“You Are Such a Disappointment!”: Negative Emotions and Parents’ Perceptions of Adult Children’s Lack of Success

PubMed Central

2013-01-01

Objectives. Parents’ perceptions of their adult children’s successes (or lack thereof) may be associated in different ways with discrete negative emotions (e.g., guilt, anger, disappointment, and worry). Furthermore, mothers and fathers may vary in their reactions to children’s success in different domains. Method. Participants included 158 mothers and fathers from the same families (N = 316) and their adult child. Mothers and fathers evaluated their adult children’s successes in (a) career and (b) relationship domains. Mothers and fathers also reported on several negative emotions in the parent–child tie: guilt, anger, disappointment, and worry. Results. For fathers, perceptions of children’s poorer career success were associated with disappointment, anger, and guilt. Mothers’ perceptions of children’s lack of career success were associated with disappointment and worry. Mothers’ perceptions of children’s poorer success in relationships were associated with each of the negative emotions, with the exception of anger. Discussion. Parents experience emotions associated with unmet goals and future concerns in relationships with less successful children. Mothers may respond emotionally to career and relationship success, whereas fathers may respond emotionally primarily to their child’s career success. Findings underscore the importance of considering the context of parents’ negative emotional experiences in ties to adult children. PMID:23733857

"You are such a disappointment!": negative emotions and parents' perceptions of adult children's lack of success.

PubMed

Cichy, Kelly E; Lefkowitz, Eva S; Davis, Eden M; Fingerman, Karen L

2013-11-01

Parents' perceptions of their adult children's successes (or lack thereof) may be associated in different ways with discrete negative emotions (e.g., guilt, anger, disappointment, and worry). Furthermore, mothers and fathers may vary in their reactions to children's success in different domains. Participants included 158 mothers and fathers from the same families (N = 316) and their adult child. Mothers and fathers evaluated their adult children's successes in (a) career and (b) relationship domains. Mothers and fathers also reported on several negative emotions in the parent-child tie: guilt, anger, disappointment, and worry. For fathers, perceptions of children's poorer career success were associated with disappointment, anger, and guilt. Mothers' perceptions of children's lack of career success were associated with disappointment and worry. Mothers' perceptions of children's poorer success in relationships were associated with each of the negative emotions, with the exception of anger. Parents experience emotions associated with unmet goals and future concerns in relationships with less successful children. Mothers may respond emotionally to career and relationship success, whereas fathers may respond emotionally primarily to their child's career success. Findings underscore the importance of considering the context of parents' negative emotional experiences in ties to adult children.

Inductive discipline, parental expression of disappointed expectations, and moral identity in adolescence.

PubMed

Patrick, Renee B; Gibbs, John C

2012-08-01

Within the fields of socialization and moral development, the relationship of parenting to adolescents' sense of morality and self has been understudied. This study investigated the relationships between perceived parental disciplinary techniques and moral identity among early and middle adolescents. Participants included 93 (54% female) 5th, 8th and 10th graders, as well as their mothers. Students completed self-report measures concerning their mothers' disciplinary techniques and moral self-concept; mothers reported specifically on parental discipline frequency. The parental discipline measure was structured in terms of Hoffman's typology of induction, love withdrawal, and power assertion. Adolescents reported the frequency of their mothers' disciplinary techniques, as well as their perceptions (fairness or appropriateness evaluations, emotional reactions) concerning their mothers' most frequently used technique. Parental induction (orienting the transgressor to the plight of the victim) and expression of disappointed expectations were viewed as more appropriate and responded to with more positive emotion and guilt relative to other disciplinary techniques (e.g., power assertion). In addition, parental use of inductive discipline (including parental disappointment) during the adolescent years related to higher moral identity, defined in terms of the ascription of specifically moral (e.g., fair, kind) over non-moral (e.g., athletic, smart) qualities to the self. In contrast, love withdrawal and power assertion did not relate to moral identity. The findings suggest that parental expression of disappointed expectations, especially when perceived favorably, plays an important role in the formation of moral identity during the adolescent years.

Twenty Years of Social Studies Textbook Content Analysis: Still "Decidedly Disappointing"?

ERIC Educational Resources Information Center

Chu, Yiting

2017-01-01

In an article published in 1993, Rahima Wade reviewed the quality of social studies textbook content analyses published in three major social studies journals between 1982 and 1992. She concluded that the quality of this research was disappointing. Borrowing and refining Wade's methods, this article presents the findings of a review of all 29…

Educational Orientation and Upward Influence: An Examination of Students' Conversations about Disappointing Grades

ERIC Educational Resources Information Center

Wright, Courtney N.

2012-01-01

The influence of student attitudes toward learning and grades on their communication with instructors about grades has received limited attention despite its potential implications for learning, performance outcomes, and student-teacher interactions. Participants (N = 194) who discussed a disappointing grade with an instructor completed measures…

Disappointment Reach, Australia as seen from STS-67 Endeavour

NASA Technical Reports Server (NTRS)

1995-01-01

A nearly vertical view of Disappointment Reach and surroundings. Ripple-like patterns extending at right angles to the tidal flow can be discerned on shoals. Relict sand dune patterns, crests unvegetated, are evident on the western side of the estuary. Red mud brought down the Mooramel River on the east side of the estuary does extend into the shallow water of the inter-tidal lagoons. Most of the light-colored water along the coast, represents shoals of lime sediment. Patterns of sediment distribution by tides, waves, streams, and wind combine to create a complex and colorful scene.

Disappointment Reach, Australia as seen from STS-67 Endeavour

NASA Image and Video Library

1995-03-14

A nearly vertical view of Disappointment Reach and surroundings. Ripple-like patterns extending at right angles to the tidal flow can be discerned on shoals. Relict sand dune patterns, crests unvegetated, are evident on the western side of the estuary. Red mud brought down the Mooramel River on the east side of the estuary does extend into the shallow water of the inter-tidal lagoons. Most of the light-colored water along the coast, represents shoals of lime sediment. Patterns of sediment distribution by tides, waves, streams, and wind combine to create a complex and colorful scene.

Alzheimer's Therapeutics: Translation of Preclinical Science to Clinical Drug Development

PubMed Central

Savonenko, Alena V; Melnikova, Tatiana; Hiatt, Andrew; Li, Tong; Worley, Paul F; Troncoso, Juan C; Wong, Phil C; Price, Don L

2012-01-01

Over the past three decades, significant progress has been made in understanding the neurobiology of Alzheimer's disease. In recent years, the first attempts to implement novel mechanism-based treatments brought rather disappointing results, with low, if any, drug efficacy and significant side effects. A discrepancy between our expectations based on preclinical models and the results of clinical trials calls for a revision of our theoretical views and questions every stage of translation—from how we model the disease to how we run clinical trials. In the following sections, we will use some specific examples of the therapeutics from acetylcholinesterase inhibitors to recent anti-Aβ immunization and γ-secretase inhibition to discuss whether preclinical studies could predict the limitations in efficacy and side effects that we were so disappointed to observe in recent clinical trials. We discuss ways to improve both the predictive validity of mouse models and the translation of knowledge between preclinical and clinical stages of drug development. PMID:21937983

"He Didn't Want Me to Feel Sad": Children's Reactions to Disappointment and Apology

ERIC Educational Resources Information Center

Smith, Craig E.; Harris, Paul L.

2012-01-01

Experimental studies of children's responses to apologies often present participants with hypothetical scenarios. This article reports on an experimental study of children's reactions to experiencing an actual disappointment and subsequent apology. Participants (ages four to seven) were told that another child was supposed to share some attractive…

Parental Expression of Disappointment: Should It Be a Factor in Hoffman's Model of Parental Discipline?

ERIC Educational Resources Information Center

Patrick, Renee B.; Gibbs, John C.

2007-01-01

The authors addressed whether parental expression of disappointment should be included as a distinct factor in M. L. Hoffman's (2000) well-established typology of parenting styles (induction, love withdrawal, power assertion). Hoffman's 3-factor model, along with a more inclusive 4-factor model (induction, love withdrawal, power assertion, and…

Preschoolers' Effortful Control and Negative Emotionality, Immediate Reactions to Disappointment, and Quality of Social Functioning

ERIC Educational Resources Information Center

Liew, Jeffrey; Eisenberg, Nancy; Reiser, Mark

2004-01-01

Relations among effortful control/low negative emotionality, immediate reactions in a situation that usually calls for the masking of disappointment (i.e., the use of display rules), and social competence/adjustment were investigated for 78 preschool children (mean age=4.87 years). Parents, teachers, and peers rated children on negative…

Communicating microarray results of uncertain clinical significance in consultation summary letters and implications for practice.

PubMed

Paul, Jean Lillian; Pope-Couston, Rachel; Wake, Samantha; Burgess, Trent; Tan, Tiong Yang

2016-01-01

Letter-writing is an integral practice for genetic health professionals. In Victoria, Australia, patients with a chromosomal variant of uncertain clinical significance (VUS) referred to a clinical geneticist (CG) for evaluation receive consultation summary letters. While communication of uncertainty has been explored in research to some extent, little has focused on how uncertainty is communicated within consultation letters. We aimed to develop a multi-layered understanding of the ways in which CGs communicate diagnostic uncertainty in consultation summary letters. We used theme-oriented discourse analysis of 49 consultation summary letters and thematic analysis of a focus group involving eight CGs. Results showed that CGs have become more confident in their description of VUS as 'contributing factors' to patients' clinical features, but remain hesitant to assign definitive causality. CGs displayed strong epistemic stance when discussing future technological improvements to provide hope and minimise potentially disappointing outcomes for patients and families. CGs reported feeling overwhelmed by their workload associated with increasing numbers of patients with VUS, and this has led to a reduction in the number of review appointments offered over time. This study provides a rich description of the content and process of summary letters discussing VUS. Our findings have implications for letter-writing and workforce management. Furthermore, these findings may be of relevance to VUS identified by genomic sequencing in clinical practice.

Disappointment and regret enhance corrugator reactivity in a gambling task

PubMed Central

Wu, Yin; Clark, Luke

2015-01-01

This study investigated how the corrugator and zygomaticus respond to decision outcomes (i.e., gains and losses). We used a gambling task in which participants were presented with obtained followed by non-obtained outcomes. Activity at the corrugator site was sensitive to decision outcomes, such that higher obtained losses (disappointment) and higher non-obtained gains (regret) both heightened corrugator reactivity. Activity at the zygomaticus site was not responsive to obtained or non-obtained outcomes, but did show sensitivity to emotional images in the same participants, in the form of a positive linear relationship with self-reported emotional valence. Corrugator activity was negatively related to emotional valence. The findings indicate the sensitivity of corrugator to objective decision outcomes and also counterfactual comparisons, highlighting the utility of facial electromyography in research on decision making and gambling behavior. PMID:25345723

Geologic map of the Cape Disappointment-Naselle River area, Pacific and Wahkiakum counties, Washington

USGS Publications Warehouse

Wells, R.E.

1989-01-01

The Cape Disappointment-Naselle River area is in southwestern Washington at the mouth of the Columbia River.  The area encompasses several major estuaries and their adjacent highlands, which reach elevations of about 2,000 feet.  Rainfall is abundant and produces heavy vegetation and deep weathering of the bedrock.  Natural bedrock exposures are restricted to stream courses along larger drainages, although a network of logging roads provides excellent access to most of the area and widespread, but somewhat ephemeral, exposures of bedrock.

Obama and the "Arab Spring": Desire, Hope and the Manufacture of Disappointment. Implications for a Transformative Pedagogy

ERIC Educational Resources Information Center

Roberts, Lorna; Schostak, John

2012-01-01

For a period, in the run up to the election (2007-2008) and the months after the election, the name "Obama" signified hope for millions, not just in America but across the world. As the hope turned to disappointment, the financial crisis deepened and the Arab Spring renewed a call for a "humanity" that could transcend the differences of nations…

Disappointment and regret enhance corrugator reactivity in a gambling task.

PubMed

Wu, Yin; Clark, Luke

2015-04-01

This study investigated how the corrugator and zygomaticus respond to decision outcomes (i.e., gains and losses). We used a gambling task in which participants were presented with obtained followed by non-obtained outcomes. Activity at the corrugator site was sensitive to decision outcomes, such that higher obtained losses (disappointment) and higher non-obtained gains (regret) both heightened corrugator reactivity. Activity at the zygomaticus site was not responsive to obtained or non-obtained outcomes, but did show sensitivity to emotional images in the same participants, in the form of a positive linear relationship with self-reported emotional valence. Corrugator activity was negatively related to emotional valence. The findings indicate the sensitivity of corrugator to objective decision outcomes and also counterfactual comparisons, highlighting the utility of facial electromyography in research on decision making and gambling behavior. © 2014 The Authors. Psychophysiology published by Wiley Periodicals, Inc. on behalf of Society for Psychophysiological Research.

Student-Faculty Interactions about Disappointing Grades: Application of the Goals-Plans-Actions Model and the Theory of Planned Behavior

ERIC Educational Resources Information Center

Henningsen, Mary Lynn Miller; Valde, Kathleen S.; Russell, Gregory A.; Russell, Gregory R.

2011-01-01

The goals-plans-actions model and the theory of planned behavior were used to predict what lead to students having a conversation about a disappointing grade with a faculty member. Participants (N = 130) completed two surveys. In the first survey, participants completed measures of primary and secondary goals, planning, decision to engage,…

Clinical providers' experiences with returning results from genomic sequencing: an interview study.

PubMed

Wynn, Julia; Lewis, Katie; Amendola, Laura M; Bernhardt, Barbara A; Biswas, Sawona; Joshi, Manasi; McMullen, Carmit; Scollon, Sarah

2018-05-08

Current medical practice includes the application of genomic sequencing (GS) in clinical and research settings. Despite expanded use of this technology, the process of disclosure of genomic results to patients and research participants has not been thoroughly examined and there are no established best practices. We conducted semi-structured interviews with 21 genetic and non-genetic clinicians returning results of GS as part of the NIH funded Clinical Sequencing Exploratory Research (CSER) Consortium projects. Interviews focused on the logistics of sessions, participant/patient reactions and factors influencing them, how the sessions changed with experience, and resources and training recommended to return genomic results. The length of preparation and disclosure sessions varied depending on the type and number of results and their implications. Internal and external databases, online resources and result review meetings were used to prepare. Respondents reported that participants' reactions were variable and ranged from enthusiasm and relief to confusion and disappointment. Factors influencing reactions were types of results, expectations and health status. A recurrent challenge was managing inflated expectations about GS. Other challenges included returning multiple, unanticipated and/or uncertain results and navigating a rare diagnosis. Methods to address these challenges included traditional genetic counseling techniques and modifying practice over time in order to provide anticipatory guidance and modulate expectations. Respondents made recommendations to improve access to genomic resources and genetic referrals to prepare future providers as the uptake of GS increases in both genetic and non-genetic settings. These findings indicate that returning genomic results is similar to return of results in traditional genetic testing but is magnified by the additional complexity and potential uncertainty of the results. Managing patient expectations, initially

Implementation of a clinical innovation: the case of advanced clinic access in the Department of Veterans Affairs.

PubMed

Lukas, Carol VanDeusen; Meterko, Mark M; Mohr, David; Seibert, Marjorie Nealon; Parlier, Renee; Levesque, Odette; Petzel, Robert A

2008-01-01

Healthcare organizations seeking to improve clinical practices often have disappointing results because the planned innovations are not successfully implemented. To increase the understanding of implementation, we analyzed the national spread of an ambulatory innovation in the Department of Veterans Affairs. This study provides support for a conceptual model that posits that the extent to which a clinical innovation is implemented will be affected by factors in 3 domains: (1) intentional activities to introduce, spread, and support the innovation; (2) the attitudes and capabilities of clinic staff responsible for implementing the innovation; and (3) the context of the facility in which the innovation is being introduced. Among the strongest predictors of successful implementation, management support for the innovation and clinic team knowledge and skills to make changes successfully were significant across both primary care and specialty clinics.

Dreams and disappointments regarding nursing: Student nurses' reasons for attrition and retention. A qualitative study design.

PubMed

Ten Hoeve, Yvonne; Castelein, Stynke; Jansen, Gerard; Roodbol, Petrie

2017-07-01

In the Netherlands, hundreds of students register annually for a nursing programme, but not all of these students manage to complete their training. The main aim of this study was to examine which factors affect student nurses' decision to leave or complete their programme. The study used an exploratory descriptive design, employing a qualitative phenomenological approach. Student nurses (n=17) at the beginning of their third year of the four-year Bachelor's programme. Data were collected at four Universities of Applied Sciences in the Netherlands, from December 2013 to January 2014. Semi-structured interviews were used to collect the data, using an interview guide. The main reasons for students to become nurses were the caring aspect, personal experiences with healthcare, role models in their immediate environment, and job opportunities. They had both altruistic and professional perceptions of their profession. Reasons for attrition were strongly related to the training programme and to their clinical placements, in particular the perceived lack of support from mentors and team. Feelings of being welcomed and working in a nice team proved to be more important reasons for completing the programme than the specific clinical field. Student nurses started their studies with many dreams, such as caring for people and having the opportunity to deliver excellent nursing care. When their expectations were not met, their dreams became disappointments which caused them to consider stopping and even to leave (attrition). The role of lecturers and mentors seems invaluable in protecting and guiding students through their programme and placements. Optimal cooperation between lecturers and mentors is of paramount importance to retain student nurses in their training programmes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Clinical trials in progressive multiple sclerosis: lessons learned and future perspectives

PubMed Central

Ontaneda, Daniel; Fox, Robert J.; Chataway, Jeremy

2015-01-01

Progressive multiple sclerosis is characterized by the gradual accrual of disability independent of relapses and can occur with disease onset (primary progressive) or preceded by a relapsing disease course (secondary progressive). An effective disease modifying treatment for progressive multiple sclerosis has not been identified, and the results of clinical trials to date have been generally disappointing. Ongoing advances in our understanding of pathogenesis, identification of novel targets for neuro-protection, and improved outcome measures have the potential to lead to effective treatments for progressive multiple sclerosis. In this review lessons learned from previous clinical trials and perspectives from current trials in progressive multiple sclerosis are summarized. Promising clinical, imaging, and biological markers will also be reviewed, along with novel clinical trial designs. PMID:25772899

Leveraging of Open EMR Architecture for Clinical Trial Accrual

PubMed Central

Afrin, Lawrence B.; Oates, James C.; Boyd, Caroline K.; Daniels, Mark S.

2003-01-01

Accrual to clinical trials is a major bottleneck in scientific progress in clinical medicine. Many methods for identifying potential subjects and improving accrual have been pursued; few have succeeded, and none have proven generally reproducible or scalable. We leveraged the open architecture of the core clinical data repository of our electronic medical record system to prototype a solution for this problem in a manner consistent with contemporary regulations and research ethics. We piloted the solution with a local investigator-initiated trial for which candidate identification was expected to be difficult. Key results in the eleven months of experience to date include automated screening of 7,296,708 lab results from 69,288 patients, detection of 1,768 screening tests of interest, identification of 70 potential candidates who met all further automated criteria, and accrual of three candidates to the trial. Hypotheses for this disappointing impact on accrual, and directions for future research, are discussed. PMID:14728125

Gratitude, protective buffering, and cognitive dissonance: How families respond to pediatric whole exome sequencing in the absence of actionable results.

PubMed

Werner-Lin, Allison; Zaspel, Lori; Carlson, Mae; Mueller, Rebecca; Walser, Sarah A; Desai, Ria; Bernhardt, Barbara A

2018-03-01

Clinical genome and exome sequencing (CGES) may identify variants leading to targeted management of existing conditions. Yet, CGES often fails to identify pathogenic diagnostic variants and introduces uncertainties by detecting variants of uncertain significance (VUS) and secondary findings. This study investigated how families understand findings and adjust their perspectives on CGES. As part of NIH's Clinical Sequencing Exploratory Research Consortium, children were recruited from clinics at the Children's Hospital of Pennsylvania (CHOP) and offered exome sequencing. Primary pathogenic and possibly pathogenic, and some secondary findings were returned. Investigators digitally recorded results disclosure sessions and conducted 3-month follow up interviews with 10 adolescents and a parent. An interdisciplinary team coded all transcripts. Participants were initially disappointed with findings, yet reactions evolved within disclosure sessions and at 3-month interviews toward acceptance and satisfaction. Families erroneously expected, and prepared extensively, to learn about risk for common conditions. During disclosure sessions, parents and adolescents varied in how they monitored and responded to each others reactions. Several misinterpreted, or overestimated, the utility of findings to attribute meaning and achieve closure for the CGES experience. Participants perceived testing as an opportunity to improve disease management despite results that did not introduce new treatments or diagnoses. Future research may examine whether families experience cognitive dissonance regarding discrepancies between expectations and findings, and how protective buffering minimizes the burden of disappointment on loved ones. As CGES is increasingly integrated into clinical care providers must contend with tempering family expectations and interpretations of findings while managing complex medical care. © 2018 Wiley Periodicals, Inc.

Ethical challenges in preclinical Alzheimer’s disease observational studies and trials: results of the Barcelona summit

PubMed Central

Molinuevo, José L.; Cami, Jordi; Carné, Xavier; Carrillo, Maria C.; Georges, Jean; Isaac, Maria B.; Khachaturian, Zaven; Kim, Scott Y. H.; Morris, John C.; Pasquier, Florence; Ritchie, Craig; Sperling, Reisa; Karlawish, Jason

2016-01-01

Alzheimer’s disease (AD) is among the most significant healthcare burdens. Disappointing results from clinical trials in late-stage AD persons combined with hopeful results from trials in persons with early-stage suggest that research in the preclinical stage of AD is necessary to define an optimal therapeutic success window. We review the justification for conducting trials in the preclinical stage and highlight novel ethical challenges that arise and are related to determining appropriate risk-benefit ratios and disclosing individuals’ biomarker status. We propose that to conduct clinical trials with these participants, we need to improve public understanding of AD using unified vocabulary, resolve the acceptable risk-benefit ratio in asymptomatic participants and disclose or not biomarker status with attention to study type (observational studies versus clinical trials). Overcoming these challenges will justify clinical trials in preclinical AD at the societal level and aid to the development of societal and legal support for trial participants. PMID:26988427

Novel drugs in clinical development for hepatocellular carcinoma.

PubMed

Waidmann, Oliver; Trojan, Jörg

2015-01-01

Sorafenib is the only systemic drug approved for the treatment of advanced hepatocellular carcinoma (HCC). Within recent years, several investigational agents mainly targeting angiogenesis failed in late-phase clinical development either due to toxicity or lack of benefit. This review covers recent clinical data on systemic agents and ongoing trials in patients with advanced HCC. In unselected patients with advanced HCC, disappointing results have been reported from several large trials. However, in two subgroups encouraging results have been achieved. Treatment with the MET inhibitor tivantinib resulted in a substantial survival benefit in the subgroup of MET overexpressing tumors in a randomized Phase II trial. Furthermore, the vascular endothelial growth factor receptor 2 antibody ramucirumab resulted in improved overall survival in patients with baseline α-fetoprotein (AFP) ≥ 400 ng/ml in a Phase III trial. These two agents, and several others, will be further developed in HCC. Moreover, immunotherapeutics such as checkpoint inhibitors, programmed death receptor-1 blocking antibodies and oncolytic viruses are under investigation in advanced HCC.

Closure of a human tissue biobank: individual, institutional, and field expectations during cycles of promise and disappointment

PubMed Central

Stephens, Neil; Dimond, Rebecca

2015-01-01

Biobanks are increasingly being established to act as mediators between patient-donors and researchers. In practice, some of these will close. This paper details the experiences of one such bank. We report interviews with the bank's staff and oversight group during the period when the bank ceased biobanking activity, reconfigured as a disseminator of best practice, before then closing altogether. The paper makes three distinct contributions: (i) to provide a detailed account of the establishment, operational challenges, and eventual closure of the bank, which makes clear the rapid turnover in a cycle of promise and disappointment; (ii) to explore this in terms of a novel analytical focus upon field, institutional, and individual expectations; and (iii) to use this typology to demonstrate how, even after the bank's closure, aspects of its work were reconfigured and reused in new contexts. This provides a unique empirical analysis of the under-reported issue of biobank closure. PMID:26740793

Granulomatous slack skin. Histopathology diagnosis preceding clinical manifestations by 12 years.

PubMed

Goldsztajn, Karen O; Moritz Trope, Beatriz; Ribeiro Lenzi, Maria Elisa; Cuzzi, Tullia; Ramos-E-Silva, Marcia

2012-12-31

Granulomatous slack skin is a very rare subtype of T-cell cutaneous lymphoma, characterized by the slow development of cutaneous sagging, especially on flexural areas. Its behavior is indolent and the treatment, in the majority of cases, disappointing. We report a 54-year-old black patient with granulomatous slack skin, who at the beginning of the investigation showed intense xeroderma and generalized lymph node enlargement. The diagnosis was established based on histopathologic findings long before the disease's characteristic clinical presentation appeared. During the twelve years of follow-up, the clinical manifestation evolved to marked skin looseness, most predominant in flexural regions, illustrating the clinical hallmark of granulomatous slack skin, long after first histological abnormalities were observed.

The expanding syndrome of amyotrophic lateral sclerosis: a clinical and molecular odyssey

PubMed Central

Turner, Martin R; Swash, Michael

2015-01-01

Recent advances in understanding amyotrophic lateral sclerosis (ALS) have delivered new questions. Disappointingly, the initial enthusiasm for transgenic mouse models of the disease has not been followed by rapid advances in therapy or prevention. Monogenic models may have inadvertently masked the true complexity of the human disease. ALS has evolved into a multisystem disorder, involving a final common pathway accessible via multiple upstream aetiological tributaries. Nonetheless, there is a common clinical core to ALS, as clear today as it was to Charcot and others. We stress the continuing relevance of clinical observations amid the increasing molecular complexity of ALS. PMID:25644224

Factors associated with reporting results for pulmonary clinical trials in ClinicalTrials.gov.

PubMed

Riley, Isaretta L; Boulware, L Ebony; Sun, Jie-Lena; Chiswell, Karen; Que, Loretta G; Kraft, Monica; Todd, Jamie L; Palmer, Scott M; Anderson, Monique L

2018-02-01

Background/aims The Food and Drug Administration Amendments Act mandates that applicable clinical trials report basic summary results to the ClinicalTrials.gov database within 1 year of trial completion or termination. We aimed to determine the proportion of pulmonary trials reporting basic summary results to ClinicalTrials.gov and assess factors associated with reporting. Methods We identified pulmonary clinical trials subject to the Food and Drug Administration Amendments Act (called highly likely applicable clinical trials) that were completed or terminated between 2008 and 2012 and reported results by September 2013. We estimated the cumulative percentage of applicable clinical trials reporting results by pulmonary disease category. Multivariable Cox regression modeling identified characteristics independently associated with results reporting. Results Of 1450 pulmonary highly likely applicable clinical trials, 380 (26%) examined respiratory neoplasms, 238 (16%) asthma, 175 (12%) chronic obstructive pulmonary disease, and 657 (45%) other respiratory diseases. Most (75%) were pharmaceutical highly likely applicable clinical trials and 71% were industry-funded. Approximately 15% of highly likely applicable clinical trials reported results within 1 year of trial completion, while 55% reported results over the 5-year study period. Earlier phase highly likely applicable clinical trials were less likely to report results compared to phase 4 highly likely applicable clinical trials (phases 1/2 and 2 (adjusted hazard ratio 0.41 (95% confidence interval: 0.31-0.54)), phases 2/3 and 3 (adjusted hazard ratio 0.55 (95% confidence interval: 0.42-0.72)) and phase not applicable (adjusted hazard ratio 0.43 (95% confidence interval: 0.29-0.63)). Pulmonary highly likely applicable clinical trials without Food and Drug Administration oversight were less likely to report results compared with those with oversight (adjusted hazard ratio 0.65 (95% confidence interval: 0

What RA patients expect of their treatment--discussion over the result of our survey.

PubMed

Funahashi, Keiko; Matsubara, Tsukasa

2012-11-01

We conducted a survey among Japanese rheumatoid arthritis (RA) patients to better understand what they expect from treatment and whether there is a difference between expectations of biologics-treated and disease-modifying antirheumatic drugs (DMARDs)-treated patients. An anonymous survey was conducted with 165 outpatients from our clinic (with informed written consent). On the survey, they wrote their age, gender, medical history, and commented on: (1) expectations for treatment, (2) disappointment with treatment, (3) experience of, and thoughts about switching treatments, (4) information wanted before starting a new treatment, (5) expectations before administration and noticeable differences after treatment, (6) level of satisfaction with current treatment, and (7) expectations of possible treatments. Patients who had never been treated with DMARDs were excluded from the survey. For "treatment goals before administration," 86 % responded with "assured efficacy," while 73 % responded "suppress joint destruction" or "recover from joint destruction." Also, more patients hoped for "long-lasting efficacy" (67 %) over "fast acting" (41 %), which suggests significance of the long-term improvement of QOL. Related to "disappointment with treatment," patients also felt anxiety over switching treatment for possibilities of not responding enough, or side effects. RA patients have high expectations for medication in terms of assured improvement of conditions and long-lasting efficacy of drugs, while the biggest concern was if they would have side effects or not, and if so, what type. The results suggest patients hope to have worries over switching medications dispelled. The results also verified those who have used biologics before have higher treatment goals than those who have not.

Rosiglitazone: a disappointing DREAM.

PubMed

Nissen, Steven

2007-09-01

Dr Steven Nissen is a heart specialist and currently holds the position of chairman of cardiovascular medicine at the Cleveland Clinic, OH, USA. His work has involved the development of miniaturised ultrasound imaging devices that can be threaded into a patient's heart that allow measurement of the size and composition of plaques, which indicate early artery damage. The ability to characterize and measure the size of plaques provided a novel, effective method to evaluate the efficacy of anticholesterol medications, and for the past two decades Dr Nissen has been using these and other techniques to examine the efficacy of drugs. He has also developed a strong interest in drug safety. His work linked COX-2 inhibitors such as Celebrex and Vioxx (Merck, NJ, USA) with heart attacks, and prevented Merck's similar product, Arcoxia, from being approved. He also highlighted the serious heart attack risk associated with the experimental drug Pargluva and the drug was subsequently not approved by the US FDA. More recently, Dr Nissen's work has focused on the drug rosiglitazone, which was shown to have high cardiovascular risks and has since been given a FDA warning. Here, Dr Nissen discusses the publication of the rosiglitazone meta-analysis and why he considers work in this area to be crucially important for patients.

[Calcifications after intra-disk injection of triamcinolone hexacetonide in lumbar disk hernia. Evaluation of therapeutical results in 3 years].

PubMed

Debiais, F; Bontoux, D; Alcalay, M; Vandermarcq, P; Azais, O; Denis, A; Azais, I; Gasquet, C

1991-10-01

The development of disk or epidural calcifications is a frequent possibility following intra-disk injection of triamcinolone hexacetonide. It was found 10 times in 26 follow-up CT scans obtained 2 to 3 years after the injection. These calcifications are often clinically silent, but they sometimes accompany a recurrence of the initial painful symptomatology. Furthermore, evaluation at 3 years of therapeutic results in a previously published series of patients who had received an intra-disk injection of triamcinolone hexacetonide showed a marked decrease in favourable results (30% vs 67% at 6 months). These two arguments: disappointing long term results and possibility of disk calcifications, are felt by the authors to justify abandoning the technique of triamcinolone hexacetonide by intra-disk injection in the treatment of lumbar disk prolapse.

The road ahead: working towards effective clinical translation of myocardial gene therapies

PubMed Central

Katz, Michael G; Fargnoli, Anthony S; Williams, Richard D; Bridges, Charles R

2014-01-01

During the last two decades the fields of molecular and cellular cardiology, and more recently molecular cardiac surgery, have developed rapidly. The concept of delivering cDNA encoding a therapeutic gene to cardiomyocytes using a vector system with substantial cardiac tropism, allowing for long-term expression of a therapeutic protein, has moved from hypothesis to bench to clinical application. However, the clinical results to date are still disappointing. The ideal gene transfer method should be explored in clinically relevant animal models of heart disease to evaluate the relative roles of specific molecular pathways in disease pathogenesis, helping to validate the potential targets for therapeutic intervention. Successful clinical cardiovascular gene therapy also requires the use of nonimmunogenic cardiotropic vectors capable of expressing the requisite amount of therapeutic protein in vivo and in situ. Depending on the desired application either regional or global myocardial gene delivery is required. Cardiac-specific delivery techniques incorporating mapping technologies for regional delivery and highly efficient methodologies for global delivery should improve the precision and specificity of gene transfer to the areas of interest and minimize collateral organ gene expression. PMID:24341816

Targeting targeted agents: open issues for clinical trial design.

PubMed

Bria, Emilio; Di Maio, Massimo; Carlini, Paolo; Cuppone, Federica; Giannarelli, Diana; Cognetti, Francesco; Milella, Michele

2009-05-22

Molecularly targeted agents for the treatment of solid tumors had entered the market in the last 5 years, with a great impact upon both the scientific community and the society. Many randomized phase III trials conducted in recent years with new targeted agents, despite previous data coming from preclinical research and from phase II trials were often promising, have produced disappointingly negative results. Some other trials have actually met their primary endpoint, demonstrating a statistically significant result favouring the experimental treatment. Unfortunately, with a few relevant exceptions, this advantage is often small, if not negligible, in absolute terms. The difference between statistical significance and clinical relevance should always be considered when translating clinical trials' results in the practice. The reason why this 'revolution' did not significantly impact on cancer treatment to displace chemotherapy from the patient' bedside is in part due to complicated, and in many cases, unknown, mechanisms of action of such drugs; indeed, the traditional way the clinical investigators were used to test the efficacy of 'older' chemotherapeutics, has become 'out of date' from the methodological perspective. As these drugs should be theoretically tailored upon featured bio-markers expressed by the patients, the clinical trial design should follow new rules based upon stronger hypotheses than those developed so far. Indeed, the early phases of basic and clinical drug development are crucial in the correct process which is able to correctly identify the target (when present). Targeted trial designs can result in easier studies, with less, better selected, and supported by stronger proofs of response evidences, patients, in order to not waste time and resources.

[Maraviroc: clinical trials results].

PubMed

Chidiac, C; Katlama, C; Yeni, P

2008-03-01

Just over a decade after identification of chemokine receptors CCR5 and CXCR4 as coreceptors for HIV, maraviroc (Celsentri), the first CCR5 antagonist, has recently obtained its Marketing Authorization in the United States and Europe, for treatment of treatment-experienced adult patients infected with only CCR5-tropic HIV-1 detectable. CCR5 antagonists, after fusion inhibitor enfuvirtide available since 2003, also belong to entry inhibitors. These molecules, unlike previous antiretrovirals, do not target the virus but its target cell by blocking viral penetration. Maraviroc has shown its clinical efficacy in patients failing other antiretroviral classes. Its safety profile was similar to placebo in two large phase III trials. However, careful assessment of both hepatic and immunologic safety of this new therapeutic class is needed. Viral tropism testing has to be investigated before using maraviroc in the clinic, because CCR5 antagonists are not active against CXCR4 viruses. For the moment indicated for the treatment-experienced patient population, maraviroc could in the future benefit to other types of patients, depending on ongoing trials results.

Key issues in the management of patients with systemic lupus erythematosus: latest developments and clinical implications

PubMed Central

Jordan, Natasha; D’Cruz, David

2015-01-01

Systemic lupus erythematous (SLE) is a chronic multisystem disease with significant associated morbidity and mortality. A deeper understanding of the pathogenesis of SLE has led to the development of biologic agents, primarily targeting B cells and others inhibiting costimulatory molecules, type I interferons and cytokines such as interleukin-6. Several of these agents have been studied in clinical trials; some have shown promise while others have yielded disappointing results. Economic and regulatory issues continue to hamper the availability of such therapies for SLE patients. With increasing recognition that recurrent flares of disease activity lead to long-term damage accrual, one of the most important recent developments in patient management has been the concept of treat-to-target in SLE while minimizing patient exposure to excessive corticosteroid and other immunosuppressive therapy. This article reviews these key issues in SLE management, outlining recent developments and clinical implications for patients. PMID:26622325

Compliance with results reporting at ClinicalTrials.gov.

PubMed

Anderson, Monique L; Chiswell, Karen; Peterson, Eric D; Tasneem, Asba; Topping, James; Califf, Robert M

2015-03-12

The Food and Drug Administration Amendments Act (FDAAA) mandates timely reporting of results of applicable clinical trials to ClinicalTrials.gov. We characterized the proportion of applicable clinical trials with publicly available results and determined independent factors associated with the reporting of results. Using an algorithm based on input from the National Library of Medicine, we identified trials that were likely to be subject to FDAAA provisions (highly likely applicable clinical trials, or HLACTs) from 2008 through 2013. We determined the proportion of HLACTs that reported results within the 12-month interval mandated by the FDAAA or at any time during the 5-year study period. We used regression models to examine characteristics associated with reporting at 12 months and throughout the 5-year study period. From all the trials at ClinicalTrials.gov, we identified 13,327 HLACTs that were terminated or completed from January 1, 2008, through August 31, 2012. Of these trials, 77.4% were classified as drug trials. A total of 36.9% of the trials were phase 2 studies, and 23.4% were phase 3 studies; 65.6% were funded by industry. Only 13.4% of trials reported summary results within 12 months after trial completion, whereas 38.3% reported results at any time up to September 27, 2013. Timely reporting was independently associated with factors such as FDA oversight, a later trial phase, and industry funding. A sample review suggested that 45% of industry-funded trials were not required to report results, as compared with 6% of trials funded by the National Institutes of Health (NIH) and 9% of trials that were funded by other government or academic institutions. Despite ethical and legal obligations to disclose findings promptly, most HLACTs did not report results to ClinicalTrials.gov in a timely fashion during the study period. Industry-funded trials adhered to legal obligations more often than did trials funded by the NIH or other government or academic

Can non‐clinical repolarization assays predict the results of clinical thorough QT studies? Results from a research consortium

PubMed Central

Park, Eunjung; Gintant, Gary A; Bi, Daoqin; Kozeli, Devi; Pettit, Syril D; Skinner, Matthew; Willard, James; Wisialowski, Todd; Koerner, John; Valentin, Jean‐Pierre

2018-01-01

Background and Purpose Translation of non‐clinical markers of delayed ventricular repolarization to clinical prolongation of the QT interval corrected for heart rate (QTc) (a biomarker for torsades de pointes proarrhythmia) remains an issue in drug discovery and regulatory evaluations. We retrospectively analysed 150 drug applications in a US Food and Drug Administration database to determine the utility of established non‐clinical in vitro IKr current human ether‐à‐go‐go‐related gene (hERG), action potential duration (APD) and in vivo (QTc) repolarization assays to detect and predict clinical QTc prolongation. Experimental Approach The predictive performance of three non‐clinical assays was compared with clinical thorough QT study outcomes based on free clinical plasma drug concentrations using sensitivity and specificity, receiver operating characteristic (ROC) curves, positive (PPVs) and negative predictive values (NPVs) and likelihood ratios (LRs). Key Results Non‐clinical assays demonstrated robust specificity (high true negative rate) but poor sensitivity (low true positive rate) for clinical QTc prolongation at low‐intermediate (1×–30×) clinical exposure multiples. The QTc assay provided the most robust PPVs and NPVs (ability to predict clinical QTc prolongation). ROC curves (overall test accuracy) and LRs (ability to influence post‐test probabilities) demonstrated overall marginal performance for hERG and QTc assays (best at 30× exposures), while the APD assay demonstrated minimal value. Conclusions and Implications The predictive value of hERG, APD and QTc assays varies, with drug concentrations strongly affecting translational performance. While useful in guiding preclinical candidates without clinical QT prolongation, hERG and QTc repolarization assays provide greater value compared with the APD assay. PMID:29181850

A Urinalysis Result Reporting System for a Clinical Laboratory

PubMed Central

Sullivan, James E.; Plexico, Perry S.; Blank, David W.

1987-01-01

A menu driven Urinalysis Result Reporting System based on multiple IBM-PC Workstations connected together by a local area network was developed for the Clinical Chemistry Section of the Clinical Pathology Department at the National Institutes of Health's Clinical Center. Two Network File Servers redundantly save the test results of each urine specimen. When all test results for a specimen are entered into the system, the results are transmitted to the Department's Laboratory Computer System where they are made available to the ordering physician. The Urinalysis Data Management System has proven easy to learn and use.

Transcatheter vessel occlusion: angiographic results versus clinical success

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

Feldman, L.; Greenfield, A.J.; Waltman, A.C.

1983-04-01

A review was made of 219 transcatheter vessel occlusion procedures performed over a ten-year period for control of hemorrhage, tumor palliation, or blood supply redistribution prior to intra-arterial chemotherapy. Complete angiographic success was obtained in 85% of the procedures, with partial success in 8%; complete clinical success was achieved in 53% of patients, with partial success in 23%. the most satisfactory clinical results were obtained with hemorrhagic gastritis and pelvic trauma. Embolizations for duodenal ulcer hemorrhage and transhepatic variceal occlusion were the least clinically successful, although isobutyl-cyanoacrylate appeared to be a significant improvement in angiographic therapy for duodenal ulcer. Themore » overall complication rate was 13%, with one third of the complications clinically silent. These results indicate that transcatheter vessel occlusion is a relatively safe and effective method for control of hemorrhage or tumor infarction.« less

Linking ClinicalTrials.gov and PubMed to Track Results of Interventional Human Clinical Trials

PubMed Central

Huser, Vojtech; Cimino, James J.

2013-01-01

Objective In an effort to understand how results of human clinical trials are made public, we analyze a large set of clinical trials registered at ClinicalTrials.gov, the world’s largest clinical trial registry. Materials and Methods We considered two trial result artifacts: (1) existence of a trial result journal article that is formally linked to a registered trial or (2) the deposition of a trial’s basic summary results within the registry. Results The study sample consisted of 8907 completed, interventional, phase 2-or-higher clinical trials that were completed in 2006-2009. The majority of trials (72.2%) had no structured trial-article link present. A total of 2367 trials (26.6%) deposited basic summary results within the registry. Of those , 969 trials (10.9%) were classified as trials with extended results and 1398 trials (15.7%) were classified as trials with only required basic results. The majority of the trials (54.8%) had no evidence of results, based on either linked result articles or basic summary results (silent trials), while a minimal number (9.2%) report results through both registry deposition and publication. Discussion Our study analyzes the body of linked knowledge around clinical trials (which we refer to as the “trialome”). Our results show that most trials do not report results and, for those that do, there is minimal overlap in the types of reporting. We identify several mechanisms by which the linkages between trials and their published results can be increased. Conclusion Our study shows that even when combining publications and registry results, and despite availability of several information channels, trial sponsors do not sufficiently meet the mandate to inform the public either via a linked result publication or basic results submission. PMID:23874614

A UML approach to process modelling of clinical practice guidelines for enactment.

PubMed

Knape, T; Hederman, L; Wade, V P; Gargan, M; Harris, C; Rahman, Y

2003-01-01

Although clinical practice guidelines (CPGs) have been suggested as a means of encapsulating best practice in evidence-based medical treatment, their usage in clinical environments has been disappointing. Criticisms of guideline representations have been that they are predominantly narrative and are difficult to incorporate into clinical information systems. This paper analyses the use of UML process modelling techniques for guideline representation and proposes the automated generation of executable guidelines using XMI. This hybrid UML-XMI approach provides flexible authoring of guideline decision and control structures whilst integrating appropriate data flow. It also uses an open XMI standard interface to allow the use of authoring tools and process control systems from multiple vendors. The paper first surveys CPG modelling formalisms followed by a brief introduction to process modelling in UMI. Furthermore, the modelling of CPGs in UML is presented leading to a case study of encoding a diabetes mellitus CPG using UML.

Clinical challenges in thyroid disease: Time for a new approach?

PubMed

Juby, A G; Hanly, M G; Lukaczer, D

2016-05-01

Thyroid disease is common, and the prevalence is rising. Traditional diagnosis and monitoring relies on thyroid stimulating hormone (TSH) levels. This does not always result in symptomatic improvement in hypothyroid symptoms, to the disappointment of both patients and physicians. A non-traditional therapeutic approach would include evaluation of GI function as well as a dietary history and micronutrient evaluation. This approach also includes assessment of thyroid peroxidase (TPO) antibodies, T3, T4, and reverse T3 levels, and in some cases may require specific T3 supplementation in addition to standard T4 therapy. Both high and low TSH levels on treatment are associated with particular medical risks. In the case of high TSH this is primarily cardiac, whereas for low TSH it is predominantly bone health. This article discusses these important clinical issues in more detail, with some practical tips especially for an approach to the "non-responders" to the current traditional therapeutic approach. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Clinical role of non-invasive assessment of portal hypertension.

PubMed

Bolognesi, Massimo; Di Pascoli, Marco; Sacerdoti, David

2017-01-07

Measurement of portal pressure is pivotal in the evaluation of patients with liver cirrhosis. The measurement of the hepatic venous pressure gradient represents the reference method by which portal pressure is estimated. However, it is an invasive procedure that requires significant hospital resources, including experienced staff, and is associated with considerable cost. Non-invasive methods that can be reliably used to estimate the presence and the degree of portal hypertension are urgently needed in clinical practice. Biochemical and morphological parameters have been proposed for this purpose, but have shown disappointing results overall. Splanchnic Doppler ultrasonography and the analysis of microbubble contrast agent kinetics with contrast-enhanced ultrasonography have shown better accuracy for the evaluation of patients with portal hypertension. A key advancement in the non-invasive evaluation of portal hypertension has been the introduction in clinical practice of methods able to measure stiffness in the liver, as well as stiffness/congestion in the spleen. According to the data published to date, it appears to be possible to rule out clinically significant portal hypertension in patients with cirrhosis ( i.e ., hepatic venous pressure gradient ≥ 10 mmHg) with a level of clinically-acceptable accuracy by combining measurements of liver stiffness and spleen stiffness along with Doppler ultrasound evaluation. It is probable that the combination of these methods may also allow for the identification of patients with the most serious degree of portal hypertension, and ongoing research is helping to ensure progress in this field.

Clinical role of non-invasive assessment of portal hypertension

PubMed Central

Bolognesi, Massimo; Di Pascoli, Marco; Sacerdoti, David

2017-01-01

Measurement of portal pressure is pivotal in the evaluation of patients with liver cirrhosis. The measurement of the hepatic venous pressure gradient represents the reference method by which portal pressure is estimated. However, it is an invasive procedure that requires significant hospital resources, including experienced staff, and is associated with considerable cost. Non-invasive methods that can be reliably used to estimate the presence and the degree of portal hypertension are urgently needed in clinical practice. Biochemical and morphological parameters have been proposed for this purpose, but have shown disappointing results overall. Splanchnic Doppler ultrasonography and the analysis of microbubble contrast agent kinetics with contrast-enhanced ultrasonography have shown better accuracy for the evaluation of patients with portal hypertension. A key advancement in the non-invasive evaluation of portal hypertension has been the introduction in clinical practice of methods able to measure stiffness in the liver, as well as stiffness/congestion in the spleen. According to the data published to date, it appears to be possible to rule out clinically significant portal hypertension in patients with cirrhosis (i.e., hepatic venous pressure gradient ≥ 10 mmHg) with a level of clinically-acceptable accuracy by combining measurements of liver stiffness and spleen stiffness along with Doppler ultrasound evaluation. It is probable that the combination of these methods may also allow for the identification of patients with the most serious degree of portal hypertension, and ongoing research is helping to ensure progress in this field. PMID:28104976

Training and capacity building evaluation: Maximizing resources and results with Success Case Method.

PubMed

Medina, L; Acosta-Pérez, E; Velez, C; Martínez, G; Rivera, M; Sardiñas, L; Pattatucci, A

2015-10-01

This article describes the use of Success Case Method (Brinkerhoff, 2003) to evaluate health promotion and public health training programs. The goal of the Office Community Research and Engagement (OCRE) of the Puerto Rico Clinical and Translational Research Consortium (PRCTRC) is to establish a stable and sustainable translational research capacity. Early efforts toward achieving this goal included sponsoring two independent research training programs. A description of the implementation of the five step Success Case Method is presented. Results reveal that SCM would deem both trainings as highly successful, based upon the overall impact of a low number of success cases. However, a traditional summative evaluation would consider this disappointing. Strengths of SCM are discussed. It was concluded that the Success Case Method is a useful and valuable evaluative method for measuring the success of health promotion and public health training initiatives and provides sufficient information for decision-making processes. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Role of the Insulin/IGF System in Cancer: Lessons Learned from Clinical Trials and the Energy Balance-Cancer Link

PubMed Central

Bowers, Laura W.; Rossi, Emily L.; O’Flanagan, Ciara H.; deGraffenried, Linda A.; Hursting, Stephen D.

2015-01-01

Numerous epidemiological and pre-clinical studies have demonstrated that the insulin/insulin-like growth factor (IGF) system plays a key role in the development and progression of several types of cancer. Insulin/IGF signaling, in cooperation with chronic low-grade inflammation, is also an important contributor to the cancer-promoting effects of obesity. However, clinical trials for drugs targeting different components of this system have produced largely disappointing results, possibly due to the lack of predictive biomarker use and problems with the design of combination therapy regimens. With careful attention to the identification of likely patient responders and optimal drug combinations, the outcome of future trials may be improved. Given that insulin/IGF signaling is known to contribute to obesity-associated cancer, further investigation regarding the efficacy of drugs targeting this system and its downstream effectors in the obese patient population is warranted. PMID:26029167

A Comparison of Expectations of Physicians and Patients with Chronic Pain for Pain Clinic Visits.

PubMed

Calpin, Pádraig; Imran, Ather; Harmon, Dominic

2017-03-01

The patient-physician encounter forms the cornerstone of every health service. However, optimal medical outcomes are often confounded by inadequate patient-physician communication. Chronic pain is estimated to affect over 25% of the population. Its effects are multifaceted with patients at increased risk of experiencing emotional and functional disturbances. Therefore, it is crucial to address all components of the patient's pain experience, including beliefs and expectations. It is our understanding that no other study to date has evaluated the expectations of physicians and compared them to those of patients for pain clinic visits. We sought to describe and compare expectations of chronic pain patients and their physicians during a clinic consultation. We performed a retrospective review on patients attending the pain clinic for the first time who were enrolled and completed a questionnaire asking their expectations for their clinic visit as well as outcomes that would satisfy and disappoint them. Pain physicians were also included. We compared physicians' to patients' responses and evaluated relationships between patient responses and age, gender, pain location, Pain Self-Efficacy, Pain Catastrophizing Scale, and the Hospital Anxiety and Depression Scale. One hundred chronic pain patients and 10 pain physicians were surveyed. Patients' clinical expectations for visits focused primarily on some pain relief (34%), education on the cause of pain (24%), and a definitive diagnosis (18%). Physician's expectations included formulation and communication of a management plan (70%), patient assessment for cause of pain (50%), and the education of patients on the cause of pain (40%) as important aims. Pain relief would satisfy the majority of patients (74%) and physicians (70%). No improvement would cause greatest dissatisfaction for patients (52%), but causing more harm would be disappointing to physicians (50%). Gender, age, pain location, and sleep quality all

Cough: an unmet clinical need

PubMed Central

Dicpinigaitis, Peter V

2011-01-01

Cough is among the most common complaints for which patients worldwide seek medical attention. Thus, the evaluation and treatment of cough result in tremendous financial expenditure and consumption of health care resources. Yet, despite the clinical significance of cough, research efforts aimed at improving diagnostic capabilities and developing more effective therapeutic agents have been, to date, disappointing in their limited scope and outcomes. Acute cough due to the common cold represents the most common type of cough. Currently, available medications for the symptomatic management of acute cough are inadequate due to lack of proven efficacy and/or their association with undesirable or intolerable side effects at anti-tussive doses. Subacute cough, often representing a prolonged post-viral response, is typically refractory to standard anti-tussive therapy. Few clinical trials have evaluated therapeutic options for subacute cough. Diagnostic challenges facing the clinician in the management of chronic cough include the determination of whether symptoms of upper airway cough syndrome (formerly, postnasal drip syndrome) or gastro-oesophageal reflux disease are indeed the underlying cause of cough. Chronic, refractory unexplained (formerly, idiopathic) cough must be distinguished from cough that has not been fully evaluated and treated according to current guideline recommendations. Eagerly awaited are new safe and effective anti-tussive agents for use when cough suppression is desired, regardless of underlying aetiology of cough, as well as practical, validated ambulatory cough counters to aid clinical assessment and future research in the field of cough. LINKED ARTICLES This article is part of a themed issue on Respiratory Pharmacology. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.163.issue-1 PMID:21198555

The ClinicalTrials.gov results database--update and key issues.

PubMed

Zarin, Deborah A; Tse, Tony; Williams, Rebecca J; Califf, Robert M; Ide, Nicholas C

2011-03-03

The ClinicalTrials.gov trial registry was expanded in 2008 to include a database for reporting summary results. We summarize the structure and contents of the results database, provide an update of relevant policies, and show how the data can be used to gain insight into the state of clinical research. We analyzed ClinicalTrials.gov data that were publicly available between September 2009 and September 2010. As of September 27, 2010, ClinicalTrials.gov received approximately 330 new and 2000 revised registrations each week, along with 30 new and 80 revised results submissions. We characterized the 79,413 registry and 2178 results of trial records available as of September 2010. From a sample cohort of results records, 78 of 150 (52%) had associated publications within 2 years after posting. Of results records available publicly, 20% reported more than two primary outcome measures and 5% reported more than five. Of a sample of 100 registry record outcome measures, 61% lacked specificity in describing the metric used in the planned analysis. In a sample of 700 results records, the mean number of different analysis populations per study group was 2.5 (median, 1; range, 1 to 25). Of these trials, 24% reported results for 90% or less of their participants. ClinicalTrials.gov provides access to study results not otherwise available to the public. Although the database allows examination of various aspects of ongoing and completed clinical trials, its ultimate usefulness depends on the research community to submit accurate, informative data.

Clinically Evaluated Cancer Drugs Inhibiting Redox Signaling.

PubMed

Kirkpatrick, D Lynn; Powis, Garth

2017-02-20

There are a number of redox-active anticancer agents currently in development based on the premise that altered redox homeostasis is necessary for cancer cell's survival. Recent Advances: This review focuses on the relatively few agents that target cellular redox homeostasis to have entered clinical trial as anticancer drugs. The success rate of redox anticancer drugs has been disappointing compared to other classes of anticancer agents. This is due, in part, to our incomplete understanding of the functions of the redox targets in normal and cancer tissues, leading to off-target toxicities and low therapeutic indexes of the drugs. The field also lags behind in the use biomarkers and other means to select patients who are most likely to respond to redox-targeted therapy. If we wish to derive clinical benefit from agents that attack redox targets, then the future will require a more sophisticated understanding of the role of redox targets in cancer and the increased application of personalized medicine principles for their use. Antioxid. Redox Signal. 26, 262-273.

Clinical Pharmacology and Therapeutics—past, present and future

PubMed Central

Reid, John L.

1997-01-01

Aims To obtain information about the speciality of clinical pharmacology and therapeutics in the United Kingdom. Methods A survey of the views of 26 individuals in academic posts in clinical pharmacology and therapeutics was carried out by postal questionnaire. Response rate was 100%. Results Of 25 assessable responses of 25 centres, there were 35 academic staff of professorial status (median 2, range 0–5) and 61 staff of reader/senior lecturer status (median 2, range 0–5) but only 20 clinical staff in training grades in 19 institutions. All had extensive clinical commitments. Two-thirds of respondents considered that the speciality was stable locally and nationally. However, recruitment of trainees was poor with only 8% of responders having several good applicants for each post and 90% reported that recruitment had deteriorated in the last 5–10 years. Likely good future careers for clinical pharmacologists in training were considered by 75–80% of respondents to likely lie in the pharmaceutical industry or regulatory authorities. Greater flexibility is required to facilitate training in clinical pharmacology and therapeutics. Conclusions Clincal pharmacology and therapeutics in the United Kingdom has a strong academic base but a sub-optimal age structure. Recent experience in recruitment into training posts was disappointing. This may reflect wider problems of recruitment into academic medicine in this country. PMID:9241105

Compliance with mandatory reporting of clinical trial results on ClinicalTrials.gov: cross sectional study.

PubMed

Prayle, Andrew P; Hurley, Matthew N; Smyth, Alan R

2012-01-03

To examine compliance with mandatory reporting of summary clinical trial results (within one year of completion of trial) on ClinicalTrials.gov for studies that fall under the recent Food and Drug Administration Amendments Act (FDAAA) legislation. Registry based study of clinical trial summaries. ClinicalTrials.gov, searched on 19 January 2011, with cross referencing with Drugs@FDA to determine for which trials mandatory reporting was required within one year. Selection criteria Studies registered on ClinicalTrials.gov with US sites which completed between 1 January and 31 December 2009. Proportion of trials for which results had been reported. The ClinicalTrials.gov registry contained 83,579 entries for interventional trials, of which 5642 were completed within the timescale of interest. We identified trials as falling within the mandatory reporting rules if they were covered by the FDAAA (trials of a drug, device, or biological agent, which have at least one US site, and are of phase II or later) and if they investigated a drug that already had approval from the Food and Drug Administration. Of these, 163/738 (22%) had reported results within one year of completion of the trial compared with 76/727 (10%) trials that were not subject to mandatory reporting (95% confidence interval for the difference in proportions 7.8% to 15.5%; χ(2) test, P = 2.6 × 10(-9)). Later phase trials were more likely to report results (P = 4.4 × 10(-11)), as were industry funded trials (P = 2.2 × 10(-16)). Most trials subject to mandatory reporting did not report results within a year of completion.

Correlation of clinical predictions and surgical results in maxillary superior repositioning.

PubMed

Tabrizi, Reza; Zamiri, Barbad; Kazemi, Hamidreza

2014-05-01

This is a prospective study to evaluate the accuracy of clinical predictions related to surgical results in subjects who underwent maxillary superior repositioning without anterior-posterior movement. Surgeons' predictions according to clinical (tooth show at rest and at the maximum smile) and cephalometric evaluation were documented for the amount of maxillary superior repositioning. Overcorrection or undercorrection was documented for every subject 1 year after the operations. Receiver operating characteristic curve test was used to find a cutoff point in prediction errors and to determine positive predictive value (PPV) and negative predictive value. Forty subjects (14 males and 26 females) were studied. Results showed a significant difference between changes in the tooth show at rest and at the maximum smile line before and after surgery. Analysis of the data demonstrated no correlation between the predictive data and the surgical results. The incidence of undercorrection (25%) was more common than overcorrection (7.5%). The cutoff point for errors in predictions was 5 mm for tooth show at rest and 15 mm at the maximum smile. When the amount of the presurgical tooth show at rest was more than 5 mm, 50.5% of clinical predictions did not match the clinical results (PPV), and 75% of clinical predictions showed the same results when the tooth show was less than 5 mm (negative predictive value). When the amount of presurgical tooth shown in the maximum smile line was more than 15 mm, 75% of clinical predictions did not match with clinical results (PPV), and 25% of the predictions had the same results because the tooth show at the maximum smile was lower than 15 mm. Clinical predictions according to the tooth show at rest and at the maximum smile have a poor correlation with clinical results in maxillary superior repositioning for vertical maxillary excess. The risk of errors in predictions increased when the amount of superior repositioning of the maxilla increased

Do clinical safety charts improve paramedic key performance indicator results? (A clinical improvement programme evaluation).

PubMed

Ebbs, Phillip; Middleton, Paul M; Bonner, Ann; Loudfoot, Allan; Elliott, Peter

2012-07-01

Is the Clinical Safety Chart clinical improvement programme (CIP) effective at improving paramedic key performance indicator (KPI) results within the Ambulance Service of New South Wales? The CIP intervention area was compared with the non-intervention area in order to determine whether there was a statistically significant improvement in KPI results. The CIP was associated with a statistically significant improvement in paramedic KPI results within the intervention area. The strategies used within this CIP are recommended for further consideration.

A chance to stop and breathe: participants’ experiences in the North American Opiate Medication Initiative clinical trial

PubMed Central

2014-01-01

Background The North American Opiate Medication Initiative (NAOMI) clinical trial compared the effectiveness of injectable diacetylmorphine (DAM) or hydromorphone (HDM) to oral methadone maintenance treatment (MMT). This study aimed to determine participants’ perceptions of treatment delivered in NAOMI. Methods A qualitative sub-study was conducted with 29 participants (12 female): 18 (62.1%) received injectable DAM or HDM and 11 (37.9%) received MMT. A phenomenological theoretical framework was used. Semi-structured interviews were audio-recorded and transcribed verbatim. A thematic analysis was used over successive phases and was driven by the semantic meanings of the data. Results Participants receiving injectable medications suggested that the supervised delivery model was stringent but provided valuable stability to their lives. Females discussed the adjustment required for the clinical setting, while males focused on the challenging clinic schedule and its impact on employment abilities. Participants receiving MMT described disappointment with being randomized to this treatment; however, positive aspects, including the quick titration time and availability of auxiliary services, were also discussed. Conclusion Treatment with injectable DAM (or HDM) is preferred by participants and considered effective in reducing the burden of opioid dependency. Engaging patients in research regarding their perceptions of treatment provides a comprehensive assessment of treatment needs and barriers. Clinical trial registration NCT00175357 PMID:25262567

Interpreting and Integrating Clinical and Anatomic Pathology Results.

PubMed

Ramaiah, Lila; Hinrichs, Mary Jane; Skuba, Elizabeth V; Iverson, William O; Ennulat, Daniela

2017-01-01

The continuing education course on integrating clinical and anatomical pathology data was designed to communicate the importance of using a weight of evidence approach to interpret safety findings in toxicology studies. This approach is necessary, as neither clinical nor anatomic pathology data can be relied upon in isolation to fully understand the relationship between study findings and the test article. Basic principles for correlating anatomic pathology and clinical pathology findings and for integrating these with other study end points were reviewed. To highlight these relationships, a series of case examples, presented jointly by a clinical pathologist and an anatomic pathologist, were used to illustrate the collaborative effort required between clinical and anatomical pathologists. In addition, the diagnostic utility of traditional liver biomarkers was discussed using results from a meta-analysis of rat hepatobiliary marker and histopathology data. This discussion also included examples of traditional and novel liver and renal biomarker data implementation in nonclinical toxicology studies to illustrate the relationship between discrete changes in biochemistry and tissue morphology.

From ClinicalTrials.gov trial registry to an analysis-ready database of clinical trial results.

PubMed

Cepeda, M Soledad; Lobanov, Victor; Berlin, Jesse A

2013-04-01

The ClinicalTrials.gov web site provides a convenient interface to look up study results, but it does not allow downloading data in a format that can be readily used for quantitative analyses. To develop a system that automatically downloads study results from ClinicalTrials.gov and provides an interface to retrieve study results in a spreadsheet format ready for analysis. Sherlock(®) identifies studies by intervention, population, or outcome of interest and in seconds creates an analytic database of study results ready for analyses. The outcome classification algorithms used in Sherlock were validated against a classification by an expert. Having a database ready for analysis that can be updated automatically, dramatically extends the utility of the ClinicalTrials.gov trial registry. It increases the speed of comparative research, reduces the need for manual extraction of data, and permits answering a vast array of questions.

The ClinicalTrials.gov Results Database — Update and Key Issues

PubMed Central

Zarin, Deborah A.; Tse, Tony; Williams, Rebecca J.; Califf, Robert M.; Ide, Nicholas C.

2011-01-01

BACKGROUND The ClinicalTrials.gov trial registry was expanded in 2008 to include a database for reporting summary results. We summarize the structure and contents of the results database, provide an update of relevant policies, and show how the data can be used to gain insight into the state of clinical research. METHODS We analyzed ClinicalTrials.gov data that were publicly available between September 2009 and September 2010. RESULTS As of September 27, 2010, ClinicalTrials.gov received approximately 330 new and 2000 revised registrations each week, along with 30 new and 80 revised results submissions. We characterized the 79,413 registry and 2178 results of trial records available as of September 2010. From a sample cohort of results records, 78 of 150 (52%) had associated publications within 2 years after posting. Of results records available publicly, 20% reported more than two primary outcome measures and 5% reported more than five. Of a sample of 100 registry record outcome measures, 61% lacked specificity in describing the metric used in the planned analysis. In a sample of 700 results records, the mean number of different analysis populations per study group was 2.5 (median, 1; range, 1 to 25). Of these trials, 24% reported results for 90% or less of their participants. CONCLUSIONS ClinicalTrials.gov provides access to study results not otherwise available to the public. Although the database allows examination of various aspects of ongoing and completed clinical trials, its ultimate usefulness depends on the research community to submit accurate, informative data. PMID:21366476

Predicting pneumococcal community-acquired pneumonia in the emergency department: evaluation of clinical parameters.

PubMed

Huijts, S M; Boersma, W G; Grobbee, D E; Gruber, W C; Jansen, K U; Kluytmans, J A J W; Kuipers, B A F; Palmen, F; Pride, M W; Webber, C; Bonten, M J M

2014-12-01

The aim of this study was to quantify the value of clinical predictors available in the emergency department (ED) in predicting Streptococcus pneumoniae as the cause of community-acquired pneumonia (CAP). A prospective, observational, cohort study of patients with CAP presenting in the ED was performed. Pneumococcal aetiology of CAP was based on either bacteraemia, or S. pneumoniae being cultured from sputum, or urinary immunochromatographic assay positivity, or positivity of a novel serotype-specific urinary antigen detection test. Multivariate logistic regression was used to identify independent predictors and various cut-off values of probability scores were used to evaluate the usefulness of the model. Three hundred and twenty-eight (31.0%) of 1057 patients with CAP had pneumococcal CAP. Nine independent predictors for pneumococcal pneumonia were identified, but the clinical utility of this prediction model was disappointing, because of low positive predictive values or a small yield. Clinical criteria have insufficient diagnostic capacity to predict pneumococcal CAP. Rapid antigen detection tests are needed to diagnose S. pneumoniae at the time of hospital admission. © 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.

PDT in clinics: indications, results, and markets.

PubMed

Patrice, Thierry; Olivier, David; Bourre, Ludovic

2006-01-01

Photodynamic therapy (PDT) is based on the selective light activation of an exogenously given drug to patients. PDT acts mainly on cell membranes either of neovascular endothelial cells or of cancer cells leading to cancer cell death. Six drugs are now marketed based on clinical assays in various indications, which showed a clear cost efficiency as compared to other classical procedures. PDT is easy to handle and can be performed in medical installations fitting the conditions of health care in developing countries. Its cost effectiveness could represent an appropriate solution to the increasing number of cancers of various origin. However despite all the clinical results now available, PDT development remains slow. The reasons for this situation include cost of development, intellectual property, and competition between pharmaceutical companies.

Implementing a sustainable clinical supervision model for Isles nurses in Orkney.

PubMed

Hall, Ian

2018-03-02

The Isles Network of Care (INOC) community nurses work at the extreme of the remote and rural continuum, working mostly as lone practitioners. Following the development of sustainable clinical supervision model for Isles nurses in Orkney, clinical supervision was found to improve both peer support and governance for this group of isolated staff. A literature overview identified the transition of clinical supervision in general nursing over 24 years from 'carrot' to 'stick'. The study included a questionnaire survey that was sent to the 2017 Queen's Nursing Institute Scotland cohort to elicit information about the nurses' experience of clinical supervision. The survey found that 55% provide supervision and 40% receive it. Health board encouragement of its use was found to be disappointingly low at 40%. The INOC nurses were surveyed about the new peer-support (restorative) model, which relies on video-conference contact to allow face to face interaction between isolated isles nurses. Feedback prompted a review of clinical supervision pairings, and the frequency and methods of meeting. The need for supervisor training led to agreement with the Remote and Rural Health Education Alliance to provide relevant support. The perceived benefits of supervision included increased support and reflection, and improved relationships with isolated colleagues.

Comparison of clinical diagnosis and microbiological test results in vaginal infections.

PubMed

Karaca, M; Bayram, A; Kocoglu, M E; Gocmen, A; Eksi, F

2005-01-01

Lower genital tract infections continue to be a problem due to the fact that the clinical diagnosis is usually inadequate, and subsequent care is suboptimal. This study aimed at evaluating the accuracy of clinical diagnosis by comparing it with microbiologic test results, and to determine the causative agents of vaginal infections. Sixty-seven nonpregnant women (18-45 years of age) with the clinical diagnosis of lower genital tract infection were enrolled in the study. Patients were not included if they had a history of vaginal infection during the previous three-month period or intrauterine device. The clinical diagnosis was based on the combinations of symptoms, direct observation of wet mount, homogeneous discharge, vaginal pH > 4.5, and detection of the amine odor after exposure of vaginal secretions to 10% KOH. Vaginal samples were taken with two cotton swabs, one was used for pH determination, and the second was utilized for microbiological tests. Gram staining and cultures with Sabouraud agar and chocolate agar were performed for microbiological diagnosis, and the results were compared. The clinical diagnoses included 26 (38.8%) candidiasis, 18 (26.8%) bacterial vaginosis, three (4.5%) trichomoniasis, and 20 (29.9%) mixed vaginal infections. Of the 26 patients with clinical diagnoses of candidiasis, 12 (46.1%) revealed Candiada albicans, nine (34.6) patients revealed microorganisms other than candida species, and five (19.2%) patients had no growth. Five (27.8%) bacterial vaginosis patients revealed Gardnarella vaginalis and 12 patients (66.6%) did not grow any microorganism. The overall rate of accurate clinical diagnoses confirmed by microbiological test results was 43.2%. Seventeen (43.6) of the 39 microbiological test results correlated with clinical diagnosis, and no growth was observed in 28 (41.8%) cultures. We conclude that the clinical diagnosis of vaginal infection is inadequate and should be confirmed with microbiological testing if the resources

Clinical results in cachexia therapeutics.

PubMed

Crawford, Jeffrey

2016-05-01

This article highlights recent developments in the area of cancer cachexia and therapeutic interventions. Therapeutic interventions in cancer cachexia have been guided by clinical studies focused on the central role of muscle and the increased use of CT imaging to measure the impact of skeletal muscle loss on clinical outcomes. At the translational level, a number of different model systems have emphasized the importance of blockade of tumor-induced inflammation and its potential impact on reversing the cachexia phenotype, including FN14, a receptor in the TNF pathway, as well as the parathyroid hormone-related protein. Clinical studies continue to demonstrate the importance of nutrition and exercise as part of a multimodality approach. Although a number of promising agents are being evaluated, both enobosarm, a selected androgen receptor modulator, and anamorelin, a ghrelin agonist have completed phase III trials. Both agents have shown significant impact on reversal of skeletal muscle loss, but inconsistent effect on physical function improvement. Anamorelin also has a positive effect on appetite and weight gain. Further analysis of these studies, along with regulatory guidance, will be critical in the further development of these and other promising agents in the clinical management of patients with cancer cachexia.

Apolipoprotein B synthesis inhibition: results from clinical trials.

PubMed

Visser, Maartje E; Kastelein, John J P; Stroes, Erik S G

2010-08-01

Mipomersen is a second-generation antisense oligonucleotide developed to inhibit the synthesis of apolipoprotein B-100 in the liver. In this review we will summarize the results of recent preclinical and clinical studies addressing safety and low-density lipoprotein-cholesterol (LDL-c) lowering efficacy of this new compound. In phase 3 clinical trials, mipomersen has been shown to significantly reduce LDL-c in patients with homozygous and heterozygous familial hypercholesterolemia on maximally tolerated lipid-lowering therapy. Injection site reactions, flu-like symptoms and increases in liver transaminases were the main adverse events. A recent safety study, designed to investigate the effects of mipomersen on intrahepatic triglyceride content, failed to show evidence of clinically relevant hepatic steatosis after 13 weeks of treatment. Mipomersen is a new agent to lower LDL-c in patients at increased risk of cardiovascular disease and/or intolerant to statins. Whereas safety concerns have focused on hepatic fat accumulation, to date no evidence of clinically relevant increases of intrahepatic triglyceride content are reported. Ongoing and future studies are eagerly awaited to assess the impact of mipomersen on hepatic triglyceride content after prolonged exposure.

The contribution of clinical neurophysiology to the comprehension of the tension-type headache mechanisms.

PubMed

Rossi, Paolo; Vollono, Catello; Valeriani, Massimiliano; Sandrini, Giorgio

2011-06-01

So far, clinical neurophysiological studies on tension-type headache (TTH) have been conducted with two main purposes: (1) to establish whether some neurophysiological parameters may act as markers of TTH, and (2) to investigate the physiopathology of TTH. With regard to the first point, the present results are disappointing, since some abnormalities found in TTH patients may be frequently observed also in migraineurs. On the other hand, clinical neurophysiology has played an important role in the debate about the pathogenesis of TTH. Studies on the exteroceptive suppression of the temporalis muscle contraction have detected a dysfunction of the brainstem excitability and of its suprasegmental control. A similar conclusion has been reached by using the trigeminocervical reflexes, whose abnormalities in TTH have suggested a reduced inhibitory activity of brainstem interneurons, reflecting abnormal endogenous pain control mechanisms. It is interesting that the neural excitability abnormality in TTH seems to be a generalized phenomenon, not limited to the cranial districts. Defective DNIC-like mechanisms have indeed been evidenced also in somatic districts by nociceptive flexion reflex studies. Unfortunately, most neurophysiological studies on TTH are marred by serious methodological flaws, which should be avoided in future researches, in order to better clarify the TTH mechanisms. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Reverse shoulder arthroplasty in 3 and 4 part proximal humeral fractures in patients aged more than 65 years: Results and complications.

PubMed

Villodre-Jiménez, J; Estrems-Díaz, V; Diranzo-García, J; Bru-Pomer, A

The treatment of 3and 4 part proximal humeral fractures in elderly patients is still controversial. The frequent co-existence of poor quality bone and rotator cuff abnormalities in patients with multiple clinical conditions and with difficulties for physical rehabilitation leads to disappointing clinical results, even when the radiological images are acceptable. To evaluate the clinical, radiological, and functional results in patients over 65 years old with complex proximal humerus fractures treated with reverse shoulder arthroplasty. A prospective review was carried out on 30 patients (26 women and 4 men) with proximal humeral fractures treated with reverse shoulder arthroplasty in our department. The mean age was 74.9 years (SD=6.3), and the mean follow-up was 34.5 months (SD=19.3). Clinical and functional results were acceptable, with a mean forward flexion of 124° and a mean external rotation of 13°. The mean abbreviated Constant abbreviated score was 49.1 (SD=14.1), 27 (SD=6.3) in the UCLA scale, and 32.2 (SD=19.2) in the QuickDASH questionnaire. The large majority (80%) of the patients are pain free, and they do not need medication to do daily activities. The complication rate was 13.3%. We consider that reverse shoulder arthroplasty is a valid option to treat 3and 4 part proximal humeral fractures in elderly patients. The surgical goals should include the anatomical reconstruction of the tuberosities, avoiding enlargement of the operated arm greater than 2cm. Copyright © 2016 SECOT. Publicado por Elsevier España, S.L.U. All rights reserved.

Reporting discrepancies between the ClinicalTrials.gov results database and peer-reviewed publications.

PubMed

Hartung, Daniel M; Zarin, Deborah A; Guise, Jeanne-Marie; McDonagh, Marian; Paynter, Robin; Helfand, Mark

2014-04-01

ClinicalTrials.gov requires reporting of result summaries for many drug and device trials. To evaluate the consistency of reporting of trials that are registered in the ClinicalTrials.gov results database and published in the literature. ClinicalTrials.gov results database and matched publications identified through ClinicalTrials.gov and a manual search of 2 electronic databases. 10% random sample of phase 3 or 4 trials with results in the ClinicalTrials.gov results database, completed before 1 January 2009, with 2 or more groups. One reviewer extracted data about trial design and results from the results database and matching publications. A subsample was independently verified. Of 110 trials with results, most were industry-sponsored, parallel-design drug studies. The most common inconsistency was the number of secondary outcome measures reported (80%). Sixteen trials (15%) reported the primary outcome description inconsistently, and 22 (20%) reported the primary outcome value inconsistently. Thirty-eight trials inconsistently reported the number of individuals with a serious adverse event (SAE); of these, 33 (87%) reported more SAEs in ClinicalTrials.gov. Among the 84 trials that reported SAEs in ClinicalTrials.gov, 11 publications did not mention SAEs, 5 reported them as zero or not occurring, and 21 reported a different number of SAEs. Among 29 trials that reported deaths in ClinicalTrials.gov, 28% differed from the matched publication. Small sample that included earliest results posted to the database. Reporting discrepancies between the ClinicalTrials.gov results database and matching publications are common. Which source contains the more accurate account of results is unclear, although ClinicalTrials.gov may provide a more comprehensive description of adverse events than the publication. Agency for Healthcare Research and Quality.

Suboptimal Dosing Parameters as Possible Factors in the Negative Phase III Clinical Trials of Progesterone for Traumatic Brain Injury.

PubMed

Howard, Randy B; Sayeed, Iqbal; Stein, Donald G

2017-06-01

To date, outcomes for all Phase III clinical trials for traumatic brain injury (TBI) have been negative. The recent disappointing results of the Progesterone for the Treatment of Traumatic Brain Injury (ProTECT) and Study of a Neuroprotective Agent, Progesterone, in Severe Traumatic Brain Injury (SyNAPSe) Phase III trials for progesterone in TBI have triggered considerable speculation about the reasons for the negative outcomes of these two studies in particular and for those of all previous Phase III TBI clinical trials in general. Among the factors proposed to explain the ProTECT III and SyNAPSe results, the investigators themselves and others have cited: 1) the pathophysiological complexity of TBI itself; 2) issues with the quality and clinical relevance of the preclinical animal models; 3) insufficiently sensitive clinical endpoints; and 4) inappropriate clinical trial designs and strategies. This paper highlights three critical trial design factors that may have contributed substantially to the negative outcomes: 1) suboptimal doses and treatment durations in the Phase II studies; 2) the strategic decision not to perform Phase IIB studies to optimize these variables before initiating Phase III; and 3) the lack of incorporation of the preclinical and Chinese Phase II results, as well as allometric scaling principles, into the Phase III designs. Given these circumstances and the exceptional pleiotropic potential of progesterone as a TBI (and stroke) therapeutic, we are advocating a return to Phase IIB testing. We advocate the incorporation of dose and schedule optimization focused on lower doses and a longer duration of treatment, combined with the addressing of other potential trial design problems raised by the authors in the recently published trial results.

Periosteoplasty for covering gingival recessions: Clinical results

PubMed Central

Virnik, Sascha; Chiari, Friedrich Michael; Gaggl, Alexander

2009-01-01

This is a case series in which a new technique for the surgical treatment of periodontal recessions is presented along with the results of the first clinical trial. A new technique of periodontal flap surgery was performed on 30 patients with severe periodontal recessions of the upper or lower front teeth. Root and soft tissue scaling was carried out with an open approach, then the periosteum was incised and mobilized at the apical part of the mucoperiosteum flap to cover the defect before the mucoperiosteum was reattached and fixed by sutures. Sulcus bleeding, periodontal probing depths, attachment loss and the length of the attached gingiva of the affected teeth were recorded preoperatively and at 3, 6, and 12 months postoperatively. Every clinical parameter was improved by surgery. No sulcus bleeding was observed at any time during the postoperative follow-up. A mean reattachment of 5.5 mm was noticed 12 months postoperatively at a mean probing depth of 0.3 mm. The mean height of the attached gingiva was 0 mm before surgery, 2.3 mm at three and six months postoperatively, and 2.2 mm at 12 months. The periosteum eversion technique is suitable for the treatment of gingival recessions resulting in good gingival function and a clear improvement in aesthetics. PMID:23674900

[Posterosuperior impingement of the shoulder in the athlete: results of arthroscopic debridement in 75 patients].

PubMed

Riand, N; Boulahia, A; Walch, G

2002-02-01

patients were very satisfied, 22 were satisfied and 45 were disappointed. Twelve patients had resumed their sports activities at their former level with loaded arm movement and one patient had interrupted all sports activities. At last follow-up, 22 patient had undergone another surgical procedure: 20 derotation osteotomies of the humerus, one anterior stabilization, one acromioplasty. The notion of posterosuperior impingement is increasingly recognized as the cause of pain in thrower athletes. Loaded arm movements produce a physiological contact between the posteriorsuperior edge of the glenoid cavity and the deep aspect of the rotator cuff. Injury results from repeated loaded arm movements in throwers. In our series, all the patients had at least one lesion, either involving the cuff or the labrum. According to the Snyder classification, 80% of the supraspinatus lesions were grade 1 or grade 2. We did not have any full thickness tears. All patients with a normal cuff were found to have a lesion of the posterosuperior labrum. At arthroscopy, dynamic assessment evidenced an impingement between the supraspinatus (or the infraspinatus) and the labrum or the bony edge of the glenoid cavity. Only three patients had a labral lesion anterior to the biceps insertion that could be considered a type 1 or 2 slap lesion. Unlike earlier reports by others, we had disappointing results after debridement: 60% of the patients were disappointed after the procedure and only 40% were satisfied (22 patients) or very satisfied (8 patients). Patient satisfaction depended greatly on the level of sports activity attained after arthroscopy, the eight very satisfied patients had resumed their former level. None of the professional athletes or those competing at the international level were very satisfied with arthroscopic debridement. There was an inverse relationship between level of competition and patient satisfaction after debridement.

eTACTS: A Method for Dynamically Filtering Clinical Trial Search Results

PubMed Central

Miotto, Riccardo; Jiang, Silis; Weng, Chunhua

2013-01-01

Objective Information overload is a significant problem facing online clinical trial searchers. We present eTACTS, a novel interactive retrieval framework using common eligibility tags to dynamically filter clinical trial search results. Materials and Methods eTACTS mines frequent eligibility tags from free-text clinical trial eligibility criteria and uses these tags for trial indexing. After an initial search, eTACTS presents to the user a tag cloud representing the current results. When the user selects a tag, eTACTS retains only those trials containing that tag in their eligibility criteria and generates a new cloud based on tag frequency and co-occurrences in the remaining trials. The user can then select a new tag or unselect a previous tag. The process iterates until a manageable number of trials is returned. We evaluated eTACTS in terms of filtering efficiency, diversity of the search results, and user eligibility to the filtered trials using both qualitative and quantitative methods. Results eTACTS (1) rapidly reduced search results from over a thousand trials to ten; (2) highlighted trials that are generally not top-ranked by conventional search engines; and (3) retrieved a greater number of suitable trials than existing search engines. Discussion eTACTS enables intuitive clinical trial searches by indexing eligibility criteria with effective tags. User evaluation was limited to one case study and a small group of evaluators due to the long duration of the experiment. Although a larger-scale evaluation could be conducted, this feasibility study demonstrated significant advantages of eTACTS over existing clinical trial search engines. Conclusion A dynamic eligibility tag cloud can potentially enhance state-of-the-art clinical trial search engines by allowing intuitive and efficient filtering of the search result space. PMID:23916863

Evaluating a web-based test results system at an urban STI clinic.

PubMed

Ling, Sarah B; Richardson, Douglas B; Mettenbrink, Christie J; Westergaard, Benton C; Sapp-Jones, Terri D; Crane, Lori A; Nyquist, Ann-Christine; McFarlane, Mary; Kachur, Rachel; Rietmeijer, Cornelis A

2010-04-01

Notifying patients of gonorrhea and chlamydia test results using online services may improve clinic efficiency and increase receipt of test results. This study evaluated the implementation of an online results system in an urban sexually transmitted infections clinic. Using the clinic's electronic medical records system to assess if and how gonorrhea and chlamydia test results were obtained, 3 time periods were examined between December 2007 and April 2009: period 1, six months before initiation of the online results system; Period 2, six months when patients could opt in for online results by creating their own access codes; and Period 3, four months when access codes were assigned. In addition, a survey was conducted to assess reasons for accepting or declining the online results system. A total of 9056 new patient visits were evaluated. During periods 1, 2, and 3, respectively 67%, 67%, and 70% patients received results either online or by telephone (NS). The proportion of patients calling the clinic for results decreased from 67% in period 1, to 51% in period 2, and 36% in period 3 (P < 0.0001). Survey results indicated that patients accepted online results primarily because of the ability to check results anytime of day. Reasons for not accepting results online included lack of Internet access or a preference to receive results via the telephone. The online results system decreased the number of phone calls to the clinic pertaining to STI test results, but had no effect on the overall proportion of patients receiving results.

Standardizing terms for clinical pharmacogenetic test results: consensus terms from the Clinical Pharmacogenetics Implementation Consortium (CPIC)

PubMed Central

Caudle, Kelly E.; Dunnenberger, Henry M.; Freimuth, Robert R.; Peterson, Josh F.; Burlison, Jonathan D.; Whirl-Carrillo, Michelle; Scott, Stuart A.; Rehm, Heidi L.; Williams, Marc S.; Klein, Teri E.; Relling, Mary V.; Hoffman, James M.

2017-01-01

Introduction: Reporting and sharing pharmacogenetic test results across clinical laboratories and electronic health records is a crucial step toward the implementation of clinical pharmacogenetics, but allele function and phenotype terms are not standardized. Our goal was to develop terms that can be broadly applied to characterize pharmacogenetic allele function and inferred phenotypes. Materials and methods: Terms currently used by genetic testing laboratories and in the literature were identified. The Clinical Pharmacogenetics Implementation Consortium (CPIC) used the Delphi method to obtain a consensus and agree on uniform terms among pharmacogenetic experts. Results: Experts with diverse involvement in at least one area of pharmacogenetics (clinicians, researchers, genetic testing laboratorians, pharmacogenetics implementers, and clinical informaticians; n = 58) participated. After completion of five surveys, a consensus (>70%) was reached with 90% of experts agreeing to the final sets of pharmacogenetic terms. Discussion: The proposed standardized pharmacogenetic terms will improve the understanding and interpretation of pharmacogenetic tests and reduce confusion by maintaining consistent nomenclature. These standard terms can also facilitate pharmacogenetic data sharing across diverse electronic health care record systems with clinical decision support. Genet Med 19 2, 215–223. PMID:27441996

Curcumin and Resveratrol in the Management of Cognitive Disorders: What is the Clinical Evidence?

PubMed

Mazzanti, Gabriela; Di Giacomo, Silvia

2016-09-17

A growing body of in vitro and in vivo evidences shows a possible role of polyphenols in counteracting neurodegeneration: curcumin and resveratrol are attractive substances in this regard. In fact, epidemiological studies highlight a neuroprotective effect of turmeric (rhizome of Curcuma longa L.), the main source of curcumin. Moreover, the consumption of red wine, the main source of resveratrol, has been related to a lower risk of developing dementia. In this review, we analyzed the published clinical trials investigating curcumin and resveratrol in the prevention or treatment of cognitive disorders. The ongoing studies were also described, in order to give an overview of the current search on this topic. The results of published trials (five for curcumin, six for resveratrol) are disappointing and do not allow to draw conclusions about the therapeutic or neuroprotective potential of curcumin and resveratrol. These compounds, being capable of interfering with several processes implicated in the early stages of dementia, could be useful in preventing or in slowing down the pathology. To this aim, an early diagnosis using peripheral biomarkers becomes necessary. Furthermore, the potential preventive activity of curcumin and resveratrol should be evaluated in long-term exposure clinical trials, using preparations with high bioavailability and that are well standardized.

eTACTS: a method for dynamically filtering clinical trial search results.

PubMed

Miotto, Riccardo; Jiang, Silis; Weng, Chunhua

2013-12-01

Information overload is a significant problem facing online clinical trial searchers. We present eTACTS, a novel interactive retrieval framework using common eligibility tags to dynamically filter clinical trial search results. eTACTS mines frequent eligibility tags from free-text clinical trial eligibility criteria and uses these tags for trial indexing. After an initial search, eTACTS presents to the user a tag cloud representing the current results. When the user selects a tag, eTACTS retains only those trials containing that tag in their eligibility criteria and generates a new cloud based on tag frequency and co-occurrences in the remaining trials. The user can then select a new tag or unselect a previous tag. The process iterates until a manageable number of trials is returned. We evaluated eTACTS in terms of filtering efficiency, diversity of the search results, and user eligibility to the filtered trials using both qualitative and quantitative methods. eTACTS (1) rapidly reduced search results from over a thousand trials to ten; (2) highlighted trials that are generally not top-ranked by conventional search engines; and (3) retrieved a greater number of suitable trials than existing search engines. eTACTS enables intuitive clinical trial searches by indexing eligibility criteria with effective tags. User evaluation was limited to one case study and a small group of evaluators due to the long duration of the experiment. Although a larger-scale evaluation could be conducted, this feasibility study demonstrated significant advantages of eTACTS over existing clinical trial search engines. A dynamic eligibility tag cloud can potentially enhance state-of-the-art clinical trial search engines by allowing intuitive and efficient filtering of the search result space. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Urinary, sexual, and cosmetic results after puberty in hypospadias repair: current results and trends.

PubMed

Rynja, Sybren P; de Kort, Laetitia M O; de Jong, Tom P V M

2012-11-01

To give an overview of the recently published long-term outcomes of hypospadias surgery performed at childhood, of patients who have had multiple previous repairs, and results of surgery done to treat late complications following hypospadias repair. Urethral function after hypospadias repair is good, but cosmesis based on the patients' opinion, on the long term, was disappointing. Also erectile function was reported to be good, although persisting curvature and ejaculation disorders were mentioned, more evidently in patients with proximal hypospadias. Long-term results using buccal mucosa repairs in hypospadias cripples are good, but the use of tissue expanders may be a good alternative. Late complications of hypospadias repair, such as urethral strictures, are difficult to treat, and have a high failure rate compared to urethroplasty for other reasons. Functional results of hypospadias repair are generally satisfactory in the long term, although improvement must be pursued. Most adult men with a history of hypospadias present themselves with urinary tract symptoms. Cosmesis judged by patients remains rather poor in the long run and better techniques should be found. Preferably, assessment of long-term results should be done by validated test methods for better comparison.

Clinical correlation of biopsy results in patients with temporal arteritis.

PubMed

Yuksel, Volkan; Guclu, Orkut; Tastekin, Ebru; Halici, Umit; Huseyin, Serhat; Inal, Volkan; Canbaz, Suat

2017-11-01

Temporal arteritis is systemic vasculitis of medium and large sized vessels. The lowest incidence rates were reported in Turkey, Japan and Israel. We aimed to investigate the results of patients with biopsy-proven temporal arteritis and those classified according to the American College of Rheumatology criteria from a low-incidence region for temporal arteritis. The results of our study are noteworthy, since there is limited data on pathologic diagnosis of temporal arteritis in Turkey. We studied the medical records, laboratory findings such as erythrocyte sedimentation rate and C-reactive protein levels, biopsy results, and postoperative complications of all the patients operated for temporal artery biopsy at our clinic. We used the computerized laboratory registry that keeps all records of 42 consecutive temporal artery biopsy results from January 2011 to December 2016. The mean age was 66±12.5 years. The most common manifestations on admission were temporal headache, optic neuritis and jaw claudication, respectively. Temporal artery biopsy  results confirmed tempoal arteritis in eight out of 42 (19%) patients. There was no statistically significant difference between biopsy-positive and biopsy-negative groups in terms of sex, age, erythrocyte sedimentation rate, C-reactive protein and biopsy length. We were not able to find a correlation between the analysis of biopsy results and clinical evaluation of patients with temporal arteritis. We suggest that diagnosis of temporal arteritis  depends on clinical suspicion. Laboratory examination results may not be helpful in accurate diagnosis of tempoal arteritis.

[Rotator cuff repair: single- vs double-row. Clinical and biomechanical results].

PubMed

Baums, M H; Kostuj, T; Klinger, H-M; Papalia, R

2016-02-01

The goal of rotator cuff repair is a high initial mechanical stability as a requirement for adequate biological recovery of the tendon-to-bone complex. Notwithstanding the significant increase in publications concerning the topic of rotator cuff repair, there are still controversies regarding surgical technique. The aim of this work is to present an overview of the recently published results of biomechanical and clinical studies on rotator cuff repair using single- and double-row techniques. The review is based on a selective literature research of PubMed, Embase, and the Cochrane Database on the subject of the clinical and biomechanical results of single- and double-row repair. In general, neither the biomechanical nor the clinical evidence can recommend the use of a double-row concept for the treatment for every rotator cuff tear. Only tears of more than 3 cm seem to benefit from better results on both imaging and in clinical outcome studies compared with the use of single-row techniques. Despite a significant increase in publications on the surgical treatment of rotator cuff tears in recent years, the clinical results were not significantly improved in the literature so far. Unique information and algorithms, from which the optimal treatment of this entity can be derived, are still inadequate. Because of the cost-effectiveness and the currently vague evidence, the double-row techniques cannot be generally recommended for the repair of all rotator cuff tears.

Weight management in obese pets: the tailoring concept and how it can improve results.

PubMed

German, Alexander J

2016-10-20

Obesity is now recognised as the most important medical disease in pets worldwide. All current strategies for weight management involve dietary energy restriction with a purpose-formulated diet. Whilst current weight management regimes can be successful, outcomes are often disappointing with the rate of weight loss progressively slowing down as time goes on. Success is most challenging for the most obese dogs and cats that are more likely to discontinue the programme before reaching target weight. To improve outcomes, clinicians must focus carefully on better tailoring programmes, paying particular to setting an appropriate target weight so as to maximise the benefits for the individual. In this opinionated review, the author will discuss findings from recent clinical research studies examining weight management in obese dogs and cats. A strategy for tailoring weight management targets will then be discussed, illustrated with case examples.

Interpretation of Blood Microbiology Results - Function of the Clinical Microbiologist.

PubMed

Kristóf, Katalin; Pongrácz, Júlia

2016-04-01

The proper use and interpretation of blood microbiology results may be one of the most challenging and one of the most important functions of clinical microbiology laboratories. Effective implementation of this function requires careful consideration of specimen collection and processing, pathogen detection techniques, and prompt and precise reporting of identification and susceptibility results. The responsibility of the treating physician is proper formulation of the analytical request and to provide the laboratory with complete and precise patient information, which are inevitable prerequisites of a proper testing and interpretation. The clinical microbiologist can offer advice concerning the differential diagnosis, sampling techniques and detection methods to facilitate diagnosis. Rapid detection methods are essential, since the sooner a pathogen is detected, the better chance the patient has of getting cured. Besides the gold-standard blood culture technique, microbiologic methods that decrease the time in obtaining a relevant result are more and more utilized today. In the case of certain pathogens, the pathogen can be identified directly from the blood culture bottle after propagation with serological or automated/semi-automated systems or molecular methods or with MALDI-TOF MS (matrix-assisted laser desorption-ionization time of flight mass spectrometry). Molecular biology methods are also suitable for the rapid detection and identification of pathogens from aseptically collected blood samples. Another important duty of the microbiology laboratory is to notify the treating physician immediately about all relevant information if a positive sample is detected. The clinical microbiologist may provide important guidance regarding the clinical significance of blood isolates, since one-third to one-half of blood culture isolates are contaminants or isolates of unknown clinical significance. To fully exploit the benefits of blood culture and other (non- culture

Clinical and experimental study of TMJ distraction: preliminary results.

PubMed

Festa, F; Galluccio, G

1998-01-01

A physiotherapeutic approach, with manual maneuvers and/or distraction appliances, is indicated in the treatment of temporomandibular joint disorders (TMDs) to prevent the progressive fibrosis of the muscle fibers. In this article, the authors report preliminary results of experimental and clinical studies conducted to assess the real effect of distraction in temporomandibular joint disorders. The experimental invivo studies confirmed the structural alteration due to compression and distraction on the capsular and condylar tissues. Clinical cases are reported to show the increase of the intraarticular vertical dimension, with a forward and downward movement of the condyles in a more physiologic condition.

Interpreting “statistical hypothesis testing” results in clinical research

PubMed Central

Sarmukaddam, Sanjeev B.

2012-01-01

Difference between “Clinical Significance and Statistical Significance” should be kept in mind while interpreting “statistical hypothesis testing” results in clinical research. This fact is already known to many but again pointed out here as philosophy of “statistical hypothesis testing” is sometimes unnecessarily criticized mainly due to failure in considering such distinction. Randomized controlled trials are also wrongly criticized similarly. Some scientific method may not be applicable in some peculiar/particular situation does not mean that the method is useless. Also remember that “statistical hypothesis testing” is not for decision making and the field of “decision analysis” is very much an integral part of science of statistics. It is not correct to say that “confidence intervals have nothing to do with confidence” unless one understands meaning of the word “confidence” as used in context of confidence interval. Interpretation of the results of every study should always consider all possible alternative explanations like chance, bias, and confounding. Statistical tests in inferential statistics are, in general, designed to answer the question “How likely is the difference found in random sample(s) is due to chance” and therefore limitation of relying only on statistical significance in making clinical decisions should be avoided. PMID:22707861

Corrections of clinical chemistry test results in a laboratory information system.

PubMed

Wang, Sihe; Ho, Virginia

2004-08-01

The recently released reports by the Institute of Medicine, To Err Is Human and Patient Safety, have received national attention because of their focus on the problem of medical errors. Although a small number of studies have reported on errors in general clinical laboratories, there are, to our knowledge, no reported studies that focus on errors in pediatric clinical laboratory testing. To characterize the errors that have caused corrections to have to be made in pediatric clinical chemistry results in the laboratory information system, Misys. To provide initial data on the errors detected in pediatric clinical chemistry laboratories in order to improve patient safety in pediatric health care. All clinical chemistry staff members were informed of the study and were requested to report in writing when a correction was made in the laboratory information system, Misys. Errors were detected either by the clinicians (the results did not fit the patients' clinical conditions) or by the laboratory technologists (the results were double-checked, and the worksheets were carefully examined twice a day). No incident that was discovered before or during the final validation was included. On each Monday of the study, we generated a report from Misys that listed all of the corrections made during the previous week. We then categorized the corrections according to the types and stages of the incidents that led to the corrections. A total of 187 incidents were detected during the 10-month study, representing a 0.26% error detection rate per requisition. The distribution of the detected incidents included 31 (17%) preanalytic incidents, 46 (25%) analytic incidents, and 110 (59%) postanalytic incidents. The errors related to noninterfaced tests accounted for 50% of the total incidents and for 37% of the affected tests and orderable panels, while the noninterfaced tests and panels accounted for 17% of the total test volume in our laboratory. This pilot study provided the rate and

Publication and reporting of clinical trial results: cross sectional analysis across academic medical centers.

PubMed

Chen, Ruijun; Desai, Nihar R; Ross, Joseph S; Zhang, Weiwei; Chau, Katherine H; Wayda, Brian; Murugiah, Karthik; Lu, Daniel Y; Mittal, Amit; Krumholz, Harlan M

2016-02-17

To determine rates of publication and reporting of results within two years for all completed clinical trials registered in ClinicalTrials.gov across leading academic medical centers in the United States. Cross sectional analysis. Academic medical centers in the United States. Academic medical centers with 40 or more completed interventional trials registered on ClinicalTrials.gov. Using the Aggregate Analysis of ClinicalTrials.gov database and manual review, we identified all interventional clinical trials registered on ClinicalTrials.gov with a primary completion date between October 2007 and September 2010 and with a lead investigator affiliated with an academic medical center. The proportion of trials that disseminated results, defined as publication or reporting of results on ClinicalTrials.gov, overall and within 24 months of study completion. We identified 4347 interventional clinical trials across 51 academic medical centers. Among the trials, 1005 (23%) enrolled more than 100 patients, 1216 (28%) were double blind, and 2169 (50%) were phase II through IV. Overall, academic medical centers disseminated results for 2892 (66%) trials, with 1560 (35.9%) achieving this within 24 months of study completion. The proportion of clinical trials with results disseminated within 24 months of study completion ranged from 16.2% (6/37) to 55.3% (57/103) across academic medical centers. The proportion of clinical trials published within 24 months of study completion ranged from 10.8% (4/37) to 40.3% (31/77) across academic medical centers, whereas results reporting on ClinicalTrials.gov ranged from 1.6% (2/122) to 40.7% (72/177). Despite the ethical mandate and expressed values and mission of academic institutions, there is poor performance and noticeable variation in the dissemination of clinical trial results across leading academic medical centers. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go

Smoking cessation results in a clinical lung cancer screening program

PubMed Central

McKee, Andrea B.; Regis, Shawn M.; Wald, Christoph; Flacke, Sebastian; McKee, Brady J.

2016-01-01

Background Lung cancer screening may provide a “teachable moment” for promoting smoking cessation. This study assessed smoking cessation and relapse rates among individuals undergoing follow-up low-dose chest computed tomography (CT) in a clinical CT lung screening program and assessed the influence of initial screening results on smoking behavior. Methods Self-reported smoking status for individuals enrolled in a clinical CT lung screening program undergoing a follow-up CT lung screening exam between 1st February, 2014 and 31st March, 2015 was retrospectively reviewed and compared to self-reported smoking status using a standardized questionnaire at program entry. Point prevalence smoking cessation and relapse rates were calculated across the entire population and compared with exam results. All individuals undergoing screening fulfilled the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology: Lung Cancer Screening v1.2012® high-risk criteria and had an order for CT lung screening. Results A total of 1,483 individuals underwent a follow-up CT lung screening exam during the study interval. Smoking status at time of follow-up exam was available for 1,461/1,483 (98.5%). A total of 46% (678/1,461) were active smokers at program entry. The overall point prevalence smoking cessation and relapse rates were 20.8% and 9.3%, respectively. Prior positive screening exam results were not predictive of smoking cessation (OR 1.092; 95% CI, 0.715–1.693) but were predictive of reduced relapse among former smokers who had stopped smoking for 2 years or less (OR 0.330; 95% CI, 0.143–0.710). Duration of program enrollment was predictive of smoking cessation (OR 0.647; 95% CI, 0.477–0.877). Conclusions Smoking cessation and relapse rates in a clinical CT lung screening program rates are more favorable than those observed in the general population. Duration of participation in the screening program correlated with increased smoking cessation rates

Standardizing terms for clinical pharmacogenetic test results: consensus terms from the Clinical Pharmacogenetics Implementation Consortium (CPIC).

PubMed

Caudle, Kelly E; Dunnenberger, Henry M; Freimuth, Robert R; Peterson, Josh F; Burlison, Jonathan D; Whirl-Carrillo, Michelle; Scott, Stuart A; Rehm, Heidi L; Williams, Marc S; Klein, Teri E; Relling, Mary V; Hoffman, James M

2017-02-01

Reporting and sharing pharmacogenetic test results across clinical laboratories and electronic health records is a crucial step toward the implementation of clinical pharmacogenetics, but allele function and phenotype terms are not standardized. Our goal was to develop terms that can be broadly applied to characterize pharmacogenetic allele function and inferred phenotypes. Terms currently used by genetic testing laboratories and in the literature were identified. The Clinical Pharmacogenetics Implementation Consortium (CPIC) used the Delphi method to obtain a consensus and agree on uniform terms among pharmacogenetic experts. Experts with diverse involvement in at least one area of pharmacogenetics (clinicians, researchers, genetic testing laboratorians, pharmacogenetics implementers, and clinical informaticians; n = 58) participated. After completion of five surveys, a consensus (>70%) was reached with 90% of experts agreeing to the final sets of pharmacogenetic terms. The proposed standardized pharmacogenetic terms will improve the understanding and interpretation of pharmacogenetic tests and reduce confusion by maintaining consistent nomenclature. These standard terms can also facilitate pharmacogenetic data sharing across diverse electronic health care record systems with clinical decision support.Genet Med 19 2, 215-223.

Results of an Oncology Clinical Trial Nurse Role Delineation Study.

PubMed

Purdom, Michelle A; Petersen, Sandra; Haas, Barbara K

2017-09-01

To evaluate the relevance of a five-dimensional model of clinical trial nursing practice in an oncology clinical trial nurse population. 
. Web-based cross-sectional survey.
. Online via Qualtrics.
. 167 oncology nurses throughout the United States, including 41 study coordinators, 35 direct care providers, and 91 dual-role nurses who provide direct patient care and trial coordination.
. Principal components analysis was used to determine the dimensions of oncology clinical trial nursing practice.
. Self-reported frequency of 59 activities.
. The results did not support the original five-dimensional model of nursing care but revealed a more multidimensional model.
. An analysis of frequency data revealed an eight-dimensional model of oncology research nursing, including care, manage study, expert, lead, prepare, data, advance science, and ethics.
. This evidence-based model expands understanding of the multidimensional roles of oncology nurses caring for patients with cancer enrolled in clinical trials.

Civil society perspectives on negative biomedical HIV prevention trial results and implications for future trials.

PubMed

Essack, Zaynab; Koen, Jennifer; Slack, Catherine; Lindegger, Graham; Newman, Peter A

2012-01-01

Community engagement is crucial to ongoing development and testing of sorely needed new biomedical HIV prevention technologies. Yet, negative trial results raise significant challenges for community engagement in HIV prevention trials, including the early termination of the Cellulose Sulfate microbicide trial and two Phase IIb HIV vaccine trials (STEP and Phambili). The present study aimed to explore the perspectives and experiences of civil society organization (CSO) representatives regarding negative HIV prevention trial results and perceived implications for future trials. We conducted in-depth interviews with 14 respondents from a broad range of South African and international CSOs, and analyzed data using thematic analysis. CSO representatives reported disappointment in response to negative trial results, but acknowledged such outcomes as inherent to clinical research. Respondents indicated that in theory negative trial results seem likely to impact on willingness to participate in future trials, but that in practice people in South Africa have continued to volunteer. Negative trial results were described as having contributed to improving ethical standards, and to a re-evaluation of the scientific agenda. Such negative results were identified as potentially impacting on funding for trials and engagement activities. Our findings indicate that trial closures may be used constructively to support opportunities for reflection and renewed vigilance in strategies for stakeholder engagement, communicating trial outcomes, and building research literacy among communities; however, these strategies require sustained resources for community engagement and capacity-building.

Ethical challenges in conducting clinical research in lung cancer

PubMed Central

Tod, Angela M.

2016-01-01

The article examines ethical challenges that arise with clinical lung cancer research focusing on design, recruitment, conduct and dissemination. Design: problems related to equipoise can arise in lung cancer studies. Equipoise is an ethics precondition for RCTs and exists where there is insufficient evidence to decide which of two or more treatments is best. Difficulties arise in deciding what level of uncertainty constitutes equipoise and who should be in equipoise, for example, patients might not be even where clinicians are. Patient and public involvement (PPI) can reduce but not remove the problems. Recruitment: (I) lung cancer studies can be complex, making it difficult to obtain good quality consent. Some techniques can help, such as continuous consent. But researchers should not expect consent to be the sole protection for participants’ welfare. This protection is primarily done elsewhere in the research process, for example, in ethics review; (II) the problem of desperate volunteers: some patients only consent to a trial because it gives them a 50/50 option of the treatment they want and can be disappointed or upset if randomised to the other arm. This is not necessarily unfair, given clinical equipoise. However, it should be avoided where possible, for example, by using alternative trial designs; (III) the so-called problem of therapeutic misconception: this is the idea that patients are mistaken if they enter trials believing this to be in their clinical best interest. We argue the problem is misconceived and relates only to certain health systems. Conduct: lung cancer trials face standard ethical challenges with regard to trial conduct. PPI could be used in decisions about criteria for stopping rules. Dissemination: as in other trial areas, it is important that all results, including negative ones, are reported. We argue also that the role of PPI with regard to dissemination is currently under-developed. PMID:27413698

Intravenous immunoglobulin in neurology--mode of action and clinical efficacy.

PubMed

Lünemann, Jan D; Nimmerjahn, Falk; Dalakas, Marinos C

2015-02-01

Intravenous immunoglobulin (IVIg)-a preparation of polyclonal serum IgG pooled from thousands of blood donors-has been used for nearly three decades, and is proving to be an efficient anti-inflammatory and immunomodulatory treatment for a growing number of neurological diseases. Evidence from controlled clinical trials has established IVIg as a first-line therapy for Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy. IVIg is also an effective rescue therapy in some patients with worsening myasthenia gravis, and is beneficial as a second-line therapy for dermatomyositis and stiff-person syndrome. IVIg has been tested in some neurodegenerative disorders, but a controlled study in Alzheimer disease yielded disappointing results. Despite its widespread use and therapeutic success, the mechanisms of action of IVIg are poorly understood. Several hypotheses, based on the function of either the variable or constant IgG fragments, have been proposed to explain IVIg's immunomodulatory activity. This Review highlights emerging data on the mechanisms of action of IVIg related to its anti-inflammatory activity, especially that involving the cellular Fcγ receptors and Fc glycosylation. We also summarize recent trials in neurological diseases, discuss potential biomarkers of efficacy, offer practical guidelines on administration, and provide a rationale for experimental trials in neuroinflammatory disorders.

Smoking cessation results in a clinical lung cancer screening program.

PubMed

Borondy Kitts, Andrea K; McKee, Andrea B; Regis, Shawn M; Wald, Christoph; Flacke, Sebastian; McKee, Brady J

2016-07-01

Lung cancer screening may provide a "teachable moment" for promoting smoking cessation. This study assessed smoking cessation and relapse rates among individuals undergoing follow-up low-dose chest computed tomography (CT) in a clinical CT lung screening program and assessed the influence of initial screening results on smoking behavior. Self-reported smoking status for individuals enrolled in a clinical CT lung screening program undergoing a follow-up CT lung screening exam between 1st February, 2014 and 31st March, 2015 was retrospectively reviewed and compared to self-reported smoking status using a standardized questionnaire at program entry. Point prevalence smoking cessation and relapse rates were calculated across the entire population and compared with exam results. All individuals undergoing screening fulfilled the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology: Lung Cancer Screening v1.2012(®) high-risk criteria and had an order for CT lung screening. A total of 1,483 individuals underwent a follow-up CT lung screening exam during the study interval. Smoking status at time of follow-up exam was available for 1,461/1,483 (98.5%). A total of 46% (678/1,461) were active smokers at program entry. The overall point prevalence smoking cessation and relapse rates were 20.8% and 9.3%, respectively. Prior positive screening exam results were not predictive of smoking cessation (OR 1.092; 95% CI, 0.715-1.693) but were predictive of reduced relapse among former smokers who had stopped smoking for 2 years or less (OR 0.330; 95% CI, 0.143-0.710). Duration of program enrollment was predictive of smoking cessation (OR 0.647; 95% CI, 0.477-0.877). Smoking cessation and relapse rates in a clinical CT lung screening program rates are more favorable than those observed in the general population. Duration of participation in the screening program correlated with increased smoking cessation rates. A positive exam result correlated with reduced

Interpreting clinical trial results by deductive reasoning: In search of improved trial design.

PubMed

Kurbel, Sven; Mihaljević, Slobodan

2017-10-01

Clinical trial results are often interpreted by inductive reasoning, in a trial design-limited manner, directed toward modifications of the current clinical practice. Deductive reasoning is an alternative in which results of relevant trials are combined in indisputable premises that lead to a conclusion easily testable in future trials. © 2017 WILEY Periodicals, Inc.

Clinical Trial Results Vary Widely, But Always Advance Research | NIH MedlinePlus the Magazine

MedlinePlus

... turn Javascript on. Feature: Clinical Trials Clinical Trial Results Vary Widely, But Always Advance Research Past Issues / ... members met with his surgeon to learn the results: 'When we first met, I told you it ...

Obtaining patient test results from clinical laboratories: a survey of state law for pharmacists.

PubMed

Witry, Matthew J; Doucette, William R

2009-01-01

To identify states with laws that restrict to whom clinical laboratories may release copies of laboratory test results and to describe how these laws may affect pharmacists' ability to obtain patient laboratory test results. Researchers examined state statutes and administrative codes for all 50 states and the District of Columbia at the University of Iowa Law Library between June and July 2007. Researchers also consulted with lawyers, state Clinical Laboratory Improvement Amendments officers, and law librarians. Laws relating to the study objective were analyzed. 34 jurisdictions do not restrict the release of laboratory test results, while 17 states have laws that restrict to whom clinical laboratories can send copies of test results. In these states, pharmacists will have to use alternative sources, such as physician offices, to obtain test results. Pharmacists must consider state law before requesting copies of laboratory test results from clinical laboratories. This may be an issue that state pharmacy associations can address to increase pharmacist access to important patient information.

Predicting HIV RNA virologic outcome at 52-weeks follow-up in antiretroviral clinical trials. The INCAS and AVANTI Study Groups.

PubMed

Raboud, J M; Rae, S; Montaner, J S

2000-08-15

To determine the ability of intermediate plasma viral load (pVL) measurements to predict virologic outcome at 52 weeks of follow-up in clinical trials of antiretroviral therapy. Individual patient data from three clinical trials (INCAS, AVANTI-2 and AVANTI-3) were combined into a single database. Virologic success was defined to be plasma viral load (pVL) <500 copies/ml at week 52. The sensitivity and specificity of intermediate pVL measurements below the limit of detection, 100, 500, 1000, and 5000 copies/ml to predict virologic success were calculated. The sensitivity, specificity, and positive and negative predictive values of a pVL measurement <1000 copies/ml at week 16 to predict virologic outcome at week 52 were 74%, 74%, 48%, and 90%, respectively, for patients on double therapy. For patients on triple therapy, the sensitivity, specificity, and positive and negative predictive values of a pVL measurement <50 copies/ml at week 16 to predict virologic outcome were 68%, 68%, 80%, and 47%, respectively. For patients receiving double therapy, a poor virologic result at an intermediate week of follow-up is a strong indicator of virologic failure at 52 weeks whereas intermediate virologic success is no guarantee of success at 1 year. For patients on triple therapy, disappointing intermediate results do not preclude virologic success at 1 year and intermediate successes are more likely to be sustained.

Auditor recommendations resulting from three clinical audit rounds in Finnish radiology units.

PubMed

Miettunen, Kirsi; Metsälä, Eija

2017-06-01

Background The purpose of clinical audits performed in radiology units is to reduce the radiation dose of patients and staff and to implement evidence-based best practices. Purpose To describe auditor recommendations in three Finnish clinical audit rounds performed in 2002-2014, and to determine if auditor recommendations have had any impact on improving medical imaging practice. Material and Methods The retrospective observational study was performed in radiology units holding a radiation safety license issued by the Finnish Radiation and Nuclear Safety Authority. The data comprised a systematic sample (n = 120) of auditor reports produced in three auditing rounds in these units during the years 2002-2014. The data were analyzed by descriptive methods and by using the Friedman two-way ANOVA test. Results The number of auditor recommendations given varied between clinical audit rounds and according to the type of imaging unit, as well as according to calculation method. Proportionally, the most recommendations in all three clinical audit rounds were given about defining and using quality assurance functions and about guidelines and practices for carrying out procedures involving radiation exposure. Demanding radiology units improved their practices more than basic imaging units towards the third round. Conclusion Auditor recommendations help to address the deficiencies in imaging practices. There is a need to develop uniform guidelines and to provide tutoring for clinical auditors in order to produce comparable clinical audit results.

[Clinical Results of Endoscopic Treatment of Greater Trochanteric Pain Syndrome].

PubMed

Zeman, P; Rafi, M; Skala, P; Zeman, J; Matějka, J; Pavelka, T

2017-01-01

PURPOSE OF THE STUDY This retrospective study aims to present short-term clinical outcomes of endoscopic treatment of patients with greater trochanteric pain syndrome (GTPS). MATERIAL AND METHODS The evaluated study population was composed of a total of 19 patients (16 women, 3 men) with the mean age of 47 years (19-63 years). In twelve cases the right hip joint was affected, in the remaining seven cases it was the left side. The retrospective evaluation was carried out only in patients with greater trochanteric pain syndrome caused by independent chronic trochanteric bursitis without the presence of m. gluteus medius tear not responding to at least 3 months of conservative treatment. In patients from the followed-up study population, endoscopic trochanteric bursectomy was performed alone or in combination with iliotibial band release. The clinical results were evaluated preoperatively and with a minimum follow-up period of 1 year after the surgery (mean 16 months). The Visual Analogue Scale (VAS) for assessment of pain and WOMAC (Western Ontario MacMaster) score were used. In both the evaluated criteria (VAS and WOMAC score) preoperative and postoperative results were compared. Moreover, duration of surgery and presence of postoperative complications were assessed. Statistical evaluation of clinical results was carried out by an independent statistician. In order to compare the parameter of WOMAC score and VAS pre- and post-operatively the Mann-Whitney Exact Test was used. The statistical significance was set at 0.05. RESULTS The preoperative VAS score ranged 5-9 (mean 7.6) and the postoperative VAS ranged 0-5 (mean 2.3). The WOMAC score ranged 56.3-69.7 (mean 64.2) preoperatively and 79.8-98.3 (mean 89.7) postoperatively. When both the evaluated parameters of VAS and WOMAC score were compared in time, a statistically significant improvement (p<0.05) was achieved postoperatively. The mean duration of surgical procedure was 68 minutes. Moreover, in peritrochanteric

Timing and Completeness of Trial Results Posted at ClinicalTrials.gov and Published in Journals

PubMed Central

Riveros, Carolina; Dechartres, Agnes; Perrodeau, Elodie; Haneef, Romana; Boutron, Isabelle; Ravaud, Philippe

2013-01-01

Background The US Food and Drug Administration Amendments Act requires results from clinical trials of Food and Drug Administration–approved drugs to be posted at ClinicalTrials.gov within 1 y after trial completion. We compared the timing and completeness of results of drug trials posted at ClinicalTrials.gov and published in journals. Methods and Findings We searched ClinicalTrials.gov on March 27, 2012, for randomized controlled trials of drugs with posted results. For a random sample of these trials, we searched PubMed for corresponding publications. Data were extracted independently from ClinicalTrials.gov and from the published articles for trials with results both posted and published. We assessed the time to first public posting or publishing of results and compared the completeness of results posted at ClinicalTrials.gov versus published in journal articles. Completeness was defined as the reporting of all key elements, according to three experts, for the flow of participants, efficacy results, adverse events, and serious adverse events (e.g., for adverse events, reporting of the number of adverse events per arm, without restriction to statistically significant differences between arms for all randomized patients or for those who received at least one treatment dose). From the 600 trials with results posted at ClinicalTrials.gov, we randomly sampled 50% (n = 297) had no corresponding published article. For trials with both posted and published results (n = 202), the median time between primary completion date and first results publicly posted was 19 mo (first quartile = 14, third quartile = 30 mo), and the median time between primary completion date and journal publication was 21 mo (first quartile = 14, third quartile = 28 mo). Reporting was significantly more complete at ClinicalTrials.gov than in the published article for the flow of participants (64% versus 48% of trials, p<0.001), efficacy results (79% versus 69%, p = 0

Timing and completeness of trial results posted at ClinicalTrials.gov and published in journals.

PubMed

Riveros, Carolina; Dechartres, Agnes; Perrodeau, Elodie; Haneef, Romana; Boutron, Isabelle; Ravaud, Philippe

2013-12-01

The US Food and Drug Administration Amendments Act requires results from clinical trials of Food and Drug Administration-approved drugs to be posted at ClinicalTrials.gov within 1 y after trial completion. We compared the timing and completeness of results of drug trials posted at ClinicalTrials.gov and published in journals. We searched ClinicalTrials.gov on March 27, 2012, for randomized controlled trials of drugs with posted results. For a random sample of these trials, we searched PubMed for corresponding publications. Data were extracted independently from ClinicalTrials.gov and from the published articles for trials with results both posted and published. We assessed the time to first public posting or publishing of results and compared the completeness of results posted at ClinicalTrials.gov versus published in journal articles. Completeness was defined as the reporting of all key elements, according to three experts, for the flow of participants, efficacy results, adverse events, and serious adverse events (e.g., for adverse events, reporting of the number of adverse events per arm, without restriction to statistically significant differences between arms for all randomized patients or for those who received at least one treatment dose). From the 600 trials with results posted at ClinicalTrials.gov, we randomly sampled 50% (n = 297) had no corresponding published article. For trials with both posted and published results (n = 202), the median time between primary completion date and first results publicly posted was 19 mo (first quartile = 14, third quartile = 30 mo), and the median time between primary completion date and journal publication was 21 mo (first quartile = 14, third quartile = 28 mo). Reporting was significantly more complete at ClinicalTrials.gov than in the published article for the flow of participants (64% versus 48% of trials, p<0.001), efficacy results (79% versus 69%, p = 0.02), adverse events (73% versus 45

Clinical and histopathological results of the adult patients with unilateral cryptorchidism

PubMed Central

Ateş, Ferhat; Soydan, Hasan; Okçelik, Sezgin; Çırakoğlu, Abdullah; Yılmaz, İsmail; Malkoç, Ercan; Karademir, Kenan

2016-01-01

Objective To evaluate the clinical and histopathological results of adult unilateral cryptorchidism patients. Material and methods Data from adult unilateral cryptorchidism patients that underwent orchiectomy in our clinic between between January 2004 and March 2013 were retrospectively evaluated. Patients were divided into three groups as intra-abdominal, inguinal canal and superficial inguinal region according to the location of the undescended testes. Patients were also grouped according to their testicular volume (<4 cc, 4.1–12 cc, and >12 cc). Histopathology results of orchiectomy specimens were classified as follows: 1. Sertoli cells only, testicular atrophy and vanished testis (anorchia) 2. Hypospermatogenesis, and 3. Maturation arrest. Patients were grouped as normospermia, azoospermia and oligo/astheno/teratospermia groups according to semen analysis results. Correlations between testicular localization, testicular size, semen analysis and pathology results were evaluated. Incidental tumor detection rates were also calculated. Results Two hundred and forty-four adult unilateral cryptorchidism patients underwent orchiectomy in our clinic. There was no a significant relationship between location of the testis and testicular pathology results (p=0.707). Most common semen analysis results was normospermia in patients with high testicular volume group however azoospermia and oligoasthenospermia observed commonly in patients with low testicular volume group. There was a significant relationship between testicular volume and semen analysis results (p=0.023). No significant relationship was observed between semen analysis and pathological results (p=0.929). After an evaluation of all factors with possible effects on the semen analysis results, only testicular volume (p=0.036) was found to have a significant impact. Only one case (0.4%) was incidentally diagnosed seminoma after a review of 233 patients with available histopathological results on record

Thoracic sympathectomy for hyperhidrosis: from surgical indications to clinical results

PubMed Central

Araújo, José Augusto

2017-01-01

Sympathectomy and its variations have been performed in thoracic surgery for more than 100 years. However, its indications have undergone profound modifications in this period. Likewise, since then the surgical technique has also evolved dramatically up to the minimally invasive techniques worldwide accessible in present days. Currently, primary hyperhidrosis is, by far, the main indication for thoracic sympathectomy and this procedure is usually carried out thoracoscopically with excellent results. However, until today, hyperhidrosis is a part of thoracic surgery still surrounded by controversy, persisting as an open field over which some confusion still resides regarding its pathophysiology, terms definitions and operative approaches. The aim of this article is to provide a wide but easily comprehensible review of the theme, discussing and clarifying the major concepts with respect to its clinical presentation, all the presently available treatment options and strategies with their potential benefits and risks, the adequate patient selection for sympathectomy, as well as the postoperative clinical results. PMID:28446983

Thoracic sympathectomy for hyperhidrosis: from surgical indications to clinical results.

PubMed

Vannucci, Fernando; Araújo, José Augusto

2017-04-01

Sympathectomy and its variations have been performed in thoracic surgery for more than 100 years. However, its indications have undergone profound modifications in this period. Likewise, since then the surgical technique has also evolved dramatically up to the minimally invasive techniques worldwide accessible in present days. Currently, primary hyperhidrosis is, by far, the main indication for thoracic sympathectomy and this procedure is usually carried out thoracoscopically with excellent results. However, until today, hyperhidrosis is a part of thoracic surgery still surrounded by controversy, persisting as an open field over which some confusion still resides regarding its pathophysiology, terms definitions and operative approaches. The aim of this article is to provide a wide but easily comprehensible review of the theme, discussing and clarifying the major concepts with respect to its clinical presentation, all the presently available treatment options and strategies with their potential benefits and risks, the adequate patient selection for sympathectomy, as well as the postoperative clinical results.

An analysis of current pharmaceutical industry practices for making clinical trial results publicly accessible.

PubMed

Viereck, Christopher; Boudes, Pol

2009-07-01

We compared the clinical trial transparency practices of US/European pharma by analyzing the publicly-accessible clinical trial results databases of major drugs (doripenem, varenicline, lapatinib, zoledronic acid, adalimumab, insulin glargine, raltegravir, gefitinib). We evaluated their accessibility and utility from the perspective of the lay public. We included databases on company websites, http://www.clinicalstudyresults.org, http://www.clinicaltrials.gov and http://clinicaltrials.ifpma.org. Only 2 of 8 company homepages provide a direct link to the results. While the use of common terms on company search engines led to results for 5 of the 8 drugs following 2-4 clicks, no logical pathway was identified. The number of clinical trials in the databases was inconsistent: 0 for doripenem to 45 for insulin glargine. Results from all phases of clinical development were provided for 2 (insulin glargine and gefitinib) of the 8 drugs. Analyses of phase III reports revealed that most critical elements of the International Conference of Harmonization E3 Structure and Content of Synopses for Clinical Trial Reports were provided for 2 (varenicline, lapatinib) of the 8 drugs. For adalimumab and zoledronic acid, only citations were provided, which the lay public would be unable to access. None of the clinical trial reports was written in lay language. User-friendly support, when provided, was of marginal benefit. Only 1 of the databases (gefitinib) permitted the user to find the most recently updated reports. None of the glossaries included explanations for adverse events or statistical methodology. In conclusion, our study indicates that the public faces significant hurdles in finding and understanding clinical trial results databases.

Reporting of statistically significant results at ClinicalTrials.gov for completed superiority randomized controlled trials.

PubMed

Dechartres, Agnes; Bond, Elizabeth G; Scheer, Jordan; Riveros, Carolina; Atal, Ignacio; Ravaud, Philippe

2016-11-30

Publication bias and other reporting bias have been well documented for journal articles, but no study has evaluated the nature of results posted at ClinicalTrials.gov. We aimed to assess how many randomized controlled trials (RCTs) with results posted at ClinicalTrials.gov report statistically significant results and whether the proportion of trials with significant results differs when no treatment effect estimate or p-value is posted. We searched ClinicalTrials.gov in June 2015 for all studies with results posted. We included completed RCTs with a superiority hypothesis and considered results for the first primary outcome with results posted. For each trial, we assessed whether a treatment effect estimate and/or p-value was reported at ClinicalTrials.gov and if yes, whether results were statistically significant. If no treatment effect estimate or p-value was reported, we calculated the treatment effect and corresponding p-value using results per arm posted at ClinicalTrials.gov when sufficient data were reported. From the 17,536 studies with results posted at ClinicalTrials.gov, we identified 2823 completed phase 3 or 4 randomized trials with a superiority hypothesis. Of these, 1400 (50%) reported a treatment effect estimate and/or p-value. Results were statistically significant for 844 trials (60%), with a median p-value of 0.01 (Q1-Q3: 0.001-0.26). For the 1423 trials with no treatment effect estimate or p-value posted, we could calculate the treatment effect and corresponding p-value using results reported per arm for 929 (65%). For 494 trials (35%), p-values could not be calculated mainly because of insufficient reporting, censored data, or repeated measurements over time. For the 929 trials we could calculate p-values, we found statistically significant results for 342 (37%), with a median p-value of 0.19 (Q1-Q3: 0.005-0.59). Half of the trials with results posted at ClinicalTrials.gov reported a treatment effect estimate and/or p-value, with significant

Clinical verification of genetic results returned to research participants: findings from a Colon Cancer Family Registry.

PubMed

Laurino, Mercy Y; Truitt, Anjali R; Tenney, Lederle; Fisher, Douglass; Lindor, Noralane M; Veenstra, David; Jarvik, Gail P; Newcomb, Polly A; Fullerton, Stephanie M

2017-11-01

The extent to which participants act to clinically verify research results is largely unknown. This study examined whether participants who received Lynch syndrome (LS)-related findings pursued researchers' recommendation to clinically verify results with testing performed by a CLIA-certified laboratory. The Fred Hutchinson Cancer Research Center site of the multinational Colon Cancer Family Registry offered non-CLIA individual genetic research results to select registry participants (cases and their enrolled relatives) from 2011 to 2013. Participants who elected to receive results were counseled on the importance of verifying results at a CLIA-certified laboratory. Twenty-six (76.5%) of the 34 participants who received genetic results completed 2- and 12-month postdisclosure surveys; 42.3% of these (11/26) participated in a semistructured follow-up interview. Within 12 months of result disclosure, only 4 (15.4%) of 26 participants reported having verified their results in a CLIA-certified laboratory; of these four cases, all research and clinical results were concordant. Reasons for pursuing clinical verification included acting on the recommendation of the research team and informing future clinical care. Those who did not verify results cited lack of insurance coverage and limited perceived personal benefit of clinical verification as reasons for inaction. These findings suggest researchers will need to address barriers to seeking clinical verification in order to ensure that the intended benefits of returning genetic research results are realized. © 2017 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

Postdoctoral Appointments and Disappointments.

ERIC Educational Resources Information Center

National Academy of Sciences - National Research Council, Washington, DC. Commission on Human Resources.

Detailed findings on a broad range of issues concerning the importance of postdoctorals to the nation's research effort and the value of postdoctoral experience to young scientists and engineers pursuing careers in research are presented. The report, the first comprehensive study of postdoctorals in 10 years, identifies the following issues: (1)…

Comparison of reporting phase I trial results in ClinicalTrials.gov and matched publications.

PubMed

Shepshelovich, D; Goldvaser, H; Wang, L; Abdul Razak, A R; Bedard, P L

2017-12-01

Background Data on completeness of reporting of phase I cancer clinical trials in publications are lacking. Methods The ClinicalTrials.gov database was searched for completed adult phase I cancer trials with reported results. PubMed was searched for matching primary publications published prior to November 1, 2016. Reporting in primary publications was compared with the ClinicalTrials.gov database using a 28-point score (2=complete; 1=partial; 0=no reporting) for 14 items related to study design, outcome measures and safety profile. Inconsistencies between primary publications and ClinicalTrials.gov were recorded. Linear regression was used to identify factors associated with incomplete reporting. Results After a review of 583 trials in ClinicalTrials.gov , 163 matching primary publications were identified. Publications reported outcomes that did not appear in ClinicalTrials.gov in 25% of trials. Outcomes were upgraded, downgraded or omitted in publications in 47% of trials. The overall median reporting score was 23/28 (interquartile range 21-25). Incompletely reported items in >25% publications were: inclusion criteria (29%), primary outcome definition (26%), secondary outcome definitions (53%), adverse events (71%), serious adverse events (80%) and dates of study start and database lock (91%). Higher reporting scores were associated with phase I (vs phase I/II) trials (p<0.001), multicenter trials (p<0.001) and publication in journals with lower impact factor (p=0.004). Conclusions Reported results in primary publications for early phase cancer trials are frequently inconsistent or incomplete compared with ClinicalTrials.gov entries. ClinicalTrials.gov may provide more comprehensive data from new cancer drug trials.

Public availability of results of observational studies evaluating an intervention registered at ClinicalTrials.gov.

PubMed

Baudart, Marie; Ravaud, Philippe; Baron, Gabriel; Dechartres, Agnes; Haneef, Romana; Boutron, Isabelle

2016-01-28

Observational studies are essential for assessing safety. The aims of this study were to evaluate whether results of observational studies evaluating an intervention with safety outcome(s) registered at ClinicalTrials.gov were published and, if not, whether they were available through posting on ClinicalTrials.gov or the sponsor website. We identified a cohort of observational studies with safety outcome(s) registered on ClinicalTrials.gov after October 1, 2007, and completed between October 1, 2007, and December 31, 2011. We systematically searched PubMed for a publication, as well as ClinicalTrials.gov and the sponsor website for results. The main outcomes were the time to the first publication in journals and to the first public availability of the study results (i.e. published or posted on ClinicalTrials.gov or the sponsor website). For all studies with results publicly available, we evaluated the completeness of reporting (i.e. reported with the number of events per arm) of safety outcomes. We identified 489 studies; 334 (68%) were partially or completely funded by industry. Results for only 189 (39%, i.e. 65% of the total target number of participants) were published at least 30 months after the study completion. When searching other data sources, we obtained the results for 53% (n = 158; i.e. 93% of the total target number of participants) of unpublished studies; 31% (n = 94) were posted on ClinicalTrials.gov and 21% (n = 64) on the sponsor website. As compared with non-industry-funded studies, industry-funded study results were less likely to be published but not less likely to be publicly available. Of the 242 studies with a primary outcome recorded as a safety issue, all these outcomes were adequately reported in 86% (114/133) when available in a publication, 91% (62/68) when available on ClinicalTrials.gov, and 80% (33/41) when available on the sponsor website. Only 39% of observational studies evaluating an intervention with safety outcome

Migration characteristics and early clinical results of the NANOS® short-stem hip arthroplasty.

PubMed

Kaipel, Martin; Grabowiecki, Phillip; Sinz, Katrina; Farr, Sebastian; Sinz, Günter

2015-05-01

Femoral short stems promise essential advantages in total hip arthroplasty. Up to now, only short- and midterm clinical studies exist. Data on early stem migration that could predict later aseptic loosening at an early stage are rare. The purpose of this study was to assess migration patterns and clinical outcome 2 years after hip replacement by a metaphyseal anchored cementless short stem. Migration data and clinical results were prospectively assessed in 49 patients. Clinical outcome was measured using the Harris Hip Score (HHS). Migration analyses were performed using the computer-assisted Einzel-Bild-Roentgen-Analyse (EBRA) system. At 2 years after surgery, none of the implants needed revision, and HHS increased from 47.9 up to 98.1. Of 49 patients, 5 (10%) showed increased vertical stem migration (1.5 mm/2a) that might predict late aseptic loosening. Of 49 stems, 44 (90%) showed stable migration patterns indicating a beneficial long-term outcome. Results of this study confirm the excellent clinical data of previous works. Migration patterns strongly suggest that short-stem arthroplasty is not only an innovative but also a reliable strategy in total hip replacement.

Breast ultrasound tomography with two parallel transducer arrays: preliminary clinical results

NASA Astrophysics Data System (ADS)

Huang, Lianjie; Shin, Junseob; Chen, Ting; Lin, Youzuo; Intrator, Miranda; Hanson, Kenneth; Epstein, Katherine; Sandoval, Daniel; Williamson, Michael

2015-03-01

Ultrasound tomography has great potential to provide quantitative estimations of physical properties of breast tumors for accurate characterization of breast cancer. We design and manufacture a new synthetic-aperture breast ultrasound tomography system with two parallel transducer arrays. The distance of these two transducer arrays is adjustable for scanning breasts with different sizes. The ultrasound transducer arrays are translated vertically to scan the entire breast slice by slice and acquires ultrasound transmission and reflection data for whole-breast ultrasound imaging and tomographic reconstructions. We use the system to acquire patient data at the University of New Mexico Hospital for clinical studies. We present some preliminary imaging results of in vivo patient ultrasound data. Our preliminary clinical imaging results show promising of our breast ultrasound tomography system with two parallel transducer arrays for breast cancer imaging and characterization.

"I couldn't do this with opposition from my colleagues": A qualitative study of physicians' experiences as clinical tutors

PubMed Central

2011-01-01

Background Clinical contact in the early curriculum and workplace learning with active tutorship are important parts of modern medical education. In a previously published study, we found that medical students' tutors experienced a heavier workload, less reasonable demands and less encouragement, than students. The aim of this interview study was to further illuminate physicians' experiences as clinical tutors. Methods Twelve tutors in the Early Professional Contact course were interviewed. In the explorative interviews, they were asked to reflect upon their experiences of working as tutors in this course. Systematic text condensation was used as the analysis method. Results In the analysis, five main themes of physicians' experiences as clinical tutors in the medical education emerged: (a) Pleasure and stimulation. Informants appreciated tutorship and meeting both students and fellow tutors, (b) Disappointment and stagnation. Occasionally, tutors were frustrated and expressed negative feelings, (c) Demands and duty. Informants articulated an ambition to give students their best; a desire to provide better medical education but also a duty to meet demands of the course management, (d) Impact of workplace relations. Tutoring was made easier when the clinic's management provided active support and colleagues accepted students at the clinic, and (e) Multitasking difficulties. Combining several duties with those of a tutorship was often reported as difficult. Conclusions It is important that tutors' tasks are given adequate time, support and preparation. Accordingly, it appears highly important to avoid multitasking and too heavy a workload among tutors in order to facilitate tutoring. A crucial factor is acceptance and active organizational support from the clinic's management. This implies that tutoring by workplace learning in medical education should play an integrated and accepted role in the healthcare system. PMID:21975057

Acceptance and barriers pertaining to a general practice decision support system for multiple clinical conditions: A mixed methods evaluation.

PubMed

Arts, Derk L; Medlock, Stephanie K; van Weert, Henk C P M; Wyatt, Jeremy C; Abu-Hanna, Ameen

2018-01-01

Many studies have investigated the use of clinical decision support systems as a means to improve care, but have thus far failed to show significant effects on patient-related outcomes. We developed a clinical decision support system that attempted to address issues that were identified in these studies. The system was implemented in Dutch general practice and was designed to be both unobtrusive and to respond in real time. Despite our efforts, usage of the system was low. In the current study we perform a mixed methods evaluation to identify remediable barriers which led to disappointing usage rates for our system. A mixed methods evaluation employing an online questionnaire and focus group. The focus group was organized to clarify free text comments and receive more detailed feedback from general practitioners. Topics consisted of items based on results from the survey and additional open questions. The response rate for the questionnaire was 94%. Results from the questionnaire and focus group can be summarized as follows: The system was perceived as interruptive, despite its design. Participants felt that there were too many recommendations and that the relevance of the recommendations varied. Demographic based recommendations (e.g. age) were often irrelevant, while specific risk-based recommendations (e.g. diagnosis) were more relevant. The other main barrier to use was lack of time during the patient visit. These results are likely to be useful to other researchers who are attempting to address the problems of interruption and alert fatigue in decision support.

Pre-analytical and analytical aspects affecting clinical reliability of plasma glucose results.

PubMed

Pasqualetti, Sara; Braga, Federica; Panteghini, Mauro

2017-07-01

The measurement of plasma glucose (PG) plays a central role in recognizing disturbances in carbohydrate metabolism, with established decision limits that are globally accepted. This requires that PG results are reliable and unequivocally valid no matter where they are obtained. To control the pre-analytical variability of PG and prevent in vitro glycolysis, the use of citrate as rapidly effective glycolysis inhibitor has been proposed. However, the commercial availability of several tubes with studies showing different performance has created confusion among users. Moreover, and more importantly, studies have shown that tubes promptly inhibiting glycolysis give PG results that are significantly higher than tubes containing sodium fluoride only, used in the majority of studies generating the current PG cut-points, with a different clinical classification of subjects. From the analytical point of view, to be equivalent among different measuring systems, PG results should be traceable to a recognized higher-order reference via the implementation of an unbroken metrological hierarchy. In doing this, it is important that manufacturers of measuring systems consider the uncertainty accumulated through the different steps of the selected traceability chain. In particular, PG results should fulfil analytical performance specifications defined to fit the intended clinical application. Since PG has tight homeostatic control, its biological variability may be used to define these limits. Alternatively, given the central diagnostic role of the analyte, an outcome model showing the impact of analytical performance of test on clinical classifications of subjects can be used. Using these specifications, performance assessment studies employing commutable control materials with values assigned by reference procedure have shown that the quality of PG measurements is often far from desirable and that problems are exacerbated using point-of-care devices. Copyright © 2017 The Canadian

Acute Respiratory Distress Syndrome Measurement Error. Potential Effect on Clinical Study Results

PubMed Central

Cooke, Colin R.; Iwashyna, Theodore J.; Hofer, Timothy P.

2016-01-01

Rationale: Identifying patients with acute respiratory distress syndrome (ARDS) is a recognized challenge. Experts often have only moderate agreement when applying the clinical definition of ARDS to patients. However, no study has fully examined the implications of low reliability measurement of ARDS on clinical studies. Objectives: To investigate how the degree of variability in ARDS measurement commonly reported in clinical studies affects study power, the accuracy of treatment effect estimates, and the measured strength of risk factor associations. Methods: We examined the effect of ARDS measurement error in randomized clinical trials (RCTs) of ARDS-specific treatments and cohort studies using simulations. We varied the reliability of ARDS diagnosis, quantified as the interobserver reliability (κ-statistic) between two reviewers. In RCT simulations, patients identified as having ARDS were enrolled, and when measurement error was present, patients without ARDS could be enrolled. In cohort studies, risk factors as potential predictors were analyzed using reviewer-identified ARDS as the outcome variable. Measurements and Main Results: Lower reliability measurement of ARDS during patient enrollment in RCTs seriously degraded study power. Holding effect size constant, the sample size necessary to attain adequate statistical power increased by more than 50% as reliability declined, although the result was sensitive to ARDS prevalence. In a 1,400-patient clinical trial, the sample size necessary to maintain similar statistical power increased to over 1,900 when reliability declined from perfect to substantial (κ = 0.72). Lower reliability measurement diminished the apparent effectiveness of an ARDS-specific treatment from a 15.2% (95% confidence interval, 9.4–20.9%) absolute risk reduction in mortality to 10.9% (95% confidence interval, 4.7–16.2%) when reliability declined to moderate (κ = 0.51). In cohort studies, the effect on risk factor associations

ClinicalTrials.gov and Drugs@FDA: A comparison of results reporting for new drug approval trials

PubMed Central

Schwartz, Lisa M.; Woloshin, Steven; Zheng, Eugene; Tse, Tony; Zarin, Deborah A.

2016-01-01

Background Pharmaceutical companies and other trial sponsors must submit certain trial results to ClinicalTrials.gov. The validity of these results is unclear. Purpose To validate results posted on ClinicalTrials.gov against publicly-available FDA reviews on Drugs@FDA. Data sources ClinicalTrials.gov (registry and results database) and Drugs@FDA (medical/statistical reviews). Study selection 100 parallel-group, randomized trials for new drug approvals (1/2013 – 7/2014) with results posted on ClinicalTrials.gov (3/15/2015). Data extraction Two assessors systematically extracted, and another verified, trial design, primary/secondary outcomes, adverse events, and deaths. Results The 100 trials were mostly phase 3 (90%) double-blind (92%), placebo-controlled (73%), representing 32 drugs from 24 companies. Of 137 primary outcomes from ClinicalTrials.gov, 134 (98%) had corresponding data in Drugs@FDA, 130 (95%) had concordant definitions, and 107 (78%) had concordant results; most differences were nominal (i.e. relative difference < 10%). Of 100 trials, primary outcome results in 14 could not be validated . Of 1,927 secondary outcomes from ClinicalTrials.gov, 1,061 (55%) definitions could be validated and 367 (19%) had results. Of 96 trials with ≥ 1 serious adverse event in either source, 14 could be compared and 7 were discordant. Of 62 trials with ≥ 1 death in either source, 25 could be compared and 17 were discordant. Limitations Unknown generalizability to uncontrolled or crossover trial results. Conclusion Primary outcome definitions and results were largely concordant between ClinicalTrials.gov and Drugs@FDA. Half of secondary outcomes could not be validated because Drugs@FDA only includes “key outcomes” for regulatory decision-making; nor could serious adverse events and deaths because Drugs@FDA frequently only includes results aggregated across multiple trials. PMID:27294570

[Correlation of clinical and radiologic results of complete subtalar release in congenital clubfoot].

PubMed

Kalenderer, Onder; Ağuş, Haluk; Ak, Mümtaz; Ozlük, Serkan

2003-01-01

We evaluated the mid-term results in patients who underwent complete subtalar release with the use of the Cincinnati incision for congenital clubfoot. Complete subtalar release was performed in 30 feet of 23 patients (16 boys, 7 girls; 7 bilateral cases). The mean age at surgery was 17.5 months (range 2 to 84 months). Clinically, cosmetic appearance, adduction of the forefoot, the range of motion of the ankle joint, and muscle strength were evaluated. Radiologic evaluations included talocalcaneal angles on antero-posterior and lateral views, talocalcaneal index, talar-first metatarsal angles, calcaneal-fifth metatarsal angles, and Bohler angles. Talar and navicular bone lengths were compared with the other side in unilateral patients. The results were evaluated according to the Simons' criteria. The mean follow-up was 9 years and 8 months (range 7 years to 14 years). The mean range of motion of the ankle joint was measured as 47 degrees (range 10 degrees to 60 degrees ). The parents of three patients were not satisfied with the clinical results. Clinically, six patients had metatarsus adductus. Radiologically, flattening of the talar head (7 patients) and the talar dome (2 patients) were detected in unilateral patients. Navicular dorsal subluxation was found in seven feet. Compared to the normal side, the mean navicular shortening was 2.6 mm (range 0 to 4 mm), the mean talar shortening was 4.8 mm (range 2 to 11 mm). According to the Simons' criteria, the results were satisfactory in 27 feet (90%) and unsatisfactory in three feet (10%). Our results suggest that complete subtalar release for the treatment of clubfoot enables correction of all components of the deformity at a single session, and that its clinical results are more favorable than radiologic results, without requiring a close cooperation of the parents.

ClinicalTrials.gov and Drugs@FDA: A Comparison of Results Reporting for New Drug Approval Trials.

PubMed

Schwartz, Lisa M; Woloshin, Steven; Zheng, Eugene; Tse, Tony; Zarin, Deborah A

2016-09-20

Pharmaceutical companies and other trial sponsors must submit certain trial results to ClinicalTrials.gov. The validity of these results is unclear. To validate results posted on ClinicalTrials.gov against publicly available U.S. Food and Drug Administration (FDA) reviews on Drugs@FDA. ClinicalTrials.gov (registry and results database) and Drugs@FDA (medical and statistical reviews). 100 parallel-group, randomized trials for new drug approvals (January 2013 to July 2014) with results posted on ClinicalTrials.gov (15 March 2015). 2 assessors extracted, and another verified, the trial design, primary and secondary outcomes, adverse events, and deaths. Most trials were phase 3 (90%), double-blind (92%), and placebo-controlled (73%) and involved 32 drugs from 24 companies. Of 137 primary outcomes identified from ClinicalTrials.gov, 134 (98%) had corresponding data at Drugs@FDA, 130 (95%) had concordant definitions, and 107 (78%) had concordant results. Most differences were nominal (that is, relative difference <10%). Primary outcome results in 14 trials could not be validated. Of 1927 secondary outcomes from ClinicalTrials.gov, Drugs@FDA mentioned 1061 (55%) and included results data for 367 (19%). Of 96 trials with 1 or more serious adverse events in either source, 14 could be compared and 7 had discordant numbers of persons experiencing the adverse events. Of 62 trials with 1 or more deaths in either source, 25 could be compared and 17 were discordant. Unknown generalizability to uncontrolled or crossover trial results. Primary outcome definitions and results were largely concordant between ClinicalTrials.gov and Drugs@FDA. Half the secondary outcomes, as well as serious events and deaths, could not be validated because Drugs@FDA includes only "key outcomes" for regulatory decision making and frequently includes only adverse event results aggregated across multiple trials. National Library of Medicine.

[Evaluation of the results of clinical trials using a new non-statistical method].

PubMed

Zofková, I

1994-04-04

The author presents information on the possibilities and some advantages associated with the application of a new nonstatistical (gnostic) method for evaluation of results in clinical trials. The mentioned method is among other properties very robust, i.e. suited for evaluation of small groups of highly scattered data, a situation very frequently encountered in clinical research.

Beyond PubMed: Searching the "Grey Literature" for Clinical Trial Results.

PubMed

Citrome, Leslie

2014-07-01

Clinical trial results have been traditionally communicated through the publication of scholarly reports and reviews in biomedical journals. However, this dissemination of information can be delayed or incomplete, making it difficult to appraise new treatments, or in the case of missing data, evaluate older interventions. Going beyond the routine search of PubMed, it is possible to discover additional information in the "grey literature." Examples of the grey literature include clinical trial registries, patent databases, company and industrywide repositories, regulatory agency digital archives, abstracts of paper and poster presentations on meeting/congress websites, industry investor reports and press releases, and institutional and personal websites.

Upper cervical injuries: Clinical results using a new treatment algorithm

PubMed Central

Joaquim, Andrei F.; Ghizoni, Enrico; Tedeschi, Helder; Yacoub, Alexandre R. D.; Brodke, Darrel S.; Vaccaro, Alexander R.; Patel, Alpesh A.

2015-01-01

Introduction: Upper cervical injuries (UCI) have a wide range of radiological and clinical presentation due to the unique complex bony, ligamentous and vascular anatomy. We recently proposed a rational approach in an attempt to unify prior classification system and guide treatment. In this paper, we evaluate the clinical results of our algorithm for UCI treatment. Materials and Methods: A prospective cohort series of patients with UCI was performed. The primary outcome was the AIS. Surgical treatment was proposed based on our protocol: Ligamentous injuries (abnormal misalignment, facet perched or locked, increase atlanto-dens interval) were treated surgically. Bone fractures without ligamentous injuries were treated with a rigid cervical orthosis, with exception of fractures in the dens base with risk factors for non-union. Results: Twenty-three patients treated initially conservatively had some follow-up (mean of 171 days, range from 60 to 436 days). All of them were neurologically intact. None of the patients developed a new neurological deficit. Fifteen patients were initially surgically treated (mean of 140 days of follow-up, ranging from 60 to 270 days). In the surgical group, preoperatively, 11 (73.3%) patients were AIS E, 2 (13.3%) AIS C and 2 (13.3%) AIS D. At the final follow-up, the American Spine Injury Association (ASIA) score was: 13 (86.6%) AIS E and 2 (13.3%) AIS D. None of the patients had neurological worsening during the follow-up. Conclusions: This prospective cohort suggested that our UCI treatment algorithm can be safely used. Further prospective studies with longer follow-up are necessary to further establish its clinical validity and safety. PMID:25788816

Clinical potential of methylphenidate in the treatment of cocaine addiction: a review of the current evidence

PubMed Central

Dürsteler, Kenneth M; Berger, Eva-Maria; Strasser, Johannes; Caflisch, Carlo; Mutschler, Jochen; Herdener, Marcus; Vogel, Marc

2015-01-01

Background Cocaine use continues to be a public health problem, yet there is no proven effective pharmacotherapy for cocaine dependence. A promising approach to treating cocaine dependence may be agonist-replacement therapy, which is already used effectively in the treatment of opioid and tobacco dependence. The replacement approach for cocaine dependence posits that administration of a long-acting stimulant medication should normalize the neurochemical and behavioral perturbations resulting from chronic cocaine use. One potential medication to be substituted for cocaine is methylphenidate (MPH), as this stimulant possesses pharmacobehavioral properties similar to those of cocaine. Aim To provide a qualitative review addressing the rationale for the use of MPH as a cocaine substitute and its clinical potential in the treatment of cocaine dependence. Methods We searched MEDLINE for clinical studies using MPH in patients with cocaine abuse/dependence and screened the bibliographies of the articles found for pertinent literature. Results MPH, like cocaine, increases synaptic dopamine by inhibiting dopamine reuptake. The discriminative properties, reinforcing potential, and subjective effects of MPH and cocaine are almost identical and, importantly, MPH has been found to substitute for cocaine in animals and human volunteers under laboratory conditions. When taken orally in therapeutic doses, its abuse liability, however, appears low, which is especially true for extended-release MPH preparations. Though there are promising data in the literature, mainly from case reports and open-label studies, the results of randomized controlled trials have been disappointing so far and do not corroborate the use of MPH as a substitute for cocaine dependence in patients without attention deficit hyperactivity disorder. Conclusion Clinical studies evaluating MPH substitution for cocaine dependence have provided inconsistent findings. However, the negative findings may be explained by

Level-set-based reconstruction algorithm for EIT lung images: first clinical results.

PubMed

Rahmati, Peyman; Soleimani, Manuchehr; Pulletz, Sven; Frerichs, Inéz; Adler, Andy

2012-05-01

We show the first clinical results using the level-set-based reconstruction algorithm for electrical impedance tomography (EIT) data. The level-set-based reconstruction method (LSRM) allows the reconstruction of non-smooth interfaces between image regions, which are typically smoothed by traditional voxel-based reconstruction methods (VBRMs). We develop a time difference formulation of the LSRM for 2D images. The proposed reconstruction method is applied to reconstruct clinical EIT data of a slow flow inflation pressure-volume manoeuvre in lung-healthy and adult lung-injury patients. Images from the LSRM and the VBRM are compared. The results show comparable reconstructed images, but with an improved ability to reconstruct sharp conductivity changes in the distribution of lung ventilation using the LSRM.

Contemporary clinical trials in ventricular tachycardia and fibrillation: implications of ESVEM, CASCADE, and CASH for clinical management.

PubMed

Anderson, J L

1995-10-01

Recent clinical trials in patients with ventricular tachycardia (VT) or fibrillation (VF) have occurred in the setting of the disappointing results of postinfarction secondary prevention studies using Class I antiarrhythmics (e.g., CAST). ESVEM addressed in a randomized trial whether electrophysiologic study (EPS) or Holter monitoring (HM) is a more accurate predictor of long-term antiarrhythmic drug efficacy in VT/VF patients (N=486) and what the relative efficacy of various antiarrhythmic agents is for VT/VF. Surprisingly, arrhythmia recurrence rates were not significantly different by the method of determining an efficacy prediction. However, arrhythmia recurrence and mortality were lower (by about 50% at 1 year) in patients treated with sotalol (a mixed Class II/III agent) than with other drugs (Class I). CASCADE evaluated empiric amiodarone versus guided (EPS or HM) standard (Class I) therapy in survivors of out-of-hospital cardiac arrest due to VF. The primary endpoint of cardiac death, resuscitated VF, or syncopal shock (in ICD patients) was reduced by amiodarone compared with conventional therapy (9% vs 23% at 1 year). An interim report of the ongoing CASH study suggested in 230 survivors of cardiac arrest that propafenone (Class IC) provided less effective prophylaxis (approximately 20% 1-year mortality) compared with randomly assigned therapies with amiodarone, metoprolol, or an ICD (approximately 14% mortality rates) and was excluded from further study. These studies have led to a paradigm shift in the approach to antiarrhythmic therapy of VT/VF: drugs with antisympathetic plus Class III (refractoriness prolonging) action (i.e., sotalol, amiodarone) are superior to traditional drugs with Class I( conduction slowing) effects, even when guided by EPS or HM.

LabRS: A Rosetta stone for retrospective standardization of clinical laboratory test results.

PubMed

Hauser, Ronald George; Quine, Douglas B; Ryder, Alex

2018-02-01

Clinical laboratories in the United States do not have an explicit result standard to report the 7 billion laboratory tests results they produce each year. The absence of standardized test results creates inefficiencies and ambiguities for secondary data users. We developed and tested a tool to standardize the results of laboratory tests in a large, multicenter clinical data warehouse. Laboratory records, each of which consisted of a laboratory result and a test identifier, from 27 diverse facilities were captured from 2000 through 2015. Each record underwent a standardization process to convert the original result into a format amenable to secondary data analysis. The standardization process included the correction of typos, normalization of categorical results, separation of inequalities from numbers, and conversion of numbers represented by words (eg, "million") to numerals. Quality control included expert review. We obtained 1.266 × 109 laboratory records and standardized 1.252 × 109 records (98.9%). Of the unique unstandardized records (78.887 × 103), most appeared <5 times (96%, eg, typos), did not have a test identifier (47%), or belonged to an esoteric test with <100 results (2%). Overall, these 3 reasons accounted for nearly all unstandardized results (98%). Current results suggest that the tool is both scalable and generalizable among diverse clinical laboratories. Based on observed trends, the tool will require ongoing maintenance to stay current with new tests and result formats. Future work to develop and implement an explicit standard for test results would reduce the need to retrospectively standardize test results. © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Managing AVN following internal fixation: treatment options and clinical results.

PubMed

Hoskinson, Simon; Morison, Zachary; Shahrokhi, Shahram; Schemitsch, Emil H

2015-03-01

Avascular necrosis (AVN) after internal fixation of intracapsular hip fractures is a progressive multifactorial disease that ultimately results in local ischemia with ensuing osteocyte necrosis and structural compromise. This disease can cause significant clinical morbidity and affects patients of any age, including young and active patients. Effective treatment of this condition among young adults is challenging due to their high functional demands. The aim of managing AVN is to relieve pain, preserve range of movement and improve function. Treatment methods vary depending on the stage of the disease and can be broadly categorised into two options, hip preserving surgery and hip arthroplasty. Although, hip preserving techniques are attractive in the young adult, they may alter the morphology of the proximal femur and make subsequent arthroplasty more challenging. Conversely, arthroplasty in the young adult may require repeat revision procedures throughout the patient's life. Current evidence suggests that modifications of prevailing treatments, in addition to new technologies, have led to the development of management strategies that may be able to alter the course of femoral head osteonecrosis. This review aims to summarise the options available for treatment of AVN in the young adult and review the clinical results. Copyright © 2014 Elsevier Ltd. All rights reserved.

Clinical pathology results from cranes with experimental West Nile Virus infection

USGS Publications Warehouse

Olsen, Glenn H.

2011-01-01

Sandhill cranes (Grus canadensis) were vaccinated for and then challenged with West Nile virus. Resulting titers demonstrated protection in the vaccinated-challenged cranes as compared to the unvaccinated-challenged cranes. Clinical pathology results showed challenged cranes, whether vaccinated or not, had a decrease in their hematocrits and an elevation of 2.5-fold in their white blood cell counts as compared to unchallenged control sandhill cranes. No differences were apparent in the differential counts of heterophils and lymphocytes.

[The external patello-tibial transfixation (EPTT). Part II: Clinical application and results].

PubMed

Ishaque, B; Gotzen, L; Ziring, E; Petermann, J

1999-07-01

In part I of the paper the biomechanical and technical background of the EPTT using the MPT fixator and the indications for this procedure have been described. In part II we report about the clinical application of the EPTT in 67 patients with a wide spectrum of repairs and reconstructions of the extensor mechanism. 48 patients had fresh injuries, 18 of them with severe concomitant knee lesions and 19 patients had neglected rsp. unsuccessfully operated injuries. There were 4 deep infections, two of them related to the MPT fixator. In the patients with uneventful healing the fixator remained in place for 7.3 weeks in average. The clinical, isokinetic and radiological results were reviewed in 17 patients with an average follow-up time of 37.3 months. There were 5 patients with partial patellectomy and tendon reattachment because of lower patella pole comminution and 12 patients with tendon reattachment ruptured at the inferior patella pole or suture repair in midsubstance rupture. The clinical results according to the IKDC score were rated in 3 patients as normal, in 10 patients as nearly normal and in 4 patients as abnormal. This rating was highly dependend on the subjective judgement by the patients who considered their operated knees not as normal as the contralateral knees. From our clinical experiences and results we can derive that the EPTT enables the surgical management of extensor mechanism disruptions with a minimum of internal fixation material and provides a safe protection of the repairs and reconstructions during the healing period. The EPTT allows immediate unrestricted functional rehabilitation and early walking without crutches. Thus the EPTT represents an effective alternative to the patello-tibial cerclage with a wire or synthetic ligaments.

[Navigated drilling for femoral head necrosis. Experimental and clinical results].

PubMed

Beckmann, J; Tingart, M; Perlick, L; Lüring, C; Grifka, J; Anders, S

2007-05-01

In the early stages of osteonecrosis of the femoral head, core decompression by exact drilling into the ischemic areas can reduce pain and achieve reperfusion. Using computer aided surgery, the precision of the drilling can be improved while simultaneously lowering radiation exposure time for both staff and patients. We describe the experimental and clinical results of drilling under the guidance of the fluoroscopically-based VectorVision navigation system (BrainLAB, Munich, Germany). A total of 70 sawbones were prepared mimicking an osteonecrosis of the femoral head. In two experimental models, bone only and obesity, as well as in a clinical setting involving ten patients with osteonecrosis of the femoral head, the precision and the duration of radiation exposure were compared between the VectorVision system and conventional drilling. No target was missed. For both models, there was a statistically significant difference in terms of the precision, the number of drilling corrections as well as the radiation exposure time. The average distance to the desired midpoint of the lesion of both models was 0.48 mm for navigated drilling and 1.06 mm for conventional drilling, the average drilling corrections were 0.175 and 2.1, and the radiation exposure time less than 1 s and 3.6 s, respectively. In the clinical setting, the reduction of radiation exposure (below 1 s for navigation compared to 56 s for the conventional technique) as well as of drilling corrections (0.2 compared to 3.4) was also significant. Computer guided drilling using the fluoroscopically based VectorVision navigation system shows a clearly improved precision with a enormous simultaneous reduction in radiation exposure. It is therefore recommended for clinical routine.

Patient engagement and attrition in pediatric obesity clinics and programs: results and recommendations.

PubMed

Hampl, Sarah; Paves, Heather; Laubscher, Katie; Eneli, Ihuoma

2011-09-01

Pediatric tertiary care institutions are well positioned to provide multidisciplinary, intensive interventions for pediatric obesity known as stage 3 treatment. One contributor to the difficulty in administering this treatment is the high rate of patient attrition. Little is known about the practices used by pediatric weight-management clinics and group-based programs to minimize attrition. Hospital members and nonmembers of FOCUS on a Fitter Future were surveyed on the methods used to engage and retain obese children in their clinics and programs. Shortly thereafter, a benchmarking activity that centered on rates of patient nonattendance at initial and follow-up clinic visits was initiated among FOCUS-group-participating hospitals. Clinic- and group-based program results were contrasted. Staff from group-based programs reported that the majority of patients did not complete even 50% of program follow-up visits. Multiple patient/family- and clinic/program-level barriers to retention were identified. Attention to successful techniques should be paid during planning for new programs and improvement of established ones.

Clinical and radiological mid-term results of the thrust plate prosthesis

PubMed Central

v.d. Daele, R.; Simon, U.; Goetze, C.

2009-01-01

The purpose of this study was to perform an objective clinical and radiological assessment of the thrust plate prosthesis (TPP). Fifty-three prostheses were evaluated clinically using the Harris hip score (HHS), visual analog scale (VAS), and radiographically before surgery, at the time of discharge, and postoperatively after on average of 8.09 (range 4.61–9.93) years. The average HHS significantly (p ≤ 0.05) improved from 48 (range 18–77) points to 95 (range 46–100) points. The VAS revealed significant (p ≤ 0.05) reduction of pain at rest and under load. Radiographic analysis showed a considerable potential for osteolysis under the thrust plate. Sixteen prostheses revealed signs of radiolucent zones. In general, there was a good clinical outcome with no major limitations in function. Radiographic changes under the thrust plate indicate an adaptation processes resulting from changed biomechanics. This study suggests that the TPP could be a good alternative in total hip replacement in younger patients. PMID:19184010

[Personalized cell therapy for early postoperative bullous keratopathy (experimental proof and clinical results)].

PubMed

Kasparov, A A; Kasparova, Evg A; Fadeeva, L L; Subbot, A M; Borodina, N V; Kasparova, E A; Kobzova, M V; Musaeva, G M; Pavliuk, A S

2013-01-01

The article presents the results of a long-term research on development and clinical application of personalized cell therapy (PCT) for treatment of early postoperative (manifesting within the first 3 months after surgery) bullous keratopathy (BK). The method of intracameral PCT implies in vitro incubation of the patient's blood sample with poly(A:U) stimulator, separation of the serum with activated leukocytes, and injection of the final cell preparation into the anterior chamber. The fundamental part of the research was aimed at a detailed description of the cell preparation and investigation of its possible mechanisms of action. Cytokine and growth factor level in the cell preparation suggested that its high clinical efficacy might be due to its ability to improve regeneration of damaged corneal endothelium. The clinical study was conducted on a group of 52 patients with early BK. A significant effect (smoothing of the Descement's membrane folds, complete resorption of corneal edema, improvement of corneal transparency, reduction of corneal thickness and increase of visual acuity by 0.49 +/- 0.27) was achieved in 44.2% of patients, while partial effect was seen in 21.1% of patients. There was no clinical effect in 34.6% of patients. In those patients who developed significant or partial clinical effect after the PCT, many endotheliocytes appeared to have multiple nuclei (2 and more). In some patients polyploid nuclei persisted for 3-5 years after the treatment. Polyploidy results from incomplete mitosis which might be due to regenerative processes in the endothelium stimulated by the PCT. Obviously, high efficacy and relative simplicity of the method should promote its further clinical introduction.

The role of an NHS library service in the UK: the perceptions of clinical managers in Portsmouth, UK.

PubMed

Blagden, Pauline

2007-06-01

Portsmouth NHS Library Service is exploring methods of raising its profile within its host organization and wishes to demonstrate its contribution to achieving organizational goals, perhaps by means of an impact study. The objective of this small scale study, regarded as a possible precursor to an impact study, was to identify areas where there is potential to increase awareness among clinical managers of the Library's contribution. An e-mail survey was sent to clinical managers to elicit their opinions regarding the contribution of the Library Service to organizational goals. Perhaps unsurprisingly, the role of the Library Service in education, research and effectiveness was most widely recognized. Of responses, 30/42 (71%) rated it as 'very important' and a further 11 (26%) rated it as 'important'. The low appreciation of the Library Service to Clinical Services is a disappointment in view of the body of research evidence. Only 12 respondents (29%) thought that the Library Service contributed 'significantly' by 'supporting informed and timely clinical decision making'. The study suggested areas where there might be scope to raise awareness of the Library contribution. In considering how best to achieve this, the benefits need to be weighed against the resource implications. Portsmouth NHS Library Service decided to increase its marketing efforts but not to carry out an impact study in the short term.

A Review of Update Clinical Results of Carbon Ion Radiotherapy

PubMed Central

Tsujii, Hirohiko; Kamada, Tadashi

2012-01-01

Among various types of ion species, carbon ions are considered to have the most balanced, optimal properties in terms of possessing physically and biologically effective dose localization in the body. This is due to the fact that when compared with photon beams, carbon ion beams offer improved dose distribution, leading to the concentration of the sufficient dose within a target volume while minimizing the dose in the surrounding normal tissues. In addition, carbon ions, being heavier than protons, provide a higher biological effectiveness, which increases with depth, reaching the maximum at the end of the beam's range. This is practically an ideal property from the standpoint of cancer radiotherapy. Clinical studies have been carried out in the world to confirm the efficacy of carbon ions against a variety of tumors as well as to develop effective techniques for delivering an efficient dose to the tumor. Through clinical experiences of carbon ion radiotherapy at the National Institute of Radiological Sciences and Gesellschaft für Schwerionenforschung, a significant reduction in the overall treatment time with acceptable toxicities has been obtained in almost all types of tumors. This means that carbon ion radiotherapy has meanwhile achieved for itself a solid place in general practice. This review describes clinical results of carbon ion radiotherapy together with physical, biological and technological aspects of carbon ions. PMID:22798685

[The Psychotherapeutic Evening Clinic: Concept and First Results].

PubMed

Dinger, Ulrike; Komo-Lang, Miriam; Schauenburg, Henning; Herzog, Wolfgang; Nikendei, Christoph

2018-05-30

This article reports about a new treatment setting, the Psychotherapeutic Evening Clinic at the University Hospital Heidelberg. The treatment intensity is ranked between intensive, full-day inpatient and day-clinic programs in hospitals and less frequent outpatient psychotherapy according to the Germany Psychotherapy Guideline. Patients attend the Evening Clinic on 3 evenings per week for 3 hours each. During this time, they receive group therapy, individual therapy, mindfulness exercises and psychotherapeutic ward rounds. The first experiences with the new setting are positive, a specific advantage is the possibility to include daily hassles and everyday stressors as well as patients' strengths and resources into the treatment. Therapeutic challenges are the potential of overburdening patients with an already high impairment. On the structural and political level it will be important to ensure funding for the new treatment setting. © Georg Thieme Verlag KG Stuttgart · New York.

Teleradiology and screening mammography: a telemammography system evaluation and comparison to clinical results

NASA Astrophysics Data System (ADS)

Leader, Joseph K.; Chough, Denise; Clearfield, Ronald J.; Ganott, Marie A.; Hakim, Christiane; Hardesty, Lara; Shindel, Betty; Sumkin, Jules H.; Drescher, John M.; Maitz, Glenn S.; Gur, David

2005-04-01

Radiologists' performance reviewing and rating breast cancer screening mammography exams using a telemammography system was evaluated and compared with the actual clinical interpretations of the same interpretations. Mammography technologists from three remote imaging sites transmitted 245 exams to a central site (radiologists), which they (the technologists) believed needed additional procedures (termed "recall"). Current exam image data and non-image data (i.e., technologist's text message, technologist's graphic marks, patient's prior report, and Computer Aided Detection (CAD) results) were transmitted to the central site and displayed on three high-resolution, portrait monitors. Seven radiologists interpreted ("recall" or "no recall") the exams using the telemammography workstation in three separate multi-mode studies. The mean telemammography recall rates ranged from 72.3% to 82.5% while the actual clinical recall rates ranged from 38.4% to 42.3% across the three studies. Mean Kappa of agreement ranged from 0.102 to 0.213 and mean percent agreement ranged from 48.7% to 57.4% across the three studies. Eighty-seven percent of the disagreement interpretations occurred when the telemammography interpretation resulted in a recommendation to recall and the clinical interpretation resulted in a recommendation not to recall. The poor agreement between the telemammography and clinical interpretations may indicate a critical dependence on images from prior screening exams rather than any text based information. The technologists were sensitive, if not specific, to the mammography features and changes that may lead to recall. Using the telemammography system the radiologists were able to reduce the recommended recalls by the technologist by approximately 25 percent.

Donepezil treatment and Alzheimer disease: can the results of randomized clinical trials be applied to Alzheimer disease patients in clinical practice?

PubMed

Tinklenberg, Jared R; Kraemer, Helena C; Yaffe, Kristine; Ross, Leslie; Sheikh, Javaid; Ashford, John W; Yesavage, Jerome A; Taylor, Joy L

2007-11-01

To determine if results from randomized clinical trials of donepezil in Alzheimer disease (AD) patients can be applied to AD patients in clinical practice by comparing the findings from a Nordic one-year randomized AD donepezil trial with data from a one-year prospective, observational study of AD patients. AD patients from a consortium of California sites were systematically followed for at least one year. Their treatment regimens, including prescription of donepezil, were determined by their individual physician according to his or her usual criteria. The 148 California patients treated with donepezil had a one-year decline of 1.3 (3.5 SD) points on the Mini-Mental State Exam compared to a decline of 3.3 (4.4 SD) in the 158 AD patients who received no anti-Alzheimer drugs. The Mini-Mental State Exam decline in Nordic sample was approximately 0.25 points for the 91 patients receiving donepezil and approximately 2.2 for the 98 placebo patients. The overall effect sizes were estimated at about 0.49 in both studies. The California data were further analyzed using propensity methods; after taking into account differences that could bias prescribing decisions, benefits associated with taking donepezil remained. A comparison of a randomized clinical trial of donepezil in AD patients and this observational study indicates that if appropriate methodological and statistical precautions are undertaken, then results from randomized clinical trials can be predictive with AD patients in clinical practice. This California study supports the modest effectiveness of donepezil in AD patients having clinical characteristics similar to those of the Nordic study.

Excerpts from the 1st international NTNU symposium on current and future clinical biomarkers of cancer: innovation and implementation, June 16th and 17th 2016, Trondheim, Norway.

PubMed

Robles, Ana I; Olsen, Karina Standahl; Tsui, Dana W T; Georgoulias, Vassilis; Creaney, Jenette; Dobra, Katalin; Vyberg, Mogens; Minato, Nagahiro; Anders, Robert A; Børresen-Dale, Anne-Lise; Zhou, Jianwei; Sætrom, Pål; Nielsen, Boye Schnack; Kirschner, Michaela B; Krokan, Hans E; Papadimitrakopoulou, Vassiliki; Tsamardinos, Ioannis; Røe, Oluf D

2016-10-19

The goal of biomarker research is to identify clinically valid markers. Despite decades of research there has been disappointingly few molecules or techniques that are in use today. The "1st International NTNU Symposium on Current and Future Clinical Biomarkers of Cancer: Innovation and Implementation", was held June 16th and 17th 2016, at the Knowledge Center of the St. Olavs Hospital in Trondheim, Norway, under the auspices of the Norwegian University of Science and Technology (NTNU) and the HUNT biobank and research center. The Symposium attracted approximately 100 attendees and invited speakers from 12 countries and 4 continents. In this Symposium original research and overviews on diagnostic, predictive and prognostic cancer biomarkers in serum, plasma, urine, pleural fluid and tumor, circulating tumor cells and bioinformatics as well as how to implement biomarkers in clinical trials were presented. Senior researchers and young investigators presented, reviewed and vividly discussed important new developments in the field of clinical biomarkers of cancer, with the goal of accelerating biomarker research and implementation. The excerpts of this symposium aim to give a cutting-edge overview and insight on some highly important aspects of clinical cancer biomarkers to-date to connect molecular innovation with clinical implementation to eventually improve patient care.

Tobacco Cessation via Public Dental Clinics: Results of a Randomized Trial

PubMed Central

Andrews, Judy A.; Albert, David A.; Crews, Karen M.; Payne, Thomas J.; Severson, Herbert H.

2010-01-01

Objectives. We sought to compare the effectiveness of a dental practitioner advice and brief counseling intervention to quit tobacco use versus usual care for patients in community health centers on tobacco cessation, reduction in tobacco use, number of quit attempts, and change in readiness to quit. Methods. We randomized 14 federally funded community health center dental clinics that serve diverse racial/ethnic groups in 3 states (Mississippi, New York, and Oregon) to the intervention (brief advice and assistance, including nicotine replacement therapy) or usual care group. Results. We enrolled 2549 smokers. Participants in the intervention group reported significantly higher abstinence rates at the 7.5-month follow-up, for both point prevalence (F1,12 = 6.84; P < .05) and prolonged abstinence (F1,12 = 14.62; P < .01) than did those in the usual care group. Conclusions. The results of our study suggest the viability and effectiveness of tobacco cessation services delivered to low-income smokers via their dental health care practitioner in community health centers. Tobacco cessation services delivered in public dental clinics have the potential to improve the health and well-being of millions of Americans. PMID:20466951

Beyond PubMed: Searching the “Grey Literature” for Clinical Trial Results

PubMed Central

2014-01-01

Clinical trial results have been traditionally communicated through the publication of scholarly reports and reviews in biomedical journals. However, this dissemination of information can be delayed or incomplete, making it difficult to appraise new treatments, or in the case of missing data, evaluate older interventions. Going beyond the routine search of PubMed, it is possible to discover additional information in the “grey literature.” Examples of the grey literature include clinical trial registries, patent databases, company and industrywide repositories, regulatory agency digital archives, abstracts of paper and poster presentations on meeting/congress websites, industry investor reports and press releases, and institutional and personal websites. PMID:25337445

Publishing interim results of randomised clinical trials in peer-reviewed journals.

PubMed

Counsell, Nicholas; Biri, Despina; Fraczek, Joanna; Hackshaw, Allan

2017-02-01

Interim analyses of randomised controlled trials are sometimes published before the final results are available. In several cases, the treatment effects were noticeably different after patient recruitment and follow-up completed. We therefore conducted a literature review of peer-reviewed journals to compare the reported treatment effects between interim and final publications and to examine the magnitude of the difference. We performed an electronic search of MEDLINE from 1990 to 2014 (keywords: 'clinical trial' OR 'clinical study' AND 'random*' AND 'interim' OR 'preliminary'), and we manually identified the corresponding final publication. Where the electronic search produced a final report in which the abstract cited interim results, we found the interim publication. We also manually searched every randomised controlled trial in eight journals, covering a range of impact factors and general medical and specialist publications (1996-2014). All paired articles were checked to ensure that the same comparison between interventions was available in both. In all, 63 studies are included in our review, and the same quantitative comparison was available in 58 of these. The final treatment effects were smaller than the interim ones in 39 (67%) trials and the same size or larger in 19 (33%). There was a marked reduction, defined as a ≥20% decrease in the size of the treatment effect from interim to final analysis, in 11 (19%) trials compared to a marked increase in 3 (5%), p = 0.057. The magnitude of percentage change was larger in trials where commercial support was reported, and increased as the proportion of final events at the interim report decreased in trials where commercial support was reported (interaction p = 0.023). There was no evidence of a difference between trials that stopped recruitment at the interim analysis where this was reported as being pre-specified versus those that were not pre-specified (interaction p = 0.87). Published interim

Generalizability of Clinical Trial Results for Adolescent Major Depressive Disorder.

PubMed

Blanco, Carlos; Hoertel, Nicolas; Franco, Silvia; Olfson, Mark; He, Jian-Ping; López, Saioa; González-Pinto, Ana; Limosin, Frédéric; Merikangas, Kathleen R

2017-12-01

Although there have been a number of clinical trials evaluating treatments for adolescents with major depressive disorder (MDD), the generalizability of those trials to samples of depressed adolescents who present for routine clinical care is unknown. Examining the generalizability of clinical trials of pharmacological and psychotherapy interventions for adolescent depression can help administrators and frontline practitioners determine the relevance of these studies for their patients and may also guide eligibility criteria for future clinical trials in this clinical population. Data on nationally representative adolescents were derived from the National Comorbidity Survey: Adolescent Supplement. To assess the generalizability of adolescent clinical trials for MDD, we applied a standard set of eligibility criteria representative of clinical trials to all adolescents in the National Comorbidity Survey: Adolescent Supplement with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of MDD ( N = 592). From the overall MDD sample, 61.9% would have been excluded from a typical pharmacological trial, whereas 42.2% would have been excluded from a psychotherapy trial. Among those who sought treatment ( n = 412), the corresponding exclusion rates were 72.7% for a pharmacological trial and 52.2% for a psychotherapy trial. The criterion leading to the largest number of exclusions was "significant risk of suicide" in both pharmacological and psychotherapy trials. Pharmacological and, to a lesser extent, psychotherapy clinical trials likely exclude most adolescents with MDD. Careful consideration should be given to balancing eligibility criteria and internal validity with applicability in routine clinical care while ensuring patient safety. Copyright © 2017 by the American Academy of Pediatrics.

[Clinical management of adrenal incidentalomas: results of a survey].

PubMed

Moreno-Fernández, Jesús; García-Manzanares, Alvaro; Sánchez-Covisa, Miguel Aguirre; García, E Inés Rosa Gómez

2009-12-01

Incidentalomas are clinically silent adrenal masses that are discovered incidentally during diagnostic testing for clinical conditions unrelated to suspicion of adrenal disease. Several decision algorithms are used in the management of adrenal masses. We evaluated the routine use of these algorithms through a clinical activity questionnaire. The questionnaire included data on the work center, initial hormonal and radiological study, imaging and hormonal tests performed to complete the study, surgical indications and clinical follow-up. Thirty-three endocrinologists (79%) attending the annual congress of the Castilla-La Mancha Society of Endocrinology, Nutrition and Diabetes completed the questionnaire. Forty-six percent considered tumoral size to be the most important factor suggesting malignancy in the initial evaluation of adrenal incidentalomas, the limit being 4 cm for 78% of the endocrinologists. Imaging study was completed by magnetic resonance imaging by 39%. All the physicians always performed screening for hypercortisolism and pheochromocytoma. Other assessments always conducted in all incidentalomas included hyperaldosteronism (76%), sex hormone-producing tumor (51%) and congenital adrenal hyperplasia (30%). Seventy-nine percent of respondents began to refer incidentalomas larger than 4 cm for surgical treatment, and 46% referred all tumors larger than 6 cm for surgical treatment. With regard to hormonal function, patients with pheochromocytoma, Cushing's syndrome, hyperaldosteronism with poorly controlled blood pressure or sex hormoneproducing tumors were more frequently referred for surgery. Seventy-six percent of endocrinologists performed clinical follow-up in adrenal incidentalomas larger than 4 cm, preferably through computerized tomography (81%), and repeated studies for hormonal hypercortisolism (97%), primary hyperaldosteronism (42%) and pheochromocytoma (76%) over a 4-5 year period (67%). Clinical practice varied among the endocrinologists

Autofluorescence of pigmented skin lesions using a pulsed UV laser with synchronized detection: clinical results

NASA Astrophysics Data System (ADS)

Cheng, Haynes P. H.; Svenmarker, Pontus; Xie, Haiyan; Tidemand-Lichtenberg, Peter; Jensen, Ole B.; Bendsoe, Niels; Svanberg, Katarina; Petersen, Paul Michael; Pedersen, Christian; Andersson-Engels, Stefan; Andersen, Peter E.

2010-04-01

We report preliminary clinical results of autofluorescence imaging of malignant and benign skin lesions, using pulsed 355 nm laser excitation with synchronized detection. The novel synchronized detection system allows high signal-tonoise ratio to be achieved in the resulting autofluorescence signal, which may in turn produce high contrast images that improve diagnosis, even in the presence of ambient room light. The synchronized set-up utilizes a compact, diode pumped, pulsed UV laser at 355 nm which is coupled to a CCD camera and a liquid crystal tunable filter. The excitation and image capture is sampled at 5 kHz and the resulting autofluorescence is captured with the liquid crystal filter cycling through seven wavelengths between 420 nm and 580 nm. The clinical study targets pigmented skin lesions and evaluates the prospects of using autofluorescence as a possible means in differentiating malignant and benign skin tumors. Up to now, sixteen patients have participated in the clinical study. The autofluorescence images, averaged over the exposure time of one second, will be presented along with histopathological results. Initial survey of the images show good contrast and diagnostic results show promising agreement based on the histopathological results.

Transpedicular Curettage and Drainage of Infective Lumbar Spondylodiscitis: Technique and Clinical Results

PubMed Central

Lee, Byung Ho; Lee, Hwan-Mo; Kim, Tae-Hwan; Kim, Hak-Sun; Moon, Eun-Soo; Park, Jin-Oh; Chong, Hyun-Soo

2012-01-01

Background Infective spondylodiscitis usually occurs in patients of older age, immunocompromisation, co-morbidity, and individuals suffering from an overall poor general condition unable to undergo reconstructive anterior and posterior surgeries. Therefore, an alternative, less aggressive surgical method is needed for these select cases of infective spondylodiscitis. This retrospective clinical case series reports our novel surgical technique for the treatment of infective spondylodiscitis. Methods Between January 2005 and July 2011, among 48 patients who were diagnosed with pyogenic lumbar spondylodiscitis or tuberculosis lumbar spondylodiscitis, 10 patients (7 males and 3 females; 68 years and 48 to 78 years, respectively) underwent transpedicular curettage and drainage. The mean postoperative follow-up period was 29 months (range, 7 to 61 months). The pedicle screws were inserted to the adjacent healthy vertebrae in the usual manner. After insertion of pedicle screws, the drainage pedicle holes were made through pedicles of infected vertebra(e) in order to prevent possible seeding of infective emboli to the healthy vertebra, as the same instruments and utensils are used for both pedicle screws and the drainage holes. A minimum of 15,000 mL of sterilized normal saline was used for continuous irrigation through the pedicular pathways until the drained fluid looked clear. Results All patients' symptoms and inflammatory markers significantly improved clinically between postoperative 2 weeks and postoperative 3 months, and they were satisfied with their clinical results. Radiologically, all patients reached the spontaneous fusion between infected vertebrae and 3 patients had the screw pulled-out but they were clinically tolerable. Conclusions We suggest that our method of transpedicular curettage and drainage is a useful technique in regards to the treatment of infectious spondylodiscitic patients, who could not tolerate conventional combined anterior and posterior

Results of extracorporeal life support implementation in routine clinical practice: single center experience

PubMed Central

Biočina, Bojan; Petričević, Mate; Belina, Dražen; Gašparović, Hrvoje; Svetina, Lucija; Konosić, Sanja; White, Alexandra; Ivančan, Višnja; Kopjar, Tomislav; Miličić, Davor

2014-01-01

Aim To describe our experience in the clinical application of extracorporeal life support (ECLS) and analyze whether ECLS leads to acceptable clinical outcomes in patients with cardiac failure. Methods Data from clinical database of University Hospital Center Zagreb, Croatia, on 75 patients undergoing ECLS support from 2009 to 2014 due to cardiac failure were retrospectively analyzed. Outcomes were defined as procedural and clinical outcomes. ECLS as a primary procedure and ECLS as a postcardiotomy procedure due to inability to wean from cardiopulmonary bypass were analyzed. Results ECLS was used in 75 adult patients, and in 24 (32%) of those procedural success was noted. ECLS was implemented as a primary procedure in 36 patients and as a postcardiotomy procedure in 39 patients. Nine out of 39 (23.08%) patients had postcardiotomy ECLS after heart transplantation. Bleeding complications occurred in 30 (40%) patients, both in primary (11/36 patients) and postcardiotomy group (19/39 patients). ECLS was established by peripheral approach in 46 patients and by central cannulation in 27 patients. In 2 patients, combined cannulation was performed, with an inflow cannula placed into the right atrium and an outflow cannula placed into the femoral artery. Eleven patients treated with peripheral approach had ischemic complications. Conclusion ECLS is a useful tool in the treatment of patients with refractory cardiac failure and its results are encouraging in patients who otherwise have an unfavorable prognosis. PMID:25559831

Confocal microendoscopy: Characterization of imaging bundles, fluorescent contrast agents, and early clinical results

NASA Astrophysics Data System (ADS)

Udovich, Joshua Anthony

Ovarian cancer is the fifth leading cause of cancer related deaths among women. Early detection improves the chances of survival following diagnosis, and new imaging modalities have the potential to reduce deaths due to this disease. The confocal microendoscope (CME) is a non-destructive in-vivo imaging device for visualization of the ovaries that operates in real-time. Two components of the CME system are evaluated in this paper, and initial results from an ongoing clinical trial are presented. Fiber-optic imaging bundles are used in the CME imaging catheter to relay images over distances of up to 20 feet. When detecting fluorescent signals from investigated tissue, any fluorescence in the system can potentially reduce contrast in images. The emission and transmission properties of three commercially available fiber optic imaging bundles were evaluated. Emission maps of fluorescence from bundles were generated at multiple excitation wavelengths to determine the profile and amount of fluorescence present in bundles manufactured by Sumitomo, Fujikura, and Schott. Results are also presented that show the variation of transmittance as a function of illumination angle in these bundles. Users of high-resolution fiber-optic imaging bundles should be aware of these properties and take them into account during system design. Contrast is improved in images obtained with the CME through the application of topical dyes. Acridine orange (AO) and SYTO 16 are two fluorescent stains that are used to show the size, shape, and distribution of cell nuclei. Unfortunately, little is known about the effects of these dyes on living tissues. This study was undertaken to evaluate the effects of dye treatment on peritoneal tissues in mice. Seventy-five Balb/c mice were split into five groups of fifteen and given peritoneal injections of dye or saline. The proportions of negative outcomes for the control and test groups were compared using confidence intervals and the Fisher's exact test

The Texas medication algorithm project: clinical results for schizophrenia.

PubMed

Miller, Alexander L; Crismon, M Lynn; Rush, A John; Chiles, John; Kashner, T Michael; Toprac, Marcia; Carmody, Thomas; Biggs, Melanie; Shores-Wilson, Kathy; Chiles, Judith; Witte, Brad; Bow-Thomas, Christine; Velligan, Dawn I; Trivedi, Madhukar; Suppes, Trisha; Shon, Steven

2004-01-01

In the Texas Medication Algorithm Project (TMAP), patients were given algorithm-guided treatment (ALGO) or treatment as usual (TAU). The ALGO intervention included a clinical coordinator to assist the physicians and administer a patient and family education program. The primary comparison in the schizophrenia module of TMAP was between patients seen in clinics in which ALGO was used (n = 165) and patients seen in clinics in which no algorithms were used (n = 144). A third group of patients, seen in clinics using an algorithm for bipolar or major depressive disorder but not for schizophrenia, was also studied (n = 156). The ALGO group had modestly greater improvement in symptoms (Brief Psychiatric Rating Scale) during the first quarter of treatment. The TAU group caught up by the end of 12 months. Cognitive functions were more improved in ALGO than in TAU at 3 months, and this difference was greater at 9 months (the final cognitive assessment). In secondary comparisons of ALGO with the second TAU group, the greater improvement in cognitive functioning was again noted, but the initial symptom difference was not significant.

Teaching: From Disappointment to Ecstasy

ERIC Educational Resources Information Center

Albers, Cheryl

2009-01-01

Unintended outcomes can derail the best of intentions in the classroom. Designing a new course for Honors students provided an opportunity to change my traditional teaching style. I envisioned a classroom where students enthusiastically became more self-directed learners. I was perplexed with mixed reactions from students; while some joined me and…

Reporting results from whole-genome and whole-exome sequencing in clinical practice: a proposal for Canada?

PubMed

Zawati, Ma'n H; Parry, David; Thorogood, Adrian; Nguyen, Minh Thu; Boycott, Kym M; Rosenblatt, David; Knoppers, Bartha Maria

2014-01-01

This article proposes recommendations for the use of whole-genome and whole-exome (WGS/WES) sequencing in clinical practice, endorsed by the board of directors of the Canadian College of Medical Geneticists. The publication of statements and recommendations by several international and national organisations on clinical WGS/WES has prompted a need for Canadian-specific guidance. A multi-disciplinary group consisting of lawyers, ethicists, genetic researchers, and clinical geneticists was assembled to review existing guidelines on WGS/WES and identify provisions relevant to the Canadian context. Definitions were provided to orient the recommendations and to minimize confusion with other recommendations. Recommendations include the following: WGS/WES should be used in a judicious and cost-efficient manner; WGS/WES should be used to answer a clinical question; and physicians need to explain to adult patients the nature of the results that could arise, so as to allow them to make informed choices over whether to take the test and which results they wish to receive. Recommendations are also provided for WGS/WES in the pediatric context, and for when results implicate patients' family members. These recommendations are only a proposal to be developed into comprehensive Canadian-based guidelines. They aim to promote discussion about the reporting of WGS/WES results, and to encourage the ethical implementation of these new technologies in the clinical setting.

An official multi-society statement: the role of clinical research results in the practice of critical care medicine.

PubMed

Tonelli, Mark R; Curtis, J Randall; Guntupalli, Kalpalatha K; Rubenfeld, Gordon D; Arroliga, Alejandro C; Brochard, Laurent; Douglas, Ivor S; Gutterman, David D; Hall, Jesse R; Kavanagh, Brian P; Mancebo, Jordi; Misak, Cheryl J; Simpson, Steven Q; Slutsky, Arthur S; Suffredini, Anthony F; Thompson, B Taylor; Ware, Lorraine B; Wheeler, Arthur P; Levy, Mitchell M

2012-05-15

While the results of clinical research are clearly valuable in the care of critically ill patients, the limitations of such information and the role of other forms of medical knowledge for clinical decision making have not been carefully examined. The leadership of three large professional societies representing critical care practitioners convened a diverse group representing a wide variety of views regarding the role of clinical research results in clinical practice to develop a document to serve as a basis for agreement and a framework for ongoing discussion. Consensus was reached on several issues. While the results of rigorous clinical research are important in arriving at the best course of action for an individual critically ill patient, other forms of medical knowledge, including clinical experience and pathophysiologic reasoning, remain essential. No single source of knowledge is sufficient to guide clinical decisions, nor does one kind of knowledge always take precedence over others. Clinicians will find clinical research compelling for a variety of reasons that go beyond study design. While clinical practice guidelines and protocols based upon clinical research may improve care and decrease variability in practice, clinicians must be able to understand and articulate the rationale as to why a particular protocol or guideline is used or why an alternative approach is taken. Making this clinical reasoning explicit is necessary to understand practice variability. Understanding the strengths and weaknesses of different kinds of medical knowledge for clinical decision making and factors beyond study design that make clinical research compelling to clinicians can provide a framework for understanding the role of clinical research in practice.

Are research papers reporting results from nutrigenetics clinical research a potential source of biohype?

PubMed

Stenne, R; Hurlimann, T; Godard, Béatrice

2012-01-01

Nutrigenetics is a promising field, but the achievability of expected benefits is challenged by the methodological limitations that are associated with clinical research in that field. The mere existence of these limitations suggests that promises about potential outcomes may be premature. Thus, benefits claimed in scientific journal articles in which these limitations are not acknowledged might stimulate biohype. This article aims to examine whether nutrigenetics clinical research articles are a potential source of biohype. Of the 173 articles identified, 16 contained claims in which clinical applications were extrapolated from study results. The methodological limitations being incompletely acknowledged, these articles could potentially be a source of biohype.

Correlations between commonly used clinical outcome scales and patient satisfaction after total knee arthroplasty.

PubMed

Kwon, Sae Kwang; Kang, Yeon Gwi; Kim, Sung Ju; Chang, Chong Bum; Seong, Sang Cheol; Kim, Tae Kyun

2010-10-01

Patient satisfaction is becoming increasingly important as a crucial outcome measure for total knee arthroplasty. We aimed to determine how well commonly used clinical outcome scales correlate with patient satisfaction after total knee arthroplasty. In particular, we sought to determine whether patient satisfaction correlates better with absolute postoperative scores or preoperative to 12-month postoperative changes. Patient satisfaction was evaluated using 4 grades (enthusiastic, satisfied, noncommittal, and disappointed) for 438 replaced knees that were followed for longer than 1 year. Outcomes scales used the American Knee Society, Western Ontario McMaster University Osteoarthritis Index scales, and Short Form-36 scores. Correlation analyses were performed to investigate the relation between patient satisfaction and the 2 different aspects of the outcome scales: postoperative scores evaluated at latest follow-ups and preoperative to postoperative changes. The Western Ontario McMaster University Osteoarthritis Index scales function score was most strongly correlated with satisfaction (correlation coefficient=0.45). Absolute postoperative scores were better correlated with satisfaction than the preoperative to postoperative changes for all scales. Level IV (retrospective case series). Copyright © 2010 Elsevier Inc. All rights reserved.

Attitudes and Beliefs of Pathology Residents Regarding the Subspecialty of Clinical Chemistry: Results of a Survey.

PubMed

Haidari, Mehran; Yared, Marwan; Olano, Juan P; Alexander, C Bruce; Powell, Suzanne Z

2017-02-01

-Previous studies suggest that training in pathology residency programs does not adequately prepare pathology residents to become competent in clinical chemistry. -To define the beliefs of pathology residents in the United States regarding their preparation for practicing clinical chemistry in their career, their attitude toward the discipline, and the attractiveness of clinical chemistry as a career. -The residents of all pathology residency programs in the United States were given the opportunity to participate in an online survey. -Three hundred thirty-six pathology residents responded to the survey. Analysis of the survey results indicates that pathology residents are more likely to believe that their income may be lower if they select a career that has a clinical chemistry focus and that their faculty do not value clinical chemistry as much as the anatomic pathology part of the residency. Residents also report that clinical chemistry is not as enjoyable as anatomic pathology rotations during residency or preferable as a sole career path. A large proportion of residents also believe that they will be slightly prepared or not prepared to practice clinical chemistry by the end of their residency and that they do not have enough background and/or time to learn clinical chemistry during their residency programs to be able to practice this specialty effectively post graduation. -Our survey results suggest that many pathology residents do not have a positive attitude toward clinical chemistry and do not experience a supportive learning environment with an expectation that they will become competent in clinical chemistry with a residency alone.

Limited accessibility to designs and results of Japanese large-scale clinical trials for cardiovascular diseases.

PubMed

Sawata, Hiroshi; Ueshima, Kenji; Tsutani, Kiichiro

2011-04-14

Clinical evidence is important for improving the treatment of patients by health care providers. In the study of cardiovascular diseases, large-scale clinical trials involving thousands of participants are required to evaluate the risks of cardiac events and/or death. The problems encountered in conducting the Japanese Acute Myocardial Infarction Prospective (JAMP) study highlighted the difficulties involved in obtaining the financial and infrastructural resources necessary for conducting large-scale clinical trials. The objectives of the current study were: 1) to clarify the current funding and infrastructural environment surrounding large-scale clinical trials in cardiovascular and metabolic diseases in Japan, and 2) to find ways to improve the environment surrounding clinical trials in Japan more generally. We examined clinical trials examining cardiovascular diseases that evaluated true endpoints and involved 300 or more participants using Pub-Med, Ichushi (by the Japan Medical Abstracts Society, a non-profit organization), websites of related medical societies, the University Hospital Medical Information Network (UMIN) Clinical Trials Registry, and clinicaltrials.gov at three points in time: 30 November, 2004, 25 February, 2007 and 25 July, 2009. We found a total of 152 trials that met our criteria for 'large-scale clinical trials' examining cardiovascular diseases in Japan. Of these, 72.4% were randomized controlled trials (RCTs). Of 152 trials, 9.2% of the trials examined more than 10,000 participants, and 42.8% examined between 1,000 and 10,000 participants. The number of large-scale clinical trials markedly increased from 2001 to 2004, but suddenly decreased in 2007, then began to increase again. Ischemic heart disease (39.5%) was the most common target disease. Most of the larger-scale trials were funded by private organizations such as pharmaceutical companies. The designs and results of 13 trials were not disclosed. To improve the quality of clinical

Why prudence is needed when interpreting articles reporting clinical trial results in mental health.

PubMed

Dal-Ré, Rafael; Bobes, Julio; Cuijpers, Pim

2017-03-28

Clinical trial results' reliability is impacted by reporting bias. This is primarily manifested as publication bias and outcome reporting bias. Mental health trials are prone to two methodological deficiencies: (1) using small numbers of participants that facilitates false positive findings and exaggerated size effects, and (2) the obligatory use of psychometric scales that require subjective assessments. These two deficiencies contribute to the publication of unreliable results. Considerable reporting bias has been found in safety and efficacy findings in psychotherapy and pharmacotherapy trials. Reporting bias can be carried forward to meta-analyses, a key source for clinical practice guidelines. The final result is the frequent overestimation of treatment effects that could impact patients and clinician-informed decisions. Prospective registration of trials and publication of results are the two major methods to reduce reporting bias. Prospective trial registration will allow checking whether they are published (so it will help to prevent publication bias) and, if published, whether those outcomes and analyses that were deemed as appropriate before trial commencement are actually published (hence helping to find out selective reporting of outcomes). Unfortunately, the rate of registered trials in mental health interventions is low and, frequently, of poor quality. Clinicians should be prudent when interpreting the results of published trials and some meta-analyses - such as those conducted by scientists working for the sponsor company or those that only include published trials. Prescribers, however, should be confident when prescribing drugs following the summary of product characteristics, since regulatory agencies have access to all clinical trial results.

Molecular imaging in neuroendocrine tumors: molecular uptake mechanisms and clinical results.

PubMed

Koopmans, Klaas P; Neels, Oliver N; Kema, Ido P; Elsinga, Philip H; Links, Thera P; de Vries, Elisabeth G E; Jager, Pieter L

2009-09-01

Neuroendocrine tumors can originate almost everywhere in the body and consist of a great variety of subtypes. This paper focuses on molecular imaging methods using nuclear medicine techniques in neuroendocrine tumors, coupling molecular uptake mechanisms of radiotracers with clinical results. A non-systematic review is presented on receptor based and metabolic imaging methods. Receptor-based imaging covers the molecular backgrounds of somatostatin, vaso-intestinal peptide (VIP), bombesin and cholecystokinin (CCK) receptors and their link with nuclear imaging. Imaging methods based on specific metabolic properties include meta-iodo-benzylguanide (MIBG) and dimercapto-sulphuric acid (DMSA-V) scintigraphy as well as more modern positron emission tomography (PET)-based methods using radio-labeled analogues of amino acids, glucose, dihydroxyphenylalanine (DOPA), dopamine and tryptophan. Diagnostic sensitivities are presented for each imaging method and for each neuroendocrine tumor subtype. Finally, a Forest plot analysis of diagnostic performance is presented for each tumor type in order to provide a comprehensive overview for clinical use.

Indirect zirconia-reinforced lithium silicate ceramic CAD/CAM restorations: Preliminary clinical results after 12 months.

PubMed

Zimmermann, Moritz; Koller, Christina; Mehl, Albert; Hickel, Reinhard

2017-01-01

No clinical data are available for the new computer-aided design/computer-assisted manufacture (CAD/CAM) material zirconia-reinforced lithium silicate (ZLS) ceramic. This study describes preliminary clinical results for indirect ZLS CAD/CAM restorations after 12 months. Indirect restorations were fabricated, using the CEREC method and intraoral scanning (CEREC Omnicam, CEREC MCXL). Sixty-seven restorations were seated adhesively (baseline). Sixty restorations were evaluated after 12 months (follow-up), using modified FDI criteria. Two groups were established, according to ZLS restorations' post-processing procedure prior to adhesive seating: group I (three-step polishing, n = 32) and group II (fire glazing, n = 28). Statistical analysis was performed with Mann-Whitney U test and Wilcoxon test (P < .05). The success rate of indirect ZLS CAD/CAM restorations after 12 months was 96.7%. Two restorations clinically failed as a result of bulk fracture (failure rate 3.3%). No statistically significant differences were found for baseline and follow-up criteria (Wilcoxon test, P > .05). Statistically significant differences were found for criteria surface gloss for group I and group II (Mann-Whitney U test, P < .05). This study demonstrates ZLS CAD/CAM restorations have a high clinical success rate after 12 months. A longer clinical evaluation period is necessary to draw further conclusions.

Combinations of Drugs in the Treatment of Obesity

PubMed Central

Halpern, Bruno; Oliveira, Eduardo S. L.; Faria, André M.; Halpern, Alfredo; de Melo, Maria Edna; Cercato, Cintia; Mancini, Marcio C.

2010-01-01

Obesity is a chronic disease associated with excess morbidity and mortality. Clinical treatment, however, currently offers disappointing results, with very high rates of weight loss failure or weight regain cycles, and only two drugs (orlistat and sibutramine) approved for long-term use. Drugs combinations can be an option for its treatment but, although widely used in clinical practice, very few data are available in literature for its validation. Our review focuses on the rationale for their use, with advantages and disadvantages; on combinations often used, with or without studies; and on new perspectives of combinations being studied mainly by the pharmaceutical industry. PMID:27713360

The Difficulty in Finding Relationships Between ERPs and Clinical Symptoms of Schizophrenia.

PubMed

Ford, Judith M

2018-01-01

It has been surprisingly difficult to find associations between neural signatures of schizophrenia and the symptoms that define it. That is, many of the legacy components of the event-related potential (ERP)- P50, N100, P200, P300-are reduced in patients with schizophrenia, in first-degree relatives of patients with schizophrenia, in schizophrenia patients early in their illness, and even in people at clinical high risk for schizophrenia. Nevertheless, these ERP components tend to be relatively insensitive to symptoms. This might be due to a number of reasons. First, this could reflect a lack of relationship, a failure to report disappointing findings, or a failure to test for relationships. Second, many ERP studies were not designed to be sensitive to symptoms or to the mechanisms that might underlie them. Third, assessing symptoms is sometimes dependent on the patients' ability to describe unfathomable experiences and the clinicians' ability to understand and interpret them. Fourth, medications and comorbidities may decouple the symptoms from the neurobiology. Finally, we must also consider the possibility that the schizophrenia diagnosis breeds truer than the symptoms it comprises.

Mitochondrial encephalopathy, lactic acidosis, and strokelike episodes: basic concepts, clinical phenotype, and therapeutic management of MELAS syndrome.

PubMed

Sproule, Douglas M; Kaufmann, Petra

2008-10-01

Since the initial description almost 25 years ago, the syndrome of mitochondrial encephalopathy, lactic acidosis, and strokelike episodes (MELAS) has been a useful model to study the complex interplay of factors that define mitochondrial disease. This syndrome, most commonly caused by an A-to-G transition mutation at position 3243 of the mitochondrial genome, is typified by characteristic neurological manifestations including seizures, encephalopathy, and strokelike episodes, as well as other frequent secondary manifestations including short stature, cognitive impairment, migraines, depression, cardiomyopathy, cardiac conduction defects, and diabetes mellitus. In this review, we discuss the history, pathogenesis, clinical features, and diagnostic and management strategies of mitochondrial disease in general and of MELAS in particular. We explore features of mitochondrial genetics, including the concepts of heteroplasmy, mitotic segregation, and threshold effect, as a basis for understanding the variability and complicated inheritance patterns seen with this group of diseases. We also describe systemic manifestations of MELAS-associated mutations, including cardiac, renal, endocrine, gastrointestinal, and endothelial abnormalities and pathology, as well as the hypothetical role of derangements to COX enzymatic function in driving the unique pathology and clinical manifestations of MELAS. Although therapeutic options for MELAS and other mitochondrial diseases remain limited, and recent trials have been disappointing, we also consider current and potential therapeutic modalities.

Communicating their individual results to participants in an environmental exposure study: Insights from clinical ethics

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

Deck, W.; Kosatsky, T.

1999-02-01

A study measuring the uptake of chemical contaminants among sport fishers who consume fish caught in the St. Lawrence river is currently being conducted in Montreal, Canada. In this study, blood, hair, and urine collected from local sport fishers is being tested for heavy metals and persistent organochlorine chemicals. The objective of this study was to formulate a framework for determining what information to communicate to individual subjects of a study measuring biomarkers of exposure, consistent with the principles of ethical clinical and research practice. Methods consisted of review of the scope of environmental exposure studies, including the use ofmore » biomarker measurement in clinical medicine and environmental research and the relevant principles of clinical ethics and research practice. An exposure biomarker study is designed to elucidate constitutional, behavioral, and environmental determinants of tissue concentrations of exogenous substances. Ethical clinical and research practice, aiming to maximize autonomy and beneficence and to minimize harm, requires that study findings concerning the determinants of exposure be communicated to study participants. In addition, investigators should reference clinical action levels beyond which individual biomarker results are routinely communicated to participants. When biomarkers have no known relation to risk, or when levels fall below action levels, it may be preferable not co communicate individual results, if this arrangement has been formalized at the time of informed consent.« less

Creating a passion for safety vs. management oversight and inspection

Treesearch

Jim Saveland

1995-01-01

I was disappointed with the OSHA report of the South Canyon Fire. My feelings are not the result of any need to defend my agency (USDA Forest Service). In another time and place, I thought the OSHA report following the death of Bill Martin (a smokejumper who died in a training jump) was right on target. In that instance I was disappointed with my agency's response...

Necrotizing fasciitis: treatment concepts and clinical results.

PubMed

Leiblein, M; Marzi, I; Sander, A L; Barker, J H; Ebert, F; Frank, J

2018-04-01

Necrotizing fasciitis is a life-threatening soft tissue infection characterized by a rapid spreading infection of the subcutaneous tissue and in particular the fascia. The management of infected tissues requires a rapid diagnosis, immediate aggressive surgical management and an extended debridement. In some cases early amputations of the affected tissues and maximum intensive care treatment, in case of sepsis, are required. Due to a rising number of cases we aimed to evaluate our patients in a retrospective review. All patients diagnosed with necrotizing fasciitis from 2014 to 2016 (21 months) in our level one trauma center were identified. Their charts were reviewed and data were analyzed in terms of demographic and social information, microbiological results, therapeutic course, socio-economic outcome and mortality. We found 15 patients with necrotizing fasciitis. None of these died in the observation period. The mean number of surgical interventions was seven. Two patients underwent limb amputation; diabetes mellitus was assigned with a significant higher risk for amputation. The mean hospitalization was 32 days, including 8 days on intensive care unit. Of the discovered bacteria 93% were sensitive to the initial antibiotic treatment with Ampicillin, Clindamycin and Clont. Surgical therapy is indicated if necrotizing fasciitis is suspected. Diabetes mellitus was a clinical predictor of limb amputation in patients with necrotizing fasciitis in our cohort. Aminopenicillin ± sulbactam in combination with clindamycin and/or metronidazole is recommended as initial calculated antibiotic treatment.

Midterm Clinical and Radiographic Results of Mobile-Bearing Revision Total Knee Arthroplasty.

PubMed

Kim, Raymond H; Martin, J Ryan; Dennis, Douglas A; Yang, Charlie C; Jennings, Jason M; Lee, Gwo-Chin

2017-06-01

Constrained implants are frequently required in revision total knee arthroplasty (TKA) and are associated with an increase in aseptic component loosening and damage or wear to the constraining mechanisms, compared with primary TKA. The purpose of the following study was to evaluate the midterm clinical and radiographic results including the incidence of bearing complications in a group of patients undergoing revision TKA using mobile-bearing revision TKA implants. We retrospectively reviewed 316 consecutive mobile-bearing revision TKAs performed at 2 centers between 2006 and 2010. There were 183 women and 133 men with a mean age of 66 years. The patients were evaluated clinically using the Knee Society scores. A radiographic analysis was performed. Bearing specific complications (ie, instability or dislocation) were recorded. Patients were followed-up for a minimum of 24 months and a median of 59.88 months (range 24-121.2). The average Knee Society knee score and function scores increased from 40.8 and 47.9 points preoperatively to 80 points and 70.3 points, respectively (P < .01). The average knee flexion improved from 105.6° preoperatively to 117.4° postoperatively (P < .01). Eight patients required subsequent implant revision. No cases of bearing complications were observed. Revision TKA using mobile-bearing revision components demonstrated favorable midterm clinical and radiographic results with no occurrence of bearing instability or dislocation. Longer follow-up is required to evaluate for potential advantages of mobile-bearings over fixed-bearing revision components in terms of polyethylene wear reduction, reduced stress transmission across fixation interfaces, and reduced stress on the polyethylene post. Copyright © 2017 Elsevier Inc. All rights reserved.

Predicting clinical trial results based on announcements of interim analyses

PubMed Central

2014-01-01

Background Announcements of interim analyses of a clinical trial convey information about the results beyond the trial’s Data Safety Monitoring Board (DSMB). The amount of information conveyed may be minimal, but the fact that none of the trial’s stopping boundaries has been crossed implies that the experimental therapy is neither extremely effective nor hopeless. Predicting success of the ongoing trial is of interest to the trial’s sponsor, the medical community, pharmaceutical companies, and investors. We determine the probability of trial success by quantifying only the publicly available information from interim analyses of an ongoing trial. We illustrate our method in the context of the National Surgical Adjuvant Breast and Bowel (NSABP) trial, C-08. Methods We simulated trials based on the specifics of the NSABP C-08 protocol that were publicly available. We quantified the uncertainty around the treatment effect using prior weights for the various possibilities in light of other colon cancer studies and other studies of the investigational agent, bevacizumab. We considered alternative prior distributions. Results Subsequent to the trial’s third interim analysis, our predictive probabilities were: that the trial would eventually be successful, 48.0%; would stop for futility, 7.4%; and would continue to completion without statistical significance, 44.5%. The actual trial continued to completion without statistical significance. Conclusions Announcements of interim analyses provide information outside the DSMB’s sphere of confidentiality. This information is potentially helpful to clinical trial prognosticators. ‘Information leakage’ from standard interim analyses such as in NSABP C-08 is conventionally viewed as acceptable even though it may be quite revealing. Whether leakage from more aggressive types of adaptations is acceptable should be assessed at the design stage. PMID:24607270

[Clinical, hemodynamic and angiographic results of total cavo-pulmonary connection].

PubMed

Jimenez, A C; Neville, P; Chamboux, C; Crenn, R; Vaillant, M C; Marchand, M; Chantepie, A

1998-05-01

The aim of the study was to assess the short and medium term results of total cavo-pulmonary connection based on analysis of the functional status, the cavo-pulmonary circulation and the surgical techniques, and the hepatic consequences. Fifteen patients with congenital defects beyond repair were treated by total cavo-pulmonary connection at Tours between March 1st 1992 and July 30th 1996. There were 12 children (mean age: 6.3 years) and 3 adults aged 25 to 28. Results were assessed by clinical examination, hepatic function tests and cardiovascular investigations including right heart catheterisation with angiography in 14 patients. There were no fatalities. Seven patients were in functional Class I and 8 in Class II at medium term (average follow-up of 33 months). Hepatic function was mildly abnormal in all patients with an increase in serum bilirubin and gamma GT, and a decrease in the coagulation factors. The mean pressures in the atrial channel were 12 mmHg (9-16 mmHg), in the superior vena 13.2 mmHg (10-18 mmHg), in the right pulmonary artery 9.5 mmHg (7-15 mmHg) and 11.6 mmHg (8-16 mmHg) in the left pulmonary artery. Significant residual stenosis of a pulmonary branch was observed in 2 cases. The cavo-pulmonary anastomoses were out of line, one from the other, in all cases. The atrial channel was tubular in 9 cases and dilated with slight stagnation of the contrast medium in its inferior region in 5 cases. Total cavo-pulmonary connection transformed the clinical status of these patients but was associated with minor abnormalities of liver function. The quality of the cavo-pulmonary circulation and the surgical anastomoses was estimated to be satisfactory in the majority of cases.

How frequently do the results from completed US clinical trials enter the public domain?--A statistical analysis of the ClinicalTrials.gov database.

PubMed

Saito, Hiroki; Gill, Christopher J

2014-01-01

Achieving transparency in clinical trials, through either publishing results in a journal or posting results to the ClinicalTrials.gov (CTG) web site, is an essential public health good. However, it remains unknown what proportion of completed studies achieve public disclosure of results (PDOR), or what factors explain these differences. We analyzed data from 400 randomly selected studies within the CTG database that had been listed as 'completed' and had at least four years in which to disclose results. Using Kaplan-Meier curves, we calculated times from completion to PDOR (defined as publishing the primary outcomes in a journal and/or posting results to CTG), and identified explanatory variables predicting these outcomes using Cox proportional hazards models. Among the 400 clinical trials, 118 (29.5%) failed to achieve PDOR within four years of completion. The median day from study completion to PDOR among 282 studies (70.5%) that achieved PDOR was 602 days (mean 647 days, SD 454 days). Studies were less likely to achieve PDOR if at earlier stages (phase 2 vs. phase 3/4, adjusted HR 0.60, 95% CI 0.47-0.78), if they only included adult subjects (adjusted HR 0.61, 95% CI 0.45-0.83), involved randomization (adjusted HR 0.62, 95% CI 0.46-0.83), or had smaller sample sizes (≤50 subjects vs. >50, adjusted HR 0.60, 95% CI 0.44-0.83). Industry-funded studies were significantly less likely to be published than non-industry or blended studies (adjusted HR 0.49, 95% CI 0.36-0.66). A significant proportion of completed studies did not achieve PDOR within the four years of follow-up, particularly smaller studies at earlier stages of development with industry funding. This constitutes reporting bias and threatens the validity of the clinical research literature in the US.

Clinical results from a noninvasive blood glucose monitor

NASA Astrophysics Data System (ADS)

Blank, Thomas B.; Ruchti, Timothy L.; Lorenz, Alex D.; Monfre, Stephen L.; Makarewicz, M. R.; Mattu, Mutua; Hazen, Kevin

2002-05-01

Non-invasive blood glucose monitoring has long been proposed as a means for advancing the management of diabetes through increased measurement and control. The use of a near-infrared, NIR, spectroscopy based methodology for noninvasive monitoring has been pursued by a number of groups. The accuracy of the NIR measurement technology is limited by challenges related to the instrumentation, the heterogeneity and time-variant nature of skin tissue, and the complexity of the calibration methodology. In this work, we discuss results from a clinical study that targeted the evaluation of individual calibrations for each subject based on a series of controlled calibration visits. While the customization of the calibrations to individuals was intended to reduce model complexity, the extensive requirements for each individual set of calibration data were difficult to achieve and required several days of measurement. Through the careful selection of a small subset of data from all samples collected on the 138 study participants in a previous study, we have developed a methodology for applying a single standard calibration to multiple persons. The standard calibrations have been applied to a plurality of individuals and shown to be persistent over periods greater than 24 weeks.

Novel Systemic Therapies in Advanced Liposarcoma: A Review of Recent Clinical Trial Results

PubMed Central

Tseng, William W.; Somaiah, Neeta; Lazar, Alexander J.; Lev, Dina C.; Pollock, Raphael E.

2013-01-01

Liposarcoma is one of the most common adult soft tissue sarcomas an consists of three histologic subtypes (well and dedifferentiated, myxoid/round cell, and pleomorphic). Surgery is the mainstay of treatment for localized disease; however for unresectable or metastatic disease, effective treatment options are currently limited. In the past decade, a better understanding of the distinct genetic and molecular aberrations for each of the three histologic subtypes has led to the development of several novel systemic therapies. Data from phase I and early phase II clinical trials have been reported. Despite challenges with conducting clinical trials in liposarcoma, preliminary results for several of these novel, biology-driven therapies are encouraging. PMID:24216990

Automated pre-processing and multivariate vibrational spectra analysis software for rapid results in clinical settings

NASA Astrophysics Data System (ADS)

Bhattacharjee, T.; Kumar, P.; Fillipe, L.

2018-02-01

Vibrational spectroscopy, especially FTIR and Raman, has shown enormous potential in disease diagnosis, especially in cancers. Their potential for detecting varied pathological conditions are regularly reported. However, to prove their applicability in clinics, large multi-center multi-national studies need to be undertaken; and these will result in enormous amount of data. A parallel effort to develop analytical methods, including user-friendly software that can quickly pre-process data and subject them to required multivariate analysis is warranted in order to obtain results in real time. This study reports a MATLAB based script that can automatically import data, preprocess spectra— interpolation, derivatives, normalization, and then carry out Principal Component Analysis (PCA) followed by Linear Discriminant Analysis (LDA) of the first 10 PCs; all with a single click. The software has been verified on data obtained from cell lines, animal models, and in vivo patient datasets, and gives results comparable to Minitab 16 software. The software can be used to import variety of file extensions, asc, .txt., .xls, and many others. Options to ignore noisy data, plot all possible graphs with PCA factors 1 to 5, and save loading factors, confusion matrices and other parameters are also present. The software can provide results for a dataset of 300 spectra within 0.01 s. We believe that the software will be vital not only in clinical trials using vibrational spectroscopic data, but also to obtain rapid results when these tools get translated into clinics.

Results of a coordination and shared clinical information programme between primary care and nephrology.

PubMed

García García, Manuel; Valenzuela Mújica, Mari Pau; Martínez Ocaña, Juan Carlos; Otero López, María del Sol; Ponz Clemente, Esther; López Alba, Thaïs; Gálvez Hernández, Enrique

2011-01-01

The high prevalence of chronic kidney disease (CKD) in the general population has created a need to coordinate specialised nephrology care and primary care. Although several systems have been developed to coordinate this process, published results are scarce and contradictory. To present the results of the application of a coordinated programme between nephrology care and primary care through consultations and a system of shared clinical information to facilitate communication and improve the criteria for referring patients. Elaboration of a coordinated care programme by the primary care management team and the nephrology department, based on the SEN-SEMFYC consensus document and a protocol for the study and management of arterial hypertension (AHT). Explanation and implementation in primary health care units. A directory of specialists’ consultations was created, both in-person and via e-mail. A continuous training programme in kidney disease and arterial hypertension was implemented in the in-person consultation sessions. The programme was progressively implemented over a three-year period (2007-2010) in an area of 426,000 inhabitants with 230 general practitioners. Use of a clinical information system named Salut en Xarxa that allows access to clinical reports, diagnoses, prescriptions, test results and clinical progression. Improved referral criteria between primary care and specialised nephrology service. Improved prioritisation of visits. Progressive increase in referrals denied by specialists (28.5% in 2009), accompanied by an explanatory report including suggestions for patient management. Decrease in first nephrology outpatient visits that have been referred from primary care (15% in 2009). Family doctors were generally satisfied with the improvement in communication and the continuous training programme. The main causes for denying referral requests were: patients >70 years with stage 3 CKD (44.15%); patients <70 years with stage 3a CKD (19

The role of Iloprost on bone edema and osteonecrosis: Safety and clinical results.

PubMed

Pountos, Ippokratis; Giannoudis, Peter V

2018-03-01

Iloprost is a commercially available prostaglandin I 2 (PGI 2 ) analogue that is shown to have antithrombotic, vasodilatative and antiproliferative effects. A number of clinical studies have shown that Iloprost can be effective in the management of bone marrow oedema and the treatment of avascular necrosis. The aim of this manuscript is to present our current understanding on the effect of Iloprost on the treatment of these conditions. Areas covered: The authors offer a comprehensive review of the existing literature on the experimental and clinical studies analysing the effect of Iloprost on bone, bone marrow oedema and avascular necrosis. Expert opinion: The available data from the clinical studies suggest that Iloprost has limited effect in advanced stages of avascular necrosis. However, literature suggests that Iloprost administration can be a viable option in the management of bone marrow oedema and early stages of osteonecrosis. Despite these promising results its effect on bone homeostasis needs further elucidation. Moreover, further data on its safety, dosage and efficiency through randomized multicenter studies are desirable in order to reach final conclusions.

Sterol Composition of Clinically Relevant Mucorales and Changes Resulting from Posaconazole Treatment.

PubMed

Müller, Christoph; Neugebauer, Thomas; Zill, Patrizia; Lass-Flörl, Cornelia; Bracher, Franz; Binder, Ulrike

2018-05-19

Mucorales are fungi with increasing importance in the clinics. Infections take a rapidly progressive course resulting in high mortality rates. The ergosterol biosynthesis pathway and sterol composition are of interest, since they are targeted by currently applied antifungal drugs. Nevertheless, Mucorales often exhibit resistance to these drugs, resulting in therapeutic failure. Here, sterol patterns of six clinically relevant Mucorales ( Lichtheimia corymbifera , Lichtheimia ramosa , Mucor circinelloides , Rhizomucor pusillus , Rhizopus arrhizus , and Rhizopus microsporus ) were analysed in a targeted metabolomics fashion after derivatization by gas chromatography-mass spectrometry. Additionally, the effect of posaconazole (POS) treatment on the sterol pattern of R. arrhizus was evaluated. Overall, fifteen different sterols were detected with species dependent variations in the total and relative sterol amount. Sterol analysis from R. arrhizus hyphae confronted with sublethal concentrations of posaconazole revealed the accumulation of 14-methylergosta-8,24-diene-3,6-diol, which is a toxic sterol that was previously only detected in yeasts. Sterol content and composition were further compared to the well-characterized pathogenic mold Aspergillus fumigatus . This work contributes to a better understanding of the ergosterol biosynthesis pathway of Mucorales, which is essential to improve antifungal efficacy, the identification of targets for novel drug design, and to investigate the combinatorial effects of drugs targeting this pathway.

Semiautomated System for Nonurgent, Clinically Significant Pathology Results.

PubMed

O'Connor, Stacy D; Khorasani, Ramin; Pochebit, Stephen M; Lacson, Ronilda; Andriole, Katherine P; Dalal, Anuj K

2018-04-01

 Failure of timely test result follow-up has consequences including delayed diagnosis and treatment, added costs, and potential patient harm. Closed-loop communication is key to ensure clinically significant test results (CSTRs) are acknowledged and acted upon appropriately. A previous implementation of the Alert Notification of Critical Results (ANCR) system to facilitate closed-loop communication of imaging CSTRs yielded improved communication of critical radiology results and enhanced adherence to institutional CSTR policies.  This article extends the ANCR application to pathology and evaluates its impact on closed-loop communication of new malignancies, a common and important type of pathology CSTR.  This Institutional Review Board-approved study was performed at a 150-bed community, academically affiliated hospital. ANCR was adapted for pathology CSTRs. Natural language processing was used on 30,774 pathology reports 13 months pre- and 13 months postintervention, identifying 5,595 reports with malignancies. Electronic health records were reviewed for documented acknowledgment for a random sample of reports. Percent of reports with documented acknowledgment within 15 days assessed institutional policy adherence. Time to acknowledgment was compared pre- versus postintervention and postintervention with and without ANCR alerts. Pathologists were surveyed regarding ANCR use and satisfaction.  Acknowledgment within 15 days was documented for 98 of 107 (91.6%) pre- and 89 of 103 (86.4%) postintervention reports ( p  = 0.2294). Median time to acknowledgment was 7 days (interquartile range [IQR], 3, 11) preintervention and 6 days (IQR, 2, 10) postintervention ( p  = 0.5083). Postintervention, median time to acknowledgment was 2 days (IQR, 1, 6) for reports with ANCR alerts versus 6 days (IQR, 2.75, 9) for reports without alerts ( p  = 0.0351). ANCR alerts were sent on 15 of 103 (15%) postintervention reports. All pathologists reported that the ANCR

Does information from ClinicalTrials.gov increase transparency and reduce bias? Results from a five-report case series.

PubMed

Adam, Gaelen P; Springs, Stacey; Trikalinos, Thomas; Williams, John W; Eaton, Jennifer L; Von Isenburg, Megan; Gierisch, Jennifer M; Wilson, Lisa M; Robinson, Karen A; Viswanathan, Meera; Middleton, Jennifer Cook; Forman-Hoffman, Valerie L; Berliner, Elise; Kaplan, Robert M

2018-04-16

We investigated whether information in ClinicalTrials.gov would impact the conclusions of five ongoing systematic reviews. We considered five reviews that included 495 studies total. Each review team conducted a search of ClinicalTrials.gov up to the date of the review's last literature search, screened the records using the review's eligibility criteria, extracted information, and assessed risk of bias and applicability. Each team then evaluated the impact of the evidence found in ClinicalTrials.gov on the conclusions in the review. Across the five reviews, the number of studies that had both a registry record and a publication varied widely, from none in one review to 43% of all studies identified in another. Among the studies with both a record and publication, there was also wide variability in the match between published outcomes and those listed in ClinicalTrials.gov. Of the 173 total ClinicalTrials.gov records identified across the five projects, between 11 and 43% did not have an associated publication. In the 14% of records that contained results, the new data provided in the ClinicalTrials.gov records did not change the results or conclusions of the reviews. Finally, a large number of published studies were not registered in ClinicalTrials.gov, but many of these were published before ClinicalTrials.gov's inception date of 2000. Improved prospective registration of trials and consistent reporting of results in ClinicalTrials.gov would help make ClinicalTrials.gov records more useful in finding unpublished information and identifying potential biases. In addition, consistent indexing in databases, such as MEDLINE, would allow for better matching of records and publications, leading to increased utility of these searches for systematic review projects.

Reprint of: B cell elimination in systemic lupus erythematosus. Clin. Immunol. 146(2) 90-103.

PubMed

Furtado, João; Isenberg, David A

2013-09-01

Systemic lupus erythematosus (SLE) is an autoimmune disorder with a worldwide distribution, potentially life-threatening with considerable morbidity. The elimination of pathogenic B cells has emerged as a rational therapeutic option. Many open label studies have reported encouraging results in which clinical and serological remission have invariably been described, often enabling the reduction of steroid and immunosuppressive treatment. However, the results from randomized controlled studies have been disappointing and several questions remain to be answered. In this review we will focus on results of B cell direct depletion in the treatment of patients with systemic lupus erythematosus. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

Malignant glioma--a nemesis which requires clinical and basic investigation in radiation oncology

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

Davis, L.W.

1989-06-01

Malignant gliomas account for 40% of all central nervous system malignancies. These are essentially localized neoplastic tumors that have defied most treatment. In spite of improved techniques, surgery is unlikely to increase survival further since true cancer operations cannot be performed. Radiation therapy has made a significant difference in outcome. Investigation in radiation oncology is essential for further improvement in the treatment of these tumors. The pattern of failure is local tumor recurrence, but the method to overcome this resistance to treatment is not clear. Radiation therapy techniques and inherent radio-resistance have been considered as possible reasons for failure. Withmore » newer imaging procedures, the extent of tumor can be more accurately defined allowing improved treatment planning. Identifying an effective treatment program is more difficult. Studies have documented the beneficial effect of radiation therapy, but the optimal dose or fractionation schedule has not been determined. Whereas some studies have reported improved survival using higher radiation doses, others have reported no benefit. More recently, studies of multiple daily fractionation schedules have been conducted using two or three daily fractions. Equally confusing results have been reported. Histologically, these tumors have necrotic areas and may be radioresistant due to hypoxic cells. Treatment methods designed to overcome the radioprotective effect of hypoxia have yielded disappointing results. The addition of hypoxic cell sensitizers has not produced the expected improvement in outcome. Studies using neutron radiation therapy report tumor control but not improved survival. Radiobiologic information is now available which may contribute to our understanding of the response of these tumors to radiation. Further laboratory and clinical investigation is required. 83 references.« less

An initiative to improve the management of clinically significant test results in a large health care network.

PubMed

Roy, Christopher L; Rothschild, Jeffrey M; Dighe, Anand S; Schiff, Gordon D; Graydon-Baker, Erin; Lenoci-Edwards, Jennifer; Dwyer, Cheryl; Khorasani, Ramin; Gandhi, Tejal K

2013-11-01

The failure of providers to communicate and follow up clinically significant test results (CSTR) is an important threat to patient safety. The Massachusetts Coalition for the Prevention of Medical Errors has endorsed the creation of systems to ensure that results can be received and acknowledged. In 2008 a task force was convened that represented clinicians, laboratories, radiology, patient safety, risk management, and information systems in a large health care network with the goals of providing recommendations and a road map for improvement in the management of CSTR and of implementing this improvement plan during the sub-force sequent five years. In drafting its charter, the task broadened the scope from "critical" results to "clinically significant" ones; clinically significant was defined as any result that requires further clinical action to avoid morbidity or mortality, regardless of the urgency of that action. The task force recommended four key areas for improvement--(1) standardization of policies and definitions, (2) robust identification of the patient's care team, (3) enhanced results management/tracking systems, and (4) centralized quality reporting and metrics. The task force faced many challenges in implementing these recommendations, including disagreements on definitions of CSTR and on who should have responsibility for CSTR, changes to established work flows, limitations of resources and of existing information systems, and definition of metrics. This large-scale effort to improve the communication and follow-up of CSTR in a health care network continues with ongoing work to address implementation challenges, refine policies, prepare for a new clinical information system platform, and identify new ways to measure the extent of this important safety problem.

Demographic, tumor and clinical features of clinical trials versus clinical practice patients with HER2-positive early breast cancer: results of a prospective study.

PubMed

Arpino, Grazia; Michelotti, Andrea; Truini, Mauro; Montemurro, Filippo; Russo, Stefania; Palumbo, Raffaella; Zamagni, Claudio; Latorre, Agnese; Bruzzese, Dario; Riccardi, Ferdinando; De Laurentiis, Michelino; Beano, Alessandra; Biganzoli, Laura; Zaniboni, Alberto; Laudadio, Lucio; Malagoli, Maria; Bilancia, Domenico; Schettini, Francesco; Giuliano, Mario; Cazzaniga, Marina Elena; De Placido, Sabino

2016-03-01

Several randomized clinical trials (RCTs) have demonstrated the efficacy of trastuzumab-based adjuvant therapy in HER2-positive breast cancer (BC). However, RCT patients may not invariably be representative of patients routinely seen in clinical practice (CP). To address this issue, we compared the clinical and tumor features of RCT and CP patients with HER2-positive BC. From January to December 2012, 650 consecutive patients with HER2-positive early BC, treated in 36 different types of Italian healthcare facilities, were enrolled in this study. Age, treatment, tumor size (T), nodes (N), grade (G), estrogen receptor (ER) and progesterone receptor (PgR) status were prospectively collected in these CP patients. The same data were extracted from the main adjuvant trastuzumab RCTs and pooled using the random-effects model of DerSimonian and Laird. RCT and CP patients were compared by using the Cochran Q statistics. Versus RCT patients, CP patients were more likely to be older than 50 years (65 vs. 49 %; p < 0.0001) and to have HR (ER and/or PgR)-positive (72 vs. 54 %; p < 0.0001) BC and less likely to have tumor >2 cm (T ≥ 2 cm 39 vs. 59 %; p < 0.0001), positive N (47 vs. 89 %; p < 0.0001) and a high G (61 vs. 67 %; p = 0.0241). CP patients more frequently received adjuvant endocrine therapy (70 vs. 57 %; p < 0.0003) and less frequently adjuvant chemotherapy (97 vs. 99.7 %; p < 0.0001). Most tumor and clinical features differed significantly between CP and RCT patients. These data raise concerns about the applicability of RCT results to CP patients.

Clinical and histopathological results following TriPollar radiofrequency skin treatments.

PubMed

Kaplan, Haim; Gat, Andrea

2009-06-01

Skin laxity, wrinkles and cellulite are common aesthetic problems associated with the aging process. These symptoms are due to the weakening and thinning of dermal connective tissue and the enlargement of hypodermal fat cells. The aim of this study was to evaluate the safety and efficacy of the TriPollar RF technology in reducing fat and collagen regeneration. Twelve healthy patients underwent weekly treatments on different body sites using the TriPollar technology. Treatment areas were photographed and measured and patient satisfaction was monitored. One abdominal patient consented to a series of TriPollar treatments prior to her scheduled abdominoplasty. A controlled histopathology analysis was performed on skin samples taken during the abdominoplasty procedure. Histopathological examination revealed marked differences between treated and non-treated abdominal skin areas. An increase of 49% in dermal thickness, focal thickening of collagen fibers and focal shrinkage of fat cells was shown following TriPollar treatments. Average patient satisfaction indicated clear satisfaction with the clinical results achieved. The TriPollar is a safe and effective non-invasive technology leading to skin tightening and body shaping. Histology results indicate changes at the dermal and fat layers following TriPollar treatments resulting in increased collagen regeneration and stimulated fat metabolism.

Clinical results of carotid artery stenting versus carotid endarterectomy

PubMed Central

Akinci, Tuba; Derle, Eda; Kibaroğlu, Seda; Harman, Ali; Kural, Feride; Cınar, Pınar; Kilinc, Munire; Akay, Hakki T.; Can, Ufuk; Benli, Ulku S.

2016-01-01

Objective: To review our results of carotid artery stenting (CAS) and carotid endarterectomy (CEA). Methods: We evaluated the medical records of patients undergoing carotid artery revascularization procedure, between 2001 and 2013 in Baskent University Hospital, Ankara, Turkey. Carotid artery stenting or CEA procedures were performed in patients with asymptomatic carotid stenosis (≥70%) or symptomatic stenosis (≥50%). Demographic data, procedural details, and clinical outcomes were recorded. Primary outcome measures were in 30-day stroke/transient ischemic attacks (TIA)/amaurosis fugax or death. Secondary outcome measures were nerve injury, bleeding complications, length of stay in hospital, stroke, restenosis (ICA patency), and all-cause death during long-term follow-up. Results: One hundred ninety-four CEA and 115 CAS procedures were performed for symptomatic and/or asymptomatic carotid artery stenosis. There is no significant differences 30-day mortality and neurologic morbidity between CAS (13%) and CEA procedures (7.7%). Length of stay in hospital were significantly longer in CEA group (p=0.001). In the post-procedural follow up, only in symptomatic patients, restenosis rate was higher in the CEA group (p=.045). The other endpoints did not differ significantly. Conclusions: Endovascular stent treatment of carotid artery atherosclerotic disease is an alternative for vascular surgery, especially for patients that are high risk for standard CEA. The increasing experience, development of cerebral protection systems and new treatment protocols increases CAS feasibility. PMID:27744460

CT densitovolumetry in children with obliterative bronchiolitis: correlation with clinical scores and pulmonary function test results*,**

PubMed Central

Mocelin, Helena; Bueno, Gilberto; Irion, Klaus; Marchiori, Edson; Sarria, Edgar; Watte, Guilherme; Hochhegger, Bruno

2013-01-01

OBJECTIVE: To determine whether air trapping (expressed as the percentage of air trapping relative to total lung volume [AT%]) correlates with clinical and functional parameters in children with obliterative bronchiolitis (OB). METHODS: CT scans of 19 children with OB were post-processed for AT% quantification with the use of a fixed threshold of −950 HU (AT%950) and of thresholds selected with the aid of density masks (AT%DM). Patients were divided into three groups by AT% severity. We examined AT% correlations with oxygen saturation (SO2) at rest, six-minute walk distance (6MWD), minimum SO2 during the six-minute walk test (6MWT_SO2), FVC, FEV1, FEV1/FVC, and clinical parameters. RESULTS: The 6MWD was longer in the patients with larger normal lung volumes (r = 0.53). We found that AT%950 showed significant correlations (before and after the exclusion of outliers, respectively) with the clinical score (r = 0.72; 0.80), FVC (r = 0.24; 0.59), FEV1 (r = −0.58; −0.67), and FEV1/FVC (r = −0.53; r = −0.62), as did AT%DM with the clinical score (r = 0.58; r = 0.63), SO2 at rest (r = −0.40; r = −0.61), 6MWT_SO2 (r = −0.24; r = −0.55), FVC (r = −0.44; r = −0.80), FEV1 (r = −0.65; r = −0.71), and FEV1/FVC (r = −0.41; r = −0.52). CONCLUSIONS: Our results show that AT% correlates significantly with clinical scores and pulmonary function test results in children with OB. PMID:24473764

Preliminary clinical results with the ISL laser

NASA Astrophysics Data System (ADS)

Hoppeler, Thomas; Gloor, Balder

1992-08-01

The ISL laser (Intelligent Surgical Lasers, Inc.), a Nd:YLF picosecond pulse laser, is currently being used under investigational device exemption to perform microsurgery of the anterior segment of the eye. At different study sites procedures for cataract fragmentation and iridotomy, as well as for posterior capsulotomy after cataract surgery, are under evaluation. Other potential applications include: sclerostomy ab interno, the cutting of membranes in the anterior and posterior segment of the eye; corneal incisions; and corneal intrastromal effects. We discuss various clinically relevant aspects of the use of this picosecond laser. An overview of different computer controlled laser patterns is given.

Revision rates after knee replacement. Cumulative results from worldwide clinical studies versus joint registers.

PubMed

Pabinger, C; Berghold, A; Boehler, N; Labek, G

2013-02-01

To assess revision rates after knee arthroplasty by comparing the cumulative results from worldwide clinical studies and arthroplasty registers. We hypothesised that the revision rate of all clinical studies of a given implant and register data would not differ significantly. A systematic review of clinical studies in indexed peer-reviewed journals was performed followed by internal and external validation. Parameters for measurement of revision were applied (Revision for any reason, Revisions per 100 observed component years). Register data served as control group. Thirty-six knee arthroplasty systems were identified to meet the inclusion criteria: 21 total knee arthroplasty (TKA) systems, 14 unicondylar knee arthroplasty (UKA) systems, one patello-femoral implant system. For 13 systems (36%), no published study was available that contained revision data. For 17 implants (47%), publications were available dealing with radiographic, surgical or technical details, but power was too weak to compare revision rates at a significant level. Six implant systems (17%) had a significant number of revisions published and were finally analysed. In general, developers report better results than independent users. Studies from developers represent an overproportional share of all observed component years. Register data report overall 10-year revision rates of TKA of 6.2% (range: 4.9-7.8%), rates for UKA are 16.5% (range: 9.7-19.6%). Revision rates of all clinical studies of a given implant do not differ significantly from register data. However, significant differences were found between the revision rates published by developers and register data. Therefore the different data need to be interpreted in the context of the source of the information. Copyright © 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Effects of Carotenoids on Health: Are All the Same? Results from Clinical Trials.

PubMed

Cicero, Arrigo F G; Colletti, Alessandro

2017-01-01

Oxidative stress is implicated in the pathogenesis of a lot of age-related pathologies and some types of cancers. Carotenoids have shown antioxidant properties, due to the ability to quench singlet oxygen and to scavenge free radicals that may prevent and treat a wide range of chronic diseases. The aim of this review is to discuss the clinical evidence present in literature about the effects of carotenoids on human health and to evaluate their effectiveness in the prevention and treatment of many chronic diseases. We reviewed studies on carotenoids claiming to show an effect in the prevention and treatment of many chronic diseases. In particular, we focused our attention on clinical trials published on Natural Medicine Comprehensive Database and PubMed. A great number of clinical trials reported the beneficial effects of carotenoids on human health, in particular against skin, eye, hepatic, cardiovascular diseases and some types of cancer. Nevertheless, a few study evaluated the intake of carotenoids alone and sometimes the results are discording. Furthermore, irrational or excessive use of antioxidants may produce risk of potential toxicity. The antioxidant activity of carotenoids, taken with the diet or through nutritional supplements, seems to benefit human health. Therefore, it is necessary to test them alone and to evaluate their safety in longterm clinical trials on a large and heterogeneous sample of people. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Test result communication in primary care: clinical and office staff perspectives.

PubMed

Litchfield, Ian J; Bentham, Louise M; Lilford, Richard J; Greenfield, Sheila M

2014-10-01

To understand how the results of laboratory tests are communicated to patients in primary care and perceptions on how the process may be improved. Qualitative study employing staff focus groups. Four UK primary care practices. Staff involved in the communication of test results. Five main themes emerged from the data: (i) the default method for communicating results differed between practices; (ii) clinical impact of results and patient characteristics such as anxiety level or health literacy influenced methods by which patients received their test result; (iii) which staff member had responsibility for the task was frequently unclear; (iv) barriers to communicating results existed, including there being no system or failsafe in place to determine whether results were returned to a practice or patient; (v) staff envisaged problems with a variety of test result communication methods discussed, including use of modern technologies, such as SMS messaging or online access. Communication of test results is a complex yet core primary care activity necessitating flexibility by both patients and staff. Dealing with the results from increasing numbers of tests is resource intensive and pressure on practice staff can be eased by greater utilization of electronic communication. Current systems appear vulnerable with no routine method of tracing delayed or missing results. Instead, practices only become aware of missing results following queries from patients. The creation of a test communication protocol for dissemination among patients and staff would help ensure both groups are aware of their roles and responsibilities. © The Author 2014. Published by Oxford University Press.

Correlation between DNA ploidy, metaphase high-resolution comparative genomic hybridization results and clinical outcome of synovial sarcoma

PubMed Central

2011-01-01

Background Although synovial sarcoma is the 3rd most commonly occurring mesenchymal tumor in young adults, usually with a highly aggressive clinical course; remarkable differences can be seen regarding the clinical outcome. According to comparative genomic hybridization (CGH) data published in the literature, the simple and complex karyotypes show a correlation between the prognosis and clinical outcome. In addition, the connection between DNA ploidy and clinical course is controversial. The aim of this study was using a fine-tuning interpretation of our DNA ploidy results and to compare these with metaphase high-resolution CGH (HR-CGH) results. Methods DNA ploidy was determined on Feulgen-stained smears in 56 synovial sarcoma cases by image cytometry; follow up was available in 46 cases (average: 78 months). In 9 cases HR-CGH analysis was also available. Results 10 cases were found DNA-aneuploid, 46 were DNA-diploid by image cytometry. With fine-tuning of the diploid cases according to the 5c exceeding events (single cell aneuploidy), 33 cases were so called "simple-diploid" (without 5c exceeding events) and 13 cases were "complex-diploid"; containing 5c exceeding events (any number). Aneuploid tumors contained large numbers of genetic alterations with the sum gain of at least 2 chromosomes (A-, B- or C-group) detected by HR-CGH. In the "simple-diploid" cases no or few genetic alterations could be detected, whereas the "complex-diploid" samples numerous aberrations (equal or more than 3) could be found. Conclusions Our results show a correlation between the DNA-ploidy, a fine-tuned DNA-ploidy and the HR-CGH results. Furthermore, we found significant correlation between the different ploidy groups and the clinical outcome (p < 0.05). PMID:22053830

Results of clinical lung transplant from uncontrolled non-heart-beating donors.

PubMed

de Antonio, David Gómez; Marcos, Roberto; Laporta, Rosalía; Mora, Gema; García-Gallo, Cristina; Gámez, Pablo; Córdoba, Mar; Moradiellos, Javier; Ussetti, Piedad; Carreño, María C; Núñez, José R; Calatayud, Joaquín; Del Río, Francisco; Varela, Andrés

2007-05-01

The scarcity of grafts for lung transplant and the growing number of candidates expecting an organ has led to an increase of deaths in patients waiting for lung transplantation. Non-heart-beating donors (NHBD) represent a promising source of grafts for those who are involved in clinical lung transplantation. We present the results of our series of 17 out-of-hospital NHBD lung transplantations performed since 2002. We have collected data from 17 donors and recipients involved in NHBD lung transplants since 2002, as well as data referring to the type of procedure and peri-operative events. We describe the incidence of post-operative complications with special attention to primary graft disfunction (PGD), bronchial healing, bronchiolitis obliterans syndrome (BOS), and survival. We used Kaplan-Meier method to obtain the survival curve. G2-G3 PGD was reported in 9 patients (53%), with a complete restoration of the partial pressure of arterial oxygen/fraction of inspired oxygen ratio in 170 hours for G2 and 168 hours for G3. There were no deaths directly related to PGD. Acute rejection was detected in 7 patients (41%), 4 of which exceeded grade 1. The incidence of BOS after transplantation was 1 (7%) of 14 patients during the first year, 2 (11%) of 9 in the second year, and 2 (50%) of 4 in the third year. Hospital mortality rate was 17%. The survival rates were 82% at 3 months, 69%, at 1 year, and 58% at 3 years. Mid-term results confirm the adequacy of uncontrolled NHBD as a promising complementary source of lung donors for clinical transplant.

Stock Market Returns and Clinical Trial Results of Investigational Compounds: An Event Study Analysis of Large Biopharmaceutical Companies

PubMed Central

Hwang, Thomas J.

2013-01-01

Background For biopharmaceutical companies, investments in research and development are risky, and the results from clinical trials are key inflection points in the process. Few studies have explored how and to what extent the public equity market values clinical trial results. Methods Our study dataset matched announcements of clinical trial results for investigational compounds from January 2011 to May 2013 with daily stock market returns of large United States-listed pharmaceutical and biotechnology companies. Event study methodology was used to examine the relationship between clinical research events and changes in stock returns. Results We identified public announcements for clinical trials of 24 investigational compounds, including 16 (67%) positive and 8 (33%) negative events. The majority of announcements were for Phase 3 clinical trials (N = 13, 54%), and for oncologic (N = 7, 29%) and neurologic (N = 6, 24%) indications. The median cumulative abnormal returns on the day of the announcement were 0.8% (95% confidence interval [CI]: –2.3, 13.4%; P = 0.02) for positive events and –2.0% (95% CI: –9.1, 0.7%; P = 0.04) for negative events, with statistically significant differences from zero. In the day immediately following the announcement, firms with positive events were associated with stock price corrections, with median cumulative abnormal returns falling to 0.4% (95% CI: –3.8, 12.3%; P = 0.33). For firms with negative announcements, the median cumulative abnormal returns were –1.7% (95% CI: –9.5, 1.0%; P = 0.03), and remained significantly negative over the two day event window. The magnitude of abnormal returns did not differ statistically by indication, by trial phase, or between biotechnology and pharmaceutical firms. Conclusions The release of clinical trial results is an economically significant event and has meaningful effects on market value for large biopharmaceutical companies. Stock return

Alpha Lipoic Acid (ALA) effects on subchorionic hematoma: preliminary clinical results.

PubMed

Porcaro, G; Brillo, E; Giardina, I; Di Iorio, R

2015-09-01

The clinic use of alpha Lipoic Acid (ALA) is linked to its capability to exert antioxidant effects and, more interestingly, to counteract the pathologic changes of complex networks of cytokines, chemokines and growth factors, restoring their physiological state. The aim of this randomized controlled clinical trial was to test the contribution of oral supplementation of ALA to the standard treatment with Progesterone vaginal suppositories, in healing subchorionic hematomas in patients with threatened miscarriage. Controls were administered only Progesterone suppositories. Nineteen pregnant women in the first trimester of gestation, with threatened miscarriage and ultrasound evidence of subchorionic hematoma, were included in the trial and randomly divided in two groups: controls, treated with 400 mg Progesterone (200 mg 2 times per day), given by vaginal suppositories, and case study treated with the same Progesterone dosage, plus ALA, given orally at the dose of 600 mg (300 mg 2 times per day, DAV®, Lo.Li. Pharma srl, Italy). Sixteen patients completed the trial. Treatment was performed until complete resolution of the clinical picture. In both groups, the subjects improved significantly but, in general, a better and faster evolution in the major signs of threatened miscarriage was observed in the subjects treated with ALA and Progesterone. In these patients, the speed of resorption of subchorionic hematoma was significantly (p ≤ 0.05) superior compared to controls. The ALA and Progesterone group showed a faster decrease or disappearance of all symptoms than that observed in the control group, however the difference was not significant. These preliminary results suggest that ALA supplementation significantly contributes to speed up the process of restoration of physiological conditions in threatened miscarriage and ameliorates the medical conditions of both the mothers and the foetus, probably modulating the networks of cytokines, growth factors and other

[Tribological properties of carbon fiber-reinforced plastic. Experimental and clinical results].

PubMed

Früh, H J; Ascherl, R; Hipp, E

1997-02-01

Wear of the articulating components (especially PE-UHMW) of total hip endoprostheses is the most important technical factor limiting the functional lifetime. To minimize wear debris, ceramic heads, according to ISO 6474 (Al2O3), have been used, from 1969 paired with Al2O3 and since 1975 paired with PE-UHMW. Al2O3 balls articulating with cups made from CFRP have been in clinical use since 1988. Laboratory experiments and in-vivo testing showed minimized wear debris and mild biological response to wear products using CFRP (carbon fiber reinforced plastic) instead of PE-UHMW as the cup material. The articulating surfaces of retrieved ceramic heads (Al2O3-Biolox) and cementless CFRP cups (carbon fiber reinforced plastic, Caproman) were compared using sphericity measurement techniques, scanning electron microscopy (SEM) and roughness measurements (including advanced roughness parameters Rvk or Rpk according to ISO 4287). Altogether, the first results of the clinical study showed that the combination Al2O3-ball/CFRP-cup came up to the expected lower wear rates compared with the conventional combinations. The wear rates are comparable with the combination Al2O3/Al2O3 without the material-related problems of ceramic components in all ceramic combinations.

Diagnosis of breast cancer using elastic-scattering spectroscopy: preliminary clinical results

NASA Astrophysics Data System (ADS)

Bigio, Irving J.; Brown, Stephen G.; Briggs, Gavin M.; Kelley, Christine; Lakhani, Sunil; Pickard, David; Ripley, Paul M.; Rose, Ian; Saunders, Christobel

2000-04-01

We report on the first stages of a clinical study designed to test elastic-scattering spectroscopy, medicated by fiberoptic probes, for three specific clinical applications in breast-tissue diagnosis: (1) a transdermal-needle (interstitial) measurement for instant diagnosis with minimal invasiveness similar to fine-needle aspiration but with sensitivity to a larger tissue volume, (2) a hand-held diagnostic probe for use in assessing tumor/resection margins during open surgery, and (3) use of the same probe for real-time assessment of the `sentinel' node during surgery to determine the presence or absence of tumor (metastatic). Preliminary results from in vivo measurements on 31 women are encouraging. Optical spectra were measured on 72 histology sites in breast tissue, and 54 histology sites in sentinel nodes. Two different artificial intelligence methods of spectral classification were studied. Artificial neural networks yielded sensitivities of 69% and 58%, and specificities of 85% and 93%, for breast tissue and sentinel nodes, respectively. Hierarchical cluster analysis yielded sensitivities of 67% and 91%, and specificities of 79% and 77%, for breast tissue and sentinel nodes, respectively. These values are expected to improve as the data sets continue to grow and more sophisticated data preprocessing is employed. The study will enroll up to 400 patients over the next two years.

Ocriplasmin for treatment of stage 2 macular holes: early clinical results.

PubMed

Miller, John B; Kim, Leo A; Wu, David M; Vavvas, Demetrios G; Eliott, Dean; Husain, Deeba

2014-01-01

To review clinical and structural outcomes of ocriplasmin for treatment of stage 2 macular holes. A retrospective review of the first patients with stage 2 macular holes to be treated with ocriplasmin at Massachusetts Eye and Ear Infirmary. All patients were imaged with spectral-domain optical coherence tomography (SD-OCT). Eight patients with stage 2 macular holes received a single injection of 125 μg of ocriplasmin. One patient (12.5%) demonstrated macular hole closure. The posterior hyaloid separated from the macula in six eyes (75%). All seven holes that remained open showed enlargement in hole diameters (narrowest, apical, and basal) at 1 week and 1 month. All seven were successfully closed with surgery. Ellipsoid zone disruptions were observed by OCT in four eyes (50%) and persisted throughout follow-up (more than 6 months on average). In early clinical results, the authors found a lower macular hole closure rate with ocriplasmin than previously reported. Enlargement was observed in all holes that failed to close with ocriplasmin. The authors found ellipsoid zone disruptions that persisted through 6 months of follow-up after ocriplasmin injection. Further work is needed to investigate the cause for these ellipsoid zone changes. Copyright 2014, SLACK Incorporated.

Baseline hematology and clinical chemistry results from captive-raised trumpeter swans

USGS Publications Warehouse

Olsen, Glenn H.; Rininger, D.L.; Ets, M.K.; Sladen, William J. L.; Rees, Eileen C.; Earnst, Susan L.; Coulson, John C.

2002-01-01

Results from hematology and clinical chemistry tests are presented for healthy captive-raised Trumpeter Swans (Cygnus buccinator) to help establish baseline data. Blood samples were obtained from 14 cygnets between the ages of three to four and seven to eight months that were the subjects of a study to teach migration routes to swans. Males and females differed significantly in asparatate aminotransferase, alanine aminotransferase and total protein. Age categories differed significantly in hematocrit, white blood cell counts, alkaline phosphatase, aspar-rate aminotransferase, glucose, cholesterol and uric acid. There were no significant differences among age categories in values of alanine aminotransferase, calcium, triglycerides and total protein.

Molecular genetics and genomics progress in urothelial bladder cancer.

PubMed

Netto, George J

2013-11-01

The clinical management of solid tumor patients has recently undergone a paradigm shift as the result of the accelerated advances in cancer genetics and genomics. Molecular diagnostics is now an integral part of routine clinical management in lung, colon, and breast cancer patients. In a disappointing contrast, molecular biomarkers remain largely excluded from current management algorithms of urologic malignancies. The need for new treatment alternatives and validated prognostic molecular biomarkers that can help clinicians identify patients in need of early aggressive management is pressing. Identifying robust predictive biomarkers that can stratify response to newly introduced targeted therapeutics is another crucially needed development. The following is a brief discussion of some promising candidate biomarkers that may soon become a part of clinical management of bladder cancers. © 2013 Published by Elsevier Inc.

Resource costing for multinational neurologic clinical trials: methods and results.

PubMed

Schulman, K; Burke, J; Drummond, M; Davies, L; Carlsson, P; Gruger, J; Harris, A; Lucioni, C; Gisbert, R; Llana, T; Tom, E; Bloom, B; Willke, R; Glick, H

1998-11-01

We present the results of a multinational resource costing study for a prospective economic evaluation of a new medical technology for treatment of subarachnoid hemorrhage within a clinical trial. The study describes a framework for the collection and analysis of international resource cost data that can contribute to a consistent and accurate intercountry estimation of cost. Of the 15 countries that participated in the clinical trial, we collected cost information in the following seven: Australia, France, Germany, the UK, Italy, Spain, and Sweden. The collection of cost data in these countries was structured through the use of worksheets to provide accurate and efficient cost reporting. We converted total average costs to average variable costs and then aggregated the data to develop study unit costs. When unit costs were unavailable, we developed an index table, based on a market-basket approach, to estimate unit costs. To estimate the cost of a given procedure, the market-basket estimation process required that cost information be available for at least one country. When cost information was unavailable in all countries for a given procedure, we estimated costs using a method based on physician-work and practice-expense resource-based relative value units. Finally, we converted study unit costs to a common currency using purchasing power parity measures. Through this costing exercise we developed a set of unit costs for patient services and per diem hospital services. We conclude by discussing the implications of our costing exercise and suggest guidelines to facilitate more effective multinational costing exercises.

Problem-based learning: a review of the educational and psychological theory.

PubMed

Onyon, Clare

2012-02-01

Problem-based learning (PBL) is a teaching method where the use of clinical problems is the starting point for learning, and it is through the process of working through these problems that students acquire the knowledge and skills required to be a doctor. Many advantages of PBL over traditional curricula have been proposed. On reviewing the evidence on the results of PBL curricula for producing better doctors, students tend to perform either a little better or a little worse in examinations. In this article the educational and psychological theories supporting PBL are described. There is a wealth of theory underpinning the use of PBL to teach clinical medicine, despite disappointing results. Future research should concentrate on the reasons behind this uncoupling of theory and outcomes. © Blackwell Publishing Ltd 2012.

[Evaluation of the clinical results of non-surgical treatment for pediatric sagittal fracture of mandibular condyle].

PubMed

Liu, Chang-kui; Tan, Xin-ying; Xu, Juan; Liu, Hua-wei; Liu, San-xia; Hu, Min

2013-11-01

To investigate the clinical results of occlusal splint in the treatment of sagittal fracture of mandibular condyle (SFMC) in children. Thirty-nine patients (48 condyles)aged 3-8 years with sagittal fracture of mandibular condyle were included in this study. All the patients were treated by occlusal splint.Slight open occlusion was maintained by occlusal splint for 3-6 months. Clinical and radiological examination was performed six mouths and every year after treatment. Good mandibular function was observed in 39 patients. Maximal mouth opening over 35 mm was achieved at 6 months. But 11 of the 39 patients presented with deviation on mouth opening at 6 months. The radiology showed an complete remodeling in 32 condyles (28 patients) and partial remodeling in 16 condyles (11 patients). Poor remodelling was not observed in any patients. Good clinical results can be obtained by using occlusal splint in the treatment of pediatric sagittal fracture of mandibular condyle.

Deimos Methane-Oxygen Rocket Engine Test Results

NASA Astrophysics Data System (ADS)

Engelen, S.; Souverein, L. J.; Twigt, D. J.

This paper presents the results of the first DEIMOS Liquid Methane/Oxygen rocket engine test campaign. DEIMOS is an acronym for `Delft Experimental Methane Oxygen propulsion System'. It is a project performed by students under the auspices of DARE (Delft Aerospace Rocket Engineering). The engine provides a theoretical design thrust of 1800 N and specific impulse of 287 s at a chamber pressure of 40 bar with a total mass flow of 637 g/s. It has links to sustainable development, as the propellants used are one of the most promising so-called `green propellants'-combinations, currently under scrutiny by the industry, and the engine is designed to be reusable. This paper reports results from the provisional tests, which had the aim of verifying the engine's ability to fire, and confirming some of the design assumptions to give confidence for further engine designs. Measurements before and after the tests are used to determine first estimates on feed pressures, propellant mass flows and achieved thrust. These results were rather disappointing from a performance point of view, with an average thrust of a mere 3.8% of the design thrust, but nonetheless were very helpful. The reliability of ignition and stability of combustion are discussed as well. An initial assessment as to the reusability, the flexibility and the adaptability of the engine was made. The data provides insight into (methane/oxygen) engine designs, leading to new ideas for a subsequent design. The ultimate goal of this project is to have an operational rocket and to attempt to set an amateur altitude record.

Appraising the methodological quality of the clinical practice guideline for diabetes mellitus using the AGREE II instrument: a methodological evaluation.

PubMed

Radwan, Mahmoud; Akbari Sari, Ali; Rashidian, Arash; Takian, Amirhossein; Abou-Dagga, Sanaa; Elsous, Aymen

2017-02-01

To evaluate the methodological quality of the Palestinian Clinical Practice Guideline for Diabetes Mellitus using the Translated Arabic Version of the AGREE II. Methodological evaluation. A cross-cultural adaptation framework was followed to translate and develop a standardised Translated Arabic Version of the AGREE II. Palestinian Primary Healthcare Centres. Sixteen appraisers independently evaluated the Clinical Practice Guideline for Diabetes Mellitus using the Translated Arabic Version of the AGREE II. Methodological quality of diabetic guideline. The Translated Arabic Version of the AGREE II showed an acceptable reliability and validity. Internal consistency ranged between 0.67 and 0.88 (Cronbach's α). Intra-class coefficient among appraisers ranged between 0.56 and 0.88. The quality of this guideline is low. Both domains 'Scope and Purpose' and 'Clarity of Presentation' had the highest quality scores (66.7% and 61.5%, respectively), whereas the scores for 'Applicability', 'Stakeholder Involvement', 'Rigour of Development' and 'Editorial Independence' were the lowest (27%, 35%, 36.5%, and 40%, respectively). The findings suggest that the quality of this Clinical Practice Guideline is disappointingly low. To improve the quality of current and future guidelines, the AGREE II instrument is extremely recommended to be incorporated as a gold standard for developing, evaluating or updating the Palestinian Clinical Practice Guidelines. Future guidelines can be improved by setting specific strategies to overcome implementation barriers with respect to economic considerations, engaging of all relevant end-users and patients, ensuring a rigorous methodology for searching, selecting and synthesising the evidences and recommendations, and addressing potential conflict of interests within the development group.

[Freiburg keratoconus registry : Example of application of smart data for clinical research and inititial results].

PubMed

Lang, S J; Böhringer, D; Reinhard, T

2016-06-01

Keratoconus is a progressive corneal disease with thinning and scarring of the cornea. Diagnostic and treatment options are usually evaluated in large prospective or retrospective trials. Big data and smart data provide the possibility to analyze routine data for clinical research. In this article we report the generation of a monocentric keratoconus registry by means of computerized data analysis of routine data. This demonstrates the potential of clinical research by means of routine data. A "clinical data warehouse" was created from all available routine electronic data. At the time of first presentation, each eye was classified into one out of four categories: suspected, early disease, late disease and status postkeratoplasty. Through integration of multiple data sources the clinical course for each patient was documented in the registry. A total of 3681 eyes from 1841 patients were included. The median follow-up time was 0.54 years. Patient age was higher in the groups with more severe stages of keratoconus, the proportion of female patients was higher in the group of suspected keratoconus and patient age and male to female ratios showed statistically significant differences between the groups (p < 0.001). We were able to create a "clinical data warehouse" by linking multiple data sources and normalizing the data. With this tool we established a novel, monocentric keratoconus registry. Only the grading of disease severity and the exclusion of false positive results were carried out manually. In our opinion establishing a structured clinical data warehouse has a huge potential for clinical and retrospective studies and proves the value of the Smart Data concept.

Generalizability of Pharmacologic and Psychotherapy Clinical Trial Results for Posttraumatic Stress Disorder to Community Samples.

PubMed

Franco, Silvia; Hoertel, Nicolas; McMahon, Kibby; Wang, Shuai; Rodríguez-Fernández, Jorge Mario; Peyre, Hugo; Limosin, Frédéric; Blanco, Carlos

2016-08-01

The present study sought to quantify the generalizability of pharmacologic and psychotherapy clinical trial results in individuals with a DSM-IV diagnosis of posttraumatic stress disorder (PTSD) to a large representative community sample. Data were derived from the 2004-2005 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a large nationally representative sample of the adult US population. We applied a standard set of exclusion criteria representative of pharmacologic and psychotherapy clinical trials to all adults with a DSM-IV diagnosis of PTSD in the previous 12 months (n = 1,715) and then to a subsample of participants seeking treatment (n = 366). Our aim was to assess how many participants with PTSD would fulfill typical eligibility criteria. We found that more than 6 of 10 respondents from the overall PTSD sample and more than 7 of 10 respondents seeking treatment for PTSD would have been excluded by 1 exclusion criterion or more in a typical pharmacologic trial. In contrast, about 2 of 10 participants in the full sample and about 3 of 10 participants seeking treatment for PTSD would have been excluded in a typical psychotherapy efficacy trial. We found that psychotherapy trial results may be applied to most patients with PTSD in routine clinical practice. The designers of pharmacologic clinical trials should carefully consider the trade-offs between the application of each exclusion criterion and its impact on representativeness. Specification a priori of the goals of the study, better justification for each exclusion criterion, and estimation of the proportion of individuals ineligible for the trial would assist study design. Developing integrated forms of pharmacotherapy and psychotherapy that simultaneously target commonly overlapping psychiatric disorders may yield more informative results for mental health care providers and research funding agencies. © Copyright 2016 Physicians Postgraduate Press, Inc.

Mid- and long-term clinical results of surgical therapy in unicameral bone cysts

PubMed Central

2011-01-01

Background Unicameral (or simple) bone cysts (UBC) are benign tumours most often located in long bones of children and adolescents. Pathological fractures are common, and due to high recurrence rates, these lesions remain a challenge to treat. Numerous surgical procedures have been proposed, but there is no general consensus of the ideal treatment. The aim of this investigation therefore was to study the long-term outcome after surgical treatment in UBC. Methods A retrospective analysis of 46 patients surgically treated for UBC was performed for short and mid-term outcome. Clinical and radiological outcome parameters were studied according to a modified Neer classification system. Long-term clinical information was retrieved via a questionnaire at a minimum follow-up of 10 years after surgery. Results Forty-six patients (17 female, 29 male) with a mean age of 10.0 ± 4.8 years and with histopathologically confirmed diagnosis of UBC were included. Pathological fractures were observed in 21 cases (46%). All patients underwent surgery for UBC (35 patients underwent curettage and bone grafting as a primary therapy, 4 curettage alone, 3 received corticoid instillation and 4 decompression by cannulated screws). Overall recurrence rate after the first surgical treatment was 39% (18/46), second (17.4% of all patients) and third recurrence (4.3%) were frequently observed and were addressed by revision surgery. Recurrence was significantly higher in young and in male patients as well as in active cysts. After a mean of 52 months, 40 out of 46 cysts were considered healed. Prognosis was significantly better when recurrence was observed later than 30 months after therapy. After a mean follow-up of 15.5 ± 6.2 years, 40 patients acknowledged clinically excellent results, while five reported mild and casual pain. Only one patient reported a mild limitation of range of motion. Conclusions Our results suggest satisfactory overall long-term outcome for the surgical treatment of UBC

Clinical development of gene therapy: results and lessons from recent successes

PubMed Central

Kumar, Sandeep RP; Markusic, David M; Biswas, Moanaro; High, Katherine A; Herzog, Roland W

2016-01-01

Therapeutic gene transfer holds the promise of providing lasting therapies and even cures for diseases that were previously untreatable or for which only temporary or suboptimal treatments were available. For some time, clinical gene therapy was characterized by some impressive but rare examples of successes and also several setbacks. However, effective and long-lasting treatments are now being reported from gene therapy trials at an increasing pace. Positive outcomes have been documented for a wide range of genetic diseases (including hematological, immunological, ocular, and neurodegenerative and metabolic disorders) and several types of cancer. Examples include restoration of vision in blind patients, eradication of blood cancers for which all other treatments had failed, correction of hemoglobinopathies and coagulation factor deficiencies, and restoration of the immune system in children born with primary immune deficiency. To date, about 2,000 clinical trials for various diseases have occurred or are in progress, and many more are in the pipeline. Multiple clinical studies reported successful treatments of pediatric patients. Design of gene therapy vectors and their clinical development are advancing rapidly. This article reviews some of the major successes in clinical gene therapy of recent years. PMID:27257611

IPS Empress crown system: three-year clinical trial results.

PubMed

Sorensen, J A; Choi, C; Fanuscu, M I; Mito, W T

1998-02-01

The IPS Empress system is a highly esthetic hot pressed glass ceramic material for fabrication of single crowns. Adhesive cementation of the system not only contributes to the esthetics but is necessary for increased strength of the crown. The purpose of this prospective clinical trials was to evaluate the longevity of 75 adhesively cemented Empress full crowns. An additional aim was to assess the adhesive cementation methodology and potential side effects. At the three-year point, one molar crown fractured for a 1.3 percent failure rate. The resin cementation technique that was employed exhibited a low incidence of microleakage with few clinical side effects. There was a 5.6 percent incidence of post-cementation sensitivity, with all symptoms subsiding by eight weeks. None of the crowns in the study required endodontic therapy.

Development of a relational database to capture and merge clinical history with the quantitative results of radionuclide renography.

PubMed

Folks, Russell D; Savir-Baruch, Bital; Garcia, Ernest V; Verdes, Liudmila; Taylor, Andrew T

2012-12-01

Our objective was to design and implement a clinical history database capable of linking to our database of quantitative results from (99m)Tc-mercaptoacetyltriglycine (MAG3) renal scans and export a data summary for physicians or our software decision support system. For database development, we used a commercial program. Additional software was developed in Interactive Data Language. MAG3 studies were processed using an in-house enhancement of a commercial program. The relational database has 3 parts: a list of all renal scans (the RENAL database), a set of patients with quantitative processing results (the Q2 database), and a subset of patients from Q2 containing clinical data manually transcribed from the hospital information system (the CLINICAL database). To test interobserver variability, a second physician transcriber reviewed 50 randomly selected patients in the hospital information system and tabulated 2 clinical data items: hydronephrosis and presence of a current stent. The CLINICAL database was developed in stages and contains 342 fields comprising demographic information, clinical history, and findings from up to 11 radiologic procedures. A scripted algorithm is used to reliably match records present in both Q2 and CLINICAL. An Interactive Data Language program then combines data from the 2 databases into an XML (extensible markup language) file for use by the decision support system. A text file is constructed and saved for review by physicians. RENAL contains 2,222 records, Q2 contains 456 records, and CLINICAL contains 152 records. The interobserver variability testing found a 95% match between the 2 observers for presence or absence of ureteral stent (κ = 0.52), a 75% match for hydronephrosis based on narrative summaries of hospitalizations and clinical visits (κ = 0.41), and a 92% match for hydronephrosis based on the imaging report (κ = 0.84). We have developed a relational database system to integrate the quantitative results of MAG3 image

Provision of test results and posttest counseling at STD clinics in 24 health departments: U.S., 2007.

PubMed

Begley, Elin; VanHandel, Michelle

2012-01-01

We determined the demographic and HIV test characteristics of tests conducted in CDC-funded sexually transmitted disease (STD) clinics with provision of test results and posttest counseling. We used CDC's HIV Counseling and Testing System data from 2007 for the 24 U.S. health departments that reported test-level data from STD clinics. We calculated and analyzed newly identified HIV positivity and the percentage of tests with provision of test results and posttest counseling (provision of posttest counseling), by demographic and HIV-related characteristics. Of 372,757 tests conducted among people without a previous HIV diagnosis by self-report, provision of posttest counseling was documented for 191,582 (51.4%) HIV tests overall and 1,922 (71.2%) newly identified HIV-positive test results. At these STD clinics, provision of posttest counseling varied by HIV serostatus, age, race/ethnicity, test type, and risk category; however, documentation of posttest counseling was missing for more than 20% of tests. The newly identified HIV positivity among all testers was 0.7%. One of the main goals of HIV counseling and testing is to inform people of their HIV status, because knowledge of one's HIV-positive serostatus can result in a reduction in risk behaviors and allow the person to access HIV medical care and treatment. STD clinics offering HIV testing may need to further their emphasis on increasing the proportion of clients who are provided posttest counseling and on improving documentation of this information.

Noninvasive assessment of mitral inertness: clinical results with numerical model validation

NASA Technical Reports Server (NTRS)

Firstenberg, M. S.; Greenberg, N. L.; Smedira, N. G.; McCarthy, P. M.; Garcia, M. J.; Thomas, J. D.

2001-01-01

Inertial forces (Mdv/dt) are a significant component of transmitral flow, but cannot be measured with Doppler echo. We validated a method of estimating Mdv/dt. Ten patients had a dual sensor transmitral (TM) catheter placed during cardiac surgery. Doppler and 2D echo was performed while acquiring LA and LV pressures. Mdv/dt was determined from the Bernoulli equation using Doppler velocities and TM gradients. Results were compared with numerical modeling. TM gradients (range: 1.04-14.24 mmHg) consisted of 74.0 +/- 11.0% inertial forcers (range: 0.6-12.9 mmHg). Multivariate analysis predicted Mdv/dt = -4.171(S/D (RATIO)) + 0.063(LAvolume-max) + 5. Using this equation, a strong relationship was obtained for the clinical dataset (y=0.98x - 0.045, r=0.90) and the results of numerical modeling (y=0.96x - 0.16, r=0.84). TM gradients are mainly inertial and, as validated by modeling, can be estimated with echocardiography.

Isavuconazole Concentration in Real-world Practice: Consistency with Results from Clinical Trials.

PubMed

Andes, David; Kovanda, Laura; Desai, A; Kitt, Theresa; Zhao, M; Walsh, Thomas J

2018-05-07

Clinical use of voriconazole, posaconazole, and itraconazole revealed the need for therapeutic drug monitoring (TDM) of plasma concentrations of these antifungal agents. This need for TDM was not evident from clinical trials of these drugs. In order to establish if this requirement also applies to isavuconazole, we examined the plasma concentrations of 283 samples receiving isavuconazole in clinical practice and compared the values to those from clinical trials. The concentration distributions from real-world use and clinical trials were nearly identical (>1 μg/mL in 90% of patients). These findings suggest that routine TDM may not be required for isavuconazole in most instances. Copyright © 2018 American Society for Microbiology.

Waves of regret: a meg study of emotion and decision-making.

PubMed

Giorgetta, Cinzia; Grecucci, Alessandro; Bonini, Nicolao; Coricelli, Giorgio; Demarchi, Gianpaolo; Braun, Christoph; Sanfey, Alan G

2013-01-01

Recent fMRI studies have investigated brain activity involved in the feeling of regret and disappointment by manipulating the feedback participants saw after making a decision to play certain gambles: full-feedback (regret: participant sees the outcomes from both the chosen and unchosen gamble) vs. partial-feedback (disappointment: participant only sees the outcome from chosen gamble). However, regret and disappointment are also characterized by differential agency attribution: personal agency for regret, external agency for disappointment. In this study, we investigate the neural correlates of these two characterizations of regret and disappointment using magnetoencephalography (MEG). To do this, we experimentally induced each emotion by manipulating feedback (chosen gamble vs. unchosen gamble), agency (human vs. computer choice) and outcomes (win vs. loss) in a fully randomized design. At the behavioral level the emotional experience of regret and disappointment were indeed affected by both feedback and agency manipulations. These emotions also differentially affect subsequent choices, with regret leading to riskier behavior. At the neural level both feedback and agency affected the brain responses associated with regret and disappointment, demonstrating differential localization in the brain for each. Notably, feedback regret showed greater brain activity in the right anterior and posterior regions, with agency regret producing greater activity in the left anterior region. These findings extend the evidence for neural activity in processing both regret and disappointment by highlighting for the first time the respective importance of feedback and agency, as well as outlining the temporal dynamics of these emotions. Copyright © 2012 Elsevier Ltd. All rights reserved.

Bench-to-bedside review: Inhaled nitric oxide therapy in adults

PubMed Central

Creagh-Brown, Benedict C; Griffiths, Mark JD; Evans, Timothy W

2009-01-01

Nitric oxide (NO) is an endogenous mediator of vascular tone and host defence. Inhaled nitric oxide (iNO) results in preferential pulmonary vasodilatation and lowers pulmonary vascular resistance. The route of administration delivers NO selectively to ventilated lung units so that its effect augments that of hypoxic pulmonary vasoconstriction and improves oxygenation. This 'Bench-to-bedside' review focuses on the mechanisms of action of iNO and its clinical applications, with emphasis on acute lung injury and the acute respiratory distress syndrome. Developments in our understanding of the cellular and molecular actions of NO may help to explain the hitherto disappointing results of randomised controlled trials of iNO. PMID:19519946

Uninformed Clinical Decisions Resulting From Lack of Adherence Assessment in Children with New Onset Epilepsy

PubMed Central

Modi, Avani C.; Wu, Yelena P.; Guilfoyle, Shanna M.; Glauser, Tracy A.

2012-01-01

This study examined the relationship between non-adherence to antiepileptic drug (AED) therapy and clinical decision-making in a cohort of 112 children with newly-diagnosed epilepsy. AED adherence was monitored using electronic monitoring over the first six months of therapy. The primary outcome measure was rate of uninformed clinical decisions as defined by number of participants with AED dosage or drug changes to address continued seizures who demonstrated non-adherence prior to the seizure. Among the 52 (47%) participants who had an AED change for continued seizures, 30 (27% of the overall cohort) had imperfect medication adherence prior to their seizures. A quarter of children with new onset epilepsy had uninformed medication changes because adherence was not rigorously assessed in clinical practice. Results highlight the importance of routinely assessing medication adherence in this population. PMID:23159375

Federating Clinical Data from Six Pediatric Hospitals: Process and Initial Results from the PHIS+ Consortium

PubMed Central

Narus, Scott P.; Srivastava, Rajendu; Gouripeddi, Ramkiran; Livne, Oren E.; Mo, Peter; Bickel, Jonathan P.; de Regt, David; Hales, Joseph W.; Kirkendall, Eric; Stepanek, Richard L.; Toth, Jamie; Keren, Ron

2011-01-01

Integrating clinical data with administrative data across disparate electronic medical record systems will help improve the internal and external validity of comparative effectiveness research. The Pediatric Health Information System (PHIS) currently collects administrative information from 43 pediatric hospital members of the Child Health Corporation of America (CHCA). Members of the Pediatric Research in Inpatient Settings (PRIS) network have partnered with CHCA and the University of Utah Biomedical Informatics Core to create an enhanced version of PHIS that includes clinical data. A specialized version of a data federation architecture from the University of Utah (“FURTHeR”) is being developed to integrate the clinical data from the member hospitals into a common repository (“PHIS+”) that is joined with the existing administrative data. We report here on our process for the first phase of federating lab data, and present initial results. PMID:22195159

[The clinical ethics committee (CEC) in the area of conflict between hospital certification, moral pragmatics and scientific approach].

PubMed

Bauer, Axel W

2007-01-01

During the last decade numerous consultative bodies for bioethical and medical ethical issues have been established. In this study we will introduce the clinical ethics committee (CEC), which can be mainly brought into action for three purposes: discussing moral problems in a hospital's everyday work, developing guidelines for the clinic, and giving further education to the hospital's staff. Starting with the denominational hospitals at the end of the 1990s, CECs have been established in the meantime at a large number of German clinics, often in an interrelation with hospital certification. We will describe the process of establishing a CEC at the university hospital in Mannheim (Baden-Württemberg) and examine its formal structure given by the statutes and the standing orders. An important issue of the CEC's activities consists in individual consultation, for instance concerning withholding or withdrawing life-supporting therapy from comatose patients. First and foremost it has to be clarified whether there is really an ethical problem which cannot be solved by those seeking advice or whether the CEC is just asked a rhetorical question in order to attain allies. In this case disappointment will often be the consequence. The quality of an ethical consultation cannot be treated as equivalent to the correspondence with preconceived moral attitudes. The CEC is not a "moral police" but a multi-professional body, in which scientific medical ethics should play an important but under no circumstances a dominating role. Meaningful criteria and measuring methods to study the effectiveness of clinical ethics committees will have to be evolved and tested in practice as soon as possible.

[THE RESULTS OF CLINICAL AND PSYCHOPATHOLOGICAL AND PSYCHOLOGICAL DIAGNOSTIC INVESTIGATIONS EMPLOYEES OF FINANCIAL INSTITUTIONS WHICH WERE IDENTIFIED NEUROTIC DISORDERS].

PubMed

Solovyova, M

2014-12-01

The article presents the results of the clinical and psychopathological and psychological diagnostic, investigations mental health employees of financial institutions, description and analysis of clinical forms identified disorders.

Nine-year outcome after anatomic stemless shoulder prosthesis: clinical and radiologic results.

PubMed

Hawi, Nael; Magosch, Petra; Tauber, Mark; Lichtenberg, Sven; Habermeyer, Peter

2017-09-01

Several stemless shoulder implants are available on the market, but only a few studies have presented results with sufficient mid- to long-term follow-up. The present study evaluated clinical and radiologic outcomes 9 years after anatomic stemless shoulder replacement. This is a prospective cohort study evaluating the stemless shoulder prosthesis since 2005. Anatomic stemless shoulder replacement using a single prosthesis was performed in 49 shoulders; 17 underwent total shoulder replacement, and 32 underwent hemiarthroplasty. Forty-three patients were clinically and radiologically monitored after a mean of 9 years (range, 90-127 months; follow-up rate, 88%). The indications for shoulder replacement were primary osteoarthritis in 7 shoulders, post-traumatic in 24, instability in 7, cuff tear arthropathy in 2, postinfectious arthritis in 1, and revision arthroplasty in 2. The Constant-Murley Score improved significantly from 52% to 79% (P < .0001). The active range of motion also increased significantly for flexion from 101° to 118° (P = .022), for abduction from 79° to 105° (P = .02), and for external rotation from 21° to 43° (P < .0001). Radiologic evaluation revealed incomplete radiolucency in 1 patient without clinical significance or further intervention. No revision caused by loosening or countersinking of the humeral implant was observed. The 9-year outcome after stemless shoulder replacement is comparable to that of third- and fourth-generation standard shoulder arthroplasty. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Stock market returns and clinical trial results of investigational compounds: an event study analysis of large biopharmaceutical companies.

PubMed

Hwang, Thomas J

2013-01-01

For biopharmaceutical companies, investments in research and development are risky, and the results from clinical trials are key inflection points in the process. Few studies have explored how and to what extent the public equity market values clinical trial results. Our study dataset matched announcements of clinical trial results for investigational compounds from January 2011 to May 2013 with daily stock market returns of large United States-listed pharmaceutical and biotechnology companies. Event study methodology was used to examine the relationship between clinical research events and changes in stock returns. We identified public announcements for clinical trials of 24 investigational compounds, including 16 (67%) positive and 8 (33%) negative events. The majority of announcements were for Phase 3 clinical trials (N = 13, 54%), and for oncologic (N = 7, 29%) and neurologic (N = 6, 24%) indications. The median cumulative abnormal returns on the day of the announcement were 0.8% (95% confidence interval [CI]: -2.3, 13.4%; P = 0.02) for positive events and -2.0% (95% CI: -9.1, 0.7%; P = 0.04) for negative events, with statistically significant differences from zero. In the day immediately following the announcement, firms with positive events were associated with stock price corrections, with median cumulative abnormal returns falling to 0.4% (95% CI: -3.8, 12.3%; P = 0.33). For firms with negative announcements, the median cumulative abnormal returns were -1.7% (95% CI: -9.5, 1.0%; P = 0.03), and remained significantly negative over the two day event window. The magnitude of abnormal returns did not differ statistically by indication, by trial phase, or between biotechnology and pharmaceutical firms. The release of clinical trial results is an economically significant event and has meaningful effects on market value for large biopharmaceutical companies. Stock return underperformance due to negative events is greater in magnitude and persists longer than

Publication proportions for registered breast cancer trials: before and following the introduction of the ClinicalTrials.gov results database.

PubMed

Asiimwe, Innocent Gerald; Rumona, Dickson

2016-01-01

To limit selective and incomplete publication of the results of clinical trials, registries including ClinicalTrials.gov were introduced. The ClinicalTrials.gov registry added a results database in 2008 to enable researchers to post the results of their trials as stipulated by the Food and Drug Administration Amendment Act of 2007. This study aimed to determine the direction and magnitude of any change in publication proportions of registered breast cancer trials that occurred since the inception of the ClinicalTrials.gov results database. A cross-sectional study design was employed using ClinicalTrials.gov, a publicly available registry/results database as the primary data source. Registry contents under the subcategories 'Breast Neoplasms' and 'Breast Neoplasms, Male' were downloaded on 1 August 2015. A literature search for included trials was afterwards conducted using MEDLINE and DISCOVER databases to determine publication status of the registered breast cancer trials. Nearly half (168/340) of the listed trials had been published, with a median time to publication of 24 months (Q1 = 14 months, Q3 = 42 months). Only 86 trials were published within 24 months of completion. There was no significant increase in publication proportions of trials that were completed before the introduction of the results database compared to those completed after (OR = 1.00, 95 % CI = .61 to 1.63; adjusted OR = 0.84, 95 % CI = .51 to 1.39). Characteristics associated with publication included trial type (observational versus interventional adjusted OR = .28, 95 % CI = .10 to .74) and completion/termination status (terminated versus completed adjusted OR = .22, 95 % CI = .09 to .51). Less than a half of breast cancer trials registered in ClinicalTrials.gov are published in peer-reviewed journals.

Biodegradable magnesium-based screw clinically equivalent to titanium screw in hallux valgus surgery: short term results of the first prospective, randomized, controlled clinical pilot study

PubMed Central

2013-01-01

Purpose Nondegradable steel-and titanium-based implants are commonly used in orthopedic surgery. Although they provide maximal stability, they are also associated with interference on imaging modalities, may induce stress shielding, and additional explantation procedures may be necessary. Alternatively, degradable polymer implants are mechanically weaker and induce foreign body reactions. Degradable magnesium-based stents are currently being investigated in clinical trials for use in cardiovascular medicine. The magnesium alloy MgYREZr demonstrates good biocompatibility and osteoconductive properties. The aim of this prospective, randomized, clinical pilot trial was to determine if magnesium-based MgYREZr screws are equivalent to standard titanium screws for fixation during chevron osteotomy in patients with a mild hallux valgus. Methods Patients (n=26) were randomly assigned to undergo osteosynthesis using either titanium or degradable magnesium-based implants of the same design. The 6 month follow-up period included clinical, laboratory, and radiographic assessments. Results No significant differences were found in terms of the American Orthopaedic Foot and Ankle Society (AOFAS) score for hallux, visual analog scale for pain assessment, or range of motion (ROM) of the first metatarsophalangeal joint (MTPJ). No foreign body reactions, osteolysis, or systemic inflammatory reactions were detected. The groups were not significantly different in terms of radiographic or laboratory results. Conclusion The radiographic and clinical results of this prospective controlled study demonstrate that degradable magnesium-based screws are equivalent to titanium screws for the treatment of mild hallux valgus deformities. PMID:23819489

Shortfalls in pediatric hydrocephalus clinical outcome analysis.

PubMed

Walid, Mohammad Sami; Robinson, Joe Sam

2012-06-01

In this paper, we used search engine technology to study outcome analysis and cost awareness of child hydrocephalus in the literature. The aggregate hospital charges of hydrocephalus treatment procedures for patients <18 years old was extracted from the Nationwide Inpatient Sample (NIS) data. Hydrocephalus literature was probed through the PubMed biomedical search engine. Aggregate hospital charges associated with ventriculo-peritoneal shunting as the principle procedure for patients <18 years old have increased 1.7-fold over a 13-year period to 235.6 million in 2009. Hospital discharges, however, decreased from 3,390 in 1997 to 2,525 in 2009 (25.5% decrease over 13 years). The number of papers in English language indexed by PubMed in relation to child hydrocephalus in humans increased from 81 papers in 1996 to 133 in 2010 (1.6-fold increase), totaling 1,694 over 15 years. Randomized controlled trials published in relation to child hydrocephalus totaled 16 over the same period (0.94% of child hydrocephalus papers). Papers related to child hydrocephalus with "costs and cost analysis" as medical subject heading totaled 13 papers (0.77%). Over the past 15 years, disappointingly the number of printed child hydrocephalus papers appeared to have only plateaued. Strikingly, only a very small number of these papers were directed toward randomized control studies, the sine qua non of high-grade clinical evidence. Moreover, very few papers make reference to cost analysis or economics in the treatment of hydrocephalus - an issue coming increasingly before the nation at this point.

Return of Individual Research Results and Incidental Findings in the Clinical Trials Cooperative Group Setting

PubMed Central

Ferriere, Michael; Van Ness, Brian

2013-01-01

The NCI funded cooperative group cancer clinical trial system develops experimental therapies and often collects patient samples for correlative research. The Cooperative Group Bank (CGB) system maintains biobanks with a current policy not to return research results to individuals. An online survey was created, and 10 directors of CGBs completed the surveys asking about understanding and attitudes in changing policies to consider return of Incidental Findings (IFs) and Individual Research Results (IRRs) of health significance. The potential impact of the ten consensus recommendations of Wolf et al. presented in this issue are examined. Re-identification of samples is often not problematic; however, changes to the current banking and clinical trial systems would require significant effort to fulfill an obligation of recontact of subjects. Additional resources, as well as a national advisory board would be required to standardize implementation. PMID:22382800

[Identification of pathologic alcohol use and its prevention. Results of employee interviews in a clinic].

PubMed

Ennenbach, M; Soyka, M

2007-05-01

After a short review of the literature about addiction in the working place, a study is presented that evaluates the alcohol use of all employees (n=301) in a clinic. The readiness to cooperate was very strong (72%). The openness (investigated with the FPI subscale for openness) was also satisfactory. Results showed a surprisingly high proportion of notable alcohol use by employees (26%). Especially the group of young female employees showed a high range of stress indicators: alcohol use (28.6%), nicotine (24.2%) and eating disorders (22.9%), and moderate-to-strong consumption of medication (12.1%). A sex-specific model of the development of addiction will be suggested based on these study results. A program of preventive measures was implemented integrating well-known components of established successful preventive measures and considering the special environment of the clinic.

Horizon 2020 in Diabetic Kidney Disease: The Clinical Trial Pipeline for Add-On Therapies on Top of Renin Angiotensin System Blockade

PubMed Central

Perez-Gomez, Maria Vanessa; Sanchez-Niño, Maria Dolores; Sanz, Ana Belen; Martín-Cleary, Catalina; Ruiz-Ortega, Marta; Egido, Jesus; Navarro-González, Juan F.; Ortiz, Alberto; Fernandez-Fernandez, Beatriz

2015-01-01

Diabetic kidney disease is the most frequent cause of end-stage renal disease. This implies failure of current therapeutic approaches based on renin-angiotensin system (RAS) blockade. Recent phase 3 clinical trials of paricalcitol in early diabetic kidney disease and bardoxolone methyl in advanced diabetic kidney disease failed to meet the primary endpoint or terminated on safety concerns, respectively. However, various novel strategies are undergoing phase 2 and 3 randomized controlled trials targeting inflammation, fibrosis and signaling pathways. Among agents currently undergoing trials that may modify the clinical practice on top of RAS blockade in a 5-year horizon, anti-inflammatory agents currently hold the most promise while anti-fibrotic agents have so far disappointed. Pentoxifylline, an anti-inflammatory agent already in clinical use, was recently reported to delay estimated glomerular filtration rate (eGFR) loss in chronic kidney disease (CKD) stage 3–4 diabetic kidney disease when associated with RAS blockade and promising phase 2 data are available for the pentoxifylline derivative CTP-499. Among agents targeting chemokines or chemokine receptors, the oral small molecule C-C chemokine receptor type 2 (CCR2) inhibitor CCX140 decreased albuminuria and eGFR loss in phase 2 trials. A dose-finding trial of the anti-IL-1β antibody gevokizumab in diabetic kidney disease will start in 2015. However, clinical development is most advanced for the endothelin receptor A blocker atrasentan, which is undergoing a phase 3 trial with a primary outcome of preserving eGFR. The potential for success of these approaches and other pipeline agents is discussed in detail. PMID:26239562

Migration characteristics and early clinical results of a novel-finned press-fit acetabular cup.

PubMed

Kaipel, Martin; Prenner, Anton; Bachl, Sebastian; Farr, Sebastian; Sinz, Günter

2014-04-01

Ana Nova® is a novel-finned press-fit acetabular cup which showed superior biomechanical characteristics in an experimental set-up. Using Einzel Bild Röntgen Analyse (EBRA) measurements should offer the opportunity to predict implant survival at an early stage. The purpose of this study was to assess migration and clinical outcome 2 years after total hip replacement by a novel-finned press-fit acetabular cup. In this study, migration and clinical results of the implant were prospectively assessed in 67 patients. Clinical outcome was assessed using the Harris hip score (HHS). Migration analyses were performed using the computer assisted EBRA system. Data were analyzed for normal distribution using the Kolmogorov-Smirnov test. Group comparisons were performed using the analysis of variance (ANOVA) test. P-values less than 0.05 were considered statistically significant. At 2 years after surgery, none of the implants needed revision and HHS increased from 39.7 up to 92.2. In contrast to the beneficial clinical outcome, 17 of 44 patients showed increased total migration ( 1 mm/2a). Adverse migration data in this study might predict aseptic loosening and decreased survival of the implant. According to previous studies, it is possible that this effect occurred because of limited accuracy of the EBRA system. In our opinion, migration analyses may not be recommended as a screening tool in a 2 year follow-up.

Clinical Examination Results in Individuals With Functional Ankle Instability and Ankle-Sprain Copers

PubMed Central

Wright, Cynthia J.; Arnold, Brent L.; Ross, Scott E.; Ketchum, Jessica; Ericksen, Jeffrey; Pidcoe, Peter

2013-01-01

Context: Why some individuals with ankle sprains develop functional ankle instability and others do not (ie, copers) is unknown. Current understanding of the clinical profile of copers is limited. Objective: To contrast individuals with functional ankle instability (FAI), copers, and uninjured individuals on both self-reported variables and clinical examination findings. Design: Cross-sectional study. Setting: Sports medicine research laboratory. Patients or Other Participants: Participants consisted of 23 individuals with a history of 1 or more ankle sprains and at least 2 episodes of giving way in the past year (FAI: Cumberland Ankle Instability Tool [CAIT] score = 20.52 ± 2.94, episodes of giving way = 5.8 ± 8.4 per month), 23 individuals with a history of a single ankle sprain and no subsequent episodes of instability (copers: CAIT score = 27.74 ± 1.69), and 23 individuals with no history of ankle sprain and no instability (uninjured: CAIT score = 28.78 ± 1.78). Intervention(s): Self-reported disability was recorded using the CAIT and Foot and Ankle Ability Measure for Activities of Daily Living and for Sports. On clinical examination, ligamentous laxity and tenderness, range of motion (ROM), and pain at end ROM were recorded. Main Outcome Measure(s): Questionnaire scores for the CAIT, Foot and Ankle Ability Measure for Activities of Daily Living and for Sports, ankle inversion and anterior drawer laxity scores, pain with palpation of the lateral ligaments, ankle ROM, and pain at end ROM. Results: Individuals with FAI had greater self-reported disability for all measures (P < .05). On clinical examination, individuals with FAI were more likely to have greater talar tilt laxity, pain with inversion, and limited sagittal-plane ROM than copers (P < .05). Conclusions: Differences in both self-reported disability and clinical examination variables distinguished individuals with FAI from copers at least 1 year after injury. Whether the deficits could be detected

Minilaparotomy vs. laparoscopic cholecystectomy: results of a randomized clinical trial.

PubMed

Velázquez-Mendoza, José Dolores; Villagrán-Murillo, Francisco Javier; González-Ojeda, Alejandro

2012-01-01

Currently, laparoscopic cholecystectomy is considered the gold standard for treatment of gallstones with advantages in regard to postoperative pain, hospital stay, early return to activities of daily living and acceptable cosmetic results. Open cholecystectomy in the form of minilaparotomy may be an effective alternative for the management of symptomatic cholelithiasis. We undertook this study to compare the results of laparoscopic cholecystectomy and minilaparotomy cholecystectomy techniques. methods: We conducted a randomized clinical trial between January 2009 and December 2009. We included patients with symptomatic cholelithiasis divided into two groups: group A--minilaparotomy and group B--laparoscopic cholecystectomy. End-point variables were age, gender, pre- and postoperative diagnosis, operative time, conversion or extension, hospital stay, complications and pain. Statistical analysis included Fisher's exact test, χ(2) test and Student t test. There were 88 patients with cholelithiasis: 37 men and 51 women. Mean age was 45.65 years. There were 45 patients in Group A and 43 patients in Group B. Mean operative time was 79.02 min for minilaparotomy and 86.04 min for laparoscopic cholecystectomy (p = 0.33). Average hospital stay was 2.75 days for minilaparotomy and of 2.02 days for laparoscopy (p = 0.60). Complications of minilaparotomy were demonstrated in 6.6% of patients and for laparoscopic cholecystectomy in 16.3% of patients (p = 0.16). There were three extensions and five conversions. Minilaparotomy cholecystectomy has results similar to laparoscopic cholecystectomy.

Clinical Trial Results Summary for Laypersons: A User Testing Study.

PubMed

Raynor, D K; Myers, L; Blackwell, K; Kress, B; Dubost, A; Joos, A

2018-01-01

To apply "user testing" to maximize readability and acceptability of a Clinical Trial Results Laypersons Summary-a new European requirement. "User testing" (using questionnaire and semistructured interview) assessed whether people could find and understand key points. Findings were used to improve content and design, prior to retesting. Participants had a range of levels of health literacy and there was a higher education group. Participants accessed the summary on screen. In round 1 we tested 12 points of information. In round 2 a revised summary addressing round 1 findings was tested, leading to a third final version. In round 1, 2 of 12 points of information did not reach the target and interviews raised further format and content issues (some distracting technical explanations and inability to find or understand the 2 main study purposes). These findings informed revisions for the version tested in round 2, with 2 different points not reaching the target (inclusion criteria relating to duration of seasonal allergies and how researchers found out about participants' symptoms). Identified problems in both rounds were addressed and reflected in the final version. Despite improvements, participants did not consistently understand that summaries were intended for the public, or to only interpret results of single trials in the context of additional trials. All readers, including those with higher education, found the clear and straightforward language acceptable. Applying "user testing" resulted in a largely health-literate summary suitable for people across a range of backgrounds.

Hemodiafiltration history, technology, and clinical results.

PubMed

Ronco, Claudio; Cruz, Dinna

2007-07-01

Hemodiafiltration (HDF) is an extracorporeal renal-replacement technique using a highly permeable membrane, in which diffusion and convection are conveniently combined to enhance solute removal in a wide spectrum of molecular weights. In this modality, ultrafiltration exceeds the desired fluid loss in the patient, and replacement fluid must be administered to achieve the target fluid balance. Over the years, various HDF variants have emerged, including acetate-free biofiltration, high-volume HDF, internal HDF, paired-filtration dialysis, middilution HDF, double high-flux HDF, push-pull HDF, and online HDF. Recent technology has allowed online production of large volumes of microbiologically ultrapure fluid for reinfusion, greatly simplifying the practice of HDF. Several advantages of HDF over purely diffusive hemodialysis techniques have been described in the literature, including a greater clearance of urea, phosphate, beta(2)-microglobulin and other larger solutes, reduction in dialysis hypotension, and improved anemia management. Although randomized controlled trials have failed to show a survival benefit of HDF, recent data from large observational studies suggest a positive effect of HDF on survival. This article provides a brief review of the history of HDF, the various HDF techniques, and summary of their clinical effects.

A review of malaria vaccine clinical projects based on the WHO rainbow table

PubMed Central

2012-01-01

Development and Phase 3 testing of the most advanced malaria vaccine, RTS,S/AS01, indicates that malaria vaccine R&D is moving into a new phase. Field trials of several research malaria vaccines have also confirmed that it is possible to impact the host-parasite relationship through vaccine-induced immune responses to multiple antigenic targets using different platforms. Other approaches have been appropriately tested but turned out to be disappointing after clinical evaluation. As the malaria community considers the potential role of a first-generation malaria vaccine in malaria control efforts, it is an apposite time to carefully document terminated and ongoing malaria vaccine research projects so that lessons learned can be applied to increase the chances of success for second-generation malaria vaccines over the next 10 years. The most comprehensive resource of malaria vaccine projects is a spreadsheet compiled by WHO thanks to the input from funding agencies, sponsors and investigators worldwide. This spreadsheet, available from WHO's website, is known as "the rainbow table". By summarizing the published and some unpublished information available for each project on the rainbow table, the most comprehensive review of malaria vaccine projects to be published in the last several years is provided below. PMID:22230255

Terminated Trials in the ClinicalTrials.gov Results Database: Evaluation of Availability of Primary Outcome Data and Reasons for Termination.

PubMed

Williams, Rebecca J; Tse, Tony; DiPiazza, Katelyn; Zarin, Deborah A

2015-01-01

Clinical trials that end prematurely (or "terminate") raise financial, ethical, and scientific concerns. The extent to which the results of such trials are disseminated and the reasons for termination have not been well characterized. A cross-sectional, descriptive study of terminated clinical trials posted on the ClinicalTrials.gov results database as of February 2013 was conducted. The main outcomes were to characterize the availability of primary outcome data on ClinicalTrials.gov and in the published literature and to identify the reasons for trial termination. Approximately 12% of trials with results posted on the ClinicalTrials.gov results database (905/7,646) were terminated. Most trials were terminated for reasons other than accumulated data from the trial (68%; 619/905), with an insufficient rate of accrual being the lead reason for termination among these trials (57%; 350/619). Of the remaining trials, 21% (193/905) were terminated based on data from the trial (findings of efficacy or toxicity) and 10% (93/905) did not specify a reason. Overall, data for a primary outcome measure were available on ClinicalTrials.gov and in the published literature for 72% (648/905) and 22% (198/905) of trials, respectively. Primary outcome data were reported on the ClinicalTrials.gov results database and in the published literature more frequently (91% and 46%, respectively) when the decision to terminate was based on data from the trial. Trials terminate for a variety of reasons, not all of which reflect failures in the process or an inability to achieve the intended goals. Primary outcome data were reported most often when termination was based on data from the trial. Further research is needed to identify best practices for disseminating the experience and data resulting from terminated trials in order to help ensure maximal societal benefit from the investments of trial participants and others involved with the study.

Spectral biopsy for skin cancer diagnosis: initial clinical results

NASA Astrophysics Data System (ADS)

Moy, Austin J.; Feng, Xu; Nguyen, Hieu T. M.; Zhang, Yao; Sebastian, Katherine R.; Reichenberg, Jason S.; Tunnell, James W.

2017-02-01

Skin cancer is the most common form of cancer in the United States and is a recognized public health issue. Diagnosis of skin cancer involves biopsy of the suspicious lesion followed by histopathology. Biopsies, which involve excision of the lesion, are invasive, at times unnecessary, and are costly procedures ( $2.8B/year in the US). An unmet critical need exists to develop a non-invasive and inexpensive screening method that can eliminate the need for unnecessary biopsies. To address this need, our group has reported on the continued development of a noninvasive method that utilizes multimodal spectroscopy towards the goal of a "spectral biopsy" of skin. Our approach combines Raman spectroscopy, fluorescence spectroscopy, and diffuse reflectance spectroscopy to collect comprehensive optical property information from suspicious skin lesions. We previously described an updated spectral biopsy system that allows acquisition of all three forms of spectroscopy through a single fiber optic probe and is composed of off-the-shelf OEM components that are smaller, cheaper, and enable a more clinic-friendly system. We present initial patient data acquired with the spectral biopsy system, the first from an extensive clinical study (n = 250) to characterize its performance in identifying skin cancers (basal cell carcinoma, squamous cell carcinoma, and melanoma). We also present our first attempts at analyzing this initial set of clinical data using statistical-based models, and with models currently being developed to extract biophysical information from the collected spectra, all towards the goal of noninvasive skin cancer diagnosis.

Implementation of a quality improvement initiative in Belgian diabetic foot clinics: feasibility and initial results.

PubMed

Doggen, Kris; Van Acker, Kristien; Beele, Hilde; Dumont, Isabelle; Félix, Patricia; Lauwers, Patrick; Lavens, Astrid; Matricali, Giovanni A; Randon, Caren; Weber, Eric; Van Casteren, Viviane; Nobels, Frank

2014-07-01

This article aims to describe the implementation and initial results of an audit-feedback quality improvement initiative in Belgian diabetic foot clinics. Using self-developed software and questionnaires, diabetic foot clinics collected data in 2005, 2008 and 2011, covering characteristics, history and ulcer severity, management and outcome of the first 52 patients presenting with a Wagner grade ≥ 2 diabetic foot ulcer or acute neuropathic osteoarthropathy that year. Quality improvement was encouraged by meetings and by anonymous benchmarking of diabetic foot clinics. The first audit-feedback cycle was a pilot study. Subsequent audits, with a modified methodology, had increasing rates of participation and data completeness. Over 85% of diabetic foot clinics participated and 3372 unique patients were sampled between 2005 and 2011 (3312 with a diabetic foot ulcer and 111 with acute neuropathic osteoarthropathy). Median age was 70 years, median diabetes duration was 14 years and 64% were men. Of all diabetic foot ulcers, 51% were plantar and 29% were both ischaemic and deeply infected. Ulcer healing rate at 6 months significantly increased from 49% to 54% between 2008 and 2011. Management of diabetic foot ulcers varied between diabetic foot clinics: 88% of plantar mid-foot ulcers were off-loaded (P10-P90: 64-100%), and 42% of ischaemic limbs were revascularized (P10-P90: 22-69%) in 2011. A unique, nationwide quality improvement initiative was established among diabetic foot clinics, covering ulcer healing, lower limb amputation and many other aspects of diabetic foot care. Data completeness increased, thanks in part to questionnaire revision. Benchmarking remains challenging, given the many possible indicators and limited sample size. The optimized questionnaire allows future quality of care monitoring in diabetic foot clinics. Copyright © 2014 John Wiley & Sons, Ltd.

Behavioral and neural reactions to emotions of others in the distribution of resources.

PubMed

Lelieveld, Gert-Jan; Van Dijk, Eric; Güroğlu, Berna; Van Beest, Ilja; Van Kleef, Gerben A; Rombouts, Serge A R B; Crone, Eveline A

2013-01-01

This study investigated the neural mechanisms involved in the interpersonal effects of emotions--i.e., how people are influenced by other people's emotions. Participants were allocators in a version of the dictator game and made a choice between two offers after receiving written emotional expressions of the recipients. The results showed that participants more often made a self-serving offer when dealing with an angry recipient than when dealing with a happy or disappointed recipient. Compared to disappointment, expressions of anger increased activation in regions associated with self-referential thinking (anterior medial prefrontal cortex, aMPFC) and (emotional) conflict (anterior cingulate cortex). We found increased activation in temporoparietal junction for receiving happy reactions in comparison with receiving angry or disappointed reactions. This study thus emphasizes that distinct emotions have distinct effects on people in terms of behavior and underlying neurological mechanisms.

Clinical epidemiology of eosinophilic pustular folliculitis: results from a nationwide survey in Japan.

PubMed

Yamamoto, Yosuke; Nomura, Takashi; Kabashima, Kenji; Miyachi, Yoshiki

2015-01-01

No epidemiological study has examined the clinical characteristics, including medication use, of patients with eosinophilic pustular folliculitis (EPF). To describe the clinical characteristics for EPF and to examine the factors associated with the effectiveness of oral indomethacin for EPF. A cross-sectional study was performed of patients with EPF who visited the dermatology departments of the 67 main teaching facilities in Japan. We documented the patient characteristics and examined factors associated with the effectiveness of oral indomethacin. A total of 145 patients with EPF were enrolled; 62.8% were prescribed oral indomethacin. A multivariable analysis revealed that female patients were more likely to exhibit complete response to oral indomethacin after adjustment for confounders (adjusted proportion ratio = 1.93, p = 0.04). Oral indomethacin has been accepted as a first-line treatment in EPF. Our results suggest that there is a sex difference in the treatment response to oral indomethacin. © 2014 S. Karger AG, Basel.

Mapping the Ethics of Translational Genomics: Situating Return of Results and Navigating the Research-Clinical Divide

PubMed Central

Wolf, Susan M.; Burke, Wylie; Koenig, Barbara A.

2015-01-01

Both bioethics and law have governed human genomics by distinguishing research from clinical practice. Yet the rise of translational genomics now makes this traditional dichotomy inadequate. This paper pioneers a new approach to the ethics of translational genomics. It maps the full range of ethical approaches needed, proposes a “layered” approach to determining the ethics framework for projects combining research and clinical care, and clarifies the key role that return of results can play in advancing translation. PMID:26479558

Not so Fast: Co-Requirements for Sonic Hedgehog Induced Brain Tumorigenesis.

PubMed

Ward, Stacey A; Rubin, Joshua B

2015-08-06

The Sonic hedgehog (Shh) pathway plays an integral role in cellular proliferation during normal brain development and also drives growth in a variety of cancers including brain cancer. Clinical trials of Shh pathway inhibitors for brain tumors have yielded disappointing results, indicating a more nuanced role for Shh signaling. We postulate that Shh signaling does not work alone but requires co-activation of other signaling pathways for tumorigenesis and stem cell maintenance. This review will focus on the interplay between the Shh pathway and these pathways to promote tumor growth in brain tumors, presenting opportunities for the study of combinatorial therapies.

Comparision of clinical and histopathological results of hyalomatrix usage in adult patients.

PubMed

Erbatur, Serkan; Coban, Yusuf Kenan; Aydın, Engin Nasuhi

2012-01-01

Clinical and histopathological results of the hyaluronic acid skin substitute treatment of the patients who admitted to Inonu University Medical Faculty Plastic Reconstructive and Aesthetic Surgery clinic between january 2011 and march 2012 were evaluated. The patients were divided into two groups. HA were used for treatment of Hypertrophic scar (HS) or Keloid (K) in 10 patients of the first group. Skin biopsies obtained at peroperative and postoperative 3rd month were subjected to histopathologic examination in this group. In the second group, 10 patients with full thickness soft tissue loss secondary to burns, trauma or excisional reasons were also treated with HA application. Vancouver scar scale were used to determine the scar quality in both groups. Mean age was 25. 2 ± 10.2 and mean follow-up duration was 6.3±3.6 months in group 1. Preoperative and postoperative VSS scores in group 1 were 10.7±1.16 and 6.2±0.91, respectively. This difference was statistically significant (p<0,005). No HS or K development was seen in any patient in group 2 during the following period. Collagenisation scores of preoperative skin biopsies were significantly higher than postoperative scores (p<0,0001).Vascularisation scores of preoperative skin biopsies were significantly lower than postoperative scores (p<0,00001). The use of HA skin substitute in adults for treatment of HS or K provided the desired clinical healing in the 6 months' follow-up periods. At the same time, HA application as an alternative to other treatment modalities led to a durable skin coverage in full thickness tissue loss in adult patients.

Vascular access clinic results before and after implementing a multidisciplinary approach adding routine Doppler ultrasound.

PubMed

Aragoncillo Sauco, Inés; Ligero Ramos, José Manuel; Vega Martínez, Almudena; Morales Muñoz, Ángel Luis; Abad Estébanez, Soraya; Macías Carmona, Nicolás; Ruiz Chiriboga, Diego; García Pajares, Rosario; Cervera Bravo, Teresa; López-Gómez, Juan Manuel; Manzano Grossi, Soledad; Menéndez Sánchez, Elena; Río Gomez, Javier; García Prieto, Ana María; Linares Grávalos, Tania; Garcia Boyano, Fernando; Reparaz Asensio, Luis Manuel; Albalate Ramón, Marta; de Sequera Ortiz, Patricia; Gil Casares, Beatriz; Ampuero Mencía, Jara; Castellano, Sandra; Martín Pérez, Belén; Conty, José Luís Martín; Santos Garcia, Alba; Luño Fernandez, José

2018-06-11

A multidisciplinary approach and Doppler ultrasound (DU) assessment for the creation and maintenance of arteriovenous fistulas (AVF) for haemodialysis can improve prevalence and patency. The aim of this study was to analyse the impact of a new multidisciplinary vascular access (VA) clinic with routine DU. We analysed the VA clinic results from 2014 and 2015, before and after the implementation of a multidisciplinary team protocol (vascular surgeon/nephrologist) with routine DU in preoperative mapping and prevalent AVF. We analysed 345 and 364 patients from 2014 and 2015 respectively. The number of surgical interventions was similar in both periods (p=.289), with a trend towards an increase in preventive surgical repair of AVF in 2015 (17 vs. 29, p=.098). 155 vs. 169 new AVF were performed in 2014 and 2015, with a significantly lower primary failure rate in 2015 (26.4 vs. 15.3%, p=.015), and a non-significant increase in radiocephalic AVF, 25.8 vs. 33.2% (n=40 vs. 56), p=.159. The concordance between the indication at the clinic and the surgery performed also increased (81.3 vs. 93.5%, p=.001). Throughout 2015 fewer complementary imaging test were requested from the clinic (78 vs. 35, p <.001), with a corresponding reduction in costs (€87,716 vs. €59,445). Multidisciplinary approach with routine DU can improve VA results, with a decrease in primary failure rate, higher likelihood of radiocephalic AVF, better management of dis-functioning AVF and lower radiological test costs. Copyright © 2018 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Update on B-cell targeted therapies for systemic lupus erythematosus.

PubMed

Mok, Chi Chiu

2014-06-01

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by flares and remission, leading to accrual of organ damage over time as a result of persistent tissue inflammation and treatment-related complications. Novel therapies aiming at better treatment response and fewer adverse effects are being tested in the pipeline. This review summarizes the B-cell abnormalities observed in patients with SLE, and updates recent data on the efficacy and safety of B-cell targeted therapies in the treatment of SLE. The pitfalls of clinical trial design and future directions of the development of SLE therapeutics are discussed. The variability of clinical response to treatment in SLE reflects the clinical and immunological heterogeneity of the disease. The treatment plan for patients with SLE should be individualized with the aim of eradicating disease activity, preventing flares and minimizing treatment-related complications. Despite the disappointment of recent clinical trials, B-cell remains the promising target of future SLE therapies. Results from ongoing clinical trials on B-cell targeted biological agents are eagerly awaited.

Influence of clinical and laboratory variables on faecal antigen ELISA results in dogs with canine parvovirus infection.

PubMed

Proksch, A L; Unterer, S; Speck, S; Truyen, U; Hartmann, K

2015-06-01

False negative faecal canine parvovirus (CPV) antigen ELISA results in dogs with CPV infection are common, but the factors that lead to these false negative results are still unknown. The aim of this study was to investigate whether dogs with a false negative faecal CPV antigen ELISA result have milder clinical signs and laboratory changes, a lower faecal virus load, higher faecal and serum CPV antibody titres and a faster recovery than dogs with a positive result. Eighty dogs with CPV infection, confirmed by the presence of clinical signs and a positive faecal CPV polymerase chain reaction (PCR), were assigned to two groups according to their faecal antigen ELISA result. Time until presentation, severity of symptoms, laboratory parameters, faecal virus load, faecal and serum antibody titres, and CPV sequencing data were compared between both groups. In 38/80 dogs that were hospitalised until recovery, the time to recovery, mortality, and the course of the disease were compared between dogs with positive and negative faecal antigen ELISA results. Of the 80 dogs included, 41 (51.3%) had a false negative faecal antigen ELISA result. ELISA-negative dogs had a significantly shorter time until presentation, lower frequency of defaecation, lower faecal virus load, and higher serum antibody concentrations than ELISA-positive dogs. Laboratory changes, CPV shedding, and outcomes were not associated with faecal antigen ELISA results. In conclusion, low faecal CPV load and antibodies binding to CPV antigen in faeces are likely to be important reasons for false negative faecal antigen ELISA results. Dogs with clinical signs of CPV infection should be retested by faecal PCR. Copyright © 2015 Elsevier Ltd. All rights reserved.

Mapping the Ethics of Translational Genomics: Situating Return of Results and Navigating the Research-Clinical Divide.

PubMed

Wolf, Susan M; Burke, Wylie; Koenig, Barbara A

2015-01-01

Both bioethics and law have governed human genomics by distinguishing research from clinical practice. Yet the rise of translational genomics now makes this traditional dichotomy inadequate. This paper pioneers a new approach to the ethics of translational genomics. It maps the full range of ethical approaches needed, proposes a "layered" approach to determining the ethics framework for projects combining research and clinical care, and clarifies the key role that return of results can play in advancing translation. © 2015 American Society of Law, Medicine & Ethics, Inc.

Clinical indications for antibiotic use in Danish general practice: results from a nationwide electronic prescription database

PubMed Central

Aabenhus, Rune; Hansen, Malene Plejdrup; Siersma, Volkert; Bjerrum, Lars

2017-01-01

Objective To assess the availability and applicability of clinical indications from electronic prescriptions on antibiotic use in Danish general practice. Design Retrospective cohort register-based study including the Danish National Prescription Register. Setting Population-based study of routine electronic antibiotic prescriptions from Danish general practice. Subjects All 975,626 patients who redeemed an antibiotic prescription at outpatient pharmacies during the 1-year study period (July 2012 to June 2013). Main outcome measures Number of prescriptions per clinical indication. Number of antibiotic prescriptions per 1000 inhabitants by age and gender. Logistic regression analysis estimated the association between patient and provider factors and missing clinical indications on antibiotic prescriptions. Results A total of 2.381.083 systemic antibiotic prescriptions were issued by Danish general practitioners in the study period. We identified three main clinical entities: urinary tract infections (n = 506.634), respiratory tract infections (n = 456.354) and unspecified infections (n = 416.354). Women were more exposed to antibiotics than men. Antibiotic use was high in children under 5 years and even higher in elderly people. In 32% of the issued prescriptions, the clinical indication was missing. This was mainly associated with antibiotic types. We found that a prescription for a urinary tract agent without a specific clinical indication was uncommon. Conclusion Clinical indications from electronic prescriptions are accessible and available to provide an overview of drug use, in casu antibiotic prescriptions, in Danish general practice. These clinical indications may be further explored in detail to assess rational drug use and congruence with guidelines, but validation and optimisation of the system is preferable. PMID:28585886

Clinical Features and Surgical Results of Right Atrial Myxoma.

PubMed

Li, Han; Guo, Hongwei; Xiong, Hui; Xu, Jianping; Wang, Wei; Hu, Shengshou

2016-01-01

We retrospectively analyzed 367 patients receiving surgical resection of cardiac myxomas in our center over six years, and analyzed the incidence and surgical results of 28 cases of right atrial myxomas. We also compared the age, gender, and attached sites between left atrial myxoma and right atrial myxoma. Between January 2007 and December 2012, 28 patients with right atrial myxomas underwent surgical resection. There were 16 males and 12 females. The mean age was 47.77 ± 13.20 years (range: 8.00-79.00 years). Associated cardiac lesions included moderate and severe tricuspid regurgitation in four, coronary atherosclerotic heart disease in five, and pulmonary embolism in one. Twenty-seven patients (96.43%) were followed from 26 to 94 months (mean 55.78 ± 21.10 months). There was no early death after operation. The incidence of right atrial myxomas among sporadic cardiac myxomas was 7.89%. One patient died of lung cancer 34 months after myxoma resection. Two patients underwent coronary artery stent implantation due to coronary atherosclerotic heart disease during the follow-up period. One patient underwent myxoma resection due to recurrence in the left atrium four years after the first operation. There was no significant difference in the age between left atrial myxoma and right atrial myxoma (p > 0.05). There was a significant difference in the gender between left atrial myxomas and right atrial myxomas (p < 0.05). The most common attached sites of left atrial myxomas and right atrial myxomas are the atrial septum. Surgical resection of the right atrial myxoma results in good clinical outcomes and a decreased incidence of recurrence. © 2015 Wiley Periodicals, Inc.

Involving clinical librarians at the point of care: results of a controlled intervention.

PubMed

Aitken, Elizabeth M; Powelson, Susan E; Reaume, Renée D; Ghali, William A

2011-12-01

To measure the effect of including a clinical librarian in the health care team on medical residents and clinical clerks. In 2009, medical residents and clinical clerks were preassigned to one of two patient care teams (intervention and control). Each team had a month-long rotation on the general medicine teaching unit. The clinical librarian joined the intervention team for morning intake, clinical rounding, or an afternoon patient list review, providing immediate literature searches, formal group instruction, informal bedside teaching, and/or individual mentoring for use of preappraised resources and evidence-based medicine search techniques. Both intervention and control teams completed pre and post surveys comparing their confidence levels and awareness of resources as well as their self-reported use of evidence for making patient care decisions. The nonintervention team was surveyed as the control group. The clinical librarian intervention had a significant positive effect on medical trainees' self-reported ability to independently locate and evaluate evidence resources to support patient care decisions. Notably, 30 of 34 (88%) reported having changed a treatment plan based on skills taught by the clinical librarian, and 27 of 34 (79%) changed a treatment plan based on the librarian's mediated search support. Clinical librarians on the care team led to positive effects on self-reported provider attitudes, provider information retrieval tendencies, and, notably, clinical decision making. Future research should evaluate economic effects of widespread implementation of on-site clinical librarians.

Clinical results of computerized tomography-based simulation with laser patient marking.

PubMed

Ragan, D P; Forman, J D; He, T; Mesina, C F

1996-02-01

Accuracy of a patient treatment portal marking device and computerized tomography (CT) simulation have been clinically tested. A CT-based simulator has been assembled based on a commercial CT scanner. This includes visualization software and a computer-controlled laser drawing device. This laser drawing device is used to transfer the setup, central axis, and/or radiation portals from the CT simulator to the patient for appropriate patient skin marking. A protocol for clinical testing is reported. Twenty-five prospectively, sequentially accessioned patients have been analyzed. The simulation process can be completed in an average time of 62 min. Under many cases, the treatment portals can be designed and the patient marked in one session. Mechanical accuracy of the system was found to be within +/- 1mm. The portal projection accuracy in clinical cases is observed to be better than +/- 1.2 mm. Operating costs are equivalent to the conventional simulation process it replaces. Computed tomography simulation is a clinical accurate substitute for conventional simulation when used with an appropriate patient marking system and digitally reconstructed radiographs. Personnel time spent in CT simulation is equivalent to time in conventional simulation.

Clinical response of the novel activating ALK-I1171T mutation in neuroblastoma to the ALK inhibitor ceritinib.

PubMed

Guan, Jikui; Fransson, Susanne; Siaw, Joachim Tetteh T; Treis, Diana; Van den Eynden, Jimmy; Chand, Damini; Umapathy, Ganesh; Svenberg, Petter; Ruuth, Kristina; Wessman, Sandra; Shamikh, Alia; Jacobsson, Hans; Gordon, Lena; Stenman, Jakob; Larsson, Erik; Svensson, Par-Johan; Hansson, Magnus; Martinsson, Tommy; Kogner, Per; Palmer, Ruth H; Hallberg, Bengt

2018-06-15

Tumors with Anaplastic Lymphoma Kinase (ALK) fusion rearrangements, including non-small cell lung cancer and anaplastic large cell lymphoma, are highly sensitive to ALK tyrosine kinase inhibitors (TKIs), underscoring the notion that such cancers are addicted to ALK activity. While mutations in ALK are heavily implicated in childhood neuroblastoma, response to the ALK TKI crizotinib has been disappointing. Embryonal tumors in patients with DNA repair defects such as Fanconi anemia (FA) often have a poor prognosis, due to lack of therapeutic options. Here we report a child with underlying FA and ALK mutant high-risk neuroblastoma responding strongly to precision therapy with the ALK TKI ceritinib. Conventional chemotherapy treatment caused severe, life-threatening toxicity. Genomic analysis of the initial biopsy identified germ-line FANCA mutations as well as a novel ALK-I1171T variant. ALK-I1171T generates a potent gain-of-function mutant, as measured in PC12 cell neurite outgrowth and NIH3T3 transformation. Pharmacological inhibition profiling of ALK-I1171T in response to various ALK TKIs identified an 11-fold improved inhibition of ALK-I1171T with ceritinib when compared with crizotinib. Immunoaffinity-coupled LC-MS/MS phosphoproteomics analysis indicated a decrease in ALK signaling in response to ceritinib. Ceritinib was therefore selected for treatment in this child. Mono-therapy with ceritinib was well tolerated and resulted in normalized catecholamine markers and tumor shrinkage. After 7.5 months treatment, residual primary tumor was surgically removed and exhibited hallmarks of differentiation together with reduced Ki67 levels. Clinical follow-up after 21 months treatment revealed complete clinical remission including all metastatic sites. Therefore, ceritinib presents a viable therapeutic option for ALK-positive neuroblastoma. Cold Spring Harbor Laboratory Press.

Receiving a summary of the results of a trial: qualitative study of participants' views

PubMed Central

Dixon-Woods, Mary; Jackson, Clare; Windridge, Kate C; Kenyon, Sara

2006-01-01

Objective To explore trial participants' responses to receiving a summary of the results of a trial in pregnancy. Design Qualitative study with semistructured interviews. Participants 20 women who had when pregnant participated in the ORACLE trial of antibiotics for preterm labour and preterm rupture of the membranes and requested a copy of the trial results. Results Less than a fifth of women who participated in the ORACLE trial indicated that they wished to receive the trial results. Reactions to the leaflet summarising the trial results were generally positive or neutral, although some women had difficulty in understanding the leaflet, and there was evidence of possible negative implications for women who had adverse outcomes. Women requested the results because they were interested in being able to complete their own personal narrative. They wished to know to which arm of the trial they had been allocated and the implications for their own pregnancy, and they were disappointed with receiving a generic summary. Women's accounts indicated some confusion about the trial findings. Conclusions Recommendations that research participants be routinely provided with the results of studies have been made without the benefit of research to show the consequences of doing this or how it should best be managed. Caution is needed, as is more evaluation of how feedback of results should be handled, and assessment of the risks, benefits, and costs. PMID:16401631

Progress with oocyte cryopreservation.

PubMed

Porcu, Eleonora; Venturoli, Stefano

2006-06-01

This article reviews human oocyte cryopreservation, one of the most stimulating challenges of assisted reproduction technology. Since the first steps in assisted reproduction technology, researchers have pursued this goal, to greatly improve the management of infertility treatments. This present review depicts the present state of research and clinical applications of this methodology. Recent literature focuses on the possible mechanisms of oocyte damage caused by temperature and cryoprotectant injury and forecasts possible technological solutions. Several papers illustrate encouraging results in the increasing clinical application of this procedure. Findings give support to several indications of human female gamete cryostorage. Oocyte cryopreservation might replace embryo freezing. Egg freezing offers an alternative to women at risk of losing their reproductive function, caused by antineoplastic treatments, endometriosis, ovarian surgery or genetic premature ovarian failure. In addition, oocyte storage may contribute to an increase in in-vitro fertilization flexibility. Despite the early disappointing results, recent technical modifications have improved the clinical efficiency greatly, with the birth of several healthy children.

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.

[Chronic complex tinnitus: therapeutic results of inpatient treatment in a tinnitus clinic].

PubMed

Hesse, G; Rienhoff, N K; Nelting, M; Laubert, A

2001-09-01

In-patient treatment of patients with chronic tinnitus is necessary only when these patients have a severe psychosomatic co-morbidity and suffer severely. However this therapeutic approach has to be supervised and evaluated properly. We present data and results of 1841 patients suffering from chronic tinnitus. Due to the severity of the symptom and psycho-neurotic side effects in-patient treatment was necessary. Therapy lasted 5 - 6 weeks, the main aspect was an intensive psychotherapeutic evaluation and stabilisation next to retraining and habituation programmes. Relaxation techniques were taught. Patients suffered from their tinnitus more than six month; 95 % further suffered from hearing-loss, mainly in high frequencies. The study evaluates results of patients from October 1994 until June 2000. Basis of the study was the evaluation of a specific tinnitus-questionnaire (TQ), published by Hallam in the UK and translated by Goebel and Hiller in Germany. Data was recorded at registration in our clinic, 4 - 6 months later during admission and at the end of the therapy. Final data was gained during a special meeting or questioning 6 months after dismissal from the clinic. Patients that suffered most showed the greatest improvement; directly after therapy there was a highly significant improvement in the TQ for an average of 13.01 points. Highly significant improvements were found in all the TQ-subscales respectively. Only 10 % of the patients did not show any improvement at all. Therapy of most severe cases of chronic tinnitus is possible, using an integrated concept of otologic and psychosomatic treatments. With large numbers of patients and sufficient data a thorough and necessary evaluation of this therapy can be achieved.

Terminated Trials in the ClinicalTrials.gov Results Database: Evaluation of Availability of Primary Outcome Data and Reasons for Termination

PubMed Central

Williams, Rebecca J.; Tse, Tony; DiPiazza, Katelyn; Zarin, Deborah A.

2015-01-01

Background Clinical trials that end prematurely (or “terminate”) raise financial, ethical, and scientific concerns. The extent to which the results of such trials are disseminated and the reasons for termination have not been well characterized. Methods and Findings A cross-sectional, descriptive study of terminated clinical trials posted on the ClinicalTrials.gov results database as of February 2013 was conducted. The main outcomes were to characterize the availability of primary outcome data on ClinicalTrials.gov and in the published literature and to identify the reasons for trial termination. Approximately 12% of trials with results posted on the ClinicalTrials.gov results database (905/7,646) were terminated. Most trials were terminated for reasons other than accumulated data from the trial (68%; 619/905), with an insufficient rate of accrual being the lead reason for termination among these trials (57%; 350/619). Of the remaining trials, 21% (193/905) were terminated based on data from the trial (findings of efficacy or toxicity) and 10% (93/905) did not specify a reason. Overall, data for a primary outcome measure were available on ClinicalTrials.gov and in the published literature for 72% (648/905) and 22% (198/905) of trials, respectively. Primary outcome data were reported on the ClinicalTrials.gov results database and in the published literature more frequently (91% and 46%, respectively) when the decision to terminate was based on data from the trial. Conclusions Trials terminate for a variety of reasons, not all of which reflect failures in the process or an inability to achieve the intended goals. Primary outcome data were reported most often when termination was based on data from the trial. Further research is needed to identify best practices for disseminating the experience and data resulting from terminated trials in order to help ensure maximal societal benefit from the investments of trial participants and others involved with the study

Kilovoltage Intrafraction Monitoring for Prostate Intensity Modulated Arc Therapy: First Clinical Results

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

Ng, Jin Aun; Institute of Medical Physics, School of Physics, University of Sydney, New South Wales; Booth, Jeremy T.

2012-12-01

Purpose: Most linear accelerators purchased today are equipped with a gantry-mounted kilovoltage X-ray imager which is typically used for patient imaging prior to therapy. A novel application of the X-ray system is kilovoltage intrafraction monitoring (KIM), in which the 3-dimensional (3D) tumor position is determined during treatment. In this paper, we report on the first use of KIM in a prospective clinical study of prostate cancer patients undergoing intensity modulated arc therapy (IMAT). Methods and Materials: Ten prostate cancer patients with implanted fiducial markers undergoing conventionally fractionated IMAT (RapidArc) were enrolled in an ethics-approved study of KIM. KIM involves acquiringmore » kV images as the gantry rotates around the patient during treatment. Post-treatment, markers in these images were segmented to obtain 2D positions. From the 2D positions, a maximum likelihood estimation of a probability density function was used to obtain 3D prostate trajectories. The trajectories were analyzed to determine the motion type and the percentage of time the prostate was displaced {>=}3, 5, 7, and 10 mm. Independent verification of KIM positional accuracy was performed using kV/MV triangulation. Results: KIM was performed for 268 fractions. Various prostate trajectories were observed (ie, continuous target drift, transient excursion, stable target position, persistent excursion, high-frequency excursions, and erratic behavior). For all patients, 3D displacements of {>=}3, 5, 7, and 10 mm were observed 5.6%, 2.2%, 0.7% and 0.4% of the time, respectively. The average systematic accuracy of KIM was measured at 0.46 mm. Conclusions: KIM for prostate IMAT was successfully implemented clinically for the first time. Key advantages of this method are (1) submillimeter accuracy, (2) widespread applicability, and (3) a low barrier to clinical implementation. A disadvantage is that KIM delivers additional imaging dose to the patient.« less

Mid- and long-term clinical results of surgical therapy in unicameral bone cysts.

PubMed

Hagmann, Sébastien; Eichhorn, Florian; Moradi, Babak; Gotterbarm, Tobias; Dreher, Thomas; Lehner, Burkhard; Zeifang, Felix

2011-12-13

Unicameral (or simple) bone cysts (UBC) are benign tumours most often located in long bones of children and adolescents. Pathological fractures are common, and due to high recurrence rates, these lesions remain a challenge to treat. Numerous surgical procedures have been proposed, but there is no general consensus of the ideal treatment. The aim of this investigation therefore was to study the long-term outcome after surgical treatment in UBC. A retrospective analysis of 46 patients surgically treated for UBC was performed for short and mid-term outcome. Clinical and radiological outcome parameters were studied according to a modified Neer classification system. Long-term clinical information was retrieved via a questionnaire at a minimum follow-up of 10 years after surgery. Forty-six patients (17 female, 29 male) with a mean age of 10.0 ± 4.8 years and with histopathologically confirmed diagnosis of UBC were included. Pathological fractures were observed in 21 cases (46%). All patients underwent surgery for UBC (35 patients underwent curettage and bone grafting as a primary therapy, 4 curettage alone, 3 received corticoid instillation and 4 decompression by cannulated screws). Overall recurrence rate after the first surgical treatment was 39% (18/46), second (17.4% of all patients) and third recurrence (4.3%) were frequently observed and were addressed by revision surgery. Recurrence was significantly higher in young and in male patients as well as in active cysts. After a mean of 52 months, 40 out of 46 cysts were considered healed. Prognosis was significantly better when recurrence was observed later than 30 months after therapy. After a mean follow-up of 15.5 ± 6.2 years, 40 patients acknowledged clinically excellent results, while five reported mild and casual pain. Only one patient reported a mild limitation of range of motion. Our results suggest satisfactory overall long-term outcome for the surgical treatment of UBC, although short-and mid

Does electronic clinical microbiology results reporting influence medical decision making: a pre- and post-interview study of medical specialists.

PubMed

Bruins, Marjan J; Ruijs, Gijs J H M; Wolfhagen, Maurice J H M; Bloembergen, Peter; Aarts, Jos E C M

2011-03-30

Clinicians view the accuracy of test results and the turnaround time as the two most important service aspects of the clinical microbiology laboratory. Because of the time needed for the culturing of infectious agents, final hardcopy culture results will often be available too late to have a significant impact on early antimicrobial therapy decisions, vital in infectious disease management. The clinical microbiologist therefore reports to the clinician clinically relevant preliminary results at any moment during the diagnostic process, mostly by telephone. Telephone reporting is error prone, however. Electronic reporting of culture results instead of reporting on paper may shorten the turnaround time and may ensure correct communication of results. The purpose of this study was to assess the impact of the implementation of electronic reporting of final microbiology results on medical decision making. In a pre- and post-interview study using a semi-structured design we asked medical specialists in our hospital about their use and appreciation of clinical microbiology results reporting before and after the implementation of an electronic reporting system. Electronic reporting was highly appreciated by all interviewed clinicians. Major advantages were reduction of hardcopy handling and the possibility to review results in relation to other patient data. Use and meaning of microbiology reports differ significantly between medical specialties. Most clinicians need preliminary results for therapy decisions quickly. Therefore, after the implementation of electronic reporting, telephone consultation between clinician and microbiologist remained the key means of communication. Overall, electronic reporting increased the workflow efficiency of the medical specialists, but did not have an impact on their decision-making. © 2011 Bruins et al; licensee BioMed Central Ltd.

Effects of canine parvovirus strain variations on diagnostic test results and clinical management of enteritis in dogs.

PubMed

Markovich, Jessica E; Stucker, Karla M; Carr, Alaina H; Harbison, Carole E; Scarlett, Janet M; Parrish, Colin R

2012-07-01

To estimate the prevalence of canine parvovirus (CPV) strains among dogs with enteritis admitted to a referral hospital in the southwestern United States during an 11-month period and to compare diagnostic test results, disease severity, and patient outcome among CPV strains. Prospective observational study. 72 dogs with histories and clinical signs of parvoviral enteritis. For each dog, a fecal sample or rectal swab specimen was evaluated for CPV antigen via an ELISA. Subsequently, fecal samples (n = 42 dogs) and pharyngeal swab specimens (16) were obtained and tested for CPV antigen via an ELISA and CPV DNA via a PCR assay. For specimens with CPV-positive results via PCR assay, genetic sequencing was performed to identify the CPV strain. 56 dogs tested positive for CPV via ELISA or PCR assay. For 42 fecal samples tested via both ELISA and PCR assay, 27 had positive results via both assays, whereas 6 had positive PCR assay results only. Ten pharyngeal swab specimens yielded positive PCR assay results. Genetic sequencing was performed on 34 fecal or pharyngeal swab specimens that had CPV-positive PCR assay results; 25 (73.5%) were identified as containing CPV type-2c, and 9 (26.5%) were identified as containing CPV type-2b. No association was found between CPV strain and disease severity or clinical outcome. CPV type-2b and CPV type-2c posed similar health risks for dogs; therefore, genetic sequencing of CPV does not appear necessary for clinical management of infected patients. The diagnostic tests used could detect CPV type-2c.

Implementation of depression screening in antenatal clinics through tablet computers: results of a feasibility study.

PubMed

Marcano-Belisario, José S; Gupta, Ajay K; O'Donoghue, John; Ramchandani, Paul; Morrison, Cecily; Car, Josip

2017-05-10

Mobile devices may facilitate depression screening in the waiting area of antenatal clinics. This can present implementation challenges, of which we focused on survey layout and technology deployment. We assessed the feasibility of using tablet computers to administer a socio-demographic survey, the Whooley questions and the Edinburgh Postnatal Depression Scale (EPDS) to 530 pregnant women attending National Health Service (NHS) antenatal clinics across England. We randomised participants to one of two layout versions of these surveys: (i) a scrolling layout where each survey was presented on a single screen; or (ii) a paging layout where only one question appeared on the screen at any given time. Overall, 85.10% of eligible pregnant women agreed to take part. Of these, 90.95% completed the study procedures. Approximately 23% of participants answered Yes to at least one Whooley question, and approximately 13% of them scored 10 points of more on the EPDS. We observed no association between survey layout and the responses given to the Whooley questions, the median EPDS scores, the number of participants at increased risk of self-harm, and the number of participants asking for technical assistance. However, we observed a difference in the number of participants at each EPDS scoring interval (p = 0.008), which provide an indication of a woman's risk of depression. A scrolling layout resulted in faster completion times (median = 4 min 46 s) than a paging layout (median = 5 min 33 s) (p = 0.024). However, the clinical significance of this difference (47.5 s) is yet to be determined. Tablet computers can be used for depression screening in the waiting area of antenatal clinics. This requires the careful consideration of clinical workflows, and technology-related issues such as connectivity and security. An association between survey layout and EPDS scoring intervals needs to be explored further to determine if it corresponds to a survey layout effect

Clinical supervision: what's going on? Results of a questionnaire.

PubMed

Bishop, V

This paper presents data obtained from a questionnaire sent to trust nurse executives in England and Scotland. While the data indicates a great deal of enthusiasm for clinical supervision, some concern must be shown for the lack of preparation and support for those involved in its implementation, a fact that will undoubtedly reflect badly in any evaluation exercise.

75 FR 16129 - Agency Information Collection Activities: Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-31

... use the Internet as a virtual collaborative met with disappointing results. Another barrier to... while attending to their financial realities. The result was Implementing Integrating Chronic Care and...

SU-C-BRE-01: 3D Conformal Micro Irradiation Results of Four Treatment Sites for Preclinical Small Animal and Clinical Treatment Plans

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

Price, S; Yaddanapudi, S; Rangaraj, D

Purpose: Small animal irradiation can provide preclinical insights necessary for clinical advancement. In order to provide clinically relevant data, these small animal irradiations must be designed such that the treatment methods and results are comparable to clinical protocols, regardless of variations in treatment size and modality. Methods: Small animal treatments for four treatment sites (brain, liver, lung and spine) were investigated, accounting for change in treatment energy and target size. Up to five orthovoltage (300kVp) beams were used in the preclinical treatments, using circular, square, and conformal tungsten apertures, based on the treatment site. Treatments were delivered using the imagemore » guided micro irradiator (microIGRT). The plans were delivered to a mouse sized phantom and dose measurements in axial and coronal planes were performed using radiochromic film. The results of the clinical and preclinical protocols were characterized in terms of conformality number, CTV coverage, dose nonuniformity ratio, and organ at risk sparing. Results: Preclinical small animal treatment conformality was within 1–16% of clinical results for all treatment sites. The volume of the CTV receiving 100% of the prescription dose was typically within 10% of clinical values. The dose non-uniformity was consistently higher for preclinical treatments compared to clinical treatments, indicating hot spots in the target. The ratios of the mean dose in the target to the mean dose in an organ at risk were comparable if not better for preclinical versus clinical treatments. Finally, QUANTEC dose constraints were applied and the recommended morbidity limits were satisfied in each small animal treatment site. Conclusion: We have shown that for four treatment sites, preclinical 3D conformal small animal treatments can be clinically comparable if clinical protocols are followed. Using clinical protocols as the standard, preclinical irradiation methods can be altered and

Clinical utility of FDG PET/CT in acute complicated pyelonephritis-results from an observational study.

PubMed

Wan, Chih-Hsing; Tseng, Jing-Ren; Lee, Ming-Hsun; Yang, Lan-Yan; Yen, Tzu-Chen

2018-03-01

Acute complicated pyelonephritis (ACP) is an upper urinary tract infection associated with coexisting urinary tract abnormalities or medical conditions that could predispose to serious outcomes or treatment failures. Although CT and magnetic resonance imaging (MRI) are frequently used in patients with ACP, the clinical value of 18 F-fluorodeoxyglucose positron emission tomography and computed tomography (FDG PET/CT) has not been systematically investigated. This single-center retrospective study was designed to evaluate the potential usefulness of FDG PET/CT in patients with ACP. Thirty-one adult patients with ACP who underwent FDG PET/CT were examined. FDG PET/CT imaging characteristics, including tracer uptake patterns, kidney volumes, and extrarenal imaging findings, were reviewed in combination with clinical data and conventional imaging results. Of the 31 patients, 19 (61%) showed focal FDG uptake. The remaining 12 study participants showed a diffuse FDG uptake pattern. After volumetric approximation, the affected kidneys were found to be significantly enlarged. Patients who showed a focal uptake pattern had a higher frequency of abscess formation requiring drainage. ACP patients showing diffuse tracer uptake patterns had a more benign clinical course. Seven patients had suspected extrarenal coinfections, and FDG PET/CT successfully confirmed the clinical suspicion in five cases. FDG PET/CT was as sensitive as CT in identifying the six patients (19%) who developed abscesses. Notably, FDG PET/CT findings caused a modification to the initial antibiotic regimen in nine patients (29%). FDG PET/CT may be clinically useful in the assessment of patients with ACP who have a progressive disease course.

Teleretinal screening for diabetic retinopathy in six Los Angeles urban safety-net clinics: final study results.

PubMed

Ogunyemi, Omolola; George, Sheba; Patty, Lauren; Teklehaimanot, Senait; Baker, Richard

2013-01-01

In a previous paper, we presented initial findings from a study on the feasibility and challenges of implementing teleretinal screening for diabetic retinopathy in an urban safety net setting facing eyecare specialist shortages. This paper presents some final results from that study, which involved six South Los Angeles safety net clinics. A total of 2,732 unique patients were screened for diabetic retinopathy by three ophthalmologist readers, with 1035 receiving a recommendation for referral to specialty care. Referrals included 48 for proliferative diabetic retinopathy, 115 for severe non-proliferative diabetic retinopathy (NPDR), 247 for moderate NPDR, 246 for mild NPDR, 97 for clinically significant macular edema, and 282 for a non-diabetic condition, such as glaucoma. Image quality was also assessed, with ophthalmologist readers grading 4% to 13% of retinal images taken at the different clinics as being inadequate for any diagnostic interpretation.

Treatment outcomes of a Numeric Rating Scale (NRS)-guided pharmacological pain management strategy in symptomatic knee and hip osteoarthritis in daily clinical practice.

PubMed

Snijders, Gijs F; van den Ende, Cornelia H M; van den Bemt, Bart J F; van Riel, Piet L C M; van den Hoogen, Frank H J; den Broeder, Alfons A

2012-01-01

To describe the results of a Numeric Rating Scale (NRS)-guided pharmacological pain management strategy in symptomatic knee and hip osteoarthritis (OA) in daily clinical practice. In this observational cohort study, standardised conservative treatment was offered to patients with symptomatic knee and/or hip OA referred to secondary care. Pain management was guided by a NRS for pain, aiming for NRS ≤4. The first step in pharmacological treatment was paracetamol (acetaminophen) in case of no recent use in adequate dose. In case of treatment failure, patients switched to a non-steroidal anti-inflammatory drug (NSAID) and eventually to a second NSAID, each after a 4-week trial period. Predictors for response to treatment were identified. Moreover, reasons for protocol violations were collected. Three-hundred and forty-seven patients were included. The proportion of patients that reached a response after paracetamol, first and second NSAID was 25% (59/234), 16% (31/190) and 11% (10/87), respectively. Non-adherence to protocol occurred in 46% of cases when switch of analgesic was advised, mainly due to unwillingness of patients to change the analgesic. Identified predictors for response to analgesics included higher age, lower patient global assessment, less stiffness and more radiographic severity. Adequate use of paracetamol and switching to a NSAID after failing paracetamol resulted in moderate treatment response percentages, whereas the result of a second NSAID was disappointing in patients with advanced knee and hip OA. Predictors for response included patient and disease related factors. A substantial part of patients with NRS >4 were unwilling to change their analgesics.

The SIGN nail for knee fusion: technique and clinical results

PubMed Central

Anderson, Duane Ray; Anderson, Lucas Aaron; Haller, Justin M.; Feyissa, Abebe Chala

2016-01-01

Purpose: Evaluate the efficacy of using the SIGN nail for instrumented knee fusion. Methods: Six consecutive patients (seven knees, three males) with an average age of 30.5 years (range, 18–50 years) underwent a knee arthrodesis with SIGN nail (mean follow-up 10.7 months; range, 8–14 months). Diagnoses included tuberculosis (two knees), congenital knee dislocation in two knees (one patient), bacterial septic arthritis (one knee), malunited spontaneous fusion (one knee), and severe gout with 90° flexion contracture (one knee). The nail was inserted through an anteromedial entry point on the femur and full weightbearing was permitted immediately. Results: All knees had clinical and radiographic evidence of fusion at final follow-up and none required further surgery. Four of six patients ambulated without assistive device, and all patients reported improved overall physical function. There were no post-operative complications. Conclusion: The technique described utilizing the SIGN nail is both safe and effective for knee arthrodesis and useful for austere environments with limited fluoroscopy and implant options. PMID:27163095

Practice-Based Research Network Infrastructure Design for Institutional Review Board Risk Assessment and Generalizability of Clinical Results.

PubMed

Curro, Frederick; Thompson, Van P; Naftolin, Frederick; Grill, Ashley; Vena, Don; Terracio, Louis; Hashimoto, Mariko; Buchholz, Matthew; McKinstry, Andrea; Cannon, Diane; Alfano, Vincent; Gooden, Thalia; Vernillo, Anthony; Czeisler, Elan

2013-01-01

Data from clinical studies generated by Practice Based Research Networks should be generalizable to the profession. For nationally representative data a broad recruitment of practitioners may pose added risks to IRB's. Infrastructure must assure data integrity while minimizing risk to assure that the clinical results are generalizable. The PEARL Network is an interdisciplinary dental/medical PBRN conducting a broad range of clinical studies. The infrastructure is designed to support the principles of Good Clinical Practice (GCP) and create a data audit trail to ensure data integrity for generalizability. As the PBRN concept becomes of greater interest, membership may expand beyond the local community, and the issue of geography versus risk management becomes of concern to the IRB. The PEARL Network describes how it resolves many of the issues related to recruiting on a National basis while maintaining study compliance to ensure patient safety and minimize risk to the IRB.

Competitive Employment for Youth with Autism Spectrum Disorders: Early Results from a Randomized Clinical Trial

ERIC Educational Resources Information Center

Wehman, Paul H.; Schall, Carol M.; McDonough, Jennifer; Kregel, John; Brooke, Valerie; Molinelli, Alissa; Ham, Whitney; Graham, Carolyn W.; Riehle, J. Erin; Collins, Holly T.; Thiss, Weston

2014-01-01

For most youth with autism spectrum disorders (ASD), employment upon graduation from high school or college is elusive. Employment rates are reported in many studies to be very low despite many years of intensive special education services. This paper presented the preliminary results of a randomized clinical trial of Project SEARCH plus ASD…

Spontaneous Regulation of Emotions in Preschool Children Who Stutter: Preliminary Findings

PubMed Central

Johnson, Kia N.; Walden, Tedra A.; Conture, Edward G.; Karrass, Jan

2013-01-01

Purpose Emotional regulation of preschool children who do (CWS) and do not stutter (CWNS) was assessed using a disappointing gift (DG) procedure (Cole, 1986; Saarni, 1984, 1992). Method Participants consisted of 16 3- to 5-year-old CWS and CWNS (11 boys and 5 girls in each talker group). After assessing each child’s knowledge of display rules about socially-appropriate expression of emotions, children participated in a DG procedure and received a desirable gift preceding a free-play task and a disappointing gift preceding a second free-play task. Dependent variables consisted of participants’ positive and negative expressive nonverbal behaviors exhibited during receipt of a desirable gift and disappointing gift, as well as conversational speech disfluencies exhibited following receipt of each gift. Results Findings indicated that CWS and CWNS exhibited no significant differences in amount of positive emotional expressions after receiving the desired gift; however, CWS, when compared to CWNS, exhibited more negative emotional expressions after receiving the undesirable gift. Furthermore, CWS were more disfluent after receiving the desired gift when compared to receiving the disappointing gift. Ancillary findings also indicated that CWS and CWNS had equivalent knowledge of display rules. Conclusion Findings suggest that efforts to concurrently regulate emotional behaviors and (non)stutterings may be problematic for preschool-age CWS. PMID:20643793

Making Sense of a Negative Clinical Trial Result: A Bayesian Analysis of a Clinical Trial of Lorazepam and Diazepam for Pediatric Status Epilepticus.

PubMed

Chamberlain, Daniel B; Chamberlain, James M

2017-01-01

We demonstrate the application of a Bayesian approach to a recent negative clinical trial result. A Bayesian analysis of such a trial can provide a more useful interpretation of results and can incorporate previous evidence. This was a secondary analysis of the efficacy and safety results of the Pediatric Seizure Study, a randomized clinical trial of lorazepam versus diazepam for pediatric status epilepticus. We included the published results from the only prospective pediatric study of status in a Bayesian hierarchic model, and we performed sensitivity analyses on the amount of pooling between studies. We evaluated 3 summary analyses for the results: superiority, noninferiority (margin <-10%), and practical equivalence (within ±10%). Consistent with the original study's classic analysis of study results, we did not demonstrate superiority of lorazepam over diazepam. There is a 95% probability that the true efficacy of lorazepam is in the range of 66% to 80%. For both the efficacy and safety outcomes, there was greater than 95% probability that lorazepam is noninferior to diazepam, and there was greater than 90% probability that the 2 medications are practically equivalent. The results were largely driven by the current study because of the sample sizes of our study (n=273) and the previous pediatric study (n=61). Because Bayesian analysis estimates the probability of one or more hypotheses, such an approach can provide more useful information about the meaning of the results of a negative trial outcome. In the case of pediatric status epilepticus, it is highly likely that lorazepam is noninferior and practically equivalent to diazepam. Copyright © 2016 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

[Long term results of exclusive chemotherapy for glottic squamous cell carcinoma complete clinical responders after induction chemotherapy].

PubMed

Vachin, F; Hans, S; Atlan, D; Brasnu, D; Menard, M; Laccourreye, O

2004-06-01

To evaluate the long-term results of exclusive chemotherapy for T1-T3N0M0 glottic squamous cell carcinoma complete clinical responders after induction chemotherapy. Between 1985 and 2000, 69 patients with glottic squamous cell carcinoma complete clinical responders after induction chemotherapy were managed with exclusive chemotherapy at our department. Chemotherapy associated platinum and fluorouracil. This retrospective analysis evaluated actuarial survival, treatment morbidity, oncologic events and laryngeal preservation. Various independent factors were tested for potential correlation with survival and local recurrence. The 5-year Kaplan-Meier actuarial survival, local control, lymph node control estimate were 83,6%, 64,8%, 98,6% respectively. Chemotherapy never resulted in death. The 10-year actuarial metachronous second primary tumors estimate was 32%. The overall laryngeal preservation rate was 98,6%. Altogether our data and the review of the literature suggest that in patients achieving a complete clinical response after and induction based chemotherapy regimen, the completion of an exclusive chemotherapy regimen appears to be a valid alternative to the conventional use of radiotherapy or chemo-radiation protocols.

Diagnostic relevance of high field MRI in clinical neuroradiology: the advantages and challenges of driving a sports car.

PubMed

Wattjes, Mike P; Barkhof, Frederik

2012-11-01

High field MRI operating at 3 T is increasingly being used in the field of neuroradiology on the grounds that higher magnetic field strength should theoretically lead to a higher diagnostic accuracy in the diagnosis of several disease entities. This Editorial discusses the exhaustive review by Wardlaw and colleagues of research comparing 3 T MRI with 1.5 T MRI in the field of neuroradiology. Interestingly, the authors found no convincing evidence of improved image quality, diagnostic accuracy, or reduced total examination times using 3 T MRI instead of 1.5 T MRI. These findings are highly relevant since a new generation of high field MRI systems operating at 7 T has recently been introduced. • Higher magnetic field strengths do not necessarily lead to a better diagnostic accuracy. • Disadvantages of high field MR systems have to be considered in clinical practice. • Higher field strengths are needed for functional imaging, spectroscopy, etc. • Disappointingly there are few direct comparisons of 1.5 and 3 T MRI. • Whether the next high field MR generation (7 T) will improve diagnostic accuracy has to be investigated.

[Level of Development of Clinical Ethics Consultation in Psychiatry - Results of a Survey Among Psychiatric Acute Clinics and Forensic Psychiatric Hospitals].

PubMed

Gather, Jakov; Kaufmann, Sarah; Otte, Ina; Juckel, Georg; Schildmann, Jan; Vollmann, Jochen

2018-04-17

The aim of this article is to assess the level of development of clinical ethics consultation in psychiatric institutions in North Rhine-Westphalia. Survey among medical directors, directors of nursing and administrative directors of all psychiatric acute clinics and forensic psychiatric hospitals in North Rhine-Westphalia. 113 persons working in psychiatric acute clinics responded (reponse rate: 48 %) and 13 persons working in forensic psychiatric hospitals (response rate 54 %). We received at least one response from 89 % of all psychiatric acute clinics and from 100 % of all forensic psychiatric hospitals. 90 % of the responding psychiatric acute clinics and 29 % of the responding forensic psychiatric hospitals have already implemented clinical ethics consultation. Clinical ethics consultation is more widespread in psychiatric institutions than was hitherto assumed. Future medical ethics research should therefore give greater attention to the methodology and the quality of clinical ethics consultation in psychiatric practice. © Georg Thieme Verlag KG Stuttgart · New York.

The Pitfalls of Companion Diagnostics: Evaluation of Discordant EGFR Mutation Results from a Clinical Laboratory and a Central Laboratory.

PubMed

Turner, Scott A; Peterson, Jason D; Pettus, Jason R; de Abreu, Francine B; Amos, Christopher I; Dragnev, Konstantin H; Tsongalis, Gregory J

2016-05-01

Accurate identification of somatic mutations in formalin-fixed, paraffin-embedded tumor tissue is required for enrollment into clinical trials for many novel targeted therapeutics, including trials requiring EGFR mutation status in non-small-cell lung carcinomas. Central clinical trial laboratories contracted to perform this analysis typically rely on US Food and Drug Administration-approved targeted assays to identify these mutations. We present two cases in which central laboratories inaccurately reported EGFR mutation status because of improper identification and isolation of tumor material and failure to accurately report assay limitations, resulting in enrollment denial. Such cases highlight the need for increased awareness by clinical trials of the limitation of these US Food and Drug Administration-approved assays and the necessity for a mechanism to reevaluate discordant results by alternative laboratory-developed procedures, including clinical next-generation sequencing. Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

A Novel Technique for Clinical Assessment of Laryngeal Nerve Conduction: Normal and Abnormal Results

PubMed Central

Sulica, Lucian; Carey, Bridget; Branski, Ryan C.

2014-01-01

Objectives/Hypothesis To describe a novel conduction study of the laryngeal nerves, including normal values and abnormal findings. Study Design Prospective nonrandomized. Methods Seventeen healthy adult volunteers, as well as three patients with clinically identified laryngeal neuropathy, underwent low-level brief electrical stimulation of the laryngeal mucosa by means of a wire inserted via a transnasal flexible laryngoscope. Bilateral hookwire electrodes recorded the result in the laryngeal adductor muscles. Results This study yields an early response ipsilateral to the side of stimulation (LR1), which is uniform and consistent (right 5 13.2 6 0.80 msec; left 5 15.2 6 1.20 msec), and late bilateral responses (ipsilateral LR2 [LR2i] and contralateral LR2 [LR2c]), which exhibit greater variation in latency and morphology (right LR2i 5 50.5 6 3.38 msec; left LR2i 5 52.2 msec; right LR2c 5 50.7 6 4.26; left LR2c 5 50.6 6 4.07). Findings in abnormal patients differ significantly from normal, consistent with the distribution of neuropathy. Conclusions We describe a novel, clinically applicable conduction study of laryngeal nerves. Normative electrodiagnostic values and variations of the reflex responses of the laryngeal adductor muscles in response to irritative stimulation of the laryngeal mucosa (Laryngeal Closure Reflex) are proposed. By enabling the determination of electrophysiological parameters of the superior laryngeal and recurrent laryngeal branches of cranial nerve X (CN X), this procedure, which is used as an adjunct to laryngeal electromyography, may provide earlier and more accurate information regarding the extent and grade of nerve injury. Because injury grade relates directly to prognosis, the information derived from this test may have clinical relevance in determining optimal treatment. Level of Evidence 4. PMID:23835889

Neutropenia as an Adverse Event following Vaccination: Results from Randomized Clinical Trials in Healthy Adults and Systematic Review

PubMed Central

Muturi-Kioi, Vincent; Lewis, David; Launay, Odile; Leroux-Roels, Geert; Anemona, Alessandra; Loulergue, Pierre; Bodinham, Caroline L.; Aerssens, Annelies; Groth, Nicola; Saul, Allan; Podda, Audino

2016-01-01

Background In the context of early vaccine trials aimed at evaluating the safety profile of novel vaccines, abnormal haematological values, such as neutropenia, are often reported. It is therefore important to evaluate how these trials should be planned not to miss potentially important safety signals, but also to understand the implications and the clinical relevance. Methodology We report and discuss the results from five clinical trials (two with a new Shigella vaccine in the early stage of clinical development and three with licensed vaccines) where the absolute neutrophil counts (ANC) were evaluated before and after vaccination. Additionally, we have performed a systematic review of the literature on cases of neutropenia reported during vaccine trials to discuss our results in a more general context. Principal Findings Both in our clinical trials and in the literature review, several cases of neutropenia have been reported, in the first two weeks after vaccination. However, neutropenia was generally transient and had a benign clinical outcome, after vaccination with either multiple novel candidates or well-known licensed vaccines. Additionally, the vaccine recipients with neutropenia frequently had lower baseline ANC than non-neutropenic vaccinees. In many instances neutropenia occurred in subjects of African descent, known to have lower ANC compared to western populations. Conclusions It is important to include ANC and other haematological tests in early vaccine trials to identify potential safety signals. Post-vaccination neutropenia is not uncommon, generally transient and clinically benign, but many vaccine trials do not have a sampling schedule that allows its detection. Given ethnic variability in the level of circulating neutrophils, normal ranges taking into account ethnicity should be used for determination of trial inclusion/exclusion criteria and classification of neutropenia related adverse events. Trial registration ClinicalTrials.gov NCT02017899

Teleretinal Screening for Diabetic Retinopathy in Six Los Angeles Urban Safety-Net Clinics: Final Study Results

PubMed Central

Ogunyemi, Omolola; George, Sheba; Patty, Lauren; Teklehaimanot, Senait; Baker, Richard

2013-01-01

In a previous paper, we presented initial findings from a study on the feasibility and challenges of implementing teleretinal screening for diabetic retinopathy in an urban safety net setting facing eyecare specialist shortages. This paper presents some final results from that study, which involved six South Los Angeles safety net clinics. A total of 2,732 unique patients were screened for diabetic retinopathy by three ophthalmologist readers, with 1035 receiving a recommendation for referral to specialty care. Referrals included 48 for proliferative diabetic retinopathy, 115 for severe non-proliferative diabetic retinopathy (NPDR), 247 for moderate NPDR, 246 for mild NPDR, 97 for clinically significant macular edema, and 282 for a non-diabetic condition, such as glaucoma. Image quality was also assessed, with ophthalmologist readers grading 4% to 13% of retinal images taken at the different clinics as being inadequate for any diagnostic interpretation. PMID:24551394

The role of ovarian reserve markers in prediction of clinical pregnancy.

PubMed

Zebitay, Ali G; Cetin, Orkun; Verit, Fatma F; Keskin, Seda; Sakar, M Nafi; Karahuseyinoglu, Sercin; Ilhan, Gulsah; Sahmay, Sezai

2017-05-01

To evaluate the role of ovarian reserve markers in the prediction of clinical pregnancy and embryo transfer accomplishment among poor responder IVF applicants. 304 female poor responder IVF applicants were included in this prospective cohort study conducted at the IVF-unit. Antral follicle count, FSH, LH, E2, AMH and IVF outcomes were compared in pregnant and non-pregnant groups as well as in ET vs. non-ET groups. The number of retrieved oocytes was significantly correlated positively with AMH and AFC, and negatively with FSH and age. Quartiles of FSH and AFC were similar to the rate of pregnancy. Quartiles of AMH (<25%/25-75% and <25%/>75%) were statistically significant. Mean serum levels for AMH were significantly lower in the non-ET group. Our findings seem to indicate that day 3 AMH values can predict ET accomplishment with a sensitivity of 96% and a specificity of 35%. Quartiles of AMH <25% (< 0.21 ng/mL) can predict the IVF results among poor responder IVF applicants. Impact statement Various cut-off values have been determined for day 3 serum AMH values. These values help to determine the groups that are expected to give normal, high or low response to stimulation and decide the treatment options. In contrast to other groups of patients, poor responders cannot reach the embryo transfer stage for several reasons. These are; absence of a mature oocyte after oocyte pick-up, fertilisation failure without male factor or poor embryo quality. In the present study; a cut-off value of 0.33 ng/mL for the prediction of ET accomplishment in poor responder patients was determined with a sensitivity of 96%. Additionally, clinical pregnancy could not be achieved under the value of 0.21 ng/mL day 3 AMH values. It is important to clarify the embryo transfer success of poor responder patients prior to expected treatment success. Pre-treatment counselling for these patients would lessen the disappointment that may develop after treatment. The cost-effectiveness of

Clinical trial transparency: an assessment of the disclosure of results of company-sponsored trials associated with new medicines approved recently in Europe.

PubMed

Rawal, Bina; Deane, Bryan R

2014-03-01

Previous studies have raised concerns around the transparency and disclosure rates of clinical trial results on clinical trial registries and in the scientific literature. The objective of this study was to assess the timely disclosure in the public domain of results of company-sponsored clinical trials related to all new medicines approved by the European Medicines Agency (EMA) over a recent 3 year period. The study surveyed various publicly available information sources for both clinical trial registration and disclosure of results (including clinical trial registries, the International Federation of Pharmaceutical Manufacturers and Associations [IFPMA] Clinical Trials Portal, EMA European Public Assessment Reports and PubMed), searched from 27 December 2012 to 31 January 2013. The study covered all 53 new medicines (except vaccines and fixed-dose combinations) approved for marketing by 34 pharmaceutical companies by the EMA in 2009, 2010 and 2011. It included all completed company-sponsored clinical trials conducted in patients and recorded on a clinical trial registry and/or included in an EPAR. OUTCOME MEASURE AND RESULTS: The main outcome measure was the proportion of trials for which results had been disclosed on a registry or in the scientific literature either within 12 months of the later of either first regulatory approval or trial completion, or by 31 January 2013 (end of survey). Of the completed clinical trials associated with all 53 new medicines approved by the EMA between 2009 and 2011, 77% had results disclosed within 12 months. By 31 January 2013, this had increased to 89%. Rates of results disclosure within 12 months were 71%, 81% and 86% for new medicines approved in 2009, 2010 and 2011 respectively. Disclosure increased to 86%, 93% and 91% respectively by 31 January 2013. Although this was a purely quantitative study which did not aim to assess the content of disclosure against any specific requirements, limitations relating to a number of

Multi-Family Group Intervention for OEF/OIF Traumatic Brain Injury Survivors and their Families

DTIC Science & Technology

2011-10-01

protocol. For example, due to a high degree of marital conflict observed in two couples in the initial Bronx group, the second group incorporated...veterans’ family members. Insufficient information can exacerbate marital or family conflict and lead to psychological distress and social isolation...disappointment, frustration, family conflict , and child distress (Collins & Kennedy, KRISTY STRAITS-TRÖSTER received her PhD in clinical psychology from the

[Clinical parameters of patients with neovascular age-related macular degeneration : Longterm treatment results of an outpatient clinic].

PubMed

Wassel, S; Tsompanidi, E; Tahmaz, E; Hörster, B; Hoerster, R

2018-05-22

The clinical outcome of neovascular age-related macular degeneration (nAMD) depends on constant follow-up and consistent treatment. Data about the long-term course of intensive anti-vascular endothelial growth factor (VEGF) therapy from outpatient clinics are rare. The aim of the study was to characterize a population of nAMD patients with long-term follow-up and intensive anti-VEGF therapy. In a supra-regional outpatient clinic, we retrospectively identified patients who had received at least 30 intravitreal anti-VEGF injections and were followed for at least 4 years. All patients received an optical coherence tomography(OCT)-controlled Pro-Re-Nata (PRN) therapy regimen according to German guidelines. We identified 43 patients. Visual acuity at baseline was 0.44 ± 0.24 (1.0-0.1) logMAR. At the end of the follow-up period, visual acuity was 0.63 ± 3.6 (1.3-0.1) logMAR. Patients received a mean of 36.3 ± 8.0 (30-62) injections and were followed for a mean of 6.1 ± 1.8 (4-12) years. They received 6.12 ± 1.5 (3.1-9.9) injections per year. The number of injections in treatment-year one was with 3.67 ± 1.9 (1-8) significantly lower than the mean (p < 0.0001). Despite intensive PRN therapy, visual acuity slowly decreased over time. The mean number of injections was comparable to that of prospective studies. The low number of injections in treatment-year 1 may have been due to a lack of experience with the new treatment agents. The slow decrease in visual acuity in clinical routine as opposed to clinical studies may be attributed to a delay between occurrence of disease activity and treatment.

A noncontact RF-based respiratory sensor: results of a clinical trial.

PubMed

Madsen, Spence; Baczuk, Jordan; Thorup, Kurt; Barton, Richard; Patwari, Neal; Langell, John T

2016-06-01

Respiratory rate (RR) is a critical vital signs monitored in health care setting. Current monitors suffer from sensor-contact failure, inaccurate data, and limited patient mobility. There is a critical need for an accurate and reliable and noncontact system to monitor RR. We developed a contact-free radio frequency (RF)-based system that measures movement using WiFi signal diffraction, which is converted into interpretable data using a Fourier transform. Here, we investigate the system's ability to measure fine movements associated with human respiration. Testing was conducted on subjects using visual cue, fixed-tempo instruction to breath at standard RRs. Blinded instruction-based RRs were compared to RF-acquired data to determine measurement accuracy. The RF-based technology was studied on postoperative ventilator-dependent patients. Blinded ventilator capnographic RR data were collected for each patient and compared to RF-acquired data to determine measurement accuracy. Respiratory rate data collected from 10 subjects breathing at a fixed RR (14, 16, 18, or 20) demonstrated 95.5% measurement accuracy between the patient's actual rate and that measured by our RF technology. Ten patients were enrolled into the clinical trial. Blinded ventilator capnographic RR data were compared to RF-based acquired data. The RF-based data showed 88.8% measurement accuracy with ventilator capnography. Initial clinical pilot trials with our contact-free RF-based monitoring system demonstrate a high degree of RR measurement accuracy when compared to capnographic data. Based on these results, we believe RF-based systems present a promising noninvasive, inexpensive, and accurate tool for continuous RR monitoring. Copyright © 2016 Elsevier Inc. All rights reserved.

Preconception Carrier Screening by Genome Sequencing: Results from the Clinical Laboratory.

PubMed

Punj, Sumit; Akkari, Yassmine; Huang, Jennifer; Yang, Fei; Creason, Allison; Pak, Christine; Potter, Amiee; Dorschner, Michael O; Nickerson, Deborah A; Robertson, Peggy D; Jarvik, Gail P; Amendola, Laura M; Schleit, Jennifer; Simpson, Dana Kostiner; Rope, Alan F; Reiss, Jacob; Kauffman, Tia; Gilmore, Marian J; Himes, Patricia; Wilfond, Benjamin; Goddard, Katrina A B; Richards, C Sue

2018-06-07

Advances in sequencing technologies permit the analysis of a larger selection of genes for preconception carrier screening. The study was designed as a sequential carrier screen using genome sequencing to analyze 728 gene-disorder pairs for carrier and medically actionable conditions in 131 women and their partners (n = 71) who were planning a pregnancy. We report here on the clinical laboratory results from this expanded carrier screening program. Variants were filtered and classified using the latest American College of Medical Genetics and Genomics (ACMG) guideline; only pathogenic and likely pathogenic variants were confirmed by orthologous methods before being reported. Novel missense variants were classified as variants of uncertain significance. We reported 304 variants in 202 participants. Twelve carrier couples (12/71 couples tested) were identified for common conditions; eight were carriers for hereditary hemochromatosis. Although both known and novel variants were reported, 48% of all reported variants were missense. For novel splice-site variants, RNA-splicing assays were performed to aid in classification. We reported ten copy-number variants and five variants in non-coding regions. One novel variant was reported in F8, associated with hemophilia A; prenatal testing showed that the male fetus harbored this variant and the neonate suffered a life-threatening hemorrhage which was anticipated and appropriately managed. Moreover, 3% of participants had variants that were medically actionable. Compared with targeted mutation screening, genome sequencing improves the sensitivity of detecting clinically significant variants. While certain novel variant interpretation remains challenging, the ACMG guidelines are useful to classify variants in a healthy population. Copyright © 2018 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Evaluation and comparison of clinical results of femoral fixation devices in arthroscopic anterior cruciate ligament reconstruction.

PubMed

Aydin, Deniz; Ozcan, Mert

2016-03-01

Several femoral fixation devices are available for hamstring tendon autograft in anterior cruciate ligament (ACL) reconstruction, but the best technique is debatable. We hypothesised that different suspensory femoral fixation techniques have no superiority over each other. The aim of this study was to evaluate and compare the clinical results of different suspensory femoral fixation devices in arthroscopic ACL reconstruction. This was a Level III, retrospective, comparative study. A total of 100 consecutive patients who underwent arthroscopic ACL reconstruction in a single institution with a mean follow-up time of 40 months (12-67 months) were divided into three groups according to femoral fixation devices as 'Endobutton' (n=34), 'Transfix' (n=35) and 'Aperfix' (n=31). The length of painful period after surgery, time to return to work and sporting activities, final range of motion, anterior drawer and Lachman tests, knee instability symptoms, International Knee Documentation Committee (IKDC) subjective knee evaluation score, Short Form 36 (SF-36) score, Lysholm knee score and Tegner point of the patients were evaluated and compared between groups. There were no significant differences between the groups. All techniques led to significant recovery in knee instability tests and symptoms. In this study, the clinical results of different suspensory femoral fixation techniques were found to be similar. We believe that different femoral fixation techniques have no effect on clinical results provided that the technique is correctly applied. The surgeon must choose a technique appropriate to his or her experience. Copyright © 2015 Elsevier B.V. All rights reserved.

Effects of different centrifugation conditions on clinical chemistry and Immunology test results

PubMed Central

2011-01-01

Background The effect of centrifugation time of heparinized blood samples on clinical chemistry and immunology results has rarely been studied. WHO guideline proposed a 15 min centrifugation time without citing any scientific publications. The centrifugation time has a considerable impact on the turn-around-time. Methods We investigated 74 parameters in samples from 44 patients on a Roche Cobas 6000 system, to see whether there was a statistical significant difference in the test results among specimens centrifuged at 2180 g for 15 min, at 2180 g for 10 min or at 1870 g for 7 min, respectively. Two tubes with different plasma separators (both Greiner Bio-One) were used for each centrifugation condition. Statistical comparisons were made by Deming fit. Results Tubes with different separators showed identical results in all parameters. Likewise, excellent correlations were found among tubes to which different centrifugation conditions were applied. Fifty percent of the slopes lay between 0.99 and 1.01. Only 3.6 percent of the statistical tests results fell outside the significance level of p < 0.05, which was less than the expected 5%. This suggests that the outliers are the result of random variation and the large number of statistical tests performed. Further, we found that our data are sufficient not to miss a biased test (beta error) with a probability of 0.10 to 0.05 in most parameters. Conclusion A centrifugation time of either 7 or 10 min provided identical test results compared to the time of 15 min as proposed by WHO under the conditions used in our study. PMID:21569233

Testing the Right Target and the Right Drug at the Right Stage

PubMed Central

Sperling, Reisa A.; Jack, Clifford R.; Aisen, Paul S.

2013-01-01

Alzheimer’s disease (AD) is the only leading cause of death for which no disease-modifying therapy is currently available. Recent disappointing trial results at the dementia stage of AD have raised multiple questions about our current approaches to the development of disease-modifying agents. Converging evidence suggests that the pathophysiological process of AD begins many years before the onset of dementia. So why do we keep testing drugs aimed at the initial stages of the disease process in patients at the end-stage of the illness? Alzheimer’s disease (AD) remains one of the most feared consequences of aging, affecting more than one out of every ten individuals over the age of 65. With more than 10,000 baby boomers turning 65 every day in the United States alone, we are truly facing an AD epidemic. Over the past decade, a string of disappointing clinical trial results have raised concerns about our current strategy for development of AD-modifying therapies. Three hypotheses can explain these recent AD trial failures: (i) We are targeting the wrong pathophysiological mechanisms; (ii) The drugs do not engage the intended targets in patients; and (iii) The drugs are hitting the right targets, but are doing so at the wrong stage of the disease. Here, we address the third supposition and suggest that specific amyloid-based therapies be directed at much earlier stages of ADperhaps even prior to the emergence of clinical symptoms. Furthermore, we argue that the field has sufficient tools to begin “secondary prevention” trials in asymptomatic individuals whoare at high risk for progression to cognitive impairment and AD dementia. PMID:22133718

Combination alpha-interferon and lamivudine therapy for alpha-interferon-resistant chronic hepatitis B infection: results of a pilot study.

PubMed

Mutimer, D; Naoumov, N; Honkoop, P; Marinos, G; Ahmed, M; de Man, R; McPhillips, P; Johnson, M; Williams, R; Elias, E; Schalm, S

1998-06-01

Alpha-interferon achieves seroconversion in about one third of naive patients. Attempts to achieve seroconversion in patients who have previously failed alpha-interferon have proved disappointing. Combination chemotherapy (alpha-interferon with a nucleoside analogue) might provide a treatment alternative for these patients. We have undertaken a phase 2 study in 20 patients who had previously failed at least one course of alpha-interferon. The study was designed to assess the safety, tolerability and efficacy of the combination. All patients were treated for 16 weeks with alpha-interferon in combination with 12 or 16 weeks of Lamivudine (3'TC). Patients were followed for 16 weeks post-treatment. Pharmacokinetic studies were performed to identify/exclude significant pharmacokinetic drug interaction. The combination was well tolerated, and side-effects of the combination were indistinguishable from the recognised side-effects of alpha-interferon. Pharmacokinetic studies performed on days 1 and 29 did not show any significant interaction. All patients achieved HBV DNA clearance during treatment, but 19 relapsed at the end of treatment. HBeAg/anti-HBe seroconversion was observed for four patients, but was sustained for a single patient (who also had sustained DNA clearance). Combination therapy with alpha-interferon and lamivudine given for 16 weeks appears safe and is well tolerated. However, for this group of patients who had previously failed interferon monotherapy, the efficacy of combination interferon/lamivudine therapy appears disappointing, and other treatment strategies should be investigated.

Clinical results of primary malignant musculoskeletal tumor treated by wide resection and recycling autograft reconstruction using liquid nitrogen.

PubMed

Paholpak, Permsak; Sirichativapee, Winai; Wisanuyotin, Taweechok; Kosuwon, Weerachai; Jeeravipoolvarn, Polasak

2015-06-01

To evaluate the clinical results of primary malignant musculoskeletal tumors treated with wide resection and recycling autograft reconstruction using liquid nitrogen. We reviewed 12 patients who had a primary malignant bone and soft tissue tumor treated by wide resection and recycling autograft reconstruction using liquid nitrogen between March 2006 and March 2013. The results were judged by recurrence, functional status and complications. Functional status was assessed according to the Musculoskeletal Tumor Society Score (MSTSS). Clinical failure was defined as need for reoperation in order to change the type of reconstruction or to amputate, and the presence of local recurrence. The most common tumor was osteosarcoma (eight cases) followed by Ewing's sarcoma (two cases). The tibia was the most frequently involved skeletal site (six cases) followed by the femur (three cases). The median follow-up period was 32 months. In 12 patients, 7 were still alive without recurrence. There were 3 clinical failures: 1 local recurrence and 2 graft complications at 28, 51 and 20 months after reconstruction, respectively. The main complication was infection (three cases). All osteotomy sites were radiographic unions, and the union time was 8.2 ± 2.7 months. The mean ± SD MSTSS score was 79% ± 11%; excellent functional results were achieved in seven patients. Recycling autograft reconstruction using liquid nitrogen had favorable clinical outcomes in terms of functional status and local recurrence. This reconstruction method, therefore, represents a reasonable alternative for limb salvage surgery. © 2014 Wiley Publishing Asia Pty Ltd.

The selective treatment of clinical mastitis based on on-farm culture results: II. Effects on lactation performance, including clinical mastitis recurrence, somatic cell count, milk production, and cow survival.

PubMed

Lago, A; Godden, S M; Bey, R; Ruegg, P L; Leslie, K

2011-09-01

The objective of this multi-state, multi-herd clinical trial was to report on the efficacy of using an on-farm culture system to guide strategic treatment decisions in cows with clinical mastitis. The study was conducted in 8 commercial dairy farms ranging in size from 144 to 1,795 cows from Minnesota, Wisconsin, and Ontario, Canada. A total of 422 cows affected with mild or moderate clinical mastitis in 449 quarters were randomly assigned to either (1) a positive-control treatment program or (2) an on-farm culture-based treatment program. Quarter cases assigned to the positive-control group received immediate on-label intramammary treatment with cephapirin sodium. Quarters assigned to the culture-based treatment program were not treated until the results of on-farm culture were determined after 18 to 24h of incubation. Quarters in the culture-based treatment program that had gram-positive growth or a mixed infection were treated according to label instruction using intramammary cephapirin sodium. Quarters assigned to the culture-based treatment program that had gram-negative or no-growth did not receive intramammary therapy. It was already reported in a companion paper that the selective treatment of clinical mastitis based on on-farm culture results decreases antibiotic use by half and tends to decrease milk withholding time without affecting short-term clinical and bacteriological outcomes. The present article reports on long-term outcomes of the aforementioned study. No statistically significant differences existed between cases assigned to the positive-control program and cases assigned to the culture-based treatment program in risk and days for recurrence of clinical mastitis in the same quarter (35% and 78 d vs. 43% and 82 d), linear somatic cell count (4.2 vs. 4.4), daily milk production (30.0 vs. 30.7 kg), and risk and days for culling or death events (28% and 160 d vs. 32% and 137 d) for the rest of the lactation after enrollment of the clinical mastitis

Does parent-child agreement vary based on presenting problems? Results from a UK clinical sample.

PubMed

Cleridou, Kalia; Patalay, Praveetha; Martin, Peter

2017-01-01

Discrepancies are often found between child and parent reports of child psychopathology, nevertheless the role of the child's presenting difficulties in relation to these is underexplored. This study investigates whether parent-child agreement on the conduct and emotional scales of the Strengths and Difficulties Questionnaire (SDQ) varied as a result of certain child characteristics, including the child's presenting problems to clinical services, age and gender. The UK-based sample consisted of 16,754 clinical records of children aged 11-17, the majority of which were female (57%) and White (76%). The dataset was provided by the Child Outcomes Research Consortium , which collects outcome measures from child services across the UK. Clinicians reported the child's presenting difficulties, and parents and children completed the SDQ. Using correlation analysis, the main findings indicated that agreement varied as a result of the child's difficulties for reports of conduct problems, and this seemed to be related to the presence or absence of externalising difficulties in the child's presentation. This was not the case for reports of emotional difficulties. In addition, agreement was higher when reporting problems not consistent with the child's presentation; for instance, agreement on conduct problems was greater for children presenting with internalising problems. Lastly, the children's age and gender did not seem to have an impact on agreement. These findings demonstrate that certain child presenting difficulties, and in particular conduct problems, may be related to informant agreement and need to be considered in clinical practice and research. Trial Registration This study was observational and as such did not require trial registration.

Endovascular Treatment of Malignant Superior Vena Cava Syndrome: Results and Predictive Factors of Clinical Efficacy

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

Fagedet, Dorothee, E-mail: DFagedet@chu-grenoble.fr; Thony, Frederic, E-mail: FThony@chu-grenoble.fr; Timsit, Jean-Francois, E-mail: JFTimsit@chu-grenoble.fr

To demonstrate the effectiveness of endovascular treatment (EVT) with self-expandable bare stents for malignant superior vena cava syndrome (SVCS) and to analyze predictive factors of EVT efficacy. Retrospective review of the 164 patients with malignant SVCS treated with EVT in our hospital from August 1992 to December 2007 and followed until February 2009. Endovascular treatment includes angioplasty before and after stent placement. We used self-expandable bare stents. We studied results of this treatment and looked for predictive factors of clinical efficacy, recurrence, and complications by statistical analysis. Endovascular treatment was clinically successful in 95% of cases, with an acceptable ratemore » of early mortality (2.4%). Thrombosis of the superior vena cava was the only independent factor for EVT failure. The use of stents over 16 mm in diameter was a predictive factor for complications (P = 0.008). Twenty-one complications (12.8%) occurred during the follow-up period. Relapse occurred in 36 patients (21.9%), with effective restenting in 75% of cases. Recurrence of SVCS was significantly increased in cases of occlusion (P = 0.01), initial associated thrombosis (P = 0.006), or use of steel stents (P = 0.004). Long-term anticoagulant therapy did not influence the risk of recurrence or complications. In malignancy, EVT with self-expandable bare stents is an effective SVCS therapy. These results prompt us to propose treatment with stents earlier in the clinical course of patients with SVCS and to avoid dilatation greater than 16 mm.« less

Thermoregulatory vs. event sweating--comparison of clinical methodologies, physiology and results.

PubMed

Biehle-Hulette, S J; Krailler, J M; Elstun, L T; Bentz, S; Benzing, K W; Spruell, R D; Hellhammer, J; Swaile, D F

2014-02-01

Although the mechanisms of sweating due to thermoregulation vs. stress are distinct, the antiperspirant industry focuses primarily on perspiration due to heat as their method of efficacy testing. To better understand the overall protection afforded by a 'Clinical Strength' over-the-counter antiperspirant product, we compare results from a standard hot-room study with results from two studies using the Trier Social Stress Test (TSST). For each study, unscented antiperspirant was applied to one axilla, leaving the other untreated for internal control. The hot-room protocol involved a 40-min warm-up period with 2-20 min sweat collections at 100 ± 2 °F (35% RH). The TSST requires naïve subjects to give an impromptu speech and conduct mental arithmetic, with collections of sweat, heart rate and other biomarkers of stress before, during and after the event. During the TSST, heart rate and salivary cortisol data indicate significant emotional stress. Wetness results show that sweat was reduced by 69.4% in the hot-room study, compared with 83.7% and 89.3% reductions in the stress studies. We have found added value in investigating antiperspirancy from several causes of sweat production to give a more encompassing picture of the protection afforded by an antiperspirant product, specifically wetness protection from heat, activity and stress-induced sweat. © 2013 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Corneal tissue water content mapping with THz imaging: preliminary clinical results (Conference Presentation)

NASA Astrophysics Data System (ADS)

Sung, Shijun; Bajwa, Neha; Deng, Sophie X.; Taylor, Zachary; Grundfest, Warren

2016-03-01

Well-regulated corneal water content is critical for ocular health and function and can be adversely affected by a number of diseases and injuries. Current clinical practice limits detection of unhealthy corneal water content levels to central corneal thickness measurements performed by ultrasound or optical coherence tomography. Trends revealing increasing or decreasing corneal thickness are fair indicators of corneal water content by individual measurements are highly inaccurate due to the poorly understood relationship between corneal thickness and natural physiologic variation. Recently the utility of THz imaging to accuarately measure corneal water content has been explored on with rabbit models. Preliminary experiments revealed that contact with dielectric windows confounded imaging data and made it nearly impossible to deconvolve thickness variations due to contact from thickness variations due to water content variation. A follow up study with a new optical design allowed the acquisition of rabbit data and the results suggest that the observed, time varying contrast was due entirely to the water dynamics of the cornea. This paper presents the first ever in vivo images of human cornea. Five volunteers with healthy cornea were recruited and their eyes were imaged three times over the course of a few minutes with our novel imaging system. Noticeable changes in corneal reflectivity were observed and attributed to the drying of the tear film. The results suggest that clinically compatible, non-contact corneal imaging is feasible and indicate that signal acquired from non-contact imaging of the cornea is a complicated coupling of stromal water content and tear film.

75 FR 5081 - Agency Information Collection Activities: Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-01

... virtual collaborative met with disappointing results. Another barrier to adoption of the CCM in settings... realities. The result was Implementing Integrating Chronic Care and Business Strategies in the Safety Net. A...

MRI predictors of clinical success in MR-guided focused ultrasound (MRgFUS) treatments of uterine fibroids: results from a single centre.

PubMed

Mindjuk, Irene; Trumm, Christoph G; Herzog, Peter; Stahl, Robert; Matzko, Matthias

2015-05-01

To assess the technical and clinical results of MRgFUS treatment and factors affecting clinical treatment success. A total of 252 women (mean age, 42.1 ± 6.9 years) with uterine fibroids underwent MRgFUS. All patients underwent MRI before treatment. Results were evaluated with respect to post-treatment nonperfused volume (NPV), symptom severity score (SSS), reintervention rate, pregnancy and safety data. NPV ratio was significantly higher in fibroids characterized by low signal intensity in contrast-enhanced T1-weighted fat saturated MR images and in fibroids distant from the spine (>3 cm). NPV ratio was lower in fibroids with septations, with subserosal component and in skin-distant fibroids (p < 0.001). NPV ratio was highly correlated with clinical success: NPV of more than 80 % resulted in clinical success in more than 80 % of patients. Reintervention rate was 12.7 % (mean follow-up time, 19.4 ± 8 months; range, 3-38). Expulsion of fibroids (21 %) was significantly correlated with a high clinical success rate. No severe adverse events were reported. Adequate patient selection and correct treatment techniques, based on the learning curve of this technology, combined with technical advances of the system, lead to higher clinical success rates with low complications rate, comparable to other uterine-sparing treatment options. • MRgFUS appears to be a valid alternative to other uterus-preserving therapies • Patient selection is a significant factor in achieving high NPV ratios • MRI screening parameters correlate with the amount of fibroid ablation in MRgFUS • NPV results of more than 80 % correlate with higher clinical success rates.

Pharmacogenetics and personalised medicine: maintain a critical approach.

PubMed

2013-06-01

The purpose of pharmacogenetics is to offer"personalised" treatment, in which a drug is only prescribed to patients in whom it is very likely to be effective, or to withhold a drug from patients at increased risk of adverse effects. Pharmacogenetics requires the use of genetic tests which, as with any other diagnostic test, must be evaluated for their discriminatory power (sensitivity, specificity, etc.). These evaluations are sometimes biased. Pharmacogenetics has been heralded as a means of tailoring cancer therapy. However large clinical trials with demanding clinical endpoints are often disappointing, despite initially encouraging results. Pharmacogenetic information is included in many summaries of product characteristics for non-cancer drugs, mainly in order to reduce the frequency of certain serious adverse effects. In summary, pharmacogenetics theoretically represents a step forward but must be evaluated in rigorous clinical trials, as is the case with all other "therapeutic tools".

Patient, physician and presentational influences on clinical decision making for breast cancer: results from a factorial experiment.

PubMed

McKinlay, J B; Burns, R B; Durante, R; Feldman, H A; Freund, K M; Harrow, B S; Irish, J T; Kasten, L E; Moskowitz, M A

1997-02-01

This study examines the influence of six patient characteristics (age, race, socioeconomic status, comorbidities, mobility and presentational style) and two physician characteristics (medical specialty and years of clinical experience) on physicians' clinical decision making behaviour in the evaluation treatment of an unknown and known breast cancer. Physicians' variability and certainty associated with diagnostic and treatment behaviour were also examined. Separate analyses explored the influence of these non-medical factors on physicians' cognitive processes. Using a fractional factorial design, 128 practising physicians were shown two videotaped scenarios and asked about possible diagnoses and medical recommendations. Results showed that physicians displayed considerable variability in response to several patient-based factors. Physician characteristics also emerged as important predictors of clinical behaviour, thus confirming the complexity of the medical decision-making process.

Clinical and electrophysiologic attributes as predictors of results of autonomic function tests

NASA Technical Reports Server (NTRS)

Wu, C. L.; Denq, J. C.; Harper, C. M.; O'Brien, P. C.; Low, P. A.

1998-01-01

Autonomic dysfunction is a feature of some neuropathies and not others. It has been suggested that some clinical and electrophysiologic attributes are predictable of autonomic impairment detected using laboratory testing; however, dear guidelines are unavailable. We evaluated 138 relatively unselected patients with peripheral neuropathy who underwent neurologic evaluation, electromyography (EMG), nerve conduction studies, and autonomic function tests to determine which variables were predictive of laboratory findings of autonomic failure. The variables evaluated were 1) clinical somatic neuropathic findings, 2) clinical autonomic symptoms, and 3) electrophysiologic findings. Autonomic symptoms were strongly predictive (Rs = 0.40, p < 0.001) of autonomic failure. Among the non-autonomic indices, absent ankle reflexes were mildly predictive (Rs = 0.19, p = 0.022) of autonomic impairment, but all others were not (duration, clinical pattern, severity, weakness, sensory loss). Electrophysiologic changes of an axonal neuropathy predicted autonomic impairment while demyelinating neuropathy did not. We conclude that autonomic studies will most likely be abnormal in patients who have symptoms of autonomic involvement and those who have an axonal neuropathy.

Exogenous Ochronosis

PubMed Central

Bhattar, Prachi A; Zawar, Vijay P; Godse, Kiran V; Patil, Sharmila P; Nadkarni, Nitin J; Gautam, Manjyot M

2015-01-01

Exogenous ochronosis (EO) is a cutaneous disorder characterized by blue-black pigmentation resulting as a complication of long-term application of skin-lightening creams containing hydroquinone but may also occur due to topical contact with phenol or resorcinol in dark-skinned individuals. It can also occur following the use of systemic antimalarials such as quinine. EO is clinically and histologically similar to its endogenous counterpart viz., alkaptonuria, which, however, exhibits systemic effects and is an inherited disorder. Dermoscopy and in vivo skin reflectance confocal microscopy are noninvasive in vivo diagnostic tools. It is very difficult to treat EO, a cosmetically disfiguring and troubling disorder with disappointing treatment options. PMID:26677264

Effects of different centrifugation conditions on clinical chemistry and Immunology test results.

PubMed

Minder, Elisabeth I; Schibli, Adrian; Mahrer, Dagmar; Nesic, Predrag; Plüer, Kathrin

2011-05-10

The effect of centrifugation time of heparinized blood samples on clinical chemistry and immunology results has rarely been studied. WHO guideline proposed a 15 min centrifugation time without citing any scientific publications. The centrifugation time has a considerable impact on the turn-around-time. We investigated 74 parameters in samples from 44 patients on a Roche Cobas 6000 system, to see whether there was a statistical significant difference in the test results among specimens centrifuged at 2180 g for 15 min, at 2180 g for 10 min or at 1870 g for 7 min, respectively. Two tubes with different plasma separators (both Greiner Bio-One) were used for each centrifugation condition. Statistical comparisons were made by Deming fit. Tubes with different separators showed identical results in all parameters. Likewise, excellent correlations were found among tubes to which different centrifugation conditions were applied. Fifty percent of the slopes lay between 0.99 and 1.01. Only 3.6 percent of the statistical tests results fell outside the significance level of p < 0.05, which was less than the expected 5%. This suggests that the outliers are the result of random variation and the large number of statistical tests performed. Further, we found that our data are sufficient not to miss a biased test (beta error) with a probability of 0.10 to 0.05 in most parameters. A centrifugation time of either 7 or 10 min provided identical test results compared to the time of 15 min as proposed by WHO under the conditions used in our study.

Pessimistic mood in decompensated narcissistic patient.

PubMed

Yang, Ping-Suen; Huang, Tiao-Lai

2004-04-01

We report the negative emotional state as pessimistic mood of a case with narcissistic personality disorder during the period of narcissistic decompensation. In addition, we identified the clinical differences between pessimistic mood and depressive disorder. An 28-year-old unmarried woman experienced herself, her life and the external object as futile and disappointing after repeated failure to satisfy her grandiose fantasies about the search for ideal love. The patient then gave up her formerly gratifying activities, and fell into a prolonged state of negative emotions and passivity dominated by pessimistic mood characterized by an overwhelming sense of futility. The patient did not respond to medical treatment with antidepressants firstly. However after a 2-year course of intensive psychotherapy, the patient was able to restore her zest to find a new boyfriend with a more rational and realistic attitude. Clinically, decompensated narcissistic patients do not exhibit the typical attitude of worthlessness or guilty feelings, and are devoid of certain specific depressive emotions (e.g., sadness, sorrow, etc.). In contrast, decompensated narcissistic patients with pessimistic mood exhibit a dominant sense of futility and other negative emotions presented as outrage and disappointment. The purpose of this case report was to emphasize the importance to recognize clinical features of pessimistic mood for the differential diagnosis and management of the decompensated narcissistic patient.

Bibliography of clinical research in malaysia: methods and brief results.

PubMed

Teng, C L; Zuhanariah, M N; Ng, C S; Goh, C C

2014-08-01

This article describes the methodology of this bibliography. A search was conducted on the following: (1) bibliographic databases (PubMed, Scopus, and other databases) using search terms that maximize the retrieval of Malaysian publications; (2) Individual journal search of Malaysian healthrelated journals; (3) A targeted search of Google and Google Scholar; (4) Searching of Malaysian institutional repositories; (5) Searching of Ministry of Health and Clinical Research Centre website. The publication years were limited to 2000- 2013. The citations were imported or manually entered into bibliographic software Refworks. After removing duplicates, and correcting data entry errors, PubMed's Medical Subject Headings (MeSH terms) were added. Clinical research is coded using the definition "patient-oriented-research or research conducted with human subjects (or on material of human origin) for which the investigator directly interacts with the human subjects at some point during the study." A bibliography of citations [n=2056] that fit the criteria of clinical research in Malaysia in selected topics within five domains was generated: Cancers [589], Cardiovascular diseases [432], Infections [795], Injuries [142], and Mental Health [582]. This is done by retrieving citations with the appropriate MESH terms, as follow: For cancers (Breast Neoplasms; Colorectal Neoplasms; Uterine Cervical Neoplasms), for cardiovascular diseases (Coronary Disease; Hypertension; Stroke), for infections (Dengue; Enterovirus Infections, HIV Infections; Malaria; Nipah Virus; Tuberculosis), for injuries (Accidents, Occupational; Accidents, Traffic; Child Abuse; Occupational Injuries), for mental health (Depression; Depressive Disorder; Depressive Disorder, Major; Drug Users; Psychotic Disorders; Suicide; Suicide, Attempted; Suicidal Ideation; Substance- Related Disorders).

Cevipabulin (TTI-237): preclinical and clinical results for a novel antimicrotubule agent.

PubMed

Ayral-Kaloustian, S; Zhang, N; Beyer, C

2009-09-01

Antimitotic agents are among the most effective drugs for the treatment of solid tumors and metastatic cancer. These drugs promote cell death by interfering with the crucial structural and regulatory function of microtubules in cells. Most of the agents of clinical relevance are natural products or semisynthetic derivatives thereof, and they fall into two major classes: microtubule stabilizers such as the taxanes, which enhance tubulin polymerization, and microtubule destabilizers such as the Vinca alkaloids, which lead to the depolymerization of existing microtubules. While these drugs are effective in inhibiting the progression of certain types of tumors, their utility is limited in part by incomplete tumor responses and/or significant side effects. In addition, inherent resistance is encountered in many tumor types, or acquired resistance may occur as a result of multiple cycles of therapy. Cevipabulin (TTI-237) is a novel, small synthetic molecule with an unusual biological mode of action. It appears to bind at the vinca site, but exhibits some properties similar to those of taxane-site ligands, such as enhancing tubulin polymerization. The compound works against a variety of tumors, including those resistant to paclitaxel and vincristine. Furthermore, cevipabulin is stable and water-soluble, and can be administered i.v. or p.o. in saline. It can be synthesized in bulk quantities efficiently. Based on these properties, cevipabulin was selected for clinical development. Copyright 2009 Prous Science, S.A.U. or its licensors. All rights reserved.

Dissemination Strategies to Improve Implementation of the PHS Smoking Cessation Guideline in MCH Public Health Clinics: Experimental Evaluation Results and Contextual Factors

ERIC Educational Resources Information Center

Manfredi, Clara; Cho, Young Ik; Warnecke, Richard; Saunders, Stephen; Sullivan, Myrtis

2011-01-01

We report results from an experimental study that tested the effectiveness of dissemination interventions to improve implementation of smoking cessation guidelines in maternal and child public health clinics. We additionally examine individual clinic results for contextual explanations not apparent from the experimental findings alone. Twelve…

Arthroscopic treatment of acute acromioclavicular dislocations using a double button device: Clinical and MRI results.

PubMed

Loriaut, P; Casabianca, L; Alkhaili, J; Dallaudière, B; Desportes, E; Rousseau, R; Massin, P; Boyer, P

2015-12-01

Arthroscopic treatment of acute grade 3 and 4 acromioclavicular dislocation is controversial, due to the risk of recurrence and of postoperative reduction defect. The purpose of the present study was to investigate whether the healing of the acromioclavicular (AC) and coracoclavicular (CC) ligaments and the accurate 3D positioning parameters of the AC joint using MRI were correlated with satisfactory functional outcome. Thirty-nine patients were enrolled from 2009 to 2011 and managed arthroscopically by CC lacing using a double-button device. Clinical assessment included the Shoulder and Hand (QuickDash) score, Constant-Murley score and visual analog scale (VAS) for residual pain. Time and rate to return to work and return to sport were assessed according to type of sport and work. Postoperative complications were recorded. Radiological examination consisted of anteroposterior clavicle and lateral axillary radiographs. AC ligament healing and 3D joint congruency were assessed on MRI and correlated to the clinical results. Mean patient age was 35.7 years (range, 20-55). Mean follow-up was 42.3±10.6 months (range, 24-60). At final follow-up, mean QuickDash score, Constant score and VAS were respectively 1.7±4 (range, 0-11), 94.7±7.3 (range, 82-100) and 0.5±1.4 (range, 0-2). Thirty-five (90%) patients were able to resume work, including heavy manual labor, and sport. Radiology found accurate 3D joint congruency in 34 patients (87%) and CC and AC ligament healing in 36 (93%). Complications included reduction loss at 6 weeks in 3 patients, requiring surgical stabilization. Satisfactory functional results were associated with accurate AC joint congruency in the coronal and axial planes (P<0.05) and good AC and CC ligament healing (P<0.04). An initial 25% reduction defect in the coronal plane was not associated with poor functional results (P=0.07). Arthroscopic treatment by CC lacing satisfactorily restored ligament and joint anatomy in the present series. These

Single-row vs. double-row arthroscopic rotator cuff repair: clinical and 3 Tesla MR arthrography results

PubMed Central

2013-01-01

Background Arthroscopic rotator cuff repair has become popular in the last few years because it avoids large skin incisions and deltoid detachment and dysfunction. Earlier arthroscopic single-row (SR) repair methods achieved only partial restoration of the original footprint of the tendons of the rotator cuff, while double-row (DR) repair methods presented many biomechanical advantages and higher rates of tendon-to-bone healing. However, DR repair failed to demonstrate better clinical results than SR repair in clinical trials. MR imaging at 3 Tesla, especially with intra-articular contrast medium (MRA), showed a better diagnostic performance than 1.5 Tesla in the musculoskeletal setting. The objective of this study was to retrospectively evaluate the clinical and 3 Tesla MRA results in two groups of patients operated on for a medium-sized full-thickness rotator cuff tear with two different techniques. Methods The first group consisted of 20 patients operated on with the SR technique; the second group consisted of 20 patients operated on with the DR technique. All patients were evaluated at a minimum of 3 years after surgery. The primary end point was the re-tear rate at 3 Tesla MRA. The secondary end points were the Constant-Murley Scale (CMS), the Simple Shoulder Test (SST) scores, surgical time and implant expense. Results The mean follow-up was 40 months in the SR group and 38.9 months in the DR group. The mean postoperative CMS was 70 in the SR group and 68 in the DR group. The mean SST score was 9.4 in the SR group and 10.1 in the DR group. The re-tear rate was 60% in the SR group and 25% in the DR group. Leakage of the contrast medium was observed in all patients. Conclusions To the best of our knowledge, this is the first report on 3 Tesla MRA in the evaluation of two different techniques of rotator cuff repair. DR repair resulted in a statistically significant lower re-tear rate, with longer surgical time and higher implant expense, despite no

The Impact of Clinical History on the Threshold Estimation of Auditory Brainstem Response Results for Infants

ERIC Educational Resources Information Center

Zaitoun, Maha; Cumming, Steven; Purcell, Alison; O'Brien, Katie

2017-01-01

Purpose: This study assesses the impact of patient clinical history on audiologists' performance when interpreting auditory brainstem response (ABR) results. Method: Fourteen audiologists' accuracy in estimating hearing threshold for 16 infants through interpretation of ABR traces was compared on 2 occasions at least 5 months apart. On the 1st…

4D co-registration of X-ray and MR-mammograms: initial clinical results and potential incremental diagnostic value.

PubMed

Dietzel, Matthias; Hopp, Torsten; Ruiter, Nicole V; Kaiser, Clemens G; Kaiser, Werner A; Baltzer, Pascal A

2015-01-01

4D co-registration of X-ray- and MR-mammograms (XM and MM) is a new method of image fusion. The present study aims to evaluate its clinical feasibility, radiological accuracy, and potential clinical value. XM and MM of 25 patients were co-registered. Results were evaluated by a blinded reader. Precision of the 4D co-registration was "very good" (mean-score [ms]=7), and lesions were "easier to delineate" (ms=5). In 88.8%, "relevant additional diagnostic information" was present, accounting for a more "confident diagnosis" in 76% (ms=5). 4D co-registration is feasible, accurate, and of potential clinical value. Copyright © 2015 Elsevier Inc. All rights reserved.

Clinical predictors of rectal lymphogranuloma venereum infection: results from a multicentre case–control study in the UK

PubMed Central

Pallawela, S N S; Sullivan, A K; Macdonald, N; French, P; White, J; Dean, G; Smith, A; Winter, A J; Mandalia, S; Alexander, S; Ison, C; Ward, H

2014-01-01

Objective Since 2003, over 2000 cases of lymphogranuloma venereum (LGV) have been diagnosed in the UK in men who have sex with men (MSM). Most cases present with proctitis, but there are limited data on how to differentiate clinically between LGV and other pathology. We analysed the clinical presentations of rectal LGV in MSM to identify clinical characteristics predictive of LGV proctitis and produced a clinical prediction model. Design A prospective multicentre case–control study was conducted at six UK hospitals from 2008 to 2010. Cases of rectal LGV were compared with controls with rectal symptoms but without LGV. Methods Data from 98 LGV cases and 81 controls were collected from patients and clinicians using computer-assisted self-interviews and clinical report forms. Univariate and multivariate logistic regression was used to compare symptoms and signs. Clinical prediction models for LGV were compared using receiver operating curves. Results Tenesmus, constipation, anal discharge and weight loss were significantly more common in cases than controls. In multivariate analysis, tenesmus and constipation alone were suggestive of LGV (OR 2.98, 95% CI 0.99 to 8.98 and 2.87, 95% CI 1.01 to 8.15, respectively) and that tenesmus alone or in combination with constipation was a significant predictor of LGV (OR 6.97, 95% CI 2.71 to 17.92). The best clinical prediction was having one or more of tenesmus, constipation and exudate on proctoscopy, with a sensitivity of 77% and specificity of 65%. Conclusions This study indicates that tenesmus alone or in combination with constipation makes a diagnosis of LGV in MSM presenting with rectal symptoms more likely. PMID:24687130

Expectations for Weight Loss and Willingness to Accept Risk Among Patients Seeking Weight Loss Surgery

PubMed Central

Wee, Christina C.; Hamel, Mary Beth; Apovian, Caroline M.; Blackburn, George L.; Bolcic-Jankovic, Dragana; Colten, Mary Ellen; Hess, Donald T.; Huskey, Karen W.; Marcantonio, Edward R.; Schneider, Benjamin E.; Jones, Daniel B.

2015-01-01

Importance Weight loss surgery (WLS) has been shown to produce long-term weight loss but is not risk free or universally effective. The weight loss expectations and willingness to undergo perioperative risk among patients seeking WLS remain unknown. Objectives To examine the expectations and motivations of WLS patients and the mortality risks they are willing to undertake and to explore the demographic characteristics, clinical factors, and patient perceptions associated with high weight loss expectations and willingness to assume high surgical risk. Design We interviewed patients seeking WLS and conducted multivariable analyses to examine the characteristics associated with high weight loss expectations and the acceptance of mortality risks of 10% or higher. Setting Two WLS centers in Boston. Participants Six hundred fifty-four patients. Main Outcome Measures Disappointment with a sustained weight loss of 20% and willingness to accept a mortality risk of 10% or higher with WLS. Results On average, patients expected to lose as much as 38% of their weight after WLS and expressed disappointment if they did not lose at least 26%. Most patients (84.8%) accepted some risk of dying to undergo WLS, but only 57.5% were willing to undergo a hypothetical treatment that produced a 20% weight loss. The mean acceptable mortality risk to undergo WLS was 6.7%, but the median risk was only 0.1%; 19.5% of all patients were willing to accept a risk of at least 10%. Women were more likely than men to be disappointed with a 20% weight loss but were less likely to accept high mortality risk. After initial adjustment, white patients appeared more likely than African American patients to have high weight loss expectations and to be willing to accept high risk. Patients with lower quality-of-life scores and those who perceived needing to lose more than 10% and 20% of weight to achieve “any” health benefits were more likely to have unrealistic weight loss expectations. Low quality

What is the clinical significance of chest CT when the chest x-ray result is normal in patients with blunt trauma?

PubMed

Kea, Bory; Gamarallage, Ruwan; Vairamuthu, Hemamalini; Fortman, Jonathan; Lunney, Kevin; Hendey, Gregory W; Rodriguez, Robert M

2013-08-01

Computed tomography (CT) has been shown to detect more injuries than plain radiography in patients with blunt trauma, but it is unclear whether these injuries are clinically significant. This study aimed to determine the proportion of patients with normal chest x-ray (CXR) result and injury seen on CT and abnormal initial CXR result and no injury on CT and to characterize the clinical significance of injuries seen on CT as determined by a trauma expert panel. Patients with blunt trauma older than 14 years who received emergency department chest imaging as part of their evaluation at 2 urban level I trauma centers were enrolled. An expert trauma panel a priori classified thoracic injuries and subsequent interventions as major, minor, or no clinical significance. Of 3639 participants, 2848 (78.3%) had CXR alone and 791 (21.7%) had CXR and chest CT. Of 589 patients who had chest CT after a normal CXR result, 483 (82.0% [95% confidence interval [CI], 78.7-84.9%]) had normal CT results, and 106 (18.0% [95% CI, 15.1%-21.3%]) had CTs diagnosing injuries-primarily rib fractures, pulmonary contusion, and incidental pneumothorax. Twelve patients had injuries classified as clinically major (2.0% [95% CI, 1.2%-3.5%]), 78 were clinically minor (13.2% [95% CI, 10.7%-16.2%]), and 16 were clinically insignificant (2.7% (95% CI, 1.7%-4.4%]). Of 202 patients with CXRs suggesting injury, 177 (87.6% [95% CI, 82.4%-91.5%]) had chest CTs confirming injury and 25 (12.4% [95% CI, 8.5%-17.6%]) had no injury on CT. Chest CT after a normal CXR result in patients with blunt trauma detects injuries, but most do not lead to changes in patient management. Copyright © 2013 Elsevier Inc. All rights reserved.

Summarising and validating test accuracy results across multiple studies for use in clinical practice.

PubMed

Riley, Richard D; Ahmed, Ikhlaaq; Debray, Thomas P A; Willis, Brian H; Noordzij, J Pieter; Higgins, Julian P T; Deeks, Jonathan J

2015-06-15

Following a meta-analysis of test accuracy studies, the translation of summary results into clinical practice is potentially problematic. The sensitivity, specificity and positive (PPV) and negative (NPV) predictive values of a test may differ substantially from the average meta-analysis findings, because of heterogeneity. Clinicians thus need more guidance: given the meta-analysis, is a test likely to be useful in new populations, and if so, how should test results inform the probability of existing disease (for a diagnostic test) or future adverse outcome (for a prognostic test)? We propose ways to address this. Firstly, following a meta-analysis, we suggest deriving prediction intervals and probability statements about the potential accuracy of a test in a new population. Secondly, we suggest strategies on how clinicians should derive post-test probabilities (PPV and NPV) in a new population based on existing meta-analysis results and propose a cross-validation approach for examining and comparing their calibration performance. Application is made to two clinical examples. In the first example, the joint probability that both sensitivity and specificity will be >80% in a new population is just 0.19, because of a low sensitivity. However, the summary PPV of 0.97 is high and calibrates well in new populations, with a probability of 0.78 that the true PPV will be at least 0.95. In the second example, post-test probabilities calibrate better when tailored to the prevalence in the new population, with cross-validation revealing a probability of 0.97 that the observed NPV will be within 10% of the predicted NPV. © 2015 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

MiDAS ENCORE: Randomized Controlled Clinical Trial Report of 6-Month Results.

PubMed

Staats, Peter S; Benyamin, Ramsin M

2016-02-01

Patients suffering from neurogenic claudication due to lumbar spinal stenosis (LSS) often experience moderate to severe pain and significant functional disability. Neurogenic claudication results from progressive degenerative changes in the spine, and most often affects the elderly. Both the MILD® procedure and epidural steroid injections (ESIs) offer interventional pain treatment options for LSS patients experiencing neurogenic claudication refractory to more conservative therapies. MILD provides an alternative to ESIs via minimally invasive lumbar decompression. Prospective, multi-center, randomized controlled clinical trial. Twenty-six US interventional pain management centers. To compare patient outcomes following treatment with either MILD (treatment group) or ESIs (active control group) in LSS patients with neurogenic claudication and verified ligamentum flavum hypertrophy. This prospective, multi-center, randomized controlled clinical trial includes 2 study arms with a 1-to-1 randomization ratio. A total of 302 patients were enrolled, with 149 randomized to MILD and 153 to the active control. Six-month follow-up has been completed and is presented in this report. In addition, one year follow-up will be conducted for patients in both study arms, and supplementary 2 year outcome data will be collected for patients in the MILD group only. Outcomes are assessed using the Oswestry Disability Index (ODI), numeric pain rating scale (NPRS) and Zurich Claudication Questionnaire (ZCQ). Primary efficacy is the proportion of ODI responders, tested for statistical superiority of the MILD group versus the active control group. ODI responders are defined as patients achieving the validated Minimal Important Change (MIC) of =10 point improvement in ODI from baseline to follow-up. Similarly, secondary efficacy includes proportion of NPRS and ZCQ responders using validated MIC thresholds. Primary safety is the incidence of device or procedure-related adverse events in each

Preliminary clinical results: an analyzing tool for 2D optical imaging in detection of active inflammation in rheumatoid arthritis

NASA Astrophysics Data System (ADS)

Adi Aizudin Bin Radin Nasirudin, Radin; Meier, Reinhard; Ahari, Carmen; Sievert, Matti; Fiebich, Martin; Rummeny, Ernst J.; No"l, Peter B.

2011-03-01

Optical imaging (OI) is a relatively new method in detecting active inflammation of hand joints of patients suffering from rheumatoid arthritis (RA). With the high number of people affected by this disease especially in western countries, the availability of OI as an early diagnostic imaging method is clinically highly relevant. In this paper, we present a newly in-house developed OI analyzing tool and a clinical evaluation study. Our analyzing tool extends the capability of existing OI tools. We include many features in the tool, such as region-based image analysis, hyper perfusion curve analysis, and multi-modality image fusion to aid clinicians in localizing and determining the intensity of inflammation in joints. Additionally, image data management options, such as the full integration of PACS/RIS, are included. In our clinical study we demonstrate how OI facilitates the detection of active inflammation in rheumatoid arthritis. The preliminary clinical results indicate a sensitivity of 43.5%, a specificity of 80.3%, an accuracy of 65.7%, a positive predictive value of 76.6%, and a negative predictive value of 64.9% in relation to clinical results from MRI. The accuracy of inflammation detection serves as evidence to the potential of OI as a useful imaging modality for early detection of active inflammation in patients with rheumatoid arthritis. With our in-house developed tool we extend the usefulness of OI imaging in the clinical arena. Overall, we show that OI is a fast, inexpensive, non-invasive and nonionizing yet highly sensitive and accurate imaging modality.-

Ultrasound-guided Interdigital Neuroma Injections: Short-term Clinical Outcomes after a Single Percutaneous Injection—Preliminary Results

PubMed Central

Adler, Ronald S.; Ciavarra, Gina A.; Pavlov, Helene

2006-01-01

Purpose To describe the procedure of ultrasound-guided Morton’s neuroma and recurrent stump neuroma injections and early clinical outcomes after a single injection. Materials and Methods Retrospective review of 44 percutaneous ultrasound-guided neuroma injections in 24 patients who had completed clinical outcomes questionnaires. A 10-point pain scale [scale of 1 (no pain) to 10 (severe pain)] in a 7-day pain log format was distributed to patients at the time percutaneous neuroma injection was performed. Results Neuromas were clearly visualized with sonography as hypoechoic nodules and were distinguishable from other causes of forefoot pain, such as metatarsophalangeal joint synovitis and intermetatarsal bursae. The sizes of the neuromas injected ranged between 4 and 19 mm. Postinjection, all neuromas displayed increased echogenicity and/or the appearance of fluid surrounding it, confirming localization of the therapeutic mixture. We arbitrarily subdivided the pain ratings into symptomatic (greater than 4) and asymptomatic (less than or equal to 4) for statistical analysis. Average pain level pre injection was 5.2 and average pain level was 3.7 at 7 days post single injection, with 62% of the initially symptomatic patients asymptomatic on day 7 (p < 0.000001). Overall, 76% of the total number of neuromas injected once were asymptomatic on day 7. Conclusion Ultrasound can be used to accurately target Morton’s neuromas and, therefore, appropriately direct therapeutic interventions, with good short-term clinical results. PMID:18751769

Statins for stroke prevention: disappointment and hope.

PubMed

Amarenco, Pierre; Tonkin, Andrew M

2004-06-15

The occurrence of stroke increases with age, particularly affecting the older elderly, a population also at higher risk for coronary heart disease (CHD). Epidemiological and observational studies have not shown a clear association between cholesterol levels and all causes of stroke. Nonetheless, large, long-term statin trials in patients with established CHD or at high risk for CHD have shown that statins decrease stroke incidence in these populations. Combined data from 9 trials including 70,070 patients indicated relative and absolute risk reductions for stroke of 21% and 0.9%, respectively, with statins. The number of strokes prevented per 1000 patients treated for 5 years in patients with CHD is 9 for statins, compared with 17.3 for antiplatelet agents. Statins have not yet been shown to reduce stroke risk in the typical general population without known CHD, nor have they been shown to prevent recurrent stroke in patients with prior stroke. Potential reasons for the effects of statins on stroke and the non-cholesterol-lowering mechanisms that may be involved are discussed. Treatment strategies based on global cardiovascular risk may be most effective. Additional studies in patients representative of the typical stroke population are needed.

Clinical pharmacogenomics: patient perspectives of pharmacogenomic testing and the incidence of actionable test results in a chronic disease cohort.

PubMed

Mukherjee, Chandrama; Sweet, Kevin M; Luzum, Jasmine A; Abdel-Rasoul, Mahmoud; Christman, Michael F; Kitzmiller, Joseph P

2017-09-01

This study aimed to examine pharmacogenomic test results and patient perspectives at an academic cardiovascular medicine clinic. Test results for three common cardiovascular drug-gene tests (warfarin- CYP2C9-VKORC1 , clopidogrel- CYP2C19 and simvastatin- SLCO1B1 ) of 208 patients in the Ohio State University-Coriell Personalized Medicine Collaborative were examined to determine the incidence of potentially actionable test results. A post-hoc, anonymous, patient survey was also conducted. Potentially actionable test results for at least one of the three drug-gene tests were determined in 170 (82%) patients. Survey responses (n = 134) suggested that patients generally considered their test results to be important (median of 7.5 on a 10-point scale of importance) and were interested (median of 7.3 on a 10-point scale of interest) in a Clinical Pharmacogenomic Service. Attitudes toward pharmacogenomic testing were generally favorable, and potentially actionable test results were not uncommon in this cardiovascular medicine cohort.

Clinical risk factors for weight gain during psychopharmacologic treatment of depression: results from 2 large German observational studies.

PubMed

Kloiber, Stefan; Domschke, Katharina; Ising, Marcus; Arolt, Volker; Baune, Bernhard T; Holsboer, Florian; Lucae, Susanne

2015-06-01

Weight gain during psychopharmacologic treatment has considerable impact on the clinical management of depression, treatment continuation, and risk for metabolic disorders. As no profound clinical risk factors have been identified so far, the aim of our analyses was to determine clinical risk factors associated with short-term weight development in 2 large observational psychopharmacologic treatment studies for major depression. Clinical variables at baseline (age, gender, depression psychopathology, anthropometry, disease history, and disease entity) were analyzed for association with percent change in body mass index (BMI; normal range, 18.5 to 25 kg/m(2)) during 5 weeks of naturalistic psychopharmacologic treatment in patients who had a depressive episode as single depressive episode, in the course of recurrent unipolar depression or bipolar disorder according to DSM-IV criteria. 703 patients participated in the Munich Antidepressant Response Signature (MARS) project, an ongoing study since 2002, and 214 patients participated in a study conducted at the University of Muenster from 2004 to 2006 in Germany. Lower BMI, weight-increasing side effects of medication, severity of depression, and psychotic symptoms could be identified as clinical risk factors associated with elevated weight gain during the initial treatment phase of 5 weeks in both studies. Based on these results, a composite risk score for weight gain consisting of BMI ≤ 25 kg/m(2), Hamilton Depression Rating Scale (17-item) score > 20, presence of psychotic symptoms, and administration of psychopharmacologic medication with potential weight-gaining side effects was highly discriminative for mean weight gain (F4,909 = 26.77, P = 5.14E-21) during short-term psychopharmacologic treatment. On the basis of our results, depressed patients with low to normal BMI, severe depression, or psychotic symptoms should be considered at higher risk for weight gain during acute antidepressant treatment. We introduce

Horizon 2020 Priorities in Clinical Mental Health Research: Results of a Consensus-Based ROAMER Expert Survey

PubMed Central

Elfeddali, Iman; van der Feltz-Cornelis, Christina M.; van Os, Jim; Knappe, Susanne; Vieta, Eduard; Wittchen, Hans-Ulrich; Obradors-Tarragó, Carla; Haro, Josep Maria

2014-01-01

Within the ROAMER project, which aims to provide a Roadmap for Mental Health Research in Europe, a two-stage Delphi survey among 86 European experts was conducted in order to identify research priorities in clinical mental health research. Expert consensus existed with regard to the importance of three challenges in the field of clinical mental health research: (1) the development of new, safe and effective interventions for mental disorders; (2) understanding the mechanisms of disease in order to be able to develop such new interventions; and (3) defining outcomes (an improved set of outcomes, including alternative outcomes) to use for clinical mental health research evaluation. Proposed actions involved increasing the utilization of tailored approaches (personalized medicine), developing blended eHealth/mHealth decision aids/guidance tools that help the clinician to choose between various treatment modalities, developing specific treatments in order to better target comorbidity and (further) development of biological, psychological and psychopharmacological interventions. The experts indicated that addressing these priorities will result in increased efficacy and impact across Europe; with a high probability of success, given that Europe has important strengths, such as skilled academics and a long research history. Finally, the experts stressed the importance of creating funding and coordinated networking as essential action needed in order to target the variety of challenges in clinical mental health research. PMID:25337940

Clinical and radiological results on the fixation of Neer type 2 distal clavicle fractures with a hook plate.

PubMed

Şükür, Erhan; Öztürkmen, Yusuf; Akman, Yunus Emre; Güngör, Mustafa

2016-10-01

The aim of this study was to analyze the clinical and functional results of hook plate fixation in Neer type 2 distal clavicle fractures. We retrospectively analyzed 16 patients (11 males, 5 females) who were diagnosed with Neer type 2 distal clavicle fractures and treated with hook plate fixation between 2013 and 2014. Mean age was 38 (range: 27-61), and mean follow-up time was 14.3 (range: 12-18) months. Complications seen on radiographs were implant failure and subacromial osteolysis. The clinical results were evaluated with modified UCLA (University of California Los Angeles) scoring system. Bone union was achieved in all patients at the end of the first 4 months. Mean modified UCLA score was 32.75 (range 31-35). In 12 patients (68%), the implants had to be removed due to complications. After removal, the complaints regressed and shoulders' range of motion increased. Clinical and radiological results on the fixation of Neer type 2 distal clavicle fractures with a hook plate are good in terms of fracture union and function. The major disadvantage of the method was the requirement of early implant removal due to the hardware related complications and good results can be achieved only after plate removal. Optimizing the length of hook plate may lower the rate of complications. Level IV, Therapeutic study. Copyright © 2016 Turkish Association of Orthopaedics and Traumatology. Production and hosting by Elsevier B.V. All rights reserved.

Differences in quantitative methods for measuring subjective cognitive decline - results from a prospective memory clinic study.

PubMed

Vogel, Asmus; Salem, Lise Cronberg; Andersen, Birgitte Bo; Waldemar, Gunhild

2016-09-01

Cognitive complaints occur frequently in elderly people and may be a risk factor for dementia and cognitive decline. Results from studies on subjective cognitive decline are difficult to compare due to variability in assessment methods, and little is known about how different methods influence reports of cognitive decline. The Subjective Memory Complaints Scale (SMC) and The Memory Complaint Questionnaire (MAC-Q) were applied in 121 mixed memory clinic patients with mild cognitive symptoms (mean MMSE = 26.8, SD 2.7). The scales were applied independently and raters were blinded to results from the other scale. Scales were not used for diagnostic classification. Cognitive performances and depressive symptoms were also rated. We studied the association between the two measures and investigated the scales' relation to depressive symptoms, age, and cognitive status. SMC and MAC-Q were significantly associated (r = 0.44, N = 121, p = 0.015) and both scales had a wide range of scores. In this mixed cohort of patients, younger age was associated with higher SMC scores. There were no significant correlations between cognitive test performances and scales measuring subjective decline. Depression scores were significantly correlated to both scales measuring subjective decline. Linear regression models showed that age did not have a significant contribution to the variance in subjective memory beyond that of depressive symptoms. Measures for subjective cognitive decline are not interchangeable when used in memory clinics and the application of different scales in previous studies is an important factor as to why studies show variability in the association between subjective cognitive decline and background data and/or clinical results. Careful consideration should be taken as to which questions are relevant and have validity when operationalizing subjective cognitive decline.

Positive outcomes influence the rate and time to publication, but not the impact factor of publications of clinical trial results.

PubMed

Suñé, Pilar; Suñé, Josep Maria; Montoro, J Bruno

2013-01-01

Publication bias may affect the validity of evidence based medical decisions. The aim of this study is to assess whether research outcomes affect the dissemination of clinical trial findings, in terms of rate, time to publication, and impact factor of journal publications. All drug-evaluating clinical trials submitted to and approved by a general hospital ethics committee between 1997 and 2004 were prospectively followed to analyze their fate and publication. Published articles were identified by searching Pubmed and other electronic databases. Clinical study final reports submitted to the ethics committee, final reports synopses available online and meeting abstracts were also considered as sources of study results. Study outcomes were classified as positive (when statistical significance favoring experimental drug was achieved), negative (when no statistical significance was achieved or it favored control drug) and descriptive (for non-controlled studies). Time to publication was defined as time from study closure to publication. A survival analysis was performed using a Cox regression model to analyze time to publication. Journal impact factors of identified publications were recorded. Publication rate was 48·4% (380/785). Study results were identified for 68·9% of all completed clinical trials (541/785). Publication rate was 84·9% (180/212) for studies with results classified as positive and 68·9% (128/186) for studies with results classified as negative (p<0·001). Median time to publication was 2·09 years (IC95 1·61-2·56) for studies with results classified as positive and 3·21 years (IC95 2·69-3·70) for studies with results classified as negative (hazard ratio 1·99 (IC95 1·55-2·55). No differences were found in publication impact factor between positive (median 6·308, interquartile range: 3·141-28·409) and negative result studies (median 8·266, interquartile range: 4·135-17·157). Clinical trials with positive outcomes have significantly

Concise Review: Apoptotic Cell-Based Therapies-Rationale, Preclinical Results and Future Clinical Developments.

PubMed

Saas, Philippe; Daguindau, Etienne; Perruche, Sylvain

2016-06-01

The objectives of this review are to summarize the experimental data obtained using apoptotic cell-based therapies, and then to discuss future clinical developments. Indeed, apoptotic cells exhibit immunomodulatory properties that are reviewed here by focusing on more recent mechanisms. These immunomodulatory mechanisms are in particular linked to the clearance of apoptotic cells (called also efferocytosis) by phagocytes, such as macrophages, and the induction of regulatory T cells. Thus, apoptotic cell-based therapies have been used to prevent or treat experimental inflammatory diseases. Based on these studies, we have identified critical steps to design future clinical trials. This includes: the administration route, the number and schedule of administration, the appropriate apoptotic cell type to be used, as well as the apoptotic signal. We also have analyzed the clinical relevancy of apoptotic-cell-based therapies in experimental models. Additional experimental data are required concerning the treatment of inflammatory diseases (excepted for sepsis) before considering future clinical trials. In contrast, apoptotic cells have been shown to favor engraftment and to reduce acute graft-versus-host disease (GvHD) in different relevant models of transplantation. This has led to the conduct of a phase 1/2a clinical trial to alleviate GvHD. The absence of toxic effects obtained in this trial may support the development of other clinical studies based on this new cell therapy. Stem Cells 2016;34:1464-1473. © 2016 AlphaMed Press.

Scanned focussed ultrasound hyperthermia: initial clinical results.

PubMed

Shimm, D S; Hynynen, K H; Anhalt, D P; Roemer, R B; Cassady, J R

1988-11-01

Between November 1986 and July, 1987, a preliminary study to determine the feasibility of scanned focussed ultrasound for clinical hyperthermia at various sites was conducted. Fourteen patient (17 tumors) have been treated using a microprocessor-controlled apparatus developed at the University of Arizona by modifying a commercially available diagnostic ultrasound unit. We have treated nine pelvic tumors, four extremity tumors, two brain tumors, and two extracranial head and neck tumors for a total of 42 treatments. Multipoint thermometry was achieved for all patients, with 2-25 (mean = 10) points monitored during each treatments within the scanned tumor volume. Average maximum temperature within the scanned tumor volume was 44.2, 44.7, 44.8, and 42.0 degrees C for pelvic, extremity brain, and extracranial head and neck tumors, respectively; similarly, 55%, 45%, 71%, and 0 of monitored points exceeded 42.5 degrees C. Pain limited applied power in 15 of 42 treatments, and bone pain with a periodicity similar to the scanning periodicity was seen in 11 treatments. A non-randomized comparison of temperatures achieved using scanned focussed ultrasound to those achieved using the microwave annular array and the CDRH Helix suggests that scanned focussed ultrasound may have promise and potential advantages in heating selected pelvic tumors.

Cannabinergic pain medicine: a concise clinical primer and survey of randomized-controlled trial results.

PubMed

Aggarwal, Sunil K

2013-02-01

This article attempts to cover pragmatic clinical considerations involved in the use of cannabinergic medicines in pain practice, including geographical and historical considerations, pharmacokinetics, pharmacodynamics, adverse effects, drug interactions, indications, and contraindications. Topics include molecular considerations such as the 10-fold greater abundance of cannabinoid type 1 receptors compared to µ-opioid receptors in the central nervous system and anatomic distributions of cannabinoid receptors in pain circuits. The article uses a narrative review methodology drawing from authoritative textbooks and journals of cannabinoid medicine, Food and Drug Administration-approved cannabinoid drug labels, and current and historical pain medicine literature to address core clinical considerations. To survey the current evidence base for pain management with cannabinergic medicines, a targeted PubMed search was performed to survey the percentage of positive and negative published randomized-controlled trial (RCT) results with this class of pain medicines, using appropriate search limit parameters and the keyword search string "cannabinoid OR cannabis-based AND pain." Of the 56 hits generated, 38 published RCTs met the survey criteria. Of these, 71% (27) concluded that cannabinoids had empirically demonstrable and statistically significant pain-relieving effects, whereas 29% (11) did not. Cannabis and other cannabinergic medicines' efficacies for relieving pain have been studied in RCTs, most of which have demonstrated a beneficial effect for this indication, although most trials are short-term. Adverse effects are generally nonserious and well tolerated. Incorporating cannabinergic medicine topics into pain medicine education seems warranted and continuing clinical research and empiric treatment trials are appropriate.

High-Dose-Rate Interstitial Brachytherapy as Monotherapy for Clinically Localized Prostate Cancer: Treatment Evolution and Mature Results

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

Zamboglou, Nikolaos; Tselis, Nikolaos, E-mail: ntselis@hotmail.com; Baltas, Dimos

2013-03-01

Purpose: To report the clinical outcome of high-dose-rate (HDR) interstitial (IRT) brachytherapy (BRT) as sole treatment (monotherapy) for clinically localized prostate cancer. Methods and Materials: Between January 2002 and December 2009, 718 consecutive patients with clinically localized prostate cancer were treated with transrectal ultrasound (TRUS)-guided HDR monotherapy. Three treatment protocols were applied; 141 patients received 38.0 Gy using one implant in 4 fractions of 9.5 Gy with computed tomography-based treatment planning; 351 patients received 38.0 Gy in 4 fractions of 9.5 Gy, using 2 implants (2 weeks apart) and intraoperative TRUS real-time treatment planning; and 226 patients received 34.5 Gy,more » using 3 single-fraction implants of 11.5 Gy (3 weeks apart) and intraoperative TRUS real-time treatment planning. Biochemical failure was defined according to the Phoenix consensus, and toxicity was evaluated using Common Toxicity Criteria for Adverse Events version 3. Results: The median follow-up time was 52.8 months. The 36-, 60-, and 96-month biochemical control and metastasis-free survival rates for the entire cohort were 97%, 94%, and 90% and 99%, 98%, and 97%, respectively. Toxicity was scored per event, with 5.4% acute grade 3 genitourinary and 0.2% acute grade 3 gastrointestinal toxicity. Late grade 3 genitourinary and gastrointestinal toxicities were 3.5% and 1.6%, respectively. Two patients developed grade 4 incontinence. No other instance of grade 4 or greater acute or late toxicity was reported. Conclusion: Our results confirm IRT-HDR-BRT is safe and effective as monotherapy for clinically localized prostate cancer.« less

Posttraumatic stress disorder and physical illness: results from clinical and epidemiologic studies.

PubMed

Boscarino, Joseph A

2004-12-01

Research indicates that exposure to traumatic stressors and psychological trauma is widespread. The association of such exposures with posttraumatic stress disorder (PTSD) and other mental health conditions is well known. However, epidemiologic research increasingly suggests that exposure to these events is related to increased health care utilization, adverse health outcomes, the onset of specific diseases, and premature death. To date, studies have linked traumatic stress exposures and PTSD to such conditions as cardiovascular disease, diabetes, gastrointestinal disease, fibromyalgia, chronic fatigue syndrome, musculoskeletal disorders, and other diseases. Evidence linking cardiovascular disease and exposure to psychological trauma is particularly strong and has been found consistently across different populations and stressor events. In addition, clinical studies have suggested the biological pathways through which stressor-induced diseases may be pathologically expressed. In particular, recent studies have implicated the hypothalamic-pituitary-adrenal (HPA) and the sympathetic-adrenal-medullary (SAM) stress axes as key in this pathogenic process, although genetic and behavioral/psychological risk factors cannot be ruled out. Recent findings, indicating that victims of PTSD have higher circulating T-cell lymphocytes and lower cortisol levels, are intriguing and suggest that chronic sufferers of PTSD may be at risk for autoimmune diseases. To test this hypothesis, we assessed the association between chronic PTSD in a national sample of 2,490 Vietnam veterans and the prevalence of common autoimmune diseases, including rheumatoid arthritis, psoriasis, insulin-dependent diabetes, and thyroid disease. Our analyses suggest that chronic PTSD, particularly comorbid PTSD or complex PTSD, is associated with all of these conditions. In addition, veterans with comorbid PTSD were more likely to have clinically higher T-cell counts, hyperreactive immune responses on

Navigating the clinical trial pathway: Conception, design, execution, and results dissemination.

PubMed

Sampalis, John S; Watson, Joanne; Boukas, Stella; Boukas, Marianna; Harvey, Natalie; Machado, Sanjay; Bordeleau, Michel; Rampakakis, Emmanouil

2017-03-01

Dr Sampalis is founder, Chief Executive Officer, and Chief Scientific Officer of JSS Medical Research Inc, founded in 1997. He is a tenured professor of Surgery and Epidemiology & Biostatistics of McGill University, the University of Montreal and University of Laval. Recognized as a leading clinical epidemiologist and one of the top trauma researchers in Canada, he possesses extensive expertise in health services research, clinical trials, and offers services as a Research and Epidemiological Consultant for numerous pharmaceutical companies, hospitals and government organizations and agencies. Mrs. Watson holds a M.Sc. in Pharmacology from Dalhousie University, and a B.Sc. from the University of Western Ontario. Her experience extends to all facets of the CRO business, and multiple therapeutic areas. She co-founded, in 1992, Integrated Research Inc, a full-service contract research organization, and served as its President and Chief Executive Officer, until merging with JSS Medical Research Inc in 2014. Mrs. Watson currently holds the position of Chief Business Officer, and is head of the business development team. Mrs. Boukas has been working with the JSS Medical Research team since its inception in the 1990s. She holds a B.A. in Psychology from McGill University with training in Epidemiology and Biostatistics, and is certified by the Society of Clinical Research Associates (SOCRA) as a Certified Clinical Research Professional (CCRP). She has over 25 years' of experience in medical research management. Currently Chief Operations Officer, Mrs. Boukas has been essential in structuring and implementing programs at JSS Medical Research Inc to facilitate project management, site recruitment, data capture and study tracking. Mrs. Boukas holds a B.A. from McGill University, a Certificate in Technical Communications from Concordia University and has received compliance training from SNC Lavalin Pharma (SLP) and SOCRA. She has over twenty-five years' experience in

The clinical impact of a false-positive urine cocaine screening result on a patient's pain management.

PubMed

Kim, James A; Ptolemy, Adam S; Melanson, Stacy E F; Janfaza, David R; Ross, Edgar L

2015-06-01

The urine of a patient admitted for chest and epigastric pain tested positive for cocaine using an immunoassay-based drug screening method (positive/negative cutoff concentration 150 ng/mL). Despite the patient's denial of recent cocaine use, this positive cocaine screening result in conjunction with a remote history of drug misuse impacted the patient's recommended pain therapy. Specifically, these factors prompted the clinical team to question the appropriateness of opioids and other potentially addictive therapeutics during the treatment of cancer pain from previously undetected advanced pancreatic carcinoma. After pain management and clinical pathology consultation, it was decided that the positive cocaine screening result should be confirmed by gas chromatography-mass spectrometry (GC-MS) testing. This more sensitive and specific analytical technique revealed that both cocaine and its primary metabolite benzoylecgonine were undetectable (i.e., less than the assay detection limit of 50 ng/mL), thus indicating that the positive urine screening result was falsely positive. With this confirmation, the pain management service team was reassured in offering intrathecal pump (ITP) therapy for pain control. ITP implantation was well tolerated, and the patient eventually achieved excellent pain relief. However, ITP therapy most likely would not have been utilized without the GC-MS confirmation testing unless alternative options failed and extensive vigilant monitoring was initiated. As exemplified in this case, confirmatory drug testing should be performed on specimens with unexpected immunoassay-based drug screening results. To our knowledge, this is the first report of a false-positive urine cocaine screening result and its impact on patient management. Wiley Periodicals, Inc.

Guide to designing, conducting, publishing and communicating results of clinical studies involving probiotic applications in human participants

PubMed Central

Cabana, Michael D; Vidry, Stéphane; Merenstein, Dan; Hummelen, Ruben; Ellis, Collin L; Heimbach, James T; Hempel, Susanne; Lynch, Susan V; Sanders, Mary Ellen; Tancredi, Daniel J

2010-01-01

The heterogeneity of human clinical trials to assess the effectiveness of probiotics presents challenges regarding interpretation and comparison. Evidence obtained from clinical trials among a population with a disease or specific risk factors may not be generalizable to healthy individuals. The evaluation of interventions in healthy persons requires careful selection of outcomes due to the absence of health indicators and the low incidence of preventable conditions. Given the tremendous resources invested in such trials, development of consistent approaches to assessing the effectiveness of probiotics would be beneficial. Furthermore, the reporting, presentation and communication of results may also affect the validity of the scientific evidence obtained from a trial. This review outlines the challenges associated with the design, implementation, data analysis and interpretation of clinical trials in humans involving probiotics. Best practices related to their design are offered along with recommendations for enhanced collaboration to advance research in this emerging field. PMID:21327031

[Mesenchymal stem cell therapy, a new hope for eye disease].

PubMed

Roubeix, C; Denoyer, A; Brignole-Baudouin, F; Baudouin, C

2015-10-01

Mesenchymal stem cells (MSC) are adult stem cells, first identified in skeletal tissues and then found in the entire body. MSC are able to not only differentiate into specialized cells within skeletal tissue - chondrocytes, osteocytes, adipocytes and fibroblasts - but also secrete a large range of soluble mediators defining their secretome and allowing their interaction with a number of cell protagonists. Thus, in a general sense, MSC are involved in tissue homeostasis through their secretome and are specifically responsible for cell turn-over in skeletal tissues. For a decade and a half, safety and efficiency of MSC has led to the development of many clinical trials in various fields. However, results were often disappointing, probably because of difficulties in methods and evaluation. At a time when the first clinical trials using MSC are emerging in ophthalmology, the goal of this literature review is to gather and put into perspective preclinical and clinical results in order to better predict the future of this innovative therapeutic pathway. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

[Generalization of the results of clinical studies through the analysis of subgroups].

PubMed

Costa, João; Fareleira, Filipa; Ascensão, Raquel; Vaz Carneiro, António

2012-01-01

Subgroup analysis in clinical trials are usually performed to define the potential heterogeneity of treatment effect in relation with the baseline risk, physiopathology, practical application of therapy or the under-utilization in clinical practice of effective interventions due to uncertainties of its benefit/risk ratio. When appropriately planned, subgroup analysis are a valid methodology the define benefits in subgroups of patients, thus providing good quality evidence to support clinical decision making. However, in order to be correct, subgroup analysis should be defined a priori, done in small numbers, should be fully reported and, most important, must endure statistical tests for interaction. In this paper we present an example of the treatment of post-menopausal osteoporosis, in which the benefits of an intervention (the higher the fracture risk is, the better the benefit is) with a specific agent (bazedoxifene) was only disclosed after a post-hoc analysis of the initial global trial sample.

Summary and Recommendations from the National Cancer Institute’s Clinical Trials Planning Meeting on Novel Therapeutics for Non-Muscle Invasive Bladder Cancer

PubMed Central

Lerner, Seth P.; Bajorin, Dean F.; Dinney, Colin P.; Efstathiou, Jason A.; Groshen, Susan; Hahn, Noah M.; Hansel, Donna; Kwiatkowski, David; O’Donnell, Michael; Rosenberg, Jonathan; Svatek, Robert; Abrams, Jeffrey S.; Al-Ahmadie, Hikmat; Apolo, Andrea B.; Bellmunt, Joaquim; Callahan, Margaret; Cha, Eugene K.; Drake, Charles; Jarow, Jonathan; Kamat, Ashish; Kim, William; Knowles, Margaret; Mann, Bhupinder; Marchionni, Luigi; McConkey, David; McShane, Lisa; Ramirez, Nilsa; Sharabi, Andrew; Sharpe, Arlene H.; Solit, David; Tangen, Catherine M.; Amiri, Abdul Tawab; Van Allen, Eliezer; West, Pamela J.; Witjes, J. A.; Quale, Diane Zipursky

2016-01-01

The NCI Bladder Cancer Task Force convened a Clinical Trials Planning Meeting (CTPM) Workshop focused on Novel Therapeutics for Non-Muscle Invasive Bladder Cancer (NMIBC). Meeting attendees included a broad and multi-disciplinary group of clinical and research stakeholders and included leaders from NCI, FDA, National Clinical Trials Network (NCTN), advocacy and the pharmaceutical and biotech industry. The meeting goals and objectives were to: 1) create a collaborative environment in which the greater bladder research community can pursue future optimally designed novel clinical trials focused on the theme of molecular targeted and immune-based therapies in NMIBC; 2) frame the clinical and translational questions that are of highest priority; and 3) develop two clinical trial designs focusing on immunotherapy and molecular targeted therapy. Despite successful development and implementation of large Phase II and Phase III trials in bladder and upper urinary tract cancers, there are no active and accruing trials in the NMIBC space within the NCTN. Disappointingly, there has been only one new FDA approved drug (Valrubicin) in any bladder cancer disease state since 1998. Although genomic-based data for bladder cancer are increasingly available, translating these discoveries into practice changing treatment is still to come. Recently, major efforts in defining the genomic characteristics of NMIBC have been achieved. Aligned with these data is the growing number of targeted therapy agents approved and/or in development in other organ site cancers and the multiple similarities of bladder cancer with molecular subtypes in these other cancers. Additionally, although bladder cancer is one of the more immunogenic tumors, some tumors have the ability to attenuate or eliminate host immune responses. Two trial concepts emerged from the meeting including a window of opportunity trial (Phase 0) testing an FGFR3 inhibitor and a second multi-arm multi-stage trial testing combinations

[Transcranial direct current stimulation (tDCS) for depression: Results of nearly a decade of clinical research].

PubMed

Palm, U; Ayache, S S; Padberg, F; Lefaucheur, J-P

2016-02-01

Since 2006 transcranial direct current stimulation (tDCS) has been investigated in the treatment of depression. In this review, we discuss the implications and clinical perspectives that tDCS may have as a therapeutic tool in depression from the results reported in this domain. A comprehensive literature review has found nearly thirty articles - all in English - on this topic, corresponding to clinical studies, placebo-controlled or not, case reports and reviews. Several meta-analyses showed that the antidepressant effects of active tDCS are significant against placebo, but variable, mainly due to the heterogeneity of the patients included in the studies, for example regarding the resistance to antidepressant treatment. Specific recommendations for the use of tDCS in treating depression may not yet be available, but some elements of good practice can be highlighted. Of particular note is that anodal tDCS of the left prefrontal cortex at 2mA for 20 minutes per day has a potential therapeutic value without risk of significant side effects: tDCS offers safe conditions for clinical use in the treatment of depression. Copyright © 2015 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

Management of advanced pancreatic cancer with gemcitabine plus erlotinib: efficacy and safety results in clinical practice.

PubMed

Diaz Beveridge, Robert; Alcolea, Vicent; Aparicio, Jorge; Segura, Ángel; García, Jose; Corbellas, Miguel; Fonfría, María; Giménez, Alejandra; Montalar, Joaquin

2014-01-10

The combination of gemcitabine and erlotinib is a standard first-line treatment for unresectable, locally advanced or metastatic pancreatic cancer. We reviewed our single centre experience to assess its efficacy and toxicity in clinical practice. Clinical records of patients with unresectable, locally advanced or metastatic pancreatic cancer who were treated with the combination of gemcitabine and erlotinib were reviewed. Univariate survival analysis and multivariate analysis were carried out to indentify independent predictors factors of overall survival. Our series included 55 patients. Overall disease control rate was 47%: 5% of patients presented complete response, 20% partial response and 22% stable disease. Median overall survival was 8.3 months). Cox regression analysis indicated that performance status and locally advanced versus metastatic disease were independent factors of overall survival. Patients who developed acne-like rash toxicity, related to erlotinib administration, presented a higher survival than those patients who did not develop this toxicity. Gemcitabine plus erlotinib doublet is active in our series of patients with advanced pancreatic cancer. This study provides efficacy and safety results similar to those of the pivotal phase III clinical trial that tested the same combination.

[Total reverse shoulder replacement. Evaluation of the clinical results and complications in a series of 52 cases].

PubMed

Cáceres-Sánchez, L; Mesa-Mateo, A; Barrionuevo-Sánchez, F J; García-Benítez, B; Expósito-Triano, S

2015-01-01

To evaluate the clinical results and analyse the complications of total reverse shoulder replacement performed in our centre over an 8 year period. A retrospective study was conducted on 50 patients (52 shoulders), with a mean age of 70.15 years (range 51 to 84 years) between December 2004 and December 2012, who received a total reverse shoulder replacement, all performed by the same surgeon. The results have been evaluated according to clinical data, radiography study, a satisfaction scale, and the Constant scale, with a minimum follow-up of 16 months. Five of the cases (9.62%) had been intervened due to fractures of the proximal end of the humerus, 6 cases (11.53%) as surgical consequence of a prosthesis revision, 10 cases (19.23%) due to fracture sequelae, and 30 cases (59.62%) were patients with arthropathy due to a massive fracture of the rotator cuff. After a mean follow up of 35.78 months (range, 16-82), satisfactory clinical results were obtained in 80% of cases, with a mean preoperative Constant of 27.7 points, and reaching 67.1 points 12 months after the operation. On the visual analogue scale, 8.25 points were obtained before the surgery, which decreased to 2.25 points 12 months later. The complications rate was 15.38%, which were due to an intra-operative fracture (1.92%), deep infection (3.84%), instability (3.84%), and early mechanical loosening (3.84%). Scapular notching was observed in the radiographic study in 9 (17.3%) cases. After the results obtained, it could be said that total reverse shoulder replacement achieved encouraging results in the short term for the treatment of glenohumeral arthrosis and massive tears of the rotary cuff. On analysing our series, it can be seen that the complications rate is much higher when it is used to treat fracture sequelae in which there is a loss of proximal humerus bone stock. Copyright © 2014 SECOT. Published by Elsevier Espana. All rights reserved.

Improving Timely Resident Follow-Up and Communication of Results in Ambulatory Clinics Utilizing a Web-Based Audit and Feedback Module.

PubMed

Boggan, Joel C; Swaminathan, Aparna; Thomas, Samantha; Simel, David L; Zaas, Aimee K; Bae, Jonathan G

2017-04-01

Failure to follow up and communicate test results to patients in outpatient settings may lead to diagnostic and therapeutic delays. Residents are less likely than attending physicians to report results to patients, and may face additional barriers to reporting, given competing clinical responsibilities. This study aimed to improve the rates of communicating test results to patients in resident ambulatory clinics. We performed an internal medicine, residency-wide, pre- and postintervention, quality improvement project using audit and feedback. Residents performed audits of ambulatory patients requiring laboratory or radiologic testing by means of a shared online interface. The intervention consisted of an educational module viewed with initial audits, development of a personalized improvement plan after Phase 1, and repeated real-time feedback of individual relative performance compared at clinic and program levels. Outcomes included results communicated within 14 days and prespecified "significant" results communicated within 72 hours. A total of 76 of 86 eligible residents (88%) reviewed 1713 individual ambulatory patients' charts in Phase 1, and 73 residents (85%) reviewed 1509 charts in Phase 2. Follow-up rates were higher in Phase 2 than Phase 1 for communicating results within 14 days and significant results within 72 hours (85% versus 78%, P  < .001; and 82% versus 70%, P  = .002, respectively). Communication of "significant" results was more likely to occur via telephone, compared with communication of nonsignificant results. Participation in a shared audit and feedback quality improvement project can improve rates of resident follow-up and communication of results, although communication gaps remained.

Improving site selection in clinical studies: a standardised, objective, multistep method and first experience results.

PubMed

Hurtado-Chong, Anahí; Joeris, Alexander; Hess, Denise; Blauth, Michael

2017-07-12

A considerable number of clinical studies experience delays, which result in increased duration and costs. In multicentre studies, patient recruitment is among the leading causes of delays. Poor site selection can result in low recruitment and bad data quality. Site selection is therefore crucial for study quality and completion, but currently no specific guidelines are available. Selection of sites adequate to participate in a prospective multicentre cohort study was performed through an open call using a newly developed objective multistep approach. The method is based on use of a network, definition of objective criteria and a systematic screening process. Out of 266 interested sites, 24 were shortlisted and finally 12 sites were selected to participate in the study. The steps in the process included an open call through a network, use of selection questionnaires tailored to the study, evaluation of responses using objective criteria and scripted telephone interviews. At each step, the number of candidate sites was quickly reduced leaving only the most promising candidates. Recruitment and quality of data went according to expectations in spite of the contracting problems faced with some sites. The results of our first experience with a standardised and objective method of site selection are encouraging. The site selection method described here can serve as a guideline for other researchers performing multicentre studies. ClinicalTrials.gov: NCT02297581. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Single-row vs. double-row arthroscopic rotator cuff repair: clinical and 3 Tesla MR arthrography results.

PubMed

Tudisco, Cosimo; Bisicchia, Salvatore; Savarese, Eugenio; Fiori, Roberto; Bartolucci, Dario A; Masala, Salvatore; Simonetti, Giovanni

2013-01-27

Arthroscopic rotator cuff repair has become popular in the last few years because it avoids large skin incisions and deltoid detachment and dysfunction. Earlier arthroscopic single-row (SR) repair methods achieved only partial restoration of the original footprint of the tendons of the rotator cuff, while double-row (DR) repair methods presented many biomechanical advantages and higher rates of tendon-to-bone healing. However, DR repair failed to demonstrate better clinical results than SR repair in clinical trials. MR imaging at 3 Tesla, especially with intra-articular contrast medium (MRA), showed a better diagnostic performance than 1.5 Tesla in the musculoskeletal setting. The objective of this study was to retrospectively evaluate the clinical and 3 Tesla MRA results in two groups of patients operated on for a medium-sized full-thickness rotator cuff tear with two different techniques. The first group consisted of 20 patients operated on with the SR technique; the second group consisted of 20 patients operated on with the DR technique. All patients were evaluated at a minimum of 3 years after surgery. The primary end point was the re-tear rate at 3 Tesla MRA. The secondary end points were the Constant-Murley Scale (CMS), the Simple Shoulder Test (SST) scores, surgical time and implant expense. The mean follow-up was 40 months in the SR group and 38.9 months in the DR group. The mean postoperative CMS was 70 in the SR group and 68 in the DR group. The mean SST score was 9.4 in the SR group and 10.1 in the DR group. The re-tear rate was 60% in the SR group and 25% in the DR group. Leakage of the contrast medium was observed in all patients. To the best of our knowledge, this is the first report on 3 Tesla MRA in the evaluation of two different techniques of rotator cuff repair. DR repair resulted in a statistically significant lower re-tear rate, with longer surgical time and higher implant expense, despite no difference in clinical outcomes. We think that

Supporting clinical engineering in Italy: results of a survey conducted by the AIIC.

PubMed

Faggiano, Francesco; Ritrovato, Matteo; Freda, Paola; Vivo, Liliana; D'Alessandro, Luigi; Derrico, Pietro

2012-01-01

This article presents the outcomes of a survey developed and conducted by the Italian Association of Clinical Engineers (AIIC) in 2010 [1]. The AIIC, affiliated with the International Federation for Medical and Biological Engineering (IFMBE) since 2003, conducted this in-depth survey to investigate the educational profile of clinical engineers (CEs) as well as the activities and organization of clinical engineering departments (CEDs) in Italy. The survey consisted of a six-section questionnaire designed by the AIIC Board, which was based on other previous international surveys of CEDs. The questionnaire was sent to the AIIC members and to the most important Italian health-care organizations.

Adaptive pathway development for Fabry disease: a clinical approach.

PubMed

Schuller, Yvonne; Arends, Maarten; Körver, Simon; Langeveld, Mirjam; Hollak, Carla E M

2018-06-01

Fabry disease (FD) is a rare X-chromosome-linked lysosomal storage disorder. Although initial expectations of enzyme replacement therapy (ERT) were high, it is now clear that real-world effectiveness is disappointing and evidence gathering has been inadequate. In retrospect, development of ERT for FD had several shortcomings. Little convincing evidence on the effectiveness existed at time of authorization. Also, post-marketing evaluation failed to generate sufficient and relevant data for adequate evaluation on effectiveness. Adaptive pathways might have benefitted ERT development by: (i) involving healthcare professionals, patients, health technology assessment bodies and payers in the development process; (ii) iterative development, starting with initial authorization in classical males; (iii) a clear real-world data collection plan; (iv) an independent disease registry; and (v) prescription control. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Clinical management of acute liver failure: Results of an international multi-center survey

PubMed Central

Rabinowich, Liane; Wendon, Julia; Bernal, William; Shibolet, Oren

2016-01-01

AIM To assess the practice of caring for acute liver failure (ALF) patients in varying geographic locations and medical centers. METHODS Members of the European Acute Liver Failure Consortium completed an 88-item questionnaire detailing management of ALF. Responses from 22 transplantation centers in 11 countries were analyzed, treating between 300 and 500 ALF cases and performing over 100 liver transplants (LT) for ALF annually. The questions pertained to details of the institution and their clinical activity, standards of care, referral and admission, ward- based care versus intensive care unit (ICU) as well as questions regarding liver transplantation - including criteria, limitations, and perceived performance. Clinical data was also collected from 13 centres over a 3 mo period. RESULTS The interval between referral and admission of ALF patients to specialized units was usually less than 24 h and once admitted, treatment was provided by a multidisciplinary team. Principles of care of patients with ALF were similar among centers, particularly in relation to recognition of severity and care of the more critically ill. Centers exhibited similarities in thresholds for ICU admission and management of severe hepatic encephalopathy. Over 80% of centers administered n-acetyl-cysteine to ICU patients for non-paracetamol-related ALF. There was significant divergence in the use of prophylactic antibiotics and anti-fungals, lactulose, nutritional support and imaging investigations in admitted patients and in the monitoring and treatment of intra-cranial pressure (ICP). ICP monitoring was employed in 12 centers, with the most common indications being papilledema and renal failure. Most patients listed for transplantation underwent surgery within an average waiting time of 1-2 d. Over a period of 3 mo clinical data from 85 ALF patients was collected. Overall patient survival at 90-d was 76%. Thirty six percent of patients underwent emergency LT, with a 90% post transplant

A multidisciplinary audit of clinical coding accuracy in otolaryngology: financial, managerial and clinical governance considerations under payment-by-results.

PubMed

Nouraei, S A R; O'Hanlon, S; Butler, C R; Hadovsky, A; Donald, E; Benjamin, E; Sandhu, G S

2009-02-01

To audit the accuracy of otolaryngology clinical coding and identify ways of improving it. Prospective multidisciplinary audit, using the 'national standard clinical coding audit' methodology supplemented by 'double-reading and arbitration'. Teaching-hospital otolaryngology and clinical coding departments. Otolaryngology inpatient and day-surgery cases. Concordance between initial coding performed by a coder (first cycle) and final coding by a clinician-coder multidisciplinary team (MDT; second cycle) for primary and secondary diagnoses and procedures, and Health Resource Groupings (HRG) assignment. 1250 randomly-selected cases were studied. Coding errors occurred in 24.1% of cases (301/1250). The clinician-coder MDT reassigned 48 primary diagnoses and 186 primary procedures and identified a further 209 initially-missed secondary diagnoses and procedures. In 203 cases, patient's initial HRG changed. Incorrect coding caused an average revenue loss of 174.90 pounds per patient (14.7%) of which 60% of the total income variance was due to miscoding of a eight highly-complex head and neck cancer cases. The 'HRG drift' created the appearance of disproportionate resource utilisation when treating 'simple' cases. At our institution the total cost of maintaining a clinician-coder MDT was 4.8 times lower than the income regained through the double-reading process. This large audit of otolaryngology practice identifies a large degree of error in coding on discharge. This leads to significant loss of departmental revenue, and given that the same data is used for benchmarking and for making decisions about resource allocation, it distorts the picture of clinical practice. These can be rectified through implementing a cost-effective clinician-coder double-reading multidisciplinary team as part of a data-assurance clinical governance framework which we recommend should be established in hospitals.

Five-Year Safety and Performance Results from the Argus II Retinal Prosthesis System Clinical Trial.

PubMed

da Cruz, Lyndon; Dorn, Jessy D; Humayun, Mark S; Dagnelie, Gislin; Handa, James; Barale, Pierre-Olivier; Sahel, José-Alain; Stanga, Paulo E; Hafezi, Farhad; Safran, Avinoam B; Salzmann, Joel; Santos, Arturo; Birch, David; Spencer, Rand; Cideciyan, Artur V; de Juan, Eugene; Duncan, Jacque L; Eliott, Dean; Fawzi, Amani; Olmos de Koo, Lisa C; Ho, Allen C; Brown, Gary; Haller, Julia; Regillo, Carl; Del Priore, Lucian V; Arditi, Aries; Greenberg, Robert J

2016-10-01

The Argus II Retinal Prosthesis System (Second Sight Medical Products, Inc, Sylmar, CA) was developed to restore some vision to patients blind as a result of retinitis pigmentosa (RP) or outer retinal degeneration. A clinical trial was initiated in 2006 to study the long-term safety and efficacy of the Argus II System in patients with bare or no light perception resulting from end-stage RP. Prospective, multicenter, single-arm clinical trial. Within-patient controls included the nonimplanted fellow eye and patients' native residual vision compared with their vision with the Argus II. Thirty participants in 10 centers in the United States and Europe. The worse-seeing eye of blind patients was implanted with the Argus II. Patients wore glasses mounted with a small camera and a video processor that converted images into stimulation patterns sent to the electrode array on the retina. The primary outcome measures were safety (the number, seriousness, and relatedness of adverse events) and visual function, as measured by 3 computer-based, objective tests. Secondary measures included functional vision performance on objectively scored real-world tasks. Twenty-four of 30 patients remained implanted with functioning Argus II Systems at 5 years after implantation. Only 1 additional serious adverse event was experienced after the 3-year time point. Patients performed significantly better with the Argus II on than off on all visual function tests and functional vision tasks. The 5-year results of the Argus II trial support the long-term safety profile and benefit of the Argus II System for patients blind as a result of RP. The Argus II is the first and only retinal implant to have market approval in the European Economic Area, the United States, and Canada. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

A Nurse-Led Smoking Cessation Clinic--Quit Rate Results and Views of Participants

ERIC Educational Resources Information Center

Thompson, K. A.; Parahoo, A. K.; Blair, N.

2007-01-01

This study evaluated the success of a community nurse-led smoking cessation clinic, based in one trust in Northern Ireland. The clinic operated a group therapy approach. The study employed quantitative and qualitative methods of data collection to measure smoking behaviour and to gain the views of participants. Smoking behaviour was measured by…

Understanding and interpreting laboratory test results in the clinical management of diabetes mellitus

USDA-ARS?s Scientific Manuscript database

The clinical chemistry of diabetes care is unique in Endocrinology, because many of the commonly performed tests, such as assays for glucose, ketones and hemoglobin A1c, are done by the patient at home or by the nurse at the bedside or clinic. Hence, some may assume that these tests are accurate and...

Clinical and imaging services for TIA and minor stroke: results of two surveys of practice across the UK

PubMed Central

Brazzelli, Miriam; Shuler, Kirsten; Quayyum, Zahid; Hadley, Donald; Muir, Keith; McNamee, Paul; De Wilde, Janet; Dennis, Martin; Sandercock, Peter; Wardlaw, Joanna M

2013-01-01

Objectives Transient ischaemic attack (TIA) is a medical emergency requiring rapid access to effective, organised, stroke prevention. There are about 90 000 TIAs per year in the UK. We assessed whether stroke-prevention services in the UK meet Government targets. Design Cross-sectional survey. Setting All UK clinical and imaging stroke-prevention services. Intervention Electronic structured survey delivered over the web with automatic recording of responses into a database; reminders to non-respondents. The survey sought information on clinic frequency, staff, case-mix, details of brain and carotid artery imaging, medical and surgical treatments. Results 114 stroke clinical and 146 imaging surveys were completed (both response rates 45%). Stroke-prevention services were available in most (97%) centres but only 31% operated 7 days/week. Half of the clinic referrals were TIA mimics, most patients (75%) were prescribed secondary prevention prior to clinic referral, and nurses performed the medical assessment in 28% of centres. CT was the most common and fastest first-line investigation; MR, used in 51% of centres, mostly after CT, was delayed up to 2 weeks in 26%; 51% of centres omitted blood-sensitive (GRE/T2*) MR sequences. Carotid imaging was with ultrasound in 95% of centres and 59% performed endarterectomy within 1 week of deciding to operate. Conclusions Stroke-prevention services are widely available in the UK. Delays to MRI, its use in addition to CT while omitting key sequences to diagnose haemorrhage, limit the potential benefit of MRI in stroke prevention, but inflate costs. Assessing TIA mimics requires clinical neurology expertise yet nurses run 28% of clinics. Further improvements are still required for optimal stroke prevention. PMID:23929917

My Pride and Joy? Predicting Favoritism and Disfavoritism in Mother-Adult Child Relations.

PubMed

Suitor, J Jill; Gilligan, Megan; Peng, Siyun; Con, Gulcin; Rurka, Marissa; Pillemer, Karl

2016-08-01

In this article, we compare predictors of mothers' differentiation among their adult children regarding emotional closeness, pride, conflict, and disappointment. We distinguish between predictors of relational (closeness, conflict) and evaluative (pride, disappointment) dimensions of favoritism and disfavoritism. Multilevel modeling using data collected from 381 older mothers regarding their relationships with 1,421 adult children indicated that adult children's similarity of values played the most prominent role in predicting mothers' favoritism and disfavoritism, followed by children's gender. Children's deviant behaviors in adulthood predicted both pride and disappointment but neither relational dimension. Contrary to expectations, the quantitative analysis indicated that children's normative adult achievements were poor predictors of both relational and evaluative dimensions of mothers' differentiation. Qualitative data shed additional light on mothers' evaluations by revealing that disappointment was shaped by children's achievements relative to their mothers' values and expectations, rather than by the achievement of specific societal, educational, career, and marital milestones.

Getting clinical trial results into practice: design, implementation, and process evaluation of the ALLHAT Dissemination Project

PubMed Central

Bartholomew, L Kay; Cushman, William C; Cutler, Jeffrey A; Davis, Barry R; Dawson, Glenna; Einhorn, Paula T; Graumlich, James F; Piller, Linda B; Pressel, Sara; Roccella, Edward J; Simpson, Lara; Whelton, Paul K; Williard, Angela

2009-01-01

Background Conventional dissemination of clinical trial results has inconsistent impact on physician practices. A more comprehensive plan to influence determinants of prescribing practices is warranted. Purpose To report the response from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial to the National Heart, Lung, and Blood Institute’s requirement for dissemination and evaluation of trials with potential immediate public health applicability. Methods ALLHAT’s dissemination plan had two-components: 1) a traditional approach of media coverage, scientific presentation and publication; and 2) a theory-based approach targeting determinants of clinician behavior. Strategies included (1) academic detailing, in which physicians approach colleagues regarding blood pressure management, (2) direct patient messages to stimulate communication with physicians regarding blood pressure control, (3) approaches to formulary systems to use educational and economic incentives for evidence-based prescription, and (4) direct professional organization appeals to clinicians. Results One hundred and forty-seven Investigator Educators reported 1698 presentations to 18,524 clinicians in 41 states and the District of Columbia. The pre- and post-test responses of 1709 clinicians in the face-to-face meetings indicated significant changes in expectations for positive patient outcomes and intention to prescribe diuretics. Information was mailed to 55 individuals representing 20 professional organizations and to eight formulary systems. Direct-to-patient messages were provided to 14 sites that host patient newsletters and Web sites such as health plans and insurance companies, 62 print mass media outlets, and 12 broadcast media sites. Limitations It was not within the scope of the project to conduct a randomized trial of the impact of the dissemination. However, impact evaluation using quasi-experimental designs is ongoing. Conclusions A large multi

Update on the use of alitretinoin in treating chronic hand eczema.

PubMed

Ghasri, Pedram; Scheinfeld, Noah

2010-04-19

Chronic hand eczema is a debilitating dermatological condition with significant economic, social, and functional impacts. To date, conventional treatments such as topical corticosteroids, phototherapy, and systemic immunosuppressants have yielded disappointing results, owing to either a lack of efficacy or significant adverse events. Oral alitretinoin (9-cis-retinoic acid) is a unique panagonist retinoid with immunomodulatory and anti-inflammatory activity that has emerged as a novel treatment for chronic hand eczema. Several large-scale clinical studies have demonstrated oral alitretinoin's high efficacy rate of 28% to 89%, its safe tolerability profile, and its positive impact on quality of life, validating it as a therapeutic option for patients with severe chronic hand eczema refractory to standard treatment.

Update on the use of alitretinoin in treating chronic hand eczema

PubMed Central

Ghasri, Pedram; Scheinfeld, Noah

2010-01-01

Chronic hand eczema is a debilitating dermatological condition with significant economic, social, and functional impacts. To date, conventional treatments such as topical corticosteroids, phototherapy, and systemic immunosuppressants have yielded disappointing results, owing to either a lack of efficacy or significant adverse events. Oral alitretinoin (9-cis-retinoic acid) is a unique panagonist retinoid with immunomodulatory and anti-inflammatory activity that has emerged as a novel treatment for chronic hand eczema. Several large-scale clinical studies have demonstrated oral alitretinoin’s high efficacy rate of 28% to 89%, its safe tolerability profile, and its positive impact on quality of life, validating it as a therapeutic option for patients with severe chronic hand eczema refractory to standard treatment. PMID:21437060

Factors Associated With Burnout Among US Hospital Clinical Pharmacy Practitioners: Results of a Nationwide Pilot Survey.

PubMed

Jones, G Morgan; Roe, Neil A; Louden, Les; Tubbs, Crystal R

2017-12-01

Background: In health care, burnout has been defined as a psychological process whereby human service professionals attempting to positively impact the lives of others become overwhelmed and frustrated by unforeseen job stressors. Burnout among various physician groups who primarily practice in the hospital setting has been extensively studied; however, no evidence exists regarding burnout among hospital clinical pharmacists. Objective: The aim of this study was to characterize the level of and identify factors independently associated with burnout among clinical pharmacists practicing in an inpatient hospital setting within the United States. Methods: We conducted a prospective, cross-sectional pilot study utilizing an online, Qualtrics survey. Univariate analysis related to burnout was conducted, with multivariable logistic regression analysis used to identify factors independently associated with the burnout. Results: A total of 974 responses were analyzed (11.4% response rate). The majority were females who had practiced pharmacy for a median of 8 years. The burnout rate was high (61.2%) and largely driven by high emotional exhaustion. On multivariable analysis, we identified several subjective factors as being predictors of burnout, including inadequate administrative and teaching time, uncertainty of health care reform, too many nonclinical duties, difficult pharmacist colleagues, and feeling that contributions are underappreciated. Conclusions: The burnout rate of hospital clinical pharmacy providers was very high in this pilot survey. However, the overall response rate was low at 11.4%. The negative effects of burnout require further study and intervention to determine the influence of burnout on the lives of clinical pharmacists and on other health care-related outcomes.

Emergency contraception. Widely available and effective but disappointing as a public health intervention: a review

PubMed Central

Baird, D.T.; Cameron, S.; Evers, J.L.H.; Gemzell-Danielsson, K.; Glasier, A.; Moreau, C.; Trussell, J.; von Hertzen, H.; Crosignani, P.G.; La Vecchia, C.; Volpe, A.; Glasier, A.; Crosignani, P.G.

2015-01-01

Emergency contraception (EC) prevents pregnancy after unprotected sex or contraceptive failure. Use of EC has increased markedly in countries where a product is available over the counter, yet barriers to availability and use remain. Although effective in clinical trials, it has not yet been possible to show a public health benefit of EC in terms of reduction of unintended pregnancy rates. Selective progesterone receptor modulators developed as emergency contraceptives offer better effectiveness than levonorgestrel, but still EC is less effective than use of ongoing regular contraception. Methods which inhibit ovulation whenever they are taken or which act after ovulation to prevent implantation and strategies to increase the uptake of effective ongoing contraception after EC use would prevent more pregnancies. PMID:25678571

Preschool vision screening in a Swedish city region: results after alteration of criteria for referral to eye clinics.

PubMed

Hård, Anna-Lena; Sjödell, Lena; Borres, Magnus P; Zetterberg, Ingrid; Sjöstrand, Johan

2002-12-01

To investigate the results of preschool vision screening and to evaluate new referral criteria in a Swedish city region. Prior to 1992, all children with visual acuity (VA) of less than 0.8 at the age of 4 years were referred to an eye clinic. Since 1992, those with slightly reduced VA (0.65 in each eye or 0.65 in one eye and 0.8 in the other) have been retested at 5.5 years of age and referred if their VA is less than 0.8. In a prospective study, the results of vision testing were collected for all children (n = 483) born in 1989-92 inclusive and registered at one child health centre at 4 years of age. The study also involved 123 other children scheduled for retesting at the age of 5.5 years. The results of the examinations and treatments at the eye clinic are evaluated. Few of the children with slightly reduced VA who were retested at the age of 5.5 years had visual defects that required treatment. In those who were treated, the results of treatment were good. The new screening criteria appear to be appropriate and are recommended.

A review of the clinical evidence for complementary and alternative therapies in Parkinson's disease.

PubMed

Bega, Danny; Gonzalez-Latapi, Paulina; Zadikoff, Cindy; Simuni, Tanya

2014-10-01

No conventional treatment has been convincingly demonstrated to slow or stop the progression of Parkinson's disease (PD). Dopaminergic therapy is the gold standard for managing the motor disability associated with PD, but it falls short of managing all of the aspects of the disease that contribute to quality of life. Perhaps for this reason, an increasing number of patients are searching for a more holistic approach to healthcare. This is not to say that they are abandoning the standard and effective symptomatic therapies for PD, but rather are complementing them with healthy living, mind-body practices, and natural products that empower patients to be active participants in their healthcare and widen the net under which disease modification might one day be achieved. Despite high rates of utilization of complementary and alternative medicine (CAM) practices, data on efficacy is generally limited, restricting physicians in providing guidance to interested patients. Exercise is now well-established as integral in the management of PD, but mind-body interventions such as Tai Chi that incorporate relaxation and mindfulness with physical activity should be routinely encouraged as well. While no comment can be made about neuroplastic or disease-modifying effects of mind-body interventions, patients should be encouraged to be as active as possible and engage with others in enjoyable and challenging activities such as dance, music therapy, and yoga. Many PD patients also choose to try herbs, vitamins, and neutraceuticals as part of a healthy lifestyle, with the added expectation that these products may lower free radical damage and protect them against further cell death. Evidence for neuroprotection is limited, but patients can be encouraged to maintain a healthy diet rich in "high-power," low-inflammatory foods, while at the same time receiving education that many promising natural products have produced disappointing results in clinical trials. It is vital that the

Heart rate prediction for coronary artery disease patients (CAD): Results of a clinical pilot study.

PubMed

Müller-von Aschwege, Frerk; Workowski, Anke; Willemsen, Detlev; Müller, Sebastian M; Hein, Andreas

2015-01-01

This paper describes the results of a pilot study with cardiac patients based on information that can be derived from a smartphone. The idea behind the study is to design a model for estimating the heart rate of a patient before an outdoor walking session for track planning, as well as using the model for guidance during an outdoor session. The model allows estimation of the heart rate several minutes in advance to guide the patient and avoid overstrain before its occurrence. This paper describes the first results of the clinical pilot study with cardiac patients taking β-blockers. 9 patients have been tested on a treadmill and during three outdoor sessions each. The results have been derived and three levels of improvement have been tested by cross validation. The overall result is an average Median Absolute Deviation (MAD) of 4.26 BPM between measured heart rate and smartphone sensor based model estimation.

North American Solitaire Stent Retriever Acute Stroke registry: post-marketing revascularization and clinical outcome results.

PubMed

Zaidat, Osama O; Castonguay, Alicia C; Gupta, Rishi; Sun, Chung-Huan J; Martin, Coleman; Holloway, William E; Mueller-Kronast, Nils; English, Joey D; Linfante, Italo; Dabus, Guilherme; Malisch, Tim W; Marden, Franklin A; Bozorgchami, Hormozd; Xavier, Andrew; Rai, Ansaar T; Froehler, Michael T; Badruddin, Aamir; Nguyen, Thanh N; Taqi, M Asif; Abraham, Michael G; Janardhan, Vallabh; Shaltoni, Hashem; Novakovic, Roberta; Yoo, Albert J; Abou-Chebl, Alex; Chen, Peng R; Britz, Gavin W; Kaushal, Ritesh; Nanda, Ashish; Issa, Mohammad A; Nogueira, Raul G

2014-10-01

Limited post-marketing data exist on the use of the Solitaire FR device in clinical practice. The North American Solitaire Stent Retriever Acute Stroke (NASA) registry aimed to assess the real world performance of the Solitaire FR device in contrast with the results from the SWIFT (Solitaire with the Intention for Thrombectomy) and TREVO 2 (Trevo versus Merci retrievers for thrombectomy revascularization of large vessel occlusions in acute ischemic stroke) trials. The investigator initiated NASA registry recruited North American sites to submit retrospective angiographic and clinical outcome data on consecutive acute ischemic stroke (AIS) patients treated with the Solitaire FR between March 2012 and February 2013. The primary outcome was a Thrombolysis in Myocardial Ischemia (TIMI) score of ≥2 or a Treatment in Cerebral Infarction (TICI) score of ≥2a. Secondary outcomes were 90 day modified Rankin Scale (mRS) score, mortality, and symptomatic intracranial hemorrhage. 354 patients underwent treatment for AIS using the Solitaire FR device in 24 centers. Mean time from onset to groin puncture was 363.4±239 min, mean fluoroscopy time was 32.9±25.7 min, and mean procedure time was 100.9±57.8 min. Recanalization outcome: TIMI ≥2 rate of 83.3% (315/354) and TICI ≥2a rate of 87.5% (310/354) compared with the operator reported TIMI ≥2 rate of 83% in SWIFT and TICI ≥2a rate of 85% in TREVO 2. 42% (132/315) of NASA patients demonstrated a 90 day mRS ≤2 compared with 37% (SWIFT) and 40% (TREVO 2). 90 day mortality was 30.2% (95/315) versus 17.2% (SWIFT) and 29% (TREVO 2). The NASA registry demonstrated that the Solitaire FR device performance in clinical practice is comparable with the SWIFT and TREVO 2 trial results. 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.

Update on the everolimus-eluting coronary stent system: results and implications from the SPIRIT clinical trial program

PubMed Central

Kirchner, R Michael; Abbott, J Dawn

2009-01-01

Drug-eluting stents (DES) have had a major impact in interventional cardiology. Compared to bare metal stents, they significantly reduce restenosis and the need for target vessel revascularization. Four DES are available in the US, the first-generation sirolimus-eluting (Cypher®) and paclitaxel-eluting (Taxus®) stents and later approved second-generation everolimus-eluting (Xience V®) and zotarolimus-eluting (Endeavor®) stents. The Xience V stent was approved on the basis of clinical efficacy and safety data from 3 studies in the SPIRIT clinical trial program. Within this trial series, the Xience V was superior to its bare metal stent counterpart, the Vision® stent, and noninferior to the paclitaxel-eluting stent for target vessel failure at 9 months. This review provides a comprehensive assessment of the data derived from both the pre- and post-approval randomized controlled trials and registry studies of Xience V that comprise the SPIRIT clinical trial program including recently published mid-term outcomes. The implications of the results in terms of interventional practice will be discussed. PMID:20057901

Home-use TriPollar RF device for facial skin tightening: Clinical study results.

PubMed

Beilin, Ghislaine

2011-04-01

Professional, non-invasive, anti-aging treatments based on radio-frequency (RF) technologies are popular for skin tightening and improvement of wrinkles. A new home-use RF device for facial treatments has recently been developed based on TriPollar™ technology. To evaluate the STOP™ home-use device for facial skin tightening using objective and subjective methods. Twenty-three female subjects used the STOP at home for a period of 6 weeks followed by a maintenance period of 6 weeks. Facial skin characteristics were objectively evaluated at baseline and at the end of the treatment and maintenance periods using a three-dimensional imaging system. Additionally, facial wrinkles were classified and subjects scored their satisfaction and sensations. Following STOP treatment, a statistically significant reduction of perioral and periorbital wrinkles was achieved in 90% and 95% of the patients, respectively, with an average periorbital wrinkle reduction of 41%. This objective result correlated well with the periorbital wrinkle classification result of 40%. All patients were satisfied to extremely satisfied with the treatments and all reported moderate to excellent visible results. The clinical study demonstrated the safety and efficacy of the STOP home-use device for facial skin tightening. Treatment can maintain a tighter and suppler skin with improvement of fine lines and wrinkles.

The management of isolated positive syphilis enzyme immunoassay results in HIV-negative patients attending a sexual health clinic.

PubMed

Thorley, Nicola; Adebayo, Michael; Smit, Erasmus; Radcliffe, Keith

2016-08-01

An unconfirmed positive treponemal enzyme immunoassay (enzyme immunoassay positive, Treponema pallidum particle agglutination negative and rapid plasma reagin negative) presents a clinical challenge to distinguish early syphilis infection from false-positive results. These cases are referred for syphilis line assay (INNO-LIA) and recalled for repeat syphilis serology. We performed a retrospective audit to establish the proportion of HIV-negative cases with unconfirmed positive enzyme immunoassay results, the proportion of these cases that received an INNO-LIA test and repeat syphilis serology testing and reviewed the clinical outcomes; 0.35% (80/22687) cases had an unconfirmed positive treponemal enzyme immunoassay result. Repeat syphilis serology was performed in 80% (64/80) cases, but no additional cases of syphilis were identified. Eighty-eight per cent (70/80) received an INNO-LIA test; 14% (5/37) unconfirmed enzyme immunoassay-positive cases with no prior history of syphilis were confirmed on INNO-LIA assay, supporting a diagnosis of latent syphilis. As a confirmatory treponemal test, the INNO-LIA assay may be more useful than repeat syphilis serological testing. © The Author(s) 2016.

Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop.

PubMed

Jabs, Douglas A; Nussenblatt, Robert B; Rosenbaum, James T

2005-09-01

To begin a process of standardizing the methods for reporting clinical data in the field of uveitis. Consensus workshop. Members of an international working group were surveyed about diagnostic terminology, inflammation grading schema, and outcome measures, and the results used to develop a series of proposals to better standardize the use of these entities. Small groups employed nominal group techniques to achieve consensus on several of these issues. The group affirmed that an anatomic classification of uveitis should be used as a framework for subsequent work on diagnostic criteria for specific uveitic syndromes, and that the classification of uveitis entities should be on the basis of the location of the inflammation and not on the presence of structural complications. Issues regarding the use of the terms "intermediate uveitis," "pars planitis," "panuveitis," and descriptors of the onset and course of the uveitis were addressed. The following were adopted: standardized grading schema for anterior chamber cells, anterior chamber flare, and for vitreous haze; standardized methods of recording structural complications of uveitis; standardized definitions of outcomes, including "inactive" inflammation, "improvement'; and "worsening" of the inflammation, and "corticosteroid sparing," and standardized guidelines for reporting visual acuity outcomes. A process of standardizing the approach to reporting clinical data in uveitis research has begun, and several terms have been standardized.

[Analysis of the results of the 2010 External Quality Control Program of the Spanish Society of Infectious Diseases and Clinical Microbiology].

PubMed

Ruiz de Gopegui Bordes, Enrique; Serrano, M del Remedio Guna; Orta Mira, Nieves; Ovies, María Rosario; Poveda, Marta; Cardona, Concepción Gimeno

2011-12-01

The External Quality Control Program of the Spanish Society of Infectious Diseases and Clinical Microbiology includes controls for bacteriology, serology, mycology, parasitology, mycobacteria, virology and molecular microbiology. This article presents the most important conclusions and lessons of the 2010 controls. As a whole, the results obtained in 2010 confirm the excellent skill and good technical standards found in previous years. However, erroneous results can be obtained in any laboratory and in clinically relevant determinations. The results of this program highlight the need to implement both internal and external controls to ensure maximal quality of microbiological tests(1). Copyright © 2011 Elsevier España S.L. All rights reserved.

Review of early clinical results and complications associated with oblique lumbar interbody fusion (OLIF).

PubMed

Phan, Kevin; Maharaj, Monish; Assem, Yusuf; Mobbs, Ralph J

2016-09-01

Lumbar interbody fusion represents an effective surgical intervention for patients with lumbar degenerative diseases, spondylolisthesis, disc herniation, pseudoarthrosis and spinal deformities. Traditionally, conventional open anterior lumbar interbody fusion and posterior/transforaminal lumbar interbody fusion techniques have been employed with excellent results, but each with their own advantages and caveats. Most recently, the antero-oblique trajectory has been introduced, providing yet another corridor to access the lumbar spine. Termed the oblique lumbar interbody fusion, this approach accesses the spine between the anterior vessels and psoas muscles, avoiding both sets of structures to allow efficient clearance of the disc space and application of a large interbody device to afford distraction for foraminal decompression and endplate preparation for rapid and thorough fusion. This review aims to summarize the early clinical results and complications of this new technique and discusses potential future directions of research. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Stalking: clinical and criminological considerations through the results of a research contribution].

PubMed

Pomilla, Antonella; D'Argenio, Alberto; Mastronardi, Vincenzo

2012-01-01

Among the extensive results supplied by the psychiatric literature on the subject of stalking, few studies focus on the analysis of persecutory behaviors carried out against mental health professionals, who also identified as one of the most affected sample of victims. Particularly, for studies conducted in this way, further examination requires differentiation according to gender type into the social and personal characteristics of the authors' behavior patterns displayed towards the victims. Aim. To obtaine results by an epidemiological survey conducted in public and private psychiatric care structures in the city of Rome, to assess the incidence of the phenomenon as well as gender differences in behavior patterns practised out by the author for the two sample considered. Methods. Administration of a questionnaire to a sample make up by psychiatrists working in out-patient services for the Departments of Mental Health (ASL) of Rome and to a sample of psychiatrists who practise their professional activity in the private sector. Results. Regarding the incidence of the phenomenon, an increased presence has been found in private mental health care settings in comparison to the public service; regarding to the distribution of the phenomenon according to the sexual identity of the authors among the two samples analyzed, a statistical prevalence of female authors has been found in the sample of private sector. Discussion. The health's professionals, so much liable of victimization, are poorly formed on the phenomenon. So it's urgent to operate with integrated approaches (informative trainings; strengthening of administrative and clinical policies of the profession; multidimensional assessment).

Clinical Outcome and Safety of Multilevel Vertebroplasty: Clinical Experience and Results

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

Mailli, Leto, E-mail: lmailli@hotmail.com; Filippiadis, Dimitrios K.; Brountzos, Elias N.

To compare safety and efficacy of percutaneous vertebroplasty (PVP) when treating up to three vertebrae or more than three vertebrae per session. We prospectively compared two groups of patients with symptomatic vertebral fractures who had no significant response to conservative therapy. Pathologic substrate included osteoporosis (n = 77), metastasis (n = 24), multiple myeloma (n = 13), hemangioma (n = 15), and lymphoma (n = 1). Group A patients (n = 94) underwent PVP of up to three treated vertebrae (n = 188). Group B patients (n = 36) underwent PVP with more than three treated vertebrae per session (nmore » = 220). Decreased pain and improved mobility were recorded the day after surgery and at 12 and 24 months after surgery per clinical evaluation and the use of numeric visual scales (NVS): the Greek Brief Pain Inventory, a linear analogue self-assessment questionnaire, and a World Health Organization questionnaire. Group A presented with a mean pain score of 7.9 {+-} 1.1 NVS units before PVP, which decreased to 2.1 {+-} 1.6, 2.0 {+-} 1.5 and 2.0 {+-} 1.5 NVS units the day after surgery and at 12 and 24 months after surgery, respectively. Group B presented with a mean pain score of 8.1 {+-} 1.3 NVS units before PVP, which decreased to 2.2 {+-} 1.3, 2.0 {+-} 1.5, and 2.1 {+-} 1.6 NVS units the day after surgery and at 12 and 24 months after surgery, respectively. Overall pain decrease and mobility improvement throughout the follow-up period presented no statistical significance neither between the two groups nor between different underlying aetiology. Reported cement leakages presented no statistical significance between the two groups (p = 0.365). PVP is an efficient and safe technique for symptomatic vertebral fractures independently of the vertebrae number treated per session.« less

Getting clinical trial results into practice: design, implementation, and process evaluation of the ALLHAT Dissemination Project.

PubMed

Bartholomew, L Kay; Cushman, William C; Cutler, Jeffrey A; Davis, Barry R; Dawson, Glenna; Einhorn, Paula T; Graumlich, James F; Piller, Linda B; Pressel, Sara; Roccella, Edward J; Simpson, Lara; Whelton, Paul K; Williard, Angela; Allhat Collaborative Research Group

2009-08-01

Conventional dissemination of clinical trial results has inconsistent impact on physician practices. A more comprehensive plan to influence determinants of prescribing practices is warranted. To report the response from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial to the National Heart, Lung, and Blood Institute's requirement for dissemination and evaluation of trials with potential immediate public health applicability. ALLHAT's dissemination plan had two-components: (1) a traditional approach of media coverage, scientific presentation, and publication; and (2) a theory-based approach targeting determinants of clinician behavior. Strategies included: (1) academic detailing, in which physicians approach colleagues regarding blood pressure management, (2) direct patient messages to stimulate communication with physicians regarding blood pressure control, (3) approaches to formulary systems to use educational and economic incentives for evidence-based prescription, and (4) direct professional organization appeals to clinicians. One hundred and forty-seven Investigator Educators reported 1698 presentations to 18,524 clinicians in 41 states and the District of Columbia. The pre- and post-test responses of 1709 clinicians in the face-to-face meetings indicated significant changes in expectations for positive patient outcomes and intention to prescribe diuretics. Information was mailed to 55 individuals representing 20 professional organizations and to eight formulary systems. Direct-to-patient messages were provided to 14 sites that host patient newsletters and Web sites such as health plans and insurance companies, 62 print mass media outlets, and 12 broadcast media sites. It was not within the scope of the project to conduct a randomized trial of the impact of the dissemination. However, impact evaluation using quasi-experimental designs is ongoing. A large multi-method dissemination of clinical trial results is feasible. Planning

Entheseal involvement in asymptomatic human immunodeficiency virus infected patients: preliminary results of a clinical and ultrasonographic study.

PubMed

Ciancio, Giovanni; Sighinolfi, Laura; Furini, Federica; Segala, Daniela; Farina, Ilaria; Galuppi, Elisa; De Stefani, Elena; Simone, Loredana; Boccia, Sergio; Grilli, Anastasio; Pazzi, Paolo; Libanore, Marco; Contini, Carlo; Govoni, Marcello

2018-05-24

As a strong association between human immunodeficiency virus (HIV) infection and spondyloarthritis (SpA) has been hypothesised, our main objective was to explore by power Doppler ultrasonography (PDUS) the presence of subclinical enthesitis in asymptomatic HIV patients. The presence of subclinical synovitis was also evaluated. Consecutive asymptomatic HIV patients were studied and compared with asymptomatic HCV patients and healthy controls (HC). All subjects underwent a clinical and PDUS bilateral examination of the following entheses and joints: epicondyle, quadriceps, patellar, Achilles and plantar fascia; wrists, II and III metacarpo-phalangeal, knee and ankle. Twenty-nine HIV, 32 HCV and 25 HC were recruited; 1.032 entheses and 860 joints were examined. Clinical diagnosis of enthesitis was made in 10.3% HIV patients, 6.2% HCV patients (p=0.66) and none HC (p=0.24). PDUS enthesitis was found in 72.4% HIV, 28.1% HCV (p=0.0008) and 12% HC (p<0.0001). Clinical diagnosis of synovitis was made in 3.4% HIV patients, 9.3% HCV patients (p=0.61) and none HC (p=1). PDUS abnormalities were documented in 24.1% HIV patients, 71.8% HCV patients (p=0.0003) and none HC (p=0.0001). In detecting enthesitis and synovitis, PDUS was more sensitive than clinical examination both in HIV and HCV patients. Our preliminary study shows the high frequency of PDUS enthesitis in asymptomatic HIV patients, which highlights the close link between HIV and SpA. Further studies are desirable on a larger number of HIV patients to confirm these results. PDUS proved to be more sensitive than clinical examination in detecting subclinical involvement of entheses and joints.

Quantum molecular resonance technology in hard-to-heal extremity wounds: histological and clinical results.

PubMed

Fraccalvieri, Marco; Salomone, Marco; Di Santo, Claudia; Ruka, Erind; Morozzo, Umberto; Bruschi, Stefano

2017-12-01

Chronic wounds are commonly associated with high morbidity rates due to the patient's need of frequent dressing changes and repeated visits to the outpatient wound clinic. Furthermore, chronic wounds are often characterised by severe pain, which can cause significant disability to the patient. New technologies aim to develop an optimal device to reduce discomfort of the patient and to heal wounds. The device Rexon-age ® is introduced for the first time in wound healing, and preliminary data on clinical and histological results are shown. From April 2014 to April 2015, 11 patients - 7 females and 4 males - were enrolled in the present study. The study was conducted at the Plastic and Reconstructive Institute of the Università degli Studi di Torino, Città della Salute e della Scienza of Torino, Italy. For histological characterisation, pre- and post-treatment biopsies on the wound bed were performed. Data regarding age, gender, weight, height, comorbidity, drug therapy and topical pre-treatment and dressings of the wound were collected as well. Moreover, local factors regarding the wound data were as follows: aetiology, time of the wound formation until first Rexon-age treatment, wound dimensions, wound bed, moisture, margins and anatomical region of the wound. A visual analogue scale (VAS) was used to monitor the pain before and after each treatment. Rexon-age treatment resulted in improvement in granulation tissue and wound contraction. Moreover, a significant reduction of pain was observed with the reduction of painkillers drug usage. Among these Rexon-age-treated patients, three patients displayed 60-80% reduction in pain intensity, and two patients showed complete pain relief. In outpatient follow-up appointments, we registered long-term durability of pain relief. As assessed by histological analyses, post-treatment biopsies of all nine patients revealed a decreased amount of inflammatory cells and lower expression levels of metalloproteinases (e.g. MMP9). We

Three clinical experiences with SNP array results consistent with parental incest: a narrative with lessons learned.

PubMed

Helm, Benjamin M; Langley, Katherine; Spangler, Brooke; Vergano, Samantha

2014-08-01

Single nucleotide polymorphism microarrays have the ability to reveal parental consanguinity which may or may not be known to healthcare providers. Consanguinity can have significant implications for the health of patients and for individual and family psychosocial well-being. These results often present ethical and legal dilemmas that can have important ramifications. Unexpected consanguinity can be confounding to healthcare professionals who may be unprepared to handle these results or to communicate them to families or other appropriate representatives. There are few published accounts of experiences with consanguinity and SNP arrays. In this paper we discuss three cases where molecular evidence of parental incest was identified by SNP microarray. We hope to further highlight consanguinity as a potential incidental finding, how the cases were handled by the clinical team, and what resources were found to be most helpful. This paper aims to contribute further to professional discourse on incidental findings with genomic technology and how they were addressed clinically. These experiences may provide some guidance on how others can prepare for these findings and help improve practice. As genetic and genomic testing is utilized more by non-genetics providers, we also hope to inform about the importance of engaging with geneticists and genetic counselors when addressing these findings.

Physicians' perspective on the clinical meaningfulness of inflammatory bowel disease trial results: an International Organization for the Study of Inflammatory Bowel Disease (IOIBD) survey.

PubMed

Olivera, P; Sandborn, W J; Panés, J; Baumann, C; D'Haens, G; Vermeire, S; Danese, S; Peyrin-Biroulet, L

2018-03-01

Several novel compounds are being developed for inflammatory bowel diseases (IBD). In addition, biosimilar drugs are being approved. An increasing number of head-to-head, superiority and non-inferiority trials in patients with IBD are expected in the future. The clinical relevance of the magnitude of the effect size is often debated. To better understand physicians' perspectives on the clinical meaningfulness of IBD trial results. We conducted an online survey among all IOIBD (International Organization for the Study of Inflammatory Bowel Diseases) members, asking their opinion on the clinical relevance of the results of IBD trials. Forty-six IOIBD members responded to the survey (52.3%). In biologic-naïve ulcerative colitis (UC) and Crohn's disease (CD) patients, most of the participants considered a 15% difference with placebo for clinical remission and endoscopic remission to be clinically relevant. In head-to-head trials, most of participants considerer a 10% difference between groups for clinical remission and endoscopic remission to be clinically relevant. Half of respondents considered 10% to be an adequate margin in non-inferiority trials. In bioequivalence studies, most of the participants considered adequate a ± 5% difference between a biosimilar and the originator for pharmacokinetic parameters, efficacy, safety and immunogenicity. Regarding safety, the difference between two drugs considered clinically relevant varied from 1% to 5%, depending on the type of adverse event. This is the first survey exploring how physicians perceive IBD trial results, providing an estimation of the magnitude of the difference between treatment arms that may directly influence clinical practice. © 2018 John Wiley & Sons Ltd.

[Statin associated myopathy in clinical practice. Results of DAMA study].

PubMed

Millán, Jesús; Pedro-Botet, Juan; Climent, Elisenda; Millán, Joaquín; Rius, Joan

Muscle symptoms, with or without elevation of creatin kinase are one of the main adverse effects of statin therapy, a fact that sometimes limits their use. The aim of this study was to evaluate the clinical characteristics of patients treated with statins who have complained muscle symptoms and to identify possible predictive factors. A cross-sectional one-visit, non-interventional, national multicenter study including patients of both sexes over 18 years of age referred for past or present muscle symptoms associated with statin therapy was conducted. 3,845 patients were recruited from a one-day record from 2,001 physicians. Myalgia was present in 78.2% of patients included in the study, myositis in 19.3%, and rhabdomyolysis in 2.5%. Patients reported muscle pain in 77.5% of statin-treated individuals, general weakness 42.7%, and cramps 28.1%. Kidney failure, intense physical exercise, alcohol consumption (>30g/d in men and 20g/d in women) and abdominal obesity were the clinical situations associated with statin myopathy. Myalgia followed by myositis are the most frequent statin-related side effects. It should be recommended control environmental factors such as intense exercise and alcohol intake as well as abdominal obesity and renal function of the patient treated with statins. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

False-Positive Xpert MTB/RIF Results in Retested Patients with Previous Tuberculosis: Frequency, Profile, and Prospective Clinical Outcomes.

PubMed

Theron, Grant; Venter, Rouxjeane; Smith, Liezel; Esmail, Aliasgar; Randall, Philippa; Sood, Vishesh; Oelfese, Suzette; Calligaro, Greg; Warren, Robin; Dheda, Keertan

2018-03-01

Globally, Xpert MTB/RIF (Xpert) is the most widely used PCR test for the diagnosis of tuberculosis (TB). Positive results in previously treated patients, which are due to old DNA or active disease, are a diagnostic dilemma. We prospectively retested sputum from 238 patients, irrespective of current symptoms, who were previously diagnosed to be Xpert positive and treated successfully. Patients who retested as Xpert positive and culture negative were exhaustively investigated (repeat culture, chest radiography, bronchoscopy with bronchoalveolar lavage, long-term clinical follow-up). We evaluated whether the duration since previous treatment completion, mycobacterial burden (the Xpert cycle threshold [ C T ] value), and reclassification of Xpert-positive results with a very low semiquantitation level to Xpert-negative results reduced the rate of false positivity. A total of 229/238 (96%) of patients were culture negative. Sixteen of 229 (7%) were Xpert positive a median of 11 months (interquartile range, 5 to 19 months) after treatment completion. The specificity was 93% (95% confidence interval [CI], 89 to 96%). Nine of 15 (40%) Xpert-positive, culture-negative patients reverted to Xpert negative after 2 to 3 months (1 patient declined further participation). Patients with false-positive Xpert results had a lower mycobacterial burden than patients with true-positive Xpert results ( C T , 28.7 [95% CI, 27.2 to 30.4] versus 17.6 [95% CI, 16.9 to 18.2]; P < 0.001), an increased likelihood of a chest radiograph not compatible with active TB (5/15 patients versus 0/5 patients; P = 0.026), and less-viscous sputum (15/16 patients versus 2/5 patients whose sputum was graded as mucoid or less; P = 0.038). All patients who initially retested as Xpert positive and culture negative ("Xpert false positive") were clinically well without treatment after follow-up. The duration since the previous treatment poorly predicted false-positive results (a duration of ≤2 years identified

European survey on ethical and legal framework of clinical trials in paediatrics: results and perspectives.

PubMed

Altavilla, Annagrazia; Giaquinto, Carlo; Ceci, Adriana

2008-09-01

This article constitutes a synthesis and analysis of the results of the "Survey on the ethical and legal frameworks existing in Europe for paediatric clinical trials" carried out by the European network TEDDY. TEDDY is a "Network of Excellence" funded by the Sixth EU Framework Programme (FP6). It began its activities in June 2005 and it is scheduled to run until 2010. It involves 19 partners in 11 countries. The overall goal of TEDDY is to promote the availability of safe and effective medicines to children in Europe by integrating existing expertise and the good practices. In the domain of ethics, the main aim of TEDDY is raise the awareness of the public and researchers concerning issues linked to biomedical research in paediatrics, by contributing to developing the debate on the ethical and legal stakes, as well as the potential deviations, in order to ensure the best possible protection of children participating in clinical trials. This study, with twenty-seven participating countries (23 EU Member States and 4 countries associated to the Fifth and Sixth EU Framework Programme), proposes to highlight the existing differences in the legislation of European countries concerning the procedure of consent, as well as the guarantee of the paediatric expertise within the Ethics Committees which are in charge of evaluating research protocols. The study shows that, even though the Directive 2001/20/EC has been transposed, the value attributed to the consent of minors who participate in clinical trials is different depending on the European state. Despite the general rule of having the written consent of the legal representative of the minor, over a certain age (different in relation to each state) and under certain conditions, to give the consent alone to participate in biomedical research. Furthermore, there is an Ethics Committee for minors in only four countries. In addition, we illustrate the lack of information and in-depth debate in Europe concerning the ethical

Heterogeneity prevails: the state of clinical trial data management in Europe - results of a survey of ECRIN centres

PubMed Central

2010-01-01

Background The use of Clinical Data Management Systems (CDMS) has become essential in clinical trials to handle the increasing amount of data that must be collected and analyzed. With a CDMS trial data are captured at investigator sites with "electronic Case Report Forms". Although more and more of these electronic data management systems are used in academic research centres an overview of CDMS products and of available data management and quality management resources for academic clinical trials in Europe is missing. Methods The ECRIN (European Clinical Research Infrastructure Network) data management working group conducted a two-part standardized survey on data management, software tools, and quality management for clinical trials. The questionnaires were answered by nearly 80 centres/units (with an overall response rate of 47% and 43%) from 12 European countries and EORTC. Results Our survey shows that about 90% of centres have a CDMS in routine use. Of these CDMS nearly 50% are commercial systems; Open Source solutions don't play a major role. In general, solutions used for clinical data management are very heterogeneous: 20 different commercial CDMS products (7 Open Source solutions) in addition to 17/18 proprietary systems are in use. The most widely employed CDMS products are MACRO™ and Capture System™, followed by solutions that are used in at least 3 centres: eResearch Network™, CleanWeb™, GCP Base™ and SAS™. Although quality management systems for data management are in place in most centres/units, there exist some deficits in the area of system validation. Conclusions Because the considerable heterogeneity of data management software solutions may be a hindrance to cooperation based on trial data exchange, standards like CDISC (Clinical Data Interchange Standard Consortium) should be implemented more widely. In a heterogeneous environment the use of data standards can simplify data exchange, increase the quality of data and prepare centres

Clinical results of resection arthrodesis by triangular external fixation for posttraumatic arthrosis of the ankle joint in 89 cases

PubMed Central

2009-01-01

The methods for ankle arthrodesis differ significantly, probably a sign that no method is clearly superior to others. In the last ten years there is a clear favour toward internal fixation. We retrospectively evaluate the technique and evaluate the clinical long term results of external fixation in a triangular frame. Patients and Methods From 1994 to 2001 a consecutive series of 95 patients with end stage arthritis of the ankle joint were treated. Retrospectively the case notes were evaluated regarding trauma history, medical complaints, further injuries and illnesses, walking and pain status and occupational issues and the clinical examination before arthrodesis. Mean age at the index procedure was 45.4 years (18-82), 67 patients were male (70.5%). Via a bilateral approach the malleoli and the joint surfaces were resected. An AO fixator was applied with two Steinmann-nails inserted with approximately 8 cm distance in the distal tibia, one in the neck of the talus and one in the dorsal calcaneus. The fixator was removed after approximately 12 weeks. Follow up examination at mean 4.4 years included a standardised questionnaire and a clinical examination including the criteria of the AOFAS-Score and radiographs. Results: Due to different complications, 8 (8.9%) further surgical procedures were necessary including 1 below knee amputation. In 4 patients a non-union of the ankle arthrodesis developed (4.5%). The mean AOFAS score improved from 20.8 to 69.3 points. Conclusion Non-union rates and clinical results of arthrodesis by triangular external fixation of the ankle joint do not differ to internal fixation methods. The complication rate and the reduced patient comfort reserve this method mainly for infected arthritis and complicated soft tissue situations. PMID:19258207

Review of Adjuvant Radiochemotherapy for Resected Pancreatic Cancer and Results From Mayo Clinic for the 5th JUCTS Symposium

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

Miller, Robert C.; Iott, Matthew J.; Corsini, Michele M.

2009-10-01

Purpose: To present an overview of Phase III trials in adjuvant therapy for pancreatic cancer and review outcomes at the Mayo Clinic after adjuvant radiochemotherapy (RT/CT) for resected pancreatic cancer. Methods and Materials: A literature review and a retrospective review of 472 patients who underwent an R0 resection for T1-3N0-1M0 invasive carcinoma of the pancreas from 1975 to 2005 at the Mayo Clinic, Rochester, MN. Patients with metastatic or unresectable disease at the time of surgery, positive surgical margins, or indolent tumors and those treated with intraoperative radiotherapy were excluded from the analysis. Median radiotherapy dose was 50.4Gy in 28more » fractions, with 98% of patients receiving concurrent 5-fluorouracil- based chemotherapy. Results: Median follow-up was 2.7 years. Median overall survival (OS) was 1.8 years. Median OS after adjuvant RT/CT was 2.1 vs. 1.6 years for surgery alone (p = 0.001). The 2-y OS was 50% vs. 39%, and 5-y was 28% vs. 17% for patients receiving RT/CT vs. surgery alone. Univariate and multivariate analysis revealed that adverse prognostic factors were positive lymph nodes (risk ratio [RR] 1.3, p < 0.001) and high histologic grade (RR 1.2, p < 0.001). T3 tumor status was found significant on univariate analysis only (RR 1.1, p = 0.07). Conclusions: Results from recent clinical trials support the use of adjuvant chemotherapy in resected pancreatic cancer. The role of radiochemotherapy in adjuvant treatment of pancreatic cancer remains a topic of debate. Results from the Mayo Clinic suggest improved outcomes after the administration of adjuvant radiochemotherapy after a complete resection of invasive pancreatic malignancies.« less

Boron neutron capture therapy (BNCT) for newly-diagnosed glioblastoma: comparison of clinical results obtained with BNCT and conventional treatment.

PubMed

Kageji, Teruyoshi; Nagahiro, Shinji; Mizobuchi, Yoshifumi; Matsuzaki, Kazuhito; Nakagawa, Yoshinobu; Kumada, Hiroaki

2014-01-01

The purpose of this study was to evaluate the clinical outcome of boron neutron capture therapy (BNCT) and conventional treatment in patients with newly diagnosed glioblastoma. Since 1998 we treated 23 newly-diagosed GBM patients with BNCT without any additional chemotherapy. Their median survival time was 19.5 months; the 2-, 3-, and 5-year survival rates were 31.8%, 22.7%, and 9.1%, respectively. The clinical results of BNCT in patients with GBM are similar to those of recent conventional treatments based on radiotherapy with concomitant and adjuvant temozolomide.

Web Support for Weight-Loss Interventions: PREDIRCAM2 Clinical Trial Baseline Characteristics and Preliminary Results.

PubMed

Alcántara-Aragón, Valeria; Rodrigo-Cano, Susana; Lupianez-Barbero, Ascension; Martinez, María José; Martinez, Carmen; Tapia, José; Iniesta, José Manuel; Tenes, Susana; Urgell, Eulalia; Navarro, Gemma; Hernando, M Elena; Merino-Torres, Juan Francisco; de Leiva, Alberto; Gonzalez, Cintia

2018-05-01

An ongoing clinical trial is testing the efficacy of web telematic support in a structured program for obesity treatment and diabetes prevention. Participants were recruited from two tertiary-care hospitals and randomized to receive either a telematic intervention (TI) supported by PREDIRCAM2 web platform or a non-telematic intervention (NTI). All receive 1-year follow-up. Both interventions consist of tailored dietary and exercise prescriptions, based on a Mediterranean dietary pattern and general WHO exercise recommendations for adults. At 6 months, both groups have received 7 contacts, 3 exclusively telematic for the TI group. This is a preliminary result intention-to-treat analysis. One hundred eighty-three participants were recruited, with a mean body mass index of 34.75 ± 2.75 kg/m 2 . General dropout rate at 6 months was 26.8%. Weight changes were statistically significant at months 3 and 6 compared to baseline, -2.915 ± 0.24 kg, -3.29 ± 0.36 kg, respectively (P < 0.001), but not statistically significant between the 3- and 6-month time points -0.37 ± 0.21 kg (P = 0.24). Mean group differences showed that the TI group lost 1.61 ± 1.88 kg more than the NTI group (P = 0.39). Waist, waist/hip ratio, resting heart rate, blood pressure, HbA1c, and low-density lipoprotein cholesterol also showed statistically significant changes at 6 months, with no significant differences between groups. Weight loss in the TI group shows similar results as the usual care NTI group for weight loss and control of obesity comorbidities. At completion of the clinical trial, these results will be reevaluated to assess the potential role of web support in weight-loss maintenance and its cost-effectiveness.

Brentuximab vedotin in relapsed/refractory Hodgkin’s lymphoma: the Italian experience and results of its use in daily clinical practice outside clinical trials

PubMed Central

Zinzani, Pier Luigi; Viviani, Simonetta; Anastasia, Antonella; Vitolo, Umberto; Luminari, Stefano; Zaja, Francesco; Corradini, Paolo; Spina, Michele; Brusamolino, Ercole; Gianni, Alessandro M.; Santoro, Armando; Botto, Barbara; Derenzini, Enrico; Pellegrini, Cinzia; Argnani, Lisa

2013-01-01

Clinical trial results indicate that brentuximab vedotin brings considerable promise for the treatment of patients with relapsed or refractory Hodgkin’s lymphoma. A retrospective multicenter study was conducted on 65 heavily pretreated patients who underwent therapy through a Named Patient Program in Italy (non trial-setting). The primary study endpoint was the objective response rate; secondary endpoints were safety, overall survival and progression-free survival. The best overall response rate (70.7%), including 21.5% complete responses, was observed at the first restaging after the third cycle of treatment. After a median follow up of 13.2 months, the overall survival rate at 20 months was 73.8% while the progression-free survival rate at 20 months was 24.2%. Globally nine patients are in continuous complete response with a median follow up of 14 months (range, 10–19 months). Four patients proceeded to autotransplantation and nine to allotransplantation. The most frequent extra-hematologic toxicity was peripheral neuropathy, observed in 21.5% of cases (9 patients with grade 1/2 and 5 patients with grade 3/4); neurological toxicity led to discontinuation of treatment in three patients and to dose reduction in four. In general the treatment was well tolerated and toxicities, both hematologic and extra-hematologic, were manageable. This report indicates and confirms that brentuximab vedotin as a single agent is effective and safe also when used in standard, everyday clinical practice outside a clinical trial. Best overall responses were recorded after three or four cycles and showed that brentuximab vedotin provides an effective bridge to further therapeutic interventions. PMID:23645687

Sub-xyphoid pleural drain as a determinant of functional capacity and clinical results after off-pump coronary artery bypass surgery: a randomized clinical trial.

PubMed

Guizilini, Solange; Alves, Daniel F; Bolzan, Douglas W; Cancio, Andreia S A; Regenga, Marisa M; Moreira, Rita S L; Trimer, Renata; Gomes, Walter J

2014-09-01

The aim of this trial was to compare functional capacity, pulmonary shunt fraction and clinical outcomes between patients undergoing pleurotomy with a pleural drain inserted in the sub-xyphoid position and patients with a pleural drain placed in the intercostal position after off-pump coronary artery bypass surgery. Patients were randomized into two groups according to the pleural drain site: Group II (n = 33 intercostal pleural drain); and Group SI (n = 35 sub-xyphoid pleural drain). Functional capacity was assessed by the distance covered on the 6-min walking test performed preoperatively and on postoperative day (POD) 5; in addition, pulmonary function test was determined preoperatively and on POD 1 and 5. Pulmonary shunt fraction was evaluated preoperatively and on POD 1, and clinical outcomes were recorded throughout the study. Group SI had better preservation of lung volumes and capacities in POD compared with Group II (P <0.05). Pulmonary shunt fraction increased in both groups postoperatively; however, Group SI showed a smaller pulmonary shunt fraction (0.26 ± 0.04 vs 0.21 ± 0.04%; P = 0.0014). Functional capacity was significantly reduced in both groups on POD 5; however, Group SI showed better preservation of functional capacity (P = 0.0001). Group SI had better postoperative clinical results, with lower incidence of atelectasis and pleural effusion (P <0.05), lower pain scores (P <0.0001), and shorter orotracheal intubation and hospitalization lengths (P <0.001). Sub-xyphoid pleural drain determined better functional capacity and exercise tolerance with a smaller pulmonary shunt fraction and improved clinical outcomes compared with intercostal pleural drainage after off-pump coronary artery bypass surgery. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Noninvasive assessment of mitral inertness [correction of inertance]: clinical results with numerical model validation.

PubMed

Firstenberg, M S; Greenberg, N L; Smedira, N G; McCarthy, P M; Garcia, M J; Thomas, J D

2001-01-01

Inertial forces (Mdv/dt) are a significant component of transmitral flow, but cannot be measured with Doppler echo. We validated a method of estimating Mdv/dt. Ten patients had a dual sensor transmitral (TM) catheter placed during cardiac surgery. Doppler and 2D echo was performed while acquiring LA and LV pressures. Mdv/dt was determined from the Bernoulli equation using Doppler velocities and TM gradients. Results were compared with numerical modeling. TM gradients (range: 1.04-14.24 mmHg) consisted of 74.0 +/- 11.0% inertial forcers (range: 0.6-12.9 mmHg). Multivariate analysis predicted Mdv/dt = -4.171(S/D (RATIO)) + 0.063(LAvolume-max) + 5. Using this equation, a strong relationship was obtained for the clinical dataset (y=0.98x - 0.045, r=0.90) and the results of numerical modeling (y=0.96x - 0.16, r=0.84). TM gradients are mainly inertial and, as validated by modeling, can be estimated with echocardiography.

The Influence of Counterfactual Thinking and Regret on Ethical Decision Making

ERIC Educational Resources Information Center

Celuch, Kevin; Saxby, Carl; Oeding, Jill

2015-01-01

The authors explore the influence of counterfactual thoughts in triggering the emotions of regret and disappointment in ethical decision making. Counterfactual thinking involves examining possible outcomes to events and is often explored in what-if scenarios. Findings support that subjects were able to transfer regret (but not disappointment)…

Evaluating the financial impact of clinical trials in oncology: results from a pilot study from the Association of American Cancer Institutes/Northwestern University clinical trials costs and charges project.

PubMed

Bennett, C L; Stinson, T J; Vogel, V; Robertson, L; Leedy, D; O'Brien, P; Hobbs, J; Sutton, T; Ruckdeschel, J C; Chirikos, T N; Weiner, R S; Ramsey, M M; Wicha, M S

2000-08-01

Medical care for clinical trials is often not reimbursed by insurers, primarily because of concern that medical care as part of clinical trials is expensive and not part of standard medical practice. In June 2000, President Clinton ordered Medicare to reimburse for medical care expenses incurred as part of cancer clinical trials, although many private insurers are concerned about the expense of this effort. To inform this policy debate, the costs and charges of care for patients on clinical trials are being evaluated. In this Association of American Cancer Institutes (AACI) Clinical Trials Costs and Charges pilot study, we describe the results and operational considerations of one of the first completed multisite economic analyses of clinical trials. Our pilot effort included assessment of total direct medical charges for 6 months of care for 35 case patients who received care on phase II clinical trials and for 35 matched controls (based on age, sex, disease, stage, and treatment period) at five AACI member cancer centers. Charge data were obtained for hospital and ancillary services from automated claims files at individual study institutions. The analyses were based on the perspective of a third-party payer. The mean age of the phase II clinical trial patients was 58.3 years versus 57.3 years for control patients. The study population included persons with cancer of the breast (n = 24), lung (n = 18), colon (n = 16), prostate (n = 4), and lymphoma (n = 8). The ratio of male-to-female patients was 3:4, with greater than 75% of patients having stage III to IV disease. Total mean charges for treatment from the time of study enrollment through 6 months were similar: $57,542 for clinical trial patients and $63,721 for control patients (1998 US$; P =.4) Multisite economic analyses of oncology clinical trials are in progress. Strategies that are not likely to overburden data managers and clinicians are possible to devise. However, these studies require careful planning

Transdiagnostic Internet-delivered cognitive behaviour therapy in Canada: An open trial comparing results of a specialized online clinic and nonspecialized community clinics.

PubMed

Hadjistavropoulos, H D; Nugent, M M; Alberts, N M; Staples, L; Dear, B F; Titov, N

2016-08-01

Effects of Internet-delivered cognitive behaviour therapy (ICBT) for anxiety and depression are not well understood when delivered in non-specialized as compared to specialized clinic settings. This open trial (n=458 patients) examined the benefits of transdiagnostic-ICBT when delivered in Canada by therapists (registered providers or graduate students) working in either a specialized online clinic or one of eight nonspecialized community clinics. Symptoms of depression and anxiety were assessed at pre-treatment, post-treatment and at 3-month follow-up. Completion rates and satisfaction were high. Significant and large reductions (effect sizes 1.17-1.31) were found on symptom measures. Completion rates, satisfaction levels and outcomes did not differ whether ICBT was delivered by therapists working in a specialized online clinic or nonspecialized community clinics. Differences were also not found between registered providers and graduate students, or therapists trained in psychology or another discipline. The findings support the public health potential of ICBT. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Clinical Results of Flexor Tendon Repair in Zone II Using a six Strand Double Loop Technique.

PubMed

Savvidou, Christiana; Tsai, Tsu-Min

2015-06-01

The purpose of this study is to report the clinical results after repair of flexor tendon zone II injuries utilizing a 6-strand double-loop technique and early post-operative active rehabilitation. We retrospectively reviewed 22 patients involving 51 cases with zone II flexor tendon repair using a six strand double loop technique from September 1996 to December 2012. Most common mechanism of injuries was sharp lacerations (86.5 %). Tendon injuries occurred equally in manual and non-manual workers and were work-related in 33 % of the cases. The Strickland score for active range of motion (ROM) postoperatively was excellent and good in the majority of the cases (81 %). The rupture rate was 1.9 %. The six strand double loop technique for Zone II flexor tendon repair leads to good and excellent motion in the majority of patients and low re- rupture rate. It is clinically effective and allows for early postoperative active rehabilitation.

Clinical examination results in individuals with functional ankle instability and ankle-sprain copers.

PubMed

Wright, Cynthia J; Arnold, Brent L; Ross, Scott E; Ketchum, Jessica; Ericksen, Jeffrey; Pidcoe, Peter

2013-01-01

Why some individuals with ankle sprains develop functional ankle instability and others do not (ie, copers) is unknown. Current understanding of the clinical profile of copers is limited. To contrast individuals with functional ankle instability (FAI), copers, and uninjured individuals on both self-reported variables and clinical examination findings. Cross-sectional study. Sports medicine research laboratory. Participants consisted of 23 individuals with a history of 1 or more ankle sprains and at least 2 episodes of giving way in the past year (FAI: Cumberland Ankle Instability Tool [CAIT] score = 20.52 ± 2.94, episodes of giving way = 5.8 ± 8.4 per month), 23 individuals with a history of a single ankle sprain and no subsequent episodes of instability (copers: CAIT score = 27.74 ± 1.69), and 23 individuals with no history of ankle sprain and no instability (uninjured: CAIT score = 28.78 ± 1.78). Self-reported disability was recorded using the CAIT and Foot and Ankle Ability Measure for Activities of Daily Living and for Sports. On clinical examination, ligamentous laxity and tenderness, range of motion (ROM), and pain at end ROM were recorded. Questionnaire scores for the CAIT, Foot and Ankle Ability Measure for Activities of Daily Living and for Sports, ankle inversion and anterior drawer laxity scores, pain with palpation of the lateral ligaments, ankle ROM, and pain at end ROM. Individuals with FAI had greater self-reported disability for all measures (P < .05). On clinical examination, individuals with FAI were more likely to have greater talar tilt laxity, pain with inversion, and limited sagittal-plane ROM than copers (P < .05). Differences in both self-reported disability and clinical examination variables distinguished individuals with FAI from copers at least 1 year after injury. Whether the deficits could be detected immediately postinjury to prospectively identify potential copers is unknown.

Transplantation of purified autologous fat: a 3-year follow-up is disappointing.

PubMed

Ersek, R A

1991-02-01

The idea of autologous fat microtransplants has recently resurfaced because of interest by the press. Past experiments have shown that small amounts of fat may be transplanted with an expected survival rate between 10 and 50 percent without ectodermis. A great fund of knowledge exists showing that skin grafts will survive quite dependably if their thickness is up to about 0.0020 inch. For the first week or so, they live by diffusion and inosculation, and then neovascularization enables them to continue viability. I have developed a technique whereby fat is harvested through a blunt cannula with minimal vacuum to prevent explosion of the cellular fat globules. Fibrin and cellular debris are removed, and the fat globules are separated from the free fat, blood, and other constituents of the aspirate. Individual, free-floating 1- to 3-mm adipose fragments are then suspended in nutrient solution and injected through an 18-gauge needle. Multiple radial pathways, with each fat segment being separated from the other by host tissue, maximizes the host-prosthesis interface and the possibility for exchange of nutrients. I have attempted this procedure in more than 100 patients with widely varying results. In acne pits of the face, no significant improvement could be noted 6 weeks after injection. For the first few weeks, a near-perfect result was obtained, but none of these transplants in scarred areas of this kind have been of benefit. Injection of 10 to 50 cc in other areas has resulted in some cells (perhaps 10 percent) surviving over 2 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical results of laparoscopic appendectomy in patients with complicated and uncomplicated appendicitis

PubMed Central

Bat, Orhan; Kaya, Hakan; Çelik, Hamit Kafkas; Şahbaz, Nuri Alper

2014-01-01

Acute appendicitis is the most common surgical emergency. The aim of this study was to evaluate the clinical results of laparoscopic appendectomy (LA) for the treatment of uncomplicated and complicated appendicitis. A retrospective analysis was performed who had undergone laparoscopic appendectomy for complicated appendicitis between January 2010 to October 2013. The diagnosis of acute appendicitis was established with physical examination, laboratory tests, and ultrasound examination. The patients were analysed for age, sex, conversion rate,operation time, postoperative infectious complications and length of hospital stay. A total of 452 patients were operated with LA. There were 362 (80.1%) uncomplicated (Group I) and 90 (19.1%) complicated Group (II) appendicitis.The intraabdominal abscess rate was 14.35% in Group I and 19.5% in Group II. The wound infection and rate of incisional hernia were also higher in Group II. The postoperative complications including intraabdominal abscess, wound infection and incisional hernia after LA in complicated appendicitis found high. LA should be performed very carefully in complicated appendicitis. PMID:25419386

Virtual reality for mobility devices: training applications and clinical results: a review.

PubMed

Erren-Wolters, Catelijne Victorien; van Dijk, Henk; de Kort, Alexander C; Ijzerman, Maarten J; Jannink, Michiel J

2007-06-01

Virtual reality technology is an emerging technology that possibly can address the problems encountered in training (elderly) people to handle a mobility device. The objective of this review was to study different virtual reality training applications as well as their clinical implication for patients with mobility problems. Computerized literature searches were performed using the MEDLINE, Cochrane, CIRRIE and REHABDATA databases. This resulted in eight peer reviewed journal articles. The included studies could be divided into three categories, on the basis of their study objective. Five studies were related to training driving skills, two to physical exercise training and one to leisure activity. This review suggests that virtual reality is a potentially useful means to improve the use of a mobility device, in training one's driving skills, for keeping up the physical condition and also in a way of leisure time activity. Although this field of research appears to be in its early stages, the included studies pointed out a promising transfer of training in a virtual environment to the real-life use of mobility devices.

Technical and Clinical Results After Percutaneous Angioplasty in Nonmedial Fibromuscular Dysplasia: Outcome After Endovascular Management of Unifocal Renal Artery Stenoses in 30 Patients

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

Barrier, Pierre, E-mail: p.barrier@gmail.com; Julien, Auriol; Guillaume, Canevet

2010-04-15

Although percutaneous transluminal renal angioplasty (PTRA) is associated with excellent results in medial fibromuscular dysplasia (FMD), the clinical and technical outcome in the less common nonmedial subtype of FMD is not clearly known. Angiographic PTRA results and clinical follow-up were documented, to report technical and clinical results in 30 patients with unifocal, nonmedial dysplastic stenoses. Balloon angioplasty was technically successful in only 65% of the lesions. Additional stenting, performed after PTRA failure in six patients, increased the initial technical success rate to 82%. Stenting was used in another lesion after restenosis, and long-term patency was achieved in only three ofmore » the seven stented lesions. Frequent restenoses and unusual complications were observed during follow-up. Stent fracture occurred in two cases. Overall, long-term clinical and technical successes were sustained in 70 and 76%, respectively. We conclude that nonmedial, unifocal renal artery dysplastic stenoses do not share the excellent prognosis of the medial type and that stenting should be avoided. Therefore, surgery should be considered in lesions remaining unresponsive to balloon dilatation, after a second PTRA attempt.« less

Impact of sending email reminders of the legal requirement for posting results on ClinicalTrials.gov: cohort embedded pragmatic randomized controlled trial.

PubMed

Maruani, Annabel; Boutron, Isabelle; Baron, Gabriel; Ravaud, Philippe

2014-09-19

To evaluate the impact of sending an email to responsible parties of completed trials that do not comply with the Food and Drug Administration Amendments Act 801 legislation, to remind them of the legal requirement to post results. Cohort embedded pragmatic randomized controlled trial. Trials registered on ClinicalTrials.gov. 190 out of 379 trials randomly selected by computer generated randomization list to receive the intervention (personalized emails structured as a survey and sent by one of us to responsible parties of the trials, indirectly reminding them of the legal requirement and potential penalties for non-compliance). The primary outcome was the proportion of results posted on ClinicalTrials.gov at three months. The secondary outcome was the proportion posted at six months. In a second step, two assessors blinded to the intervention group collected the date of the first results being received on ClinicalTrials.gov. A post hoc sensitivity analysis excluding trials wrongly included was performed. Among 379 trials included, 190 were randomized to receive the email intervention. The rate of posting of results did not differ at three months between trials with or without the intervention: 36/190 (19%) v 24/189 (13%), respectively (relative risk 1.5, 95% confidence interval 0.9 to 2.4, P=0.096) but did at six months: 46/190 (24%) v 27/189 (14%), 1.7, 1.1 to 2.6, P=0.014. In the sensitivity analysis, which excluded 48/379 trials (13%), 26/190 (14%) and 22/189 (12%), respectively, results were significant at three months (relative risk 5.1, 1.1 to 22.9, P=0.02) and at six months (4.1, 1.3 to 10.6, P=0.001). Sending email reminders about the FDA's legal requirement to post results at ClinicalTrials.gov improved significantly the posting rate at six months but not at three months.Trial registration ClinicalTrials.gov NCT01658254. © Maruani et al 2014.

Clinical evaluation of fiber-reinforced composite crowns in pulp-treated primary molars: 12-month results

PubMed Central

Mohammadzadeh, Zahra; Parisay, Iman; Mehrabkhani, Maryam; Madani, Azam Sadat; Mazhari, Fatemeh

2016-01-01

Objective: The aim of this study was to evaluate the clinical performance of tooth-colored fiber-reinforced composite (FRC) crowns in pulp-treated second primary mandibular teeth. Materials and Methods: This split-mouth randomized, clinical trial performed on 67 children between 3 and 6 years with two primary mandibular second molars requiring pulp treatment. After pulp therapy, the teeth were randomly assigned to stainless steel crown (SSC) or FRC crown groups. Modified United States Public Health Service criteria were used to evaluate marginal integrity, marginal discoloration, and secondary caries in FRC crowns at intervals of 3, 6, and 12 months. Retention rate and gingival health were also compared between the two groups. The data were analyzed using Friedman, Cochran, and McNemar's tests at a significance level of 0.05. Results: Intact marginal integrity in FRC crowns at 3, 6, and 12 months were 93.2%, 94.8%, and 94.2%, respectively. Marginal discoloration and secondary caries were not found at any of the FRC crowns. The retention rates of the FRC crowns were 100%, 98.3%, and 89.7% at 3, 6 and 12 months, respectively, whereas all the SSCs were found to be present and intact after 12 months (P = 0.016). There was no statistically significant difference between the two groups in gingival health. Conclusion: According to the results of this study, it seems that when esthetics is a concern, in cooperative patients with good oral hygiene, FRC crowns can be considered as a valuable procedure. PMID:28042269

Emergency contraception. Widely available and effective but disappointing as a public health intervention: a review.

PubMed

2015-04-01

Emergency contraception (EC) prevents pregnancy after unprotected sex or contraceptive failure. Use of EC has increased markedly in countries where a product is available over the counter, yet barriers to availability and use remain. Although effective in clinical trials, it has not yet been possible to show a public health benefit of EC in terms of reduction of unintended pregnancy rates. Selective progesterone receptor modulators developed as emergency contraceptives offer better effectiveness than levonorgestrel, but still EC is less effective than use of ongoing regular contraception. Methods which inhibit ovulation whenever they are taken or which act after ovulation to prevent implantation and strategies to increase the uptake of effective ongoing contraception after EC use would prevent more pregnancies. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Surrogate endpoints for clinical trials in primary sclerosing cholangitis: Review and results from an International PSC Study Group consensus process.

PubMed

Ponsioen, Cyriel Y; Chapman, Roger W; Chazouillères, Olivier; Hirschfield, Gideon M; Karlsen, Tom H; Lohse, Ansgar W; Pinzani, Massimo; Schrumpf, Erik; Trauner, Michael; Gores, Gregory J

2016-04-01

Primary sclerosing cholangitis (PSC) is a rare, but serious, cholestatic disease for which, to date, no effective therapy exists to halt disease progression toward end-stage liver disease. Clinical trial design to study drugs that improve prognosis is hampered by the relatively low event rate of clinically relevant endpoints. To overcome this shortcoming, there is an urgent need to identify appropriate surrogate endpoints. At present, there are no established surrogate endpoints. This article provides a critical review and describes the results of a consensus process initiated by the International PSC Study Group to delineate appropriate candidate surrogate endpoints at present for clinical trials in this frequently dismal disease. The consensus process resulted in a shortlist of five candidates as surrogate endpoints for measuring disease progression: alkaline phosphatase (ALP); transient elastography (TE); histology; combination of ALP+histology; and bilirubin. Of these, histology, ALP, and TE came out as the most promising. However, the expert panel concluded that no biomarker currently exceeds level 3 validation. Combining multiple endpoints is advisable. At present, there are insufficient data to support level 2 validation for any surrogate endpoint in PSC. Concerted efforts by all stakeholders are highly needed. Novel, promising noninvasive biomarkers are under study and should be incorporated as exploratory endpoints in clinical trials. © 2015 by the American Association for the Study of Liver Diseases.

Clinically applied procedures for human ovarian tissue cryopreservation result in different levels of efficacy and efficiency.

PubMed

Bastings, Lobke; Westphal, Johan R; Beerendonk, Catharina C M; Bekkers, Ruud L M; Zusterzeel, Petra L M; Hendriks, Jan C M; Braat, Didi D M; Peek, Ronald

2016-12-01

Different protocols are being used worldwide for the cryopreservation of human ovarian tissue for fertility preservation purposes. The efficiency and efficacy of the majority of these protocols has not been extensively evaluated, possibly resulting in sub-optimally cryopreserved ovarian tissue. To address the impact of this issue, we assessed the effects of two clinically successful human ovarian tissue slow-freezing cryopreservation procedures on the quality of the cryopreserved tissue. To differentiate between cryopreservation ( C ) versus thawing ( T ) related effects, four combinations of these two (A and B) very different cryopreservation/thawing protocols (A C A T , A C B T , B C A T , B C B T ) were studied. Before and after cryopreservation and thawing, the percentage of living and morphologically normal follicles, as well as the overall tissue viability, was assessed. Our experiments revealed that the choice of the cryopreservation protocol noticeably affected the overall tissue viability and percentage of living follicles, with a higher viability after protocol B C when compared to A C . No statistically significant differences in tissue viability were observed between the two thawing protocols, but thawing protocol B T required considerably more human effort and materials than thawing protocol A T . Tissue morphology was best retained using the B C A T combination. Our results indicate that extensive and systematical evaluation of clinically used protocols is warranted.

Do clinical practice education groups result in sustained change in GP prescribing?

PubMed

Richards, Dee; Toop, Les; Graham, Patrick

2003-04-01

Concern has been expressed at the poor uptake of evidence into clinical practice. This is despite the fact that continuing education is an embedded feature of quality assurance in general practice. There are a variety of clinical practice education methods available for dissemination of new evidence. Recent systematic reviews indicate that the effectiveness of these different strategies is extremely variable. Our aim was to determine whether a peer-led small group education pilot programme used to promote rational GP prescribing is an effective tool in changing practice when added to prescribing audit and feedback, academic detailing and educational bulletins, and to determine whether any effect seen decays over time. A retrospective analysis of a controlled trial of a small group education strategy with 24 month follow-up was carried out. The setting was an independent GPs association (IPA) of 230 GPs in the Christchurch New Zealand urban area. All intervention and control group GPs were already receiving prescribing audit and feedback, academic detailing and educational bulletins. The intervention group were the first 52 GPs to respond to an invitation to pilot the project. Two control groups were used, one group who joined the pilot later and a second group which included all other GPs in the IPA. The main outcome measures were targeted prescribing data for 12 months before and 24 months after each of four education sessions. An effect in the expected direction was seen in six of the eight key messages studied. This effect was statistically significant for five of the eight messages studied. The effect size varied between 7 and 40%. Where a positive effect was seen, the effect decayed with time but persisted to a significant level for 6-24 months of observation. The results support a positive effect of the education strategy on prescribing behaviour in the intervention group for most outcomes measured. The effect seen is statistically significant, sustained and

[Comparability study of analytical results between a group of clinical laboratories].

PubMed

Alsius-Serra, A; Ballbé-Anglada, M; López-Yeste, M L; Buxeda-Figuerola, M; Guillén-Campuzano, E; Juan-Pereira, L; Colomé-Mallolas, C; Caballé-Martín, I

2015-01-01

To describe the study of the comparability of the measurements levels of biological tests processed in biochemistry in Catlab's 4 laboratories. Quality requirements, coefficients of variation and total error (CV% and TE %) were established. Controls were verified with the precision requirements (CV%) in each test and each individual laboratory analyser. Fresh serum samples were used for the comparability study. The differences were analysed using a Microsoft Access® application that produces modified Bland-Altman plots. The comparison of 32 biological parameters that are performed in more than one laboratory and/or analyser generated 306 Bland-Altman graphs. Of these, 101 (33.1%) fell within the accepted range of values based on biological variability, and 205 (66.9%) required revision. Data were re-analysed based on consensus minimum specifications for analytical quality (consensus of the Asociación Española de Farmacéuticos Analistas (AEFA), the Sociedad Española de Bioquímica Clínica y Patología Molecular (SEQC), the Asociación Española de Biopatología Médica (AEBM) and the Sociedad Española de Hematología y Hemoterapia (SEHH), October 2013). With the new specifications, 170 comparisons (56%) fitted the requirements and 136 (44%) required additional review. Taking into account the number of points that exceeded the requirement, random errors, range of results in which discrepancies were detected, and range of clinical decision, it was shown that the 44% that required review were acceptable, and the 32 tests were comparable in all laboratories and analysers. The analysis of the results showed that the consensus requirements of the 4 scientific societies were met. However, each laboratory should aim to meet stricter criteria for total error. Copyright © 2015 SECA. Published by Elsevier Espana. All rights reserved.

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

Clinical Results and Mechanical Properties of the Carotid CGUARD Double-Layered Embolic Prevention Stent.

PubMed

Wissgott, Christian; Schmidt, Wolfram; Brandt-Wunderlich, Christoph; Behrens, Peter; Andresen, Reimer

2017-02-01

To report early clinical outcomes with a novel double-layer stent for the internal carotid artery (ICA) and the in vitro investigation of the stent's mechanical properties. A prospective single-center study enrolled 30 consecutive patients (mean age 73.1±6.3 years; 21 men) with symptomatic (n=25) or high-grade (n=5) ICA stenosis treated with the new double-layer carotid CGUARD Embolic Prevention System (EPS) stent, which has an inner open-cell nitinol design with an outer closed-cell polyethylene terephthalate layer. The average stenosis of the treated arteries was 84.1%±7.9% with a mean lesion length of 16.6±2.1 mm. In the laboratory, 8×40-mm stents where tested in vitro with respect to their radial force during expansion, the bending stiffness of the stent system and the expanded stent, as well as the collapse pressure in a thin and flexible sheath. The wall adaptation was assessed using fluoroscopy after stent release in step and curved vessel models. The stent was successfully implanted in all patients. No peri- or postprocedural complications occurred; no minor or major stroke was observed in the 6-month follow-up. The bending stiffness of the expanded stent was 63.1 N·mm 2 and (not unexpectedly) was clearly lower than that of the stent system (601.5 N·mm 2 ). The normalized radial force during expansion of the stent to 7.0 mm, consistent with in vivo sizing, was relatively high (0.056 N/mm), which correlates well with the collapse pressure of 0.17 bars. Vessel wall adaptation was harmonic and caused no straightening of the vessel after clinical application. Because of its structure, the novel CGUARD EPS stent is characterized by a high flexibility combined with a high radial force and very good plaque coverage. These first clinical results demonstrate a very safe implantation behavior without any stroke up to 6 months after the procedure.

An Integral Study of Galactic Black Hole States

NASA Technical Reports Server (NTRS)

2005-01-01

XTE 51550-564 was clearly detected with INTEGRAL out to 600 keV with the SPI, and is one of only two sources detected with IBISPICSIT. Software difficulties in analyzing the data prevented us from progressing with the analysis past the most elementary stages (see last year's report). The support from the INTEGRAL help desk has been very disappointing. People affiliated with INTEGRAL published a paper on the results of our data before we could master the reduction and analysis software. We are not the only group that got stuck with the analysis without adequate support from the INTEGRAL help desk. This was a rather disappointing experience as we lost many months of valuable time and efforts.

Enhancement of plaque removal efficacy by tooth brushing with baking soda dentifrices: results of five clinical studies.

PubMed

Putt, Mark S; Milleman, Kimberly R; Ghassemi, Annahita; Vorwerk, Linda M; Hooper, William J; Soparkar, Pramod M; Winston, Anthony E; Proskin, Howard M

2008-01-01

An earlier clinical study demonstrated that brushing with a commercial Arm & Hammer dentifrice containing baking soda physically removed significantly more plaque than brushing with either of two commercial dentifrices which did not contain baking soda. However, little has been done to confirm these results and to compare baking soda-containing dentifrices with more recently commercialized non-baking soda dentifrice formulations. The objective of this study was to compare commercial dentifrices containing 20% to 65% baking soda and commercial dentifrices without baking soda in enhancing plaque removal efficacy of tooth brushing. Five randomized, controlled, blinded, crossover clinical studies were performed among healthy adult volunteers who provided informed consent. After approximately 24 hours without oral hygiene, subjects with sufficient plaque were enrolled in the study phase. Plaque was scored before and after supervised brushing for one minute using the Turesky, et al. modification of the Quigley-Hein Plaque Index at six sites per tooth according to Soparkar's modification as described by Lobene, et al. In each study, wash-out periods with a regular dentifrice not evaluated in the study separated each product treatment. In all studies, every dentifrice exhibited a significant (p < 0.0001) reduction in 24-hour plaque scores. Between-group comparisons of whole mouth plaque scores in all five studies demonstrated that brushing with baking soda dentifrices resulted in statistically greater (p < 0.01) reductions in whole mouth mean plaque scores than brushing with dentifrices that did not contain baking soda. Results on other tooth surfaces, such as facial, lingual, proximal, and gingival surfaces also demonstrated statistically greater (p < 0.05) reductions in mean plaque scores for the baking soda-containing dentifrices as compared to the baking soda-free dentifrices. In three of the studies comparing different levels of baking soda, brushing with dentifrices

Application of topical mitomycin C to the base of shave-removed keloid scars to prevent their recurrence.

PubMed

Bailey, J N R; Waite, A E; Clayton, W J; Rustin, M H A

2007-04-01

Keloid scars are formed by over-activity of fibroblasts producing collagen and they cause significant morbidity both from their appearance and from their symptoms. Existing treatments are often unsatisfactory. Topical mitomycin C is known to inhibit fibroblast proliferation. To determine whether application of mitomycin C to the base of shave-removed keloids would prevent their recurrence. Ten patients had all or part of their keloid shave-removed. After haemostasis topical mitomycin C 1 mg mL(-1) was applied for 3 min. This application was repeated after 3 weeks. The keloids were photographed before treatment and the patients were reviewed every 2 months for a total of 6 months when a final photograph of the keloid site was taken. The patients and the Clinical Trials Unit staff scored the outcome on a linear analogue scale of 0-10, where 0 = disappointed and 10 = delighted. The pretreatment and 6-month post-treatment photographs were also assessed by two dermatologists who were not involved in the clinical trial. Four of the 10 patients were delighted with the outcome of treatment and only one was disappointed. On average there was an 80% satisfied outcome. This new treatment of keloids has been shown to be effective in the majority of patients but further studies are required to confirm this benefit.

[First clinical results using a pulsed dye laser Rhodamine 590 lithotripter in treatment of ureteral calculi].

PubMed

Jichlinski, P; Bonard, M; von Niederhäusern, W; Delacrétaz, G; Rink, K; Lambelet, P; Klohn, M; Bolle, J F; Graber, P

1991-09-01

A collaborative study about a pulsed dye laser Rhodamin 590 was undergone, 2 years ago, between the laser application center of EPFL and both urological departments of the university of Geneva and the university of Lausanne. First clinical results are presented. Ten patients have been treated for various ureteral stones, mainly calcium oxalate stones. Laser fragmentation was successful in seven cases. No serious complication was noted. Fragmentation efficiency seems better with a 320 microns fiber than with a 200 microns fiber.

Results from EuCliD (European Clinical Dialysis Database): impact of shifting treatment modality.

PubMed

Merello Godino, J I; Rentero, R; Orlandini, G; Marcelli, D; Ronco, C

2002-11-01

(3.93 +/- 0.43 vs. 3.94 +/- 0.43 g/dL) between the two modalities of treatment. The level of beta2-microglobulin significantly decreased during high-flux dialysis (33.5 +/- 14.4 vs. 26.3 +/- 8.6 mg/dL, p < 0.001). All above mentioned results may have as a common denominator an improved blood purification from uremic toxins and a reduced level of chronic sub-clinical inflammation. All together, these results seem to confirm the superiority of high-flux dialysis in terms of clinical and physiological outcomes.

Research funders' roles and perceived responsibilities in relation to the implementation of clinical research results: a multiple case study of Swedish research funders.

PubMed

Brantnell, Anders; Baraldi, Enrico; van Achterberg, Theo; Winblad, Ulrika

2015-07-17

Implementation of clinical research results is challenging, yet the responsibility for implementation is seldom addressed. The process from research to the use of clinical research results in health care can be facilitated by research funders. In this paper, we report the roles of ten Swedish research funders in relation to implementation and their views on responsibilities in implementation. Ten cases were studied and compared using semi-structured interviews. In addition, websites and key documents were reviewed. Eight facilitative roles for research funders in relation to the implementation of clinical research results were identified. Three of them were common for several funders: "Advocacy work," "Monitoring implementation outcomes," and "Dissemination of knowledge." Moreover, the research funders identified six different actors responsible for implementation, five of which belonged to the healthcare setting. Collective and organizational responsibilities were the most common forms of responsibilities among the identified actors responsible for implementation. The roles commonly identified by the Swedish funders, "Advocacy work," "Monitoring implementation outcomes," and "Dissemination of knowledge," seem feasible facilitative roles in relation to the implementation of clinical research results. However, many actors identified as responsible for implementation together with the fact that collective and organizational responsibilities were the most common forms of responsibilities entail a risk of implementation becoming no one's responsibility.

[The Basel interdisciplinary clinic for parents with infants and toddlers: concept and empirical results].

PubMed

von Wyl, Agnes; Watson, Michael; Glanzmann, René; von Klitzing, Kai

2008-01-01

The Basel clinic for parents with infants and toddlers is a special interdisciplinary service. The authors present the concept and practice of treatment. Further they show the results of documentation and evaluation. In most cases regulation and sleeping disorders are treated. Temperament ratings made by the mothers of the treated children exhibit more difficult behaviour in comparison to a normal sample. These ratings had no correlation with the mothers' depression scores which rank much higher than the control group. The outcome ratings by the psychotherapists show that despite the short duration of the treatment and severe cases therapeutical success could be achieved. This outlines the importance of such specialized services for early infant crying and other disturbances of the early childhood.

Patient preferences and performance bias in a weight loss trial with a usual care arm☆☆☆

PubMed Central

McCambridge, Jim; Sorhaindo, Annik; Quirk, Alan; Nanchahal, Kiran

2014-01-01

Objectives This qualitative study examines performance bias, i.e. unintended differences between groups, in the context of a weight loss trial in which a novel patient counseling program was compared to usual care in general practice. Methods 14/381 consecutive interviewees (6 intervention group, 8 control group) within the CAMWEL (Camden Weight Loss) effectiveness trial process study were asked about their engagement with various features of the research study and a thematic content analysis undertaken. Results Decisions to participate were interwoven with decisions to change behavior, to the extent that for many participants the two were synonymous. The intervention group were satisfied with their allocation. The control group spoke of their disappointment at having been offered usual care when they had taken part in the trial to access new forms of help. Reactions to disappointment involved both movements toward and away from behavior change. Conclusion There is a prima facie case that reactions to disappointment may introduce bias, as they lead the randomized groups to differ in ways other than the intended experimental contrast. Practice implications In-depth qualitative studies nested within trials are needed to understand better the processes through which bias may be introduced. PMID:24492159

Experiences of being a control group: lessons from a UK-based randomized controlled trial of group singing as a health promotion initiative for older people.

PubMed

Skingley, Ann; Bungay, Hilary; Clift, Stephen; Warden, June

2014-12-01

Existing randomized controlled trials within the health field suggest that the concept of randomization is not always well understood and that feelings of disappointment may occur when participants are not placed in their preferred arm. This may affect a study's rigour and ethical integrity if not addressed. We aimed to test whether these issues apply to a healthy volunteer sample within a health promotion trial of singing for older people. Written comments from control group participants at two points during the trial were analysed, together with individual semi-structured interviews with a small sample (n = 11) of this group. We found that motivation to participate in the trial was largely due to the appeal of singing and disappointment resulted from allocation to the control group. Understanding of randomization was generally good and feelings of disappointment lessened over time and with a post-research opportunity to sing. Findings suggest that measures should be put in place to minimize the potential negative impacts of randomized controlled trials in health promotion research. © The Author (2013). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

[Implantation of the paclitaxel-eluting stent Apollo in patients with stable angina pectoris: long-term angiographic and clinical results].

PubMed

Batyraliev, T A; Fettser, D V; Samko, A N; Sidorenko, B A

2010-01-01

to assess the long-term angiographic and clinical results of percutaneous coronary interventions (PCI) with implantation of the drug-eluting stent (DES) Apollo in patients with stable angina pectoris. The study enrolled 48 patients with stable angina who had been implanted with 59 stents. A follow-up of the patients lasted 12 months. The intervention was successful in 100% patients. Following 12 months, 81.3% of the patients underwent angiography that demonstrated that the vascular diameter decreased by 0.32 +/- 0.45 mm and the rate of restenosis was reduced by only 5.3%. The frequency of evident cardiac complications over 12 months was as high as 11.6%. The DES Apollo provides a way of safely performing PCI, by achieving a high of angiographic success rate. The application of this stent yields long-term good angiographic and clinical results in patients with stable angina pectoris.

Sex differences in sub-clinical psychosis--results from a community study over 30 years.

PubMed

Rössler, Wulf; Hengartner, Michael P; Ajdacic-Gross, Vladeta; Haker, Helene; Angst, Jules

2012-08-01

Sex differences in schizophrenia have long been reported. They are found within almost all aspects of the disease, from incidence and prevalence, age of onset, symptomatology, and course to its psycho-social outcome. Many sex-related hypotheses have been developed about the biology, psychology, or sociology of that disease. A further approach to study sex differences would be to examine such differences in sub-clinical psychotic states as well. If factors related to full-blown psychosis were equally meaningful over the entire psychosis continuum, we should expect that "true" sex differences could also be identified in sub-clinical psychosis. Here, we studied sex differences in sub-clinical psychosis within a community cohort in Zurich, Switzerland. This population was followed for over 30 years and included males and females between the ages of 20/21 and 49/50. We applied two different measures of sub-clinical psychosis representing schizotypal signs and schizophrenia nuclear symptoms. Using cross-sectional and longitudinal analyses, we found no significant sex differences in sub-clinical psychosis over time with respect to age of onset, symptomatology, course, or psycho-social outcome. Thus it appears that sex differences in psychosis manifest themselves at the high end of the continuum (full-blown schizophrenia) rather than within the sub-threshold range. Possibly males and females have separate thresholds for certain symptoms because they are differently vulnerable or exposed to various risk factors. Copyright © 2012. Published by Elsevier B.V.

Results of clinical olfactometric studies.

PubMed

Kittel, G

1976-09-01

A modification of a flow olfactometer with a new application appartus, with which "quasi-free" nasal respiration allows the elimination of adaptation without a special testing room, subsequent results using this device to examine olfactory thresholds before and after septum operations, as well as reference to threshold increases in 57 post-operative cases of cheilognathopalatoschisis are reported. An esthesio-neuroblastoma as well as the deformity syndrome with cheilognathopalatoschisis and encephalodystrophy are used as examples for combined olfactory transmission and perception disorders. Studies of 55 smokers with primary neurosensory disorders demonstrated a threefold increase in the olfactory threshold and an up to 50% decrease "fatique-time". A mean acetone deviation factor of 1.93 was seen in 100 students from 20-27 years of age before and after eating. Correspondingly, after a substantial breakfast and lunch, the olfactory threshold attained its maximum daily value within 90 minutes, much more pronounced than after intake of 80 grams of glucose solution. In contrast to the literature, the olfactory threshold was seen to continuously increase, dependent on age. Studies of the perceptive and recognition threshold on 100 normal individuals and 28 patients with hyposmia exhibited with 3 sigma, a significant difference. In patients with hyposmia, the absolute values for the two threshold types vary greatly, however not their deviation factors. More importance should be attached to the sense of smell as the so-called lesser senses give us the greatest pleasures.

Training models and status of clinical neuropsychologists in Europe: results of a survey on 30 countries.

PubMed

Hokkanen, Laura; Lettner, Sandra; Barbosa, Fernando; Constantinou, Marios; Harper, Lauren; Kasten, Erich; Mondini, Sara; Persson, Bengt; Varako, Nataliya; Hessen, Erik

2018-06-20

The aims of the study were to analyze the current European situation of specialist education and training within clinical neuropsychology, and the legal and professional status of clinical neuropsychologists in different European countries. An online survey was prepared in 2016 by a Task Force established by the European Federation of Psychological Associations, and representatives of 30 countries gave their responses. Response rate was 76%. Only three countries were reported to regulate the title of clinical neuropsychologist as well as the education and practice of clinical neuropsychologists by law. The most common university degree required to practice clinical neuropsychology was the master's degree; a doctoral degree was required in two countries. The length of the specialist education after the master's degree varied between 12 and 60 months. In one third of the countries, no commonly agreed upon model for specialist education existed. A more systematic training model and a longer duration of training were associated with independence in the work of clinical neuropsychologists. As legal regulation is mostly absent and training models differ, those actively practicing clinical neuropsychology in Europe have a very heterogeneous educational background and skill level. There is a need for a European standardization of specialist training in clinical neuropsychology. Guiding principles for establishing the common core requirements are presented.

Sexual Function After Stereotactic Body Radiotherapy for Prostate Cancer: Results of a Prospective Clinical Trial

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

Wiegner, Ellen A.; King, Christopher R., E-mail: crking@stanford.ed

Purpose: To study the sexual quality of life for prostate cancer patients after stereotactic body radiotherapy (SBRT). Methods and Materials: Using the Expanded Prostate Cancer Index Composite (EPIC)-validated quality-of-life questionnaire, the sexual function of 32 consecutive patients who received prostate SBRT in a prospective Phase II clinical trial were analyzed at baseline, and at median times of 4, 12, 20, and 50 months after treatment. SBRT consisted of 36.25 Gy in five fractions of 7.25 Gy using the Cyberknife. No androgen deprivation therapy was given. The use of erectile dysfunction (ED) medications was monitored. A comprehensive literature review for radiotherapy-alonemore » modalities based on patient self-reported questionnaires served as historical comparison. Results: Median age at treatment was 67.5 years, and median follow-up was 35.5 months (minimum 12 months). The mean EPIC sexual domain summary score, sexual function score, and sexual bother score decreased by 45%, 49%, and 25% respectively at 50 months follow-up. These differences reached clinical relevance by 20 months after treatment. Baseline ED rate was 38% and increased to 71% after treatment (p = 0.024). Use of ED medications was 3% at baseline and progressed to 25%. For patients aged <70 years at follow-up, 60% maintained satisfactory erectile function after treatment compared with only 12% aged {>=}70 years (p = 0.008). Penile bulb dose was not associated with ED. Conclusions: The rates of ED after treatment appear comparable to those reported for other modalities of radiotherapy. Given the modest size of this study and the uncertainties in the physiology of radiotherapy-related ED, these results merit further investigations.« less

Clinical results of resection arthrodesis by triangular external fixation for posttraumatic arthrosis of the ankle joint in 89 cases.

PubMed

Kiene, J; Schulz, Arndt P; Hillbricht, S; Jürgens, Ch; Paech, A

2009-01-28

The methods for ankle arthrodesis differ significantly, probably a sign that no method is clearly superior to others. In the last ten years there is a clear favour toward internal fixation. We retrospectively evaluate the technique and evaluate the clinical long term results of external fixation in a triangular frame. From 1994 to 2001 a consecutive series of 95 patients with end stage arthritis of the ankle joint were treated. Retrospectively the case notes were evaluated regarding trauma history, medical complaints, further injuries and illnesses, walking and pain status and occupational issues and the clinical examination before arthrodesis. Mean age at the index procedure was 45.4 years (18-82), 67 patients were male (70.5%). Via a bilateral approach the malleoli and the joint surfaces were resected. An AO fixator was applied with two Steinmann-nails inserted with approximately 8 cm distance in the distal tibia, one in the neck of the talus and one in the dorsal calcaneus. The fixator was removed after approximately 12 weeks. Follow up examination at mean 4.4 years included a standardised questionnaire and a clinical examination including the criteria of the AOFAS-Score and radiographs. Due to different complications, 8 (8.9%) further surgical procedures were necessary including 1 below knee amputation. In 4 patients a non-union of the ankle arthrodesis developed (4.5%). The mean AOFAS score improved from 20.8 to 69.3 points. Non-union rates and clinical results of arthrodesis by triangular external fixation of the ankle joint do not differ to internal fixation methods. The complication rate and the reduced patient comfort reserve this method mainly for infected arthritis and complicated soft tissue situations.

Long term safety of methotrexate in routine clinical care: discontinuation is unusual and rarely the result of laboratory abnormalities

PubMed Central

Yazici, Y; Sokka, T; Kautiainen, H; Swearingen, C; Kulman, I; Pincus, T

2005-01-01

Objective: To analyse patients with rheumatoid arthritis, treated with methotrexate in a weekly academic rheumatology clinic over 13 years, for continuation of courses and reasons for discontinuation. Methods: All 248 patients with an analysable longitudinal course who took methotrexate in standard care between 1990 and 2003 were studied. Continuation of courses was analysed using life tables. All abnormal and severely abnormal values for aspartate aminotransferase (AST) >40 U/l, >80 U/l, albumin <35 g/l, <30 g/l, white blood cell (WBC) count <4.0x109/l, <3.0x109/l, and platelet count <150x109/l, <100x109/l, were identified. Responses of the clinician and subsequent laboratory values were reviewed. Results: Over 1007 person-years, the probability of continuing methotrexate over five years was 79% (95% confidence interval, 72% to 84%). Severe laboratory abnormalities occurred in 2.9 per 100 person-years, specifically 0.9 for AST >80 U/l, 1.1 for albumin <30 g/l, 0.7 for WBC <3.0x109/l, and 0.3 for platelets <100x109/l. No severe laboratory abnormality progressed to further severity or clinical disease. Permanent discontinuations of methotrexate occurred in 46 patients (19%), 26 (10% of all patients) for adverse effects, 15 (32.6%) for inefficacy; only two discontinuations resulted from laboratory abnormalities, both of WBC, possibly from other sources. Conclusions: Methotrexate was associated with a high rate of continuation, and few clinically significant laboratory abnormalities. Discontinuation primarily reflected clinical rather than laboratory findings. Vigilance for methotrexate toxicity is required but methotrexate appears among the safest treatments for rheumatoid arthritis. PMID:15208176

Metabolic immune restraints: implications for anticancer vaccines.