yujie; Huang, Chaoyuan; Liu, Tianwen; Mo, Chuanwei; Li, Haiwen; Chen, Bin; Xu, Qian; Hou, Zhengkun; He, Weiling; Liu, Fengbin

2016-06-01

Evidence-based studies are increasingly being focused on evaluating the efficacy and safety of adalimumab (ADA) for moderately to severely active ulcerative colitis (UC). However, the dosage pattern of ADA for UC management is still not clear. A meta-analysis was conducted to evaluate the efficacy and safety of different ADA dosage regimens for moderately to severely active UC. The Medline, EMBASE, ISI Web of Knowledge, and Cochrane databases were searched from their inception to January 2015. Randomized controlled trials (RCTs) comparing ADA with placebo were eligible for initial inclusion. The efficacy and side effects were evaluated for ADA 160/80 (ADA 160/80 mg at weeks 0/2 and then 40 mg at weeks 4 and 6), and ADA 80/40 (ADA 80/40 mg at weeks 0/2 and then 40 mg at weeks 4 and 6) induction therapy, with ADA 40 mg every other week (EOW) for maintenance therapy of 52 weeks. The pooled risk ratio (RR) and its 95 % confidence interval (CI) were calculated. Three RCTs were included. All of the studies were considered to have a low risk of bias. ADA 160/80 was more effective than placebo for induction of clinical remission (RR 1.62, 95 % CI 1.15-2.29), clinical response (RR 1.37, 95 % CI 1.19-1.59), mucosal healing (RR 1.27, 95 % CI 1.08-1.50), and inflammatory bowel disease questionnaire (IBDQ) response (RR 1.22, 95 % CI 1.05-1.43) and did not increase adverse events (RR 1.10, 95 % CI 0.95-1.27). Compared with placebo, ADA 80/40 did not show significant differences for induction of clinical remission and clinical response and did not increase adverse events. ADA 40 mg EOW was superior to placebo in maintaining clinical remission (RR 2.38, 95 % CI 1.57-3.59), clinical response (RR 1.69, 95 % CI 1.29-2.21), mucosal healing (RR 1.69, 95 % CI 1.26-2.28), and IBDQ response (RR 1.73, 95 % CI 1.28-2.34). Compared with placebo, ADA 40 mg EOW increased adverse events (RR 1.28, 95 % CI 1.06-1.54). ADA 160/80 was a safe and effective treatment for induction management of moderately to severely active UC, but the benefits of ADA 80/40 application were limited. ADA 40 mg EOW was effective for maintenance management of UC. Additional well designed RCTs are needed to confirm these results.

Revisions to the International Neuroblastoma Response Criteria: A Consensus Statement From the National Cancer Institute Clinical Trials Planning Meeting

PubMed Central

Bagatell, Rochelle; Cohn, Susan L.; Pearson, Andrew D.; Villablanca, Judith G.; Berthold, Frank; Burchill, Susan; Boubaker, Ariane; McHugh, Kieran; Nuchtern, Jed G.; London, Wendy B.; Seibel, Nita L.; Lindwasser, O. Wolf; Maris, John M.; Brock, Penelope; Schleiermacher, Gudrun; Ladenstein, Ruth; Matthay, Katherine K.; Valteau-Couanet, Dominique

2017-01-01

Purpose More than two decades ago, an international working group established the International Neuroblastoma Response Criteria (INRC) to assess treatment response in children with neuroblastoma. However, this system requires modification to incorporate modern imaging techniques and new methods for quantifying bone marrow disease that were not previously widely available. The National Cancer Institute sponsored a clinical trials planning meeting in 2012 to update and refine response criteria for patients with neuroblastoma. Methods Multidisciplinary investigators from 13 countries reviewed data from published trials performed through cooperative groups, consortia, and single institutions. Data from both prospective and retrospective trials were used to refine the INRC. Monthly international conference calls were held from 2011 to 2015, and consensus was reached through review by working group leadership and the National Cancer Institute Clinical Trials Planning Meeting leadership council. Results Overall response in the revised INRC will integrate tumor response in the primary tumor, soft tissue and bone metastases, and bone marrow. Primary and metastatic soft tissue sites will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) and iodine-123 (123I) –metaiodobenzylguanidine (MIBG) scans or [18F]fluorodeoxyglucose–positron emission tomography scans if the tumor is MIBG nonavid. 123I-MIBG scans, or [18F]fluorodeoxyglucose–positron emission tomography scans for MIBG-nonavid disease, replace technetium-99m diphosphonate bone scintigraphy for osteomedullary metastasis assessment. Bone marrow will be assessed by histology or immunohistochemistry and cytology or immunocytology. Bone marrow with ≤ 5% tumor involvement will be classified as minimal disease. Urinary catecholamine levels will not be included in response assessment. Overall response will be defined as complete response, partial response, minor response, stable disease, or progressive disease. Conclusion These revised criteria will provide a uniform assessment of disease response, improve the interpretability of clinical trial results, and facilitate collaborative trial designs. PMID:28471719

Adapting Social Neuroscience Measures for Schizophrenia Clinical Trials, Part 1: Ferrying Paradigms Across Perilous Waters

PubMed Central

Green, Michael F.

2013-01-01

Social cognitive impairment is prominent in schizophrenia, and it is closely related to functional outcome. Partly for these reasons, it has rapidly become a target for both training and psychopharmacological interventions. However, there is a paucity of reliable and valid social cognitive endpoints that can be used to evaluate treatment response in clinical trials. Also, clinical studies in schizophrenia have benefited rather little from the surge of activity and knowledge in nonclinical social neuroscience. The National Institute of Mental Health-sponsored study, “Social Cognition and Functioning in Schizophrenia” (SCAF), attempted to address this translational challenge by selecting paradigms from social neuroscience that could be adapted for use in schizophrenia. The project also evaluated the psychometric properties and external validity of the tasks to determine their suitability for multisite clinical trials. This first article in the theme section presents the goals, conceptual background, and rationale for the SCAF project. PMID:24072811

[Research Progress and Prospect of Applications of Finite Element Method in Lumbar Spine Biomechanics].

PubMed

Zhang, Zhenjun; Li, Yang; Liao, Zhenhua; Liu, Weiqiang

2016-12-01

Based on the application of finite element analysis in spine biomechanics,the research progress of finite element method applied in lumbar spine mechanics is reviewed and the prospect is forecasted.The related works,including lumbar ontology modeling,clinical application research,and occupational injury and protection,are summarized.The main research areas of finite element method are as follows:new accurate modeling process,the optimized simulation method,diversified clinical effect evaluation,and the clinical application of artificial lumbar disc.According to the recent research progress,the application prospects of finite element method,such as automation and individuation of modeling process,evaluation and analysis of new operation methods and simulation of mechanical damage and dynamic response,are discussed.The purpose of this paper is to provide the theoretical reference and practical guidance for the clinical lumbar problems by reviewing the application of finite element method in the field of the lumbar spine biomechanics.

When Progressive Disease Does Not Mean Treatment Failure: Reconsidering the Criteria for Progression

PubMed Central

2012-01-01

Although progression-based endpoints, such as progression-free survival, are often key clinical trial endpoints for anticancer agents, the clinical meaning of “objective progression” is much less certain. As scrutiny of progression-based endpoints in clinical trials increases, it should be remembered that the Response Evaluation Criteria In Solid Tumors (RECIST) progression criteria were not developed as a surrogate for survival. Now that progression-free survival has come to be an increasingly important trial endpoint, the criteria that define progression deserve critical evaluation to determine whether alternate definitions of progression might facilitate the development of stronger surrogate endpoints and more meaningful trial results. In this commentary, we review the genesis of the criteria for progression, highlight recent data that question their value as a marker of treatment failure, and advocate for several research strategies that could lay the groundwork for a clinically validated definition of disease progression in solid tumor oncology. PMID:22927506

Comparison of warfarin therapy clinical outcomes following implementation of an automated mobile phone-based critical laboratory value text alert system.

PubMed

Lin, Shu-Wen; Kang, Wen-Yi; Lin, Dong-Tsamn; Lee, James; Wu, Fe-Lin; Chen, Chuen-Liang; Tseng, Yufeng J

2014-01-01

Computerized alert and reminder systems have been widely accepted and applied to various patient care settings, with increasing numbers of clinical laboratories communicating critical laboratory test values to professionals via either manual notification or automated alerting systems/computerized reminders. Warfarin, an oral anticoagulant, exhibits narrow therapeutic range between treatment response and adverse events. It requires close monitoring of prothrombin time (PT)/international normalized ratio (INR) to ensure patient safety. This study was aimed to evaluate clinical outcomes of patients on warfarin therapy following implementation of a Personal Handy-phone System-based (PHS) alert system capable of generating and delivering text messages to communicate critical PT/INR laboratory results to practitioners' mobile phones in a large tertiary teaching hospital. A retrospective analysis was performed comparing patient clinical outcomes and physician prescribing behavior following conversion from a manual laboratory result alert system to an automated system. Clinical outcomes and practitioner responses to both alert systems were compared. Complications to warfarin therapy, warfarin utilization, and PT/INR results were evaluated for both systems, as well as clinician time to read alert messages, time to warfarin therapy modification, and monitoring frequency. No significant differences were detected in major hemorrhage and thromboembolism, warfarin prescribing patterns, PT/INR results, warfarin therapy modification, or monitoring frequency following implementation of the PHS text alert system. In both study periods, approximately 80% of critical results led to warfarin discontinuation or dose reduction. Senior physicians' follow-up response time to critical results was significantly decreased in the PHS alert study period (46.3% responded within 1 day) compared to the manual notification study period (24.7%; P = 0.015). No difference in follow-up response time was detected for junior physicians. Implementation of an automated PHS-based text alert system did not adversely impact clinical or safety outcomes of patients on warfarin therapy. Approximately 80% immediate recognition of text alerts was achieved. The potential benefits of an automated PHS alert for senior physicians were demonstrated.

Concordance between patient and clinician assessment of dry eye severity and treatment response in Taiwan.

PubMed

Yeh, Po-Ting; Chien, Hsu-Chih; Ng, Kwong; Tseng, Sung-Huei; Chen, Wei-Li; Hou, Yu-Chih; Wang, I-Jong; Chu, Hsiao-Sung; Kao Yang, Yea-Huei; Hu, Fung-Rong

2015-05-01

Accurate diagnosis and early recognition of dry eye symptoms are important in the management of dry eye disease (DED). This study aimed to evaluate concordance between patient and clinician assessment of DED severity and treatment response. This cross-sectional study was conducted in 2 ophthalmology clinics in Taiwan. Clinicians assessed severity based on the Dry Eye Workshop severity grading (levels 1-4; where 4 = most severe), whereas patients completed the Ocular Surface Disease Index questionnaire. To evaluate the treatment response, patients completed the Subject Global Assessment scale, and clinicians independently assessed patients using the Clinical Global Impression scale. A total of 466 patients were included. Clinicians graded 88.3% of patients as level 1/2, 9.0% as level 3, and 2.7% as level 4 Dry Eye Workshop severity, whereas 44.9% of patients reported normal/mild symptoms, 17.1% with moderate severity, and 38.0% with severe DED. Patients were primarily treated with artificial tears. The clinician assessed 10.3% of patients as unchanged on disease severity after treatment and 88.0% as improved, whereas 49.2% of patients reported dry eye symptoms being almost the same after treatment and 34.6% reported improved symptoms. There was low agreement between clinician and patient assessments in terms of disease severity (rho = 0.17, P < 0.001) and treatment response (rho = 0.22, P < 0.001). There were marked differences in the degree of DED severity and treatment response between patient and clinician assessment. Clinicians may underestimate DED severity and persistence of dry eye symptoms after treatment with artificial tears.Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01942226.

Cytologic anaplasia is a prognostic factor in osteosarcoma biopsies, but mitotic rate or extent of spontaneous tumor necrosis are not: a critique of the College of American Pathologists Bone Biopsy template.

PubMed

Cates, Justin Mm; Dupont, William D

2017-01-01

The current College of American Pathologists cancer template for reporting biopsies of bone tumors recommends including information that is of unproven prognostic significance for osteosarcoma, such as the presence of spontaneous tumor necrosis and mitotic rate. Conversely, the degree of cytologic anaplasia (degree of differentiation) is not reported in this template. This retrospective cohort study of 125 patients with high-grade osteosarcoma was performed to evaluate the prognostic impact of these factors in diagnostic biopsy specimens in predicting the clinical outcome and response to neoadjuvant chemotherapy. Multivariate Cox regression was performed to adjust survival analyses for well-established prognostic factors. Multivariate logistic regression was used to determine odds ratios for good chemotherapy response (≥90% tumor necrosis). Osteosarcomas with severe anaplasia were independently associated with increased overall and disease-free survival, but mitotic rate and spontaneous necrosis had no prognostic impact after controlling for other confounding factors. Mitotic rate showed a trend towards increased odds of a good histologic response, but this effect was diminished after controlling for other predictive factors. Neither spontaneous necrosis nor the degree of cytologic anaplasia observed in biopsy specimens was predictive of a good response to chemotherapy. Mitotic rate and spontaneous tumor necrosis observed in pretreatment biopsy specimens of high-grade osteosarcoma are not strong independent prognostic factors for clinical outcome or predictors of response to neoadjuvant chemotherapy. Therefore, reporting these parameters for osteosarcoma, as recommended in the College of American Pathologists Bone Biopsy template, does not appear to have clinical utility. In contrast, histologic grading schemes for osteosarcoma based on the degree of cytologic anaplasia may have independent prognostic value and should continue to be evaluated.

An adult Xp11.2 translocation renal carcinoma showing response to treatment with sunitinib.

PubMed

Pwint, Thinn P; Macaulay, Valentine; Roberts, Ian S D; Sullivan, Mark; Protheroe, Andrew

2011-01-01

A rare variant of renal cell carcinoma (RCC) with a translocation involving Xp11.2 has become increasingly recognized as a separate entity in the 2004 World Health Organization (WHO) kidney carcinoma classification. These tumors predominantly affect children and young adults and tend to present with advanced stage disease. Although reported to be indolent in children, adult cases run a more aggressive course. Little is known about their natural history, prognosis and response to therapy. We report a case of Xp11 translocation renal cancer in a 33-year-old male patient who presented with widespread rapidly progressive metastatic disease involving extensive intra-thoracic lymph nodes, supra-clavicular, retroperitoneal lymph nodes, lung nodules, and peritoneal mass. He had failed to respond to treatment with high dose interleukin 2, but showed a significant clinical response to treatment with the multikinase inhibitor sunitinib. CT scan performed after 3 cycles (18 weeks) of therapy revealed more than 65% reduction of measurable disease by response evaluation criteria in solid tumors (RECIST) criteria, resolution of other assessable lesions, and a clinical benefit that lasted for over 13 months. But unfortunately, this was subsequently followed by a rapidly progressive course. The well-recognized clinical efficacy of multikinase inhibitors such as sunitinib and sorafenib is based on the outcomes in patients with clear cell histology. There is limited data on efficacy in non-clear cell RCC, but activity in translocation RCC has not been reported. To our knowledge, this is the first documented case of Xp11 translocation carcinoma to have demonstrated an objective durable response to sunitinib. It remains unclear how resistance to sunitinib develops, but the results to date support further evaluation of sunitinib in cases of translocation RCC. Copyright © 2011 Elsevier Inc. All rights reserved.

A randomized clinical trial evaluating plasma rich in growth factors (PRGF-Endoret) versus hyaluronic acid in the short-term treatment of symptomatic knee osteoarthritis.

PubMed

Sánchez, Mikel; Fiz, Nicolás; Azofra, Juan; Usabiaga, Jaime; Aduriz Recalde, Enmanuel; Garcia Gutierrez, Antonio; Albillos, Javier; Gárate, Ramón; Aguirre, Jose Javier; Padilla, Sabino; Orive, Gorka; Anitua, Eduardo

2012-08-01

This multicenter, double-blind clinical trial evaluated and compared the efficacy and safety of PRGF-Endoret (BTI Biotechnology Institute, Vitoria-Gasteiz, Spain), an autologous biological therapy for regenerative purposes, versus hyaluronic acid (HA) as a short-term treatment for knee pain from osteoarthritis. We randomly assigned 176 patients with symptomatic knee osteoarthritis to receive infiltrations with PRGF-Endoret or with HA (3 injections on a weekly basis). The primary outcome measure was a 50% decrease in knee pain from baseline to week 24. As secondary outcomes, we also assessed pain, stiffness, and physical function using the Western Ontario and McMaster Universities Osteoarthritis Index; the rate of response using the criteria of the Outcome Measures for Rheumatology Committee and Osteoarthritis Research Society International Standing Committee for Clinical Trials Response Criteria Initiative (OMERACT-OARSI); and safety. The mean age of the patients was 59.8 years, and 52% were women. Compared with the rate of response to HA, the rate of response to PRGF-Endoret was 14.1 percentage points higher (95% confidence interval, 0.5 to 27.6; P = .044). Regarding the secondary outcome measures, the rate of response to PRGF-Endoret was higher in all cases, although no significant differences were reached. Adverse events were mild and evenly distributed between the groups. Plasma rich in growth factors showed superior short-term results when compared with HA in a randomized controlled trial, with a comparable safety profile, in alleviating symptoms of mild to moderate osteoarthritis of the knee. Level I, randomized controlled multicenter trial. Copyright © 2012 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

A randomized trial of tigecycline versus ampicillin-sulbactam or amoxicillin-clavulanate for the treatment of complicated skin and skin structure infections

PubMed Central

2012-01-01

Background Complicated skin and skin structure infections (cSSSIs) frequently result in hospitalization with significant morbidity and mortality. Methods In this phase 3b/4 parallel, randomized, open-label, comparative study, 531 subjects with cSSSI received tigecycline (100 mg initial dose, then 50 mg intravenously every 12 hrs) or ampicillin-sulbactam 1.5-3 g IV every 6 hrs or amoxicillin-clavulanate 1.2 g IV every 6-8 hrs. Vancomycin could be added at the discretion of the investigator to the comparator arm if methicillin-resistant Staphylococcus aureus (MRSA) was confirmed or suspected within 72 hrs of enrollment. The primary endpoint was clinical response in the clinically evaluable (CE) population at the test-of-cure (TOC) visit. Microbiologic response and safety were also assessed. The modified intent-to-treat (mITT) population comprised 531 subjects (tigecycline, n = 268; comparator, n = 263) and 405 were clinically evaluable (tigecycline, n = 209; comparator, n = 196). Results In the CE population, 162/209 (77.5%) tigecycline-treated subjects and 152/196 (77.6%) comparator-treated subjects were clinically cured (difference 0.0; 95% confidence interval [CI]: -8.7, 8.6). The eradication rates at the subject level for the microbiologically evaluable (ME) population were 79.2% in the tigecycline treatment group and 76.8% in the comparator treatment group (difference 2.4; 95% CI: -9.6, 14.4) at the TOC assessment. Nausea, vomiting, and diarrhea rates were higher in the tigecycline group. Conclusions Tigecycline was generally safe and effective in the treatment of cSSSIs. Trial registration ClinicalTrials.gov NCT00368537 PMID:23145952

Population pharmacokinetics of rituximab in patients with diffuse large B-cell lymphoma and association with clinical outcome.

PubMed

Rozman, Samo; Grabnar, Iztok; Novaković, Srdjan; Mrhar, Ales; Jezeršek Novaković, Barbara

2017-08-01

Pharmacokinetic (PK) studies suggest that there is a room for improvement in clinical use of rituximab through more individualized treatment. The objective of this study was to characterize rituximab PK in 29 newly diagnosed patients with diffuse large B-cell lymphoma treated with rituximab in combination with cyclophosphamide, doxorubicin, vincristine and methylprednisolone every 3 weeks. We also evaluated the association of rituximab PK with clinical outcome. Rituximab serum levels were determined by enzyme-linked immunosorbent assay and evaluated by a population PK analysis applying nonlinear mixed effects modelling. The data were best described by a two-compartment model comprising linear nonspecific clearance of 0.252 [95% confidence interval (CI): 0.227-0.279] l day -1 and time-varying specific clearance of 0.278 (95% CI: 0.181-0.390) l day -1 , corresponding to target-mediated drug disposition of rituximab. Nonspecific clearance was lower in older patients and those with lower body weight. Additionally, volume of the central compartment was higher in males. A clear association of clinical response with rituximab PK has been observed. Rate constant of specific clearance decay was 0.143 day -1 (95% CI: 0.0478-0.418) in patients with no disease progression, while in patients with disease progression it was 82.2% lower (95% CI: 33.4-95.0). This finding indicates that time-changes in clearance could serve as a predictive marker of response to rituximab. Our report demonstrates the rationale for studies evaluating higher doses of rituximab in selected patients. © 2017 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

A randomized trial of tigecycline versus ampicillin-sulbactam or amoxicillin-clavulanate for the treatment of complicated skin and skin structure infections.

PubMed

Matthews, Peter; Alpert, Marc; Rahav, Galia; Rill, Denise; Zito, Edward; Gardiner, David; Pedersen, Ron; Babinchak, Timothy; McGovern, Paul C

2012-11-12

Complicated skin and skin structure infections (cSSSIs) frequently result in hospitalization with significant morbidity and mortality. In this phase 3b/4 parallel, randomized, open-label, comparative study, 531 subjects with cSSSI received tigecycline (100 mg initial dose, then 50 mg intravenously every 12 hrs) or ampicillin-sulbactam 1.5-3 g IV every 6 hrs or amoxicillin-clavulanate 1.2 g IV every 6-8 hrs. Vancomycin could be added at the discretion of the investigator to the comparator arm if methicillin-resistant Staphylococcus aureus (MRSA) was confirmed or suspected within 72 hrs of enrollment. The primary endpoint was clinical response in the clinically evaluable (CE) population at the test-of-cure (TOC) visit. Microbiologic response and safety were also assessed. The modified intent-to-treat (mITT) population comprised 531 subjects (tigecycline, n = 268; comparator, n = 263) and 405 were clinically evaluable (tigecycline, n = 209; comparator, n = 196). In the CE population, 162/209 (77.5%) tigecycline-treated subjects and 152/196 (77.6%) comparator-treated subjects were clinically cured (difference 0.0; 95% confidence interval [CI]: -8.7, 8.6). The eradication rates at the subject level for the microbiologically evaluable (ME) population were 79.2% in the tigecycline treatment group and 76.8% in the comparator treatment group (difference 2.4; 95% CI: -9.6, 14.4) at the TOC assessment. Nausea, vomiting, and diarrhea rates were higher in the tigecycline group. Tigecycline was generally safe and effective in the treatment of cSSSIs. ClinicalTrials.gov NCT00368537.

Improving the evaluation of therapeutic interventions in multiple sclerosis: the role of new psychometric methods.

PubMed

Hobart, J; Cano, S

2009-02-01

In this monograph we examine the added value of new psychometric methods (Rasch measurement and Item Response Theory) over traditional psychometric approaches by comparing and contrasting their psychometric evaluations of existing sets of rating scale data. We have concentrated on Rasch measurement rather than Item Response Theory because we believe that it is the more advantageous method for health measurement from a conceptual, theoretical and practical perspective. Our intention is to provide an authoritative document that describes the principles of Rasch measurement and the practice of Rasch analysis in a clear, detailed, non-technical form that is accurate and accessible to clinicians and researchers in health measurement. A comparison was undertaken of traditional and new psychometric methods in five large sets of rating scale data: (1) evaluation of the Rivermead Mobility Index (RMI) in data from 666 participants in the Cannabis in Multiple Sclerosis (CAMS) study; (2) evaluation of the Multiple Sclerosis Impact Scale (MSIS-29) in data from 1725 people with multiple sclerosis; (3) evaluation of test-retest reliability of MSIS-29 in data from 150 people with multiple sclerosis; (4) examination of the use of Rasch analysis to equate scales purporting to measure the same health construct in 585 people with multiple sclerosis; and (5) comparison of relative responsiveness of the Barthel Index and Functional Independence Measure in data from 1400 people undergoing neurorehabilitation. Both Rasch measurement and Item Response Theory are conceptually and theoretically superior to traditional psychometric methods. Findings from each of the five studies show that Rasch analysis is empirically superior to traditional psychometric methods for evaluating rating scales, developing rating scales, analysing rating scale data, understanding and measuring stability and change, and understanding the health constructs we seek to quantify. There is considerable added value in using Rasch analysis rather than traditional psychometric methods in health measurement. Future research directions include the need to reproduce our findings in a range of clinical populations, detailed head-to-head comparisons of Rasch analysis and Item Response Theory, and the application of Rasch analysis to clinical practice.

Atezolizumab in Platinum-treated Locally Advanced or Metastatic Urothelial Carcinoma: Outcomes by Prior Number of Regimens.

PubMed

Perez-Gracia, Jose Luis; Loriot, Yohann; Rosenberg, Jonathan E; Powles, Thomas; Necchi, Andrea; Hussain, Syed A; Morales-Barrera, Rafael; Retz, Margitta M; Niegisch, Günter; Durán, Ignacio; Théodore, Christine; Grande, Enrique; Shen, Xiaodong; Wang, Jingjing; Nelson, Betty; Derleth, Christina L; van der Heijden, Michiel S

2017-12-19

Patients with metastatic urothelial carcinoma (mUC) who progress after platinum-based chemotherapy have had few treatment options and uniformly poor outcomes. Atezolizumab (anti-programmed death-ligand 1) was approved in the USA for cisplatin-ineligible and platinum-treated mUC based on IMvigor210, a phase 2, single-arm, two-cohort study. To evaluate the efficacy and safety of atezolizumab by the number of prior lines of systemic therapy in patients with pretreated mUC. IMvigor210 enrolled 315 patients with mUC with progression during or following platinum-based therapy at 70 international sites between May 2014 and November 2014. Key inclusion criteria included age ≥18 yr, creatinine clearance ≥30ml/min, and Eastern Cooperative Oncology Group performance status 0-1, with no limit on prior lines of treatment. Patients in this cohort received atezolizumab 1200mg intravenously every 3 wk until loss of clinical benefit. Centrally assessed Response Evaluation Criteria In Solid Tumors v1.1 objective response rate (ORR), median duration of response, overall survival (OS), and adverse events were evaluated by prior treatment. Potential differences between subgroups were evaluated using log-rank (for OS) and chi-square (for ORR and adverse events frequencies) testing. Three hundred and ten patients were efficacy and safety evaluable (median follow-up, 21 mo). Objective responses and prolonged OS occurred across all prespecified subgroups; median duration of response was not reached in most subgroups. In patients without prior systemic mUC therapy (first-line subgroup), ORR was 25% (95% confidence interval: 14-38), and median OS was 9.6 mo (95% confidence interval: 5.9-15.8). No significant differences in efficacy or toxicity by therapy line were observed. Atezolizumab demonstrated comparable efficacy and safety in previously treated patients with mUC across all lines of therapy evaluated. We investigated effects of previous treatment in patients with metastatic urothelial carcinoma that progressed after platinum-based therapy. Atezolizumab was active and tolerable no matter how many treatment regimens patients had received. ClinicalTrials.gov, NCT02108652. Copyright © 2017. Published by Elsevier B.V.

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

PubMed

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.

Prospective evaluation of a 5 × 4 Gy prescription for palliation of canine nasal tumors.

PubMed

Tan-Coleman, Birgitte; Lyons, Jarred; Lewis, Craig; Rosenberg, Mona; Ruiz, Azucena

2013-01-01

We evaluated the efficacy of palliative radiation therapy using 5 × 4 Gy given daily in 18 dogs with nasal tumors. Dogs with malignant nasal tumors were evaluated for response rate, response duration, and survival. Seventy-eight percent of the dogs achieved complete resolution of clinical signs, and 16.5% had partial resolution of their signs. Overall median response duration for all dogs was 178 days after one course of radiation therapy. Six dogs received a second course of therapy when their disease progressed using the same daily 5 × 4 Gy scheme, and all six responded for a median time of 129.5 days for an overall median survival time in these six dogs of 309 days. Based on these results, a radiation prescription of 5 × 4 Gy appears to be useful palliatively in dogs with a malignant nasal tumor. © 2012 Veterinary Radiology & Ultrasound.

Comparison of patients' assessments of the quality of stroke care with audit findings.

PubMed

Howell, Esther; Graham, Chris; Hoffman, A; Lowe, D; McKevitt, Christopher; Reeves, Rachel; Rudd, A G

2007-12-01

To determine the extent of correlation between stroke patients' experiences of hospital care with the quality of services assessed in a national audit. Patients' assessments of their care derived from survey data were linked to data obtained in the National Sentinel Stroke Audit 2004 for 670 patients in 51 English NHS trusts. A measure of patients' experience of hospital stroke care was derived by summing responses to 31 survey items and grouping these into three broad concept domains: quality of care; information; and relationships with staff. Audit data were extracted from hospital admissions data and management information to assess the organisation of services, and obtained retrospectively from patient records to evaluate the delivery of care. Patient survey responses were compared with audit measures of organisation of care and compliance with clinical process standards. Patient experience scores were positively correlated with clinicians' assessment of the organisational quality of stroke care, but were largely unrelated to clinical process standards. Responses to individual questions regarding communication about diagnosis revealed a discrepancy between clinicians' and patients' reports. Better organised stroke care is associated with more positive patient experiences. Examining areas of disparity between patients' and clinicians' reports is important for understanding the complex nature of healthcare and for identifying areas for quality improvement. Future evaluations of the quality of stroke services should include a validated patient experience survey in addition to audit of clinical records.

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

PubMed

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.).

Clinical course of severe colitis: a comparison between Crohn’s Disease and ulcerative colitis.

PubMed

Sinagra, E; Orlando, A; Mocciaro, F; Criscuoli, V; Oliva, L; Maisano, S; Giunta, M; La Seta, F; Solina, G; Rizzo, A G; Leone, A; Tomasello, G; Cappello, F; Cottone, M

2018-01-01

Few data are available about the clinical course of severe colonic Crohn’s disease (CD). The aim of this study is to describe the clinical course of severe Crohn’s colitis in a patient cohort with isolated colonic or ileocolonic CD, and to compare it with the clinical course of patients with severe ulcerative colitis (UC). Thirty-four patients with severe Crohn’s colitis were prospectively identified in our cohort of 593 consecutive hospitalized patients through evaluation of the Crohn’s Disease Activity Index score and the Harvey-Bradshaw Index. One hundred sixty-nine patients with severe ulcerative colitis were prospectively identified in our cohort of 449 consecutive hospitalized patients through evaluation of the Lichtiger score and the Truelove-Witts score. We evaluated the following data/aspects: response to steroids, response to biologics, colectomy rate in acute, colectomy rate during follow-up, megacolon and cytomegalovirus infection rate. We did not find significant differences in the response to steroids and to biologics, in the percentage of cytomegalovirus infection and of megacolon, while the rate of colectomy in acute turned out to be greater in patients with severe Crohn’s colitis compared to patients with severe UC, and this difference appeared to be the limit of statistical significance (Chi-squared 3.31, p = 0.069, OR 0.39); the difference between the colectomy rates at the end of the follow-up was also not significant. In the whole population, by univariate analysis, according to the linear regression model, a young age at diagnosis is associated with a higher overall colectomy rate (p = 0.024) and a higher elective colectomy rate (p = 0.022), but not with a higher acute colectomy rate, and an elevated ESR is correlated with a higher overall colectomy rate (p = 0.014) and a higher acute colectomy rate (p = 0.032), but not with a higher elective colectomy rate. This correlation was significant on multivariate analysis. The overall rate of colectomy in the cohort of patients with severe Crohn’s colitis was greater than that of the cohort of patients with severe UC, but this figure is not supported by a different clinical response to steroid therapy or rescue therapy with biologics. The clinical course of severe Crohn’s colitis requires to be clarified by prospective studies that include a larger number of patients in this subgroup of disease.

Difference in blood pressure response to ACE-Inhibitor monotherapy between black and white adults with arterial hypertension: a meta-analysis of 13 clinical trials.

PubMed

Peck, Robert N; Smart, Luke R; Beier, Rita; Liwa, Anthony C; Grosskurth, Heiner; Fitzgerald, Daniel W; Schmidt, Bernhard M W

2013-09-26

Among African-Americans adults, arterial hypertension is both more prevalent and associated with more complications than among white adults. Hypertension is also epidemic among black adults in sub-Saharan Africa. The treatment of hypertension among black adults may be complicated by lesser response to certain classes of anti-hypertensive agents. We systematically searched literature for clinical trials of ACE-inhibitors among hypertensive adults comparing blood pressure response between whites and blacks. Meta-analysis was performed to determine the difference in systolic and diastolic blood pressure response. Further analysis including meta-regressions, funnel plots, and one-study-removed analyses were performed to investigate possible sources of heterogeneity or bias. In a meta-analysis of 13 trials providing 17 different patient groups for evaluation, black race was associated with a lesser reduction in systolic (mean difference: 4.6 mmHg (95% CI 3.5-5.7)) and diastolic (mean difference: 2.8 mmHg (95% CI 2.2-3.5)) blood pressure response to ACE-inhibitors, with little heterogeneity. Meta-regression revealed only ACE-inhibitor dosage as a significant source of heterogeneity. There was little evidence of publication bias. Black race is consistently associated with a clinically significant lesser reduction in both systolic and diastolic blood pressure to ACE-inhibitor therapy in clinical trials in the USA and Europe. In black adults requiring monotherapy for uncomplicated hypertension, drugs other than ACE-inhibitors may be preferred, though the proven benefits of ACE-inhibitors in some sub-groups and the large overlap of response between blacks and whites must be remembered. These data are particularly important for interpretation of clinical drug trials for hypertensive black adults in sub-Saharan Africa and for the development of treatment recommendations in this population.

Long-Lasting Complete Responses in Patients with Metastatic Melanoma after Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes and an Attenuated IL2 Regimen.

PubMed

Andersen, Rikke; Donia, Marco; Ellebaek, Eva; Borch, Troels Holz; Kongsted, Per; Iversen, Trine Zeeberg; Hölmich, Lisbet Rosenkrantz; Hendel, Helle Westergren; Met, Özcan; Andersen, Mads Hald; Thor Straten, Per; Svane, Inge Marie

2016-08-01

Adoptive cell transfer therapy (ACT) based on autologous tumor-infiltrating lymphocytes (TIL) has achieved impressive clinical results in several phase I and II trials performed outside of Europe. Although transient, the toxicities associated with high-dose (HD) bolus IL2 classically administered together with TILs are severe. To further scrutinize whether similar results can be achieved with lower doses of IL2, we have carried out a phase I/II trial of TIL transfer after classical lymphodepleting chemotherapy followed by an attenuated IL2 regimen. Twenty-five patients with progressive treatment-refractory metastatic melanoma, good clinical performance, age < 70 years, and at least one resectable metastasis were eligible. TIL infusion was preceded by standard lymphodepleting chemotherapy and followed by attenuated doses of IL2 administered in an intravenous, continuous decrescendo regimen (ClinicalTrials.gov Identifier: NCT00937625). Classical IL2-related toxicities were observed but patients were manageable in a general oncology ward without the need for intervention from the intensive care unit. RECIST 1.0 evaluation displayed three complete responses and seven partial responses (ORR 42%). Median overall survival was 21.8 months. Tumor regression was associated with a higher absolute number of infused tumor-reactive T cells. Moreover, induction and persistence of antimelanoma T-cell responses in the peripheral blood was strongly correlated to clinical response to treatment. TIL-ACT with a reduced IL2 decrescendo regimen results in long-lasting complete responses in patients with treatment-refractory melanoma. Larger randomized trials are needed to elucidate whether clinical efficacy is comparable with TIL-ACT followed by HD bolus IL2. Clin Cancer Res; 22(15); 3734-45. ©2016 AACR. ©2016 American Association for Cancer Research.

Double-blind evaluation of deanol in tardive dyskinesia.

PubMed

Penovich, P; Morgan, J P; Kerzner, B; Karch, F; Goldblatt, D

1978-05-12

We administered deanol acetamidobenzoate, 2.0 g/day for four weeks, a double-blind, placebo-controlled crossover trial, to 14 patients with tardive dyskineasia. The patient population included both inpatients and outpatients. The response was evaluated by subjective clinical impression and scoring of filmed sequences. Patients' conditions improved significantly from baseline scores while receiving both deanol and placebo, but there was no distinction between the two treatments.

A randomized, double-blind, vehicle-controlled efficacy and safety study of naftifine 2% cream in the treatment of tinea pedis.

PubMed

Parish, Lawrence Charles; Parish, Jennifer L; Routh, Hirak B; Fleischer, Alan B; Avakian, Edward V; Plaum, Stefan; Hardas, Bhushan

2011-11-01

Naftifine HCl 2% cream (NAFT-2) is a topical allylamine antifungal agent under development in the United States. This randomized, double-blind, vehicle-controlled, phase 3 trial evaluated the efficacy and safety of two weeks of NAFT-2 treatment in subjects with tinea pedis. Naftifine 1% cream (NAFT-1) treatment for four weeks and vehicle were also evaluated as a positive control. 709 subjects were randomly assigned 2:1:2:1 to one of four treatment groups: (i) NAFT-2 (n= 235), (ii) two-week vehicle (n=118), (iii) NAFT-1 (n=237), or (iv) four-week vehicle (n=119). Efficacy was evaluated at baseline, week 2, week 4, and week 6 and consisted of mycology determination (KOH and dermatophyte culture) and scoring of clinical symptom severity (erythema, scaling, and pruritus). Efficacy was only analyzed in 425 subjects with positive baseline dermatophyte culture. Safety was evaluated by adverse events (AE) and laboratory values in 707 subjects. At week 6, NAFT-2 subjects achieved 18 percent complete cure rate, 67 percent mycological cure rate, 57 percent treatment effectiveness, 22 percent clinical cure rate, and 78 percent clinical success rate compared to respective vehicle rates of seven percent (one-sided, P<0.01), 21 percent (P<0.001), 20 percent (P<0.001), 11 percent (P=0.04) and 49 percent (P<0.001). Week 6 efficacy responses in NAFT-1-treated subjects were significantly higher than vehicle subjects and almost identical to NAFT-2 subjects. Mycological cure and clinical response rates in both NAFT-2 and NAFT-1 increased from week 2 to week 6. Treatment-related AEs occurred in five percent of NAFT-2 subjects, seven percent of vehicle subjects, four percent of NAFT-1 subjects and eight percent of vehicle subjects. The most common AEs for all groups were application site pruritus and skin irritation. Topical NAFT-2 for two weeks is safe and provides significantly superior antifungal treatment than vehicle in tinea pedis subjects. NAFT-2 produces equivalent efficacy responses to four weeks of NAFT-1 treatment. The fungicidal activity of naftifine continues to increase for at least one month after treatment is completed. (Clinical Trials Identification Numbe=NCT00750139). J Drugs Dermatol. 2011;10(11):1282-1288.

The development of an instrument for evaluating clinical teachers: involving stakeholders to determine content validity.

PubMed

Stalmeijer, Renée E; Dolmans, Diana H J M; Wolfhagen, Ineke H A P; Muijtjens, Arno M M; Scherpbier, Albert J J A

2008-01-01

Research indicates that the quality of supervision strongly influences the learning of medical students in clinical practice. Clinical teachers need feedback to improve their supervisory skills. The available instruments either lack a clear theoretical framework or are not suitable for providing feedback to individual teachers. We developed an evaluation instrument based on the 'cognitive apprenticeship model'. The aim was to estimate the content validity of the developed instrument. Item relevance was rated on a five-point scale (1 = highly irrelevant, 5 = highly relevant) by three groups of stakeholders in undergraduate clinical teaching: educationalists (N = 12), doctors (N = 16) and students (N = 12). Additionally, stakeholders commented on content, wording and omission of items. The items were generally rated as very relevant (Mean = 4.3, SD = 0.38, response = 95%) and any differences between the stakeholder groups were small. The results led to elimination of 4 items, rewording of 13 items and addition of 1 item. The cognitive apprenticeship model appears to offer a useful framework for the development of an evaluation instrument aimed at providing feedback to individual clinical teachers on the quality of student supervision. Further studies in larger populations will have to establish the instrument's statistical validity and generalizability.

Treatment modifications in tumour necrosis factor-α (TNF)-based isolated limb perfusion in patients with advanced extremity soft tissue sarcomas.

PubMed

Deroose, Jan P; Grünhagen, Dirk J; de Wilt, Johannes H W; Eggermont, Alexander M M; Verhoef, Cornelis

2015-02-01

Tumour necrosis factor-α (TNF) and melphalan based isolated limb perfusion (TM-ILP) is an attractive treatment option for advanced extremity soft tissue sarcomas (STS). This study reports on a 20-year single centre experience and discusses the evolution and changes in methodology since the introduction of TNF in ILP. We performed 306 TM-ILPs in 275 patients with extremity STS. All patients were candidates for amputation or mutilating surgery in order to achieve local control. Clinical response evaluation consisted of clinical examination and magnetic resonance imaging. To evaluate the importance of TNF-dose, treatment results of two periods (1991-2003 high dose (3-4 mg) TNF; 2003-2012 reduced dose (1-2mg) TNF) were compared. During the study period, more femoral perfusions were done instead of iliac perfusions. Reduction of TNF dose and reduction of total ILP time did not lead to different clinical response rates (70% and 69% for periods 1 and 2 respectively) or different local recurrence rates, but was associated with less local toxicity (23% and 14% for periods 1 and 2 respectively). Hospital stay was significantly reduced during the study period. There was an improved pathological response in the high dose TNF group without consequences for clinical outcome. TM-ILP remains a very effective treatment modality for limb threatening extremity STS. Moreover, reduction of dose and the growing experience in ILP led to less local toxicity and shorter hospital stay. Copyright © 2014 Elsevier Ltd. All rights reserved.

A program to provide antiretroviral therapy to residents of an urban slum in Nairobi, Kenya.

PubMed

Marston, Barbara J; Macharia, Doris K; Nga'nga, Lucy; Wangai, Mary; Ilako, Festus; Muhenje, Odylia; Kjaer, Mette; Isavwa, Anthony; Kim, Andrea; Chebet, Kenneth; DeCock, Kevin M; Weidle, Paul J

2007-06-01

To evaluate retention in care and response to therapy for patients enrolled in an antiretroviral treatment program in a severely resource-constrained setting. We evaluated patients enrolled between February 26, 2003, and February 28, 2005, in a community clinic in Kibera, an informal settlement, in Nairobi, Kenya. Midlevel providers offered simplified, standardized antiretroviral therapy (ART) regimens and monitored patients clinically and with basic laboratory tests. Clinical, immunologic, and virologic indicators were used to assess response to ART; adherence was determined by 3-day recall. A total of 283 patients (70% women; median baseline CD4 count, 157 cells/ mm(3); viral load, 5.16 log copies/mL) initiated ART and were followed for a median of 7.1 months (n = 2384 patient-months). At 1 year, the median CD4 count change was +124.5 cells/mm(3) (n = 74; interquartile range, 42 to 180), and 71 (74%) of 96 patients had viral load <400 copies/mL. The proportion of patients reporting 100% adherence over the 3 days before monthly clinic visits was 94% to 100%. As of February 28, 2005, a total of 239 patients (84%) remained in care, 22 (8%) were lost to follow-up, 12 (4%) were known to have died, 5 (2%) had stopped ART, 3 (1%) moved from the area, and 2 (< 1% ) transferred care. Response to ART in this slum population was comparable to that seen in industrialized settings. With government commitment, donor support, and community involvement, it is feasible to implement successful ART programs in extremely challenging social and environmental conditions.

Fractional ablative and nonablative radiofrequency for skin resurfacing and rejuvenation of Thai patients.

PubMed

Thanasarnaksorn, Wilai; Siramangkhalanon, Vorapot; Duncan, Diane Irvine; Belenky, Inna

2018-04-01

Fractional radiofrequency (RF) technology is often the preferable skin resurfacing treatment, especially among Asian patients. Second generation fractional RF technology has exclusive capability to produce separate biological responses (ablation, coagulation, or a combination of both) with 3 distinguished penetration depth programs. The aim of this study was to evaluate the efficacy and safety of a fractional RF handpiece such as this, on the Thai population. Fifty-five Thai patients were treated with a fractional RF handpiece. The clinical assessment included a pain score, satisfaction survey, physician assessment, a combined patient and physician's assessment of skin condition, and clinical photographic assessments. The wound healing response was evaluated according to 5-time points: immediately after applying a pulse, post 24 hours, post 7 days, post 1 month and post 8 weeks. The obtained patient satisfaction score was "very satisfied" among 74% of the patients, post 3 sessions. Positive correlation was found between patient satisfaction and the physician's assessment. The skin condition assessment showed an increase from an average of 4.2 to 7.9. All treated symptoms improved after each treatment and the clinical outcome lasted at least up to 3-5 months. No significant adverse events were recorded. The in vivo prospective study showed a dose-related response in the deepness of the coagulation injury. In addition, there was evidence for a progressive healing process beginning shortly after exposure and completed within a week. This study clinically and histologically supports the efficacy of fractional RF handpiece in question with a high safety profile. © 2017 Wiley Periodicals, Inc.

Utility analysis and calibration of QOL assessment in disease management.

PubMed

Liu, Mo

2018-05-02

In clinical trials, the assessment of health-related quality of life (QOL) (or patient-reported outcome [PRO] measure) has become very popular especially for clinical studies conducted for evaluating clinical benefits of patients with chronic, severe, and/or life threatening diseases. Health-related QOL information and PRO measures are useful for disease management for achieving best clinical practice. In this article, we will focus on health-related QOL assessment. The concept, design, and analysis of health-related QOL in clinical trials are reviewed. Validation of the use of health-related QOL instrument in terms of some key performance characteristics such as accuracy, reliability, sensitivity, and responsibility for assuring quality, integrity, and validity of collected QOL data are discussed. The concept of utility analysis and calibration (e.g., with respect to life events) for achieving the optimization of disease management are proposed. The change of the QOL could be translated into different life events for effective disease management. These translations could evaluate the treatment effect by more directly displaying the change of the QOL.

Therapeutic interventions in sepsis: current and anticipated pharmacological agents

PubMed Central

Shukla, Prashant; Rao, G Madhava; Pandey, Gitu; Sharma, Shweta; Mittapelly, Naresh; Shegokar, Ranjita; Mishra, Prabhat Ranjan

2014-01-01

Sepsis is a clinical syndrome characterized by a multisystem response to a pathogenic assault due to underlying infection that involves a combination of interconnected biochemical, cellular and organ–organ interactive networks. After the withdrawal of recombinant human-activated protein C (rAPC), researchers and physicians have continued to search for new therapeutic approaches and targets against sepsis, effective in both hypo- and hyperinflammatory states. Currently, statins are being evaluated as a viable option in clinical trials. Many agents that have shown favourable results in experimental sepsis are not clinically effective or have not been clinically evaluated. Apart from developing new therapeutic molecules, there is great scope for for developing a variety of drug delivery strategies, such as nanoparticulate carriers and phospholipid-based systems. These nanoparticulate carriers neutralize intracorporeal LPS as well as deliver therapeutic agents to targeted tissues and subcellular locations. Here, we review and critically discuss the present status and new experimental and clinical approaches for therapeutic intervention in sepsis. PMID:24977655

Quantification of abnormal intracranial pressure waves and isotope cisternography for diagnosis of occult communicating hydrocephalus

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

Cardoso, E.R.; Piatek, D.; Del Bigio, M.R.

1989-01-01

Nineteen consecutive patients with suspected occult communicating hydrocephalus were investigated by means of clinical evaluation, neuropsychological testing, isotope cisternography, computed tomography scanning, and continuous intracranial pressure monitoring. Semi-quantitative grading systems were used in the evaluation of the clinical, neuropsychological, and cisternographic assessments. Clinical examination, neuropsychological testing, and computed tomography scanning were repeated 3 months after ventriculoperitoneal shunting. All patients showed abnormal intracranial pressure waves and all improved after shunting. There was close correlation between number, peak, and pulse pressures of B waves and the mean intracranial pressure. However, quantification of B waves by means of number, frequency, and amplitude didmore » not help in predicting the degree of clinical improvement postshunting. The most sensitive predictor of favorable response to shunting was enlargement of the temporal horns on computed tomography scan. Furthermore, the size of temporal horns correlated with mean intracranial pressure. There was no correlation between abnormalities on isotope cisternography and clinical improvement.« less

Evaluation of two carrier protein–angiotensin I conjugate vaccines to assess their future potential to control high blood pressure (hypertension) in man

PubMed Central

Downham, M R; Auton, T R; Rosul, A; Sharp, H L; Sjöström, L; Rushton, A; Richards, J P; Mant, T G K; Gardiner, S M; Bennett, T; Glover, J F

2003-01-01

Aims We aim to modulate the renin–angiotensin system (RAS) by active immunization against angiotensin I hormone (AI), potentially providing a novel conjugate vaccine treatment for hypertension in man. Methods Immunization studies in rat and human subjects compare the effectiveness of tetanus toxoid (TT) and keyhole limpet haemocyanin (KLH) vaccines for immunotherapy following conjugation with an AI peptide analogue (AI). Cardiovascular responses were assessed in immunized rats and human subjects (two-dose trial only), following increasing i.v. infusions of either AI or angiotensin II hormone (AII). Results The AI–TT and AI–KLH conjugate vaccines induced an equivalent immune response, and inhibition of the pressor effects to exogenous AI in rats. Single-dose clinical trials with both conjugate vaccines only resulted in an immune response to the KLH carrier protein. A two-dose clinical trial of AI–KLH conjugate vaccine resulted in a significant immune response to AI. A shift in diastolic blood pressure (DBP) dose–response was demonstrated following challenge with AI and AII for the study volunteer showing the largest anti-AI IgG induction. Conclusion KLH was shown to be a suitable alternative to TT as a carrier protein for AI, thus supporting continued evaluation of our AI–KLH conjugate vaccine for treatment of hypertension in man. PMID:14651724

Performance characteristics of a conformal ultra-wideband multilayer applicator (CUMLA) for hyperthermia in veterinary patients: a pilot evaluation of its use in the adjuvant treatment of non-resectable tumours.

PubMed

Smrkovski, O A; Koo, Y; Kazemi, R; Lembcke, L M; Fathy, A; Liu, Q; Phillips, J C

2013-03-01

Performance and clinical characteristics of a novel hyperthermia antenna operating at 434 MHz were evaluated for the adjuvant treatment of locally advanced superficial tumours in cats, dogs and horses. Electromagnetic simulations were performed to determine electric field characteristics and compared to simulations for a flat microwave antenna with similar dimensions. Simulation results show a reduced skin surface and backfield irradiation and improved directional irradiation (at broadside) compared to a flat antenna. Radiated power and penetration is notably increased with a penetration depth of 4.59 cm compared to 2.74 cm for the flat antenna. Clinical use of the antenna was then evaluated in six animals with locoregionally advanced solid tumours receiving adjuvant chemotherapy. During clinical applications, therapeutic temperatures were achieved at depths ≥4 cm. Objective responses were seen in all patients; tissue toxicity in one case limited further therapy. This antenna provides compact, efficient, focused and deep-penetrating clinical hyperthermia for the treatment of solid tumours in veterinary patients. © 2011 Blackwell Publishing Ltd.

Progression of leprosy neuropathy: a case series study

PubMed Central

Vital, Robson T; Illarramendi, Ximena; Nascimento, Osvaldo; Hacker, Mariana A; Sarno, Euzenir N; Jardim, Marcia R

2012-01-01

A need still exists to determine the clinical and neurophysiological characteristics of leprosy neuropathy at distinct times of the disease by different methods that measure the various nerve fiber functions. A prospective clinical study was performed with 10 paucibacillary (PB) and 12 multibacillary (MB) patients evaluated at diagnosis and one year after cessation of multidrug therapy (MDT). Peripheral nerve function was assessed clinically and by means of the sympathetic skin response, skin vasomotor reflex, and nerve conduction study (NCS). At diagnosis, 73% of the total 22 patients had nerve function impairment (NFI). Autonomic function (χ2= 5.5, P= 0.019) and NCS (χ2= 7.765, P= 0.01) were significantly more altered in MB than PB patients. At final evaluation, NFI of the MB patients had worsened, especially among the six who had leprosy reaction. As the NFI of PB patients showed improvement, a significant difference between the two groups (χ2= 12.320, P= 0.001) was observed. A high prevalence of neuropathy was observed in newly diagnosed patients. Associating different tests with a thorough clinical neurological evaluation increases detection rates. PMID:22741099

Comparative responsiveness and minimal clinically important differences for idiopathic ulnar impaction syndrome.

PubMed

Kim, Jae Kwang; Park, Eun Soo

2013-05-01

Patient-reported questionnaires have been widely used to predict symptom severity and functional disability in musculoskeletal disease. Importantly, questionnaires can detect clinical changes in patients; however, this impact has not been determined for ulnar impaction syndrome. We asked (1) which of Patient-Rated Wrist Evaluation (PRWE), DASH, and other physical measures was more responsive to clinical improvements, and (2) what was the minimal clinically important difference for the PRWE and DASH after ulnar shortening osteotomy for idiopathic ulnar impaction syndrome. All patients who underwent ulnar shortening osteotomy between March 2008 and February 2011 for idiopathic ulnar impaction syndrome were enrolled in this study. All patients completed the PRWE and DASH questionnaires, and all were evaluated for grip strength and wrist ROM, preoperatively and 12 months postoperatively. We compared the effect sizes observed by each of these instruments. Effect size is calculated by dividing the mean change in a score of each instrument during a specified interval by the standard deviation of the baseline score. In addition, patient-perceived overall improvement was used as the anchor to determine the minimal clinically important differences on the PRWE and DASH 12 months after surgery. The average score of each item except for wrist flexion and supination improved after surgery. The PRWE was more sensitive than the DASH or than physical measurements in detecting clinical changes. The effect sizes and standardized response means of the outcome measures were as follows: PRWE (1.51, 1.64), DASH (1.12, 1.24), grip strength (0.59, 0.68), wrist pronation (0.33, 0.41), and wrist extension (0.28, 0.36). Patient-perceived overall improvement and score changes of the PRWE and DASH correlated significantly. Minimal clinically important differences were 17 points (of a possible 100) for the PRWE and 13.5 for the DASH (also of 100), and minimal detectable changes were 7.7 points for the PRWE and 9.3 points for the DASH. Although the PRWE and DASH were highly sensitive to clinical changes, the PRWE was more sensitive in terms of detecting clinical changes after ulnar shortening osteotomy for idiopathic ulnar impaction syndrome. A minimal change of 17 PRWE points or 13.5 DASH points was necessary to achieve a benefit that patients perceived as clinically important. The minimal clinically important differences using these instruments were higher than the values produced by measurement errors.

Factor Structure, Factorial Invariance, and Validity of the Multidimensional Shame-Related Response Inventory-21 (MSRI-21)

PubMed Central

Garcia, Antonio F.; Acosta, Melina; Pirani, Saifa; Edwards, Daniel; Osman, Augustine

2017-01-01

We describe 2 studies designed to evaluate scores on the Multidimensional Shame-related Response Inventory-21 (MSRI-21), a recently developed instrument that measures affective and behavioral responses to shame. The inventory assesses shame-related responses in 3 categories: negative self-evaluation, fear of social consequences, and maladaptive behavior tendency. For Study 1, (N = 743) undergraduates completed the MSRI-21. Confirmatory factor analysis supported the validity of the MSRI-21 3-factor structure. Latent variable modeling of coefficient-α provided strong evidence for the internal consistency of scores on each scale. In Study 2, (N = 540) undergraduates completed the instrument along with 5 concurrent measures chosen for clinical significance. Achievement of factorial invariance supported the use of MSRI-21 scale scores to make valid mean comparisons across gender. In addition, MSRI-21 scale scores were associated as expected with scores on measures of self-harm, suicide, and other risk factors. Taken together, results of 2 studies support the internal consistency reliability, factorial validity, factorial invariance, and convergent validity of scores on the MSRI-21. Further work is needed to assess the temporal stability of the MSRI-21 scale scores, invariance across clinical status and other groupings, item-level measurement properties, and viability in highly symptomatic samples. PMID:28182490

Helper T lymphocyte response in the peripheral blood of patients with intraepithelial neoplasia submitted to immunotherapy with pegylated interferon-α.

PubMed

Michelin, Márcia Antoniazi; Montes, Letícia; Nomelini, Rosekeila Simões; Trovó, Marco Aurélio; Murta, Eddie Fernando Candido

2015-03-10

Immunotherapy in cancer patients is a very promising treatment and the development of new protocols and the study of the mechanisms of regression is imperative. The objective of this study was to evaluate the production of cytokines in helper T (CD4+) lymphocytes during immunotherapy with pegylated IFN-α in patients with cervical intraepithelial neoplasia (CIN). We conducted a prospective study with 17 patients with CIN II-III using immunotherapy with pegylated IFN-α subcutaneouly weekly, and using flow cytometry we evaluated the peripheric CD4+ T lymphocytes. The results show that in the regression group the patients presented a significant increase in the amount of IFN-γ during the entire immunotherapy, compared with the group without a response. The amount of CD4+ T lymphocytes positive for IL-2, IL-4, IL-10 and TGF-β is significantly lower in patients with good clinical response. The results also demonstrate that patients with regression have a higher amount of intracellular TNF-α in CD4+ T lymphocytes before the start of treatment. Analyzing these data sets, it can be concluded that immunotherapy is a viable clinical treatment for patients with high-grade CIN and that the regression is dependent on the change in the immune response to a Th1 pattern.

Leptomeningeal metastases: a RANO proposal for response criteria

PubMed Central

Junck, Larry; Brandsma, Dieta; Soffietti, Riccardo; Rudà, Roberta; Raizer, Jeffrey; Boogerd, Willem; Taillibert, Sophie; Groves, Morris D.; Rhun, Emilie Le; Walker, Julie; van den Bent, Martin; Wen, Patrick Y.; Jaeckle, Kurt A.

2017-01-01

Abstract Leptomeningeal metastases (LM) currently lack standardization with respect to response assessment. A Response Assessment in Neuro-Oncology (RANO) working group with expertise in LM developed a consensus proposal for evaluating patients treated for this disease. Three basic elements in assessing response in LM are proposed: a standardized neurological examination, cerebral spinal fluid (CSF) cytology or flow cytometry, and radiographic evaluation. The group recommends that all patients enrolling in clinical trials undergo CSF analysis (cytology in all cancers; flow cytometry in hematologic cancers), complete contrast-enhanced neuraxis MRI, and in instances of planned intra-CSF therapy, radioisotope CSF flow studies. In conjunction with the RANO Neurological Assessment working group, a standardized instrument was created for assessing the neurological exam in patients with LM. Considering that most lesions in LM are nonmeasurable and that assessment of neuroimaging in LM is subjective, neuroimaging is graded as stable, progressive, or improved using a novel radiological LM response scorecard. Radiographic disease progression in isolation (ie, negative CSF cytology/flow cytometry and stable neurological assessment) would be defined as LM disease progression. The RANO LM working group has proposed a method of response evaluation for patients with LM that will require further testing, validation, and likely refinement with use. PMID:28039364

RECIST 1.1 - Standardisation and disease-specific adaptations: Perspectives from the RECIST Working Group.

PubMed

Schwartz, Lawrence H; Seymour, Lesley; Litière, Saskia; Ford, Robert; Gwyther, Stephen; Mandrekar, Sumithra; Shankar, Lalitha; Bogaerts, Jan; Chen, Alice; Dancey, Janet; Hayes, Wendy; Hodi, F Stephen; Hoekstra, Otto S; Huang, Erich P; Lin, Nancy; Liu, Yan; Therasse, Patrick; Wolchok, Jedd D; de Vries, Elisabeth

2016-07-01

Radiologic imaging of disease sites plays a pivotal role in the management of patients with cancer. Response Evaluation Criteria in Solid Tumours (RECIST), introduced in 2000, and modified in 2009, has become the de facto standard for assessment of response in solid tumours in patients on clinical trials. The RECIST Working Group considers the ability of the global oncology community to implement and adopt updates to RECIST in a timely manner to be critical. Updates to RECIST must be tested, validated and implemented in a standardised, methodical manner in response to therapeutic and imaging technology advances as well as experience gained by users. This was the case with the development of RECIST 1.1, where an expanded data warehouse was developed to test and validate modifications. Similar initiatives are ongoing, testing RECIST in the evaluation of response to non-cytotoxic agents, immunotherapies, as well as in specific diseases. The RECIST Working Group has previously outlined the level of evidence considered necessary to formally and fully validate new imaging markers as an appropriate end-point for clinical trials. Achieving the optimal level of evidence desired is a difficult feat for phase III trials; this involves a meta-analysis of multiple prospective, randomised multicentre clinical trials. The rationale for modifications should also be considered; the modifications may be proposed to improve surrogacy, to provide a more mechanistic imaging technique, or be designed to improve reproducibility of the imaging biomarker. Here, we present the commonly described modifications of RECIST, each of which is associated with different levels of evidence and validation. Copyright © 2016. Published by Elsevier Ltd.

Patient-reported questionnaires in MS rehabilitation: responsiveness and minimal important difference of the multiple sclerosis questionnaire for physiotherapists (MSQPT).

PubMed

van der Maas, Nico Arie

2017-03-16

The Multiple Sclerosis Questionnaire for Physical Therapists (MSQPT) is a patient-rated outcome questionnaire for evaluating the rehabilitation of persons with multiple sclerosis (MS). Responsiveness was evaluated, and minimal important difference (MID) estimates were calculated to provide thresholds for clinical change for four items, three sections and the total score of the MSQPT. This multicentre study used a combined distribution- and anchor-based approach with multiple anchors and multiple rating of change questions. Responsiveness was evaluated using effect size, standardized response mean (SRM), modified SRM and relative efficiency. For distribution-based MID estimates, 0.2 and 0.33 standard deviations (SD), standard error of measurement (SEM) and minimal detectable change were used . Triangulation of anchor- and distribution-based MID estimates provided a range of MID values for each of the four items, the three sections and the total score of the MSQPT. The MID values were tested for their sensitivity and specificity for amelioration and deterioration for each of the four items, the three sections and the total score of the MSQPT. The MID values of each item and section and of the total score with the best sensitivity and specificity were selected as thresholds for clinical change. The outcome measures were the MSQPT, Hamburg Quality of Life Questionnaire for Multiple Sclerosis (HAQUAMS), rating of change questionnaires, Expanded Disability Status Scale, 6-metre timed walking test, Berg Balance Scale and 6-minute walking test. The effect size ranged from 0.46 to 1.49. The SRM data showed comparable results. The modified SRM ranged from 0.00 to 0.60. Anchor-based MID estimates were very low and were comparable with SD- and SEM-based estimates. The MSQPT was more responsive than the HAQUAMS in detecting improvement but less responsive in finding deterioration. The best MID estimates of the items, sections and total score, expressed in percentage of their maximum score, were between 5.4% (activity) and 22% (item 10) change for improvement and between 5.7% (total score) and 22% (item 10) change for deterioration. The MSQPT is a responsive questionnaire with an adequate MID that may be used as threshold for change during rehabilitation of MS patients. This trial was retrospectively (01/24/2015) registered in ClinicalTrials.gov as NCT02346279.

Neurostimulation options for failed back surgery syndrome: The need for rational and objective measurements. Proposal of an international clinical network using an integrated database and health economic analysis: the PROBACK network.

PubMed

Rigoard, P; Slavin, K

2015-03-01

In the context of failed back surgery syndrome (FBSS) treatment, the current practice in neurostimulation varies from center-to-center and most clinical decisions are based on an individual diagnosis. Neurostimulation evaluation tools and pain relief assessment are of major concern, as they now constitute one of the main biases of clinical trials. Moreover, the proliferation of technological devices, in a fertile and unsatisfied market, fosters and only furthers the confusion. There are three options available to apply scientific debates to our daily neurostimulation practice: intentional ignorance, standardized evidence-based practice or alternative data mining approach. In view of the impossibility of conducting multiple randomized clinical trials comparing various devices, one by one, the proposed concept would be to redefine the indications and the respective roles of the various spinal cord and peripheral nerve stimulation devices with large-scale computational modeling/data mining approach, by conducting a multicenter prospective database registry, supported by a clinician's global network called "PROBACK". We chose to specifically analyze 6 parameters: device coverage performance/coverage selectivity/persistence of the long-term electrical response (technical criteria) and comparative mapping of patient pain relief/persistence of the long-term clinical response/safety and complications occurrence (clinical criteria). Two types of analysis will be performed: immediate analysis (including cost analysis) and computational analysis, i.e. demonstration of the robustness of certain correlations of variables, in order to extract response predictors. By creating an international prospective database, the purpose of the PROBACK project was to set up a process of extraction and comparative analysis of data derived from the selection, implantation and follow-up of FBSS patients candidates for implanted neurostimulation. This evaluation strategy should help to change the opinions of each implanter and each health system towards a more rational decision-making approach subtended by mathematical reality. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

IL-6 blockade in systemic juvenile idiopathic arthritis - achievement of inactive disease and remission (data from the German AID-registry).

PubMed

Bielak, M; Husmann, E; Weyandt, N; Haas, J-P; Hügle, B; Horneff, G; Neudorf, U; Lutz, T; Lilienthal, E; Kallinich, T; Tenbrock, K; Berendes, R; Niehues, T; Wittkowski, H; Weißbarth-Riedel, E; Heubner, G; Oommen, P; Klotsche, J; Foell, Dirk; Lainka, E

2018-04-05

Systemic juvenile idiopathic arthritis (sJIA) is a complex disease with an autoinflammatory component of unknown etiology related to the innate immune system. A major role in the pathogenesis has been ascribed to proinflammatory cytokines like interleukin-6 (IL-6), and effective drugs inhibiting their signaling are being developed. This study evaluates sJIA patients treated with the IL-6 inhibitor tocilizumab (TCZ) concerning clinical response rate, disease course and adverse effects in a real-life clinical setting. In 2009 a clinical and research consortium was established, including an online registry for autoinflammatory diseases (AID) ( https://aid-register.de ). Data for this retrospective TCZ study were documented by 13 centers. From 7/2009 to 4/2014, 200 patients with sJIA were recorded in the AID-registry. Out of these, 46 (19 m, 27 f, age 1-18 years) received therapy with TCZ. Long term treatment (median 23 months) has been documented in 24/46 patients who were evaluated according to Wallace criteria (active disease 6/24, inactive disease 5/24, remission 13/24 cases). Under observation co-medication were used in 40/46 cases. Adverse events were reported in 11/46 patients. The clinical response rate (no clinical manifestation, no increased inflammation parameters) within the first 12 weeks of treatment was calculated to be 35%. Out of 200 sJIA children reported in the German AID-registry, 46 were treated with TCZ, showing a clinical response rate of 35% during the first 12 weeks, and inactive disease and/or remission under medication in 75% after one year. Adverse events were seen in 24% and severe adverse events in 4%. The AID-Registry is funded by the BMBF (01GM08104, 01GM1112D, 01GM1512D).

Strengthening the afferent limb of rapid response systems: an educational intervention using web-based learning for early recognition and responding to deteriorating patients.

PubMed

Liaw, Sok Ying; Wong, Lai Fun; Ang, Sophia Bee Leng; Ho, Jasmine Tze Yin; Siau, Chiang; Ang, Emily Neo Kim

2016-06-01

The timely recognition and response to patients with clinical deteriorations constitute the afferent limb failure of a rapid response system (RRS). This area is a persistent problem in acute healthcare settings worldwide. In this study, we evaluated the effect of an educational programme on improving the nurses' knowledge and performances in recognising and responding to clinical deterioration. The interactive web-based programme addressed three areas: (1) early detection of changes in vital signs; (2) performance of nursing assessment and interventions using airway, breathing, circulation, disability and expose/examine and (3) reporting clinical deterioration using identity, situation, background, assessment and recommendation. Sixty-seven registered nurses participated in the randomised control study. The experimental group underwent a 3 h programme while the control group received no intervention. Pretests and post-tests, a mannequin-based assessment and a multiple-choice knowledge questionnaire were conducted. We evaluated the participants' performances in assessing, managing and reporting the deterioration of a patient using a validated performance tool. A significantly higher number of nurses from the experimental group than the control group monitored respiratory rates (48.2% vs 25%, p<0.05) and pulse rates (74.3% vs 37.5%, p<0.01) in the simulated environment, after the intervention. The post-test mean scores of the experimental group was significantly higher than the control group for knowledge (21.29 vs 18.28, p<0.001), performance in assessing and managing clinical deterioration (25.83 vs 19.50, p<0.001) and reporting clinical deterioration (12.83 vs 10.97, p<0.001). A web-based educational programme developed for hospital nurses to strengthen the afferent limb of the RRS significantly increased their knowledge and performances in assessing, managing and reporting clinical deterioration. 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/

Vestibular evoked myogenic potentials in patients with ankylosing spondylitis.

PubMed

Özgür, Abdulkadir; Serdaroğlu Beyazal, Münevver; Terzi, Suat; Coşkun, Zerrin Özergin; Dursun, Engin

2016-10-01

Ankylosing spondylitis (AS) is a chronic systemic inflammatory disease with unknown etiology. Although sacroiliac joint involvement is the classic sign along with the formed immune mediators, it may result in immune-mediated inner ear disease and may cause damage to the audiovestibular system. Vestibular evoked myogenic potentials (VEMP) is a clinical reflex test used in the diagnosis of vestibular diseases and is performed by recording and evaluating the muscle potentials resulting from the stimulation of the vestibular system with different stimuli. The aim of this study is to evaluate the cervical VEMP test results in AS patients without vestibular symptoms. Thirty-three patients with AS and a control group of 30 healthy volunteers with similar demographic characteristics were evaluated in the study. VEMP wave latency, P13-N23 wave amplitude, and VEMP asymmetry ratio (VAR) values were compared between the groups. The relationship between clinical and laboratory findings of the AS patients and VEMP data were also investigated. Compared with healthy people, this study shows the response rate of patients with ankylosing spondylitis was reduced in the VEMP test, and P13-N23 wave amplitude showed a decrease in AS patients who had VEMP response (p < 0.001). There was no correlation between the clinical and laboratory findings and VEMP findings in patients with ankylosing spondylitis. The data obtained from this study suggest that AS may lead to decreased sensitivity of the vestibular system.

Evaluation of an intragastric challenge model for Shigella dysenteriae 1 in rhesus monkeys (Macaca mulatta) for the pre-clinical assessment of Shigella vaccine formulations

PubMed Central

Islam, Dilara; Ruamsap, Nattaya; Khantapura, Patchariya; Aksomboon, Ajchara; Srijan, Apichai; Wongstitwilairoong, Boonchai; Bodhidatta, Ladaporn; Gettayacamin, Montip; Venkatesan, Malabi M; Mason, Carl J

2014-01-01

Shigellosis is a worldwide disease, characterized by abdominal pain, fever, vomiting, and the passage of blood- and mucus-streaked stools. Rhesus monkeys and other primates are the only animals that are naturally susceptible to shigellosis. A suitable animal model is required for the pre-clinical evaluation of vaccines candidates. In this study, the minimal dose of Shigella dysenteriae1 1617 strain required to produce dysentery in four of five (80% attack rate) monkeys using an escalating dose range for three groups [2 × 108, 2 × 109 and 2 × 1010 colony forming unit (CFU)] was determined. In addition, the monkeys were re-infected. The identified optimal challenge dose was 2 × 109 CFU; this dose elicited 60% protection in monkeys when they were re-challenged with a one log higher dose (2 × 1010 CFU). The challenge dose, 2 × 1010 CFU, produced severe dysentery in all monkeys, with one monkey dying within 24 h, elicited 100% protection when re-challenged with the same dose. All monkeys exhibited immune responses. This study concludes that the rhesus monkey model closely mimics the disease and immune response seen in humans and is a suitable animal model for the pre-clinical evaluation of Shigella vaccine candidates. Prior infection with the 1617 strain can protect monkeys against subsequent re-challenges with homologous strains. PMID:24028276

Hyper-hydration: a new perspective on wound cleansing, debridement and healing.

PubMed

2016-06-01

In a recent symposium organised by Hartmann, the involvement of moisture and hydration in healing was re-evaluated and the use of hyper-hydration in promoting healing was examined. The distinction between hyperhydration and maceration was also discussed. Clinical studies were presented to give an overview of the clinical evidence to how Hydro-Responsive Wound Dressings can aid in healing via cleansing, debridement and desloughing of several wound types.

Eyelid dermatitis.

PubMed

Beltrani, V S

2001-07-01

Cosmetic alteration of a patient's orbital skin is a common reason for professional consultation. This review presents the differential diagnosis and recommended evaluation of inflamed eyelids. To better understand the diseases, each is individually addressed clinically, pathogenetically, and therapeutically. It is critical to recognize the lesions correctly and to have full knowledge of the putative clinical disease process. An algorithm for an appropriate work-up for each disease is offered. With this background, a successful therapeutic response can be anticipated.

Developing nursing and midwifery students' capacity for coping with bullying and aggression in clinical settings: Students' evaluation of a learning resource.

PubMed

Hogan, Rosemarie; Orr, Fiona; Fox, Deborah; Cummins, Allison; Foureur, Maralyn

2018-03-01

An innovative blended learning resource for undergraduate nursing and midwifery students was developed in a large urban Australian university, following a number of concerning reports by students on their experiences of bullying and aggression in clinical settings. The blended learning resource included interactive online learning modules, comprising film clips of realistic clinical scenarios, related readings, and reflective questions, followed by in-class role-play practice of effective responses to bullying and aggression. On completion of the blended learning resource 210 participants completed an anonymous survey (65.2% response rate). Qualitative data was collected and a thematic analysis of the participants' responses revealed the following themes: 'Engaging with the blended learning resource'; 'Responding to bullying' and 'Responding to aggression'. We assert that developing nursing and midwifery students' capacity to effectively respond to aggression and bullying, using a self-paced blended learning resource, provides a solution to managing some of the demands of the clinical setting. The blended learning resource, whereby nursing and midwifery students were introduced to realistic portrayals of bullying and aggression in clinical settings, developed their repertoire of effective responding and coping skills for use in their professional practice. Copyright © 2017 Elsevier Ltd. All rights reserved.

Improved clinical outcome and biomarkers in adults with papulopustular rosacea treated with doxycycline modified-release capsules in a randomized trial.

PubMed

Di Nardo, Anna; Holmes, Anna D; Muto, Yumiko; Huang, Eugene Y; Preston, Norman; Winkelman, Warren J; Gallo, Richard L

2016-06-01

Patients with rosacea have increased amounts of cathelicidin and protease activity but their usefulness as disease biomarkers is unclear. We sought to evaluate the effect of doxycycline treatment on cathelicidin expression, protease activity, and clinical response in rosacea. In all, 170 adults with papulopustular rosacea were treated for 12 weeks with doxycycline 40-mg modified-release capsules or placebo in a multicenter, randomized, double-blind, placebo-controlled study. Clinical response was compared with cathelicidin and protease activity in stratum corneum samples obtained by tape strip and in skin biopsy specimens obtained from a random subset of patients. Treatment with doxycycline significantly reduced inflammatory lesions and improved investigator global assessment scores compared with placebo. Cathelicidin expression and protein levels decreased over the course of 12 weeks in patients treated with doxycycline. Low levels of protease activity and cathelicidin expression at 12 weeks correlated with treatment success. Low protease activity at baseline was a predictor of clinical response in the doxycycline treatment group. Healthy control subjects were not studied. Improved clinical outcome correlated with reduced cathelicidin and protease activity, supporting both the mechanism of doxycycline and the potential of these molecules as biomarkers for rosacea. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Recommendations for standardized pathological characterization of residual disease for neoadjuvant clinical trials of breast cancer by the BIG-NABCG collaboration.

PubMed

Bossuyt, V; Provenzano, E; Symmans, W F; Boughey, J C; Coles, C; Curigliano, G; Dixon, J M; Esserman, L J; Fastner, G; Kuehn, T; Peintinger, F; von Minckwitz, G; White, J; Yang, W; Badve, S; Denkert, C; MacGrogan, G; Penault-Llorca, F; Viale, G; Cameron, D

2015-07-01

Neoadjuvant systemic therapy (NAST) provides the unique opportunity to assess response to treatment after months rather than years of follow-up. However, significant variability exists in methods of pathologic assessment of response to NAST, and thus its interpretation for subsequent clinical decisions. Our international multidisciplinary working group was convened by the Breast International Group-North American Breast Cancer Group (BIG-NABCG) collaboration and tasked to recommend practical methods for standardized evaluation of the post-NAST surgical breast cancer specimen for clinical trials that promote accurate and reliable designation of pathologic complete response (pCR) and meaningful characterization of residual disease. Recommendations include multidisciplinary communication; clinical marking of the tumor site (clips); and radiologic, photographic, or pictorial imaging of the sliced specimen, to map the tissue sections and reconcile macroscopic and microscopic findings. The information required to define pCR (ypT0/is ypN0 or ypT0 yp N0), residual ypT and ypN stage using the current AJCC/UICC system, and the Residual Cancer Burden system were recommended for quantification of residual disease in clinical trials. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Issues related to diagnosing oral lichen planus among oral pathologists in South India: A pilot survey.

PubMed

Sanketh, D Sharathkumar; Srinivasan, Samuel Raj; Patil, Shankargouda; Ranganathan, Kannan

2017-11-01

In the present study, we simulated clinical scenarios by explicitly describing the history and clinical and histological features of hypothetical patients presenting with oral lichen planus (OLP), oral lichenoid lesion, and epithelial dysplasia in a self-designed questionnaire. By doing so, we aimed to elicit a diagnosis from oral pathologists and trainees, analyze their responses, appraise issues, and propose solutions regarding the diagnosis of OLP. The questionnaire was distributed to 100 oral pathologists and trainees in South India. Six questions were designed to assess awareness of the diagnostic aspects of OLP. Ten questions were hypothetical clinical scenarios (HCS) devised to evaluate respondents' knowledge of diagnostic guidelines and the criteria used by the respondents to render a diagnosis. There were 60 of 100 responses to the questionnaire. More than half the respondents were aware of the World Health Organization and modified guidelines of OLP. We observed considerable variations in diagnoses for the HCS. Our study illustrates the ambiguity in rendering an accurate diagnosis, despite adequate guidelines. Based on the responses for the HCS, we hypothesized that changes in the distribution (unilateral or bilateral) and clinical characteristic of OLP, and habits of patients, have a significant bearing on the clinical and final diagnoses of the lesion. © 2016 John Wiley & Sons Australia, Ltd.

Electrically-evoked frequency-following response (EFFR) in the auditory brainstem of guinea pigs.

PubMed

He, Wenxin; Ding, Xiuyong; Zhang, Ruxiang; Chen, Jing; Zhang, Daoxing; Wu, Xihong

2014-01-01

It is still a difficult clinical issue to decide whether a patient is a suitable candidate for a cochlear implant and to plan postoperative rehabilitation, especially for some special cases, such as auditory neuropathy. A partial solution to these problems is to preoperatively evaluate the functional integrity of the auditory neural pathways. For evaluating the strength of phase-locking of auditory neurons, which was not reflected in previous methods using electrically evoked auditory brainstem response (EABR), a new method for recording phase-locking related auditory responses to electrical stimulation, called the electrically evoked frequency-following response (EFFR), was developed and evaluated using guinea pigs. The main objective was to assess feasibility of the method by testing whether the recorded signals reflected auditory neural responses or artifacts. The results showed the following: 1) the recorded signals were evoked by neuron responses rather than by artifact; 2) responses evoked by periodic signals were significantly higher than those evoked by the white noise; 3) the latency of the responses fell in the expected range; 4) the responses decreased significantly after death of the guinea pigs; and 5) the responses decreased significantly when the animal was replaced by an electrical resistance. All of these results suggest the method was valid. Recording obtained using complex tones with a missing fundamental component and using pure tones with various frequencies were consistent with those obtained using acoustic stimulation in previous studies.

Adverse Reactions to Vaccination: From Anaphylaxis to Autoimmunity.

PubMed

Gershwin, Laurel J

2018-03-01

Vaccines are important for providing protection from infectious diseases. Vaccination initiates a process that stimulates development of a robust and long-lived immune response to the disease agents in the vaccine. Side effects are sometimes associated with vaccination. These vary from development of acute hypersensitivity responses to vaccine components to local tissue reactions that are annoying but not significantly detrimental to the patient. The pathogenesis of these responses and the consequent clinical outcomes are discussed. Overstimulation of the immune response and the potential relationship to autoimmunity is evaluated in relation to genetic predisposition. Copyright © 2017 Elsevier Inc. All rights reserved.

Assessing Competence in Pediatric Cardiology

ERIC Educational Resources Information Center

Johnson, Apul E.; And Others

1976-01-01

In response to the need to assure physician competence, a rating scale was developed at the University of Minnesota Medical School for use in evaluating clinical competence in pediatric cardiology. It was tested on first- and second-year specialists. Development and testing procedures are described. (JT)

Memantine in moderately-severe-to-severe Alzheimer's disease: a postmarketing surveillance study.

PubMed

Clerici, Francesca; Vanacore, Nicola; Elia, Antonietta; Spila-Alegiani, Stefania; Pomati, Simone; Da Cas, Roberto; Raschetti, Roberto; Mariani, Claudio

2009-01-01

Postmarketing surveillance studies (PMS) are an important tool for evaluating a drug's effectiveness and safety in clinical practice. To our knowledge, no PMS on memantine monotherapy for moderately-severe-to-severe Alzheimer's disease (AD) according to National Institute of Neurological and Communicative Disorders and Stroke - Alzheimer's Disease and Related Disorders Association criteria has been conducted to date. The Lombardy Health Office, Italy, promoted this PMS to evaluate the effectiveness and safety of memantine in the treatment of moderately-severe-to-severe AD in clinical practice. A total of 451 patients with moderately-severe-to-severe AD (mean age 77 +/- 7 years; 72% female), free of cholinergic medication, received memantine (standard titration to 10 mg twice daily). After 6 months of therapy, treatment effectiveness was evaluated according to two definitions of response ('no deterioration' and 'improvement'), as measured by changes in baseline scores on the Clinical Global Impression of Change, Mini-Mental State Examination, Neuropsychiatric Inventory and Activities of Daily Living scales. The safety measure was the frequency of adverse events (AEs). At 6-month assessment, 26.8% of subjects showed no deterioration and 3.8% showed improvement. In those showing no deterioration, response to treatment at the 3-month assessment was associated with a greater probability of a response at 6 months (adjusted odds ratio = 8.54; 95% CI 4.54, 16.05). Seventy patients (15.5%) experienced at least one AE and 39 (8.6%) discontinued treatment prematurely because of an AE. Of those who experienced an AE, 27 (38.6%) manifested behavioural and psychological symptoms of dementia. The proportion of responders to memantine treatment in this PMS was similar to that reported in a previous randomized clinical trial (26.8% vs 29%, respectively). The proportion of patients who discontinued treatment prematurely because of an AE (8.6%) was similar to that reported in two previous randomized clinical trials (10% and 12.4%). This PMS provides additional evidence that both the effectiveness and the tolerability of memantine may be transferred into real world medicine, where AD patients receiving treatment are not selected according to strict criteria.

Rationale and design of the East-West late lumen loss study: Comparison of late lumen loss between Eastern and Western drug-eluting stent study cohorts.

PubMed

Harrison, Robert W; Radhakrishnan, Vaishnavi; Lam, Peter S; Allocco, Dominic J; Brar, Sandeep; Fahy, Martin; Fisher, Rebecca; Ikeno, Fumiaki; Généreux, Philippe; Kimura, Takeshi; Liu, Minglei; Lye, Weng Kit; Mintz, Gary S; Nagai, Hirofumi; Suzuki, Yuka; White, Roseann; Allen, John C; Krucoff, Mitchell W

2016-12-01

The contemporary evaluation of novel drug-eluting stents (DES) includes mechanistic observations that characterize postdeployment stent behavior. Quantification of late lumen loss due to neointimal hyperplasia 8-13 months after stent implantation, via quantitative coronary angiography (QCA), constitutes such an observation and is required by most regulatory authorities. Late lumen loss, as determined by QCA, has been validated as a surrogate for clinical endpoints such as target vessel revascularization. The mechanistic response to DES has not been directly compared across predominantly Asian or Western populations, whereas understanding their comparability across geographic populations could enhance global DES evaluation. The East-West late lumen loss study is designed to demonstrate whether the residual differences in late lumen loss, as assessed by QCA, is different between Eastern and Western DES recipients from studies with protocol angiography at 8-13 months of follow-up. Data from independent core laboratories that have characterized angiographic late lumen loss in DES clinical trials with protocol follow-up angiography will be compiled and dichotomized into Eastern and Western populations. A prospectively developed propensity score model incorporating clinical and anatomic variables affecting late lumen loss will be used to adjust comparisons of QCA measurements. Documentation of whether there are clinically meaningful differences in mechanistic response to DES implantation across genetically unique geographies could facilitate both the quality and efficiency of global device evaluation requiring invasive follow-up for novel stent designs. Copyright © 2016 Elsevier Inc. All rights reserved.

Increasing specialty care access through use of an innovative home telehealth-based spinal cord injury disease management protocol (SCI DMP)

PubMed Central

Seton, Jacinta M.; Washington, Monique; Tomlinson, Suk C.; Phrasavath, Douangmala; Farrell, Karen R.; Goldstein, Barry

2016-01-01

Background A spinal cord injury disease management protocol (SCI DMP) was developed to address the unique medical, physical, functional, and psychosocial needs of those living with spinal cord injuries and disorders (SCI/D). The SCI DMP was piloted to evaluate DMP clinical content and to identify issues for broader implementation across the Veterans Affairs (VA) SCI System of Care. Methods Thirty-three patients with SCI/D from four VA SCI centers participated in a 6-month pilot. Patients received customized SCI DMP questions through a data messaging device (DMD). Nurse home telehealth care coordinators (HTCC) monitored responses and addressed clinical alerts daily. One site administered the Duke Severity of Illness (DUSOI) Checklist and Short Form-8 (SF-8™) to evaluate the changes in comorbidity severity and health-related quality of life while on the SCI DMP. Results Patients remained enrolled an average of 116 days, with a mean response rate of 56%. The average distance between patient's home and their VA SCI center was 59 miles. Feedback on SCI DMP content and the DMD included requests for additional clinical topics, changes in administration frequency, and adapting the DMD for functional impairments. Improvement in clinical outcomes was seen in a subset of patients enrolled on the SCI DMP. Conclusion SCI HTCCs and patients reported that the program was most beneficial for newly injured patients recently discharged from acute rehabilitation that live far from specialty SCI care facilities. SCI DMP content changes and broader implementation strategies are currently being evaluated based on lessons learned from the pilot. PMID:24617497

Increasing specialty care access through use of an innovative home telehealth-based spinal cord injury disease management protocol (SCI DMP).

PubMed

Woo, Christine; Seton, Jacinta M; Washington, Monique; Tomlinson, Suk C; Phrasavath, Douangmala; Farrell, Karen R; Goldstein, Barry

2016-01-01

A spinal cord injury disease management protocol (SCI DMP) was developed to address the unique medical, physical, functional, and psychosocial needs of those living with spinal cord injuries and disorders (SCI/D). The SCI DMP was piloted to evaluate DMP clinical content and to identify issues for broader implementation across the Veterans Affairs (VA) SCI System of Care. Thirty-three patients with SCI/D from four VA SCI centers participated in a 6-month pilot. Patients received customized SCI DMP questions through a data messaging device (DMD). Nurse home telehealth care coordinators (HTCC) monitored responses and addressed clinical alerts daily. One site administered the Duke Severity of Illness (DUSOI) Checklist and Short Form-8 (SF-8™) to evaluate the changes in comorbidity severity and health-related quality of life while on the SCI DMP. Patients remained enrolled an average of 116 days, with a mean response rate of 56%. The average distance between patient's home and their VA SCI center was 59 miles. Feedback on SCI DMP content and the DMD included requests for additional clinical topics, changes in administration frequency, and adapting the DMD for functional impairments. Improvement in clinical outcomes was seen in a subset of patients enrolled on the SCI DMP. SCI HTCCs and patients reported that the program was most beneficial for newly injured patients recently discharged from acute rehabilitation that live far from specialty SCI care facilities. SCI DMP content changes and broader implementation strategies are currently being evaluated based on lessons learned from the pilot.

Impact of aspirin resistance on outcomes among patients following coronary artery bypass grafting: exploratory analysis from randomized controlled trial (NCT01159639).

PubMed

Petricevic, Mate; Kopjar, Tomislav; Gasparovic, Hrvoje; Milicic, Davor; Svetina, Lucija; Zdilar, Boris; Boban, Marko; Mihaljevic, Martina Zrno; Biocina, Bojan

2015-05-01

Individual variability in the response to aspirin, has been established by various platelet function assays, however, the clinical relevance of aspirin resistance (AR) in patients undergoing coronary artery bypass grafting (CABG) has to be evaluated. Our working group conducted a randomized controlled trial (NCT01159639) with the aim to assess impact of dual antiplatelet therapy (APT) on outcomes among patients with AR following CABG. Patients that were aspirin resistant on fourth postoperative day (POD 4) were randomly assigned to receive either dual APT with clopidogrel (75 mg) plus aspirin (300 mg)-intervention arm or monotherapy with aspirin (300 mg)-control arm. This exploratory analysis compares clinical outcomes between aspirin resistant patients allocated to control arm and patients that have had adequate platelet inhibitory response to aspirin at POD 4. Both groups were treated with 300 mg of aspirin per day following surgery. We sought to evaluate the impact of early postoperative AR on outcomes among patients following CABG. Exploratory analysis included a total number of 325 patients. Of those, 215 patients with adequate response to aspirin and 110 patients with AR allocated to aspirin monotherapy following randomization protocol. The primary efficacy end point (MACCEs-major adverse cardiac and cardiovascular events) occurred in 10 and 6 % of patients with AR and with adequate aspirin response, respectively (p = 0.27). Non-significant differences were observed in bleeding events occurrence. Subgroup analysis of the primary end point revealed that aspirin resistant patients with BMI > 30 kg/m(2) tend to have a higher occurrence of MACCEs 18 versus 5 % (relative risk 0.44 [95 % CI 0.16-1.16]; p = 0.05). This exploratory analysis did not reveal significant impact of aspirin resistance on outcomes among patients undergoing CABG. Further, sufficiently powered studies are needed in order to evaluate clinical relevance of AR in patients undergoing CABG.

Diagnostic criteria for chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS).

PubMed

Tobin, W Oliver; Guo, Yong; Krecke, Karl N; Parisi, Joseph E; Lucchinetti, Claudia F; Pittock, Sean J; Mandrekar, Jay; Dubey, Divyanshu; Debruyne, Jan; Keegan, B Mark

2017-09-01

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a central nervous system inflammatory syndrome predominantly affecting the brainstem, cerebellum, and spinal cord. Following its initial description, the salient features of CLIPPERS have been confirmed and expanded upon, but the lack of formalized diagnostic criteria has led to reports of patients with dissimilar features purported to have CLIPPERS. We evaluated clinical, radiological and pathological features of patients referred for suspected CLIPPERS and propose diagnostic criteria to discriminate CLIPPERS from non-CLIPPERS aetiologies. Thirty-five patients were evaluated for suspected CLIPPERS. Clinical and neuroimaging data were reviewed by three neurologists to confirm CLIPPERS by consensus agreement. Neuroimaging and neuropathology were reviewed by experienced neuroradiologists and neuropathologists, respectively, both of whom were blinded to the clinical data. CLIPPERS was diagnosed in 23 patients (18 male and five female) and 12 patients had a non-CLIPPERS diagnosis. CLIPPERS patients' median age of onset was 58 years (interquartile range, 24-72) and were followed a median of 44 months (interquartile range 38-63). Non-CLIPPERS patients' median age of onset was 52 years (interquartile range, 39-59) and were followed a median of 27 months (interquartile range, 14-47). Clinical symptoms of gait ataxia, diplopia, cognitive impairment, and facial paraesthesia did not discriminate CLIPPERS from non-CLIPPERS. Marked clinical and radiological corticosteroid responsiveness was observed in CLIPPERS (23/23), and clinical worsening occurred in all 12 CLIPPERS cases when corticosteroids were discontinued. Corticosteroid responsiveness was common but not universal in non-CLIPPERS [clinical improvement (8/12); radiological improvement (2/12); clinical worsening on discontinuation (3/8)]. CLIPPERS patients had brainstem predominant perivascular gadolinium enhancing lesions on magnetic resonance imaging that were discriminated from non-CLIPPERS by: homogenous gadolinium enhancing nodules <3 mm in diameter without ring-enhancement or mass effect, and homogenous T2 signal abnormality not significantly exceeding the T1 enhancement. Brain neuropathology on 14 CLIPPERS cases demonstrated marked CD3-positive T-lymphocyte, mild B-lymphocyte and moderate macrophage infiltrates, with perivascular predominance as well as diffuse parenchymal infiltration (14/14), present in meninges, white and grey matter, associated with variable tissue destruction, astrogliosis and secondary myelin loss. Clinical, radiological and pathological feature define CLIPPERS syndrome and are differentiated from non-CLIPPERS aetiologies by neuroradiological and neuropathological findings. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Vaginal and Sexual Health Treatment Strategies within a Female Sexual Medicine Program for Cancer Patients and Survivors

PubMed Central

Carter, Jeanne; Stabile, Cara; Seidel, Barbara; Baser, Raymond E.; Goldfarb, Shari; Goldfrank, Deborah J.

2016-01-01

Purpose We sought to evaluate patient adherence and response to simple vaginal and sexual health treatment strategies in female cancer patients receiving treatment at a female sexual medicine and health program, and identify improvements of physical symptoms, per patient and clinical evaluation. Methods Evalubility criteria included gynecologic exam at initial visit; at least one follow-up with gynecologic exam within 8 months of initial visit; and all consecutive follow-ups <6 months apart. Demographics, medical information, and clinical assessments from 175 evaluable patients with at least 1 follow-up from 09/12–10/14 were analyzed. The majority of patients were being treated for or had a history of breast (n=90, 53%), gynecologic (n=54, 32%), or colorectal/anal (n=15, 9%) cancers. An assessment form included a clinician evaluation, Vaginal Assessment Scale (VAS), Vulvar Assessment Scale (VuAS), and patient-reported outcomes. Compliance with treatment recommendations were summarized, and changes over time were compared for clinical outcomes. Results Mean number of visits was 3.43. Mean age was 55.4 years; 92% (n=155/169) were in menopause. Treatment strategies included rationale and instruction for use of vaginal moisturizers, lubricants, pelvic floor exercises and dilator therapy, in addition to psychosexual education regarding sexual changes (response, anatomy and function) associated with cancer treatment and support. At last assessment, 89% had complied with the clinical recommendation (moisturize 2–5+ times/week). Vaginal pH scores >6.5 declined over time (p=0.03). VAS scores improved by last assessment (p<0.001), as did VuAS scores (p=0.001). Sexual function scores significantly improved (p<0.001), confidence about future sexual activity increased (p=0.004), and sexual/vaginal health concerns decreased (p=0.00003). Conclusion Significant changes were observed in women using treatment strategies, with improvement in vulvovaginal symptoms, a decrease in elevated vaginal pH and pain with exams, enhanced sexual function, and intimacy confidence. Implications for Cancer Survivors These findings have high clinical relevance for symptom management with improvement of sexual function using simple strategies and clinical tools in the oncology setting. PMID:27868156

Efficacy of vedolizumab as induction therapy in refractory IBD patients: Amulticenter cohort

PubMed Central

Shelton, Edward; Allegretti, Jessica R.; Stevens, Betsy; Lucci, Matthew; Khalili, Hamed; Nguyen, Deanna D.; Sauk, Jenny; Giallourakis, Cosmas; Garber, John; Hamilton, Matthew J; Tomczak, Michal; Makrauer, Fredrick; Burakoff, Robert B; Levine, Jonathan; de Silva, Punyaganie; Friedman, Sonia; Ananthakrishnan, Ashwin; Korzenik, Joshua R.; Yajnik, Vijay

2015-01-01

Background Vedolizumab (VDZ) demonstrated efficacy in Crohn's disease (CD) and ulcerative colitis (UC) in the GEMINI trials. Our aim was to evaluate the efficacy of VDZ at week 14 in inflammatory bowel disease (IBD) in a multicenter cohort of patients. Methods Patients at Massachusetts General Hospital and Brigham and Women's Hospital were considered for inclusion. VDZ (300mg) was administered at weeks 0, 2, 6 and 14. Efficacy was assessed using the Harvey Bradshaw index (HBI) for CD, the simple clinical colitis activity index (SCCAI) for UC and physician assessment, along with C-reactive protein (CRP) and decrease of corticosteroid therapy. Clinical response was defined as decrease in HBI ≥ 3 and SCCAI ≥ 3 and remission as HBI ≤ 4, SCCAI ≤ 2 and physician assessment of response and remission. Results Our study included 172 patients (107 CD, 59 UC, 6 IBD-U, male 48.3%, mean age 40 years and disease duration 14 years). Fourteen patients had an ostomy and 9 an ileoanal pouch and only 35.5% fulfilled eligibility for the GEMINI trials. Previous treatment failures with ≥ 2 anti-TNFs occurred in 70.9%, one-third were on an immunomodulator and 46% systemic steroids at baseline. In CD, 48.9% and 23.9% and in UC, 53.9% and 29.3% had clinical response and clinical remission at week 14. Adverse events occurred in 10.5%. Conclusions VDZ is safe and well tolerated in refractory IBD patients in a clinical practice with efficacy in UC and CD with responses similar to what was seen in clinical trials. PMID:26288002

Real-world data on Len/Dex combination at second-line therapy of multiple myeloma: treatment at biochemical relapse is a significant prognostic factor for progression-free survival.

PubMed

Katroditou, Eirini; Kyrtsonis, Marie-Christine; Delimpasi, Sosana; Kyriakou, Despoina; Symeonidis, Argiris; Spanoudakis, Emmanouil; Vasilopoulos, Georgios; Anagnostopoulos, Achilles; Kioumi, Anna; Zikos, Panagiotis; Aktypi, Anthi; Briasoulis, Evangelos; Megalakaki, Aikaterini; Repousis, Panayiotis; Adamopoulos, Ioannis; Gogos, Dimitrios; Kotsopoulou, Maria; Pappa, Vassiliki; Papadaki, Eleni; Fotiou, Despoina; Nikolaou, Eftychia; Giannopoulou, Evlambia; Hatzimichael, Eleftheria; Giannakoulas, Nikolaos; Douka, Vassiliki; Kokoviadou, Kyriaki; Timotheatou, Despoina; Terpos, Evangelos

2018-05-13

We evaluated progression-free survival (PFS) rate of patients treated with lenalidomide/dexamethasone (Len/Dex), the efficacy of the combination, and the prognostic significance of treatment at biochemical vs. clinical relapse on PFS in 207 consecutive myeloma patients treated with Len/Dex in second line, according to routine clinical practice in Greece. First-line treatment included bortezomib-based (63.3%) or immunomodulatory drug-based (34.8%) therapies; 25% of patients underwent autologous stem cell transplantation. Overall response rate was 73.4% (17.8% complete response and 23.7% very good partial response); median time to best response was 6.7 months. Overall, median PFS and 12-month PFS rate was 19.2 months and 67.6%, respectively. 67.5% of patients had biochemical relapse and 32.5% had clinical relapse prior to initiation of Len/Dex. Median PFS was 24 months for patients treated at biochemical relapse vs. 13.2 months for those treated at clinical relapse (HR:0.63, p = 0.006) and the difference remained significant after adjustment for other prognostic factors. Type of relapse was the strongest prognostic factor for PFS in multivariate analysis. These real-world data confirm the efficacy of Len/Dex combination at first relapse; more importantly, it is demonstrated for the first time outside a clinical trial setting that starting therapy with Len/Dex at biochemical, rather than at clinical relapse, is a significant prognostic factor for PFS, inducing a 37% reduction of the probability of disease progression or death.

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

PubMed Central

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 subtype-B-infected counterparts. Clinical deterioration was associated with low baseline CD4 counts and older age. The lack of differences in virologic outcomes suggests that all patients have opportunities for virologic suppression. PMID:23138836

Biomagnetic Pair Therapy and Typhoid Fever: A Pilot Study.

PubMed

Frank, Bryan L

2017-10-01

Objective: This pilot study examined the laboratory responses of patients with laboratory-documented typhoid fever who were treated with Biomagnetic Pair Therapy (BPT; medical biomagnetism), a specific application of pairs of magnets for various ailments that are infectious and otherwise. Materials and Methods: This study was an assessment of patients' response to treatment with only BPT for Salmonella typhi infections (typhoid fever) using standard conventional laboratory techniques. The research was conducted in an outpatient village clinic in Kenya. There were 52 participants who were evaluated for possible systemic illness, including typhoid fever, from an open-label study. Participants who felt sick and requested testing for possible typhoid fever were tested with a standard Widal test by a certified laboratory technician. Participants who tested positive (13 patients) were then treated with BPT (a "First Aid" approach) only. These participants then returned for follow-up laboratory and clinical evaluations after 2 days. Results: Most of the participants (10 of 13) retested as negative, and all patients reported symptomatic clinical improvement. Conclusions: As a significant majority of participants demonstrated clearing of their S. typhi after BPT, this technique should be studied further in larger trials for its efficacy in treating typhoid fever.

Predictors of the patency of self-expandable metallic stents in malignant gastroduodenal obstruction.

PubMed

Kim, Seung Han; Chun, Hoon Jai; Yoo, In Kyung; Lee, Jae Min; Nam, Seung Joo; Choi, Hyuk Soon; Kim, Eun Sun; Keum, Bora; Seo, Yeon Seok; Jeen, Yoon Tae; Lee, Hong Sik; Um, Soon Ho; Kim, Chang Duck

2015-08-14

To investigate the predictive factors of self-expandable metallic stent patency after stent placement in patients with inoperable malignant gastroduodenal obstruction. A total of 116 patients underwent stent placements for inoperable malignant gastroduodenal obstruction at a tertiary academic center. Clinical success was defined as acceptable decompression of the obstructive lesion within the malignant gastroduodenal neoplasm. We evaluated patient comorbidities and clinical statuses using the World Health Organization's scoring system and categorized patient responses to chemotherapy using the Response Evaluation Criteria in Solid Tumors criteria. We analyzed the relationships between possible predictive factors and stent patency. Self-expandable metallic stent placement was technically successful in all patients (100%), and the clinical success rate was 84.2%. In a multivariate Cox proportional hazards model, carcinoembryonic antigen (CEA) levels were correlated with a reduction in stent patency [P = 0.006; adjusted hazard ratio (aHR) = 2.92, 95%CI: 1.36-6.25]. Palliative chemotherapy was statistically associated with an increase in stent patency (P = 0.009; aHR = 0.27, 95%CI: 0.10-0.72). CEA levels can easily be measured at the time of stent placement and may help clinicians to predict stent patency and determine the appropriate stent procedure.

Recent Advances in Allograft Vasculopathy

PubMed Central

Merola, Jonathan; Jane-Wit, Daniel D.; Pober, Jordan S.

2017-01-01

Purpose of review Despite considerable advances in controlling acute rejection, the longevity of cardiac and renal allografts remains significantly limited by chronic rejection in the form of allograft vasculopathy (AV). This review discusses recently reported mechanistic insights of AV pathogenesis as well recent clinical evaluations of new therapeutic approaches. Recent findings Although adaptive immunity is the major driver of AV, natural killer cells mediate vasculopathic changes in a transplanted mouse heart following treatment with donor-specific antibody (DSA). However, NK cells may also dampen chronic inflammatory responses by killing donor-derived tissue-resident CD4 T cells that provide help to host B cells, the source of DSA. DSA may directly contribute to vascular inflammation by inducing intracellular signaling cascades that upregulate leukocyte adhesion molecules, facilitating recruitment of neutrophils and monocytes. DSA-mediated complement activation additionally enhances endothelial alloimmunogenicity through activation of non-canonical NF-κB signaling. New clinical studies evaluating mTOR and proteasome inhibitors to target these pathways have been reported. Summary AV is a pathology resultant from several innate and adaptive alloimmune responses. Mechanistic insights from preclinical studies have identified agents that are currently being investigated in clinical trials. PMID:27898462

[Study of quality of a branch laboratory--an opinion of a laboratory manager].

PubMed

Yazawa, Naoyuki

2006-11-01

At the stage of establishing a branch laboratory, quality evaluation is extremely difficult. Even the results of a control survey by the headquarters of the branch laboratory are unhelpful. For a clinical laboratory, the most important function is to provide reliable data all the time, and to maintain the reliability of clinical doctors with informed responses. We mostly refer to control surveys and daily quality control data to evaluate a clinical laboratory, but we rarely check its fundamental abilities, such as planning events, preserving statistical data about the standard range, using the right method for quality control and others. This is generally disregarded and it is taken for granted that they will be correct the first time. From my six years of experience working with X's branch laboratory, I realized that there might be some relation between the quality of a branch laboratory and the fundamental abilities of the company itself. I would never argue that all branch laboratories are ineffective, but they should be conscious of fundamental activities. The referring laboratory, not the referral laboratory, should be responsible for ensuring that the referral laboratory's examination results and findings are correct.

Preliminary results of a phase I/II clinical trial using in situ photoimmunotherapy combined with imiquimod for metastatic melanoma patients

NASA Astrophysics Data System (ADS)

Li, Xiaosong; Naylor, Mark F.; Nordquist, Robert E.; Teague, T. Kent; Howard, C. Anthony; Murray, Cynthia; Chen, Wei R.

2010-02-01

In Situ Photoimmunotherapy (ISPI), a newly developed modality for cancer therapy, has been shown to be able to modulate the body's own immune response. This clinical trial was designed to evaluate the safety and therapeutic effect of ISPI, using imiquimod as its immunoadjuvant for metastatic melanoma patients. ISPI consisted of three main components applied directly to the cutaneous metastases: 1) local application of topical imiquimod; 2) injection of indocyanine green; and 3) an 805 nm laser for local irradiation. All patients completed at least one cycle of treatment. All the patients completed at least one cycle of treatments; one patient received 6 cycles. The most common adverse effects were rash, pruritus, pain, fatigue and anorexia. Fever, chills, vomiting and cellulitis were relative rare. No grade 4 toxicity was observed. Complete Response (CR) was observed in 6 patients. Median overall survival of the 11 evaluated patients was 12.2 months. Six of the eleven patients were still alive at the time of this report. Treatment of ISPI using imiquimod is safe and well tolerant. Our preliminary clinical results suggest that this new method can be a promising modality for metastatic melanoma.

A Survey of Practice Patterns in Concussion Assessment and Management.

PubMed

Ferrara, Michael S.; McCrea, Michael; Peterson, Connie L.; Guskiewicz, Kevin M.

2001-06-01

OBJECTIVES: To identify methods used by athletic trainers to assess concussions and the use of that information to assist in return-to-play decisions and to determine athletic trainers' familiarity with new standardized methods of concussion assessment. DESIGN AND SETTING: A 21-item questionnaire was distributed to attendees of a minicourse at the 1999 National Athletic Trainers' Association Annual Meeting and Clinical Symposia entitled "Use of Standardized Assessment of Concussion (SAC) in the Immediate Sideline Evaluation of Injured Athletes." SUBJECTS: A total of 339 valid surveys were returned by the attendees of the minicourse. MEASUREMENTS: We used frequency analysis and descriptive statistics. RESULTS: Clinical examination (33%) and a symptom checklist (15.3%) were the most common evaluative tools used to assess concussions. The Colorado Guidelines (28%) were used more than other concussion management guidelines. Athletic trainers (34%) and team physicians (40%) were primarily responsible for making decisions regarding return to play. A large number of respondents (83.5%) believed that the use of a standardized method of concussion assessment provided more information than routine clinical and physical examination alone. CONCLUSIONS: Athletic trainers are using a variety of clinical tools to evaluate concussions in athletes. Clinical evaluation and collaboration with physicians still appear to be the primary methods used for return-to-play decisions. However, athletic trainers are beginning to use standardized methods of concussion to evaluate these injuries and to assist them in assessing the severity of injury and deciding when it is safe to return to play.

Phase I/II evaluation of RV1001, a novel PI3Kδ inhibitor, in spontaneous canine lymphoma.

PubMed

Gardner, Heather L; Rippy, Sarah B; Bear, Misty D; Cronin, Kim L; Heeb, Heather; Burr, Holly; Cannon, Claire M; Penmetsa, Kumar V; Viswanadha, Srikant; Vakkalanka, Swaroop; London, Cheryl A

2018-01-01

RV1001 is a novel, potent, and selective PI3Kδ inhibitor. The purpose of this study was to evaluate the safety and efficacy of RV1001 in canine Non-Hodgkin lymphoma (NHL). Inhibition of endogenous pAKT by RV1001 in primary canine NHL cells was determined by Western blotting. A phase I study of RV1001 was performed in 21 dogs with naïve and drug resistant T and B-cell NHL to assess safety, pharmacokinetic profile, and response to therapy. The objective response rate was 62% (complete response (CR) n = 3; partial response (PR) n = 10), and responses were observed in both naïve and chemotherapy-resistant B and T cell NHL. This study provided the recommended starting dose for a phase II, non-pivotal, exploratory, open label multi-centered clinical trial in 35 dogs with naïve and drug resistant T and B-cell NHL, to further define the efficacy and safety profile of RV1001. The objective response rate in the phase II study was 77% (CR n = 1; PR n = 26). Clinical toxicities were primarily hepatobiliary and gastrointestinal, and were responsive to dose modifications and/or temporary drug discontinuation. Hepatotoxicity was the primary dose limiting toxicity. RV1001 exhibits good oral bioavailability, an acceptable safety profile, and biologic activity with associated inhibition of pAKT in dogs with B and T cell NHL. Data from these studies can be leveraged to help inform the design of future studies involving isoform-selective PI3K inhibitors in humans.