Identification of a Heterozygous SPG11 Mutation by Clinical Exome Sequencing in a Patient With Hereditary Spastic Paraplegia: A Case Report.

PubMed

Oh, Ja-Young; Do, Hyun Jung; Lee, Seungok; Jang, Ja-Hyun; Cho, Eun-Hae; Jang, Dae-Hyun

2016-12-01

Next-generation sequencing, such as whole-genome sequencing, whole-exome sequencing, and targeted panel sequencing have been applied for diagnosis of many genetic diseases, and are in the process of replacing the traditional methods of genetic analysis. Clinical exome sequencing (CES), which provides not only sequence variation data but also clinical interpretation, aids in reaching a final conclusion with regards to genetic diagnosis. Sequencing of genes with clinical relevance rather than whole exome sequencing might be more suitable for the diagnosis of known hereditary disease with genetic heterogeneity. Here, we present the clinical usefulness of CES for the diagnosis of hereditary spastic paraplegia (HSP). We report a case of patient who was strongly suspected of having HSP based on her clinical manifestations. HSP is one of the diseases with high genetic heterogeneity, the 72 different loci and 59 discovered genes identified so far. Therefore, traditional approach for diagnosis of HSP with genetic analysis is very challenging and time-consuming. CES with TruSight One Sequencing Panel, which enriches about 4,800 genes with clinical relevance, revealed compound heterozygous mutations in SPG11 . One workflow and one procedure can provide the results of genetic analysis, and CES with enrichment of clinically relevant genes is a cost-effective and time-saving diagnostic tool for diseases with genetic heterogeneity, including HSP.

Clinical teaching with emotional intelligence: A teaching toolbox

PubMed Central

Omid, Athar; Haghani, Fariba; Adibi, Peyman

2016-01-01

Background: Emotional intelligence (EI) helps humans to perceive their own and others’ emotions. It helps to make better interpersonal communication that consequently leads to an increase in everyday performance and professional career. Teaching, particularly teaching in the clinical environment, is among the professions that need a high level of EI due to its relevance to human interactions. Materials and Methods: We adopted EI competencies with characteristics of a good clinical teacher. As a result, we extracted 12 strategies and then reviewed the literatures relevant to these strategies. Results: In the present article, 12 strategies that a clinical teacher should follow to use EI in her/his teaching were described. Conclusion: To apply EI in clinical settings, a teacher should consider all the factors that can bring about a more positive emotional environment and social interactions. These factors will increase students’ learning, improve patients’ care, and maintain her/his well-being. In addition, he/she will be able to evaluate her/his teaching to improve its effectiveness. PMID:27904573

Decaying Relevance of Clinical Data Towards Future Decisions in Data-Driven Inpatient Clinical Order Sets

PubMed Central

Chen, Jonathan H; Alagappan, Muthuraman; Goldstein, Mary K; Asch, Steven M; Altman, Russ B

2017-01-01

Objective Determine how varying longitudinal historical training data can impact prediction of future clinical decisions. Estimate the “decay rate” of clinical data source relevance. Materials and Methods We trained a clinical order recommender system, analogous to Netflix or Amazon’s “Customers who bought A also bought B…” product recommenders, based on a tertiary academic hospital’s structured electronic health record data. We used this system to predict future (2013) admission orders based on different subsets of historical training data (2009 through 2012), relative to existing human-authored order sets. Results Predicting future (2013) inpatient orders is more accurate with models trained on just one month of recent (2012) data than with 12 months of older (2009) data (ROC AUC 0.91 vs. 0.88, precision 27% vs. 22%, recall 52% vs. 43%, all P<10−10). Algorithmically learned models from even the older (2009) data was still more effective than existing human-authored order sets (ROC AUC 0.81, precision 16% recall 35%). Training with more longitudinal data (2009–2012) was no better than using only the most recent (2012) data, unless applying a decaying weighting scheme with a “half-life” of data relevance about 4 months. Discussion Clinical practice patterns (automatically) learned from electronic health record data can vary substantially across years. Gold standards for clinical decision support are elusive moving targets, reinforcing the need for automated methods that can adapt to evolving information. Conclusions and Relevance Prioritizing small amounts of recent data is more effective than using larger amounts of older data towards future clinical predictions. PMID:28495350

How Long Should Routine EEG Be Recorded to Get Relevant Information?

PubMed

Doudoux, Hannah; Skaare, Kristina; Geay, Thomas; Kahane, Philippe; Bosson, Jean L; Sabourdy, Cécile; Vercueil, Laurent

2017-03-01

The optimal duration of routine EEG (rEEG) has not been determined on a clinical basis. This study aims to determine the time required to obtain relevant information during rEEG with respect to the clinical request. All rEEGs performed over 3 months in unselected patients older than 14 years in an academic hospital were analyzed retrospectively. The latency required to obtain relevant information was determined for each rEEG by 2 independent readers blinded to the clinical data. EEG final diagnoses and latencies were analyzed with respect to the main clinical requests: subacute cognitive impairment, spells, transient focal neurologic manifestation or patients referred by epileptologists. From 430 rEEGs performed in the targeted period, 364 were analyzed: 92% of the pathological rEEGs were provided within the first 10 minutes of recording. Slowing background activity was diagnosed from the beginning, whereas interictal epileptiform discharges were recorded over time. Moreover, the time elapsed to demonstrate a pattern differed significantly in the clinical groups: in patients with subacute cognitive impairment, EEG abnormalities appeared within the first 10 minutes, whereas in the other groups, data could be provided over time. Patients with subacute cognitive impairment differed from those in the other groups significantly in the elapsed time required to obtain relevant information during rEEG, suggesting that 10-minute EEG recordings could be sufficient, arguing in favor of individualized rEEG. However, this conclusion does not apply to intensive care unit patients.

Clinical Relevance of Nontuberculous Mycobacteria Isolated from Sputum in a Gold Mining Workforce in South Africa: An Observational, Clinical Study

PubMed Central

van Halsema, Clare L.; Chihota, Violet N.; Gey van Pittius, Nicolaas C.; Fielding, Katherine L.; Lewis, James J.; van Helden, Paul D.; Churchyard, Gavin J.; Grant, Alison D.

2015-01-01

Background. The clinical relevance of nontuberculous mycobacteria (NTM), detected by liquid more than solid culture in sputum specimens from a South African mining workforce, is uncertain. We aimed to describe the current spectrum and relevance of NTM in this population. Methods. An observational study including individuals with sputum NTM isolates, recruited at workforce tuberculosis screening and routine clinics. Symptom questionnaires were administered at the time of sputum collection and clinical records and chest radiographs reviewed retrospectively. Results. Of 232 individuals included (228 (98%) male, median age 44 years), M. gordonae (60 individuals), M. kansasii (50), and M. avium complex (MAC: 38) were the commonest species. Of 38 MAC isolates, only 2 (5.3%) were from smear-positive sputum specimens and 30/38 grew in liquid but not solid culture. MAC was especially prevalent among symptomatic, HIV-positive individuals. HIV prevalence was high: 57/74 (77%) among those tested. No differences were found in probability of death or medical separation by NTM species. Conclusions. M. gordonae, M. kansasii, and MAC were the commonest NTM among miners with suspected tuberculosis, with most MAC from smear-negative specimens in liquid culture only. HIV testing and identification of key pathogenic NTM in this setting are essential to ensure optimal treatment. PMID:26180817

[Analysis of the results of the SEIMC External Quality Control Program. Year 2012].

PubMed

de Gopegui Bordes, Enrique Ruiz; Guna Serrano, M del Remedio; Orta Mira, Nieves; Ovies, María Rosario; Poveda, Marta; Gimeno Cardona, Concepción

2014-02-01

The External Quality Control Program of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) include controls for bacteriology, serology, mycology, parasitology, mycobacteria, virology and molecular microbiology. This article presents the most relevant conclusions and lessons from the 2012 controls. As a whole, the results obtained in 2012 confirm the excellent skill and good technical standards found in previous editions. However, erroneous results can be obtained in any laboratory and in clinically relevant determinations. Once again, the results of this program highlighted the need to implement both internal and external controls in order to assure the maximal quality of the microbiological tests. Copyright © 2014 Elsevier España, S.L. All rights reserved.

[Analysis of the results of the SEIMC External Quality Control Program. Year 2014].

PubMed

Gopegui Bordes, Enrique Ruiz de; Guna Serrano, M Del Remedio; Orta Mira, Nieves; Medina González, Rafael; Rosario Ovies, María; Poveda, Marta; Gimeno Cardona, Concepción

2016-07-01

The External Quality Control Program of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) include controls for bacteriology, serology, mycology, parasitology, mycobacteria, virology and molecular microbiology. This article presents the most relevant conclusions and lessons from the 2014 controls. As a whole, the results obtained in 2014 confirm the excellent skill and good technical standards found in previous editions. However, erroneous results can be obtained in any laboratory and in clinically relevant determinations. Once again, the results of the SEIMC program highlighted the need to implement both internal and external controls in order to assure the maximal quality of the microbiological tests. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Hyperglycaemia, Insulin Therapy and Critical Penumbral Regions for Prognosis in Acute Stroke: Further Insights from the INSULINFARCT Trial

PubMed Central

Rosso, Charlotte; Pires, Christine; Corvol, Jean-Christophe; Baronnet, Flore; Crozier, Sophie; Leger, Anne; Deltour, Sandrine; Valabregue, Romain; Amor-Sahli, Mélika; Lehéricy, Stéphane; Dormont, Didier; Samson, Yves

2015-01-01

Background Recently, the concept of ‘clinically relevant penumbra’ was defined as an area saved by arterial recanalization and correlated with stroke outcome. This clinically relevant penumbra was located in the subcortical structures, especially the periventricular white matter. Our aims were to confirm this hypothesis, to investigate the impact of admission hyperglycemia and of insulin treatment on the severity of ischemic damages in this area and to study the respective contributions of infarct volume and ischemic damage severity of the clinically relevant penumbra on 3-month outcome. Methods We included 99 patients from the INSULINFARCT trial. Voxel-Based Analysis was carried on the Apparent Diffusion Coefficient (ADC) maps obtained at day one to localize the regions, which were more damaged in patients i) with poor clinical outcomes at three months and ii) without arterial recanalization. We determined the intersection of the detected areas, which represents the clinically relevant penumbra and investigated whether hyperglycemic status and insulin regimen affected the severity of ischemic damages in this area. We performed logistic regression to examine the contribution of infarct volume or early ADC decrease in this strategic area on 3-month outcome. Findings Lower ADC values were found in the corona radiata in patients with poor prognosis (p< 0.0001) and in those without arterial recanalization (p< 0.0001). The tracking analysis showed that lesions in this area interrupted many important pathways. ADC values in this area were lower in hyperglycemic than in normoglycemic patients (average decrease of 41.6 ± 20.8 x10−6mm2/s) and unaffected by the insulin regimen (p: 0.10). ADC values in the clinically relevant penumbra, but not infarct volumes, were significant predictors of 3-month outcome. Conclusion These results confirm that the deep hemispheric white matter is part of the clinically relevant penumbra and show that hyperglycaemia exacerbates the apparition of irreversible ischemic damage within 24 hours in this area. However, early intensive insulin therapy fails to protect this area from infarction. Trial Registration ClinicalTrials.gov NCT00472381 PMID:25793765

Increasing clinical relevance in oral radiology: Benefits and challenges when implementing digital assessment.

PubMed

de Lange, T; Møystad, A; Torgersen, G R

2018-02-13

The aims of the study were to investigate benefits and challenges in implementing a digital examination and study the clinical relevance of the digital examination in relation to clinical training and practice. The study was based on semi-structured focus-group interviews from two distinct student populations (2016 and 2017) in a bachelor programme in dental hygiene. In addition, conversational data from a plenary discussion from the whole second student population (2017) were collected and analysed. The data were approached on basis of content analysis. A benefit experienced in the digital examination was the ease in typing and editing answers on the computer. This suggests an increased effectiveness in computer-based compared to analogue examinations. An additional advantage was the experienced relevance of the examination related to the clinic. This finding refers not only to the digital presentations of images, but also to the entire setting in the clinic and dental practice. The limitations reported by the students were non-optimal viewing conditions for presenting radiographic images and difficulties in obtaining an overview of the assignments compared to paper-based examinations due to the linear digital examination format. The last finding on lacking overview revealed an influence on student performances which should be taken seriously in designing digital examinations. In conclusion, the digital layout increases efficiency and clinical relevance of examinations to a certain extent. Obstacles were found in limitations related to image presentation and lack of overview of the examination. The latter challenge raises questions related to developing suitable assessment software. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Case-based reasoning using electronic health records efficiently identifies eligible patients for clinical trials

PubMed Central

Miotto, Riccardo

2015-01-01

Objective To develop a cost-effective, case-based reasoning framework for clinical research eligibility screening by only reusing the electronic health records (EHRs) of minimal enrolled participants to represent the target patient for each trial under consideration. Materials and Methods The EHR data—specifically diagnosis, medications, laboratory results, and clinical notes—of known clinical trial participants were aggregated to profile the “target patient” for a trial, which was used to discover new eligible patients for that trial. The EHR data of unseen patients were matched to this “target patient” to determine their relevance to the trial; the higher the relevance, the more likely the patient was eligible. Relevance scores were a weighted linear combination of cosine similarities computed over individual EHR data types. For evaluation, we identified 262 participants of 13 diversified clinical trials conducted at Columbia University as our gold standard. We ran a 2-fold cross validation with half of the participants used for training and the other half used for testing along with other 30 000 patients selected at random from our clinical database. We performed binary classification and ranking experiments. Results The overall area under the ROC curve for classification was 0.95, enabling the highlight of eligible patients with good precision. Ranking showed satisfactory results especially at the top of the recommended list, with each trial having at least one eligible patient in the top five positions. Conclusions This relevance-based method can potentially be used to identify eligible patients for clinical trials by processing patient EHR data alone without parsing free-text eligibility criteria, and shows promise of efficient “case-based reasoning” modeled only on minimal trial participants. PMID:25769682

An Empirically Derived Taxonomy for Personality Diagnosis: Bridging Science and Practice in Conceptualizing Personality

PubMed Central

Westen, Drew; Shedler, Jonathan; Bradley, Bekh; DeFife, Jared A.

2013-01-01

Objective The authors describe a system for diagnosing personality pathology that is empirically derived, clinically relevant, and practical for day-to-day use. Method A random national sample of psychiatrists and clinical psychologists (N=1,201) described a randomly selected current patient with any degree of personality dysfunction (from minimal to severe) using the descriptors in the Shedler-Westen Assessment Procedure–II and completed additional research forms. Results The authors applied factor analysis to identify naturally occurring diagnostic groupings within the patient sample. The analysis yielded 10 clinically coherent personality diagnoses organized into three higher-order clusters: internalizing, externalizing, and borderline-dysregulated. The authors selected the most highly rated descriptors to construct a diagnostic prototype for each personality syndrome. In a second, independent sample, research interviewers and patients’ treating clinicians were able to diagnose the personality syndromes with high agreement and minimal comorbidity among diagnoses. Conclusions The empirically derived personality prototypes described here provide a framework for personality diagnosis that is both empirically based and clinically relevant. PMID:22193534

Linking the Tinnitus Questionnaire and the subjective Clinical Global Impression: Which differences are clinically important?

PubMed Central

2012-01-01

Background Development of new tinnitus treatments requires prospective placebo-controlled randomized trials to prove their efficacy. The Tinnitus Questionnaire (TQ) is a validated and commonly used instrument for assessment of tinnitus severity and has been used in many clinical studies. Defining the Minimal Clinically Important Difference (MCID) for TQ changes is an important step to a better interpretation of the clinical relevance of changes observed in clinical trials. In this study we aimed to estimate the minimum change of the TQ score that could be considered clinically relevant. Methods 757 patients with chronic tinnitus were pooled from the TRI database and the RESET study. An anchor-based approach using the Clinical Global Impression (CGI) scale and distributional approaches were used to estimate MCID. Receiver Operating Characteristic (ROC) curves were calculated to define optimal TQ change cutoffs discriminating between minimally changed and unchanged subjects. Results The relationship between TQ change scores and CGI ratings of change was good (r = 0.52, p < 0.05). Mean change scores associated with minimally better and minimally worse CGI categories were −6.65 and +2.72 respectively. According to the ROC method MCID for improvement was −5 points and for deterioration +1 points. Conclusion Distribution and anchor-based methods yielded comparable results in identifying MCIDs. ΔTQ scores of −5 and +1 points were identified as the minimal clinically relevant change for improvement and worsening respectively. The asymmetry of the MCIDs for improvement and worsening may be related to expectation effects. PMID:22781703

Developing an International Register of Clinical Prediction Rules for Use in Primary Care: A Descriptive Analysis

PubMed Central

Keogh, Claire; Wallace, Emma; O’Brien, Kirsty K.; Galvin, Rose; Smith, Susan M.; Lewis, Cliona; Cummins, Anthony; Cousins, Grainne; Dimitrov, Borislav D.; Fahey, Tom

2014-01-01

PURPOSE We describe the methodology used to create a register of clinical prediction rules relevant to primary care. We also summarize the rules included in the register according to various characteristics. METHODS To identify relevant articles, we searched the MEDLINE database (PubMed) for the years 1980 to 2009 and supplemented the results with searches of secondary sources (books on clinical prediction rules) and personal resources (eg, experts in the field). The rules described in relevant articles were classified according to their clinical domain, the stage of development, and the clinical setting in which they were studied. RESULTS Our search identified clinical prediction rules reported between 1965 and 2009. The largest share of rules (37.2%) were retrieved from PubMed. The number of published rules increased substantially over the study decades. We included 745 articles in the register; many contained more than 1 clinical prediction rule study (eg, both a derivation study and a validation study), resulting in 989 individual studies. In all, 434 unique rules had gone through derivation; however, only 54.8% had been validated and merely 2.8% had undergone analysis of their impact on either the process or outcome of clinical care. The rules most commonly pertained to cardiovascular disease, respiratory, and musculoskeletal conditions. They had most often been studied in the primary care or emergency department settings. CONCLUSIONS Many clinical prediction rules have been derived, but only about half have been validated and few have been assessed for clinical impact. This lack of thorough evaluation for many rules makes it difficult to retrieve and identify those that are ready for use at the point of patient care. We plan to develop an international web-based register of clinical prediction rules and computer-based clinical decision support systems. PMID:25024245

Effectiveness-implementation Hybrid Designs

PubMed Central

Curran, Geoffrey M.; Bauer, Mark; Mittman, Brian; Pyne, Jeffrey M.; Stetler, Cheryl

2013-01-01

Objectives This study proposes methods for blending design components of clinical effectiveness and implementation research. Such blending can provide benefits over pursuing these lines of research independently; for example, more rapid translational gains, more effective implementation strategies, and more useful information for decision makers. This study proposes a “hybrid effectiveness-implementation” typology, describes a rationale for their use, outlines the design decisions that must be faced, and provides several real-world examples. Results An effectiveness-implementation hybrid design is one that takes a dual focus a priori in assessing clinical effectiveness and implementation. We propose 3 hybrid types: (1) testing effects of a clinical intervention on relevant outcomes while observing and gathering information on implementation; (2) dual testing of clinical and implementation interventions/strategies; and (3) testing of an implementation strategy while observing and gathering information on the clinical intervention’s impact on relevant outcomes. Conclusions The hybrid typology proposed herein must be considered a construct still in evolution. Although traditional clinical effectiveness and implementation trials are likely to remain the most common approach to moving a clinical intervention through from efficacy research to public health impact, judicious use of the proposed hybrid designs could speed the translation of research findings into routine practice. PMID:22310560

Clinical studies of fiber posts: a literature review.

PubMed

Cagidiaco, Maria C; Goracci, Cecilia; Garcia-Godoy, Franklin; Ferrari, Marco

2008-01-01

This literature review aimed to find answers to relevant questions regarding the clinical outcome of endontically treated teeth restored with fiber posts. All clinical studies published since 1990 in journals indexed in MEDLINE were retrieved by searching PubMed with the query terms "fiber posts and clinical studies." The reference list of the collected articles was also screened for further relevant citations. The strength of the evidence provided by the reviewed papers was assessed according to the criteria of evidence-based dentistry. Five randomized controlled trials (RCTs) on fiber posts have been published in peer-reviewed journals. A meta-analysis is not applicable to these studies since they do not address the same specific clinical question. Retrospective and prospective trials without controls are also available. Two RCTs indicate that fiber-reinforced composite posts outperform metal posts in the restoration of endontically treated teeth. However, this evidence cannot be considered as conclusive. Longer-term RCTs would be desirable. The placement of a fiber-reinforced composite post protects against failure, especially under conditions of extensive coronal destruction. The most common type of failure with fiber-reinforced composite posts is debonding.

Use of FEV1 in Cystic Fibrosis Epidemiologic Studies and Clinical Trials: A Statistical Perspective for the Clinical Researcher

PubMed Central

Szczesniak, Rhonda; Heltshe, Sonya L.; Stanojevic, Sanja; Mayer-Hamblett, Nicole

2017-01-01

Background Forced expiratory volume in 1 second (FEV1) is an established marker of cystic fibrosis (CF) disease progression that is used to capture clinical course and evaluate therapeutic efficacy. The research community has established FEV1 surveillance data through a variety of observational data sources such as patient registries, and there is a growing pipeline of new CF therapies demonstrated to be efficacious in clinical trials by establishing improvements in FEV1. Results In this review, we summarize from a statistical perspective the clinical relevance of FEV1 based on its association with morbidity and mortality in CF, its role in epidemiologic studies of disease progression and comparative effectiveness, and its utility in clinical trials. In addition, we identify opportunities to advance epidemiologic research and the clinical development pipeline through further statistical considerations. Conclusions Our understanding of CF disease course, therapeutics, and clinical care has evolved immensely in the past decades, in large part due to the thoughtful application of rigorous research methods and meaningful clinical endpoints such as FEV1. A continued commitment to conduct research that minimizes the potential for bias, maximizes the limited patient population, and harmonizes approaches to FEV1 analysis while maintaining clinical relevance, will facilitate further opportunities to advance CF care. PMID:28117136

Systematic review on the use of matrix-bound sealants in pancreatic resection

PubMed Central

Smits, F Jasmijn; van Santvoort, Hjalmar C; Besselink, Marc G H; Borel Rinkes, Inne H M; Molenaar, I Quintus

2015-01-01

Background Pancreatic fistula is a potentially life-threatening complication after a pancreatic resection. The aim of this systematic review was to evaluate the role of matrix-bound sealants after a pancreatic resection in terms of preventing or ameliorating the course of a post-operative pancreatic fistula. Methods A systematic search was performed in the literature from May 2005 to April 2015. Included were clinical studies using matrix-bound sealants after a pancreatic resection, reporting a post-operative pancreatic fistula (POPF) according to the International Study Group on Pancreatic Fistula classification, in which grade B and C fistulae were considered clinically relevant. Results Two were studies on patients undergoing pancreatoduodenectomy (sealants n = 67, controls n = 27) and four studies on a distal pancreatectomy (sealants n = 258, controls n = 178). After a pancreatoduodenectomy, 13% of patients treated with sealants versus 11% of patients without sealants developed a POPF (P = 0.76), of which 4% versus 4% were clinically relevant (P = 0.87). After a distal pancreatectomy, 42% of patients treated with sealants versus 52% of patients without sealants developed a POPF (P = 0.03). Of these, 9% versus 12% were clinically relevant (P = 0.19). Conclusions The present data do not support the routine use of matrix-bound sealants after a pancreatic resection, as there was no effect on clinically relevant POPF. Larger, well-designed studies are needed to determine the efficacy of sealants in preventing POPF after a pancreatoduodenectomy. PMID:26292846

The anticoagulant effects of warfarin and the bleeding risk associated with its use in patients with chronic thromboembolic pulmonary hypertension at a specialist center in Japan: a retrospective cohort study

PubMed Central

Jujo-Sanada, Takayuki; Tanabe, Nobuhiro; Sakao, Seiichiro; Sugiura, Toshihiko; Sekine, Ayumi; Nishimura, Rintaro; Suda, Rika; Naito, Akira; Miwa, Hideki; Yamamoto, Keiko; Sasaki, Akane; Matsumura, Akane; Ema, Ryogo; Kasai, Hajime; Kato, Fumiaki; Tatsumi, Koichiro

2017-01-01

Patients with chronic thromboembolic pulmonary hypertension (CTEPH) require lifelong anticoagulation therapy. However, the bleeding risk and recurrence of venous thromboembolism (VTE) in CTEPH patients who are administered warfarin have not been adequately evaluated. The purpose of this study was to evaluate the risk of clinically relevant bleeding, recurrent VTE, and clinical worsening in patients with CTEPH who were administered warfarin. The clinical records of 72 patients with CTEPH who regularly visited our institution and were administered warfarin were retrospectively reviewed between 1 January 2011 and 31 December 2015. We investigated the incidence of clinically relevant bleeding events, recurrent VTE, and hospitalization for the deterioration of pulmonary hypertension or right heart failure (RHF) during the observation period. The mean observation period for the 72 patients was 3.60 ± 1.60 person-years. Clinically relevant bleeding, RHF, and recurrent VTE occurred in 21 (29.2%), eight (11.1%), and three (4.2%) of 72 patients, respectively, and the incidence rates for these events were 8.1%/person-year, 3.1%/person-year, and 1.2%/person-year, respectively. The incidence rates for the major and non-major bleeding events were 5.0%/person-year and 3.9%/person-year, respectively. The incidence of clinically relevant bleeding events was 20.8%/person-year during medical treatment with a soluble guanylate cyclase stimulator. One of 35 patients (2.9%) during the post-pulmonary endarterectomy period experienced hemoptysis during observation period (> 6 months after pulmonary endarterectomy). No bleeding events occurred during the post-balloon pulmonary angioplasty period. In conclusion, warfarin effectively prevents VTE recurrence in CTEPH patients, but its effects may be associated with a considerable bleeding risk. PMID:28604280

Exploring the Educational Value of Clinical Vignettes from the Society of General Internal Medicine National Meeting in the Internal Medicine Clerkship

PubMed Central

Wofford, James L; Singh, Sonal

2006-01-01

INTRODUCTION Whether the clinical vignettes presented at the Society of General Internal Medicine (SGIM) annual meeting could be of educational value to third year students in the Internal Medicine clerkship has not been studied. OBJECTIVE To explore the relevance and learning value of clinical vignettes from the SGIM national meeting in the Internal Medicine clerkship. SETTING Third year Ambulatory Internal Medicine clerkship at one academic medical center (academic year 2005 to 2006). METHODS Students were introduced to the clinical vignette and oriented to the database of clinical vignettes available through the SGIM annual meeting website. Students then reviewed 5 to 10 clinical vignettes using a worksheet, and rated the learning value of each vignette using a 5-point Likert scale (1 = least, 5 = greatest). A single investigator evaluated congruence of the vignette with the Clerkship Directors of Internal Medicine (CDIM)-SGIM curriculum to assess relevance. MAIN RESULTS A total of 42 students evaluated 371 clinical vignettes from the 2004 and 2005 meetings. The clinical vignettes were curriculum-congruent in 42.6% (n = 175), and clearly incongruent in 40.4% (n = 164). The mean rating for learning value was 3.8 (±1.0) (5 signifying greatest learning value). Curriculum-congruent vignettes had a higher mean learning value compared with curriculum-incongruent vignettes (4.0 vs 3.6, Student's t-test, P =.017). CONCLUSION The clinical vignettes presented at the national SGIM meeting offer clinical content that is relevant and of some educational value for third year clerkship students. Based on this pilot study, the educational value and strategies for their use in the clinical clerkships deserve further study. PMID:17026730

Performance appraisal of online MEDLINE access routes.

PubMed Central

Walker, C. J.; McKibbon, K. A.; Haynes, R. B.; Johnston, M. E.

1992-01-01

OBJECTIVE: To compare the performance and cost of 11 online MEDLINE systems with MEDLINE at Elhill. DESIGN: Comparative study. SYSTEMS: Eleven online daytime systems commercially available in North America offering the MEDLINE database. MEASURES: Number of relevant citations, number of irrelevant citations, proportion of searches producing no relevant citations and cost per relevant citation were analyzed for each system. Relevance and cost for each system were compared with direct searching of MEDLINE through NLM for librarian and clinician search strategies for 18 clinical questions. The citations retrieved by both strategies were pooled and rated for relevance on a 7-point scale. RESULTS: Numbers of relevant and irrelevant citations and cost per relevant citation were higher for clinician searches than librarian searches, reflecting the higher total number of citations retrieved by the clinician approaches. A lower proportion of clinician searches produced no relevant citations than librarian searches. CONCLUSIONS: Eleven daytime MEDLINE systems performed similarly in terms of retrieval and cost within similar searching groups. Clinicians, however, tended to capture larger overall retrievals resulting in higher numbers of relevant and irrelevant citations than librarians. PMID:1482922

Contextualizing the relevance of basic sciences: small-group simulation with debrief for first- and second-year medical students in an integrated curriculum.

PubMed

Ginzburg, Samara B; Brenner, Judith; Cassara, Michael; Kwiatkowski, Thomas; Willey, Joanne M

2017-01-01

There has been a call for increased integration of basic and clinical sciences during preclinical years of undergraduate medical education. Despite the recognition that clinical simulation is an effective pedagogical tool, little has been reported on its use to demonstrate the relevance of basic science principles to the practice of clinical medicine. We hypothesized that simulation with an integrated science and clinical debrief used with early learners would illustrate the importance of basic science principles in clinical diagnosis and management of patients. Small groups of first- and second-year medical students were engaged in a high-fidelity simulation followed by a comprehensive debrief facilitated by a basic scientist and clinician. Surveys including anchored and open-ended questions were distributed at the conclusion of each experience. The majority of the students agreed that simulation followed by an integrated debrief illustrated the clinical relevance of basic sciences (mean ± standard deviation: 93.8% ± 2.9% of first-year medical students; 96.7% ± 3.5% of second-year medical students) and its importance in patient care (92.8% of first-year medical students; 90.4% of second-year medical students). In a thematic analysis of open-ended responses, students felt that these experiences provided opportunities for direct application of scientific knowledge to diagnosis and treatment, improving student knowledge, simulating real-world experience, and developing clinical reasoning, all of which specifically helped them understand the clinical relevance of basic sciences. Small-group simulation followed by a debrief that integrates basic and clinical sciences is an effective means of demonstrating the relationship between scientific fundamentals and patient care for early learners. As more medical schools embrace integrated curricula and seek opportunities for integration, our model is a novel approach that can be utilized.

Is there a benefit of using an arbitrary facebow for the fabrication of a stabilization appliance?

PubMed

Shodadai, S P; Türp, J C; Gerds, T; Strub, J R

2001-01-01

The aim of this clinical study was to evaluate if an arbitrary facebow registration and transfer provides significant advantages for the fabrication of an occlusal appliance in comparison with the omission of such a procedure. For 20 fully dentate adult patients diagnosed with bruxism, two Michigan occlusal splints were constructed. One of the two upper dental casts was transferred to the articulator with an arbitrary earpiece facebow; the other maxillary cast was mounted arbitrarily using a flat occlusal plane indicator. Upon splint delivery, the number of intraoral occlusal contacts and the time needed for chairside occlusal adjustment were recorded. The number of occlusal contacts on the appliance fabricated with or without facebow was similar in most cases both in the articulator and in the mouth. The one-sided Wilcoxon rank sum test showed with high probability that the use of an arbitrary facebow does not yield a clinically relevant improvement with regard to the number of occlusal contacts or the chairside adjustment time. From this pilot study, it appears that for the fabrication of an occlusal appliance, registration and transfer with an arbitrary earpiece facebow does not yield clinically relevant benefits. Of course, this conclusion cannot be transferred to other facebows and is restricted to the levels of clinical relevance defined in the study.

Can the theoretical domains framework account for the implementation of clinical quality interventions?

PubMed Central

2013-01-01

Background The health care quality improvement movement is a complex enterprise. Implementing clinical quality initiatives requires attitude and behaviour change on the part of clinicians, but this has proven to be difficult. In an attempt to solve this kind of behavioural challenge, the theoretical domains framework (TDF) has been developed. The TDF consists of 14 domains from psychological and organisational theory said to influence behaviour change. No systematic research has been conducted into the ways in which clinical quality initiatives map on to the domains of the framework. We therefore conducted a qualitative mapping experiment to determine to what extent, and in what ways, the TDF is relevant to the implementation of clinical quality interventions. Methods We conducted a thematic synthesis of the qualitative literature exploring clinicians’ perceptions of various clinical quality interventions. We analysed and synthesised 50 studies in total, in five domains of clinical quality interventions: clinical quality interventions in general, structural interventions, audit-type interventions, interventions aimed at making practice more evidence-based, and risk management interventions. Data were analysed thematically, followed by synthesis of these themes into categories and concepts, which were then mapped to the domains of the TDF. Results Our results suggest that the TDF is highly relevant to the implementation of clinical quality interventions. It can be used to map most, if not all, of the attitudinal and behavioural barriers and facilitators of uptake of clinical quality interventions. Each of these 14 domains appeared to be relevant to many different types of clinical quality interventions. One possible additional domain might relate to perceived trustworthiness of those instituting clinical quality interventions. Conclusions The TDF can be usefully applied to a wide range of clinical quality interventions. Because all 14 of the domains emerged as relevant, and we did not identify any obvious differences between different kinds of clinical quality interventions, our findings support an initially broad approach to identifying barriers and facilitators, followed by a “drilling down” to what is most contextually salient. In future, it may be possible to establish a model of clinical quality policy implementation using the TDF. PMID:24359085

BRIEF REPORT: Beyond Clinical Experience: Features of Data Collection and Interpretation That Contribute to Diagnostic Accuracy

PubMed Central

Nendaz, Mathieu R; Gut, Anne M; Perrier, Arnaud; Louis-Simonet, Martine; Blondon-Choa, Katherine; Herrmann, François R; Junod, Alain F; Vu, Nu V

2006-01-01

BACKGROUND Clinical experience, features of data collection process, or both, affect diagnostic accuracy, but their respective role is unclear. OBJECTIVE, DESIGN Prospective, observational study, to determine the respective contribution of clinical experience and data collection features to diagnostic accuracy. METHODS Six Internists, 6 second year internal medicine residents, and 6 senior medical students worked up the same 7 cases with a standardized patient. Each encounter was audiotaped and immediately assessed by the subjects who indicated the reasons underlying their data collection. We analyzed the encounters according to diagnostic accuracy, information collected, organ systems explored, diagnoses evaluated, and final decisions made, and we determined predictors of diagnostic accuracy by logistic regression models. RESULTS Several features significantly predicted diagnostic accuracy after correction for clinical experience: early exploration of correct diagnosis (odds ratio [OR] 24.35) or of relevant diagnostic hypotheses (OR 2.22) to frame clinical data collection, larger number of diagnostic hypotheses evaluated (OR 1.08), and collection of relevant clinical data (OR 1.19). CONCLUSION Some features of data collection and interpretation are related to diagnostic accuracy beyond clinical experience and should be explicitly included in clinical training and modeled by clinical teachers. Thoroughness in data collection should not be considered a privileged way to diagnostic success. PMID:17105525

Biomarkers and surrogate endpoints in glaucoma clinical trials.

PubMed

Medeiros, Felipe A

2015-05-01

Surrogate endpoints are often used as replacements for true clinically relevant endpoints in several areas of medicine, as they enable faster and less expensive clinical trials. However, without proper validation, the use of surrogates may lead to incorrect conclusions about the efficacy and safety of treatments. This article reviews the general requirements for validating surrogate endpoints and provides a critical assessment of the use of intraocular pressure (IOP), visual fields, and structural measurements of the optic nerve as surrogate endpoints in glaucoma clinical trials. A valid surrogate endpoint must be able to predict the clinically relevant endpoint and fully capture the effect of an intervention on that endpoint. Despite its widespread use in clinical trials, no proper validation of IOP as a surrogate endpoint has ever been conducted for any class of IOP-lowering treatments. Evidence has accumulated with regard to the role of imaging measurements of optic nerve damage as surrogate endpoints in glaucoma. These measurements are predictive of functional losses in the disease and may explain, at least in part, treatment effects on clinically relevant endpoints. The use of composite endpoints in glaucoma trials may overcome weaknesses of the use of structural or functional endpoints in isolation. Unless research is dedicated to fully develop and validate suitable endpoints that can be used in glaucoma clinical trials, we run the risk of inappropriate judgments about the value of new therapies. 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.

Suitability of the PROMIS Alcohol Use Short Form for Screening in a HIV Clinical Care Setting*

PubMed Central

Gibbons, Laura E.; Fredericksen, Rob; Merrill, Joseph O.; McCaul, Mary E.; Chander, Geetanjali; Hutton, Heidi; Lober, William B.; Mathews, W. Chris; Mayer, Kenneth; Burkholder, Greer; Willig, James H.; Mugavero, Michael J.; Saag, Michael S.; Kitahata, Mari M.; Edwards, Todd C.; Patrick, Donald L; Crane, Heidi M.; Crane, Paul K.

2016-01-01

Background At-risk alcohol use is important to identify in clinical settings to facilitate interventions. The Patient-Reported Outcomes Measurement Information System (PROMIS) Alcohol Use Short Form was developed through an item response theory process, but its utility as a screening instrument in clinical care has not been reported. Objective To determine the ability of the PROMIS Alcohol Use Short Form to identify people with current or future at-risk alcohol use defined by the Alcohol Use Disorders Identification Test consumption (AUDIT-C) instrument. Methods Observational study of people living with HIV (PLWH) in clinical care at four sites across the US. Patients completed a tablet-based clinical assessment prior to seeing their providers at clinic appointments. We used 3 definitions of clinically-relevant at-risk alcohol use and determined the proportion of PLWH with current or future at-risk drinking identified by the PROMIS instrument. Results Of 2,497 PLWH who endorsed ≥1 drink in the prior 12 months, 1,500 PLWH (60%) endorsed “never” for all PROMIS items. In that group, 26% had clinically-relevant at-risk alcohol use defined by one or more AUDIT-C definitions. At follow-up (N=1,608), high baseline PROMIS scores had 55% sensitivity for at-risk drinking among those with at-risk drinking at baseline, and 22% sensitivity among those without baseline risk. Conclusions The PROMIS Alcohol Use Short Form cannot be used alone to identify PLWH with clinically-relevant at-risk alcohol use. Optimal assessment of problem drinking behavior is not clear, but there does not seem to be an important role for the PROMIS instrument in this clinical setting. PMID:27209223

Rapid targeted somatic mutation analysis of solid tumors in routine clinical diagnostics.

PubMed

Magliacane, Gilda; Grassini, Greta; Bartocci, Paola; Francaviglia, Ilaria; Dal Cin, Elena; Barbieri, Gianluca; Arrigoni, Gianluigi; Pecciarini, Lorenza; Doglioni, Claudio; Cangi, Maria Giulia

2015-10-13

Tumor genotyping is an essential step in routine clinical practice and pathology laboratories face a major challenge in being able to provide rapid, sensitive and updated molecular tests. We developed a novel mass spectrometry multiplexed genotyping platform named PentaPanel to concurrently assess single nucleotide polymorphisms in 56 hotspots of the 5 most clinically relevant cancer genes, KRAS, NRAS, BRAF, EGFR and PIK3CA for a total of 221 detectable mutations. To both evaluate and validate the PentaPanel performance, we investigated 1025 tumor specimens of 6 different cancer types (carcinomas of colon, lung, breast, pancreas, and biliary tract, and melanomas), systematically addressing sensitivity, specificity, and reproducibility of our platform. Sanger sequencing was also performed for all the study samples. Our data showed that PentaPanel is a high throughput and robust tool, allowing genotyping for targeted therapy selection of 10 patients in the same run, with a practical turnaround time of 2 working days. Importantly, it was successfully used to interrogate different DNAs isolated from routinely processed specimens (formalin-fixed paraffin embedded, frozen, and cytological samples), covering all the requirements of clinical tests. In conclusion, the PentaPanel platform can provide an immediate, accurate and cost effective multiplex approach for clinically relevant gene mutation analysis in many solid tumors and its utility across many diseases can be particularly relevant in multiple clinical trials, including the new basket trial approach, aiming to identify appropriate targeted drug combination strategies.

Clinical Practice Guidelines for Delirium Management: Potential Application in Palliative Care

PubMed Central

Bush, Shirley H.; Bruera, Eduardo; Lawlor, Peter G.; Kanji, Salmaan; Davis, Daniel H.J.; Agar, Meera; Wright, David; Hartwick, Michael; Currow, David C.; Gagnon, Bruno; Simon, Jessica; Pereira, José L.

2014-01-01

Context Delirium occurs in patients across a wide array of health care settings. The extent to which formal management guidelines exist or are adaptable to palliative care is unclear. Objectives This review aims to 1) source published delirium management guidelines with potential relevance to palliative care settings, 2) discuss the process of guideline development, 3) appraise their clinical utility, and 4) outline the processes of their implementation and evaluation and make recommendations for future guideline development. Methods We searched PubMed (1990–2013), Scopus, U.S. National Guideline Clearinghouse, Google, and relevant reference lists to identify published guidelines for the management of delirium. This was supplemented with multidisciplinary input from delirium researchers and other relevant stakeholders at an international delirium study planning meeting. Results There is a paucity of high-level evidence for pharmacological and non-pharmacological interventions in the management of delirium in palliative care. However, multiple delirium guidelines for clinical practice have been developed, with recommendations derived from “expert opinion” for areas where research evidence is lacking. In addition to their potential benefits, limitations of clinical guidelines warrant consideration. Guidelines should be appraised and then adapted for use in a particular setting before implementation. Further research is needed on the evaluation of guidelines, as disseminated and implemented in a clinical setting, focusing on measurable outcomes in addition to their impact on quality of care. Conclusion Delirium clinical guidelines are available but the level of evidence is limited. More robust evidence is required for future guideline development. PMID:24766743

Quantifying App Store Dynamics: Longitudinal Tracking of Mental Health Apps

PubMed Central

Nicholas, Jennifer; Christensen, Helen

2016-01-01

Background For many mental health conditions, mobile health apps offer the ability to deliver information, support, and intervention outside the clinical setting. However, there are difficulties with the use of a commercial app store to distribute health care resources, including turnover of apps, irrelevance of apps, and discordance with evidence-based practice. Objective The primary aim of this study was to quantify the longevity and rate of turnover of mental health apps within the official Android and iOS app stores. The secondary aim was to quantify the proportion of apps that were clinically relevant and assess whether the longevity of these apps differed from clinically nonrelevant apps. The tertiary aim was to establish the proportion of clinically relevant apps that included claims of clinical effectiveness. We performed additional subgroup analyses using additional data from the app stores, including search result ranking, user ratings, and number of downloads. Methods We searched iTunes (iOS) and the Google Play (Android) app stores each day over a 9-month period for apps related to depression, bipolar disorder, and suicide. We performed additional app-specific searches if an app no longer appeared within the main search Results On the Android platform, 50% of the search results changed after 130 days (depression), 195 days (bipolar disorder), and 115 days (suicide). Search results were more stable on the iOS platform, with 50% of the search results remaining at the end of the study period. Approximately 75% of Android and 90% of iOS apps were still available to download at the end of the study. We identified only 35.3% (347/982) of apps as being clinically relevant for depression, of which 9 (2.6%) claimed clinical effectiveness. Only 3 included a full citation to a published study. Conclusions The mental health app environment is volatile, with a clinically relevant app for depression becoming unavailable to download every 2.9 days. This poses challenges for consumers and clinicians seeking relevant and long-term apps, as well as for researchers seeking to evaluate the evidence base for publicly available apps. PMID:27507641

World Endometriosis Research Foundation Endometriosis Phenome and biobanking harmonization project: II. Clinical and covariate phenotype data collection in endometriosis research

PubMed Central

Vitonis, Allison F.; Vincent, Katy; Rahmioglu, Nilufer; Fassbender, Amelie; Buck Louis, Germaine M.; Hummelshoj, Lone; Giudice, Linda C.; Stratton, Pamela; Adamson, G. David; Becker, Christian M.; Zondervan, Krina T.; Missmer, Stacey A.

2014-01-01

Objective To harmonize the collection of nonsurgical clinical and epidemiologic data relevant to endometriosis research, allowing large-scale collaboration. Design An international collaboration involving 34 clinical/academic centers and three industry collaborators from 16 countries on five continents. Setting In 2013, two workshops followed by global consultation, bringing together 54 leaders in endometriosis research. Patients None. Intervention(s) Development of a self-administered endometriosis patient questionnaire (EPQ), based on [1] systematic comparison of questionnaires from eight centers that collect data from endometriosis cases (and controls/comparison women) on a medium to large scale (publication on >100 cases); [2] literature evidence; and [3] several global consultation rounds. Main Outcome Measure(s) Standard recommended and minimum required questionnaires to capture detailed clinical and covariate data. Result(s) The standard recommended (EPHect EPQ-S) and minimum required (EPHect EPQ-M) questionnaires contain questions on pelvic pain, subfertility and menstrual/reproductive history, hormone/medication use, medical history, and personal information. Conclusion(s) The EPQ captures the basic set of patient characteristics and exposures considered by the WERF EPHect Working Group to be most critical for the advancement of endometriosis research, but is also relevant to other female conditions with similar risk factors and/or symptomatology. The instruments will be reviewed based on feedback from investigators, and–after a first review after 1 year–triannually through systematic follow-up surveys. Updated versions will be made available through http://endometriosisfoundation.org/ephect. PMID:25256930

Performances of 27 MEDLINE systems tested by searches with clinical questions.

PubMed Central

Haynes, R B; Walker, C J; McKibbon, K A; Johnston, M E; Willan, A R

1994-01-01

OBJECTIVE: To compare the performances of online and compact-disc (CD-ROM) versions of the National Library of Medicine's (NLM) MEDLINE database. DESIGN: Analytic survey. INTERVENTION: Clinical questions were drawn from 18 searches originally conducted spontaneously by clinicians from wards and clinics who had used Grateful Med Version 4.0. Clinicians' search strategies were translated to meet the specific requirements of 13 online and 14 CD-ROM MEDLINE systems. A senior librarian and vendors' representatives constructed independent searches from the clinicians' questions. The librarian and clinician searches were run through each system, in command mode for the librarian and menu mode for clinicians, when available. Vendor searches were run through the vendors' own systems only. MAIN MEASUREMENTS: Numbers of relevant and irrelevant citations retrieved, cost (for online systems only), and time. RESULTS: Systems varied substantially for all searches, and for librarian and clinician searches separately, with respect to the numbers of relevant and irrelevant citations retrieved (p < 0.001 for both) and the cost per relevant citation (p = 0.012), but not with respect to the time per search. Based on combined rankings for the highest number of relevant and the lowest number of irrelevant citations retrieved, the SilverPlatter CD-ROM MEDLINE clinical journal subset performed best for librarian searches, while the PaperChase online system worked best for clinician searches. For cost per relevant citation retrieved, Dialog's Knowledge Index performed best for both librarian and clinician searches. CONCLUSIONS: There were substantial differences in the performances of competing MEDLINE systems, and performance was affected by search strategy, which was conceived by a librarian or by clinicians. PMID:7719810

Systematic reviews of complementary therapies – an annotated bibliography. Part 2: Herbal medicine

PubMed Central

Linde, Klaus; ter Riet, Gerben; Hondras, Maria; Vickers, Andrew; Saller, Reinhard; Melchart, Dieter

2001-01-01

Background Complementary therapies are widespread but controversial. We aim to provide a comprehensive collection and a summary of systematic reviews of clinical trials in three major complementary therapies (acupuncture, herbal medicine, homeopathy). This article is dealing with herbal medicine. Potentially relevant reviews were searched through the register of the Cochrane Complementary Medicine Field, the Cochrane Library, Medline, and bibliographies of articles and books. To be included articles had to review prospective clinical trials of herbal medicines; had to describe review methods explicitly; had to be published; and had to focus on treatment effects. Information on conditions, interventions, methods, results and conclusions was extracted using a pre-tested form and summarized descriptively. Results From a total of 79 potentially relevant reviews pre-selected in the screening process 58 met the inclusion criteria. Thirty of the reports reviewed ginkgo (for dementia, intermittent claudication, tinnitus, and macular degeneration), hypericum (for depression) or garlic preparations (for cardiovascular risk factors and lower limb atherosclerosis). The quality of primary studies was criticized in the majority of the reviews. Most reviews judged the available evidence as promising but definitive conclusions were rarely possible. Conclusions Systematic reviews are available on a broad range of herbal preparations prescribed for defined conditions. There is very little evidence on the effectiveness of herbalism as practised by specialist herbalists who combine herbs and use unconventional diagnosis. PMID:11518548

Beyond Cue Reactivity: Non-Drug-Related Motivationally Relevant Stimuli Are Necessary to Understand Reactivity to Drug-Related Cues.

PubMed

Versace, Francesco; Engelmann, Jeffrey M; Deweese, Menton M; Robinson, Jason D; Green, Charles E; Lam, Cho Y; Minnix, Jennifer A; Karam-Hage, Maher A; Wetter, David W; Schembre, Susan M; Cinciripini, Paul M

2017-06-01

Neurobiological models of addiction posit that drug use can alter reward processes in two ways: (1) by increasing the motivational relevance of drugs and drug-related cues and (2) by reducing the motivational relevance of non-drug-related rewards. Here, we discuss the results from a series of neuroimaging studies in which we assessed the extent to which these hypotheses apply to nicotine dependence. In these studies, we recorded smokers’ and nonsmokers’ brain responses to a wide array of motivationally relevant visual stimuli that included pleasant, unpleasant, cigarette-related, and neutral images. Based on these findings, we highlight the flaws of the traditional cue reactivity paradigm and we conclude that responses to non-drug-related motivationally relevant stimuli should be used to appropriately gauge the motivational relevance of cigarette-related cues and to identify smokers attributing higher motivational relevance to drug-related cues than to non-drug-related rewards. Identifying these individuals is clinically relevant as they achieve lower rates of long-term smoking abstinence when attempting to quit. Finally, we show how this approach may be extended beyond nicotine dependence to inform theoretical and clinical research in the study of obesity. The cue reactivity paradigm (ie, comparing responses evoked by drug-related cues to those evoked by neutral cues) cannot provide conclusive information about the motivational relevance of drug-related cues. Responses to non-drug-related motivationally relevant stimuli should be used to appropriately gauge the level of motivational relevance that substance-dependent individuals attribute to drug-related cues. © The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Consensus Conference Follow-up: Inter-rater Reliability Assessment of the Best Evidence in Emergency Medicine (BEEM) Rater Scale, a Medical Literature Rating Tool for Emergency Physicians

PubMed Central

Worster, Andrew; Kulasegaram, Kulamakan; Carpenter, Christopher R.; Vallera, Teresa; Upadhye, Suneel; Sherbino, Jonathan; Haynes, R. Brian

2011-01-01

Background Studies published in general and specialty medical journals have the potential to improve emergency medicine (EM) practice, but there can be delayed awareness of this evidence because emergency physicians (EPs) are unlikely to read most of these journals. Also, not all published studies are intended for or ready for clinical practice application. The authors developed “Best Evidence in Emergency Medicine” (BEEM) to ameliorate these problems by searching for, identifying, appraising, and translating potentially practice-changing studies for EPs. An initial step in the BEEM process is the BEEM rater scale, a novel tool for EPs to collectively evaluate the relative clinical relevance of EM-related studies found in more than 120 journals. The BEEM rater process was designed to serve as a clinical relevance filter to identify those studies with the greatest potential to affect EM practice. Therefore, only those studies identified by BEEM raters as having the highest clinical relevance are selected for the subsequent critical appraisal process and, if found methodologically sound, are promoted as the best evidence in EM. Objectives The primary objective was to measure inter-rater reliability (IRR) of the BEEM rater scale. Secondary objectives were to determine the minimum number of EP raters needed for the BEEM rater scale to achieve acceptable reliability and to compare performance of the scale against a previously published evidence rating system, the McMaster Online Rating of Evidence (MORE), in an EP population. Methods The authors electronically distributed the title, conclusion, and a PubMed link for 23 recently published studies related to EM to a volunteer group of 134 EPs. The volunteers answered two demographic questions and rated the articles using one of two randomly assigned seven-point Likert scales, the BEEM rater scale (n = 68) or the MORE scale (n = 66), over two separate administrations. The IRR of each scale was measured using generalizability theory. Results The IRR of the BEEM rater scale ranged between 0.90 (95% confidence interval [CI] = 0.86 to 0.93) to 0.92 (95% CI = 0.89 to 0.94) across administrations. Decision studies showed a minimum of 12 raters is required for acceptable reliability of the BEEM rater scale. The IRR of the MORE scale was 0.82 to 0.84. Conclusions The BEEM rater scale is a highly reliable, single-question tool for a small number of EPs to collectively rate the relative clinical relevance within the specialty of EM of recently published studies from a variety of medical journals. It compares favorably with the MORE system because it achieves a high IRR despite simply requiring raters to read each article’s title and conclusion. PMID:22092904

A Laparoscopic Swine Model of Noncompressible Torso Hemorrhage

DTIC Science & Technology

2014-01-01

Various porcine models of hemorrhage have been developed for civilian and military trauma research. However, the predominant contemporary models lack...significant predictors of mortality. CONCLUSION: This study describes a model of NCTH that reflects clinically relevant physiology in trauma and...uncontrolled hemorrhage. In addition, it quantitatively assesses the role of the swine contractile spleen in the described model. (J Trauma Acute Care Surg

[Analysis of the results of the SEIMC External Quality Control Program. Year 2011].

PubMed

Ruiz de Gopegui Bordes, Enrique; Guna Serrano, M del Remedio; Orta Mira, Nieves; Ovies, María Rosario; Poveda, Marta; Gimeno Cardona, Concepción

2013-02-01

The External Quality Control Program of the Spanish Society of Infectious Diseases and Clinical Microbiology (Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica [SEIMC]) includes controls for bacteriology, serology, mycology, parasitology, mycobacteria, virology, and molecular microbiology. This article presents the most relevant conclusions and lessons from the 2011 controls. Overall, the results obtained in 2011 confirm the excellent skill and good technical standards found in previous years. Nevertheless, 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, such as those offered by the SEIMC program, in order to ensure maximal quality of microbiological tests. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Infection does not increase long-term mortality in patients with acute severe alcoholic hepatitis treated with corticosteroids

PubMed Central

Dhanda, Ashwin D; Sinha, Ashish; Hunt, Vicky; Saleem, Sarah; Cramp, Matthew E; Collins, Peter L

2017-01-01

AIM To determine whether infection in patients with acute severe alcoholic hepatitis (AAH) treated with corticosteroids is associated with increased mortality. METHODS Consecutive patients with AAH were treated with steroids and recruited to the study. Clinically relevant infections (body temperature > 38 °C or < 36 °C for more than 4 h, ascitic neutrophil count > 0.25 ×109/L, consolidation on chest radiograph or clinically relevant positive microbiological culture of bodily fluid) were recorded prospectively. Clinical and laboratory parameters were recorded and survival at 90 d and 6 mo was determined. Univariate analysis of factors associated with 90-d mortality was performed and significant variables included in a multivariate analysis. RESULTS Seventy-two patients were included in the final analysis (mean age 47.9 years, 26% female, mean discriminant function 53.0). Overall mortality in the group occurred in 15 (21%), 23 (32%) and 31 (43%) at day 28, day 90 and 1 year respectively. 36 (50%) had a clinically relevant infection during their hospitalisation (23 after initiation of steroids). The median time to development of incident infection after commencement of steroids was 10 d. The commonest site of infection was ascites (31%) and bacteraemia (31%) followed by urinary tract (19%) and respiratory tract (8%). Forty-one separate organisms were isolated in 33 patients; the most frequent genus was Escherichia (22%) and Enterococcus (20%). Infection was not associated with 90-d or 1 year mortality but was associated with higher creatinine, model for end-stage liver disease and Lille score. Baseline urea was the only independent predictor of 90-d mortality. CONCLUSION Clinically relevant infections are common in patients with AAH but are not associated with increased 90-d or 1 year mortality. PMID:28373772

Examining Curricular Integration Strategies To Optimize Learning Of The Anatomical Sciences

NASA Astrophysics Data System (ADS)

Lisk, Kristina Adriana Ayako

Background: Integration of basic and clinical science knowledge is essential to clinical practice. Although the importance of these two knowledge domains is well-recognized, successfully supporting the development of learners' integrated basic and clinical science knowledge, remains an educational challenge. In this dissertation, I examine curricular integration strategies to optimize learning of the anatomical sciences. Objectives: The studies were designed to achieve the following research aims: 1) to objectively identify clinically relevant content for an integrated musculoskeletal anatomy curriculum; 2) to examine the value of integrated anatomy and clinical science instruction compared to clinical science instruction alone on novices' diagnostic accuracy and diagnostic reasoning process; 3) to compare the effect of integrating and segregating anatomy and clinical science instruction along with a learning strategy (self-explanation) on novices' diagnostic accuracy. Methods: A modified Delphi was used to objectively select clinically relevant content for an integrated musculoskeletal anatomy curriculum. Two experimental studies were created to compare different instructional strategies to optimize learning of the curricular content. In both of these studies, novice learners were taught the clinical features of musculoskeletal pathologies using different learning approaches. Diagnostic performance was measured immediately after instruction and one-week later. Results: The results show that the Delphi method is an effective strategy to select clinically relevant content for integrated anatomy curricula. The findings also demonstrate that novices who were explicitly taught the clinical features of musculoskeletal diseases using causal basic science descriptions had superior diagnostic accuracy and a better understanding of the relative importance of key clinical features for disease categories. Conclusions: This research demonstrates how integration strategies can be applied at multiple levels of the curriculum. Further, this work shows the value of cognitive integration of anatomy and clinical science and it emphasizes the importance of purposefully linking the anatomical and clinical sciences in day-to-day teaching.

How do Supervising Clinicians of a University Hospital and Associated Teaching Hospitals Rate the Relevance of the Key Competencies within the CanMEDS Roles Framework in Respect to Teaching in Clinical Clerkships?

PubMed Central

Jilg, Stefanie; Möltner, Andreas; Berberat, Pascal; Fischer, Martin R.; Breckwoldt, Jan

2015-01-01

Background and aim: In German-speaking countries, the physicians’ roles framework of the “Canadian Medical Education Directives for Specialists” (CanMEDS) is increasingly used to conceptualize postgraduate medical education. It is however unclear, whether it may also be applied to the final year of undergraduate education within clinical clerkships, called “Practical Year” (PY). Therefore, the aim of this study was to explore how clinically active physicians at a university hospital and at associated teaching hospitals judge the relevance of the seven CanMEDS roles (and their (role-defining) key competencies) in respect to their clinical work and as learning content for PY training. Furthermore, these physicians were asked whether the key competencies were actually taught during PY training. Methods: 124 physicians from internal medicine and surgery rated the relevance of the 28 key competencies of the CanMEDS framework using a questionnaire. For each competency, following three aspects were rated: “relevance for your personal daily work”, “importance for teaching during PY”, and “implementation into actual PY teaching”. Results: In respect to the main study objective, all questionnaires could be included into analysis. All seven CanMEDS roles were rated as relevant for personal daily work, and also as important for teaching during PY. Furthermore, all roles were stated to be taught during actual PY training. The roles “Communicator”, “Medical Expert”, and “Collaborator” were rated as significantly more important than the other roles, for all three sub-questions. No differences were found between the two disciplines internal medicine and surgery, nor between the university hospital and associated teaching hospitals. Conclusion: Participating physicians rated all key competencies of the CanMEDS model to be relevant for their personal daily work, and for teaching during PY. These findings support the suitability of the CanMEDS framework as a conceptual element of PY training. PMID:26413171

Clinically relevant safety issues associated with St. John's wort product labels

PubMed Central

Clauson, Kevin A; Santamarina, Marile L; Rutledge, Jennifer C

2008-01-01

Background St. John's wort (SJW), used to treat depression, is popular in the USA, Canada, and parts of Europe. However, there are documented interactions between SJW and prescription medications including warfarin, cyclosporine, indinavir, and oral contraceptives. One source of information about these safety considerations is the product label. The aim of this study was to evaluate the clinically relevant safety information included on labeling in a nationally representative sample of SJW products from the USA. Methods Eight clinically relevant safety issues were identified: drug interactions (SJW-HIV medications, SJW-immunosupressants, SJW-oral contraceptives, and SJW-warfarin), contraindications (bipolar disorder), therapeutic duplication (antidepressants), and general considerations (phototoxicity and advice to consult a healthcare professional (HCP)). A list of SJW products was identified to assess their labels. Percentages and totals were used to present findings. Results Of the seventy-four products evaluated, no product label provided information for all 8 evaluation criteria. Three products (4.1%) provided information on 7 of the 8 criteria. Four products provided no safety information whatsoever. Percentage of products with label information was: SJW-HIV (8.1%), SJW-immunosupressants (5.4%), SJW-OCPs (8.1%), SJW-warfarin (5.4%), bipolar (1.4%), antidepressants (23.0%), phototoxicity (51.4%), and consult HCP (87.8%). Other safety-related information on labels included warnings about pregnancy (74.3%), lactation (64.9%), discontinue if adverse reaction (23.0%), and not for use in patients under 18 years old (13.5%). The average number of a priori safety issues included on a product label was 1.91 (range 0–8) for 23.9% completeness. Conclusion The vast majority of SJW products fail to adequately address clinically relevant safety issues on their labeling. A few products do provide an acceptable amount of information on clinically relevant safety issues which could enhance the quality of counseling by HCPs and health store clerks. HCPs and consumers may benefit if the FDA re-examined labeling requirements for dietary supplements. PMID:18637192

Body posture changes in women with migraine with or without temporomandibular disorders

PubMed Central

Ferreira, Mariana C.; Bevilaqua-Grossi, Débora; Dach, Fabíola É.; Speciali, José G.; Gonçalves, Maria C.; Chaves, Thais C.

2014-01-01

Background Migraine and temporomandibular disorders (TMDs) are reported to be associated. However, there are no reports on the association among migraines, TMDs and changes in body posture. Objectives To assess changes in body posture in women suffering migraines with or without TMD compared with a control group. Method Sixty-six women with a mean age of 18 to 45 years participated in this study. The groups were composed of 22 volunteers with migraine and TMD (MTMD), 22 volunteers with migraines without TMD (MG) and 22 women in the control group (CG). Static posture was assessed by photogrammetry, and 19 angles were measured. Results Postural asymmetry was observed in the face for 4 angles measured on the frontal plane in the MG group and for 4 angles of the trunk in the MG and MTMD groups with respect to CG. However, for comparisons between MTMD and CG, clinical relevance was identified for two angles of the sagittal plane (Cervical and Lumbar Lordosis, Effect Size - ES - moderate: 0.53 and 0.60). For comparisons between the MG and CG, the clinical relevance/potential was verified for three angles with moderate ES (ES>0.42). The clinical relevance when comparing MTMD and CG was identified for four angles of facial symmetry head inclination (ES>0.54) and for two angles between MG and CG (ES>0.48). Conclusion The results demonstrated the presence of postural changes compared with a control group in women with migraines with or without TMD, and there were similar clinically relevant postural changes among the patients with migraines with and without TMD. PMID:24675909

Clinical relevance of metronidazole and peripheral neuropathy: a systematic review of the literature.

PubMed

Goolsby, Tiffany A; Jakeman, Bernadette; Gaynes, Robert P

2018-03-01

The objective of this paper was to review and evaluate the literature on metronidazole-associated peripheral neuropathy and determine the relevance in clinical practice. MEDLINE/PubMed, EBSCO, and Google Scholar were searched through February 2017 using the search terms metronidazole and peripheral neuropathy, or polyneuropathy, or paresthesia, or neurotoxicity. Relevant case reports, retrospective studies, surveys, and review articles were included. Bibliographies of all relevant articles were reviewed for additional sources. Overall, metronidazole is generally well tolerated, but serious neurotoxicity, including peripheral neuropathy, has been reported. The overall incidence of peripheral neuropathy associated with metronidazole is unknown. Our review found 36 case reports (40 unique patients) of metronidazole-associated peripheral neuropathy, with most cases (31/40) receiving a >42 g total (>4 weeks) of therapy. In addition, we reviewed 13 clinical studies and found varying rates of peripheral neuropathy from 0 to 50%. Within these clinical studies, we found a higher incidence of peripheral neuropathy in patients receiving >42 g total (>4 weeks) of metronidazole compared with those patients receiving ≤42 g total (17.9% vs. 1.7%). Nearly all patients had complete resolution of symptoms. In conclusion, peripheral neuropathy is rare in patients who receive ≤42 g total of metronidazole. Patients who receive higher total doses may be at higher risk of peripheral neuropathy, but symptoms resolve after discontinuation of therapy in most patients. Antimicrobial stewardship programs may consider use of antibiotic combinations that include metronidazole over broad-spectrum alternatives when treating with ≤42 g total of the drug (≤4 weeks). Published by Elsevier B.V.

Practical Problems with Medication Use that Older People Experience: A Qualitative Study

PubMed Central

Notenboom, Kim; Beers, Erna; van Riet-Nales, Diana A; Egberts, Toine C G; Leufkens, Hubert G M; Jansen, Paul A F; Bouvy, Marcel L

2014-01-01

Objectives To identify the practical problems that older people experience with the daily use of their medicines and their management strategies to address these problems and to determine the potential clinical relevance thereof. Design Qualitative study with semistructured face-to-face interviews. Setting A community pharmacy and a geriatric outpatient ward. Participants Community-dwelling people aged 70 and older (N = 59). Measurements Participants were interviewed at home. Two researchers coded the reported problems and management strategies independently according to a coding scheme. An expert panel classified the potential clinical relevance of every identified practical problem and associated management strategy using a 3-point scale. Results Two hundred eleven practical problems and 184 management strategies were identified. Ninety-five percent of the participants experienced one or more practical problems with the use of their medicines: problems reading and understanding the instructions for use, handling the outer packaging, handling the immediate packaging, completing preparation before use, and taking the medicine. For 10 participants, at least one of their problems, in combination with the applied management strategy, had potential clinical consequences and 11 cases (5% of the problems) had the potential to cause moderate or severe clinical deterioration. Conclusion Older people experience a number of practical problems using their medicines, and their strategies to manage these problems are sometimes suboptimal. These problems can lead to incorrect medication use with clinically relevant consequences. The findings pose a challenge for healthcare professionals, drug developers, and regulators to diminish these problems. PMID:25516030

A Review of the Medical Education Literature for Graduate Medical Education Teachers

PubMed Central

Locke, Kenneth A.; Bates, Carol K.; Karani, Reena; Chheda, Shobhina G.

2013-01-01

Background A rapidly evolving body of literature in medical education can impact the practice of clinical educators in graduate medical education. Objective To aggregate studies published in the medical education literature in 2011 to provide teachers in general internal medicine with an overview of the current, relevant medical education literature. Review We systematically searched major medical education journals and the general clinical literature for medical education studies with sound design and relevance to the educational practice of graduate medical education teachers. We chose 12 studies, grouped into themes, using a consensus method, and critiqued these studies. Results Four themes emerged. They encompass (1) learner assessment, (2) duty hour limits and teaching in the inpatient setting, (3) innovations in teaching, and (4) learner distress. With each article we also present recommendations for how readers may use them as resources to update their clinical teaching. While we sought to identify the studies with the highest quality and greatest relevance to educators, limitation of the studies selected include their single-site and small sample nature, and the frequent lack of objective measures of outcomes. These limitations are shared with the larger body of medical education literature. Conclusions The themes and the recommendations for how to incorporate this information into clinical teaching have the potential to inform the educational practice of general internist educators as well as that of teachers in other specialties. PMID:24404262

Evaluation of the safety profile of an electronic vapour product used for two years by smokers in a real-life setting.

PubMed

Walele, Tanvir; Bush, Jim; Koch, Annelize; Savioz, Rebecca; Martin, Claire; O'Connell, Grant

2018-02-01

The safety profile of Puritane™, a closed system electronic vapour product (EVP), was evaluated when used by smokers of conventional cigarettes (CCs) for 24 months in a real-life setting. The study was a two-centre ambulatory clinical study with 209 healthy volunteers. Outcome measures included adverse events (AEs), vital signs, electrocardiogram, lung function tests, exposure to nicotine and selected smoke constituents, nicotine withdrawal effects and smoking desire. No serious AEs related to EVP use were observed. The most frequently reported AEs were headache, nasopharyngitis, sore throat and cough, reported by 28.7%, 28.7%, 19.6% and 16.7% of subjects, respectively, which dissipated over time. Small decreases in lung function were not considered clinically relevant. No clinically relevant findings were observed in the other safety parameters. From Month 2, nicotine withdrawal symptoms decreased. Smoking desire and CC consumption steadily decreased over time in all subjects. EVP use was associated with reduced exposure to cigarette smoke constituents, whereas urinary nicotine levels remained close to baseline. Body weight did not increase in CC subjects switching to the EVP. In conclusion, the aerosol of the EVP at study was well tolerated and not associated with any clinically relevant health concerns after usage for up to 24 months. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Clinical laboratory sciences data transmission : the NPU coding system

PubMed Central

PONTET, Françoise; PETERSEN, Ulla MAGDAL; FUENTES-ARDERIU, Xavier; NORDIN, Gunnar; BRUUNSHUUS, Ivan; IHALAINEN, Jarkko; KARLSSON, Daniel; FORSUM, Urban; DYBKAER, René; SCHADOW, Gunther; KUELPMANN, Wolf; FÉRARD, Georges; KANG, Dongchon; McDONALD, Clement; HILL, Gilbert

2011-01-01

Introduction In health care services, technology requires that correct information be duly available to professionals, citizens and authorities, worldwide. Thus, clinical laboratory sciences require standardized electronic exchanges for results of laboratory examinations. Methods. The NPU (Nomenclature, Properties and Units) coding system provides a terminology for identification of result values (property values). It is structured according to BIPM, ISO, IUPAC and IFCC recommendations. It uses standard terms for established concepts and structured definitions describing: which part of the universe is examined, which component of relevance in that part, which kind-of-property is relevant. Unit and specifications can be added where relevant [System(spec) Component(spec); kind-of-property(spec) = ? unit]. Results. The English version of this terminology is freely accessible at http://dior.imt.liu.se/cnpu/ and http://www.labterm.dk, directly or through the IFCC and IUPAC websites. It has been nationally used for more than 10 years in Denmark and Sweden and has been translated into 6 other languages. Conclusions. The NPU coding system provides a terminology for dedicated kinds-of-property following the international recommendations. It fits well in the health network and is freely accessible. Clinical laboratory professionals worldwide will find many advantages in using the NPU coding system, notably with regards to an accreditation process. PMID:19745311

Psychopharmacological and Other Treatments in Preschool Children with Attention-Deficit/Hyperactivity Disorder: Current Evidence and Practice

PubMed Central

Arnold, L. Eugene; Anthony, Bruno J.

2008-01-01

Abstract Objective This article reviews rational approaches to treating attention-deficit/hyperactivity disorder (ADHD) in preschool children, including pharmacological and nonpharmacological treatments. Implications for clinical practice are discussed. Data Sources We searched MEDLINE, PsychINFO, Cumulative Index to Nursing & Allied Health, Educational Resources Information Center, Cochrane Database of Systematic Reviews and Database of Abstracts of Reviews of Effects for relevant literature published in English from 1967 to 2007 on preschool ADHD. We also reviewed the references cited in identified reports. Study Selection Studies were reviewed if the sample included at least some children younger than 6 years of age or attending kindergarten, the study participants had a diagnosis of ADHD or equivalent symptoms, received intervention aimed at ADHD symptoms, and included a relevant outcome measure. Data Extraction Studies were reviewed for type of intervention and outcome relevant to ADHD and were rated for the level of evidence for adequacy of the data to inform clinical practice. Conclusions The current level of evidence for adequacy of empirical data to inform clinical practice for short-term treatment of ADHD in preschool children is Level A for methylphenidate and Level B for parent behavior training, child training, and additive-free elimination diet. PMID:18844482

Laboratory Exercises to Teach Clinically Relevant Chemistry of Antibiotics

PubMed Central

Chelette, Candace T.

2014-01-01

Objectives. To design, implement, and evaluate student performance on clinically relevant chemical and spectral laboratory exercises on antibiotics. Design. In the first of 2 exercises, second-year pharmacy students enrolled in an integrated laboratory sequence course studied the aqueous stability of ß-lactam antibiotics using a spectral visual approach. In a second exercise, students studied the tendency of tetracycline, rifamycins, and fluoroquinolones to form insoluble chelate complexes (turbidity) with polyvalent metals. Assessment. On a survey to assess achievement of class learning objectives, students agreed the laboratory activities helped them better retain important information concerning antibiotic stability and interactions. A significant improvement was observed in performance on examination questions related to the laboratory topics for 2012 and 2013 students compared to 2011 students who did not complete the laboratory. A 1-year follow-up examination question administered in a separate course showed >75% of the students were able to identify rifamycins-food interactions compared with <25% of students who had not completed the laboratory exercises. Conclusion. The use of spectral visual approaches allowed students to investigate antibiotic stability and interactions, thus reinforcing the clinical relevance of medicinal chemistry. Students’ performance on questions at the 1-year follow-up suggested increased retention of the concepts learned as a result of completing the exercises. PMID:24672070

A Novel Clinically Relevant Strategy to Abrogate Autoimmunity and Regulate Alloimmunity in NOD Mice

PubMed Central

Vergani, Andrea; D'Addio, Francesca; Jurewicz, Mollie; Petrelli, Alessandra; Watanabe, Toshihiko; Liu, Kaifeng; Law, Kenneth; Schuetz, Christian; Carvello, Michele; Orsenigo, Elena; Deng, Shaoping; Rodig, Scott J.; Ansari, Javeed M.; Staudacher, Carlo; Abdi, Reza; Williams, John; Markmann, James; Atkinson, Mark; Sayegh, Mohamed H.; Fiorina, Paolo

2010-01-01

OBJECTIVE To investigate a new clinically relevant immunoregulatory strategy based on treatment with murine Thymoglobulin mATG Genzyme and CTLA4-Ig in NOD mice to prevent allo- and autoimmune activation using a stringent model of islet transplantation and diabetes reversal. RESEARCH DESIGN AND METHODS Using allogeneic islet transplantation models as well as NOD mice with recent onset type 1 diabetes, we addressed the therapeutic efficacy and immunomodulatory mechanisms associated with a new immunoregulatory protocol based on prolonged low-dose mATG plus CTLA4-Ig. RESULTS BALB/c islets transplanted into hyperglycemic NOD mice under prolonged mATG+CTLA4-Ig treatment showed a pronounced delay in allograft rejection compared with untreated mice (mean survival time: 54 vs. 8 days, P < 0.0001). Immunologic analysis of mice receiving transplants revealed a complete abrogation of autoimmune responses and severe downregulation of alloimmunity in response to treatment. The striking effect on autoimmunity was confirmed by 100% diabetes reversal in newly hyperglycemic NOD mice and 100% indefinite survival of syngeneic islet transplantation (NOD.SCID into NOD mice). CONCLUSIONS The capacity to regulate alloimmunity and to abrogate the autoimmune response in NOD mice in different settings confirmed that prolonged mATG+CTLA4-Ig treatment is a clinically relevant strategy to translate to humans with type 1 diabetes. PMID:20805386

Integration of Evidence into a Detailed Clinical Model-based Electronic Nursing Record System

PubMed Central

Park, Hyeoun-Ae; Jeon, Eunjoo; Chung, Eunja

2012-01-01

Objectives The purpose of this study was to test the feasibility of an electronic nursing record system for perinatal care that is based on detailed clinical models and clinical practice guidelines in perinatal care. Methods This study was carried out in five phases: 1) generating nursing statements using detailed clinical models; 2) identifying the relevant evidence; 3) linking nursing statements with the evidence; 4) developing a prototype electronic nursing record system based on detailed clinical models and clinical practice guidelines; and 5) evaluating the prototype system. Results We first generated 799 nursing statements describing nursing assessments, diagnoses, interventions, and outcomes using entities, attributes, and value sets of detailed clinical models for perinatal care which we developed in a previous study. We then extracted 506 recommendations from nine clinical practice guidelines and created sets of nursing statements to be used for nursing documentation by grouping nursing statements according to these recommendations. Finally, we developed and evaluated a prototype electronic nursing record system that can provide nurses with recommendations for nursing practice and sets of nursing statements based on the recommendations for guiding nursing documentation. Conclusions The prototype system was found to be sufficiently complete, relevant, useful, and applicable in terms of content, and easy to use and useful in terms of system user interface. This study has revealed the feasibility of developing such an ENR system. PMID:22844649

Roles of caloric restriction, ketogenic diet and intermittent fasting during initiation, progression and metastasis of cancer in animal models: a systematic review and meta-analysis.

PubMed

Lv, Mengmeng; Zhu, Xingya; Wang, Hao; Wang, Feng; Guan, Wenxian

2014-01-01

The role of dietary restriction regimens such as caloric restriction, ketogenic diet and intermittent fasting in development of cancers has been detected via abundant preclinical experiments. However, the conclusions are controversial. We aim to review the relevant animal studies systematically and provide assistance for further clinical studies. Literatures on associations between dietary restriction and cancer published in PubMed in recent twenty years were comprehensively searched. Animal model, tumor type, feeding regimen, study length, sample size, major outcome, conclusion, quality assessment score and the interferential step of cancer were extracted from each eligible study. We analyzed the tumor incidence rates from 21 studies about caloric restriction. Fifty-nine studies were involved in our system review. The involved studies explored roles of dietary restriction during initiation, progression and metastasis of cancer. About 90.9% of the relevant studies showed that caloric restriction plays an anti-cancer role, with the pooled OR (95%CI) of 0.20 (0.12, 0.34) relative to controls. Ketogenic diet was also positively associated with cancer, which was indicated by eight of the nine studies. However, 37.5% of the related studies obtained a negative conclusion that intermittent fasting was not significantly preventive against cancer. Caloric restriction and ketogenic diet are effective against cancer in animal experiments while the role of intermittent fasting is doubtful and still needs exploration. More clinical experiments are needed and more suitable patterns for humans should be investigated.

Medical student attitudes toward kidney physiology and nephrology: a qualitative study.

PubMed

Roberts, John K; Sparks, Matthew A; Lehrich, Ruediger W

2016-11-01

Interest in nephrology among trainees is waning in the USA. Early perceptions and attitudes to subject matter can be linked to the quality of pre-clinical curricula. We wanted to explore these attitudes in the setting of modern curriculum redesign. We utilized Q methodology to understand first-year medical student attitudes after an innovative kidney physiology curriculum redesign that focuses on blending multiple learning methods. First-year medical students were invited to take a Q sort survey at the conclusion of a kidney physiology course. Students prioritized statements related to their understanding of kidney physiology, learning preferences, preferred course characteristics, perceived clinical relevance of kidney physiology, and interest in nephrology as a career. Factor analysis was performed to identify different student viewpoints. At the conclusion of our modified course, all students (n = 108) were invited to take the survey and 44 (41%) Q sorts were returned. Two dominant viewpoints were defined according to interest in nephrology. The Potentials are students who understand kidney physiology, perceive kidney physiology as clinically relevant, attend class sessions, utilize videos, and are willing to shadow a nephrologist. The Uninterested are students who are less satisfied with their kidney physiology knowledge, prefer to study alone with a textbook, avoid lectures, and are not interested in learning about nephrology. In an updated renal physiology course, students that use multiple learning methods also have favorable attitudes toward learning kidney physiology. Thus, modern curriculum changes that accommodate a variety of learning styles may promote positive attitudes toward nephrology.

Rare Variation in TET2 Is Associated with Clinically Relevant Prostate Carcinoma in African-Americans

PubMed Central

Koboldt, Daniel C.; Kanchi, Krishna L.; Gui, Bin; Larson, David E.; Fulton, Robert S.; Isaacs, William B.; Kraja, Aldi; Borecki, Ingrid B.; Jia, Li; Wilson, Richard K.; Mardis, Elaine R.; Kibel, Adam S.

2016-01-01

Background Common variants have been associated with prostate cancer risk. Unfortunately, few are reproducibly linked to aggressive disease, the phenotype of greatest clinical relevance. One possible explanation is that rare genetic variants underlie a significant proportion of the risk for aggressive disease. Method To identify such variants, we performed a two staged approach using whole exome sequencing followed by targeted sequencing of 800 genes in 652 aggressive prostate cancer patients and 752 disease-free controls in both African and European Americans. In each population, we tested rare variants for association using two gene-based aggregation tests. We established a study-wide significance threshold of 3.125 × 10−5 to correct for multiple testing. Results TET2 in African-Americans was associated with aggressive disease with 24.4% of cases harboring a rare deleterious variant compared to 9.6% of controls (FET p = 1.84×10−5, OR=3.0; SKAT-O p= 2.74×10−5). We report 8 additional genes with suggestive evidence of association, including the DNA repair genes PARP2 and MSH6. Finally, we observed an excess of rare truncation variants in 5 genes including the DNA repair genes MSH6, BRCA1 and BRCA2. This adds to the growing body of evidence that DNA repair pathway defects may influence susceptibility to aggressive prostate cancer. Conclusion Our findings suggest that rare variants influence risk of clinically relevant prostate cancer and, if validated, could serve to identify men for screening, prophylaxis and treatment. Impact This study provides evidence that rare variants in TET2 may help identify African-American men at increased risk for clinically relevant prostate cancer. PMID:27486019

Correlates of a Good Death and the Impact of Hospice Involvement: Findings from the National Survey of Households Affected by Cancer

PubMed Central

Cagle, John G.; Pek, Jolynn; Clifford, Maggie; Guralnik, Jack; Zimmerman, Sheryl

2017-01-01

Purpose Knowing how to improve the dying experience for patients with end-stage cancer is essential for cancer professionals. However, there is little evidence on the relationship between clinically relevant factors and quality of death. Also, while hospice has been linked with improved outcomes, our understanding of factors that contribute to a “good death” when hospice is involved remains limited. This study (1) identified correlates of a good death; and, (2) provided evidence on the impact of hospice on quality of death. Methods Using data from a survey of US households affected by cancer (N=930, response rate 51%), we fit regression models with a subsample of 158 respondents who had experienced the death of a family member with cancer. Measures included quality of death (good/bad) and clinically relevant factors including: hospice involvement, symptoms during treatment, whether wishes were followed, provider knowledge/expertise and compassion. Results Respondents were 60% female, 89% White, and averaged 57 years old. Decedents were most often a respondent's spouse (46%). While 73% of respondents reported a good death, Hispanics were less likely to experience good death (p=.007). Clinically relevant factors, including hospice, were associated with good death (p<.05) -- an exception being whether the physician said the cancer was curable/fatal. With adjustments, perceptions of provider knowledge/expertise was the only clinical factor that remained associated with good death. Conclusions Enhanced provider training/communication, referrals to hospice and greater attention to symptom management may facilitate improved quality of dying. Additionally, the cultural relevance of the concept of a “good death” warrants further research. PMID:25194877

Clinical Research Informatics: Supporting the Research Study Lifecycle.

PubMed

Johnson, S B

2017-08-01

Objectives: The primary goal of this review is to summarize significant developments in the field of Clinical Research Informatics (CRI) over the years 2015-2016. The secondary goal is to contribute to a deeper understanding of CRI as a field, through the development of a strategy for searching and classifying CRI publications. Methods: A search strategy was developed to query the PubMed database, using medical subject headings to both select and exclude articles, and filtering publications by date and other characteristics. A manual review classified publications using stages in the "research study lifecycle", with key stages that include study definition, participant enrollment, data management, data analysis, and results dissemination. Results: The search strategy generated 510 publications. The manual classification identified 125 publications as relevant to CRI, which were classified into seven different stages of the research lifecycle, and one additional class that pertained to multiple stages, referring to general infrastructure or standards. Important cross-cutting themes included new applications of electronic media (Internet, social media, mobile devices), standardization of data and procedures, and increased automation through the use of data mining and big data methods. Conclusions: The review revealed increased interest and support for CRI in large-scale projects across institutions, regionally, nationally, and internationally. A search strategy based on medical subject headings can find many relevant papers, but a large number of non-relevant papers need to be detected using text words which pertain to closely related fields such as computational statistics and clinical informatics. The research lifecycle was useful as a classification scheme by highlighting the relevance to the users of clinical research informatics solutions. Georg Thieme Verlag KG Stuttgart.

What do evidence-based secondary journals tell us about the publication of clinically important articles in primary healthcare journals?

PubMed Central

McKibbon, Kathleen Ann; Wilczynski, Nancy L; Haynes, Robert Brian

2004-01-01

Background We conducted this analysis to determine i) which journals publish high-quality, clinically relevant studies in internal medicine, general/family practice, general practice nursing, and mental health; and ii) the proportion of clinically relevant articles in each journal. Methods We performed an analytic survey of a hand search of 170 general medicine, general healthcare, and specialty journals for 2000. Research staff assessed individual articles by using explicit criteria for scientific merit for healthcare application. Practitioners assessed the clinical importance of these articles. Outcome measures were the number of high-quality, clinically relevant studies published in the 170 journal titles and how many of these were published in each of four discipline-specific, secondary "evidence-based" journals (ACP Journal Club for internal medicine and its subspecialties; Evidence-Based Medicine for general/family practice; Evidence-Based Nursing for general practice nursing; and Evidence-Based Mental Health for all aspects of mental health). Original studies and review articles were classified for purpose: therapy and prevention, screening and diagnosis, prognosis, etiology and harm, economics and cost, clinical prediction guides, and qualitative studies. Results We evaluated 60,352 articles from 170 journal titles. The pass criteria of high-quality methods and clinically relevant material were met by 3059 original articles and 1073 review articles. For ACP Journal Club (internal medicine), four titles supplied 56.5% of the articles and 27 titles supplied the other 43.5%. For Evidence-Based Medicine (general/family practice), five titles supplied 50.7% of the articles and 40 titles supplied the remaining 49.3%. For Evidence-Based Nursing (general practice nursing), seven titles supplied 51.0% of the articles and 34 additional titles supplied 49.0%. For Evidence-Based Mental Health (mental health), nine titles supplied 53.2% of the articles and 34 additional titles supplied 46.8%. For the disciplines of internal medicine, general/family practice, and mental health (but not general practice nursing), the number of clinically important articles was correlated withScience Citation Index (SCI) Impact Factors. Conclusions Although many clinical journals publish high-quality, clinically relevant and important original studies and systematic reviews, the articles for each discipline studied were concentrated in a small subset of journals. This subset varied according to healthcare discipline; however, many of the important articles for all disciplines in this study were published in broad-based healthcare journals rather than subspecialty or discipline-specific journals. PMID:15350200

Evaluation of an Instructional Model to Teach Clinically Relevant Medicinal Chemistry in a Campus and a Distance Pathway

PubMed Central

Galt, Kimberly A.

2008-01-01

Objectives To evaluate an instructional model for teaching clinically relevant medicinal chemistry. Methods An instructional model that uses Bloom's cognitive and Krathwohl's affective taxonomy, published and tested concepts in teaching medicinal chemistry, and active learning strategies, was introduced in the medicinal chemistry courses for second-professional year (P2) doctor of pharmacy (PharmD) students (campus and distance) in the 2005-2006 academic year. Student learning and the overall effectiveness of the instructional model were assessed. Student performance after introducing the instructional model was compared to that in prior years. Results Student performance on course examinations improved compared to previous years. Students expressed overall enthusiasm about the course and better understood the value of medicinal chemistry to clinical practice. Conclusion The explicit integration of the cognitive and affective learning objectives improved student performance, student ability to apply medicinal chemistry to clinical practice, and student attitude towards the discipline. Testing this instructional model provided validation to this theoretical framework. The model is effective for both our campus and distance-students. This instructional model may also have broad-based applications to other science courses. PMID:18483599

Food for Thought Look Back in Anger – What Clinical Studies Tell Us About Preclinical Work

PubMed Central

Hartung, Thomas

2013-01-01

Summary Misled by animal studies and basic research? Whenever we take a closer look at the outcome of clinical trials in a field such as, most recently, stroke or septic shock, we see how limited the value of our preclinical models was. For all indications, 95% of drugs that enter clinical trials do not make it to the market, despite all promise of the (animal) models used to develop them. Drug development has started already to decrease its reliance on animal models: In Europe, for example, despite increasing R&D expenditure, animal use by pharmaceutical companies dropped by more than 25% from 2005 to 2008. In vitro studies are likewise limited: questionable cell authenticity, over-passaging, mycoplasma infections, and lack of differentiation as well as non-homeostatic and non-physiologic culture conditions endanger the relevance of these models. The standards of statistics and reporting often are poor, further impairing reliability. Alarming studies from industry show miserable reproducibility of landmark studies. This paper discusses factors contributing to the lack of reproducibility and relevance of pre-clinical research. The conclusion: Publish less but of better quality and do not rely on the face value of animal studies. PMID:23861075

A methodological approach to identify external factors for indicator-based risk adjustment illustrated by a cataract surgery register

PubMed Central

2014-01-01

Background Risk adjustment is crucial for comparison of outcome in medical care. Knowledge of the external factors that impact measured outcome but that cannot be influenced by the physician is a prerequisite for this adjustment. To date, a universal and reproducible method for identification of the relevant external factors has not been published. The selection of external factors in current quality assurance programmes is mainly based on expert opinion. We propose and demonstrate a methodology for identification of external factors requiring risk adjustment of outcome indicators and we apply it to a cataract surgery register. Methods Defined test criteria to determine the relevance for risk adjustment are “clinical relevance” and “statistical significance”. Clinical relevance of the association is presumed when observed success rates of the indicator in the presence and absence of the external factor exceed a pre-specified range of 10%. Statistical significance of the association between the external factor and outcome indicators is assessed by univariate stratification and multivariate logistic regression adjustment. The cataract surgery register was set up as part of a German multi-centre register trial for out-patient cataract surgery in three high-volume surgical sites. A total of 14,924 patient follow-ups have been documented since 2005. Eight external factors potentially relevant for risk adjustment were related to the outcome indicators “refractive accuracy” and “visual rehabilitation” 2–5 weeks after surgery. Results The clinical relevance criterion confirmed 2 (“refractive accuracy”) and 5 (“visual rehabilitation”) external factors. The significance criterion was verified in two ways. Univariate and multivariate analyses revealed almost identical external factors: 4 were related to “refractive accuracy” and 7 (6) to “visual rehabilitation”. Two (“refractive accuracy”) and 5 (“visual rehabilitation”) factors conformed to both criteria and were therefore relevant for risk adjustment. Conclusion In a practical application, the proposed method to identify relevant external factors for risk adjustment for comparison of outcome in healthcare proved to be feasible and comprehensive. The method can also be adapted to other quality assurance programmes. However, the cut-off score for clinical relevance needs to be individually assessed when applying the proposed method to other indications or indicators. PMID:24965949

Clinical relevance vs. statistical significance: Using neck outcomes in patients with temporomandibular disorders as an example.

PubMed

Armijo-Olivo, Susan; Warren, Sharon; Fuentes, Jorge; Magee, David J

2011-12-01

Statistical significance has been used extensively to evaluate the results of research studies. Nevertheless, it offers only limited information to clinicians. The assessment of clinical relevance can facilitate the interpretation of the research results into clinical practice. The objective of this study was to explore different methods to evaluate the clinical relevance of the results using a cross-sectional study as an example comparing different neck outcomes between subjects with temporomandibular disorders and healthy controls. Subjects were compared for head and cervical posture, maximal cervical muscle strength, endurance of the cervical flexor and extensor muscles, and electromyographic activity of the cervical flexor muscles during the CranioCervical Flexion Test (CCFT). The evaluation of clinical relevance of the results was performed based on the effect size (ES), minimal important difference (MID), and clinical judgement. The results of this study show that it is possible to have statistical significance without having clinical relevance, to have both statistical significance and clinical relevance, to have clinical relevance without having statistical significance, or to have neither statistical significance nor clinical relevance. The evaluation of clinical relevance in clinical research is crucial to simplify the transfer of knowledge from research into practice. Clinical researchers should present the clinical relevance of their results. Copyright © 2011 Elsevier Ltd. All rights reserved.

Update on Medical Practices that should be questioned in 2015

PubMed Central

Morgan, Daniel J.; Dhruva, Sanket S.; Wright, Scott M.; Korenstein, Deborah

2016-01-01

Importance Overuse of medical care, consisting primarily of overdiagnosis and overtreatment, is a common clinical problem. Objective To identify and highlight articles published in 2014 that are most likely to impact overuse, organized into the categories of overdiagnosis, overtreatment, and methods to avoid overuse. These manuscripts were reviewed and interpreted for their importance to clinical medicine. Evidence Review A structured review of English-language articles on PubMed published in 2014 and review of tables of contents of relevant journals to identify potential articles that related to medical overuse in adults. Findings We reviewed 910 articles, of which 440 addressed overuse. Of these, 104 were deemed most relevant based on the presentation of original data, quality of methodology, magnitude of clinical impact, and the number of patients potentially affected. The 10 most influential articles were selected by author consensus using the same criteria. Findings included lack of benefit for screening pelvic examinations (positive predictive value <5%), carotid artery and thyroid ultrasounds. Harms of cancer screening included unnecessary surgery and complications. Head CT scans were an overused diagnostic test (4% with clinically significant findings) and overtreatment included acetaminophen for low back pain, prolonged opioid use after surgery (3% of patients on >90 days), perioperative aspirin, medications to increase HDL, and stenting for renal artery stenosis. Conclusions and Relevance Many common medical practices should be reconsidered. It is hoped that our review promotes reflection on these 10 articles and lead to questioning other non-evidence based practices. PMID:26551354

Gender Research in the National Institute on Drug Abuse National Treatment Clinical Trials Network: A Summary of Findings

PubMed Central

Greenfield, Shelly F.; Rosa, Carmen; Putnins, Susan I.; Green, Carla A.; Brooks, Audrey J.; Calsyn, Donald A.; Cohen, Lisa R.; Erickson, Sarah; Gordon, Susan M.; Haynes, Louise; Killeen, Therese; Miele, Gloria; Tross, Susan; Winhusen, Theresa

2011-01-01

Background The NIDA National Drug Abuse Treatment Clinical Trials Network (CTN) was established to foster translation of research into practice in substance abuse treatment settings. The CTN provides a unique opportunity to examine in multi-site, translational clinical trials, the outcomes of treatment interventions targeting vulnerable sub-groups of women; the comparative effectiveness of gender-specific protocols to reduce risk behaviors; and gender differences in clinical outcomes. Objectives To review gender-related findings from published CTN clinical trials and related studies from January, 2000 through March, 2010. Methods CTN studies were selected for review if they focused on treatment outcomes or services for special populations of women with substance use disorders (SUDs) including those with trauma histories, pregnancy, co-occurring eating and other psychiatric disorders and HIV risk behaviors; or implemented gender-specific protocols. Results The CTN has randomized 11,500 participants (41% women) across 200 clinics in 24 randomized clinical trials in community settings, of which 4 have been gender-specific. This paper summarizes gender-related findings from CTN clinical trials and related studies, focusing on trauma histories, pregnancy, co-occurring eating and other psychiatric disorders, and HIV risk behaviors. Conclusions These published studies have expanded the evidence base regarding interventions for vulnerable groups of women with SUDs as well as gender-specific interventions to reduce HIV risk behaviors in substance using men and women. The results also underscore the complexity of accounting for gender in the design of clinical trials and analysis of results. Scientific Relevance To fully understand the relevance of gender-specific moderators and mediators of outcome, it is essential that future translational studies adopt more sophisticated approaches to understanding and measuring gender-relevant factors and plan sample sizes that are adequate to support more nuanced analytic methods. PMID:21854272

Is lavender an anxiolytic drug? A systematic review of randomised clinical trials.

PubMed

Perry, R; Terry, R; Watson, L K; Ernst, E

2012-06-15

Lavender (Lavandula angustifolia) is often recommended for stress/anxiety relief and believed to possess anxiolytic effects. To critically evaluate the efficacy/effectiveness of lavender for the reduction of stress/anxiety. Seven electronic databases were searched to identify all relevant studies. All methods of lavender administration were included. Data extraction and the assessment of the methodological quality of all included trials were conducted by two independent reviewers. Fifteen RCTs met the inclusion criteria. Two trials scored 4 points on the 5-point Jadad scale, the remaining 13 scored two or less. Results from seven trials appeared to favour lavender over controls for at least one relevant outcome. Methodological issues limit the extent to which any conclusions can be drawn regarding the efficacy/effectiveness of lavender. The best evidence suggests that oral lavender supplements may have some therapeutic effects. However, further independent replications are needed before firm conclusions can be drawn. Copyright © 2012 Elsevier GmbH. All rights reserved.

Clinical analysis of genome next-generation sequencing data using the Omicia platform

PubMed Central

Coonrod, Emily M; Margraf, Rebecca L; Russell, Archie; Voelkerding, Karl V; Reese, Martin G

2013-01-01

Aims Next-generation sequencing is being implemented in the clinical laboratory environment for the purposes of candidate causal variant discovery in patients affected with a variety of genetic disorders. The successful implementation of this technology for diagnosing genetic disorders requires a rapid, user-friendly method to annotate variants and generate short lists of clinically relevant variants of interest. This report describes Omicia’s Opal platform, a new software tool designed for variant discovery and interpretation in a clinical laboratory environment. The software allows clinical scientists to process, analyze, interpret and report on personal genome files. Materials & Methods To demonstrate the software, the authors describe the interactive use of the system for the rapid discovery of disease-causing variants using three cases. Results & Conclusion Here, the authors show the features of the Opal system and their use in uncovering variants of clinical significance. PMID:23895124

Beyond misdiagnosis, misunderstanding and mistrust: relevance of the historical perspective in the medical and mental health treatment of people of color.

PubMed Central

Suite, Derek H.; La Bril, Robert; Primm, Annelle; Harrison-Ross, Phyllis

2007-01-01

In this article, we discuss the relationship and relevance of the historical interaction primarily between African-American culture and the medical and mental health communities, and explore the role of historical experience in contributing to mistrust and underutilization of services by people of color. We conclude that failure on the part of practitioners to go beyond clinical history gathering to recognize and acknowledge the larger historical perspectives from which they and their patients of color draw conclusions and make decisions contributes to the mistrust of the medical and mental health communities and to perpetuation of the current climate of healthcare disparities. PMID:17722664

Introduction to Genetics and Childhood Obesity: Relevance to Nursing Practice

PubMed Central

Seal, Nuananong

2013-01-01

Purpose The aims for this article are to provide an overview of the current state of research on genetic contributions to the development of childhood obesity and to suggest genetic-focused nursing practices to prevent childhood obesity. Organizing Constructs Genetic epidemiology of childhood obesity, modes to identifying obesity genes, types of human obesity genes, and nursing implications are discussed. Clinical Relevance The successful integration of genetics into nursing practice will provide opportunities for nurses to participate fully as major agents and collaborators in the health care revolution. Conclusions Practicing nurses across the profession will need to become knowledgeable about genetics and take part in obesity prevention through genetic assessment of susceptibility and appropriate environmental interventions. PMID:20798151

Infections in the differential diagnosis of Bell's palsy: a plea for performing CSF analysis.

PubMed

Henkel, Katrin; Lange, Peter; Eiffert, Helmut; Nau, Roland; Spreer, Annette

2017-04-01

Peripheral facial nerve palsy (FP) is the most common single nerve affection. Most cases are idiopathic, but a relevant fraction is caused by potentially treatable aetiologies including infections. Not all current diagnosis and treatment guidelines recommend routine cerebrospinal fluid (CSF) analysis in the diagnostic workup of this symptom. In this study, we evaluated frequency of aetiologies and relevance of CSF analysis in an interdisciplinary cohort. We retrospectively analysed all cases of newly diagnosed FP treated at a German university medical centre in a 3-year period. Diagnostic certainty was classified for infectious aetiologies according to clinical and CSF parameters. 380 patients with FP were identified, 63 children and 317 adults. Idiopathic Bell´s palsy was predominant in 61 %. 25 % of FP was attributed to infections, and other causes were identified in 14 %. Clinical presentation alone was not conclusive for infectious aetiology, in almost half of patients with infection-attributed FP the reported symptoms or clinical signs did not differ from common symptoms of idiopathic Bell`s palsy. Determination of C-reactive protein or white blood cell count was not helpful in the identification of infectious causes, and radiological imaging was performed in a high proportion of adult patients without conclusive results. Nuchal rigidity was found only in 7 % of patients with CSF pleocytosis. The predominant infectious agents were Borrelia burgdorferi, VZV and HSV, and in most of these cases diagnosis relied on the findings of CSF analysis. This study outlines the importance of careful differential diagnosis to identify infectious causes of facial nerve palsy. The high incidence and frequent unspecific clinical presentation of infectious FP underlines the importance of including CSF analysis in the diagnostic routine workup of FP.

An Experiment Comparing Lexical and Statistical Methods for Extracting MeSH Terms from Clinical Free Text

PubMed Central

Cooper, Gregory F.; Miller, Randolph A.

1998-01-01

Abstract Objective: A primary goal of the University of Pittsburgh's 1990-94 UMLS-sponsored effort was to develop and evaluate PostDoc (a lexical indexing system) and Pindex (a statistical indexing system) comparatively, and then in combination as a hybrid system. Each system takes as input a portion of the free text from a narrative part of a patient's electronic medical record and returns a list of suggested MeSH terms to use in formulating a Medline search that includes concepts in the text. This paper describes the systems and reports an evaluation. The intent is for this evaluation to serve as a step toward the eventual realization of systems that assist healthcare personnel in using the electronic medical record to construct patient-specific searches of Medline. Design: The authors tested the performances of PostDoc, Pindex, and a hybrid system, using text taken from randomly selected clinical records, which were stratified to include six radiology reports, six pathology reports, and six discharge summaries. They identified concepts in the clinical records that might conceivably be used in performing a patient-specific Medline search. Each system was given the free text of each record as an input. The extent to which a system-derived list of MeSH terms captured the relevant concepts in these documents was determined based on blinded assessments by the authors. Results: PostDoc output a mean of approximately 19 MeSH terms per report, which included about 40% of the relevant report concepts. Pindex output a mean of approximately 57 terms per report and captured about 45% of the relevant report concepts. A hybrid system captured approximately 66% of the relevant concepts and output about 71 terms per report. Conclusion: The outputs of PostDoc and Pindex are complementary in capturing MeSH terms from clinical free text. The results suggest possible approaches to reduce the number of terms output while maintaining the percentage of terms captured, including the use of UMLS semantic types to constrain the output list to contain only clinically relevant MeSH terms. PMID:9452986

Clinically Relevant Cognitive Impairment in Middle-Aged Adults With Childhood-Onset Type 1 Diabetes

PubMed Central

Nunley, Karen A.; Ryan, Christopher M.; Jennings, J. Richard; Aizenstein, Howard J.; Zgibor, Janice C.; Costacou, Tina; Boudreau, Robert M.; Miller, Rachel; Orchard, Trevor J.; Saxton, Judith A.

2015-01-01

OBJECTIVE The aim of this study was to investigate the presence and correlates of clinically relevant cognitive impairment in middle-aged adults with childhood-onset type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS During 2010–2013, 97 adults diagnosed with T1D and aged <18 years (age and duration 49 ± 7 and 41 ± 6 years, respectively; 51% female) and 138 similarly aged adults without T1D (age 49 ± 7 years; 55% female) completed extensive neuropsychological testing. Biomedical data on participants with T1D were collected periodically since 1986–1988. Cognitive impairment status was based on the number of test scores ≥1.5 SD worse than demographically appropriate published norms: none, mild (only one test), or clinically relevant (two or more tests). RESULTS The prevalence of clinically relevant cognitive impairment was five times higher among participants with than without T1D (28% vs. 5%; P < 0.0001), independent of education, age, or blood pressure. Effect sizes were large (Cohen d 0.6–0.9; P < 0.0001) for psychomotor speed and visuoconstruction tasks and were modest (d 0.3–0.6; P < 0.05) for measures of executive function. Among participants with T1D, prevalent cognitive impairment was related to 14-year average A1c >7.5% (58 mmol/mol) (odds ratio [OR] 3.0; P = 0.009), proliferative retinopathy (OR 2.8; P = 0.01), and distal symmetric polyneuropathy (OR 2.6; P = 0.03) measured 5 years earlier; higher BMI (OR 1.1; P = 0.03); and ankle-brachial index ≥1.3 (OR 4.2; P = 0.01) measured 20 years earlier, independent of education. CONCLUSIONS Clinically relevant cognitive impairment is highly prevalent among these middle-aged adults with childhood-onset T1D. In this aging cohort, chronic hyperglycemia and prevalent microvascular disease were associated with cognitive impairment, relationships shown previously in younger populations with T1D. Two additional potentially modifiable risk factors for T1D-related cognitive impairment, vascular health and BMI, deserve further study. PMID:26153270

Is Diabetes a Risk Factor for a Severe Clinical Presentation of Dengue? - Review and Meta-analysis

PubMed Central

Htun, Nan Shwe Nwe; Odermatt, Peter; Eze, Ikenna C.; Boillat-Blanco, Noémie; D’Acremont, Valérie; Probst-Hensch, Nicole

2015-01-01

Background The mean age of acute dengue has undergone a shift towards older ages. This fact points towards the relevance of assessing the influence of age-related comorbidities, such as diabetes, on the clinical presentation of dengue episodes. Identification of factors associated with a severe presentation is of high relevance, because timely treatment is the most important intervention to avert complications and death. This review summarizes and evaluates the published evidence on the association between diabetes and the risk of a severe clinical presentation of dengue. Methodology/Findings A systematic literature review was conducted using the MEDLINE database to access any relevant association between dengue and diabetes. Five case-control studies (4 hospital-based, 1 population-based) compared the prevalence of diabetes (self-reported or abstracted from medical records) of persons with dengue (acute or past; controls) and patients with severe clinical manifestations. All except one study were conducted before 2009 and all studies collected information towards WHO 1997 classification system. The reported odds ratios were formally summarized by random-effects meta-analyses. A diagnosis of diabetes was associated with an increased risk for a severe clinical presentation of dengue (OR 1.75; 95% CI: 1.08–2.84, p = 0.022). Conclusions/Significance Large prospective studies that systematically and objectively obtain relevant signs and symptoms of dengue fever episodes as well as of hyperglycemia in the past, and at the time of dengue diagnosis, are needed to properly address the effect of diabetes on the clinical presentation of an acute dengue fever episode. The currently available epidemiological evidence is very limited and only suggestive. The increasing global prevalence of both dengue and diabetes justifies further studies. At this point, confirmation of dengue infection as early as possible in diabetes patients with fever if living in dengue endemic regions seems justified. The presence of this co-morbidity may warrant closer observation for glycemic control and adapted fluid management to diminish the risk for a severe clinical presentation of dengue. PMID:25909658

Infant formula supplementation with long-chain polyunsaturated fatty acids has no effect on Bayley developmental scores at 18 months of age--IPD meta-analysis of 4 large clinical trials.

PubMed

Beyerlein, Andreas; Hadders-Algra, Mijna; Kennedy, Katherine; Fewtrell, Mary; Singhal, Atul; Rosenfeld, Eva; Lucas, Alan; Bouwstra, Hylco; Koletzko, Berthold; von Kries, Rüdiger

2010-01-01

To find out whether supplementation of formula milk by long-chain polyunsaturated fatty acids (LCPUFA) affects neurodevelopment at 18 months of age in term or preterm infants by an individual patient data (IPD) meta-analysis. Data of 870 children from 4 large randomised clinical trials for formula milk with and without LCPUFAs allowed for assessing the effect of LCPUFA with adjustment for potential confounders and extensive subgroup analysis on prematurity, LCPUFA source, and dosage. Any additional clinical trials examining the effect of LCPUFA supplementation on Bayley Scales of Infant Development at 18 months were regarded as relevant. Two relevant studies were identified by MEDLINE, but were not available to us. An IPD meta-analysis was performed with subgroup analyses by preterm delivery, very low birth weight (<1500 g), trials with higher amounts of docosahexaenoic acid (DHA) and arachidonic acid (AA), and specific sources of LCPUFA. The sample size of 870 children was sufficient to detect clinically relevant differences in Bayley Scales even in subgroups. There were no significant differences in mental or psychomotor developmental indexes between LCPUFA-supplemented and control groups for all children or in subgroups. This was confirmed with adjustment for the possible confounders: sex, gestational age, birth weight, maternal age, and maternal smoking. The adjusted mean differences in mental developmental index and psychomotor developmental index for all of the children were -0.8 (95% confidence interval -2.8 to 1.2) and -1.0 (-2.7 to 0.7), respectively. These data based on considerable sample size provide substantial evidence that LCPUFA supplementation of infant formula does not have a clinically meaningful effect on the neurodevelopment as assessed by Bayley scores at 18 months. Inclusion of all relevant data should not have led to differing conclusions except, possibly, for very-low-birth-weight infants.

Development of a Simple 12-Item Theory-Based Instrument to Assess the Impact of Continuing Professional Development on Clinical Behavioral Intentions

PubMed Central

Légaré, France; Borduas, Francine; Freitas, Adriana; Jacques, André; Godin, Gaston; Luconi, Francesca; Grimshaw, Jeremy

2014-01-01

Background Decision-makers in organizations providing continuing professional development (CPD) have identified the need for routine assessment of its impact on practice. We sought to develop a theory-based instrument for evaluating the impact of CPD activities on health professionals' clinical behavioral intentions. Methods and Findings Our multipronged study had four phases. 1) We systematically reviewed the literature for instruments that used socio-cognitive theories to assess healthcare professionals' clinically-oriented behavioral intentions and/or behaviors; we extracted items relating to the theoretical constructs of an integrated model of healthcare professionals' behaviors and removed duplicates. 2) A committee of researchers and CPD decision-makers selected a pool of items relevant to CPD. 3) An international group of experts (n = 70) reached consensus on the most relevant items using electronic Delphi surveys. 4) We created a preliminary instrument with the items found most relevant and assessed its factorial validity, internal consistency and reliability (weighted kappa) over a two-week period among 138 physicians attending a CPD activity. Out of 72 potentially relevant instruments, 47 were analyzed. Of the 1218 items extracted from these, 16% were discarded as improperly phrased and 70% discarded as duplicates. Mapping the remaining items onto the constructs of the integrated model of healthcare professionals' behaviors yielded a minimum of 18 and a maximum of 275 items per construct. The partnership committee retained 61 items covering all seven constructs. Two iterations of the Delphi process produced consensus on a provisional 40-item questionnaire. Exploratory factorial analysis following test-retest resulted in a 12-item questionnaire. Cronbach's coefficients for the constructs varied from 0.77 to 0.85. Conclusion A 12-item theory-based instrument for assessing the impact of CPD activities on health professionals' clinical behavioral intentions showed adequate validity and reliability. Further studies could assess its responsiveness to behavior change following CPD activities and its capacity to predict health professionals' clinical performance. PMID:24643173

Expression of young HERV-H loci in the course of colorectal carcinoma and correlation with molecular subtypes

PubMed Central

Naville, Magali; Bressan, Cédric; Hühns, Maja; Gock, Michael; Kühn, Florian; Volff, Jean-Nicolas; Trillet-Lenoir, Véronique

2015-01-01

Background Expression of the human endogenous retrovirus (HERV)-H family has been associated with colorectal carcinomas (CRC), yet no individual HERV-H locus expression has been thoroughly correlated with clinical data. Here, we characterized HERV-H reactivations in clinical CRC samples by integrating expression profiles, molecular patterns and clinical data. Expression of relevant HERV-H sequences was analyzed by qRT-PCR on two well-defined clinical cohorts (n = 139 pairs of tumor and adjacent normal colon tissue) including samples from adenomas (n = 21) and liver metastases (n = 16). Correlations with clinical and molecular data were assessed. Results CRC specific HERV-H sequences were validated and found expressed throughout CRC disease progression. Correlations between HERV-H expression and lymph node invasion of tumor cells (p = 0.0006) as well as microsatellite instable tumors (p < 0.0001) were established. No association with regard to age, tumor localization, grading or common mutations became apparent. Interestingly, CRC expressed elements belonged to specific young HERV-H subfamilies and their 5′ LTR often presented active histone marks. Conclusion These results suggest a functional role of HERV-H sequences in colorectal carcinogenesis. The pronounced connection with microsatellite instability warrants a more detailed investigation. Thus, HERV-H sequences in addition to tumor specific mutations may represent clinically relevant, truly CRC specific markers for diagnostic, prognostic and therapeutic purposes. PMID:26517682

The Identification and Assessment of Late-life ADHD in Memory Clinics

PubMed Central

Fischer, Barbara L.; Gunter-Hunt, Gail; Steinhafel, Courtney Holm; Howell, Timothy

2013-01-01

INTRODUCTION Little data exists about attention deficit hyperactivity disorder (ADHD) in late life. While evaluating patients’ memory problems, our Memory Clinic staff has periodically identified ADHD in previously undiagnosed adults. We conducted a survey to assess the extent to which other memory clinics view ADHD as a relevant clinical issue. METHOD We developed and sent a questionnaire to Memory Clinics in the United States to ascertain how ADHD was identified and addressed. The percentage of responding memory clinics’ means of assessing and managing late-life ADHD comprised the measurements for this study. RESULTS Approximately one-half of responding memory clinics reported seeing ADHD patients. Of these, one-half reported identifying previously diagnosed cases, and almost one-half reported diagnosing ADHD themselves. One fifth of clinics reported screening regularly for ADHD, and few clinics described treatment methods. CONCLUSION Our results suggest that U.S. memory clinics may not adequately identify and address ADHD in late life. PMID:22173147

The Evidence Base for Interventions Delivered to Children in Primary Care: An Overview of Cochrane Systematic Reviews

PubMed Central

Gill, Peter J.; Wang, Kay Yee; Mant, David; Hartling, Lisa; Heneghan, Carl; Perera, Rafael; Klassen, Terry; Harnden, Anthony

2011-01-01

Background As a first step in developing a framework to evaluate and improve the quality of care of children in primary care there is a need to identify the evidence base underpinning interventions relevant to child health. Our objective was to identify all Cochrane systematic reviews relevant to the management of childhood conditions in primary care and to assess the extent to which Cochrane reviews reflect the burden of childhood illness presenting in primary care. Methodology/Principal Findings We used the Cochrane Child Health Field register of child-relevant systematic reviews to complete an overview of Cochrane reviews related to the management of children in primary care. We compared the proportion of systematic reviews with the proportion of consultations in Australia, US, Dutch and UK general practice in children. We identified 396 relevant systematic reviews; 358 included primary studies on children while 251 undertook a meta-analysis. Most reviews (n = 218, 55%) focused on chronic conditions and over half (n = 216, 57%) evaluated drug interventions. Since 2000, the percentage of pediatric primary care relevant reviews only increased by 2% (7% to 9%) compared to 18% (10% to 28%) in all child relevant reviews. Almost a quarter of reviews (n = 78, 23%) were published on asthma treatments which only account for 3–5% of consultations. Conversely, 15–23% of consultations are due to skin conditions yet they represent only 7% (n = 23) of reviews. Conclusions/Significance Although Cochrane systematic reviews focus on clinical trials and do not provide a comprehensive picture of the evidence base underpinning the management of children in primary care, the mismatch between the focus of the published research and the focus of clinical activity is striking. Clinical trials are an important component of the evidence base and the lack of trial evidence to demonstrate intervention effectiveness in substantial areas of primary care for children should be addressed. PMID:21829691

Quality Control of Next-generation Sequencing-based In vitro Diagnostic Test for Onco-relevant Mutations Using Multiplex Reference Materials in Plasma.

PubMed

Liu, Donglai; Zhou, Haiwei; Shi, Dawei; Shen, Shu; Tian, Yabin; Wang, Lin; Lou, Jiatao; Cong, Rong; Lu, Juan; Zhang, Henghui; Zhao, Meiru; Zhu, Shida; Cao, Zhisheng; Jin, Ruilin; Wang, Yin; Zhang, Xiaoni; Yang, Guohua; Wang, Youchun; Zhang, Chuntao

2018-01-01

Background: Widespread clinical implementation of next-generation sequencing (NGS)-based cancer in vitro diagnostic tests (IVDs) highlighted the urgency to establish reference materials which could provide full control of the process from nucleic acid extraction to test report generation. The formalin-fixed, paraffin-embedded (FFPE) tissue and blood plasma containing circulating tumor deoxyribonucleic acid (ctDNA) were mostly used for clinically detecting onco-relevant mutations. Methods: We respectively developed multiplex FFPE and plasma reference materials covering three clinically onco-relevant mutations within the epidermal growth factor receptor ( EGFR ) gene at serial allelic frequencies. All reference materials were quantified and validated via droplet digital polymerase chain reaction (ddPCR), and then were distributed to eight domestic manufacturers for the collaborative evaluation of the performance of several domestic NGS-based cancer IVDs covering four major NGS platforms (NextSeq, HiSeq, Ion Proton and BGISEQ). Results: All expected mutations except one at extremely low allelic frequencies were detected, despite some differences in coefficient of variation (CV) which increased with the decrease of allelic frequency (CVs ranging from 18% to 106%). It was worth noting that the CV value seemed to correlate with a particular mutation as well. The repeatability of determination of different mutations was L858R>T790M>19del. Conclusions: The results indicated our reference materials would be pivotal for quality control of NGS-based cancer IVDs and would guide the further development of reference materials covering more onco-relevant mutations.

[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.

Surgical stabilization of shoulder luxation in a pot-bellied pig.

PubMed

Rubio-Martínez, Luis M; Rioja, Eva; Shakespeare, A S

2013-03-15

Case Description-A 4.6-month-old pot-bellied pig was evaluated because of non-weight-bearing lameness (grade 5/5) in the right forelimb of 4 days' duration. Clinical Findings-Clinical and radiographic examination revealed a closed, lateral luxation of the right shoulder joint. Treatment and Outcome-Initial attempts at closed reduction failed to provide adequate stability of the shoulder joint. Open reduction and internal fixation by placement of 2 lateral tension sutures with a system designed for canine cranial cruciate ligament repair provided adequate joint stability and a successful outcome. Conclusions and Clinical Relevance-Stabilization of the shoulder joint with lateral tension sutures after open reduction should be considered for management of lateral shoulder luxation in pot-bellied pigs.

Countertransference in Child and Adolescent Psychiatry-A Forgotten Concept?

PubMed Central

Rasic, Daniel

2010-01-01

Objectives: The purpose of this paper is to review the evolution of the concept of countertransference, its clinical utility and unique features in the child and adolescent psychiatry setting. Methods: This article employs a selective literature review of papers relevant to countertransference in general and in child and adolescent psychiatry. Results: Reviewed papers indicate that countertransference is a ubiquitous phenomenon in child and adolescent psychiatric practice and that it can have important clinical implications. Conclusions: Recognition and management of countertransference is a crucial skill in child and adolescent psychiatry. Recommendations are made regarding its incorporation in residency training and psychiatric practice. PMID:21037914

Structural, functional and spectroscopic MRI studies of methamphetamine addiction.

PubMed

Salo, Ruth; Fassbender, Catherine

2012-01-01

This chapter reviews selected neuroimaging findings related to long-term amphetamine and methamphetamine (MA) use. An overview of structural and functional (fMRI) MR studies, Diffusion Tensor Imaging (DTI), Magnetic Resonance Spectroscopy (MRS) and Positron Emission Tomography (PET) studies conducted in long-term MA abusers is presented. The focus of this chapter is to present the relevant studies as tools to understand brain changes following drug abstinence and recovery from addiction. The behavioral relevance of these neuroimaging studies is discussed as they relate to clinical symptoms and treatment. Within each imaging section this chapter includes a discussion of the relevant imaging studies as they relate to patterns of drug use (i.e., duration of MA use, cumulative lifetime dose and time MA abstinent) as well as an overview of studies that link the imaging findings to cognitive measures. In our conclusion we discuss some of the future directions of neuroimaging as it relates to the pathophysiology of addiction.

Therapist Adherence in Brief Strategic Family Therapy for Adolescent Drug Abusers

PubMed Central

Robbins, Michael S.; Feaster, Daniel J.; Horigian, Viviana E.; Puccinelli, Marc J.; Henderson, Craig; Szapocznik, José

2012-01-01

Objective Therapist adherence has been shown to predict clinical outcomes in family therapy. In prior studies, adherence has been represented broadly by core principles and a consistent family (vs. individual) focus. To date, these studies have not captured the range of clinical skills that are represented in complex family-based approaches or examined how variations in these skills predict different clinically relevant outcomes over the course of treatment. In this study, the authors examined the reliability and validity of an observational adherence measure and the relationship between adherence and outcome in a sample of drug-using adolescents who received brief strategic family therapy within a multisite effectiveness study. Method Participants were 480 adolescents (age 12–17) and their family members, who were randomized to the Brief Strategic Family Therapist treatment condition (J. Szapocznik, U. Hervis, & S. Schwartz, 2003) or treatment as usual. The adolescents were mostly male (377 vs. 103 female) and Hispanic (213), whereas 148 were White, and 110 were Black. Therapists were also randomly assigned to treatment condition within agencies. Results Results supported the proposed factor structure of the adherence measure, providing evidence that it is possible to capture and discriminate between distinct dimensions of family therapy. Analyses demonstrated that the mean levels of the factors varied over time in theoretically and clinically relevant ways and that therapist adherence was associated with engagement and retention in treatment, improvements in family functioning, and reductions in adolescent drug use. Conclusions Clinical implications and future research directions are discussed, including the relevance of these findings on training therapists and studies focusing on mechanisms of action in family therapy. PMID:21261433

Factors affecting receipt of chemotherapy in women with breast cancer

PubMed Central

Morimoto, Libby; Coalson, Jenna; Mowat, Fionna; O’Malley, Cynthia

2010-01-01

Aims: To review literature describing factors associated with receipt of chemotherapy for breast cancer, to better understand what factors are most relevant to women’s health and whether health disparities are apparent, and to assess how these factors might affect observational studies and outcomes research. Patterns of care for metastatic breast cancer, for which no standard-of-care exists, were of particular interest. Methods: Relevant studies written in English, Italian, French, or Spanish, published in 2000 or later, were identified through MEDLINE and reviewed. Review articles and clinical trials were excluded; all observational studies and surveys were considered. Articles were reviewed for any discussion of patient characteristics, hospital/physician/insurance characteristics, psychosocial characteristics, and clinical characteristics affecting receipt of chemotherapy by breast cancer patients. Results: In general, factors associated with increased likelihood of receiving chemotherapy included younger age, being Caucasian, having good general health and few co-morbidities, having more severe clinical disease, having responded well to previous treatment, and having breast cancer that is estrogen- or progesterone-receptor-negative. Many of the clinical factors found to increase the likelihood of receiving chemotherapy were consistent with current oncology guidelines. Of the relevant 19 studies identified, only six (32%) reported data specific to metastatic cancer; most studies aggregated women with stage I–IV for purposes of analysis. Conclusion: Studies of patterns of care in breast cancer treatment can help identify challenges in health care provided to particular subgroups of women and can aid researchers in designing studies that account for such factors in clinical and outcomes research. Although scarce, studies evaluating only women with metastatic breast cancer indicate that factors affecting decisions related to receipt of chemotherapy are similar across stage for this disease. PMID:21072304

From data to evidence: evaluative methods in evidence-based medicine.

PubMed

Landry, M D; Sibbald, W J

2001-11-01

The amount of published information is increasing exponentially, and recent technologic advances have created systems whereby mass distribution of this information can occur at an infinite rate. This is particularly true in the broad field of medicine, as the absolute volume of data available to the practicing clinician is creating new challenges in the management of relevant information flow. Evidence-based medicine (EBM) is an information management and learning strategy that seeks to integrate clinical expertise with the best evidence available in order to make effective clinical decisions that will ultimately improve patient care. The systematic approach underlying EBM encourages the clinician to formulate specific and relevant questions, which are answered in an iterative manner through accessing the best available published evidence. The arguments against EBM stem from the idea that there are inherent weaknesses in research methodologies and that emphasis placed on published research may ignore clinical skills and individual patient needs. Despite these arguments, EBM is gaining momentum and is consistently used as a method of learning and improving health care delivery. However, if EBM is to be effective, the clinician needs to have a critical understanding of research methodology in order to judge the value and level of a particular data source. Without critical analysis of research methodology, there is an inherent risk of drawing incorrect conclusions that may affect clinical decision-making. Currently, there is a trend toward using secondary pre-appraised data rather than primary sources as best evidence. We review the qualitative and quantitative methodology commonly used in EBM and argue that it is necessary for the clinician to preferentially use primary rather than secondary sources in making clinically relevant decisions.

Pirfenidone for Idiopathic Pulmonary Fibrosis: A Systematic Review and Meta-Analysis

PubMed Central

Venegas, Carmen; Arenas, Alex; Rada, Gabriel

2015-01-01

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with poor prognosis. In the last decades pirfenidone an anti-inflammatory and anti-fibrotic agent has shown benefit in inhibit collagen production and has also demonstrated benefit in decline progression in IPF in physiological outcomes as Forced vital capacity (FVC), in clinical outcomes such as progression free survival (PFS) and a benefit in mortality but no in clinically relevant outcomes as exacerbations or worsening of IPF. Methods: We conducted a systematic review to evaluate the effectiveness of physiological and clinical outcomes of pirfenidone compared to placebo in IPF. We performed a search with no language restriction. Two researchers performed literature search, quality assessment, data extraction and analysis. And was performed a summary of findings table following the GRADE approach. Results: We included 5 RCTs (Randomized controlled trials) in analysis. The meta-analysis resulted in a decrease in all cause-mortality (RR 0.52 IC 0.32–0.88) and IPF related mortality (RR 0.32 IC 0.14–0.75); other outcomes evaluated were worsening of IPF (RR 0.64 IC 0.50–0.83) and acute exacerbation (RR: 0.72 IC 0.30–1.66 respectively). Also there was a decrease in progression free survival (PFS) (RR 0.83 IC 0.74–0.92) compared to placebo. Conclusions: We observed significant differences in physiologic and clinically relevant outcomes such as reduction in all-cause mortality, IPF related mortality, worsening and exacerbation of IPF and PFS. So pirfenidone treatment should be considered not only for its benefits in pulmonary function tests but also by its clinically relevant outcomes. PMID:26308723

Patch test results in children and adolescents. Study from the Santa Casa de Belo Horizonte Dermatology Clinic, Brazil, from 2003 to 2010*

PubMed Central

Rodrigues, Dulcilea Ferraz; Goulart, Eugênio Marcos Andrade

2015-01-01

BACKGROUND Patch testing is an efficient method to identify the allergen responsible for allergic contact dermatitis. OBJECTIVE To evaluate the results of patch tests in children and adolescents comparing these two age groups' results. METHODS Cross-sectional study to assess patch test results of 125 children and adolescents aged 1-19 years, with suspected allergic contact dermatitis, in a dermatology clinic in Brazil. Two Brazilian standardized series were used. RESULTS Seventy four (59.2%) patients had "at least one positive reaction" to the patch test. Among these positive tests, 77.0% were deemed relevant. The most frequent allergens were nickel (36.8%), thimerosal (18.4%), tosylamide formaldehyde resin (6.8%), neomycin (6.4%), cobalt (4.0%) and fragrance mix I (4.0%). The most frequent positive tests came from adolescents (p=0.0014) and females (p=0.0002). There was no relevant statistical difference concerning contact sensitizations among patients with or without atopic history. However, there were significant differences regarding sensitization to nickel (p=0.029) and thimerosal (p=0.042) between the two age groups under study, while adolescents were the most affected. CONCLUSION Nickel and fragrances were the only positive (and relevant) allergens in children. Nickel and tosylamide formaldehyde resin were the most frequent and relevant allergens among adolescents. PMID:26560213

Using Wireless Handheld Computers to Seek Information at the Point of Care: An Evaluation by Clinicians

PubMed Central

Hauser, Susan E.; Demner-Fushman, Dina; Jacobs, Joshua L.; Humphrey, Susanne M.; Ford, Glenn; Thoma, George R.

2007-01-01

Objective To evaluate: (1) the effectiveness of wireless handheld computers for online information retrieval in clinical settings; (2) the role of MEDLINE® in answering clinical questions raised at the point of care. Design A prospective single-cohort study: accompanying medical teams on teaching rounds, five internal medicine residents used and evaluated MD on Tap, an application for handheld computers, to seek answers in real time to clinical questions arising at the point of care. Measurements All transactions were stored by an intermediate server. Evaluators recorded clinical scenarios and questions, identified MEDLINE citations that answered the questions, and submitted daily and summative reports of their experience. A senior medical librarian corroborated the relevance of the selected citation to each scenario and question. Results Evaluators answered 68% of 363 background and foreground clinical questions during rounding sessions using a variety of MD on Tap features in an average session length of less than four minutes. The evaluator, the number and quality of query terms, the total number of citations found for a query, and the use of auto-spellcheck significantly contributed to the probability of query success. Conclusion Handheld computers with Internet access are useful tools for healthcare providers to access MEDLINE in real time. MEDLINE citations can answer specific clinical questions when several medical terms are used to form a query. The MD on Tap application is an effective interface to MEDLINE in clinical settings, allowing clinicians to quickly find relevant citations. PMID:17712085

Influence of varus/valgus positioning of the Nanos® and Metha® short-stemmed prostheses on stress shielding of metaphyseal bone.

PubMed

Brinkmann, V; Radetzki, F; Gutteck, N; Delank, S; Zeh, A

2017-03-01

The aim of this study was to analyze bone remodeling around the Nanos® (Smith & Nephew) and Metha® (Aesculap AG) implants as a function of varus/valgus stem positioning. In 75 patients with diagnosed coxarthrosis, either Nanos® (n= 51) or Metha® (n= 24) prostheses were implanted. Digital assessment of plain radiographs immediately, 97 days, and 381 days after THA showed no clinically-relevant migration, angulation, or change in offset and center of rotation. The DEXA scans showed significant BMD changes in Gruen zones 1 (-12.8%), 2 (-3.3%), 6 (+6.4%), and 7(-7.8%)(t-test). The pre/postoperative CCD for the Nanos® was 129°/ 135° and for the Metha® 131°/ 127°. Linear regression analysis showed no prediction for BMD by postoperative CCD or stem type. In conclusion, there was no clinically-relevant influence on proximal femur BMD according to varus/valgus implantation of the Nanos® or Metha® prostheses.

Representation of Time-Relevant Common Data Elements in the Cancer Data Standards Repository: Statistical Evaluation of an Ontological Approach

PubMed Central

Chen, Henry W; Du, Jingcheng; Song, Hsing-Yi; Liu, Xiangyu; Jiang, Guoqian

2018-01-01

Background Today, there is an increasing need to centralize and standardize electronic health data within clinical research as the volume of data continues to balloon. Domain-specific common data elements (CDEs) are emerging as a standard approach to clinical research data capturing and reporting. Recent efforts to standardize clinical study CDEs have been of great benefit in facilitating data integration and data sharing. The importance of the temporal dimension of clinical research studies has been well recognized; however, very few studies have focused on the formal representation of temporal constraints and temporal relationships within clinical research data in the biomedical research community. In particular, temporal information can be extremely powerful to enable high-quality cancer research. Objective The objective of the study was to develop and evaluate an ontological approach to represent the temporal aspects of cancer study CDEs. Methods We used CDEs recorded in the National Cancer Institute (NCI) Cancer Data Standards Repository (caDSR) and created a CDE parser to extract time-relevant CDEs from the caDSR. Using the Web Ontology Language (OWL)–based Time Event Ontology (TEO), we manually derived representative patterns to semantically model the temporal components of the CDEs using an observing set of randomly selected time-related CDEs (n=600) to create a set of TEO ontological representation patterns. In evaluating TEO’s ability to represent the temporal components of the CDEs, this set of representation patterns was tested against two test sets of randomly selected time-related CDEs (n=425). Results It was found that 94.2% (801/850) of the CDEs in the test sets could be represented by the TEO representation patterns. Conclusions In conclusion, TEO is a good ontological model for representing the temporal components of the CDEs recorded in caDSR. Our representative model can harness the Semantic Web reasoning and inferencing functionalities and present a means for temporal CDEs to be machine-readable, streamlining meaningful searches. PMID:29472179

How good is "evidence" from clinical studies of drug effects and why might such evidence fail in the prediction of the clinical utility of drugs?

PubMed

Naci, Huseyin; Ioannidis, John P A

2015-01-01

Promising evidence from clinical studies of drug effects does not always translate to improvements in patient outcomes. In this review, we discuss why early evidence is often ill suited to the task of predicting the clinical utility of drugs. The current gap between initially described drug effects and their subsequent clinical utility results from deficits in the design, conduct, analysis, reporting, and synthesis of clinical studies-often creating conditions that generate favorable, but ultimately incorrect, conclusions regarding drug effects. There are potential solutions that could improve the relevance of clinical evidence in predicting the real-world effectiveness of drugs. What is needed is a new emphasis on clinical utility, with nonconflicted entities playing a greater role in the generation, synthesis, and interpretation of clinical evidence. Clinical studies should adopt strong design features, reflect clinical practice, and evaluate outcomes and comparisons that are meaningful to patients. Transformative changes to the research agenda may generate more meaningful and accurate evidence on drug effects to guide clinical decision making.

Endoscopic ultrasound as an adjunctive evaluation in patients with esophageal motor disorders subtyped by high-resolution manometry

PubMed Central

Krishnan, Kumar; Lin, Chen-Yuan; Keswani, Rajesh; Pandolfino, John E; Kahrilas, Peter J; Komanduri, Srinadh

2015-01-01

Background and aims Esophageal motor disorders are a heterogenous group of conditions identified by esophageal manometry that lead to esophageal dysfunction. The aim of this study was to assess the clinical utility of endoscopic ultrasound in the further evaluation of patients with esophageal motor disorders categorized using the updated Chicago Classification. Methods We performed a retrospective, single center study of 62 patients with esophageal motor disorders categorized according to the Chicago Classification. All patients underwent standard radial endosonography to assess for extra esophageal findings or alternative explanations for esophageal outflow obstruction. Secondary outcomes included esophageal wall thickness among the different patient subsets within the Chicago Classification Key Results EUS identified 9/62 (15%) clinically relevant findings that altered patient management and explained the etiology of esophageal outflow obstruction. We further identified substantial variability in esophageal wall thickness in a proportion of patients including some with a significantly thickened non-muscular layer. Conclusions EUS findings are clinically relevant in a significant number of patients with motor disorders and can alter clinical management. Variability in esophageal wall thickness of the muscularis propria and non-muscular layers identified by EUS may also explain the observed variability in response to standard therapies for achalasia. PMID:25041229

A narrative review on cervical interventions in adults with chronic whiplash-associated disorder

PubMed Central

Yeung, Euson; Tong, Tiffany; Reed, Nick

2018-01-01

Introduction Whiplash injuries are common in society, but clinical interventions are inconclusive on the most effective treatment. Research and reviews have been completed with the goal of determining clinical interventions that are effective for whiplash injuries and disorders, but literature has not recently been summarised on best practices for cervical spine interventions for adults with chronic whiplash. Purpose The objective of this narrative review is to update and expand on previous works, to provide recommendations for clinical interventions and future research in the area of cervical spine rehabilitation for adults with chronic whiplash-associated disorder. Method The Arskey and O’Malley methodology was used for this narrative review. CINHAL, EMBASE, Medline, PsychInfo, Scopus, Web of Science, as well as grey literature, were searched from 2003 to April 2017. Two reviewers screened titles and abstracts for relevance to the review, and content analysis summarised the study findings. A total of 14 citations were included in the final review. Findings Exercise-based interventions targeted at the cervical spine appear most beneficial for adults with chronic whiplash-associated disorder (WAD). Invasive interventions still require more rigorous studies to deem their effectiveness for this population. Conclusion Further research is required to investigate and determine clinically relevant results for cervical spine intervention in patients with chronic WAD. PMID:29719724

Peri-operative anaesthetic myocardial preconditioning and protection – cellular mechanisms and clinical relevance in cardiac anaesthesia

PubMed Central

Kunst, G; Klein, A A

2015-01-01

Preconditioning has been shown to reduce myocardial damage caused by ischaemia–reperfusion injury peri-operatively. Volatile anaesthetic agents have the potential to provide myocardial protection by anaesthetic preconditioning and, in addition, they also mediate renal and cerebral protection. A number of proof-of-concept trials have confirmed that the experimental evidence can be translated into clinical practice with regard to postoperative markers of myocardial injury; however, this effect has not been ubiquitous. The clinical trials published to date have also been too small to investigate clinical outcome and mortality. Data from recent meta-analyses in cardiac anaesthesia are also not conclusive regarding intra-operative volatile anaesthesia. These inconclusive clinical results have led to great variability currently in the type of anaesthetic agent used during cardiac surgery. This review summarises experimentally proposed mechanisms of anaesthetic preconditioning, and assesses randomised controlled clinical trials in cardiac anaesthesia that have been aimed at translating experimental results into the clinical setting. PMID:25764404

Clinical relevance in anesthesia journals.

PubMed

Lauritsen, Jakob; Møller, Ann M

2006-04-01

The purpose of this review is to present the latest knowledge and research on the definition and distribution of clinically relevant articles in anesthesia journals. It will also discuss the importance of the chosen methodology and outcome of articles. In the last few years, more attention has been paid to evidence-based medicine in anesthesia. Several articles on the subject have focused on the need to base clinical decisions on sound research employing both methodological rigor and clinically relevant outcomes. The number of systematic reviews in anesthesia literature is increasing as well as the focus on diminishing the number of surrogate outcomes. It has been shown that the impact factor is not a valid measure of establishing the level of clinical relevance to a journal. This review presents definitions of clinically relevant anesthesia articles. A clinically relevant article employs both methodological rigor and a clinically relevant outcome. The terms methodological rigor and clinical outcomes are fully discussed in the review as well as problems with journal impact factors.

Pharmacoepidemiology of Clinically Relevant Hypothyroidism and Hypertension from Sunitinib and Sorafenib

PubMed Central

Aubert, Ronald E.; La‐Beck, Ninh M.; Clore, Gosia; Herrera, Vivian; Kourlas, Helen; Epstein, Robert S.; McLeod, Howard L.

2017-01-01

Abstract Background. Thyroid dysfunction and hypertension (HTN) have been sporadically reported with sunitinib (SUN) and sorafenib (SOR). Determination of the side effect incidence will enhance monitoring and management recommendations. Methods. An observational cohort study was performed using deidentified pharmacy claims data from a 3‐year period to evaluate patients prescribed SUN, SOR, or capecitabine (CAP; comparison group). The primary outcome was time to first prescription for thyroid replacement or HTN treatment. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated by Cox proportional hazards models. Results. A total of 20,061 patients were eligible for evaluation of thyroid replacement therapy, which was initiated in 11.6% of those receiving SUN (HR, 16.77; 95% CI, 13.54–20.76), 2.6% of those receiving SOR (HR, 3.47; 95% CI, 2.46–4.98), and 1% of those receiving CAP, with median time to initiation of 4 months (range, 1–35 months). A total of 14,468 patients were eligible for evaluation of HTN therapy, which was initiated in 21% of SUN recipients (HR, 4.91; 95% CI, 4.19–5.74), 14% of SOR recipients (HR, 3.25; 95% CI, 2.69–3.91), and 5% of CAP recipients, with median time to initiation of 1 month (range, 1–18 months) for SOR and 2 months (range, 1–25 months) for SUN. Conclusion. SUN and SOR significantly increased the risk for clinically relevant hypothyroidism; the risk was at least 4 times greater with SUN than with SOR. Patients receiving SUN and SOR had a similar elevated risk for clinically relevant HTN. These data provide robust measures of the incidence and time to onset of these clinically actionable adverse events. Implications for Practice. The side effect profiles for novel therapies are typically used to create monitoring and management recommendations using clinical trial data from patient populations that may not represent those seen in standard clinical practice. This analysis using a large pharmacy claims database better reflects typical patients treated with sorafenib or sunitinib outside of a clinical trial. The findings of increased need for thyroid replacement in patients receiving sunitinib compared with sorafenib and a similar increase in need for hypertension therapy with both agents can be used to form clinically relevant monitoring recommendations for these agents. PMID:28167571

To Compare PubMed Clinical Queries and UpToDate in Teaching Information Mastery to Clinical Residents: A Crossover Randomized Controlled Trial

PubMed Central

Sayyah Ensan, Ladan; Faghankhani, Masoomeh; Javanbakht, Anna; Ahmadi, Seyed-Foad; Baradaran, Hamid Reza

2011-01-01

Purpose To compare PubMed Clinical Queries and UpToDate regarding the amount and speed of information retrieval and users' satisfaction. Method A cross-over randomized trial was conducted in February 2009 in Tehran University of Medical Sciences that included 44 year-one or two residents who participated in an information mastery workshop. A one-hour lecture on the principles of information mastery was organized followed by self learning slide shows before using each database. Subsequently, participants were randomly assigned to answer 2 clinical scenarios using either UpToDate or PubMed Clinical Queries then crossed to use the other database to answer 2 different clinical scenarios. The proportion of relevantly answered clinical scenarios, time to answer retrieval, and users' satisfaction were measured in each database. Results Based on intention-to-treat analysis, participants retrieved the answer of 67 (76%) questions using UpToDate and 38 (43%) questions using PubMed Clinical Queries (P<0.001). The median time to answer retrieval was 17 min (95% CI: 16 to 18) using UpToDate compared to 29 min (95% CI: 26 to 32) using PubMed Clinical Queries (P<0.001). The satisfaction with the accuracy of retrieved answers, interaction with UpToDate and also overall satisfaction were higher among UpToDate users compared to PubMed Clinical Queries users (P<0.001). Conclusions For first time users, using UpToDate compared to Pubmed Clinical Querries can lead to not only a higher proportion of relevant answer retrieval within a shorter time, but also a higher users' satisfaction. So, addition of tutoring pre-appraised sources such as UpToDate to the information mastery curricula seems to be highly efficient. PMID:21858142

Nursing students' perceptions of their clinical learning environment in placements outside traditional hospital settings

PubMed Central

Bjørk, Ida T; Berntsen, Karin; Brynildsen, Grethe; Hestetun, Margrete

2014-01-01

Aims and objectives To explore students' opinions of the learning environment during clinical placement in settings outside traditional hospital settings. Background Clinical placement experiences may influence positively on nursing students attitudes towards the clinical setting in question. Most studies exploring the quality of clinical placements have targeted students' experience in hospital settings. The number of studies exploring students' experiences of the learning environment in healthcare settings outside of the hospital venue does not match the growing importance of such settings in the delivery of health care, nor the growing number of nurses needed in these venues. Design A survey design was used. Method The Clinical Learning Environment Inventory was administered to two cohorts of undergraduate nursing students (n = 184) after clinical placement in mental health care, home care and nursing home care. Results Nursing students' overall contentment with the learning environment was quite similar across all three placement areas. Students in mental health care had significantly higher scores on the subscale individualisation, and older students had significantly higher scores on the total scale. Compared with other studies where the Clinical Learning Environment Inventory has been used, the students' total scores in this study are similar or higher than scores in studies including students from hospital settings. Conclusion Results from this study negate the negative views on clinical placements outside the hospital setting, especially those related to placements in nursing homes and mental healthcare settings. Relevance to clinical practice Students' experience of the learning environment during placements in mental health care, home care and nursing homes indicates the relevance of clinical education in settings outside the hospital setting. PMID:24460862

Methodologic quality and relevance of references in pharmaceutical advertisements in a Canadian medical journal.

PubMed Central

Lexchin, J; Holbrook, A

1994-01-01

OBJECTIVE: To evaluate the methodologic quality and relevance of references in pharmaceutical advertisements in the Canadian Medical Association Journal (CMAJ). DESIGN: Analytic study. DATA SOURCE: All 114 references cited in the first 22 distinct pharmaceutical advertisements in volume 146 of CMAJ. MAIN OUTCOME MEASURES: Mean methodologic quality score (modified from the 6-point scale used to assess articles in the American College of Physicians' Journal Club) and mean relevance score (based on a new 5-point scale) for all references in each advertisement. MAIN RESULTS: Twenty of the 22 companies responded, sending 78 (90%) of the 87 references requested. The mean methodologic quality score was 58% (95% confidence limits [CL] 51% and 65%) and the mean relevance score 76% (95% CL 72% and 80%). The two mean scores were statistically lower than the acceptable score of 80% (p < 0.05), and the methodologic quality score was outside the preset clinically significant difference of 15%. The poor rating for methodologic quality was primarily because of the citation of references to low-quality review articles and "other" sources (i.e., other than reports of clinical trials). Half of the advertisements had a methodologic quality score of less than 65%, but only five had a relevance score of less than 65%. CONCLUSIONS: Although the relevance of most of the references was within minimal acceptable limits, the methodologic quality was often unacceptable. Because advertisements are an important part of pharmaceutical marketing and education, we suggest that companies develop written standards for their advertisements and monitor their advertisements for adherence to these standards. We also suggest that the Pharmaceutical Advertising Advisory Board develop more stringent guidelines for advertising and that it enforce these guidelines in a consistent, rigorous fashion. PMID:8004560

Clostridium Difficile Infection Due to Pneumonia Treatment: Mortality Risk Models.

PubMed

Chmielewska, M; Zycinska, K; Lenartowicz, B; Hadzik-Błaszczyk, M; Cieplak, M; Kur, Z; Wardyn, K A

2017-01-01

One of the most common gastrointestinal infection after the antibiotic treatment of community or nosocomial pneumonia is caused by the anaerobic spore Clostridium difficile (C. difficile). The aim of this study was to retrospectively assess mortality due to C. difficile infection (CDI) in patients treated for pneumonia. We identified 94 cases of post-pneumonia CDI out of the 217 patients with CDI. The mortality issue was addressed by creating a mortality risk models using logistic regression and multivariate fractional polynomial analysis. The patients' demographics, clinical features, and laboratory results were taken into consideration. To estimate the influence of the preceding respiratory infection, a pneumonia severity scale was included in the analysis. The analysis showed two statistically significant and clinically relevant mortality models. The model with the highest prognostic strength entailed age, leukocyte count, serum creatinine and urea concentration, hematocrit, coexisting neoplasia or chronic obstructive pulmonary disease. In conclusion, we report on two prognostic models, based on clinically relevant factors, which can be of help in predicting mortality risk in C. difficile infection, secondary to the antibiotic treatment of pneumonia. These models could be useful in preventive tailoring of individual therapy.

The Impact of Continuous Medicaid Enrollment on Diagnosis, Treatment, and Survival in Six Surgical Cancers

PubMed Central

Dawes, Aaron J; Louie, Rachel; Nguyen, David K; Maggard-Gibbons, Melinda; Parikh, Punam; Ettner, Susan L; Ko, Clifford Y; Zingmond, David S

2014-01-01

Objective To examine the effect of Medicaid enrollment on the diagnosis, treatment, and survival of six surgically relevant cancers among poor and underserved Californians. Data Sources California Cancer Registry (CCR), California's Patient Discharge Database (PDD), and state Medicaid enrollment files between 2002 and 2008. Study Design We linked clinical and administrative records to differentiate patients continuously enrolled in Medicaid from those receiving coverage at the time of their cancer diagnosis. We developed multivariate logistic regression models to predict death within 1 year for each cancer after controlling for sociodemographic and clinical variables. Data Collection/Extraction Methods All incident cases of six cancers (colon, esophageal, lung, pancreas, stomach, and ovarian) were identified from CCR. CCR records were linked to hospitalizations (PDD) and monthly Medicaid enrollment. Principal Findings Continuous enrollment in Medicaid for at least 6 months prior to diagnosis improves survival in three surgically relevant cancers. Discontinuous Medicaid patients have higher stage tumors, undergo fewer definitive operations, and are more likely to die even after risk adjustment. Conclusions Expansion of continuous insurance coverage under the Affordable Care Act is likely to improve both access and clinical outcomes for cancer patients in California. PMID:25256223

Clinical and Prognostic Effect of Plasma Fibrinogen in Renal Cell Carcinoma: A Meta-Analysis.

PubMed

Tian, Yuejun; Hong, Mei; Jing, Suoshi; Liu, Xingchen; Wang, Hanzhang; Wang, Xinping; Kaushik, Dharam; Rodriguez, Ronald; Wang, Zhiping

2017-01-01

Background . Although numerous studies have shown that plasma fibrinogen is linked to renal cell carcinoma (RCC) risk, the consistency and magnitude of the effect of plasma fibrinogen are unclear. The aim of the study was to explore the association between plasma fibrinogen and RCC prognosis. Methods . An electronic search of Embase, PubMed/MEDLINE, and the Cochrane databases was performed to identify relevant studies published prior to June 1, 2016. Results . A total of 3744 patients with RCC from 7 published studies were included in the meta-analysis. The prognostic and clinical relevance of plasma fibrinogen are evaluated in RCC patients. Statistical significance of the combined hazard ratio (HR) was detected for overall survival, cancer-specific survival, and disease-free survival. Our pooled results showed that elevated plasma fibrinogen was significantly associated with clinical stage and Fuhrman grading. The level of plasma fibrinogen was not found to be associated with tumor type and gender. Conclusions . Elevated plasma fibrinogen is a strong indicator of poorer prognosis of patients with RCC, whereas the plasma fibrinogen is not significantly associated with tumor type. Therefore, plasma fibrinogen could be used in patients with RCC for risk stratification and decision providing a proper therapeutic strategy.

Infrared sauna in patients with rheumatoid arthritis and ankylosing spondylitis. A pilot study showing good tolerance, short-term improvement of pain and stiffness, and a trend towards long-term beneficial effects.

PubMed

Oosterveld, Fredrikus G J; Rasker, Johannes J; Floors, Mark; Landkroon, Robert; van Rennes, Bob; Zwijnenberg, Jan; van de Laar, Mart A F J; Koel, Gerard J

2009-01-01

To study the effects of infrared (IR) Sauna, a form of total-body hyperthermia in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) patients were treated for a 4-week period with a series of eight IR treatments. Seventeen RA patients and 17 AS patients were studied. IR was well tolerated, and no adverse effects were reported, no exacerbation of disease. Pain and stiffness decreased clinically, and improvements were statistically significant (p < 0.05 and p < 0.001 in RA and AS patients, respectively) during an IR session. Fatigue also decreased. Both RA and AS patients felt comfortable on average during and especially after treatment. In the RA and AS patients, pain, stiffness, and fatigue also showed clinical improvements during the 4-week treatment period, but these did not reach statistical significance. No relevant changes in disease activity scores were found, indicating no exacerbation of disease activity. In conclusion, infrared treatment has statistically significant short-term beneficial effects and clinically relevant period effects during treatment in RA and AS patients without enhancing disease activity. IR has good tolerability and no adverse effects.

[Gene mutation and clinical phenotype analysis of patients with Noonan syndrome and hypertrophic cardiomyopathy].

PubMed

Liu, X H; Ding, W W; Han, L; Liu, X R; Xiao, Y Y; Yang, J; Mo, Y

2017-10-02

Objective: To analyze the gene mutations and clinical features of patients with Noonan syndrome and hypertrophic cardiomyopathy. Method: Determined the mutation domain in five cases diagnosed with Noonan syndrome and hypertrophic cardiomyopathy and identified the relationship between the mutant domain and hypertrophic cardiomyopathy by searching relevant articles in pubmed database. Result: Three mutant genes (PTPN11 gene in chromosome 12, RIT1 gene in chromosome 1 and RAF1 gene in chromosome 3) in five cases all had been reported to be related to hypertrophic cardiomyopathy. The reported hypertrophic cardiomyopathy relevant genes MYPN, MYH6 and MYBP3 had also been found in case 1 and 2. Patients with same gene mutation had different clinical manifestations. Both case 4 and 5 had RAF1 mutation (c.770C>T). However, case 4 had special face, low IQ, mild pulmonary artery stenosis, and only mild ventricular hypertrophy. Conclusion: Noonan syndrome is a genetic heterogeneity disease. Our study identified specific gene mutations that could result in Noonan syndrome with hypertrophic cardiomyopathy through molecular biology methods. The results emphasize the importance of gene detection in the management of Noonan syndrome.

Systemic Sclerosis Disease Modification Clinical Trials Design: Quo Vadis?

PubMed Central

Mendoza, Fabian A.; Keyes-Elstein, Lynette L.; Jimenez, Sergio A.

2012-01-01

The purpose of this manuscript is to discuss relevant aspects of clinical trials for Systemic Sclerosis (SSc) and to identify important considerations for the design of SSc disease modification clinical trials. Placebo randomized controlled trials with appropriate identification of SSc patients with diffuse progressive SSc skin involvement of recent onset, along with a rescue strategy for patients with worsening lung and skin involvement are suggested. If change in skin thickening is a major outcome of the study, the selection of patients with recent onset of disease and a predetermined degree of skin involvement are crucial requirements. The trial duration should be of at least 12 months. Sample size calculations should consider differences that exceed the Minimal Important Difference. Other relevant trial designs and potential threats to study validity are also discussed. Previous SSc-disease modifying trials have been beset by high dropout rates. Analyses on the subset of subjects completing the trial or applying the last-observation-carried-forward approach can potentially lead to biased estimates and false conclusions. Strategies for retention of subjects should be included at the design stage and analyses to account for missing data should be performed. PMID:22422541

Publications in anesthesia journals: quality and clinical relevance.

PubMed

Lauritsen, Jakob; Moller, Ann M

2004-11-01

Clinicians performing evidence-based anesthesia rely on anesthesia journals for clinically relevant information. The objective of this study was to analyze the proportion of clinically relevant articles in five high impact anesthesia journals. We evaluated all articles published in Anesthesiology, Anesthesia & Analgesia, British Journal of Anesthesia, Anesthesia, and Acta Anaesthesiologica Scandinavica from January to June, 2000. Articles were assessed and classified according to type, outcome, and design; 1379 articles consisting of 5468 pages were evaluated and categorized. The most common types of article were animal and laboratory research (31.2%) and randomized clinical trial (20.4%). A clinically relevant article was defined as an article that used a statistically valid method and had a clinically relevant end-point. Altogether 18.6% of the pages had as their subject matter clinically relevant trials. We compared the Journal Impact Factor (a measure of the number of citations per article in a journal) and the proportion of clinically relevant pages and found that they were inversely proportional to each other.

Heart rate variability measurement and clinical depression in acute coronary syndrome patients: narrative review of recent literature

PubMed Central

Harris, Patricia RE; Sommargren, Claire E; Stein, Phyllis K; Fung, Gordon L; Drew, Barbara J

2014-01-01

Aim We aimed to explore links between heart rate variability (HRV) and clinical depression in patients with acute coronary syndrome (ACS), through a review of recent clinical research literature. Background Patients with ACS are at risk for both cardiac autonomic dysfunction and clinical depression. Both conditions can negatively impact the ability to recover from an acute physiological insult, such as unstable angina or myocardial infarction, increasing the risk for adverse cardiovascular outcomes. HRV is recognized as a reflection of autonomic function. Methods A narrative review was undertaken to evaluate state-of-the-art clinical research, using the PubMed database, January 2013. The search terms “heart rate variability” and “depression” were used in conjunction with “acute coronary syndrome”, “unstable angina”, or “myocardial infarction” to find clinical studies published within the past 10 years related to HRV and clinical depression, in patients with an ACS episode. Studies were included if HRV measurement and depression screening were undertaken during an ACS hospitalization or within 2 months of hospital discharge. Results Nine clinical studies met the inclusion criteria. The studies’ results indicate that there may be a relationship between abnormal HRV and clinical depression when assessed early after an ACS event, offering the possibility that these risk factors play a modest role in patient outcomes. Conclusion While a definitive conclusion about the relevance of HRV and clinical depression measurement in ACS patients would be premature, the literature suggests that these measures may provide additional information in risk assessment. Potential avenues for further research are proposed. PMID:25071372

A model for integrating clinical care and basic science research, and pitfalls of performing complex research projects for addressing a clinical challenge.

PubMed

Steck, R; Epari, D R; Schuetz, M A

2010-07-01

The collaboration of clinicians with basic science researchers is crucial for addressing clinically relevant research questions. In order to initiate such mutually beneficial relationships, we propose a model where early career clinicians spend a designated time embedded in established basic science research groups, in order to pursue a postgraduate qualification. During this time, clinicians become integral members of the research team, fostering long term relationships and opening up opportunities for continuing collaboration. However, for these collaborations to be successful there are pitfalls to be avoided. Limited time and funding can lead to attempts to answer clinical challenges with highly complex research projects characterised by a large number of "clinical" factors being introduced in the hope that the research outcomes will be more clinically relevant. As a result, the complexity of such studies and variability of its outcomes may lead to difficulties in drawing scientifically justified and clinically useful conclusions. Consequently, we stress that it is the basic science researcher and the clinician's obligation to be mindful of the limitations and challenges of such multi-factorial research projects. A systematic step-by-step approach to address clinical research questions with limited, but highly targeted and well defined research projects provides the solid foundation which may lead to the development of a longer term research program for addressing more challenging clinical problems. Ultimately, we believe that it is such models, encouraging the vital collaboration between clinicians and researchers for the work on targeted, well defined research projects, which will result in answers to the important clinical challenges of today. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Is Escitalopram Really Relevantly Superior to Citalopram in Treatment of Major Depressive Disorder? A Meta-analysis of Head-to-head Randomized Trials

PubMed Central

Trkulja, Vladimir

2010-01-01

Aim To evaluate clinical relevance of differences between escitalopram and citalopram (equimolar) for major depressive disorder. Methods Review and meta-analysis of comparative randomized controlled trials (RCT). Comparisons were in relation to Montgomery-Asberg depression rating scale (MADRS) score reduction at weeks 1 (5 RCTs), 4 (5 RCTs), 6 (4 RCTs), 8 (5 RCTs), and 24 (1 RCT); proportion of responders at weeks 2, 4, 6 (2 RCTs for each time point), 8 (5 RCTs), and 24 (1 RCT); clinical global impression-severity (CGI-S) reduction at weeks 6 (1 RCT), 8 (5 RCTs), and 24 (1 RCT), and discontinuation due to adverse events or inefficacy during short-term (up to 8 weeks) and medium-term (24 weeks) treatment. Results MADRS reduction was greater with escitalopram, but 95% confidence intervals (CI) around the mean difference were entirely or largely below 2 scale points (minimally important difference) and CI around the effect size (ES) was below 0.32 (“small”) at all time points. Risk of response was higher with escitalopram at week 8 (relative risk, 1.14; 95% CI, 1.04 to 1.26) but number needed to treat was 14 (95% CI, 7 to 111). All 95% CIs around the mean difference and ES of CGI-S reduction at week 8 were below 0.32 points and the limit of “small,” respectively. Data for severe patients (MADRS≥30) are scarce (only 1 RCT), indicating somewhat greater efficacy (response rate and MADRS reduction at week 8, but not CGI-S reduction) of escitalopram, but without compelling evidence of clinically relevant differences. Discontinuations due to adverse events or inefficacy up to 8 weeks of treatment were comparable. Data for the period up to 24 weeks are scarce and inconclusive. Conclusion Presently, the claims about clinically relevant superiority of escitalopram over citalopram in short-to-medium term treatment of major depressive disorder are not supported by evidence. PMID:20162747

Reference intervals and allometric scaling of two-dimensional echocardiographic measurements in 150 healthy cats.

PubMed

Karsten, Schober; Stephanie, Savino; Vedat, Yildiz

2017-11-10

The objective of the study was to evaluate the effects of body weight (BW), breed, and sex on two-dimensional (2D) echocardiographic measures, reference ranges, and prediction intervals using allometrically-scaled data of left atrial (LA) and left ventricular (LV) size and LV wall thickness in healthy cats. Study type was retrospective, observational, and clinical cohort. 150 healthy cats were enrolled and 2D echocardiograms analyzed. LA diameter, LV wall thickness, and LV dimension were quantified using three different imaging views. The effect of BW, breed, sex, age, and interaction (BW*sex) on echocardiographic variables was assessed using univariate and multivariate regression and linear mixed model analysis. Standard (using raw data) and allometrically scaled (Y=a × M b ) reference intervals and prediction intervals were determined. BW had a significant (P<0.05) independent effect on 2D variables whereas breed, sex, and age did not. There were clinically relevant differences between reference intervals using mean ± 2SD of raw data and mean and 95% prediction interval of allometrically-scaled variables, most prominent in larger (>6 kg) and smaller (<3 kg) cats. A clinically relevant difference between thickness of the interventricular septum (IVS) and dimension of the LV posterior wall (LVPW) was identified. In conclusion, allometric scaling and BW-based 95% prediction intervals should be preferred over conventional 2D echocardiographic reference intervals in cats, in particular in small and large cats. These results are particularly relevant to screening examinations for feline hypertrophic cardiomyopathy.

Effect of Therapeutic Touch in Patients with Cancer: a Literature Review

PubMed Central

Tabatabaee, Amir; Tafreshi, Mansoureh Zagheri; Rassouli, Maryam; Aledavood, Seyed Amir; AlaviMajd, Hamid; Farahmand, Seyed Kazem

2016-01-01

Background: The use of complementary and alternative medicine (CAM) techniques has been growing. The National Center for Complementary and Alternative Medicine places therapeutic touch (TT) into the category of bio field energy. This literature review is aimed at critically evaluating the data from clinical trials examining the clinical efficacy of therapeutic touch as a supportive care modality in adult patients with cancer. Methods: Electronic databases (PubMed, Scopus, Scholar Google, and Science Direct) were searched from the year 1990 to 2015 to locate potentially relevant peer-reviewed articles using the key words therapeutic touch, touch therapy, neoplasm, cancer, and CAM. Additionally, relevant journals and references of all the located articles were manually searched for other potentially relevant studies. Results: The number of 334 articles was found on the basis of the key words, of which 17 articles related to the clinical trial were examined in accordance with the objectives of the study. A total of 6 articles were in the final dataset in which several examples of the positive effects of healing touch on pain, nausea, anxiety and fatigue, and life quality and also on biochemical parameters were observed. Conclusion: Based on the results of this study, an affirmation can be made regarding the use of TT, as a non-invasive intervention for improving the health status in patients with cancer. Moreover, therapeutic touch was proved to be a useful strategy for adult patients with cancer. PMID:27194823

Heuristics in Managing Complex Clinical Decision Tasks in Experts’ Decision Making

PubMed Central

Islam, Roosan; Weir, Charlene; Del Fiol, Guilherme

2016-01-01

Background Clinical decision support is a tool to help experts make optimal and efficient decisions. However, little is known about the high level of abstractions in the thinking process for the experts. Objective The objective of the study is to understand how clinicians manage complexity while dealing with complex clinical decision tasks. Method After approval from the Institutional Review Board (IRB), three clinical experts were interviewed the transcripts from these interviews were analyzed. Results We found five broad categories of strategies by experts for managing complex clinical decision tasks: decision conflict, mental projection, decision trade-offs, managing uncertainty and generating rule of thumb. Conclusion Complexity is created by decision conflicts, mental projection, limited options and treatment uncertainty. Experts cope with complexity in a variety of ways, including using efficient and fast decision strategies to simplify complex decision tasks, mentally simulating outcomes and focusing on only the most relevant information. Application Understanding complex decision making processes can help design allocation based on the complexity of task for clinical decision support design. PMID:27275019

Establishing Common Cost Measures to Evaluate the Economic Value of Patient Navigation Programs

PubMed Central

Whitley, Elizabeth; Valverde, Patricia; Wells, Kristen; Williams, Loretta; Teschner, Taylor; Shih, Ya-Chen Tina

2011-01-01

Background Patient navigation is an intervention aimed at reducing barriers to healthcare for underserved populations as a means to reduce cancer health disparities. Despite the proliferation of patient navigation programs across the United States, information related to the economic impact and sustainability of these programs is lacking. Method Following a review of the relevant literature, the Health Services Research (HSR) cost workgroup of the American Cancer Society National Patient Navigator Leadership Summit met to examine cost data relevant to assessing the economic impact of patient navigation and to propose common cost metrics. Results Recognizing that resources available for data collection, management and analysis vary, five categories of core and optional cost measures were identified related to patient navigator programs, including, program costs, human capital costs, direct medical costs, direct non-medical costs and indirect costs. Conclusion(s) Information demonstrating economic as well as clinical value is necessary to make decisions about sustainability of patient navigation programs. Adoption of these common cost metrics are recommended to promote understanding of the economic impact of patient navigation and comparability across diverse patient navigation programs. PMID:21780096

Clinical Summarization Capabilities of Commercially-available and Internally-developed Electronic Health Records

PubMed Central

Laxmisan, A.; McCoy, A.B.; Wright, A.; Sittig, D.F.

2012-01-01

Objective Clinical summarization, the process by which relevant patient information is electronically summarized and presented at the point of care, is of increasing importance given the increasing volume of clinical data in electronic health record systems (EHRs). There is a paucity of research on electronic clinical summarization, including the capabilities of currently available EHR systems. Methods We compared different aspects of general clinical summary screens used in twelve different EHR systems using a previously described conceptual model: AORTIS (Aggregation, Organization, Reduction, Interpretation and Synthesis). Results We found a wide variation in the EHRs’ summarization capabilities: all systems were capable of simple aggregation and organization of limited clinical content, but only one demonstrated an ability to synthesize information from the data. Conclusion Improvement of the clinical summary screen functionality for currently available EHRs is necessary. Further research should identify strategies and methods for creating easy to use, well-designed clinical summary screens that aggregate, organize and reduce all pertinent patient information as well as provide clinical interpretations and synthesis as required. PMID:22468161

Implementing human factors in clinical practice

PubMed Central

Timmons, Stephen; Baxendale, Bryn; Buttery, Andrew; Miles, Giulia; Roe, Bridget; Browes, Simon

2015-01-01

Objectives To understand whether aviation-derived human factors training is acceptable and useful to healthcare professionals. To understand whether and how healthcare professionals have been able to implement human factors approaches to patient safety in their own area of clinical practice. Methods Qualitative, longitudinal study using semi-structured interviews and focus groups, of a multiprofessional group of UK NHS staff (from the emergency department and operating theatres) who have received aviation-derived human factors training. Results The human factors training was evaluated positively, and thought to be both acceptable and relevant to practice. However, the staff found it harder to implement what they had learned in their own clinical areas, and this was principally attributed to features of the informal organisational cultures. Conclusions In order to successfully apply human factors approaches in hospital, careful consideration needs to be given to the local context and informal culture of clinical practice. PMID:24631959

Clinical implications of infection with a novel metastrongyloid species in the red panda (Ailurus fulgens).

PubMed

Willesen, Jakob L; Meyland-Smith, Frederik; Wiinberg, Bo; Monrad, Jesper; Bertelsen, Mads F

2012-06-01

In a recent survey, 30% of the European red panda (Ailurus fulgens) population was found to be infected with a newly discovered metastrongyloid nematode. In a following prospective study, four naturally infected captive-bred red pandas infected with this parasite were examined and compared with two uninfected control animals. On clinical examination, no abnormalities were detected with respect to vital parameters and cardiovascular system in all six examined animals. Similarly, few and nonspecific changes were recorded on serum biochemistry. No changes on pulmonary pattern were noted on thoracic radiographs. Vertebral heart scores were between 7.2 to 8.6, and no difference was noted between infected and control animals. Two animals had slightly prolonged clotting time and reaction time on thromboelastography but not likely to be of clinical relevance. In conclusion, infection with the newly identified metastrongyloid nematode in the red pandas seems to have little or no clinical importance.

Increasing conclusiveness of clinical breath analysis by improved baseline correction of multi capillary column - ion mobility spectrometry (MCC-IMS) data.

PubMed

Szymańska, Ewa; Tinnevelt, Gerjen H; Brodrick, Emma; Williams, Mark; Davies, Antony N; van Manen, Henk-Jan; Buydens, Lutgarde M C

2016-08-05

Current challenges of clinical breath analysis include large data size and non-clinically relevant variations observed in exhaled breath measurements, which should be urgently addressed with competent scientific data tools. In this study, three different baseline correction methods are evaluated within a previously developed data size reduction strategy for multi capillary column - ion mobility spectrometry (MCC-IMS) datasets. Introduced for the first time in breath data analysis, the Top-hat method is presented as the optimum baseline correction method. A refined data size reduction strategy is employed in the analysis of a large breathomic dataset on a healthy and respiratory disease population. New insights into MCC-IMS spectra differences associated with respiratory diseases are provided, demonstrating the additional value of the refined data analysis strategy in clinical breath analysis. Copyright © 2016 Elsevier B.V. All rights reserved.

Physiotherapy in the intensive care unit: an evidence-based, expert driven, practical statement and rehabilitation recommendations

PubMed Central

Sommers, Juultje; Engelbert, Raoul HH; Dettling-Ihnenfeldt, Daniela; Gosselink, Rik; Spronk, Peter E; Nollet, Frans; van der Schaaf, Marike

2015-01-01

Objective: To develop evidence-based recommendations for effective and safe diagnostic assessment and intervention strategies for the physiotherapy treatment of patients in intensive care units. Methods: We used the EBRO method, as recommended by the ‘Dutch Evidence Based Guideline Development Platform’ to develop an ‘evidence statement for physiotherapy in the intensive care unit’. This method consists of the identification of clinically relevant questions, followed by a systematic literature search, and summary of the evidence with final recommendations being moderated by feedback from experts. Results: Three relevant clinical domains were identified by experts: criteria to initiate treatment; measures to assess patients; evidence for effectiveness of treatments. In a systematic literature search, 129 relevant studies were identified and assessed for methodological quality and classified according to the level of evidence. The final evidence statement consisted of recommendations on eight absolute and four relative contra-indications to mobilization; a core set of nine specific instruments to assess impairments and activity restrictions; and six passive and four active effective interventions, with advice on (a) physiological measures to observe during treatment (with stopping criteria) and (b) what to record after the treatment. Conclusions: These recommendations form a protocol for treating people in an intensive care unit, based on best available evidence in mid-2014. PMID:25681407

Application of Multilabel Learning Using the Relevant Feature for Each Label in Chronic Gastritis Syndrome Diagnosis

PubMed Central

Liu, Guo-Ping; Yan, Jian-Jun; Wang, Yi-Qin; Fu, Jing-Jing; Xu, Zhao-Xia; Guo, Rui; Qian, Peng

2012-01-01

Background. In Traditional Chinese Medicine (TCM), most of the algorithms are used to solve problems of syndrome diagnosis that only focus on one syndrome, that is, single label learning. However, in clinical practice, patients may simultaneously have more than one syndrome, which has its own symptoms (signs). Methods. We employed a multilabel learning using the relevant feature for each label (REAL) algorithm to construct a syndrome diagnostic model for chronic gastritis (CG) in TCM. REAL combines feature selection methods to select the significant symptoms (signs) of CG. The method was tested on 919 patients using the standard scale. Results. The highest prediction accuracy was achieved when 20 features were selected. The features selected with the information gain were more consistent with the TCM theory. The lowest average accuracy was 54% using multi-label neural networks (BP-MLL), whereas the highest was 82% using REAL for constructing the diagnostic model. For coverage, hamming loss, and ranking loss, the values obtained using the REAL algorithm were the lowest at 0.160, 0.142, and 0.177, respectively. Conclusion. REAL extracts the relevant symptoms (signs) for each syndrome and improves its recognition accuracy. Moreover, the studies will provide a reference for constructing syndrome diagnostic models and guide clinical practice. PMID:22719781

An exploratory analysis of PubMed's free full-text limit on citation retrieval for clinical questions

PubMed Central

Krieger, Mary M.; Richter, Randy R.; Austin, Tricia M.

2008-01-01

Objective: The research sought to determine (1) how use of the PubMed free full-text (FFT) limit affects citation retrieval and (2) how use of the FFT limit impacts the types of articles and levels of evidence retrieved. Methods: Four clinical questions based on a research agenda for physical therapy were searched in PubMed both with and without the use of the FFT limit. Retrieved citations were examined for relevancy to each question. Abstracts of relevant citations were reviewed to determine the types of articles and levels of evidence. Descriptive analysis was used to compare the total number of citations, number of relevant citations, types of articles, and levels of evidence both with and without the use of the FFT limit. Results: Across all 4 questions, the FFT limit reduced the number of citations to 11.1% of the total number of citations retrieved without the FFT limit. Additionally, high-quality evidence such as systematic reviews and randomized controlled trials were missed when the FFT limit was used. Conclusions: Health sciences librarians play a key role in educating users about the potential impact the FFT limit has on the number of citations, types of articles, and levels of evidence retrieved. PMID:18974812

Completeness of Reporting of Patient-Relevant Clinical Trial Outcomes: Comparison of Unpublished Clinical Study Reports with Publicly Available Data

PubMed Central

Wieseler, Beate; Wolfram, Natalia; McGauran, Natalie; Kerekes, Michaela F.; Vervölgyi, Volker; Kohlepp, Petra; Kamphuis, Marloes; Grouven, Ulrich

2013-01-01

Background Access to unpublished clinical study reports (CSRs) is currently being discussed as a means to allow unbiased evaluation of clinical research. The Institute for Quality and Efficiency in Health Care (IQWiG) routinely requests CSRs from manufacturers for its drug assessments. Our objective was to determine the information gain from CSRs compared to publicly available sources (journal publications and registry reports) for patient-relevant outcomes included in IQWiG health technology assessments (HTAs) of drugs. Methods and Findings We used a sample of 101 trials with full CSRs received for 16 HTAs of drugs completed by IQWiG between 15 January 2006 and 14 February 2011, and analyzed the CSRs and the publicly available sources of these trials. For each document type we assessed the completeness of information on all patient-relevant outcomes included in the HTAs (benefit outcomes, e.g., mortality, symptoms, and health-related quality of life; harm outcomes, e.g., adverse events). We dichotomized the outcomes as “completely reported” or “incompletely reported.” For each document type, we calculated the proportion of outcomes with complete information per outcome category and overall. We analyzed 101 trials with CSRs; 86 had at least one publicly available source, 65 at least one journal publication, and 50 a registry report. The trials included 1,080 patient-relevant outcomes. The CSRs provided complete information on a considerably higher proportion of outcomes (86%) than the combined publicly available sources (39%). With the exception of health-related quality of life (57%), CSRs provided complete information on 78% to 100% of the various benefit outcomes (combined publicly available sources: 20% to 53%). CSRs also provided considerably more information on harms. The differences in completeness of information for patient-relevant outcomes between CSRs and journal publications or registry reports (or a combination of both) were statistically significant for all types of outcomes. The main limitation of our study is that our sample is not representative because only CSRs provided voluntarily by pharmaceutical companies upon request could be assessed. In addition, the sample covered only a limited number of therapeutic areas and was restricted to randomized controlled trials investigating drugs. Conclusions In contrast to CSRs, publicly available sources provide insufficient information on patient-relevant outcomes of clinical trials. CSRs should therefore be made publicly available. Please see later in the article for the Editors' Summary PMID:24115912

Hypoglycaemia in hospitalised neonatal calves: Prevalence, associated conditions and impact on prognosis.

PubMed

Trefz, F M; Feist, M; Lorenz, I

2016-11-01

Hypoglycaemia has traditionally been associated with neonatal diarrhoea and endotoxaemia in calves, but the clinical relevance of this finding in spontaneously diseased calves has not previously been evaluated. To determine the prevalence and prognostic relevance of severe hypoglycaemia (plasma glucose concentration < 2 mmol/L), data from 10,060 hospitalised calves (≤21 days of age) were retrospectively analysed. Additionally, clinical findings and diagnoses in a subset of 100 calves with severe hypoglycaemia were compared with those in 100 randomly selected calves with initial plasma glucose concentrations in the reference range (4.4-6.9 mmol/L). The prevalence of severe hypoglycaemia in the whole study sample was 6.3%. Severe hypoglycaemia was associated with a poor survival rate of 20.6% vs. 74.0% discharged animals in the group of calves with initial normoglycaemia. Review of medical records revealed that severe hypoglycaemia was significantly associated with clinical or necropsy evidence of septicaemia, hypothermia, history or clinical evidence of malnutrition, and peritonitis of varied origin, but not with the presence of neonatal diarrhoea. Only 10 of 100 calves with severe hypoglycaemia showed central nervous involvement such as seizures and opisthotonus. In conclusion, severe hypoglycaemia has a low prevalence in diseased calves in a hospital setting, but is associated with serious health problems and therefore a high risk of non-survival. Severe hypoglycaemia was not easily diagnosed based on clinical signs, but should be suspected in calves with clinical evidence of septicaemia, hypothermia, acute abdominal emergencies, and a history or clinical evidence of malnutrition. Copyright © 2016. Published by Elsevier Ltd.

A systematic review of the evidence of reduced allergenicity and clinical benefit of food hydrolysates in dogs with cutaneous adverse food reactions.

PubMed

Olivry, Thierry; Bizikova, Petra

2010-02-01

Several hydrolysate-based diets have been commercialized for helping diagnose or treat dogs with cutaneous adverse food reactions (CAFR). This systematic review was performed to examine the evidence in favour of reduced immunological and clinical allergenicity of hydrolysates in dogs with CAFR. Citation databases, meeting abstracts and article bibliographies were scanned for relevant citations, and companies were contacted to provide unpublished reports. Eleven studies relevant to this study were identified. Some evidence of reduced serum IgE binding to a soy hydrolysate (1 study) and decreased intradermal test reactivity to hydrolysed proteins (three studies) was found. In four reports, the feeding of dogs suspected of having CAFR with hydrolysate-based diets reduced or eliminated clinical signs in a variable proportion of subjects. The percentage of dogs with CAFR that still reacted to these hydrolysate-based diets could not be assessed, however. Importantly, up to 50% of dogs with CAFR enrolled in three controlled studies exhibited increases in clinical signs after ingesting partial hydrolysates derived from foods to which they were hypersensitive. In conclusion, the limited number of studies undertaken point to reduced - but not eliminated - immunological and clinical allergenicity of hydrolysate-based commercial diets. A variable proportion of dogs with CAFR will exhibit a worsening of clinical signs when fed partial hydrolysates. Clinicians must weigh the clinical benefit of these diets versus their high cost and low risk of reduced appetence or gastrointestinal sign development. At this time, hydrolysate-containing diets are probably best used in dogs suspected not to be hypersensitive to their individual components.

Salmonella infection and carriage in reptiles in a zoological collection.

PubMed

Clancy, Meredith M; Davis, Meghan; Valitutto, Marc T; Nelson, Kenrad; Sykes, John M

2016-05-01

OBJECTIVE To identify important subspecies and serovars of Salmonella enterica in a captive reptile population and clinically relevant risk factors for and signs of illness in Salmonella-positive reptiles. DESIGN Retrospective cross-sectional study. ANIMALS 11 crocodilians (4 samples), 78 snakes (91 samples), 59 lizards (57 samples), and 34 chelonians (23 samples) at the Bronx Zoo from 2000 through 2012. PROCEDURES Data pertaining to various types of biological samples obtained from reptiles with positive Salmonella culture results and the reptiles themselves were analyzed to determine period prevalence of and risk factors for various Salmonella-related outcomes. RESULTS Serovar distribution differences were identified for sample type, reptile phylogenetic family, and reptile origin and health. Salmonella enterica subsp enterica was the most common subspecies in Salmonella cultures (78/175 [45%]), identified across all reptilian taxa. Salmonella enterica subsp diarizonae was also common (42/175 [24%]) and was recovered almost exclusively from snakes (n = 33), many of which had been clinically ill (17). Clinically ill reptiles provided 37% (64) of Salmonella cultures. Factors associated with an increased risk of illness in reptiles with a positive culture result were carnivorous diet and prior confiscation. Snakes had a higher risk of illness than other reptile groups, whereas lizards had a lower risk. Bony changes, dermatitis, and anorexia were the most common clinical signs. CONCLUSIONS AND CLINICAL RELEVANCE This study provided new information on Salmonella infection or carriage and associated clinical disease in reptiles. Associations identified between serovars or subspecies and reptile groups or clinical disease can guide management of Salmonella-positive captive reptiles.

PRION-1 scales analysis supports use of functional outcome measures in prion disease

PubMed Central

Mead, S.; Ranopa, M.; Gopalakrishnan, G.S.; Thompson, A.G.B.; Rudge, P.; Wroe, S.; Kennedy, A.; Hudson, F.; MacKay, A.; Darbyshire, J.H.; Walker, A.S.

2011-01-01

Objectives: Human prion diseases are heterogeneous but invariably fatal neurodegenerative disorders with no known effective therapy. PRION-1, the largest clinical trial in prion disease to date, showed no effect of the potential therapeutic quinacrine on survival. Although there are several limitations to the usefulness of survival as an outcome measure, there have been no comprehensive studies of alternatives. Methods: To address this we did comparative analyses of neurocognitive, psychiatric, global, clinician-rated, and functional scales, focusing on validity, variability, and impact on statistical power over 77 person-years follow-up in 101 symptomatic patients in PRION-1. Results: Quinacrine had no demonstrable benefit on any of the 8 scales (p > 0.4). All scales had substantial numbers of patients with the worst possible score at enrollment (Glasgow Coma Scale score being least affected) and were impacted by missing data due to disease progression. These effects were more significant for cognitive/psychiatric scales than global, clinician-rated, or functional scales. The Barthel and Clinical Dementia Rating scales were the most valid and powerful in simulated clinical trials of an effective therapeutic. A combination of selected subcomponents from these 2 scales gave somewhat increased power, compared to use of survival, to detect clinically relevant effects in future clinical trials of feasible size. Conclusions: Our findings have implications for the choice of primary outcome measure in prion disease clinical trials. Prion disease presents the unusual opportunity to follow patients with a neurodegenerative disease through their entire clinical course, and this provides insights relevant to designing outcome measures in related conditions. PMID:22013183

Out-of-Field Dose Equivalents Delivered by Passively Scattered Therapeutic Proton Beams for Clinically Relevant Field Configurations

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

Wroe, Andrew; Centre for Medical Radiation Physics, University of Wollongong, Wollongong; Clasie, Ben

2009-01-01

Purpose: Microdosimetric measurements were performed at Massachusetts General Hospital, Boston, MA, to assess the dose equivalent external to passively delivered proton fields for various clinical treatment scenarios. Methods and Materials: Treatment fields evaluated included a prostate cancer field, cranial and spinal medulloblastoma fields, ocular melanoma field, and a field for an intracranial stereotactic treatment. Measurements were completed with patient-specific configurations of clinically relevant treatment settings using a silicon-on-insulator microdosimeter placed on the surface of and at various depths within a homogeneous Lucite phantom. The dose equivalent and average quality factor were assessed as a function of both lateral displacement frommore » the treatment field edge and distance downstream of the beam's distal edge. Results: Dose-equivalent value range was 8.3-0.3 mSv/Gy (2.5-60-cm lateral displacement) for a typical prostate cancer field, 10.8-0.58 mSv/Gy (2.5-40-cm lateral displacement) for the cranial medulloblastoma field, 2.5-0.58 mSv/Gy (5-20-cm lateral displacement) for the spinal medulloblastoma field, and 0.5-0.08 mSv/Gy (2.5-10-cm lateral displacement) for the ocular melanoma field. Measurements of external field dose equivalent for the stereotactic field case showed differences as high as 50% depending on the modality of beam collimation. Average quality factors derived from this work ranged from 2-7, with the value dependent on the position within the phantom in relation to the primary beam. Conclusions: This work provides a valuable and clinically relevant comparison of the external field dose equivalents for various passively scattered proton treatment fields.« less

Key factors of clinical research network capacity building.

PubMed

Li, Guowei; Wu, Qianyu; Jin, Yanling; Vanniyasingam, Thuva; Thabane, Lehana

2018-01-01

In general, clinical research network capacity building refers to programs aimed at enhancing networks of researchers to conduct clinical research. Although in the literature there is a large body of research on how to develop and build capacity in clinical research networks, the conceptualizations and implementations remain controversial and challenging. Moreover, the experiences learnt from the past accomplishments and failures can assist in the future capacity building efforts to be more practical, effective and efficient. In this paper, we aim to provide an overview of capacity building in clinical research network by (1) identifying the key barriers to clinical research network capacity building, (2) providing insights into how to overcome those obstacles, and (3) sharing our experiences in collaborating with national and international partners to build capacity in clinical research networks. In conclusion, we have provided some insight into how to address the key factors of clinical research network capacity building and shared some empirical experiences. A successful capacity building practice requires a joint endeavor to procure sufficient resources and support from the relevant stakeholders, to ensure its efficiency, cost-effectiveness, and sustainability.

Search for relevant indications for selenium supplementation in thyroid diseases.

PubMed

Wojciechowska-Durczynska, Katarzyna; Lewinski, Andrzej

2017-08-01

Selenium plays a significant role in the thyroid function and its deficiency is considered by some authors to be a cause of thyroid disorders. The potential therapeutic influence of selenium supplementation in thyroid disease was investigated in several studies and some results were encouraging, however results were inconsistent and did not allow conclusion to be drawn. For that reason, we have performed a review study on relevance of selenium supplementation in thyroid disease. Till now, there is no strong evidence that selenium supplementation leads to clinical improvement in the course of autoimmune thyroiditis, nodular goitre or thyroid cancer. On the other hand, there is some evidence that selenium is effective in the treatment of orbitopathy; thus, the European Group on Graves' Orbitopathy (EUGOGO) recommends selenium administration in mild active orbitopathy.

Verbal Memory Impairment in Polydrug Ecstasy Users: A Clinical Perspective

PubMed Central

Kuypers, Kim P. C.; Theunissen, Eef L.; van Wel, Janelle H. P.; de Sousa Fernandes Perna, Elizabeth B.; Linssen, Anke; Sambeth, Anke; Schultz, Benjamin G.; Ramaekers, Johannes G.

2016-01-01

Background Ecstasy use has been associated with short-term and long-term memory deficits on a standard Word Learning Task (WLT). The clinical relevance of this has been debated and is currently unknown. The present study aimed at evaluating the clinical relevance of verbal memory impairment in Ecstasy users. To that end, clinical memory impairment was defined as decrement in memory performance that exceeded the cut-off value of 1.5 times the standard deviation of the average score in the healthy control sample. The primary question was whether being an Ecstasy user (E-user) was predictive of having clinically deficient memory performance compared to a healthy control group. Methods WLT data were pooled from four experimental MDMA studies that compared memory performance during placebo and MDMA intoxication. Control data were taken from healthy volunteers with no drug use history who completed the WLT as part of a placebo-controlled clinical trial. This resulted in a sample size of 65 E-users and 65 age- and gender-matched healthy drug-naïve controls. All participants were recruited by similar means and were tested at the same testing facilities using identical standard operating procedures. Data were analyzed using linear mixed-effects models, Bayes factor, and logistic regressions. Results Findings were that verbal memory performance of placebo-treated E-users did not differ from that of controls, and there was substantial evidence in favor of the null hypothesis. History of use was not predictive of memory impairment. During MDMA intoxication of E-users, verbal memory was impaired. Conclusion The combination of the acute and long-term findings demonstrates that, while clinically relevant memory impairment is present during intoxication, it is absent during abstinence. This suggests that use of Ecstasy/MDMA does not lead to clinically deficient memory performance in the long term. Additionally, it has to be investigated whether the current findings apply to more complex cognitive measures in diverse ‘user categories’ using a combination of genetics, imaging techniques and neuropsychological assessments. PMID:26907605

Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement

PubMed Central

Bianco, Antonio C.; Bauer, Andrew J.; Burman, Kenneth D.; Cappola, Anne R.; Celi, Francesco S.; Cooper, David S.; Kim, Brian W.; Peeters, Robin P.; Rosenthal, M. Sara; Sawka, Anna M.

2014-01-01

Background: A number of recent advances in our understanding of thyroid physiology may shed light on why some patients feel unwell while taking levothyroxine monotherapy. The purpose of this task force was to review the goals of levothyroxine therapy, the optimal prescription of conventional levothyroxine therapy, the sources of dissatisfaction with levothyroxine therapy, the evidence on treatment alternatives, and the relevant knowledge gaps. We wished to determine whether there are sufficient new data generated by well-designed studies to provide reason to pursue such therapies and change the current standard of care. This document is intended to inform clinical decision-making on thyroid hormone replacement therapy; it is not a replacement for individualized clinical judgment. Methods: Task force members identified 24 questions relevant to the treatment of hypothyroidism. The clinical literature relating to each question was then reviewed. Clinical reviews were supplemented, when relevant, with related mechanistic and bench research literature reviews, performed by our team of translational scientists. Ethics reviews were provided, when relevant, by a bioethicist. The responses to questions were formatted, when possible, in the form of a formal clinical recommendation statement. When responses were not suitable for a formal clinical recommendation, a summary response statement without a formal clinical recommendation was developed. For clinical recommendations, the supporting evidence was appraised, and the strength of each clinical recommendation was assessed, using the American College of Physicians system. The final document was organized so that each topic is introduced with a question, followed by a formal clinical recommendation. Stakeholder input was received at a national meeting, with some subsequent refinement of the clinical questions addressed in the document. Consensus was achieved for all recommendations by the task force. Results: We reviewed the following therapeutic categories: (i) levothyroxine therapy, (ii) non–levothyroxine-based thyroid hormone therapies, and (iii) use of thyroid hormone analogs. The second category included thyroid extracts, synthetic combination therapy, triiodothyronine therapy, and compounded thyroid hormones. Conclusions: We concluded that levothyroxine should remain the standard of care for treating hypothyroidism. We found no consistently strong evidence for the superiority of alternative preparations (e.g., levothyroxine–liothyronine combination therapy, or thyroid extract therapy, or others) over monotherapy with levothyroxine, in improving health outcomes. Some examples of future research needs include the development of superior biomarkers of euthyroidism to supplement thyrotropin measurements, mechanistic research on serum triiodothyronine levels (including effects of age and disease status, relationship with tissue concentrations, as well as potential therapeutic targeting), and long-term outcome clinical trials testing combination therapy or thyroid extracts (including subgroup effects). Additional research is also needed to develop thyroid hormone analogs with a favorable benefit to risk profile. PMID:25266247

Incidental findings in multislice computed tomography prior to transcatheter aortic valve implantation: frequency, clinical relevance and outcome.

PubMed

Trenkwalder, Teresa; Lahmann, Anna Lena; Nowicka, Magdalena; Pellegrini, Costanza; Rheude, Tobias; Mayr, N Patrick; Voss, Stephanie; Bleiziffer, Sabine; Lange, Rüdiger; Joner, Michael; Kasel, Albert M; Kastrati, Adnan; Schunkert, Heribert; Husser, Oliver; Hadamitzky, Martin; Hengstenberg, Christian

2018-02-21

Multislice computed tomography (MSCT) has emerged as the mainstay in patients planned for transcatheter aortic valve implantation (TAVI). Incidental findings (IF) in MSCT are common. However, the exact incidence, clinical relevance and further consequences of IF are unclear and it is controversial whether IF adversely affect patients' outcome. We analyzed MSCT data of 1050 patients screened for TAVI between January 2011 and December 2014. Median follow-up of patients was 20 months. In total, 3194 IF were identified, which were classified into clinically non-relevant IF (2872, 90%) and clinically relevant IF (322, 10%). In 25% of patients (258/1050) at least one clinically relevant IF was present. Age (80 ± 7 vs. 80 ± 7 years; p = 0.198) and EuroSCORE II (3.6% [2.1-5.7] vs. 3.6% [2.1-5.9]; p = 0.874) was similar between patients with and without a clinically relevant IF. TAVI was performed less frequently in patients with a clinically relevant IF (76% vs. 85%; p < 0.001), with more patients receiving surgical aortic valve replacement in that group (14% vs. 11%; p = 0.042), possibly due to the high rate of incidental aneurysms of the ascending aorta (n = 48). If TAVI was performed mortality did not differ (30-days: 4% vs. 3%; p = 0.339, 1-year: 11% vs. 14%; p = 0.226) between patients with and without a clinically relevant IF. Our study is the largest study to analyze prevalence, clinical relevance and therapeutic consequences of IF during screening for TAVI. IF in pre-procedural MSCT are common and clinically relevant in one-quarter of patients. However, these findings had no impact on overall mortality.

Phenotype Instance Verification and Evaluation Tool (PIVET): A Scaled Phenotype Evidence Generation Framework Using Web-Based Medical Literature

PubMed Central

Ke, Junyuan; Ho, Joyce C; Ghosh, Joydeep; Wallace, Byron C

2018-01-01

Background Researchers are developing methods to automatically extract clinically relevant and useful patient characteristics from raw healthcare datasets. These characteristics, often capturing essential properties of patients with common medical conditions, are called computational phenotypes. Being generated by automated or semiautomated, data-driven methods, such potential phenotypes need to be validated as clinically meaningful (or not) before they are acceptable for use in decision making. Objective The objective of this study was to present Phenotype Instance Verification and Evaluation Tool (PIVET), a framework that uses co-occurrence analysis on an online corpus of publically available medical journal articles to build clinical relevance evidence sets for user-supplied phenotypes. PIVET adopts a conceptual framework similar to the pioneering prototype tool PheKnow-Cloud that was developed for the phenotype validation task. PIVET completely refactors each part of the PheKnow-Cloud pipeline to deliver vast improvements in speed without sacrificing the quality of the insights PheKnow-Cloud achieved. Methods PIVET leverages indexing in NoSQL databases to efficiently generate evidence sets. Specifically, PIVET uses a succinct representation of the phenotypes that corresponds to the index on the corpus database and an optimized co-occurrence algorithm inspired by the Aho-Corasick algorithm. We compare PIVET’s phenotype representation with PheKnow-Cloud’s by using PheKnow-Cloud’s experimental setup. In PIVET’s framework, we also introduce a statistical model trained on domain expert–verified phenotypes to automatically classify phenotypes as clinically relevant or not. Additionally, we show how the classification model can be used to examine user-supplied phenotypes in an online, rather than batch, manner. Results PIVET maintains the discriminative power of PheKnow-Cloud in terms of identifying clinically relevant phenotypes for the same corpus with which PheKnow-Cloud was originally developed, but PIVET’s analysis is an order of magnitude faster than that of PheKnow-Cloud. Not only is PIVET much faster, it can be scaled to a larger corpus and still retain speed. We evaluated multiple classification models on top of the PIVET framework and found ridge regression to perform best, realizing an average F1 score of 0.91 when predicting clinically relevant phenotypes. Conclusions Our study shows that PIVET improves on the most notable existing computational tool for phenotype validation in terms of speed and automation and is comparable in terms of accuracy. PMID:29728351

What's wrong with my mouse cage? Methodological considerations for modeling lifestyle factors and gene-environment interactions in mice.

PubMed

Mo, Christina; Renoir, Thibault; Hannan, Anthony J

2016-05-30

The mechanistic understanding of lifestyle contributions to disease has been largely driven by work in laboratory rodent models using environmental interventions. These interventions show an array of methodologies and sometimes unclear collective conclusions, hampering clinical interpretations. Here we discuss environmental enrichment, exercise and stress interventions to illustrate how different protocols can affect the interpretations of environmental factors in disease. We use Huntington's disease (HD) as an example because its mouse models exhibit excellent validity and HD was the first genetic animal model in which environmental stimulation was found to be beneficial. We make a number of observations and recommendations. Firstly, environmental enrichment and voluntary exercise generally show benefits across laboratories and mouse models. However, the extent to which these environmental interventions have beneficial effects depends on parameters such as the structural complexity of the cage in the case of enrichment, the timing of the intervention and the nature of the control conditions. In particular, clinical interpretations should consider deprived control living conditions and the ethological relevance of the enrichment. Secondly, stress can have negative effects on the phenotype in mouse models of HD and other brain disorders. When modeling stress, the effects of more than one type of experimental stressor should be investigated due to the heterogeneity and complexity of stress responses. With stress in particular, but ideally in all studies, both sexes should be used and the randomized group sizes need to be sufficiently powered to detect any sex effects. Opportunities for clinical translation will be guided by the 'environmental construct validity' of the preclinical data, including the culmination of complementary protocols across multiple animal models. Environmental interventions in mouse models of HD provide illustrative examples of how valid preclinical studies can lead to conclusions relevant to clinical populations. Copyright © 2015 Elsevier B.V. All rights reserved.

Detection of clinically relevant copy-number variants by exome sequencing in a large cohort of genetic disorders

PubMed Central

Pfundt, Rolph; del Rosario, Marisol; Vissers, Lisenka E.L.M.; Kwint, Michael P.; Janssen, Irene M.; de Leeuw, Nicole; Yntema, Helger G.; Nelen, Marcel R.; Lugtenberg, Dorien; Kamsteeg, Erik-Jan; Wieskamp, Nienke; Stegmann, Alexander P.A.; Stevens, Servi J.C.; Rodenburg, Richard J.T.; Simons, Annet; Mensenkamp, Arjen R.; Rinne, Tuula; Gilissen, Christian; Scheffer, Hans; Veltman, Joris A.; Hehir-Kwa, Jayne Y.

2017-01-01

Purpose: Copy-number variation is a common source of genomic variation and an important genetic cause of disease. Microarray-based analysis of copy-number variants (CNVs) has become a first-tier diagnostic test for patients with neurodevelopmental disorders, with a diagnostic yield of 10–20%. However, for most other genetic disorders, the role of CNVs is less clear and most diagnostic genetic studies are generally limited to the study of single-nucleotide variants (SNVs) and other small variants. With the introduction of exome and genome sequencing, it is now possible to detect both SNVs and CNVs using an exome- or genome-wide approach with a single test. Methods: We performed exome-based read-depth CNV screening on data from 2,603 patients affected by a range of genetic disorders for which exome sequencing was performed in a diagnostic setting. Results: In total, 123 clinically relevant CNVs ranging in size from 727 bp to 15.3 Mb were detected, which resulted in 51 conclusive diagnoses and an overall increase in diagnostic yield of ~2% (ranging from 0 to –5.8% per disorder). Conclusions: This study shows that CNVs play an important role in a broad range of genetic disorders and that detection via exome-based CNV profiling results in an increase in the diagnostic yield without additional testing, bringing us closer to single-test genomics. Genet Med advance online publication 27 October 2016 PMID:28574513

Pathogenesis and mechanisms of antibody-mediated hemolysis

PubMed Central

Flegel, Willy A

2015-01-01

Background The clinical consequences of antibodies to red blood cells (RBC) have been studied for a century. Most clinically relevant antibodies can be detected by sensitive in vitro assays. Several mechanisms of antibody-mediated hemolysis are well understood. Such hemolysis following transfusion is reliably avoided in a donor/recipient pair, if one individual is negative for the cognate antigen to which the other has the antibody. Study design and results Mechanisms of antibody-mediated hemolysis were reviewed based on a presentation at the Strategies to Address Hemolytic Complications of Immune Globulin Infusions Workshop addressing intravenous immunoglobulin (IVIG) and ABO antibodies. The presented topics included the rates of intravascular and extravascular hemolysis; IgM and IgG isoagglutinins; auto- and alloantibodies; antibody specificity; A, B, A,B and A1 antigens; A1 versus A2 phenotypes; monocytes/macrophages, other immune cells and complement; monocyte monolayer assay (MMA); antibody-dependent cell-mediated cytotoxicity (ADCC); and transfusion reactions due to ABO and other antibodies. Conclusion Several clinically relevant questions remained unresolved, and diagnostic tools were lacking to routinely and reliably predict the clinical consequences of RBC antibodies. Most hemolytic transfusion reactions associated with IVIG were due to ABO antibodies. Reducing the titers of such antibodies in IVIG may lower the frequency of this kind of adverse event. The only way to stop these events is to have no anti-A or anti-B antibodies in the IVIG products. PMID:26174897

Establishment and Characterization of Primary Glioblastoma Cell Lines from Fresh and Frozen Material: A Detailed Comparison

PubMed Central

Mullins, Christina Susanne; Schneider, Björn; Stockhammer, Florian; Krohn, Mathias; Classen, Carl Friedrich; Linnebacher, Michael

2013-01-01

Background Development of clinically relevant tumor model systems for glioblastoma multiforme (GBM) is important for advancement of basic and translational biology. High molecular heterogeneity of GBM tumors is well recognized, forming the rationale for molecular tests required before administration of several of the novel therapeutics rapidly entering the clinics. One model that has gained wide acceptance is the primary cell culture model. The laborious and time consuming process is rewarded with a relative high success rate (about 60%). We here describe and evaluate a very simple cryopreservation procedure for GBM tissue prior to model establishment that will considerably reduce the logistic complexity. Methods Twenty-seven GBM samples collected ad hoc were prepared for primary cell culture freshly from surgery (#1) and after cryopreservation (#2). Results Take rates after cryopreservation (59%) were as satisfactory as from fresh tissue (63%; p = 1.000). We did not observe any relevant molecular or phenotypic differences between cell lines established from fresh or vitally frozen tissue. Further, sensitivity both towards standard chemotherapeutic agents (Temozolomide, BCNU and Vincristine) and novel agents like the receptor tyrosine kinase inhibitor Imatinib did not differ. Conclusions Our simple cryopreservation procedure facilitates collection, long-time storage and propagation (modeling) of clinical GBM specimens (potentially also from distant centers) for basic research, (pre-) clinical studies of novel therapies and individual response prediction. PMID:23951083

Limited clinical relevance of imaging techniques in the follow-up of patients with advanced chronic lymphocytic leukemia: results of a meta-analysis.

PubMed

Eichhorst, Barbara F; Fischer, Kirsten; Fink, Anna-Maria; Elter, Thomas; Wendtner, Clemens M; Goede, Valentin; Bergmann, Manuela; Stilgenbauer, Stephan; Hopfinger, Georg; Ritgen, Matthias; Bahlo, Jasmin; Busch, Raymonde; Hallek, Michael

2011-02-10

The clinical value of imaging is well established for the follow-up of many lymphoid malignancies but not for chronic lymphocytic leukemia (CLL). A meta-analysis was performed with the dataset of 3 German CLL Study Group phase 3 trials (CLL4, CLL5, and CLL8) that included 1372 patients receiving first-line therapy for CLL. Response as well as progression during follow-up was reassessed according to the National Cancer Institute Working Group1996 criteria. A total of 481 events were counted as progressive disease during treatment or follow-up. Of these, 372 progressions (77%) were detected by clinical symptoms or blood counts. Computed tomography (CT) scans or ultrasound were relevant in 44 and 29 cases (9% and 6%), respectively. The decision for relapse treatment was determined by CT scan or ultrasound results in only 2 of 176 patients (1%). CT scan results had an impact on the prognosis of patients in complete remission only after the administration of conventional chemotherapy but not after chemoimmunotherapy. In conclusion, physical examination and blood count remain the methods of choice for staging and clinical follow-up of patients with CLL as recommended by the International Workshop on Chronic Lymphocytic Leukemia 2008 guidelines. These trials are registered at http://www.isrctn.org as ISRCTN 75653261 and ISRCTN 36294212 and at http://www.clinicaltrials.gov as NCT00281918.

Pedagogical Approaches to Diagnostic Imaging Education: A Narrative Review of the Literature

PubMed Central

Linaker, Kathleen L.

2015-01-01

Objective The purpose of this study was to examine literature on how radiology is taught and learned by both radiology residents and undergraduates in the health professions. Methods A review of the literature was performed using relevant key words. Articles were retrieved through December 2012 using PubMed, ScienceDirect, ERIC, Proquest, and ICL databases along with a manual review of references. Results Of the 4716 unique abstracts reviewed by the author, 91 were found to be relevant to the purpose of this study. The literature retrieved reported pedagogical approaches to teaching radiology including the following: problem solving, technology as teacher, independent learning tools, visiting lectureships, case based teaching, and conferences. There was some exploration of the relative effectiveness of educational formats. Suggestions for future research identify 7 areas of relative consistency. Conclusion Radiology is a clinical skill that requires integration science, clinical information, clinical experiences, and information recorded on diagnostic imaging studies. The research in this area focuses on problem solving, the use of algorithm/scripts, introducing uncertainty in clinical scenarios, incorporating technology in learning environments, active learning techniques, and methods of independent learning. Although the literature in this area is still in its infancy, the research examining the relative effectiveness of these various educational formats is often contradictory, suggesting that this is a complex area of study with numerous factors influencing student learning. PMID:26770173

A Cross-Sectional Study of the Psychological Needs of Adults Living with Cystic Fibrosis

PubMed Central

Pakhale, Smita; Baron, Justine; Armstrong, Michael; Tasca, Georgio; Gaudet, Ena; Aaron, Shawn; Cameron, William; Balfour, Louise

2015-01-01

Background Depression and anxiety are prevalent in people with cystic fibrosis (CF), yet psychological services are rarely accessible in CF clinics. This cross-sectional single center study reports on a psychological needs assessment of people with CF. Methods We asked adults attending a CF clinic, without integrated psychological services, to complete a psychological needs assessment survey that included items on: a) past access to psychological services (via a CF referral service), b) concerns relevant to discuss with a psychologist, and c) their likelihood of accessing psychological services if available at the CF clinic, and standardized measures of depression (CES-D) and anxiety (GAD-7). Results We enrolled 49 participants and 45 (91.8%) completed the survey. Forty percent reported elevated symptoms of depression and 13% had elevated anxiety. A majority of individuals (72.2% and 83.3%, respectively) indicated they would be likely to use psychological services, if available at the clinic. Concerns considered most relevant to discuss with a psychologist were: 1) worries (51.1%), 2) mood (44.4%), 3) life stress (46.6%), 4) adjustment to CF (42.2%), 5) life transitions (42.2%) and 6) quality of life (42.2%). Conclusions This study highlights the rationale for screening adults with CF for depression and anxiety, and to facilitate provision of psychological services and preventative mental health interventions as an integral component of multi-disciplinary CF care. PMID:26102351

Spinal Muscular Atrophy Biomarker Measurements from Blood Samples in a Clinical Trial of Valproic Acid in Ambulatory Adults

PubMed Central

Renusch, Samantha R.; Harshman, Sean; Pi, Hongyang; Workman, Eileen; Wehr, Allison; Li, Xiaobai; Prior, Thomas W.; Elsheikh, Bakri H.; Swoboda, Kathryn J.; Simard, Louise R.; Kissel, John T.; Battle, Daniel; Parthun, Mark R.; Freitas, Michael A.; Kolb, Stephen J.

2015-01-01

Abstract Background: Clinical trials of therapies for spinal muscular atrophy (SMA) that are designed to increase the expression the SMN protein ideally include careful assessment of relevant SMN biomarkers. Objective: In the SMA VALIANT trial, a recent double-blind placebo-controlled crossover study of valproic acid (VPA) in ambulatory adult subjects with SMA, we investigated relevant pharmacodynamic biomarkers in blood samples from SMA subjects by direct longitudinal measurement of histone acetylation and SMN mRNA and protein levels in the presence and absence of VPA treatment. Methods: Thirty-three subjects were randomized to either VPA or placebo for the first 6 months followed by crossover to the opposite arm for an additional 6 months. Outcome measures were compared between the two treatments (VPA and placebo) using a standard crossover analysis. Results: A significant increase in histone H4 acetylation was observed with VPA treatment (p = 0.005). There was insufficient evidence to suggest a treatment effect with either full length or truncated SMN mRNA transcript levels or SMN protein levels. Conclusions: These measures were consistent with the observed lack of change in the primary clinical outcome measure in the VALIANT trial. These results also highlight the added benefit of molecular and pharmacodynamic biomarker measurements in the interpretation of clinical trial outcomes. PMID:27858735

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

PubMed Central

Qi, Xing-Shun

2017-01-01

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

Outcomes of Implementing the Women's Health Assessment Tool and Clinical Decision Support Tool Kit

PubMed Central

Silvestrin, Terry; Steenrod, Anna; Coyne, Karin; Gross, David; Esinduy, Canan; Kodsi, Angela; Slifka, Gayle; Abraham, Lucy; Araiza, Anna; Bushmakin, Andrew; Luo, Xuemei

2016-01-01

Aim: To evaluate outcomes after implementing the women's health assessment tool (WHAT) and clinical decision support toolkit during annual well-women visits. Methods: An observational project involved women aged 45–64 years attending one of three medical sites in Washington (WA, USA). Responses to the WHAT questionnaire and patients' health resource utilization prepost toolkit implementation were analyzed. Results: A total of 110 women completed the WHAT questionnaire. Majority of women were postmenopausal (77.3%) and experienced depressive mood (63.6%), hot flashes (61.8%) or anxiety (60.9%) in the last 3 months. There was a 72.2% increase in the number of diagnoses made during the annual visit versus the previous 12 months. Conclusion: The WHAT/clinical decision support toolkit helped identify conditions relevant to mid-life women. PMID:27188377

Development of imaging biomarkers and generation of big data.

PubMed

Alberich-Bayarri, Ángel; Hernández-Navarro, Rafael; Ruiz-Martínez, Enrique; García-Castro, Fabio; García-Juan, David; Martí-Bonmatí, Luis

2017-06-01

Several image processing algorithms have emerged to cover unmet clinical needs but their application to radiological routine with a clear clinical impact is still not straightforward. Moving from local to big infrastructures, such as Medical Imaging Biobanks (millions of studies), or even more, Federations of Medical Imaging Biobanks (in some cases totaling to hundreds of millions of studies) require the integration of automated pipelines for fast analysis of pooled data to extract clinically relevant conclusions, not uniquely linked to medical imaging, but in combination to other information such as genetic profiling. A general strategy for the development of imaging biomarkers and their integration in the cloud for the quantitative management and exploitation in large databases is herein presented. The proposed platform has been successfully launched and is being validated nowadays among the early adopters' community of radiologists, clinicians, and medical imaging researchers.

Molecular characterization of NRXN1 deletions from 19,263 clinical microarray cases identifies exons important for neurodevelopmental disease expression

PubMed Central

Lowther, Chelsea; Speevak, Marsha; Armour, Christine M.; Goh, Elaine S.; Graham, Gail E.; Li, Chumei; Zeesman, Susan; Nowaczyk, Malgorzata J.M.; Schultz, Lee-Anne; Morra, Antonella; Nicolson, Rob; Bikangaga, Peter; Samdup, Dawa; Zaazou, Mostafa; Boyd, Kerry; Jung, Jack H.; Siu, Victoria; Rajguru, Manjulata; Goobie, Sharan; Tarnopolsky, Mark A.; Prasad, Chitra; Dick, Paul T.; Hussain, Asmaa S.; Walinga, Margreet; Reijenga, Renske G.; Gazzellone, Matthew; Lionel, Anath C.; Marshall, Christian R.; Scherer, Stephen W.; Stavropoulos, Dimitri J.; McCready, Elizabeth; Bassett, Anne S.

2016-01-01

Purpose The purpose of the current study was to assess the penetrance of NRXN1 deletions. Methods We compared the prevalence and genomic extent of NRXN1 deletions identified among 19,263 clinically referred cases to that of 15,264 controls. The burden of additional clinically relevant CNVs was used as a proxy to estimate the relative penetrance of NRXN1 deletions. Results We identified 41 (0.21%) previously unreported exonic NRXN1 deletions ascertained for developmental delay/intellectual disability, significantly greater than in controls [OR=8.14 (95% CI 2.91–22.72), p< 0.0001)]. Ten (22.7%) of these had a second clinically relevant CNV. Subjects with a deletion near the 3′ end of NRXN1 were significantly more likely to have a second rare CNV than subjects with a 5′ NRXN1 deletion [OR=7.47 (95% CI 2.36–23.61), p=0.0006]. The prevalence of intronic NRXN1 deletions was not statistically different between cases and controls (p=0.618). The majority (63.2%) of intronic NRXN1 deletion cases had a second rare CNV, a two-fold greater prevalence than for exonic NRXN1 deletion cases (p=0.0035). Conclusions The results support the importance of exons near the 5′ end of NRXN1 in the expression of neurodevelopmental disorders. Intronic NRXN1 deletions do not appear to substantially increase the risk for clinical phenotypes. PMID:27195815

International guidelines for the in vivo assessment of skin properties in non-clinical settings: part 1. pH

PubMed Central

Stefaniak, Aleksandr B; du Plessis, Johan; John, Swen M; Eloff, Fritz; Agner, Tove; Chou, Tzu-Chieh; Nixon, Rosemary; Steiner, Markus F C; Kudla, Irena; Holness, D Linn

2013-01-01

Background Skin surface pH is known to influence the dissolution and partitioning of chemicals and may influence exposures that lead to skin diseases. Non-clinical environments (e.g. workplaces) are highly variable, thereby presenting unique measurement challenges that are not typically encountered in clinical settings. Hence, guidelines are needed for consistent measurement of skin surface pH in environments that are difficult to control. Methods An expert workshop was convened at the 5th International Conference on Occupational and Environmental Exposure of Skin to Chemicals to review available data on factors that could influence the determination of skin surface pH in non-clinical settings with emphasis on the workplace as a worst case scenario. Results The key elements of the guidelines are: (i) minimize, to the extent feasible, the influences of relevant endogenous (anatomical position, skin health, time of day), exogenous (hand washing, barrier creams, soaps and detergents, occlusion), environmental (seasonality), and measurement (atmospheric conditions) factors; (ii) report pH measurements results as a difference or percent change (not absolute values) using a measure of central tendency and variability; and (iii) report notable deviations from these guidelines and other relevant factors that may influence measurements. Conclusion Guidelines on the measurement and reporting of skin surface pH in non-clinical settings should promote consistency in data reporting, facilitate inter-comparison of study results, and aid in understanding and preventing occupational skin diseases. PMID:23279097

"What I believe is true": Belief-confirming reasoning bias in social anxiety disorder.

PubMed

Vroling, Maartje S; Glashouwer, Klaske A; Lange, Wolf-Gero; Allart-van Dam, Esther; de Jong, Peter J

2016-12-01

Research shows that people tend to consider believable conclusions as valid and unbelievable conclusions as invalid (belief bias). When applied to anxiogenic beliefs, this belief bias could well hinder the correction of dysfunctional convictions. Previous work has shown that high socially anxious students indeed display such fear-confirming, belief biased, reasoning. A critical next question is whether these findings translate to a clinical population of people with social anxiety disorder (SAD). We test whether (i) patients with SAD show belief bias with regard to SAD-relevant themes, (ii) this belief bias is specific for SAD patients or can also be found in panic disorder (PD) patients, (iii) differential belief bias effects in SAD are restricted to social anxiety concerns or are also evident in the context of reasoning with neutral themes. 45 SAD patients, 24 PD patients, and 45 non-symptomatic controls (NSCs) completed a syllogistic belief bias task with SAD-relevant and neutral content. SAD patients displayed belief bias for social anxiety related materials, while the PD group and the NSC group did not. Yet, the difference between SAD and PD was not significant. All groups showed similar belief bias effects for neutral content. Content of the belief bias task was not tailored to idiosyncratic beliefs. The study lacked power to detect medium or small differences. SAD patients showed concern-congruent belief biased interference effects when judging the logical validity of social anxiety relevant syllogisms. Such concern-relevant belief bias may contribute to the persistence of anxiogenic beliefs. Copyright © 2016 Elsevier Ltd. All rights reserved.

CLINICAL AUTONOMIC NEUROPHYSIOLOGY AND THE MALE SEXUAL RESPONSE: AN OVERVIEW

PubMed Central

Yang, Claire C.; Jiang, Xiaogang

2009-01-01

Introduction Clinical neurophysiology is the study of the human nervous system through the recording of bioelectrical activity. In the realm of male sexual functioning, this includes using electrophysiologic techniques to study the nerves subserving erection, emission, ejaculation, and orgasm. Aim To introduce the reader to the principles of clinical neurophysiology as they relate to the male sexual response, particularly erection. Methods We review the pertinent autonomic neuroanatomy and neurophysiology of reflexes relevant to the male sexual response, as well as summarize the genital electrodiagnostic tests that are being used to interrogate the autonomic innervation pertinent to male sexual functioning. Conclusions The male sexual response is a coordinated series of interactions between the somatic and the autonomic nervous systems. Measurement of the autonomically mediated portions of the sexual reflexes is of great clinical interest, particularly in relation to erection. Advances in clinical electrodiagnostics now allow for consistent recording of evoked and spontaneous intra-penile electrical activity. However, before broad and widespread use of these techniques is possible, more investigations are needed. PMID:19267845

Pharmacological validation of a novel nonhuman primate measure of thermal responsivity with utility for predicting analgesic effects

PubMed Central

Vardigan, Joshua D; Houghton, Andrea K; Lange, Henry S; Adarayan, Emily D; Pall, Parul S; Ballard, Jeanine E; Henze, Darrell A; Uslaner, Jason M

2018-01-01

Introduction The development of novel analgesics to treat acute or chronic pain has been a challenge due to a lack of translatable measurements. Preclinical end points with improved translatability are necessary to more accurately inform clinical testing paradigms, which may help guide selection of viable drug candidates. Methods In this study, a nonhuman primate biomarker which is sensitive to standard analgesics at clinically relevant plasma concentrations, can differentiate analgesia from sedation and utilizes a protocol very similar to that which can be employed in human clinical studies is described. Specifically, acute heat stimuli were delivered to the volar forearm using a contact heat thermode in the same manner as the clinical setting. Results Clinically efficacious exposures of morphine, fentanyl, and tramadol produced robust analgesic effects, whereas doses of diazepam that produce sedation had no effect. Conclusion We propose that this assay has predictive utility that can help improve the probability of success for developing novel analgesics. PMID:29692626

A systematic review of the factors that influence the quality and effectiveness of telesupervision for health professionals.

PubMed

Martin, Priya; Lizarondo, Lucylynn; Kumar, Saravana

2018-05-01

Introduction Whilst telesupervision (clinical supervision undertaken using communication technology) is being used more frequently, there is limited information on what factors influence its effectiveness and quality. We undertook this systematic review to address this gap. Methods Eligible telesupervision studies were identified following targeted search of electronic databases and the grey literature. Data were synthesised thematically, resulting in development of core themes. Results We identified 286 papers for initial relevancy screening by title and abstract. The full text of 36 papers were then retrieved and assessed for further relevance. A total of 11 papers were included in the final analysis. We identified eight themes that contribute to effective and high-quality telesupervision: supervisee characteristics, supervisor characteristics, supervision characteristics, supervisory relationship, communication strategies, prior face-to-face contact, environmental factors and technological considerations. Conclusion From the available evidence, telesupervision can be a feasible and acceptable form of clinical supervision if set up well. Further studies with robust designs are required to strengthen the existing evidence on what makes telesupervision effective, as well as to examine its cost-effectiveness.

A report on older-age bipolar disorder from the International Society for Bipolar Disorders Task Force

PubMed Central

Sajatovic, Martha; Strejilevich, Sergio A; Gildengers, Ariel G; Dols, Annemiek; Al Jurdi, Rayan K; Forester, Brent P; Kessing, Lars Vedel; Beyer, John; Manes, Facundo; Rej, Soham; Rosa, Adriane R; Schouws, Sigfried NTM; Tsai, Shang-Ying; Young, Robert C; Shulman, Kenneth I

2015-01-01

Objectives In the coming generation, older adults with bipolar disorder (BD) will increase in absolute numbers as well as proportion of the general population. This is the first report of the International Society for Bipolar Disorder (ISBD) Task Force on Older-Age Bipolar Disorder (OABD). Methods This task force report addresses the unique aspects of OABD including epidemiology and clinical features, neuropathology and biomarkers, physical health, cognition, and care approaches. Results The report describes an expert consensus summary on OABD that is intended to advance the care of patients, and shed light on issues of relevance to BD research across the lifespan. Although there is still a dearth of research and health efforts focused on older adults with BD, emerging data has brought some answers, innovative questions, and novel perspectives related to the notion of late onset, medical comorbidity, and the vexing issue of cognitive impairment and decline. Conclusions Improving our understanding of the biological, clinical, and social underpinnings relevant to OABD is an indispensable step in building a complete map of BD across the lifespan. PMID:26384588

Transcultural adaptation and new proposal for the nursing outcome, Physical condition (2004)

PubMed Central

Navarrete, Jessica Rojas; Pérez, Paloma Echevarría; Costa, César Leal

2018-01-01

ABSTRACT Objectives: cross-culturally adapt to the Spanish context and make a new proposal for the nursing outcome, Physical Condition (2004), of the Nursing Outcomes Classification (NOC) for its precise use in clinical practice. Method: a cross-cultural adaptation study and a proposal for the nursing outcome, Physical Condition, was conducted and supported by the opinion of 26 experts. The data was obtained through an electronic form, and a quantitative analysis was conducted, using the SPSS software. Results: the version adapted to the Spanish context was obtained and the proposal of the outcome, Physical Condition, received agreement from 26 experts, with a mean score greater than 7.6 for adequacy of the outcome definition and its indicators, and 8.5 for the relevance of the indicators. Conclusions: the version adapted to the Spanish context and a new proposal for Physical Condition were obtained. The results obtained indicate a high level of adequacy and relevance, an instrument of great utility in the clinic, and research was obtained to evaluate the interventions directed to the improvement of the physical condition. PMID:29791669

A Case for the Standardized Assessment of Testamentary Capacity

PubMed Central

Brenkel, Megan; Whaley, Kimberley; Herrmann, Nathan; Crawford, Kerri; Hazan, Elias; Cardiff, Laura; Owen, Adrian M.

2018-01-01

Background With an increasingly aged, frail population that holds a disproportionate amount of wealth, clinicians (especially those with expertise in older adults) may be asked with more frequency to offer a clinical opinion on testamentary capacity (TC), the mental capacity to make a will. Method This paper reviews the legal criteria as well as the empirical research on assessment tools for determining testamentary capacity (TC). We also review the relevance of instruments used for the assessment of other decisional capacities in order to evince the potential value of developing a standardized assessment of TC for clinician experts. Results The legal criteria, often referred to as a “test”, for determining requisite TC (Banks v. Goodfellow) have remained much the same since 1870 with minimal clinical input and, as such, there has been little development in TC assessment instruments. Decisional instruments designed to assess Consent to Treatment may have relevance for TC. Conclusion We make the case for a semi-structured interview that includes standardized criteria for the legal test for TC, supplemented by a validated brief neuropsychological assessment, which together comprise a Contemporaneous Assessment Instrument (CAI) for TC. PMID:29581818

Activating Akt1 mutations alter DNA double strand break repair and radiosensitivity

PubMed Central

Oeck, S.; Al-Refae, K.; Riffkin, H.; Wiel, G.; Handrick, R.; Klein, D.; Iliakis, G.; Jendrossek, V.

2017-01-01

The survival kinase Akt has clinical relevance to radioresistance. However, its contributions to the DNA damage response, DNA double strand break (DSB) repair and apoptosis remain poorly defined and often contradictory. We used a genetic approach to explore the consequences of genetic alterations of Akt1 for the cellular radiation response. While two activation-associated mutants with prominent nuclear access, the phospho-mimicking Akt1-TDSD and the clinically relevant PH-domain mutation Akt1-E17K, accelerated DSB repair and improved survival of irradiated Tramp-C1 murine prostate cancer cells and Akt1-knockout murine embryonic fibroblasts in vitro, the classical constitutively active membrane-targeted myrAkt1 mutant had the opposite effects. Interestingly, DNA-PKcs directly phosphorylated Akt1 at S473 in an in vitro kinase assay but not vice-versa. Pharmacological inhibition of DNA-PKcs or Akt restored radiosensitivity in tumour cells expressing Akt1-E17K or Akt1-TDSD. In conclusion, Akt1-mediated radioresistance depends on its activation state and nuclear localization and is accessible to pharmacologic inhibition. PMID:28209968

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 iteratively improved to achieve a clinically relevant irradiation model.« less

Some controversial multiple testing problems in regulatory applications.

PubMed

Hung, H M James; Wang, Sue-Jane

2009-01-01

Multiple testing problems in regulatory applications are often more challenging than the problems of handling a set of mathematical symbols representing multiple null hypotheses under testing. In the union-intersection setting, it is important to define a family of null hypotheses relevant to the clinical questions at issue. The distinction between primary endpoint and secondary endpoint needs to be considered properly in different clinical applications. Without proper consideration, the widely used sequential gate keeping strategies often impose too many logical restrictions to make sense, particularly to deal with the problem of testing multiple doses and multiple endpoints, the problem of testing a composite endpoint and its component endpoints, and the problem of testing superiority and noninferiority in the presence of multiple endpoints. Partitioning the null hypotheses involved in closed testing into clinical relevant orderings or sets can be a viable alternative to resolving the illogical problems requiring more attention from clinical trialists in defining the clinical hypotheses or clinical question(s) at the design stage. In the intersection-union setting there is little room for alleviating the stringency of the requirement that each endpoint must meet the same intended alpha level, unless the parameter space under the null hypothesis can be substantially restricted. Such restriction often requires insurmountable justification and usually cannot be supported by the internal data. Thus, a possible remedial approach to alleviate the possible conservatism as a result of this requirement is a group-sequential design strategy that starts with a conservative sample size planning and then utilizes an alpha spending function to possibly reach the conclusion early.

Intake assessment of problematic use of medications in a chronic noncancer pain clinic

PubMed Central

Pink, Leah R; Smith, Andrew J; Peng, Philip WH; Galonski, Marilyn J; Tumber, Paul S; Evans, David; Gourlay, Doug L; Gordon, Lesley; Bellingham, Geoff A; Nijjar, Satnam S; Picard, Larry M; Gordon, Allan S

2012-01-01

BACKGROUND: The present article outlines the process of instituting an assessment of risk of problematic use of medications with new patients in an ambulatory chronic noncancer pain (CNCP) clinic. It is hoped that the authors’ experience through this iterative process will fill the gap in the literature by setting an example of an application of the ‘universal precautions’ approach to chronic pain management. OBJECTIVES: To assess the feasibility and utility of the addition of a new risk assessment process and to provide a snapshot of the risk of problematic use of medications in new patients presenting to a tertiary ambulatory clinic treating CNCP. METHODS: Charts for the first three months following the institution of an intake assessment for risk of problematic medication use were reviewed. Health care providers at the Wasser Pain Management Centre (Toronto, Ontario) were interviewed to discuss the preliminary findings and provide feedback about barriers to completing the intake assessments, as well as to identify the items that were clinically relevant and useful to their practice. RESULTS: Data were analyzed and examined for completeness. While some measures were considered to be particularly helpful, other items were regarded as repetitive, problematic or time consuming. Feedback was then incorporated into revisions of the risk assessment tool. DISCUSSION: Overall, it is feasible and useful to assess risk for problematic use of medications in new patients presenting to CNCP clinics. CONCLUSION: To facilitate the practice of assessment, the risk assessment tool at intake must be concise, clinically relevant and feasible given practitioner time constraints. PMID:22891193

Refining prognosis in lung cancer: A report on the quality and relevance of clinical prognostic tools

PubMed Central

Mahar, Alyson L.; Compton, Carolyn; McShane, Lisa M.; Halabi, Susan; Asamura, Hisao; Rami-Porta, Ramon; Groome, Patti A.

2015-01-01

Introduction Accurate, individualized prognostication for lung cancer patients requires the integration of standard patient and pathologic factors, biologic, genetic, and other molecular characteristics of the tumor. Clinical prognostic tools aim to aggregate information on an individual patient to predict disease outcomes such as overall survival, but little is known about their clinical utility and accuracy in lung cancer. Methods A systematic search of the scientific literature for clinical prognostic tools in lung cancer published Jan 1, 1996-Jan 27, 2015 was performed. In addition, web-based resources were searched. A priori criteria determined by the Molecular Modellers Working Group of the American Joint Committee on Cancer were used to investigate the quality and usefulness of tools. Criteria included clinical presentation, model development approaches, validation strategies, and performance metrics. Results Thirty-two prognostic tools were identified. Patients with metastases were the most frequently considered population in non-small cell lung cancer. All tools for small cell lung cancer covered that entire patient population. Included prognostic factors varied considerably across tools. Internal validity was not formally evaluated for most tools and only eleven were evaluated for external validity. Two key considerations were highlighted for tool development: identification of an explicit purpose related to a relevant clinical population and clear decision-points, and prioritized inclusion of established prognostic factors over emerging factors. Conclusions Prognostic tools will contribute more meaningfully to the practice of personalized medicine if better study design and analysis approaches are used in their development and validation. PMID:26313682

Identifying a clinical signature of suicidality among patients with mood disorders: a pilot study using a machine learning approach

PubMed Central

Passos, Ives Cavalcante; Mwangi, Benson; Cao, Bo; Hamilton, Jane E; Wu, Mon-Ju; Zhang, Xiang Yang; Zunta-Soares, Giovana B.; Quevedo, Joao; Kauer-Sant'Anna, Marcia; Kapczinski, Flávio; Soares, Jair C.

2016-01-01

Objective A growing body of evidence has put forward clinical risk factors associated with patients with mood disorders that attempt suicide. However, what is not known is how to integrate clinical variables into a clinically useful tool in order to estimate the probability of an individual patient attempting suicide. Method A total of 144 patients with mood disorders were included. Clinical variables associated with suicide attempts among patients with mood disorders and demographic variables were used to ‘train’ a machine learning algorithm. The resulting algorithm was utilized in identifying novel or ‘unseen’ individual subjects as either suicide attempters or non-attempters. Three machine learning algorithms were implemented and evaluated. Results All algorithms distinguished individual suicide attempters from non-attempters with prediction accuracy ranging between 65%-72% (p<0.05). In particular, the relevance vector machine (RVM) algorithm correctly predicted 103 out of 144 subjects translating into 72% accuracy (72.1% sensitivity and 71.3% specificity) and an area under the curve of 0.77 (p<0.0001). The most relevant predictor variables in distinguishing attempters from non-attempters included previous hospitalizations for depression, a history of psychosis, cocaine dependence and post-traumatic stress disorder (PTSD) comorbidity. Conclusion Risk for suicide attempt among patients with mood disorders can be estimated at an individual subject level by incorporating both demographic and clinical variables. Future studies should examine the performance of this model in other populations and its subsequent utility in facilitating selection of interventions to prevent suicide. PMID:26773901

Folded concave penalized learning in identifying multimodal MRI marker for Parkinson’s disease

PubMed Central

Liu, Hongcheng; Du, Guangwei; Zhang, Lijun; Lewis, Mechelle M.; Wang, Xue; Yao, Tao; Li, Runze; Huang, Xuemei

2016-01-01

Background Brain MRI holds promise to gauge different aspects of Parkinson’s disease (PD)-related pathological changes. Its analysis, however, is hindered by the high-dimensional nature of the data. New method This study introduces folded concave penalized (FCP) sparse logistic regression to identify biomarkers for PD from a large number of potential factors. The proposed statistical procedures target the challenges of high-dimensionality with limited data samples acquired. The maximization problem associated with the sparse logistic regression model is solved by local linear approximation. The proposed procedures then are applied to the empirical analysis of multimodal MRI data. Results From 45 features, the proposed approach identified 15 MRI markers and the UPSIT, which are known to be clinically relevant to PD. By combining the MRI and clinical markers, we can enhance substantially the specificity and sensitivity of the model, as indicated by the ROC curves. Comparison to existing methods We compare the folded concave penalized learning scheme with both the Lasso penalized scheme and the principle component analysis-based feature selection (PCA) in the Parkinson’s biomarker identification problem that takes into account both the clinical features and MRI markers. The folded concave penalty method demonstrates a substantially better clinical potential than both the Lasso and PCA in terms of specificity and sensitivity. Conclusions For the first time, we applied the FCP learning method to MRI biomarker discovery in PD. The proposed approach successfully identified MRI markers that are clinically relevant. Combining these biomarkers with clinical features can substantially enhance performance. PMID:27102045

When Educational Material Is Delivered: A Mixed Methods Content Validation Study of the Information Assessment Method

PubMed Central

2017-01-01

Background The Information Assessment Method (IAM) allows clinicians to report the cognitive impact, clinical relevance, intention to use, and expected patient health benefits associated with clinical information received by email. More than 15,000 Canadian physicians and pharmacists use the IAM in continuing education programs. In addition, information providers can use IAM ratings and feedback comments from clinicians to improve their products. Objective Our general objective was to validate the IAM questionnaire for the delivery of educational material (ecological and logical content validity). Our specific objectives were to measure the relevance and evaluate the representativeness of IAM items for assessing information received by email. Methods A 3-part mixed methods study was conducted (convergent design). In part 1 (quantitative longitudinal study), the relevance of IAM items was measured. Participants were 5596 physician members of the Canadian Medical Association who used the IAM. A total of 234,196 ratings were collected in 2012. The relevance of IAM items with respect to their main construct was calculated using descriptive statistics (relevance ratio R). In part 2 (qualitative descriptive study), the representativeness of IAM items was evaluated. A total of 15 family physicians completed semistructured face-to-face interviews. For each construct, we evaluated the representativeness of IAM items using a deductive-inductive thematic qualitative data analysis. In part 3 (mixing quantitative and qualitative parts), results from quantitative and qualitative analyses were reviewed, juxtaposed in a table, discussed with experts, and integrated. Thus, our final results are derived from the views of users (ecological content validation) and experts (logical content validation). Results Of the 23 IAM items, 21 were validated for content, while 2 were removed. In part 1 (quantitative results), 21 items were deemed relevant, while 2 items were deemed not relevant (R=4.86% [N=234,196] and R=3.04% [n=45,394], respectively). In part 2 (qualitative results), 22 items were deemed representative, while 1 item was not representative. In part 3 (mixing quantitative and qualitative results), the content validity of 21 items was confirmed, and the 2 nonrelevant items were excluded. A fully validated version was generated (IAM-v2014). Conclusions This study produced a content validated IAM questionnaire that is used by clinicians and information providers to assess the clinical information delivered in continuing education programs. PMID:28292738

Live Attenuated Influenza Virus Increases Pneumococcal Translocation and Persistence Within the Middle Ear

PubMed Central

Mina, Michael J.; Klugman, Keith P.; Rosch, Jason W.; McCullers, Jonathan A.

2015-01-01

Background. Infection with influenza A virus (IAV) increases susceptibility to respiratory bacterial infections, resulting in increased bacterial carriage and complications such acute otitis media, pneumonia, bacteremia, and meningitis. Recently, vaccination with live attenuated influenza virus (LAIV) was reported to enhance subclinical bacterial colonization within the nasopharynx, similar to IAV. Although LAIV does not predispose to bacterial pneumonia, whether it may alter bacterial transmigration toward the middle ear, where it could have clinically relevant implications, has not been investigated. Methods. BALB/c mice received LAIV or phosphate-buffered saline 1 or 7 days before or during pneumococcal colonization with either of 2 clinical isolates, 19F or 7F. Middle ear bacterial titers were monitored daily via in vivo imaging. Results. LAIV increased bacterial transmigration to and persistence within the middle ear. When colonization followed LAIV inoculation, a minimum LAIV incubation period of 4 days was required before bacterial transmigration commenced. Conclusions. While LAIV vaccination is safe and effective at reducing IAV and coinfection with influenza virus and bacteria, LAIV may increase bacterial transmigration to the middle ear and could thus increase the risk of clinically relevant acute otitis media. These data warrant further investigations into interactions between live attenuated viruses and naturally colonizing bacterial pathogens. PMID:25505300

Plasma-Lyte 148: A clinical review

PubMed Central

Weinberg, Laurence; Collins, Neil; Van Mourik, Kiara; Tan, Chong; Bellomo, Rinaldo

2016-01-01

AIM To outline the physiochemical properties and specific clinical uses of Plasma-Lyte 148 as choice of solution for fluid intervention in critical illness, surgery and perioperative medicine. METHODS We performed an electronic literature search from Medline and PubMed (via Ovid), anesthesia and pharmacology textbooks, and online sources including studies that compared Plasma-Lyte 148 to other crystalloid solutions. The following keywords were used: “surgery”, “anaesthesia”, “anesthesia”, “anesthesiology”, “anaesthesiology”, “fluids”, “fluid therapy”, “crystalloid”, “saline”, “plasma-Lyte”, “plasmalyte”, “hartmann’s”, “ringers” “acetate”, “gluconate”, “malate”, “lactate”. All relevant articles were accessed in full. We summarized the data and reported the data in tables and text. RESULTS We retrieved 104 articles relevant to the choice of Plasma-Lyte 148 for fluid intervention in critical illness, surgery and perioperative medicine. We analyzed the data and reported the results in tables and text. CONCLUSION Plasma-Lyte 148 is an isotonic, buffered intravenous crystalloid solution with a physiochemical composition that closely reflects human plasma. Emerging data supports the use of buffered crystalloid solutions in preference to saline in improving physicochemical outcomes. Further large randomized controlled trials assessing the comparative effectiveness of Plasma-Lyte 148 and other crystalloid solutions in measuring clinically important outcomes such as morbidity and mortality are needed. PMID:27896148

Use and perceptions of information among family physicians: sources considered accessible, relevant, and reliable

PubMed Central

Kosteniuk, Julie G.; Morgan, Debra G.; D'Arcy, Carl K.

2013-01-01

Objectives: The research determined (1) the information sources that family physicians (FPs) most commonly use to update their general medical knowledge and to make specific clinical decisions, and (2) the information sources FPs found to be most physically accessible, intellectually accessible (easy to understand), reliable (trustworthy), and relevant to their needs. Methods: A cross-sectional postal survey of 792 FPs and locum tenens, in full-time or part-time medical practice, currently practicing or on leave of absence in the Canadian province of Saskatchewan was conducted during the period of January to April 2008. Results: Of 666 eligible physicians, 331 completed and returned surveys, resulting in a response rate of 49.7% (331/666). Medical textbooks and colleagues in the main patient care setting were the top 2 sources for the purpose of making specific clinical decisions. Medical textbooks were most frequently considered by FPs to be reliable (trustworthy), and colleagues in the main patient care setting were most physically accessible (easy to access). Conclusions: When making specific clinical decisions, FPs were most likely to use information from sources that they considered to be reliable and generally physically accessible, suggesting that FPs can best be supported by facilitating easy and convenient access to high-quality information. PMID:23405045

Multimodal interventions including nutrition in the prevention and management of disease-related malnutrition in adults: a systematic review of randomised control trials.

PubMed

Thorne, Frances; Baldwin, Christine

2014-06-01

There has been a move to improve nutritional status in malnourished patients through the use of multimodal interventions (MI). There are currently no systematic reviews that have examined their effectiveness. This analysis aimed to examine the effects on nutritional, clinical, functional and patient-centred outcomes. A systematic review and meta-analysis using Cochrane methodology. 15 studies were included in the analysis, 13 comparing MI with usual care and 2 comparing MI with a nutrition intervention alone. Quality of studies varied and studies reported few relevant outcomes. Only 3 outcomes were compatible with meta-analysis; weight, mortality and length of stay (LOS). No statistically significant differences between groups were found. Narrative review was inconclusive. There was no evidence of benefit in the intervention groups in relation to body composition, functional status or quality of life (QoL). Intervention groups appeared to show a trend towards increased energy and protein intake however data was provided by only 2 studies (301 participants). No conclusive evidence of benefit for MI on any of the reviewed outcomes was found. Well designed, high quality trials addressing the impact of MI on relevant nutritional, functional and clinical outcomes are required. Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Scientific Skills as Core Competences in Medical Education: What do medical students think?

NASA Astrophysics Data System (ADS)

Ribeiro, Laura; Severo, Milton; Pereira, Margarida; Amélia Ferreira, Maria

2015-08-01

Background: Scientific excellence is one of the most fundamental underpinnings of medical education and its relevance is unquestionable. To be involved in research activities enhances students' critical thinking and problem-solving capacities, which are mandatory competences for new achievements in patient care and consequently to the improvement of clinical practice. Purposes: This work aimed to study the relevance given by Portuguese medical students to a core of scientific skills, and their judgment about their own ability to execute those skills. Methods: A cross-sectional study was conducted on students attending the first, fourth and sixth years of medical course in the same period. An assessment istrument, exploring the importance given by Portuguese medical students to scientific skills in high school, to clinical practice and to their own ability to execute them, was designed, adapted and applied specifically to this study. Results: Students' perceptions were associated with gender, academic year, previous participation in research activities, positive and negative attitudes toward science, research integration into the curriculum and motivation to undertake research. The viewpoint of medical students about the relevance of scientific skills overall, and the ability to execute them, was independently associated with motivation to be enrolled in research. Conclusions: These findings have meaningful implications in medical education regarding the inclusion of a structural research program in the medical curriculum. Students should be aware that clinical practice would greatly benefit from the enrollment in research activities. By developing a solid scientific literacy future physicians will be able to apply new knowledge in patient care.

SU-E-I-65: The Joint Commission's Requirements for Annual Diagnostic Physics Testing of Nuclear Medicine Equipment, and a Clinically Relevant Methodology for Testing Low-Contrast Resolution

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

West, W. Geoffrey; Gray, David Clinton

Purpose: To introduce the Joint Commission's requirements for annual diagnostic physics testing of all nuclear medicine equipment, effective 7/1/2014, and to highlight an acceptable methodology for testing lowcontrast resolution of the nuclear medicine imaging system. Methods: The Joint Commission's required diagnostic physics evaluations are to be conducted for all of the image types produced clinically by each scanner. Other accrediting bodies, such as the ACR and the IAC, have similar imaging metrics, but do not emphasize testing low-contrast resolution as it relates clinically. The proposed method for testing low contrast resolution introduces quantitative metrics that are clinically relevant. The acquisitionmore » protocol and calculation of contrast levels will utilize a modified version of the protocol defined in AAPM Report #52. Results: Using the Rose criterion for lesion detection with a SNRpixel = 4.335 and a CNRlesion = 4, the minimum contrast levels for 25.4 mm and 31.8 mm cold spheres were calculated to be 0.317 and 0.283, respectively. These contrast levels are the minimum threshold that must be attained to guard against false positive lesion detection. Conclusion: Low contrast resolution, or detectability, can be properly tested in a manner that is clinically relevant by measuring the contrast level of cold spheres within a Jaszczak phantom using pixel values within ROI's placed in the background and cold sphere regions. The measured contrast levels are then compared to a minimum threshold calculated using the Rose criterion and a CNRlesion = 4. The measured contrast levels must either meet or exceed this minimum threshold to prove acceptable lesion detectability. This research and development activity was performed by the authors while employed at West Physics Consulting, LLC. It is presented with the consent of West Physics, which has authorized the dissemination of the information and/or techniques described in the work.« less

[Moderate hypoglycemia in the preterm infant: is it relevant?].

PubMed

Wayenberg, J-L; Pardou, A

2008-02-01

Glucose monitoring and management of hypoglycaemia in preterm infants remain controversial. However, recent animal studies have shown that hypoglycaemia is associated to increased generation of reactive oxygen and nitrogen species, to inhibition of cellular maturation and to apoptosis in brain. Despite potential consequences of hypoglycaemia on brain development in preterm infants, only few studies are available on this topic. Available clinical studies on neurological development of hypoglycaemic preterm infants are not conclusive but suggest detrimental effect of repeated mild hypoglycaemia on brain development. Both experimental and clinical arguments are sufficient to mind to this problem with great awareness. Therefore, routine repeated measurements of blood glucose concentration are necessary and active intervention is proposed if glucose plasma level decreases below 2.5 mmol/l.

Opisthorchiasis and viral hepatitis b: clinical cases.

PubMed

Kotelevska, Tetiana M; Pryimenko, Nataliia O; Dubynska, Galyna M; Iziumska, Olena M; Bodnar, Vadym A

2018-01-01

Introduction: Among the cases of biohelminthosis, which are registered in Ukraine, opisthorchiasis is the most common and constitutes the second largest centre in Europe. Due to the growth of migration processes and global tourism, opisthorchiasis is becoming increasingly relevant for the countries of the European Union and the United States. Under modern conditions, the clinical course of many infectious and parasitic diseases has changed. The aim: The present paper discusses and analyzes the cases of opisthorchiasis and hepatitis B virus which are challenging in terms of diagnostics and choice of treatment tactics. Conclusion: The course of acute infections, the formation of results and the effectiveness of treatment are influenced by a number of factors, among which mixed infections are of particular interest.

Therapeutic Applications of Classic Hallucinogens.

PubMed

Bogenschutz, Michael P; Ross, Stephen

2018-01-01

This chapter reviews what is known about the therapeutic uses of the serotonergic or classic hallucinogens, i.e., psychoactive drugs such as LSD and psilocybin that exert their effects primarily through agonist activity at serotonin 2A (5HT2A) receptors. Following a review of the history of human use and scientific study of these drugs, the data from clinical research are summarized, including extensive work on the use of classic hallucinogens in the treatment of alcoholism and other addictions, studies of the use of LSD and psilocybin to relieve distress concerning death, particularly in patients with advanced or terminal cancer, and more limited data concerning the use of classic hallucinogens to treat mood and anxiety disorders. A survey of possible mechanisms of clinically relevant effects is provided. The well-established safety of classic hallucinogens is reviewed. To provide a clinical perspective, case summaries are provided of two individuals who received treatment in recent controlled trials of psilocybin: one being treated for alcoholism, the other suffering from anxiety and depression related to fear of death due to a cancer diagnosis. Although promising early phase research conducted from the 1950s through the early 1970s was discontinued before firm conclusions could be reached concerning the efficacy of any of the classic hallucinogens for any clinical condition, the research that was conducted in that era strongly suggests that classic hallucinogens have clinically relevant effects, particularly in the case of LSD treatment of alcoholism. In the past decade, clinical trials have resumed investigating the effects of classic hallucinogens in the treatment of existential distress in the face of cancer, and in the treatment of addictions including alcoholism and nicotine addiction. The studies that have been completed to date are not sufficient to establish efficacy, but the outcomes have been very encouraging, and larger trials, up to and including phase 3, are now underway or being planned. Although research has elucidated many of the acute neurobiological and psychological effects of classic hallucinogens on humans, animals, and in vitro systems, the mechanisms of clinically relevant persisting effects remain poorly understood.

Sexual intercourse for cervical ripening and induction of labour.

PubMed

Kavanagh, J; Kelly, A J; Thomas, J

2001-01-01

The role of prostaglandins for cervical ripening and induction of labour has been examined extensively. Human semen is the biological source that is presumed to contain the highest prostaglandin concentration. The role of sexual intercourse in the initiation of labour is uncertain. The action of sexual intercourse in stimulating labour is unclear, it may in part be due to the physical stimulation of the lower uterine segment, or endogenous release of oxytocin as a result of orgasm or from the direct action of prostaglandins in semen. Furthermore nipple stimulation may be part of the process of initiation. This is one of a series of reviews of methods of cervical ripening and labour induction using standardised methodology. To determine the effects of sexual intercourse for third trimester cervical ripening or induction of labour in comparison with other methods of induction. The Cochrane Pregnancy and Childbirth Group trials register, the Cochrane Controlled Trials Register and bibliographies of relevant papers. Last searched: November 2000. (1) clinical trials comparing sexual intercourse for third trimester cervical ripening or labour induction with placebo/no treatment or other methods listed above it on a predefined list of labour induction methods; (2) random allocation to the treatment or control group; (3) adequate allocation concealment; (4) violations of allocated management not sufficient to materially affect conclusions; (5) clinically meaningful outcome measures reported; (6) data available for analysis according to the random allocation; (7) missing data insufficient to materially affect the conclusion. A strategy has been developed to deal with the large volume and complexity of trial data relating to labour induction. This involves a two-stage method of data extraction. There was one included study of 28 women which reported very limited data, from which no meaningful conclusions can be drawn. The role of sexual intercourse as a method of induction of labour is uncertain. Any future trials investigating sexual intercourse as a method of induction need to be of sufficient power to detect clinically relevant differences in standard outcomes. However, it may prove difficult to standardise sexual intercourse as an intervention to allow meaningful comparisons with other methods of induction of labour.

Comparison of the cytotoxicity of clinically relevant cobalt-chromium and alumina ceramic wear particles in vitro.

PubMed

Germain, M A; Hatton, A; Williams, S; Matthews, J B; Stone, M H; Fisher, J; Ingham, E

2003-02-01

Concern over polyethylene wear particle induced aseptic loosening of metal-on-polyethylene hip prostheses has led to renewed interest in alternative materials such as metal-on-metal and alumina ceramic-on-alumina ceramic for total hip replacement. This study compared the effects of clinically relevant cobalt-chromium and alumina ceramic wear particles on the viability of U937 histiocytes and L929 fibroblasts in vitro. Clinically relevant cobalt-chromium wear particles were generated using a flat pin-on-plate tribometer. The mean size of the clinically relevant metal particles was 29.5+/-6.3 nm (range 5-200 nm). Clinically relevant alumina ceramic particles were generated in the Leeds MkII anatomical hip simulator from a Mittelmieier prosthesis using micro-separation motion. This produced particles with a bimodal size distribution. The majority (98%) of the clinically relevant alumina ceramic wear debris was 5-20 nm in size. The cytotoxicity of the clinically relevant wear particles was compared to commercially available cobalt-chromium (9.87 microm+/-5.67) and alumina ceramic (0.503+/-0.19 microm) particles. The effects of the particles on the cells over a 5 day period at different particle volume (microm(3)) to cell number ratios were tested and viability determined using ATP-Lite(TM). Clinically relevant cobalt-chromium particles 50 and 5 microm(3) per cell reduced the viability of U937 cells by 97% and 42% and reduced the viability of L929 cells by 95% and 73%, respectively. At 50 microm(3) per cell, the clinically relevant ceramic particles reduced U937 cell viability by 18%. None of the other concentrations of the clinically relevant particles were toxic. The commercial cobalt-chromium and alumina particles did not affect the viability of either the U937 histiocytes or the L929 fibroblasts.Thus at equivalent particle volumes the clinically relevant cobalt-chromium particles were more toxic then the alumina ceramic particles. This study has emphasised the fact that the nature, size and volume of particles are important in assessing biological effects of wear debris on cells in vitro.

Impact of Glucose Measurement Processing Delays on Clinical Accuracy and Relevance

PubMed Central

Jangam, Sujit R.; Hayter, Gary; Dunn, Timothy C.

2013-01-01

Background In a hospital setting, glucose is often measured from venous blood in the clinical laboratory. However, laboratory glucose measurements are typically not available in real time. In practice, turn-around times for laboratory measurements can be minutes to hours. This analysis assesses the impact of turn-around time on the effective clinical accuracy of laboratory measurements. Methods Data obtained from an earlier study with 58 subjects with type 1 diabetes mellitus (T1DM) were used for this analysis. In the study, glucose measurements using a YSI glucose analyzer were obtained from venous blood samples every 15 min while the subjects were at the health care facility. To simulate delayed laboratory results, each YSI glucose value from a subject was paired with one from a later time point (from the same subject) separated by 15, 30, 45, and 60 min. To assess the clinical accuracy of a delayed YSI result relative to a real-time result, the percentage of YSI pairs that meet the International Organization for Standardization (ISO) 15197:2003(E) standard for glucose measurement accuracy (±15 mg/dl for blood glucose < 75 mg/dl, ±20% for blood glucose ≥ 75 mg/dl) was calculated. Results It was observed that delays of 15 min or more reduce clinical accuracy below the ISO 15197:2003(E) recommendation of 95%. The accuracy was less than 65% for delays of 60 min. Conclusion This analysis suggests that processing delays in glucose measurements reduce the clinical relevance of results in patients with T1DM and may similarly degrade the clinical value of measurements in other patient populations. PMID:23759399

Exome Sequencing in the Clinical Diagnosis of Sporadic or Familial Cerebellar Ataxia

PubMed Central

Fogel, Brent L.; Lee, Hane; Deignan, Joshua L.; Strom, Samuel P.; Kantarci, Sibel; Wang, Xizhe; Quintero-Rivera, Fabiola; Vilain, Eric; Grody, Wayne W.; Perlman, Susan; Geschwind, Daniel H.; Nelson, Stanley F.

2015-01-01

IMPORTANCE Cerebellar ataxias are a diverse collection of neurologic disorders with causes ranging from common acquired etiologies to rare genetic conditions. Numerous genetic disorders have been associated with chronic progressive ataxia and this consequently presents a diagnostic challenge for the clinician regarding how to approach and prioritize genetic testing in patients with such clinically heterogeneous phenotypes. Additionally, while the value of genetic testing in early-onset and/or familial cases seems clear, many patients with ataxia present sporadically with adult onset of symptoms and the contribution of genetic variation to the phenotype of these patients has not yet been established. OBJECTIVE To investigate the contribution of genetic disease in a population of patients with predominantly adult- and sporadic-onset cerebellar ataxia. DESIGN, SETTING, AND PARTICIPANTS We examined a consecutive series of 76 patients presenting to a tertiary referral center for evaluation of chronic progressive cerebellar ataxia. MAIN OUTCOMES AND MEASURES Next-generation exome sequencing coupled with comprehensive bioinformatic analysis, phenotypic analysis, and clinical correlation. RESULTS We identified clinically relevant genetic information in more than 60% of patients studied (n = 46), including diagnostic pathogenic gene variants in 21% (n = 16), a notable yield given the diverse genetics and clinical heterogeneity of the cerebellar ataxias. CONCLUSIONS AND RELEVANCE This study demonstrated that clinical exome sequencing in patients with adult-onset and sporadic presentations of ataxia is a high-yield test, providing a definitive diagnosis in more than one-fifth of patients and suggesting a potential diagnosis in more than one-third to guide additional phenotyping and diagnostic evaluation. Therefore, clinical exome sequencing is an appropriate consideration in the routine genetic evaluation of all patients presenting with chronic progressive cerebellar ataxia. PMID:25133958

Modelling Conditions and Health Care Processes in Electronic Health Records: An Application to Severe Mental Illness with the Clinical Practice Research Datalink

PubMed Central

Olier, Ivan; Springate, David A.; Ashcroft, Darren M.; Doran, Tim; Reeves, David; Planner, Claire; Reilly, Siobhan; Kontopantelis, Evangelos

2016-01-01

Background The use of Electronic Health Records databases for medical research has become mainstream. In the UK, increasing use of Primary Care Databases is largely driven by almost complete computerisation and uniform standards within the National Health Service. Electronic Health Records research often begins with the development of a list of clinical codes with which to identify cases with a specific condition. We present a methodology and accompanying Stata and R commands (pcdsearch/Rpcdsearch) to help researchers in this task. We present severe mental illness as an example. Methods We used the Clinical Practice Research Datalink, a UK Primary Care Database in which clinical information is largely organised using Read codes, a hierarchical clinical coding system. Pcdsearch is used to identify potentially relevant clinical codes and/or product codes from word-stubs and code-stubs suggested by clinicians. The returned code-lists are reviewed and codes relevant to the condition of interest are selected. The final code-list is then used to identify patients. Results We identified 270 Read codes linked to SMI and used them to identify cases in the database. We observed that our approach identified cases that would have been missed with a simpler approach using SMI registers defined within the UK Quality and Outcomes Framework. Conclusion We described a framework for researchers of Electronic Health Records databases, for identifying patients with a particular condition or matching certain clinical criteria. The method is invariant to coding system or database and can be used with SNOMED CT, ICD or other medical classification code-lists. PMID:26918439

Understanding the Research–Policy Divide for Oral Health Inequality

PubMed Central

Bell, Erica; Crocombe, Leonard; Campbell, Steven; Goldberg, Lynette R.; Seidel, Bastian M.

2014-01-01

Background: No studies exist of the congruence of research in oral health to policy. This study aimed to examine the broad congruence of oral health research to policy, and implications for developing oral health research that is more policy relevant, particularly for the wider challenge of addressing unequal oral health outcomes, rather than specific policy translation issues. Methods: Bayesian-based software was used in a multi-layered method to compare the conceptual content of 127,193 oral health research abstracts published between 2000–2012 with eight current oral health policy documents from Organisation for Economic Co-operation and Development countries. Findings: Fifty-five concepts defined the research abstracts, of which only eight were policy-relevant, and six of which were minor research concepts. Conclusions The degree of disconnection between clinical concepts and healthcare system and workforce development concepts was striking. This study shows that, far from being “lost in translation,” oral health research and policy are so different as to raise doubts about the extent to which research is policy-relevant and policy is research-based. The notion of policy relevance encompasses the lack of willingness of policy makers to embrace research, and the need for researchers to develop research that is, and is seen to be, policy-relevant. PMID:25617516

Bicarbonate in diabetic ketoacidosis - a systematic review

PubMed Central

2011-01-01

Objective This study was designed to examine the efficacy and risk of bicarbonate administration in the emergent treatment of severe acidemia in diabetic ketoacidosis (DKA). Methods PUBMED database was used to identify potentially relevant articles in the pediatric and adult DKA populations. DKA intervention studies on bicarbonate administration versus no bicarbonate in the emergent therapy, acid-base studies, studies on risk association with cerebral edema, and related case reports, were selected for review. Two reviewers independently conducted data extraction and assessed the citation relevance for inclusion. Results From 508 potentially relevant articles, 44 were included in the systematic review, including three adult randomized controlled trials (RCT) on bicarbonate administration versus no bicarbonate in DKA. We observed a marked heterogeneity in pH threshold, concentration, amount, and timing for bicarbonate administration in various studies. Two RCTs demonstrated transient improvement in metabolic acidosis with bicarbonate treatment within the initial 2 hours. There was no evidence of improved glycemic control or clinical efficacy. There was retrospective evidence of increased risk for cerebral edema and prolonged hospitalization in children who received bicarbonate, and weak evidence of transient paradoxical worsening of ketosis, and increased need for potassium supplementation. No studies involved patients with an initial pH < 6.85. Conclusions The evidence to date does not justify the administration of bicarbonate for the emergent treatment of DKA, especially in the pediatric population, in view of possible clinical harm and lack of sustained benefits. PMID:21906367

Clinical relevance of cytogenetics to pediatric practice. Postnatal findings of Patau syndrome – Review of 5 cases

PubMed Central

PLAIASU, Vasilica; OCHIANA, Diana; MOTEI, Gabriela; ANCA, Ioana; GEORGESCU, Adrian

2010-01-01

ABSTRACT Introduction: Patau syndrome (trisomy 13) is one of the most common chromosomal anomalies clinically characterized by the presence of numerous malformations with a limited survival rate for most cases. Babies are usually identified at birth and the diagnosis is confirmed with genetic testing. Materials and methods: In this review we outline the clinical and cytogenetic aspects of trisomy 13 and associated phenotypes for 5 cases analyzed in the last 3 years, referred to our Clinical Genetics Department. For each child cytogenetic analysis was performed to determine the genetic variant; also, the patients were investigated for other associated malformations (cardiac, cerebral, renal, ocular anomalies). Discussion: All 5 cases presented multiple malformations, including some but not all signs of the classical clinical triad suggestive of Patau syndrome. The cytogenetic investigation confirmed for each case the suspected diagnosis and also indicated the specific genetic variant, this being a valuable information for the genetic counselling of the families. Conclusion: The application of genetic analysis can increase diagnosis and prognosis accuracy and have an impact on clinical management. PMID:21977150

Utility of registries for post-marketing evaluation of medicines. A survey of Swedish health care quality registries from a regulatory perspective

PubMed Central

Feltelius, Nils; Gedeborg, Rolf; Holm, Lennart; Zethelius, Björn

2017-01-01

Aim The aim of this study was to describe content and procedures in some selected Swedish health care quality registries (QRs) of relevance to regulatory decision-making. Methods A workshop was organized with participation of seven Swedish QRs which subsequently answered a questionnaire regarding registry content on drug treatments and outcomes. Patient populations, coverage, data handling and quality control, as well as legal and ethical aspects are presented. Scientific publications from the QRs are used as a complementary measure of quality and scientific relevance. Results The registries under study collect clinical data of high relevance to regulatory and health technology agencies. Five out of seven registries provide information on the drug of interest. When applying external quality criteria, we found a high degree of fulfillment, although information on medication was not sufficient to answer all questions of regulatory interest. A notable strength is the option for linkage to the Prescribed Drug Registry and to information on education and socioeconomic status. Data on drugs used during hospitalization were also collected to some extent. Outcome measures collected resemble those used in relevant clinical trials. All registries collected patient-reported outcome measures. The number of publications from the registries was substantial, with studies of appropriate design, including randomized registry trials. Conclusions Quality registries may provide a valuable source of post-marketing data on drug effectiveness, safety, and cost-effectiveness. Closer collaboration between registries and regulators to improve quality and usefulness of registry data could benefit both regulatory utility and value for health care providers. PMID:28276780

Immunological network signatures of cancer progression and survival

PubMed Central

2011-01-01

Background The immune contribution to cancer progression is complex and difficult to characterize. For example in tumors, immune gene expression is detected from the combination of normal, tumor and immune cells in the tumor microenvironment. Profiling the immune component of tumors may facilitate the characterization of the poorly understood roles immunity plays in cancer progression. However, the current approaches to analyze the immune component of a tumor rely on incomplete identification of immune factors. Methods To facilitate a more comprehensive approach, we created a ranked immunological relevance score for all human genes, developed using a novel strategy that combines text mining and information theory. We used this score to assign an immunological grade to gene expression profiles, and thereby quantify the immunological component of tumors. This immunological relevance score was benchmarked against existing manually curated immune resources as well as high-throughput studies. To further characterize immunological relevance for genes, the relevance score was charted against both the human interactome and cancer information, forming an expanded interactome landscape of tumor immunity. We applied this approach to expression profiles in melanomas, thus identifying and grading their immunological components, followed by identification of their associated protein interactions. Results The power of this strategy was demonstrated by the observation of early activation of the adaptive immune response and the diversity of the immune component during melanoma progression. Furthermore, the genome-wide immunological relevance score classified melanoma patient groups, whose immunological grade correlated with clinical features, such as immune phenotypes and survival. Conclusions The assignment of a ranked immunological relevance score to all human genes extends the content of existing immune gene resources and enriches our understanding of immune involvement in complex biological networks. The application of this approach to tumor immunity represents an automated systems strategy that quantifies the immunological component in complex disease. In so doing, it stratifies patients according to their immune profiles, which may lead to effective computational prognostic and clinical guides. PMID:21453479

Diagnostic Yield of Recommendations for Chest CT Examination Prompted by Outpatient Chest Radiographic Findings

PubMed Central

Harvey, H. Benjamin; Gilman, Matthew D.; Wu, Carol C.; Cushing, Matthew S.; Halpern, Elkan F.; Zhao, Jing; Pandharipande, Pari V.; Shepard, Jo-Anne O.

2015-01-01

Purpose To evaluate the diagnostic yield of recommended chest computed tomography (CT) prompted by abnormalities detected on outpatient chest radiographic images. Materials and Methods This HIPAA-compliant study had institutional review board approval; informed consent was waived. Reports of all outpatient chest radiographic examinations performed at a large academic center during 2008 (n = 29 138) were queried to identify studies that included a recommendation for a chest CT imaging. The radiology information system was queried for these patients to determine if a chest CT examination was obtained within 1 year of the index radiographic examination that contained the recommendation. For chest CT examinations obtained within 1 year of the index chest radiographic examination and that met inclusion criteria, chest CT images were reviewed to determine if there was an abnormality that corresponded to the chest radiographic finding that prompted the recommendation. All corresponding abnormalities were categorized as clinically relevant or not clinically relevant, based on whether further work-up or treatment was warranted. Groups were compared by using t test and Fisher exact test with a Bonferroni correction applied for multiple comparisons. Results There were 4.5% (1316 of 29138 [95% confidence interval {CI}: 4.3%, 4.8%]) of outpatient chest radiographic examinations that contained a recommendation for chest CT examination, and increasing patient age (P < .001) and positive smoking history (P = .001) were associated with increased likelihood of a recommendation for chest CT examination. Of patients within this subset who met inclusion criteria, 65.4% (691 of 1057 [95% CI: 62.4%, 68.2%) underwent a chest CT examination within the year after the index chest radiographic examination. Clinically relevant corresponding abnormalities were present on chest CT images in 41.4% (286 of 691 [95% CI: 37.7%, 45.2%]) of cases, nonclinically relevant corresponding abnormalities in 20.6% (142 of 691 [95% CI: 17.6%, 23.8%]) of cases, and no corresponding abnormalities in 38.1% (263 of 691 [95% CI: 34.4%, 41.8%]) of cases. Newly diagnosed, biopsy-proven malignancies were detected in 8.1% (56 of 691 [95% CI: 6.2%, 10.4%]) of cases. Conclusion A radiologist recommendation for chest CT to evaluate an abnormal finding on an outpatient chest radiographic examination has a high yield of clinically relevant findings. © RSNA, 2014 PMID:25531242

Clinical features of olfactory disorders in patients seeking medical consultation

PubMed Central

Chen, Guowei; Wei, Yongxiang; Miao, Xutao; Li, Kunyan; Ren, Yuanyuan; Liu, Jia

2013-01-01

Background Olfactory disorders are common complaints in ENT clinics. We investigated causes and relevant features of olfactory disorders and the need for gustatory testing in patients with olfactory dysfunction. Material/Methods A total of 140 patients seeking medical consultations were enrolled. All patients were asked about their olfactory disorders in a structured interview of medical history and underwent thorough otolaryngologic examinations and imaging of the head. Results Causes of olfactory disorders were classified as: upper respiratory tract infection (URTI), sinonasal diseases (NSD), head trauma, idiopathic, endoscopic sinus surgery, congenital anosmia, and other causes. Each of the various causes of olfactory dysfunction had its own distinct clinical features. Nineteen of 54 patients whose gustation was assessed had gustatory disorders. Conclusions The leading causes of olfactory dysfunction were URTI, NSD, head trauma, and idiopathic causes. Gustatory disorders were fairly common in patients with olfactory dysfunction. High priority should be given to complaints of olfactory disorders. PMID:23748259

21 CFR 1271.75 - How do I screen a donor?

Code of Federal Regulations, 2011 CFR

2011-04-01

...) Risk factors for, and clinical evidence of, relevant communicable disease agents and diseases... risk factors for and clinical evidence of relevant cell-associated communicable disease agents and... having either of the following: (1) A risk factor for or clinical evidence of any of the relevant...

Clinical Scenarios for Discordant Anti-Xa

PubMed Central

Vera-Aguilera, Jesus; Yousef, Hindi; Beltran-Melgarejo, Diego; Teng, Teng Hugh; Jan, Ramos; Mok, Mary; Vera-Aguilera, Carlos; Moreno-Aguilera, Eduardo

2016-01-01

Anti-Xa test measures the activity of heparin against the activity of activated coagulation factor X; significant variability of anti-Xa levels in common clinical scenarios has been observed. Objective. To review the most common clinical settings in which anti-Xa results can be bias. Evidence Review. Guidelines and current literature search: we used PubMed, Medline, Embase, and MEDION, from 2000 to October 2013. Results. Anti-Xa test is widely used; however the assay underestimates heparin concentration in the presence of significant AT deficiency, pregnancy, end stage renal disease, and postthrombolysis and in patients with hyperbilirubinemia; limited published data evaluating the safety and effectiveness of anti-Xa assays for managing UH therapy is available. Conclusions and Relevance. To our knowledge this is the first paper that summarizes the most common causes in which this assay can be affected, several “day to day” clinical scenarios can modify the outcomes, and we concur that these rarely recognized scenarios can be affected by negative outcomes in the daily practice. PMID:27293440

[POLYGYNAX IN THE TREATMENT OF VAGINAL INFECTIONS IN PREGNANT AND NON-PREGNANT WOMEN--CLINICAL EXPERIENCE].

PubMed

Popovski, N; Popovski, K; Nedelkovski, V

2016-01-01

Vaginal infections /VI/ represent some of the most common diseases by infection of FGS. The aim of this study is to analyze clinical and bacteriological efficacy of Polygynax in the treatment of vaginal infections and to take into account the correlation between the results of microbiological controls and reduction of clinical symptoms. The study included 100 patients, including 50 pregnant and non-pregnant 50 for a period of 3 months. All of them was diagnosed with vaginitis clinical examination, taken material from vagina for microbiological testing. The studied women was conducted targeted therapy Polygynax 12 capsules, in the form of vaginal capsules for 12 days, after which the sample control microbiology. Behind the subjective complaints of the patient and to reduce them as a result of treatment. The effective implementation of Polygynax 12 capsules is equally good as in non-pregnant and pregnant women. In a summary of the survey data to make relevant analyzes and conclusions from the results.

Development of a pharmacogenetic-guided warfarin dosing algorithm for Puerto Rican patients

PubMed Central

Ramos, Alga S; Seip, Richard L; Rivera-Miranda, Giselle; Felici-Giovanini, Marcos E; Garcia-Berdecia, Rafael; Alejandro-Cowan, Yirelia; Kocherla, Mohan; Cruz, Iadelisse; Feliu, Juan F; Cadilla, Carmen L; Renta, Jessica Y; Gorowski, Krystyna; Vergara, Cunegundo; Ruaño, Gualberto; Duconge, Jorge

2012-01-01

Aim This study was aimed at developing a pharmacogenetic-driven warfarin-dosing algorithm in 163 admixed Puerto Rican patients on stable warfarin therapy. Patients & methods A multiple linear-regression analysis was performed using log-transformed effective warfarin dose as the dependent variable, and combining CYP2C9 and VKORC1 genotyping with other relevant nongenetic clinical and demographic factors as independent predictors. Results The model explained more than two-thirds of the observed variance in the warfarin dose among Puerto Ricans, and also produced significantly better ‘ideal dose’ estimates than two pharmacogenetic models and clinical algorithms published previously, with the greatest benefit seen in patients ultimately requiring <7 mg/day. We also assessed the clinical validity of the model using an independent validation cohort of 55 Puerto Rican patients from Hartford, CT, USA (R2 = 51%). Conclusion Our findings provide the basis for planning prospective pharmacogenetic studies to demonstrate the clinical utility of genotyping warfarin-treated Puerto Rican patients. PMID:23215886

Prevalence and clinical characteristics of adult-onset atopic dermatitis with positive skin prick testing to mites.

PubMed

Kulthanan, Kanokvalai; Chularojanamontri, Leena; Manapajon, Araya; Nuchkull, Piyavadee

2011-12-01

The clinical role of house dust mite (HDM) in atopic dermatitis (AD) is still controversial. The aim of the study is to assess the prevalence, clinical relevance and characteristics of adult-onset AD patients with positive skin prick tests (SPT) to mites. The case record forms of adult-onset AD patients who underwent SPT at the Skin Allergy Clinic, Siriraj Hospital were reviewed. Forty-one of 62 patients (66.1%) had positive SPT to mites. The frequency of intrinsic AD among adult-onset AD was 4.8% (3/62). SPT to HDM tended to be positive in patients who had personal or family history of atopy, positive SPT to several specific antigens or who presented with elevated serum IgE, chelitis, recurrent conjunctivitis and perifollicular accentuation, respectively. CONCLUSION The prevalence of adult-onset AD patients with mite sensitivity was high. There were some notable features that tended to be present in mite sensitive adult-onset AD patients.

Dependence and caring in clinical communication: The relevance of attachment and other theories

PubMed Central

Salmon, Peter; Young, Bridget

2009-01-01

Objective Clinical relationships are usually asymmetric, being defined by patients’ dependence and practitioners’ care. Our aims are to: (i) identify literature that can contribute to theory for researching and teaching clinical communication from this perspective; (ii) highlight where theoretical development is needed; and (iii) test the utility of the emerging theory by identifying whether it leads to implications for educational practice. Methods Selective and critical review of research concerned with dependence and caring in clinical and non-clinical relationships. Results Attachment theory helps to understand patients’ need to seek safety in relationships with expert and authoritative practitioners but is of limited help in understanding practitioners’ caring. Different theories that formulate practitioners’ care as altruistic, rewarded by personal connection or as a contract indicate the potential importance of practitioners’ emotions, values and sense of role in understanding their clinical communication. Conclusion Extending the theoretical grounding of clinical communication can accommodate patients’ dependence and practitioners’ caring without return to medical paternalism. Practice implications A broader theoretical base will help educators to address the inherent subjectivity of clinical relationships, and researchers to distinguish scientific questions about how patients and clinicians are from normative questions about how they should be. PMID:19157761

Intercultural Usage of Mori Folium: Comparison Review from a Korean Medical Perspective

PubMed Central

Joh, Byungjin; Jeon, Eun Sang; Lim, Su Hye; Park, Yu Lee; Park, Wansu

2015-01-01

Objectives. A review on studies related to the use of Mori folium, the leaves of Morus alba, was conducted with the goal of identifying new clinical applications in Korean medicine. Methods. Global literature search was conducted using three electronic databases up to January 2015 with the term Morus alba and its Korean terms. KM literatures including textbooks and standard pharmacopoeia were separately hand-searched and reviewed to provide comparison. Data were extracted according to predetermined criteria, and clinical uses were standardized with ICD-10 categories. Results. 159 potentially relevant studies were identified, and 18 articles including 12 ethnopharmacologic and 6 clinical studies were finally included in this analysis. Ethnopharmacologic studies from 8 countries provided 17 clinical uses. We found that five out of six clinical trials were related to diabetes and suggested a moderate short-term to mild long-term effect. And 43 Korean texts also provided 156 clinical uses in 35 categories including ocular and respiratory disorders. Discussion and Conclusions. Though majority of the clinical uses were also found in Korean medicine literature, treatment of infertility, jaundice, cognitive disorder, and hyperpigmentation was found to be effective and diabetes with Morus alba was recognized to have clinical importance. PMID:26539223

Inconsistent Results of Diagnostic Tools Hamper the Differentiation between Bee and Vespid Venom Allergy

PubMed Central

Sturm, Gunter J.; Jin, Chunsheng; Kranzelbinder, Bettina; Hemmer, Wolfgang; Sturm, Eva M.; Griesbacher, Antonia; Heinemann, Akos; Vollmann, Jutta; Altmann, Friedrich; Crailsheim, Karl; Focke, Margarete; Aberer, Werner

2011-01-01

Background Double sensitization (DS) to bee and vespid venom is frequently observed in the diagnosis of hymenoptera venom allergy, but clinically relevant DS is rare. Therefore it is sophisticated to choose the relevant venom for specific immunotherapy and overtreatment with both venoms may occur. We aimed to compare currently available routine diagnostic tests as well as experimental tests to identify the most accurate diagnostic tool. Methods 117 patients with a history of a bee or vespid allergy were included in the study. Initially, IgE determination by the ImmunoCAP, by the Immulite, and by the ADVIA Centaur, as well as the intradermal test (IDT) and the basophil activation test (BAT) were performed. In 72 CAP double positive patients, individual IgE patterns were determined by western blot inhibition and component resolved diagnosis (CRD) with rApi m 1, nVes v 1, and nVes v 5. Results Among 117 patients, DS was observed in 63.7% by the Immulite, in 61.5% by the CAP, in 47.9% by the IDT, in 20.5% by the ADVIA, and in 17.1% by the BAT. In CAP double positive patients, western blot inhibition revealed CCD-based DS in 50.8%, and the CRD showed 41.7% of patients with true DS. Generally, agreement between the tests was only fair and inconsistent results were common. Conclusion BAT, CRD, and ADVIA showed a low rate of DS. However, the rate of DS is higher than expected by personal history, indicating that the matter of clinical relevance is still not solved even by novel tests. Furthermore, the lack of agreement between these tests makes it difficult to distinguish between bee and vespid venom allergy. At present, no routinely employed test can be regarded as gold standard to find the clinically relevant sensitization. PMID:21698247

A Systematic Review of Clinician and Staff Views on the Acceptability of Incorporating Remote Monitoring Technology into Primary Care

PubMed Central

Freeman, Michele; Kaye, Jeffrey; Vuckovic, Nancy; Buckley, David I.

2014-01-01

Abstract Objective: Remote monitoring technology (RMT) may enhance healthcare quality and reduce costs. RMT adoption depends on perceptions of the end-user (e.g., patients, caregivers, healthcare providers). We conducted a systematic review exploring the acceptability and feasibility of RMT use in routine adult patient care, from the perspectives of primary care clinicians, administrators, and clinic staff. Materials and Methods: We searched the databases of Medline, IEEE Xplore, and Compendex for original articles published from January 1996 through February 2013. We manually screened bibliographies of pertinent studies and consulted experts to identify English-language studies meeting our inclusion criteria. Results: Of 939 citations identified, 15 studies reported in 16 publications met inclusion criteria. Studies were heterogeneous by country, type of RMT used, patient and provider characteristics, and method of implementation and evaluation. Clinicians, staff, and administrators generally held positive views about RMTs. Concerns emerged regarding clinical relevance of RMT data, changing clinical roles and patterns of care (e.g., reduced quality of care from fewer patient visits, overtreatment), insufficient staffing or time to monitor and discuss RMT data, data incompatibility with a clinic's electronic health record (EHR), and unclear legal liability regarding response protocols. Conclusions: This small body of heterogeneous literature suggests that for RMTs to be adopted in primary care, researchers and developers must ensure clinical relevance, support adequate infrastructure, streamline data transmission into EHR systems, attend to changing care patterns and professional roles, and clarify response protocols. There is a critical need to engage end-users in the development and implementation of RMT. PMID:24731239

Sustainability and performance of the National Cancer Institute’s Community Clinical Oncology Program

PubMed Central

Carpenter, William R.; Fortune-Greeley, Alice K.; Zullig, Leah L.; Lee, Shoou-Yih; Weiner, Bryan J.

2011-01-01

Introduction The National Cancer Institute’s (NCI) Community Clinical Oncology Program (CCOP) contributes one third of NCI treatment trial enrollment (“accrual”) and most cancer prevention and control (CP/C) trial enrollment. Prior research indicated that the local clinical environment influenced CCOP accrual performance during the 1990s. As the NCI seeks to improve the operations of the clinical trials system following critical reports by the Institute of Medicine and the NCI Operational Efficiency Working Group, the current relevance of the local environmental context on accrual performance is unknown. Materials and methods This longitudinal quasi-experimental study used panel data on 45 CCOPs nationally for years 2000–2007. Multivariable models examine organizational, research network, and environmental factors associated with accrual to treatment trials, CP/C trials, and trials overall. Results For total trial accrual and treatment trial accrual, the number of active CCOP physicians and the number of trials were associated with CCOP performance. Factors differ for CP/C trials. CCOPs in areas with fewer medical school-affiliated hospitals had greater treatment trial accrual. Conclusions Findings suggest a shift in the relevance of the clinical environment since the 1990s, as well as changes in CCOP structure associated with accrual performance. Rather than a limited number of physicians being responsible for the preponderance of trial accrual, there is a trend toward accrual among a larger number of physicians each accruing relatively fewer patients to trial. Understanding this dynamic in the context of CCOP efficiency may inform and strengthen CCOP organization and physician practice. PMID:21986391

GOLD Stage and Treatment in COPD: A 500 Patient Point Prevalence Study.

PubMed

Safka, Katherine A; Wald, Joshua; Wang, Hongyu; McIvor, Luke; McIvor, Andrew

2016-12-22

Background and Objective: The Global initiative for chronic Obstructive Lung Disease (GOLD) guidelines recommend using a combination of spirometry, symptoms and exacerbation history to classify patients into 4 categories (A, B, C, D) to guide treatment decisions along with a stepwise increase in therapy. Our objectives were to identify the GOLD stage of patients in respiratory outpatient clinics and assess how treatment compares to guideline recommendations. Methods: This was a point prevalence study using a convenience sample of 500 patients with chronic obstructive pulmonary disease (COPD) from a single tertiary care outpatient respiratory clinic. Results: Patients' GOLD classification was determined based on symptoms (modified Medical Research Council [mMRC] dyspnea scale, COPD Assessment Test [CAT]), spirometry and self-reported exacerbation history. A total of 8.2% of patients were in the GOLD group A, 28.3% in group B, 4.2% in group C and 59.2% in group D. Conclusions: In this 500 patient point prevalence study we report a low proportion of patients in GOLD group C and a high level of inhaled corticosteroids (ICS)/ long-acting beta2-agonist (LABA) and triple therapy use throughout all GOLD categories. Clinical Implications: The GOLD guidelines have attempted to provide direction to practitioners by grouping patients into 4 groups based on symptoms and exacerbations however, the low prevalence of GOLD group C may indicate that not all of these groupings are clinically relevant. Future research is needed to better identify clinically relevant phenotypes that predict benefit from ICS and methods to promote guideline concordant management in COPD.

Oropharynx HPV status and its relation to HIV infection

PubMed Central

Carneiro, Fabiana Pirani; Amorim, Rivadavio; Guerra, Eliete Neves da Silva; Cavalcanti Neto, Florêncio Figueiredo; Tiziani, Valdenize; Motoyama, Andrea Barretto; Bocca, Anamélia Lorenzetti

2018-01-01

Background The number of oropharyngeal lesions caused by HPV (Human papillomavirus) has been increasing worldwide in the past years. In spite of the clinical relevance of HPV infection in the anogenital tract of HIV-positive patients, the relevance of oropharynx HPV infection in these patients is not clear. The aim of the present study was to detect HPV infection, and clinical and cytological changes in the oropharynx of HIV-positive patients. Methods Samples collected from the oropharynx of 100 HIV-positive patients were subjected to hybrid capture (HC), conventional and liquid-based cytology. Clinical data were also collected to investigate the relation with HPV status. Results High and low-risk types of HPV were present in 8% and 16.7% of the total sample. The mean ± sd (maximum-minimum) of the relative ratio light unit (RLU)/cutoff (CO) was 2.94 ± 2.58 (1.09–7.87) and 1.61 ± 0.65 (1.07–2.8) for high- and low-risk-HPV, respectively. By cytology, dysplasia was not detected, but atypical squamous cells of undetermined significance (ASC-US) were diagnosed in two samples. No clinical change, suggestive of dysplasia/cancer, was detected. Conclusion Our study was able to detect and characterize HPV infection by hybrid capture, which may represent a good tool for screening and follow-up of HPV in the studied population. The frequency and viral load of HPV were low. Neither clinical nor cytological changes suggestive of dysplasia/neoplasia were observed in oropharynx of HIV-positive patients. PMID:29593938

Mobile phone interference with medical equipment and its clinical relevance: a systematic review.

PubMed

Lawrentschuk, Nathan; Bolton, Damien M

2004-08-02

To conduct a systematic review of studies on clinically relevant digital mobile phone electromagnetic interference with medical equipment. MEDLINE and SUMSEARCH were searched for the period 1966-2004. The Cochrane Library and Database of Abstracts of Reviews of Effects were also searched for systematic reviews. Studies were eligible if published in a peer-reviewed journal in English, and if they included testing of digital mobile phones for clinically relevant interference with medical equipment used to monitor or treat patients, but not implantable medical devices. As there was considerable heterogeneity in medical equipment studied and the conduct of testing, results were summarised rather than subjected to meta-analysis. Clinically relevant electromagnetic interference (EMI) secondary to mobile phones potentially endangering patients occurred in 45 of 479 devices tested at 900 MHz and 14 of 457 devices tested at 1800 MHz. However, in the largest studies, the prevalence of clinically relevant EMI was low. Most clinically relevant EMI occurred when mobile phones were used within 1 m of medical equipment. Although testing was not standardised between studies and equipment tested was not identical, it is of concern that at least 4% of devices tested in any study were susceptible to clinically relevant EMI. All studies recommend some type of restriction of mobile phone use in hospitals, with use greater than 1 m from equipment and restrictions in clinical areas being the most common.

The potential role of the medial olivocochlear bundle in the generation of tinnitus: controversies and weaknesses in the existing clinical studies.

PubMed

Riga, Maria; Katotomichelakis, Michael; Danielides, Vasilios

2015-02-01

The physiology of the efferent cochlear innervation and the pathophysiology of tinnitus are 2 important but rather obscure chapters of neuro-otology. The possible interference of the medial olivocochlear bundle (MOCB) in the pathophysiology of tinnitus is not only a matter of strong controversy but also a field with possible important clinical and therapeutic implications. The aim of this study was to reveal the differences in study population, design, and methodology that may have attributed the conflicting results in the existing clinical trials. A review of the relevant literature published between January 1990 and June 2013 was conducted via the PubMed database (www.pubmed.org) with the search terms "tinnitus" and "otoacoustic emissions and suppression or efferent." Clinical studies on patients with additional pathologic abnormalities that may implicate the MOCB, such as hyperacousis or auditory neuropathy, were excluded. The 15 relevant studies were reviewed for critical differences in the recruitment of their study population and control group, as well as their methods of testing and evaluating the results. The different methods and study parameters are compared to each other. Factors known to attribute different MOCB responses, possibly responsible for the controversial results, are highlighted. The remarkable heterogeneity of the existing studies does not allow for safe conclusions. Insufficient knowledge on the physiology of the MOCB reflex seems to preclude the formation of a consensus on the optimal protocol for the evaluation of its function. Further research is definitely needed.

The Telephone Interview for Cognitive Status: Creating a crosswalk with the Mini-Mental State Exam

PubMed Central

Fong, Tamara G.; Fearing, Michael A.; Jones, Richard N.; Shi, Peilin; Marcantonio, Edward R.; Rudolph, James L.; Yang, Frances M.; Kiely, Dan K.; Inouye, Sharon K.

2009-01-01

Background Brief cognitive screening measures are valuable tools for both research and clinical applications. The most widely used instrument, the Mini-Mental State Examination (MMSE) is limited in that it must be administered face-to-face, cannot be used in participants with visual or motor impairments, and is protected by copyright. Alternative screening instruments, such as the Telephone Interview for Cognitive Status (TICS) have been developed and may provide a valid alternative with comparable cut point scores to rate global cognitive function. Methods MMSE, TICS-30, and TICS-40 scores from 746 community dwelling elders who participated in the Aging, Demographics, and Memory Study (ADAMS) were analyzed with equipercentile equating, a statistical process of determining comparable scores based on percentile equivalents on different forms of an examination. Results Scores from the MMSE and the TICS-30 and TICS-40 corresponded well and clinically relevant cut point scores were determined; for example, an MMSE score of 23 is equivalent to 17 and 20 on the TICS-30 and TICS-40, respectively. Conclusions These findings provide scores that can be used to link TICS and MMSE scores directly. Clinically relevant and important MMSE cut points and the respective ADAMS TICS-30 and TICS-40 cut point scores have been included to identify the degree of cognitive impairment among respondents with any type of cognitive disorder. These results will help with the widespread application of the TICS in both research and clinical practice. PMID:19647495

Recommendations for Selecting Drug-Drug Interactions for Clinical Decision Support

PubMed Central

Tilson, Hugh; Hines, Lisa E.; McEvoy, Gerald; Weinstein, David M.; Hansten, Philip D.; Matuszewski, Karl; le Comte, Marianne; Higby-Baker, Stefanie; Hanlon, Joseph T.; Pezzullo, Lynn; Vieson, Kathleen; Helwig, Amy L.; Huang, Shiew-Mei; Perre, Anthony; Bates, David W.; Poikonen, John; Wittie, Michael A.; Grizzle, Amy J.; Brown, Mary; Malone, Daniel C.

2016-01-01

Purpose To recommend principles for including drug-drug interactions (DDIs) in clinical decision support. Methods A conference series was conducted to improve clinical decision support (CDS) for DDIs. The Content Workgroup met monthly by webinar from January 2013 to February 2014, with two in-person meetings to reach consensus. The workgroup consisted of 20 experts in pharmacology, drug information, and CDS from academia, government agencies, health information (IT) vendors, and healthcare organizations. Workgroup members addressed four key questions: (1) What process should be used to develop and maintain a standard set of DDIs?; (2) What information should be included in a knowledgebase of standard DDIs?; (3) Can/should a list of contraindicated drug pairs be established?; and (4) How can DDI alerts be more intelligently filtered? Results To develop and maintain a standard set of DDIs for CDS in the United States, we recommend a transparent, systematic, and evidence-driven process with graded recommendations by a consensus panel of experts and oversight by a national organization. We outline key DDI information needed to help guide clinician decision-making. We recommend judicious classification of DDIs as contraindicated, as only a small set of drug combinations are truly contraindicated. Finally, we recommend more research to identify methods to safely reduce repetitive and less relevant alerts. Conclusion A systematic ongoing process is necessary to select DDIs for alerting clinicians. We anticipate that our recommendations can lead to consistent and clinically relevant content for interruptive DDIs, and thus reduce alert fatigue and improve patient safety. PMID:27045070

A Double-Blind Placebo-Controlled Randomized Clinical Trial With Magnesium Oxide to Reduce Intrafraction Prostate Motion for Prostate Cancer Radiotherapy

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

Lips, Irene M., E-mail: i.m.lips@umcutrecht.nl; Gils, Carla H. van; Kotte, Alexis N.T.J.

2012-06-01

Purpose: To investigate whether magnesium oxide during external-beam radiotherapy for prostate cancer reduces intrafraction prostate motion in a double-blind, placebo-controlled randomized trial. Methods and Materials: At the Department of Radiotherapy, prostate cancer patients scheduled for intensity-modulated radiotherapy (77 Gy in 35 fractions) using fiducial marker-based position verification were randomly assigned to receive magnesium oxide (500 mg twice a day) or placebo during radiotherapy. The primary outcome was the proportion of patients with clinically relevant intrafraction prostate motion, defined as the proportion of patients who demonstrated in {>=}50% of the fractions an intrafraction motion outside a range of 2 mm. Secondarymore » outcome measures included quality of life and acute toxicity. Results: In total, 46 patients per treatment arm were enrolled. The primary endpoint did not show a statistically significant difference between the treatment arms with a percentage of patients with clinically relevant intrafraction motion of 83% in the magnesium oxide arm as compared with 80% in the placebo arm (p = 1.00). Concerning the secondary endpoints, exploratory analyses demonstrated a trend towards worsened quality of life and slightly more toxicity in the magnesium oxide arm than in the placebo arm; however, these differences were not statistically significant. Conclusions: Magnesium oxide is not effective in reducing the intrafraction prostate motion during external-beam radiotherapy, and therefore there is no indication to use it in clinical practice for this purpose.« less

Peyronie’s Disease: AUA Guideline

PubMed Central

Nehra, Ajay; Alterowitz, Ralph; Culkin, Daniel J.; Faraday, Martha M.; Hakim, Lawrence S.; Heidelbaugh, Joel J.; Khera, Mohit; Kirkby, Erin; McVary, Kevin T.; Miner, Martin M.; Nelson, Christian J.; Sadeghi-Nejad, Hossein; Seftel, Allen D.; Shindel, Alan W.; Burnett, Arthur L.

2016-01-01

Purpose The purpose of this guideline is to provide a clinical framework for the diagnosis and treatment of Peyronie’s disease. Materials and Methods A systematic review of the literature using the PubMed®, EMBASE® and Cochrane databases (search dates 1/1/1965 to 1/26/15) was conducted to identify peer-reviewed publications relevant to the diagnosis and treatment of PD. The review yielded an evidence base of 303 articles after application of inclusion/exclusion criteria. Results The systematic review was used to create guideline statements regarding treatment of PD. When sufficient evidence existed, the body of evidence for a particular treatment was assigned a strength rating of A (high quality evidence; high certainty), B (moderate quality evidence; moderate certainty), or C (low quality evidence; low certainty). Evidence-based statements of Strong, Moderate, or Conditional Recommendation were developed based on benefits and risks/burdens to patients. Additional consensus statements related to the diagnosis of PD are provided as Clinical Principles and Expert Opinions due to insufficient published evidence. Conclusions There is a continually expanding literature on PD; the Panel notes that this document constitutes a clinical strategy and is not intended to be interpreted rigidly. The most effective approach for a particular patient is best determined by the individual clinician and patient in the context of that patient’s history, values, and goals for treatment. As the science relevant to PD evolves and improves, the strategies presented here will be amended to remain consistent with the highest standards of clinical care. PMID:26066402

Clinical effects of vinorelbine administration in the management of various malignant tumor types in dogs: 58 cases (1997–2012)

PubMed Central

Wouda, Raelene M.; Miller, Mairin E.; Chon, Esther; Stein, Timothy J.

2016-01-01

Objective To evaluate the effectiveness of vinorelbine in the management of various malignant tumor types in dogs. Design Retrospective case series. Animals 58 dogs with malignant tumors, including pulmonary carcinoma (n = 31), histiocytic sarcoma (9), mast cell tumor (5), lymphoma (4), melanoma (2), and 7 other tumor types (1 each). Procedures Medical records of dogs treated with vinorelbine from December 1997 to December 2012 were reviewed for data regarding signalment, clinical signs, physical examination findings, clinicopathologic test results, diagnostic imaging results, vinorelbine doses and dose frequency, surgery and radiotherapy details when applicable, other chemotherapeutics administered, and outcomes. Descriptive, comparative, and survival statistics were computed for all dogs and for dogs by histologic subgroup of tumors. Results Vinorelbine was administered palliatively to 44 (76%) dogs. One (2%) dog had a complete response for 162 days, 5 (11%) dogs had a partial response for a median duration of 91 days, 19 (43%) dogs had stable disease for a median duration of 68 days, and 19 (43%) dogs developed progressive disease after a median duration of 21 days. Clinical benefit was more difficult to assess in the remaining 14 (24%) dogs that received vinorelbine as an adjuvant treatment. Overall median time to tumor progression was 103 days (range, 5 to 1,533 days). Conclusions and Clinical Relevance Vinorelbine appeared to be effective in the treatment of several tumor types in dogs. Follow-up prospective studies of the clinical benefit of the drug in specific clinical scenarios will be necessary to support this conclusion. PMID:25970220

Clinical relevance of positive voltage-gated potassium channel (VGKC)-complex antibodies: experience from a tertiary referral centre

PubMed Central

Paterson, Ross W; Zandi, Michael S; Armstrong, Richard; Vincent, Angela; Schott, Jonathan M

2014-01-01

Background Voltage-gated potassium channel (VGKC)-complex antibodies can be associated with a range of immunotherapy-responsive clinical presentations including limbic encephalitis, Morvan's syndrome and acquired neuromyotonia. However, there are patients with positive levels in whom the significance is uncertain. Objective To evaluate the clinical significance associated with positive (>100 pM) VGKC-complex antibodies. Methods Over a 4-year period, 1053 samples were sent for testing of which 55 were positive. The clinical presentations, final diagnoses and responses to immunotherapies, when given, were assessed retrospectively and the likelihood of autoimmunity was categorised as definite, possible, unlikely or undetermined (modified from Zuliani et al 2012). Results Only 4 of the 32 patients with low-positive (100–400 pM) levels were considered definitely autoimmune, 3 with peripheral nerve hyperexcitability and 1 with a thymoma; 3 were given immunotherapies. Of the remaining 28 with low-positive levels, 13 (3 of whom had tumours) were considered possibly autoimmune, and 15 were unlikely or undetermined; 1 was given immunotherapy unsuccessfully. Of the 23 patients with high-positive (>400 pM) levels, 12 were given immunotherapies, 11 of whom showed a good response. 11 were considered definitely autoimmune, 10 with limbic encephalitis (antibody specificity: 5 LGI1, 1 contactin2, 2 negative, 2 untested) and 1 with a tumour. In the remaining 12, autoimmunity was considered possible (n=9; most had not received immunotherapies), or unlikely (n=3). Conclusions As antibody testing becomes more widely available, and many samples are referred from patients with less clear-cut diagnoses, it is important to assess the utility of the results. VGKC-complex antibodies in the range of 100–400 pM (0.1–0.4 nM) were considered clinically relevant in rare conditions with peripheral nerve hyperexcitability and appeared to associate with tumours (12.5%). By contrast high-positive (>400 pM; >0.4 nM) levels were considered definitely (38%) or possibly (49%) clinically relevant, but not all patients had a ‘classical’ limbic encephalitis and some did not receive immunotherapies. PMID:23757422

Clinical Decision Support Tools for Osteoporosis Disease Management: A Systematic Review of Randomized Controlled Trials

PubMed Central

Straus, Sharon E.

2008-01-01

BACKGROUND Studies indicate a gap between evidence and clinical practice in osteoporosis management. Tools that facilitate clinical decision making at the point of care are promising strategies for closing these practice gaps. OBJECTIVE To systematically review the literature to identify and describe the effectiveness of tools that support clinical decision making in osteoporosis disease management. DATA SOURCES Medline, EMBASE, CINAHL, and EBM Reviews (CDSR, DARE, CCTR, and ACP J Club), and contact with experts in the field. REVIEW METHODS Randomized controlled trials (RCTs) in any language from 1966 to July 2006 investigating disease management interventions in patients at risk for osteoporosis. Outcomes included fractures and bone mineral density (BMD) testing. Two investigators independently assessed articles for relevance and study quality, and extracted data using standardized forms. RESULTS Of 1,246 citations that were screened for relevance, 13 RCTs met the inclusion criteria. Reported study quality was generally poor. Meta-analysis was not done because of methodological and clinical heterogeneity; 77% of studies included a reminder or education as a component of their intervention. Three studies of reminders plus education targeted to physicians and patients showed increased BMD testing (RR range 1.43 to 8.67) and osteoporosis medication use (RR range 1.60 to 8.67). A physician reminder plus a patient risk assessment strategy found reduced fractures [RR 0.58, 95% confidence interval (CI) 0.37 to 0.90] and increased osteoporosis therapy (RR 2.44, CI 1.43 to 4.17). CONCLUSION Multi-component tools that are targeted to physicians and patients may be effective for supporting clinical decision making in osteoporosis disease management. Electronic supplementary material The online version of this article (doi:10.1007/s11606-008-0812-9) contains supplementary material, which is available to authorized users. PMID:18836782

The clinical, occupational and financial outcomes associated with a bespoke specialist clinic for military aircrew—a cohort study

PubMed Central

Pavitt, A.J.; Pavitt, C.W.; Harron, K.; Jones, M.; Timperley, A.C.; Reid, A.N.C.; Mcloughlin, D.; d'Arcy, J.

2016-01-01

Objectives: To assess the clinical, occupational and financial outcomes of a new Clinical Aviation Medicine Service (CAMS) for UK military personnel. Methods: Consecutive patients over a 2 year period were included. Predictors of flying restrictions at referral and final outcome following consultation were modelled using logistic regression. National Health Service (NHS) Payment by Results tariffs and Defence capitation data were used to assess the financial impact of the service. Results: Eight hundred and sixteen new referrals (94.5% male, median age 45 years (range 19–75)) were received and 1025 consultations performed. Cardiovascular disease was the commonest reason for referral. CAMS clinical activity cost at NHS tariff was £453 310 representing a saving of £316 173 (£137 137 delivery cost). In total, 310/816 (38%) patients had employment restrictions on referral and 49.0% of this group returned to full employment following their initial consultation. Compared with cardiology, general medicine and respiratory patients were more likely to have been occupationally restricted prior to referral (50 vs. 35%, OR 1.81; 95% CI 1.18–2.76, P values=0.006 and 53 vs. 35%, OR 2.12; 95% CI 1.15–3.90, P values = 0.016, respectively). Overall 581/816 (71.2%) of patients returned to unrestricted employment while 98/816 (12.0%) were unable to continue in any aircrew role. The service saved 7000 lost working days per year at an estimated occupational saving of ∼£1 million per annum. Conclusions: This bespoke service has allowed rapid, occupationally relevant clinical care to be delivered with both time and financial savings. The model may have significant occupational and financial relevance for other environmental and occupational medical organizations. PMID:26424788

Querying phenotype-genotype relationships on patient datasets using semantic web technology: the example of cerebrotendinous xanthomatosis

PubMed Central

2012-01-01

Background Semantic Web technology can considerably catalyze translational genetics and genomics research in medicine, where the interchange of information between basic research and clinical levels becomes crucial. This exchange involves mapping abstract phenotype descriptions from research resources, such as knowledge databases and catalogs, to unstructured datasets produced through experimental methods and clinical practice. This is especially true for the construction of mutation databases. This paper presents a way of harmonizing abstract phenotype descriptions with patient data from clinical practice, and querying this dataset about relationships between phenotypes and genetic variants, at different levels of abstraction. Methods Due to the current availability of ontological and terminological resources that have already reached some consensus in biomedicine, a reuse-based ontology engineering approach was followed. The proposed approach uses the Ontology Web Language (OWL) to represent the phenotype ontology and the patient model, the Semantic Web Rule Language (SWRL) to bridge the gap between phenotype descriptions and clinical data, and the Semantic Query Web Rule Language (SQWRL) to query relevant phenotype-genotype bidirectional relationships. The work tests the use of semantic web technology in the biomedical research domain named cerebrotendinous xanthomatosis (CTX), using a real dataset and ontologies. Results A framework to query relevant phenotype-genotype bidirectional relationships is provided. Phenotype descriptions and patient data were harmonized by defining 28 Horn-like rules in terms of the OWL concepts. In total, 24 patterns of SWQRL queries were designed following the initial list of competency questions. As the approach is based on OWL, the semantic of the framework adapts the standard logical model of an open world assumption. Conclusions This work demonstrates how semantic web technologies can be used to support flexible representation and computational inference mechanisms required to query patient datasets at different levels of abstraction. The open world assumption is especially good for describing only partially known phenotype-genotype relationships, in a way that is easily extensible. In future, this type of approach could offer researchers a valuable resource to infer new data from patient data for statistical analysis in translational research. In conclusion, phenotype description formalization and mapping to clinical data are two key elements for interchanging knowledge between basic and clinical research. PMID:22849591

Systematic Review of Chinese Medicine for Miscarriage during Early Pregnancy

PubMed Central

Leung, Ping Chung; Chung, Tony Kwok Hung; Wang, Chi Chiu

2014-01-01

Background. Miscarriage is a very common complication during early pregnancy. So far, clinical therapies have limitation in preventing the early pregnancy loss. Chinese Medicine, regarded as gentle, effective, and safe, has become popular and common as a complementary and alternative treatment for miscarriages. However, the evidence to support its therapeutic efficacy and safety is still very limited. Objectives and Methods. To summarize the clinical application of Chinese Medicine for pregnancy and provide scientific evidence on the efficacy and safety of Chinese medicines for miscarriage, we located all the relevant pieces of literature on the clinical applications of Chinese Medicine for miscarriage and worked out this systematic review. Results. 339,792 pieces of literature were identified, but no placebo was included and only few studies were selected for systematic review and conducted for meta-analysis. A combination of Chinese medicines and Western medicines was more effective than Chinese medicines alone. No specific safety problem was reported, but potential adverse events by certain medicines were identified. Conclusions. Studies vary considerably in design, interventions, and outcome measures; therefore conclusive results remain elusive. Large scales of randomized controlled trials and more scientific evidences are still necessary to confirm the efficacy and safety of Chinese medicines during early pregnancy. PMID:24648851

Mobile Technology in Undergraduate Nursing Education: A Systematic Review

PubMed Central

Lee, Hyejung; Oh, Su-mi; Shim, Kaka

2018-01-01

Objectives This study aimed to identify and systematically review the literature on the use of mobile technology in nursing education. The research findings could evidence the effectiveness of mobile technology in undergraduate nursing students' learning outcomes. Methods Computerized searches were conducted using the Ovid-MEDLINE, Ovid-EMBASE, Cochrane Library, and CINAHL databases for relevant primary studies and limited to those between 2000 and February 2018. Only randomized controlled trials (RCTs) and quasi-experimental studies published in either English or Korean were included and critically appraised using Joanna Briggs Institute tools. Results Seven RCTs and 7 quasi-experimental studies were identified. The mobile device and intervention applied varied throughout all the studies. Studies published earlier in the 2000s found that immediate access to clinical and pharmacological referencing information through the mobile device increased students' efficacy in clinical practice. Later studies, which were mostly conducted in Korea, reported that smartphone-based applications could promote nursing students' learning motivation and satisfaction but not their clinical skills and knowledge. Conclusions We still seem to be in the beginning stage of implementing mobile technology in nursing education due to the limited implication of mobile technology and inconsistent research conclusions. In the future, rigorous primary empirical studies are needed to suggest the effective use of mobile devices in nursing education. PMID:29770243

Clinical relevance of findings in trials of CBT for depression.

PubMed

Lepping, P; Whittington, R; Sambhi, R S; Lane, S; Poole, R; Leucht, S; Cuijpers, P; McCabe, R; Waheed, W

2017-09-01

Cognitive behavioural therapy (CBT) is beneficial in depression. Symptom scores can be translated into Clinical Global Impression (CGI) scale scores to indicate clinical relevance. We aimed to assess the clinical relevance of findings of randomised controlled trials (RCTs) of CBT in depression. We identified RCTs of CBT that used the Hamilton Rating Scale for Depression (HAMD). HAMD scores were translated into Clinical Global Impression - Change scale (CGI-I) scores to measure clinical relevance. One hundred and seventy datasets from 82 studies were included. The mean percentage HAMD change for treatment arms was 53.66%, and 29.81% for control arms, a statistically significant difference. Combined active therapies showed the biggest improvement on CGI-I score, followed by CBT alone. All active treatments had better than expected HAMD percentage reduction and CGI-I scores. CBT has a clinically relevant effect in depression, with a notional CGI-I score of 2.2, indicating a significant clinical response. The non-specific or placebo effect of being in a psychotherapy trial was a 29% reduction of HAMD. Copyright © 2017. Published by Elsevier Masson SAS.

Direct toxic effects of aqueous extract of cigarette smoke on cardiac myocytes at clinically relevant concentrations

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

Yamada, Shigeyuki; Zhang Xiuquan; Kadono, Toshie

Aims: Our goal was to determine if clinically relevant concentrations of aqueous extract of cigarette smoke (CSE) have direct deleterious effects on ventricular myocytes during simulated ischemia, and to investigate the mechanisms involved. Methods: CSE was prepared with a smoking chamber. Ischemia was simulated by metabolic inhibition (MI) with cyanide (CN) and 0 glucose. Adult rabbit and mouse ventricular myocyte [Ca{sup 2+}]{sub i} was measured by flow cytometry using fluo-3. Mitochondrial [Ca{sup 2+}] was measured with confocal microscopy, and Rhod-2 fluorescence. The mitochondrial permeability transition (MPT) was detected by TMRM fluorescence and myocyte contracture. Myocyte oxidative stress was quantified bymore » dichlorofluorescein (DCF) fluorescence with confocal microscopy. Results: CSE 0.1% increased myocyte contracture caused by MI. The nicotine concentration (HPLC) in 0.1% CSE was 15 ng/ml, similar to that in humans after smoking cigarettes. CSE 0.1% increased mitochondrial Ca{sup 2+} uptake, and increased the susceptibility of mitochondria to the MPT. CSE 0.1% increased DCF fluorescence in isolated myocytes, and increased [Ca{sup 2+}]{sub i} in paced myocytes exposed to 2.0 mM CN, 0 glucose (P-MI). These effects were inhibited by the superoxide scavenger Tiron. The effect of CSE on [Ca{sup 2+}]{sub i} during P-MI was also prevented by ranolazine. Conclusions: CSE in clinically relevant concentrations increases myocyte [Ca{sup 2+}]{sub i} during simulated ischemia, and increases myocyte susceptibility to the MPT. These effects appear to be mediated at least in part by oxidative radicals in CSE, and likely contribute to the effects of cigarette smoke to increase myocardial infarct size, and to decrease angina threshold.« less

Clinical Decision Support Tools for Selecting Interventions for Patients with Disabling Musculoskeletal Disorders: A Scoping Review.

PubMed

Gross, Douglas P; Armijo-Olivo, Susan; Shaw, William S; Williams-Whitt, Kelly; Shaw, Nicola T; Hartvigsen, Jan; Qin, Ziling; Ha, Christine; Woodhouse, Linda J; Steenstra, Ivan A

2016-09-01

Purpose We aimed to identify and inventory clinical decision support (CDS) tools for helping front-line staff select interventions for patients with musculoskeletal (MSK) disorders. Methods We used Arksey and O'Malley's scoping review framework which progresses through five stages: (1) identifying the research question; (2) identifying relevant studies; (3) selecting studies for analysis; (4) charting the data; and (5) collating, summarizing and reporting results. We considered computer-based, and other available tools, such as algorithms, care pathways, rules and models. Since this research crosses multiple disciplines, we searched health care, computing science and business databases. Results Our search resulted in 4605 manuscripts. Titles and abstracts were screened for relevance. The reliability of the screening process was high with an average percentage of agreement of 92.3 %. Of the located articles, 123 were considered relevant. Within this literature, there were 43 CDS tools located. These were classified into 3 main areas: computer-based tools/questionnaires (n = 8, 19 %), treatment algorithms/models (n = 14, 33 %), and clinical prediction rules/classification systems (n = 21, 49 %). Each of these areas and the associated evidence are described. The state of evidentiary support for CDS tools is still preliminary and lacks external validation, head-to-head comparisons, or evidence of generalizability across different populations and settings. Conclusions CDS tools, especially those employing rapidly advancing computer technologies, are under development and of potential interest to health care providers, case management organizations and funders of care. Based on the results of this scoping review, we conclude that these tools, models and systems should be subjected to further validation before they can be recommended for large-scale implementation for managing patients with MSK disorders.

Pediatric hydrocephalus: systematic literature review and evidence-based guidelines. Part 3: Endoscopic computer-assisted electromagnetic navigation and ultrasonography as technical adjuvants for shunt placement.

PubMed

Flannery, Ann Marie; Duhaime, Ann-Christine; Tamber, Mandeep S; Kemp, Joanna

2014-11-01

This systematic review was undertaken to answer the following question: Do technical adjuvants such as ventricular endoscopic placement, computer-assisted electromagnetic guidance, or ultrasound guidance improve ventricular shunt function and survival? The US National Library of Medicine PubMed/MEDLINE database and the Cochrane Database of Systematic Reviews were queried using MeSH headings and key words specifically chosen to identify published articles detailing the use of cerebrospinal fluid shunts for the treatment of pediatric hydrocephalus. Articles meeting specific criteria that had been delineated a priori were then examined, and data were abstracted and compiled in evidentiary tables. These data were then analyzed by the Pediatric Hydrocephalus Systematic Review and Evidence-Based Guidelines Task Force to consider evidence-based treatment recommendations. The search yielded 163 abstracts, which were screened for potential relevance to the application of technical adjuvants in shunt placement. Fourteen articles were selected for full-text review. One additional article was selected during a review of literature citations. Eight of these articles were included in the final recommendations concerning the use of endoscopy, ultrasonography, and electromagnetic image guidance during shunt placement, whereas the remaining articles were excluded due to poor evidence or lack of relevance. The evidence included 1 Class I, 1 Class II, and 6 Class III papers. An evidentiary table of relevant articles was created. CONCLUSIONS/RECOMMENDATION: There is insufficient evidence to recommend the use of endoscopic guidance for routine ventricular catheter placement. Level I, high degree of clinical certainty. The routine use of ultrasound-assisted catheter placement is an option. Level III, unclear clinical certainty. The routine use of computer-assisted electromagnetic (EM) navigation is an option. Level III, unclear clinical certainty.

Health-Related Quality of Life up to Six Years After {sup 125}I Brachytherapy for Early-Stage Prostate Cancer

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

Roeloffzen, Ellen M.A., E-mail: E.M.A.Roeloffzen@UMCUtrecht.n; Lips, Irene M.; Gellekom, Marion P.R. van

2010-03-15

Purpose: Health-related quality of life (HRQOL) after prostate brachytherapy has been extensively described in published reports but hardly any long-term data are available. The aim of the present study was to prospectively assess long-term HRQOL 6 years after {sup 125}I prostate brachytherapy. Methods and Materials: A total of 127 patients treated with {sup 125}I brachytherapy for early-stage prostate cancer between December 2000 and June 2003 completed a HRQOL questionnaire at five time-points: before treatment and 1 month, 6 months, 1 year, and 6 years after treatment. The questionnaire included the RAND-36 generic health survey, the cancer-specific European Organization for Researchmore » and Treatment of Cancer core questionnaire (EORTCQLQ-C30), and the tumor-specific EORTC prostate cancer module (EORTC-PR25). A change in a score of >=10 points was considered clinically relevant. Results: Overall, the HRQOL at 6 years after {sup 125}I prostate brachytherapy did not significantly differ from baseline. Although a statistically significant deterioration in HRQOL at 6 years was seen for urinary symptoms, bowel symptoms, pain, physical functioning, and sexual activity (p <.01), most changes were not clinically relevant. A statistically significant improvement at 6 years was seen for mental health, emotional functioning, and insomnia (p <.01). The only clinically relevant changes were seen for emotional functioning and sexual activity. Conclusion: This is the first study presenting prospective HRQOL data up to 6 years after {sup 125}I prostate brachytherapy. HRQOL scores returned to approximately baseline values at 1 year and remained stable up to 6 years after treatment. {sup 125}I prostate brachytherapy did not adversely affect patients' long-term HRQOL.« less

SU-E-E-01: ABR Diagnostic Radiology Core Exam: Was Our Redesigned Physics Course Successful in Teaching Physics to Radiology Residents?

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

Kanal, K; Hoff, M; Dickinson, R

Purpose: Our purpose is to evaluate the effectiveness of our two year physics course in preparing radiology residents for the American Board of Radiology (ABR) diagnostic radiology exam. Methods: We designed a new two-year physics course that integrates radiology clinical content and practice and is primarily based on the AAPM curriculum and RSNA/AAPM physics modules. Biweekly classes focus on relevant concepts from assigned reading and use audience response systems to encourage participation. Teaching efficiency is optimized through lecturer rotations of physicists, radiologists, and guest speakers. An emphasis is placed on clinical relevance by requiring lab work and providing equipment demonstrations.more » Periodic quiz were given during the course. The course website was also redesigned for usability, and physics review lectures were conducted two weeks before the board exam to refresh key concepts. At the completion of our first two-year course, we conducted a confidential evaluation of the faculty and course. The evaluation assessed metrics such as overall organization, clinical relevance of content, and level of difficulty, with a rating scale from poor to excellent. Results: Our evaluation indicated that the redesigned course provided effective board exam preparation, with most responses between good and excellent. There was some criticism on the course length and on chronological discontinuity, but the review lectures were appreciated by the residents. All of our residents passed the physics component of the ABR exam with scores exceeding the minimum passing score by a significant margin. Conclusion: The course evaluation and board exam results indicate that our new two-year course format provides valuable board exam preparation. This is possible thanks to the time and effort taken by the physics faculty on ensuring the residents get quality physics education.« less

Pooled population pharmacokinetic model of imipenem in plasma and the lung epithelial lining fluid

PubMed Central

Rizk, Matthew L.; Lala, Mallika; Chavez‐Eng, Cynthia; Visser, Sandra A. G.; Kerbusch, Thomas; Danhof, Meindert; Rao, Gauri; van der Graaf, Piet H.

2016-01-01

Aims Several clinical trials have confirmed the therapeutic benefit of imipenem for treatment of lung infections. There is however no knowledge of the penetration of imipenem into the lung epithelial lining fluid (ELF), the site of action relevant for lung infections. Furthermore, although the plasma pharmacokinetics (PK) of imipenem has been widely studied, most studies have been based on selected patient groups. The aim of this analysis was to characterize imipenem plasma PK across populations and to quantify imipenem ELF penetration. Methods A population model for imipenem plasma PK was developed using data obtained from healthy volunteers, elderly subjects and subjects with renal impairment, in order to identify predictors for inter‐individual variability (IIV) of imipenem PK. Subsequently, a clinical study which measured plasma and ELF concentrations of imipenem was included in order to quantify lung penetration. Results A two compartmental model best described the plasma PK of imipenem. Creatinine clearance and body weight were included as subject characteristics predictive for IIV on clearance. Typical estimates for clearance, central and peripheral volume, and inter‐compartmental clearance were 11.5 l h–1, 9.37 l, 6.41 l, 13.7 l h–1, respectively (relative standard error (RSE) <8%). The distribution of imipenem into ELF was described using a time‐independent penetration coefficient of 0.44 (RSE 14%). Conclusion The identified lung penetration coefficient confirms the clinical relevance of imipenem for treatment of lung infections, while the population PK model provided insights into predictors of IIV for imipenem PK and may be of relevance to support dose optimization in various subject groups. PMID:26852277

Drug development in neuropsychopharmacology.

PubMed

Fritze, Jürgen

2008-03-01

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

The Dreyfus model of clinical problem-solving skills acquisition: a critical perspective

PubMed Central

Peña, Adolfo

2010-01-01

Context The Dreyfus model describes how individuals progress through various levels in their acquisition of skills and subsumes ideas with regard to how individuals learn. Such a model is being accepted almost without debate from physicians to explain the ‘acquisition’ of clinical skills. Objectives This paper reviews such a model, discusses several controversial points, clarifies what kind of knowledge the model is about, and examines its coherence in terms of problem-solving skills. Dreyfus' main idea that intuition is a major aspect of expertise is also discussed in some detail. Relevant scientific evidence from cognitive science, psychology, and neuroscience is reviewed to accomplish these aims. Conclusions Although the Dreyfus model may partially explain the ‘acquisition’ of some skills, it is debatable if it can explain the acquisition of clinical skills. The complex nature of clinical problem-solving skills and the rich interplay between the implicit and explicit forms of knowledge must be taken into consideration when we want to explain ‘acquisition’ of clinical skills. The idea that experts work from intuition, not from reason, should be evaluated carefully. PMID:20563279

Clinical Research Informatics for Big Data and Precision Medicine

PubMed Central

Kahn, M. G.

2016-01-01

Summary Objectives To reflect on the notable events and significant developments in Clinical Research Informatics (CRI) in the year of 2015 and discuss near-term trends impacting CRI. Methods We selected key publications that highlight not only important recent advances in CRI but also notable events likely to have significant impact on CRI activities over the next few years or longer, and consulted the discussions in relevant scientific communities and an online living textbook for modern clinical trials. We also related the new concepts with old problems to improve the continuity of CRI research. Results The highlights in CRI in 2015 include the growing adoption of electronic health records (EHR), the rapid development of regional, national, and global clinical data research networks for using EHR data to integrate scalable clinical research with clinical care and generate robust medical evidence. Data quality, integration, and fusion, data access by researchers, study transparency, results reproducibility, and infrastructure sustainability are persistent challenges. Conclusion The advances in Big Data Analytics and Internet technologies together with the engagement of citizens in sciences are shaping the global clinical research enterprise, which is getting more open and increasingly stakeholder-centered, where stakeholders include patients, clinicians, researchers, and sponsors. PMID:27830253

RELEVANCE OF WHOLE BODY VIBRATION EXERCISE IN SPORT: A SHORT REVIEW WITH SOCCER, DIVER AND COMBAT SPORT

PubMed Central

Morel, Danielle Soares; Dionello, Carla da Fontoura; Moreira-Marconi, Eloá; Brandão-Sobrinho-Neto, Samuel; Paineiras-Domingos, Laisa Liane; Souza, Patrícia Lopes; Sá-Caputo, Danúbia da Cunha; Dias, Glenda; Figueiredo, Claudia; Carmo, Roberto Carlos Resende; Paiva, Patrícia de Castro; Sousa-Gonçalves, Cintia Renata; Kütter, Cristiane Ribeiro; Guedes-Aguiar, Eliane de Oliveira; Cloak, Ross; Bernardo-Filho, Mario

2017-01-01

Background: Whole body vibration exercise (WBVE) has been used as a safe and accessible exercise and important reviews have been published about the use of this exercise to manage diseases and to improve physical conditions of athletes The aim of this paper is to highlight the relevance of WBVE to soccer players, divers and combat athletes. Material and methods: This study was made through a systematic review of publications involving WBVE and the selected sports in two databases (Pubmed and PEDRo). Results: It were identified 10 studies involving WBVE and sports (6 of soccer, 2 of diving and 2 of sport combat) with 156 subjects (80 soccer players, 32 divers and 44 combat athletes), with age from 17 to 44 years old. Conclusion: The use of WBVE has proven to be a safe and useful strategy to improve the physical conditions of players of different sports. These findings may have clinical relevance and should be considered as a strategy to be used to try improve the physical conditions of players. PMID:28740940

3D postural balance with regard to gravity line: an evaluation in the transversal plane on 93 patients and 23 asymptomatic volunteers

PubMed Central

Obeid, Ibrahim; Aurouer, Nicolas; Hauger, Olivier; Vital, Jean-Marc; Dubousset, Jean; Skalli, Wafa

2009-01-01

Relevance of posture assessment has been reported in case of spine disorders. This study explores the interest in quantifying posture using 3D reconstruction from biplanar X-rays in free standing position and a force plate. 93 patients consulting for spine disorders were divided (‘3D deformity’, ‘sagittal imbalance’ and ‘mild deformity’) and compared with 23 asymptomatic volunteers. Registration of the gravity line (GL) in reconstruction yielded transversal position of the center of acoustic meati (CAM) T1, T4, T9, L3, S1 and hip axis (HA) with regard to GL. Transversal position of CAM and L3 appeared as relevant parameters to discriminate patients from volunteers. Sagittal inclination of the axis linking the CAM to HA was correlated with position of the CAM to GL (r = 0.92 for patients). In conclusion, observing posture in 3D with regard to GL provides clinical relevant information. CAM-HA inclination may improve postural evaluation without force plate. PMID:20035359

Dental students' motivation and the context of learning.

PubMed

Kristensen, Bettina Tjagvad; Netterstrom, Ingeborg; Kayser, Lars

2009-02-01

This qualitative study shows dental students' motives for choosing the dental education and how the motives influence their motivation at the first semester of study. Further the study demonstrates the relevance of the context of learning. This issue is of importance when planning a curriculum for the dental education. The material consists of interviews with eight dental students. The results show that dental students were focused on their future professional role, its practical dimensions and their future working conditions. Their motivation for choosing the dental education was found to influence their motivation for studying and their experience of the relevance of the first semester. The dental students who had co-education with the medical students at the first year of study missed a dental context and courses with clinically relevant contents. In conclusion, our data signify the importance of the context of learning. It is recommended that a future curriculum for the dental school should be designed in a way where basic science subjects are taught with both theoretically as well as practically oriented subjects and in a context which is meaningful for the students.

Biological monitoring of carcinogens: current status and perspectives.

PubMed

Pavanello, Sofia; Lotti, Marcello

2012-04-01

Biomonitoring exposures to carcinogens is common practice and a variety of biomarkers have been developed to assess both exposures and biochemical/biological effects. However, their clinical and preventive relevance is still uncertain. The understanding of cancer as a genetic disease has dramatically evolved during last decades, showing that cancer cell types acquire their characteristics with different strategies, time frames and microenvironments. Therefore, the place of current biomarkers within this complex scenario of gene-environment interactions leading to cancer cannot be defined. Reasons are manifold. Most studies assessed cancer risk on a group basis through snapshots taken at unknown time-points of the postulated chain of events. Little attention has been paid to the variety and variability of exposures, and no prospective study validated the indicators of biochemical/biological effects. New opportunities and suggestions for biomonitoring exposures to carcinogens could derive from exploring the exposome that combines exposures from all sources both external and internal. The discovery of new biomarkers and the identification of relevant gene-specific pathways could be achieved through metabolomic and genome-wide studies. In conclusion, it is possible to envisage personalized biomonitoring procedures, such as those already implemented in the context of nutrition and clinical oncology.

From radioimmunoassay to mass spectrometry: a new method to quantify orexin-A (hypocretin-1) in cerebrospinal fluid

PubMed Central

Hirtz, Christophe; Vialaret, Jérôme; Gabelle, Audrey; Nowak, Nora; Dauvilliers, Yves; Lehmann, Sylvain

2016-01-01

I125 radioimmunoassay (RIA) is currently the standard technique for quantifying cerebrospinal fluid (CSF) orexin-A/hypocretin-1, a biomarker used to diagnose narcolepsy type 1. However, orexin-A RIA is liable to undergo cross-reactions with matrix constituents generating interference, high variability between batches, low precision and accuracy, and requires special radioactivity precautions. Here we developed the first quantitative mass spectrometry assay of orexin-A based on a multiple reaction monitoring (MRM) approach. This method was tested in keeping with the Clinical and Laboratory Standards Institute (CLSI) guidelines and its clinical relevance was confirmed by comparing patients with narcolepsy type 1 versus patients with other neurological conditions. The results obtained using MRM and RIA methods were highly correlated, and Bland–Altman analysis established their interchangeability. However, the MRM values had a wider distribution and were 2.5 time lower than the RIA findings. In conclusion, this method of assay provides a useful alternative to RIA to quantify orexin-A, and may well replace it not only in narcolepsy type 1, but also in the increasing number of pathologies in which the quantification of this analyte is relevant. PMID:27165941

MALDI-TOF MS identification of anaerobic bacteria: assessment of pre-analytical variables and specimen preparation techniques.

PubMed

Hsu, Yen-Michael S; Burnham, Carey-Ann D

2014-06-01

Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has emerged as a tool for identifying clinically relevant anaerobes. We evaluated the analytical performance characteristics of the Bruker Microflex with Biotyper 3.0 software system for identification of anaerobes and examined the impact of direct formic acid (FA) treatment and other pre-analytical factors on MALDI-TOF MS performance. A collection of 101 anaerobic bacteria were evaluated, including Clostridium spp., Propionibacterium spp., Fusobacterium spp., Bacteroides spp., and other anaerobic bacterial of clinical relevance. The results of our study indicate that an on-target extraction with 100% FA improves the rate of accurate identification without introducing misidentification (P<0.05). In addition, we modify the reporting cutoffs for the Biotyper "score" yielding acceptable identification. We found that a score of ≥1.700 can maximize the rate of identification. Of interest, MALDI-TOF MS can correctly identify anaerobes grown in suboptimal conditions, such as on selective culture media and following oxygen exposure. In conclusion, we report on a number of simple and cost-effective pre- and post-analytical modifications could enhance MALDI-TOF MS identification for anaerobic bacteria. Copyright © 2014 Elsevier Inc. All rights reserved.

The Quest for Evidence for Proton Therapy: Model-Based Approach and Precision Medicine

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

Widder, Joachim, E-mail: j.widder@umcg.nl; Schaaf, Arjen van der; Lambin, Philippe

Purpose: Reducing dose to normal tissues is the advantage of protons versus photons. We aimed to describe a method for translating this reduction into a clinically relevant benefit. Methods and Materials: Dutch scientific and health care governance bodies have recently issued landmark reports regarding generation of relevant evidence for new technologies in health care including proton therapy. An approach based on normal tissue complication probability (NTCP) models has been adopted to select patients who are most likely to experience fewer (serious) adverse events achievable by state-of-the-art proton treatment. Results: By analogy with biologically targeted therapies, the technology needs to be testedmore » in enriched cohorts of patients exhibiting the decisive predictive marker: difference in normal tissue dosimetric signatures between proton and photon treatment plans. Expected clinical benefit is then estimated by virtue of multifactorial NTCP models. In this sense, high-tech radiation therapy falls under precision medicine. As a consequence, randomizing nonenriched populations between photons and protons is predictably inefficient and likely to produce confusing results. Conclusions: Validating NTCP models in appropriately composed cohorts treated with protons should be the primary research agenda leading to urgently needed evidence for proton therapy.« less

Mental capacity to consent to treatment and the association with outcome: a longitudinal study in patients with anorexia nervosa

PubMed Central

Danner, Unna N.; Sternheim, Lot C.; McNeish, Daniel; Hoek, Hans W.; van Elburg, Annemarie A.

2017-01-01

Background Relevance of diminished mental capacity in anorexia nervosa (AN) to course of disorder is unknown. Aims To examine prognostic relevance of diminished mental capacity in AN. Method A longitudinal study was conducted in 70 adult female patients with severe AN. At baseline, mental capacity was assessed by psychiatrists, and clinical and neuropsychological data (decision-making) were collected. After 1 and 2 years, clinical and neuropsychological assessments were repeated, and remission and admission rates were calculated. Results People with AN with diminished mental capacity had a less favourable outcome with regard to remission and were admitted more frequently. Their appreciation of illness remained hampered. Decision-making did not improve, in contrast to people with full mental capacity. Conclusions People with AN with diminished mental capacity seem to do less well in treatment and display decision-making deficiencies that do not ameliorate with weight improvement. Declaration of interest None. Copyright and usage © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license. PMID:28584660

Is effective a prior multiparametric magnetic resonance scan in patients candidates to prostate biopsy? CAT Study.

PubMed

Ramos Rodríguez, J R; Molinero Pérez, M; Herrera Imbroda, B; Domínguez Pinos, M D

2016-01-01

We carried out a critically appraised topic (CAT)-type study to determine whether the relevant scientific evidence supports the recommendation of doing a multiparametric magnetic resonance imaging study of the prostate in all patients who are candidates for prostate biopsy with the aim of improving the detection of clinically significant prostate cancer and stratifying patients to receive active surveillance or treatment. After a formal literature search and an analysis of the two most relevant articles it found, we reached the conclusion that, despite promising results that point to the potential usefulness of this approach, there is still not enough clear scientific evidence to endorse it categorically. Before this approach can be endorsed, we need evidence from well-designed prospective randomized trials using widely agreed upon criteria and including large numbers of patients at multiple centers. Copyright © 2016 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

Cross-Cultural Studies of Personality Traits and their Relevance to Psychiatry

PubMed Central

Terracciano, Antonio; McCrae, Robert R.

2009-01-01

Aims This article provides a brief review of recent cross-cultural research on personality traits at both individual and culture levels, highlighting the relevance of recent findings for psychiatry. Method In most cultures around the world, personality traits can be clearly summarized by the five broad dimensions of the Five-Factor Model (FFM), which makes it feasible to compare cultures on personality and psychopathology. Results Maturational patterns and sex differences in personality traits generally show cultural invariance, which generates the hypothesis that age of onset, clinical evolution, and sex differences in the prevalence of psychiatric disorders might follow similar universal patterns. The average personality profiles from 51 cultures show meaningful geographical distributions and associations with culture-level variables, but are clearly unrelated to national character stereotypes. Conclusions Aggregate personality scores can potentially be related to epidemiological data on psychiatric disorders, and dimensional personality models have implications for psychiatric diagnosis and treatment around the world. PMID:17128620

[Food, health claims and drugs. Conclusions - recommendations. The National Academy of Pharmacy].

PubMed

Bourlioux, P

2008-01-01

Even if the activity of health claim foods is not relevant to the activity of drugs, we are just at the frontier of two fields which needs the greatest attention. Since foods and drugs are present in the same domain of prevention, the French Academy of Pharmacy draws attention on the necessary relevant and scientifically proven demonstration of the health claims using the same quality standard than those used for drugs (good clinical practises, methodologies correspondent to the current requirement, etc.). It is why the Academy wishes to express five recommendations fearing that the risks of confusion and abuse prevail on the possibilities of information and control. Make sure that foods are not mistaken with drugs; largely spread the lists of authorised claims; introduce the new notion of "nutrivigilance"; make sure that the only authorised health claims use advertising; reject the terms "alicaments" and "nutraceuticals" which are confusing with drugs.

Medical Emergency Exceptions in State Abortion Statutes: The Statistical Record.

PubMed

Linton, Paul Benjamin

2016-01-01

This article attempts to determine, first, whether emergency exceptions in statutes regulating abortion have been abused and, second, whether the standard used in such an exception--subjective or objective--makes a difference in the reported incidence of such emergencies. A review of the statistical data supports two conclusions. First, physicians who perform abortions and have complied with state reporting requirements have not relied upon the medical emergency exceptions in state abortion statutes to evade the requirements of those statutes. Second, the use of an objective standard for evaluating medical emergencies ("reasonable medical judgment") has not been associated with fewer reported emergencies (per number of abortions performed) than the use of a subjective standard ("good faith clinical judgment"). Both of these conclusions may be relevant in drafting other abortion statutes including prohibitions (e.g., post-viability abortions).

RECOVER evidence and knowledge gap analysis on veterinary CPR. Part 6: Post-cardiac arrest care.

PubMed

Smarick, Sean D; Haskins, Steve C; Boller, Manuel; Fletcher, Daniel J

2012-06-01

To systematically examine the evidence for interventions after the return of spontaneous circulation (ROSC) on outcomes from veterinary cardiopulmonary resuscitation and to determine important knowledge gaps. Standardized, systematic evaluation of the literature, categorization of relevant articles according to level of evidence and quality, and development of consensus on conclusions for application of the concepts to clinical post-cardiac arrest care. Academia, referral practice, and general practice. Fifteen standardized clinical questions important for post-cardiac arrest care were asked and research articles relevant to answering these questions were identified through structured, explicit literature database searches. The majority of these articles report research in species other than dogs or cats or consisted of experimental work in canine cardiac arrest models. Outcome metrics reported in these studies widely varied and ranged from quantification of mechanistic endpoints, such as elaboration of reactive oxygen species, to survival, and functional neurologic outcome. Despite the near complete absence of clinical veterinary studies, the process allowed the formulation of statements for several postcardiac arrest treatments that were either supportive, such as mild therapeutic hypothermia or controlled reoxygenation, or neutral, such as for mannitol administration or seizure prophylaxis. Evidence grading allowed transparency in regards to the strength of these recommendations. Moreover, numerous knowledge gaps emerged that will allow generation of a road map for progress in veterinary post-cardiac arrest care. © Veterinary Emergency and Critical Care Society 2012.

Audit of practice in sudden unexpected death in epilepsy (SUDEP) post mortems and neuropathological findings

PubMed Central

Michalak, Zuzanna; Wright, Gabriella; Dawson, Timothy; Hilton, David; Joshi, Abhijit; Diehl, Beate; Koepp, Matthias; Lhatoo, Samden; Sander, Josemir W.; Sisodiya, Sanjay M.

2015-01-01

Aims Sudden unexpected death in epilepsy (SUDEP) is one of the leading causes of death in people with epilepsy. For classification of definite SUDEP, a post mortem (PM), including anatomical and toxicological examination, is mandatory to exclude other causes of death. We audited PM practice as well as the value of brain examination in SUDEP. Methods We reviewed 145 PM reports in SUDEP cases from four UK neuropathology centres. Data were extracted for clinical epilepsy details, circumstances of death and neuropathological findings. Results Macroscopic brain abnormalities were identified in 52% of cases. Mild brain swelling was present in 28%, and microscopic pathologies relevant to cause or effect of seizures were seen in 89%. Examination based on whole fixed brains (76.6% of all PMs), and systematic regional sampling was associated with higher detection rates of underlying pathology (P < 0.01). Information was more frequently recorded regarding circumstances of death and body position/location than clinical epilepsy history and investigations. Conclusion Our findings support the contribution of examination of the whole fixed brain in SUDEP, with high rates of detection of relevant pathology. Availability of full clinical epilepsy‐related information at the time of PM could potentially further improve detection through targeted tissue sampling. Apart from confirmation of SUDEP, complete neuropathological examination contributes to evaluation of risk factors as well as helping to direct future research into underlying causes. PMID:26300477

Practical considerations for volumetric wear analysis of explanted hip arthroplasties

PubMed Central

Langton, D. J.; Sidaginamale, R. P.; Holland, J. P.; Deehan, D.; Joyce, T. J.; Nargol, A. V. F.; Meek, R. D.; Lord, J. K.

2014-01-01

Objectives Wear debris released from bearing surfaces has been shown to provoke negative immune responses in the recipient. Excessive wear has been linked to early failure of prostheses. Analysis using coordinate measuring machines (CMMs) can provide estimates of total volumetric material loss of explanted prostheses and can help to understand device failure. The accuracy of volumetric testing has been debated, with some investigators stating that only protocols involving hundreds of thousands of measurement points are sufficient. We looked to examine this assumption and to apply the findings to the clinical arena. Methods We examined the effects on the calculated material loss from a ceramic femoral head when different CMM scanning parameters were used. Calculated wear volumes were compared with gold standard gravimetric tests in a blinded study. Results Various scanning parameters including point pitch, maximum point to point distance, the number of scanning contours or the total number of points had no clinically relevant effect on volumetric wear calculations. Gravimetric testing showed that material loss can be calculated to provide clinically relevant degrees of accuracy. Conclusions Prosthetic surfaces can be analysed accurately and rapidly with currently available technologies. Given these results, we believe that routine analysis of explanted hip components would be a feasible and logical extension to National Joint Registries. Cite this article: Bone Joint Res 2014;3:60–8. PMID:24627327

The Netherlands XTC Toxicity (NeXT) study: objectives and methods of a study investigating causality, course, and clinical relevance.

PubMed

De Win, Maartje M L; Jager, Gerry; Vervaeke, Hylke K E; Schilt, Thelma; Reneman, Liesbeth; Booij, Jan; Verhulst, Frank C; Den Heeten, Gerard J; Ramsey, Nick F; Korf, Dirk J; Van den Brink, Wim

2005-01-01

This paper describes the objectives and methods of The Netherlands XTC Toxicity (NeXT) study focussing on the causality, course, and clinical relevance of ecstasy neurotoxicity. Previous studies suggest that ecstasy (3,4 methylene-dioxymethamphetamine, MDMA, XTC) is toxic toward brain serotonin axons, but most of these studies have serious methodological limitations. The current study is a combination of different approaches with three substudies: (1) a crosssectional substudy among heavy ecstasy users and controls with variation in drug use, which will provide information about potential neurotoxic consequences of ecstasy in relation to other drugs; (2) a prospective cohort substudy in ecstasy-naive subjects with high risk for future ecstasy use, which will provide information on the causality and short-term course of ecstasy use and potential neurotoxicity, and (3) a retrospective cohort substudy in lifetime ecstasy users and matched controls of an existing epidemiological sample that will provide information on long-term course and outcome of ecstasy use in the general population. Neurotoxicity is studied using (a) different imaging techniques (beta-CIT SPECT, 1H-MR spectroscopy, diffusion tensor imaging, perfusion weighted imaging and functional magnetic resonance imaging), and (b) neuropsychological and psychiatric assessments of memory, depression, and personality. The combined results will lead to conclusions that can be used in prevention messages, clinical decision making, and the development of an (inter)national ecstasy policy.

Anti-citrullinated peptide antibodies are the strongest predictor of clinically relevant radiographic progression in rheumatoid arthritis patients achieving remission or low disease activity: A post hoc analysis of a nationwide cohort in Japan

PubMed Central

Okada, Akitomo; Fukuda, Takaaki; Hidaka, Toshihiko; Ishii, Tomonori; Ueki, Yukitaka; Kodera, Takao; Nakashima, Munetoshi; Takahashi, Yuichi; Honda, Seiyo; Horai, Yoshiro; Watanabe, Ryu; Okuno, Hiroshi; Aramaki, Toshiyuki; Izumiyama, Tomomasa; Takai, Osamu; Miyashita, Taiichiro; Sato, Shuntaro; Kawashiri, Shin-ya; Iwamoto, Naoki; Ichinose, Kunihiro; Tamai, Mami; Origuchi, Tomoki; Nakamura, Hideki; Aoyagi, Kiyoshi; Eguchi, Katsumi; Kawakami, Atsushi

2017-01-01

Objectives To determine prognostic factors of clinically relevant radiographic progression (CRRP) in patients with rheumatoid arthritis (RA) achieving remission or low disease activity (LDA) in clinical practice. Methods Using data from a nationwide, multicenter, prospective study in Japan, we evaluated 198 biological disease-modifying antirheumatic drug (bDMARD)-naïve RA patients who were in remission or had LDA at study entry after being treated with conventional synthetic DMARDs (csDMARDs). CRRP was defined as the yearly progression of modified total Sharp score (mTSS) >3.0 U. We performed a multiple logistic regression analysis to explore the factors to predict CRRP at 1 year. We used receiver operating characteristic (ROC) curve to estimate the performance of relevant variables for predicting CRRP. Results The mean Disease Activity Score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) was 2.32 ± 0.58 at study entry. During the 1-year observation, remission or LDA persisted in 72% of the patients. CRRP was observed in 7.6% of the patients. The multiple logistic regression analysis revealed that the independent variables to predict the development of CRRP were: anti-citrullinated peptide antibodies (ACPA) positivity at baseline (OR = 15.2, 95%CI 2.64–299), time-integrated DAS28-ESR during the 1 year post-baseline (7.85-unit increase, OR = 1.83, 95%CI 1.03–3.45), and the mTSS at baseline (13-unit increase, OR = 1.22, 95%CI 1.06–1.42). Conclusions ACPA positivity was the strongest independent predictor of CRRP in patients with RA in remission or LDA. Physicians should recognize ACPA as a poor-prognosis factor regarding the radiographic outcome of RA, even among patients showing a clinically favorable response to DMARDs. PMID:28505163

Real-time feedback to improve gait in children with cerebral palsy.

PubMed

van Gelder, Linda; Booth, Adam T C; van de Port, Ingrid; Buizer, Annemieke I; Harlaar, Jaap; van der Krogt, Marjolein M

2017-02-01

Real-time feedback may be useful for enhancing information gained from clinical gait analysis of children with cerebral palsy (CP). It may also be effective in functional gait training, however, it is not known if children with CP can adapt gait in response to real-time feedback of kinematic parameters. Sixteen children with cerebral palsy (age 6-16; GMFCS I-III), walking with a flexed-knee gait pattern, walked on an instrumented treadmill with virtual reality in three conditions: regular walking without feedback (NF), feedback on hip angle (FH) and feedback on knee angle (FK). Clinically relevant gait parameters were calculated and the gait profile score (GPS) was used as a measure of overall gait changes between conditions. All children, except one, were able to improve hip and/or knee extension during gait in response to feedback, with nine achieving a clinically relevant improvement. Peak hip extension improved significantly by 5.1±5.9° (NF: 8.9±12.8°, FH: 3.8±10.4°, p=0.01). Peak knee extension improved significantly by 7.7±7.1° (NF: 22.2±12.0°, FK: 14.5±12.7°, p<0.01). GPS did not change between conditions due to increased deviations in other gait parameters. Responders to feedback were shown to have worse initial gait as measured by GPS (p=0.005) and functional selectivity score (p=0.049). In conclusion, ambulatory children with CP show adaptability in gait and are able to respond to real-time feedback, resulting in significant and clinically relevant improvements in peak hip and knee extension. These findings show the potential of real-time feedback as a tool for functional gait training and advanced gait analysis in CP. Copyright © 2016 Elsevier B.V. All rights reserved.

Clinical Relevance of Vilazodone Treatment in Patients With Major Depressive Disorder: Categorical Improvement in Symptoms

PubMed Central

Culpepper, Larry; Mathews, Maju; Ghori, Razi; Edwards, John

2014-01-01

Objective: To assess clinically relevant symptom improvement in patients with major depressive disorder (MDD) receiving vilazodone by using the Montgomery-Asberg Depression Rating Scale (MADRS), a clinician-rated scale used to measure MDD symptom severity and improvement. Method: Pooled data from 2 positive, phase 3, 8-week, double-blind, randomized, placebo-controlled trials in patients with MDD were analyzed. Patients received vilazodone 40 mg/d or placebo; post hoc analyses were conducted on study completers. Depression symptom improvement was evaluated by analyzing the proportions of patients who shifted from the baseline MADRS single-item symptom severity category of ≥ 2 (mild to severe symptoms) to an end-of-study category < 2 (minimal to no symptoms) or from ≥ 4 (moderate to severe symptoms) to ≤ 2 (mild to no symptoms). The proportion of patients who shifted from anxious depression to no anxious depression was also analyzed. Results: The percentage of patients who completed these studies with severity category shift from baseline ≥ 2 to end of study < 2 was significantly higher for vilazodone versus placebo on all MADRS items (odds ratio [OR] range, 1.4–1.7, P < .05) except reduced appetite (OR = 1.3, P = .232). A significantly greater proportion of vilazodone-treated versus placebo-treated patients shifted from baseline ≥ 4 to end of study ≤ 2 on MADRS items of apparent sadness, reported sadness, inner tension, reduced sleep, and lassitude (OR range, 1.5–2.0, P < .05). Additionally, a significantly greater proportion of vilazodone-treated versus placebo-treated patients shifted from anxious depression at baseline to no anxious depression at end of study (OR = 1.5, P = .031). Conclusions: These results suggest that vilazodone treatment is associated with clinically relevant changes in depression symptoms in patients with MDD. Trial Registration: ClinicalTrials.gov identifiers: NCT00285376 and NCT00683592 PMID:24940525

Systematic review on the recurrence of postoperative nausea and vomiting after a first episode in the recovery room – implications for the treatment of PONV and related clinical trials

PubMed Central

Eberhart, Leopold HJ; Frank, Silke; Lange, Henning; Morin, Astrid M; Scherag, André; Wulf, Hinnerk; Kranke, Peter

2006-01-01

Background Despite the presence of a plethora of publications on the prevention of postoperative nausea and vomiting (PONV) only little is known how to treat established symptoms. Besides the high effort of performing these efficacy trials (much more patients must give their consent than are actually included in a study) and ethical concerns, little is known about the rate of re-occurring PONV/vomiting after placebo. As a consequence investigators will have difficulties defining a clinically relevant effect for the new treatment which is crucial for any planning. A quantitative systematic review was performed in order to provide more reliable estimates of the incidence of re-occurring PONV/vomiting after placebo and to help investigators defining a clinically relevant treatment effect. Methods A systematic search of the literature was performed using an extended search strategy of a previous review. Data on the recurrence of PONV (any nausea or emetic symptom) and vomiting (retching or vomiting) was extracted from published reports treating PONV with placebo and unpublished results from two observational trials where no treatment was given. A nonlinear random effects model was used to calculate estimates of the recurrence of symptoms and their 95%-confidence intervals (95%-CI). Results A total of 29 trials (including the unpublished data) were eligible for the calculations. Depending on the length of observation after administering placebo or no treatment the recurrence rate of PONV was between 65% (95%-CI: 53%...75%) and 84% (95%-CI: 73%...91%) and that of vomiting was between 65% (95%-CI: 44%...81%) and 78% (95%-CI: 59%...90%). Conclusion Almost all trials showed a considerable and consistently high rate of recurrence of emetic symptoms after placebo highlighting the need for a consequent antiemetic treatment. Future (placebo) controlled efficacy trials may use the presented empirical estimates for defining clinically relevant effects and for statistical power considerations. PMID:17166262

Free software to analyse the clinical relevance of drug interactions with antiretroviral agents (SIMARV®) in patients with HIV/AIDS.

PubMed

Giraldo, N A; Amariles, P; Monsalve, M; Faus, M J

Highly active antiretroviral therapy has extended the expected lifespan of patients with HIV/AIDS. However, the therapeutic benefits of some drugs used simultaneously with highly active antiretroviral therapy may be adversely affected by drug interactions. The goal was to design and develop a free software to facilitate analysis, assessment, and clinical decision making according to the clinical relevance of drug interactions in patients with HIV/AIDS. A comprehensive Medline/PubMed database search of drug interactions was performed. Articles that recognized any drug interactions in HIV disease were selected. The publications accessed were limited to human studies in English or Spanish, with full texts retrieved. Drug interactions were analyzed, assessed, and grouped into four levels of clinical relevance according to gravity and probability. Software to systematize the information regarding drug interactions and their clinical relevance was designed and developed. Overall, 952 different references were retrieved and 446 selected; in addition, 67 articles were selected from the citation lists of identified articles. A total of 2119 pairs of drug interactions were identified; of this group, 2006 (94.7%) were drug-drug interactions, 1982 (93.5%) had an identified pharmacokinetic mechanism, and 1409 (66.5%) were mediated by enzyme inhibition. In terms of clinical relevance, 1285 (60.6%) drug interactions were clinically significant in patients with HIV (levels 1 and 2). With this information, a software program that facilitates identification and assessment of the clinical relevance of antiretroviral drug interactions (SIMARV ® ) was developed. A free software package with information on 2119 pairs of antiretroviral drug interactions was designed and developed that could facilitate analysis, assessment, and clinical decision making according to the clinical relevance of drug interactions in patients with HIV/AIDS. Copyright © 2016 Elsevier Inc. All rights reserved.

Cognitive conflicts in major depression: Between desired change and personal coherence

PubMed Central

Feixas, Guillem; Montesano, Adrián; Compañ, Victoria; Salla, Marta; Dada, Gloria; Pucurull, Olga; Trujillo, Adriana; Paz, Clara; Muñoz, Dámaris; Gasol, Miquel; Saúl, Luis Ángel; Lana, Fernando; Bros, Ignasi; Ribeiro, Eugenia; Winter, David; Carrera-Fernández, María Jesús; Guàrdia, Joan

2014-01-01

Objectives The notion of intrapsychic conflict has been present in psychopathology for more than a century within different theoretical orientations. However, internal conflicts have not received enough empirical attention, nor has their importance in depression been fully elaborated. This study is based on the notion of cognitive conflict, understood as implicative dilemma (ID), and on a new way of identifying these conflicts by means of the Repertory Grid Technique. Our aim was to explore the relevance of cognitive conflicts among depressive patients. Design Comparison between persons with a diagnosis of major depressive disorder and community controls. Methods A total of 161 patients with major depression and 110 non-depressed participants were assessed for presence of IDs and level of symptom severity. The content of these cognitive conflicts was also analysed. Results Repertory grid analysis indicated conflict (presence of ID/s) in a greater proportion of depressive patients than in controls. Taking only those grids with conflict, the average number of IDs per person was higher in the depression group. In addition, participants with cognitive conflicts displayed higher symptom severity. Within the clinical sample, patients with IDs presented lower levels of global functioning and a more frequent history of suicide attempts. Conclusions Cognitive conflicts were more prevalent in depressive patients and were associated with clinical severity. Conflict assessment at pre-therapy could aid in treatment planning to fit patient characteristics. Practitioner points Internal conflicts have been postulated in clinical psychology for a long time but there is little evidence about its relevance due to the lack of methods to measure them. We developed a method for identifying conflicts using the Repertory Grid Technique. Depressive patients have higher presence and number of conflicts than controls. Conflicts (implicative dilemmas) can be a new target for intervention in depression. Cautions/Limitations A cross-sectional design precluded causal conclusions. The role of implicative dilemmas in the causation or maintenance of depression cannot be ascertained from this study. PMID:24734969

Symbrachydactyly.

PubMed

Goodell, Parker B; Bauer, Andrea S; Sierra, Francisco J A; James, Michelle A

2016-09-01

Background: Symbrachydactyly is a unilateral congenital hand malformation characterized by failure of formation of fingers and the presence of rudimentary digit nubbins. The management is variable and are investigated in this review. Methods: A detailed review of the literature was compiled into succinct clinically relevant categories. Results: Etiology, classification, non-surgical management, surgical intervention, and patient oriented outcomes are discussed. Conclusions: All interventions should prioritize realistic, evidence-supported appearance and functional gains. Studies of the baseline function and quality of life of children with symbrachydactyly would allow surgeons to better understand functional changes associated with various interventions and would help surgeons and parents to make the best treatment decisions.

[Highlights of hospital-based internal medicine in 2010: chief residents' perspective].

PubMed

Uhlmann, Marc; Burnard, Jérôme; Cosma Rochat, Monica; Gabus, Vincent; Micheloud, Valérie Geiser; Gobin, Niels; Laurent, Jean-Christophe; Marino, Laura; Méan, Marie; Merz, Laurent; Regamey, Julien; Stadelmann, Raphaël

2011-02-02

Applying knowledge acquired from recent medical studies to patient care poses a daily challenge to physicians. Chief residents from the Department of Internal Medicine at the University Hospital of Lausanne carried out a review of some of the issues they considered important. The conclusions of these various publications may have a significant impact on the daily practice of hospital-based internal medicine. Modern medicine based on scientific studies is a reminder that in spite of the essential importance of clinical experience, it is crucial to confront it with the results of relevant publications from the medical literature.

Clinically-relevant consecutive treatment with isoproterenol and adenosine protects the failing heart against ischaemia and reperfusion

PubMed Central

2014-01-01

Background Consecutive treatment of normal heart with a high dose of isoproterenol and adenosine (Iso/Ade treatment), confers strong protection against ischaemia/reperfusion injury. In preparation for translation of this cardioprotective strategy into clinical practice during heart surgery, we further optimised conditions for this intervention using a clinically-relevant dose of Iso and determined its cardioprotective efficacy in hearts isolated from a model of surgically-induced heart failure. Methods Isolated Langendorff-perfused rat hearts were treated sequentially with 5 nM Iso and 30 μM Ade followed by different durations of washout prior to 30 min global ischaemia and 2 hrs reperfusion. Reperfusion injury was assessed by measuring haemodynamic function, lactate dehydrogenase (LDH) release and infarct size. Protein kinase C (PKC) activity and glycogen content were measured in hearts after the treatment. In a separate group of hearts, Cyclosporine A (CsA), a mitochondria permeability transition pore (MPTP) inhibitor, was added with Iso/Ade. Failing hearts extracted after 16 weeks of ligation of left coronary artery in 2 months old rats were also subjected to Iso/Ade treatment followed by ischaemia/reperfusion. Results Recovery of the rate pressure product (RPP) in Iso/Ade-treated hearts was significantly higher than in controls. Thus in Iso/Ade treated hearts with 5 nM Iso and no washout period, RPP recovery was 76.3 ± 6.9% of initial value vs. 28.5 ± 5.2% in controls. This was associated with a 3 fold reduction in LDH release irrespective to the duration of the washout period. Hearts with no washout of the drugs (Ade) had least infarct size, highest PKC activity and also showed reduced glycogen content. Cardioprotection with CsA was not additive to the effect of Iso/Ade treatment. Iso/Ade treatment conferred significant protection to failing hearts. Thus, RPP recovery in failing hearts subjected to the treatment was 69.0 ± 16.3% while in Control hearts 19.7 ± 4.0%. LDH release in these hearts was also 3 fold lower compared to Control. Conclusions Consecutive Iso/Ade treatment of normal heart can be effective at clinically-relevant doses and this effect appears to be mediated by glycogen depletion and inhibition of MPTP. This intervention protects clinically relevant failing heart model making it a promising candidate for clinical use. PMID:24885907

Clinicomanometric factors associated with clinically relevant esophagogastric junction outflow obstruction from the Sandhill high-resolution manometry system.

PubMed

Song, B G; Min, Y W; Lee, H; Min, B-H; Lee, J H; Rhee, P-L; Kim, J J

2018-03-01

Integrated relaxation pressure (IRP) is a key metric for diagnosing esophagogastric junction outflow obstruction (EGJOO). However, its normal value might be different according to the manufacturer of high-resolution manometry (HRM). This study aimed to investigate optimal value of IRP for diagnosing EGJOO in Sandhill HRM and to find clinicomanometric variables to segregate clinically relevant EGJOO. We analyzed 262 consecutive subjects who underwent HRM between June 2011 and December 2016 showing elevated median IRP (> 15 mm Hg) but did not satisfy criteria for achalasia. Clinically relevant subjects were defined as follows: (i) subsequent HRM met achalasia criteria during follow-up (early achalasia); (ii) Eckardt score was decreased at least two points without exceeding a score of 3 after pneumatic dilatation (variant achalasia); and (iii) significant passage disturbance on esophagogram without structural abnormality (possible achalasia). Seven subjects were clinically relevant, including two subjects with early achalasia, four subjects with variant achalasia, and one subject with possible achalasia. All clinically relevant subjects had IRP 20 mm Hg or above. Among subjects (n = 122) with IRP 20 mm Hg or more, clinically relevant group (n = 7) had significantly higher rate of dysphagia (100% vs 24.3%, P < .001) and compartmentalized pressurization (85.7% vs 21.7%, P = .001) compared to clinically non-relevant group (n = 115). Our results suggest that IRP of 20 mm Hg or higher could segregate clinically relevant subjects showing EGJOO in Sandhill HRM. Additionally, if subjects have both dysphagia and compartmentalized pressurization, careful follow-up is essential. © 2017 John Wiley & Sons Ltd.

Dignity in end-of-life care: results of a national survey of US physicians

PubMed Central

Antiel, Ryan M.; Curlin, Farr A.; James, Katherine M.; Sulmasy, Daniel P.; Tilburt, Jon C.

2014-01-01

Context Debates persist about the relevance of “dignity” as an ethical concept in US healthcare, especially in end-of-life care. Objective To describe the attitudes and beliefs regarding the usefulness and meaning of the concept of dignity and to examine judgments about a clinical scenario in which dignity might be relevant. Methods 2000 practicing U.S. physicians, from all specialties, were mailed a survey. Main measures included physician’s judgments about an end-of-life clinical scenario (criterion variable), attitudes about the concept of dignity (predictors), and their religious characteristics (predictors). Results 1032 eligible physicians (54%) responded. Nine out of ten (90%) physicians reported that dignity was relevant to their practice. After controlling for age, gender, region, and specialty, physicians who judged that the case patient had either some dignity or full dignity, and who agreed that dignity is given by a creator, were all positively associated with believing that the patient’s life was worth living [OR 10.2 (5.8–17.8), OR 20.5 (11.4–36.8), OR 4.7 (3.1–7.0), respectively]. Respondents who strongly agreed that “all living humans have the same amount of dignity” were also more likely to believe that the patient’s life was worth living [OR 1.8 (1.2–2.7)]. Religious characteristics were also associated with believing that the case patient’s life was worth living [OR 4.1 (2.4–7.2), OR 3.2 (1.6–6.3), OR 9.2 (4.3–19.5), respectively]. Conclusion US physicians view the concept of dignity as useful. Those views are associated with their judgments about common end-of-life scenarios in which dignity concepts may be relevant. PMID:22762966

Researchers’ and Clinicians’ Perceptions of Recruiting Participants to Clinical Research: A Thematic Meta-Synthesis

PubMed Central

Newington, Lisa; Metcalfe, Alison

2014-01-01

Background Recruiting the desired number of research participants is frequently problematic with resulting financial and clinical implications. The views of individuals responsible for participant recruitment have not been previously reviewed. This systematic review and thematic meta-synthesis explores researchers’ and clinicians’ experiences and perceptions of recruiting participants to clinical research, with the aim of informing improved recruitment systems and strategies. Methods Studies published between January 1995 and May 2013 were identified from: Ovid MEDLINE, Ovid EMBASE, Ovid PSYCHINFO, ASSIA, British Nursing Index, Scopus, Web of Science, CINAHL and PubMed. Included studies were original peer reviewed research, with qualitative methodologies and an aim of exploring the views of clinicians and/or researchers on recruitment to clinical research. Studies discussing the recruitment of patients unable to give informed consent were excluded. The findings sections of the relevant studies were free coded to identify key concepts which were grouped into hierarchical themes. The quality of the identified studies was assessed and the relative contribution of each paper was checked to ensure individual studies did not dominate in any theme. Results Eighteen relevant papers were identified which examined the views of researchers and clinicians in 10 clinical specialties. Five main themes emerged: building a research community, securing resources, the nature of research, professional identities and recruitment strategies. The views of researchers and clinicians were similar, although the role of ‘researcher’ was inconsistently defined. Conclusions The general experience of recruiting participants to clinical research was one of competition and compromise. Competition arose over funding, staffing and participants, and between clinical and research responsibilities. Compromise was needed to create study designs that were acceptable to patients, clinicians and researchers. Forging relationships between clinical and research teams featured extensively, however the involvement of patients and the public within the research community was rarely discussed. PMID:24734142

Team-based efforts to improve quality of care, the fundamental role of ethics, and the responsibility of health managers: monitoring and management strategies to enhance teamwork.

PubMed

Kossaify, A; Hleihel, W; Lahoud, J-C

2017-12-01

Highlight the importance of teamwork in health care institutions by performing a review and discussion of the relevant literature. Review paper. A MEDLINE/Pubmed search was performed starting from 1990, and the terms 'team, teamwork, managers, healthcare, and cooperation' were searched in titles, abstracts, keywords, and conclusions; other terms 'patient safety, ethics, audits and quality of care' were specifically searched in abstracts and were used as additional filters criteria to select relevant articles. Thirty-three papers were found relevant; factors affecting the quality of care in health care institutions are multiple and varied, including issues related to individual profile, to administrative structure and to team-based effort. Issues affecting teamwork include mainly self-awareness, work environment, leadership, ethics, cooperation, communication, and competition. Moreover, quality improvement plans aiming to enhance and expand teams are essential in this context. Team monitoring and management are vital to achieve efficient teamwork with all the required qualities for a safer health system. In all cases, health managers' responsibility plays a fundamental role in creating and sustaining a teamwork atmosphere. Teamwork is known to improve outcomes in medicine, whether at the clinical, organizational, or scientific level. Teamwork in health care institutions must increasingly be encouraged, given that individual effort is often insufficient for optimal clinical outcome. Copyright © 2017 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

[Terbinafine : Relevant drug interactions and their management].

PubMed

Dürrbeck, A; Nenoff, P

2016-09-01

The allylamine terbinafine is the probably most frequently prescribed systemic antifungal agent in Germany for the treatment of dermatomycoses and onychomycoses. According to the German drug law, terbinafine is approved for patients who are 18 years and older; however, this antifungal agent is increasingly used off-label for treatment of onychomycoses and tinea capitis in children. Terbinafine is associated with only a few interactions with other drugs, which is why terbinafine can generally be used without problems in older and multimorbid patients. Nevertheless, some potential interactions of terbinafine with certain drug substances are known, including substances of the group of antidepressants/antipsychotics and some cardiovascular drugs. Decisive for the relevance of interactions is-along with the therapeutic index of the substrate and the possible alternative degradation pathways-the genetically determined type of metabolism. When combining terbinafine with tricyclic antidepressants or selective serotonin reuptake inhibitors and serotonin/noradrenalin reuptake inhibitors, the clinical response and potential side effects must be monitored. Problematic is the use of terbinafine with simultaneous treatment with tamoxifen. The administration of potent CYP2D6 inhibitors leads to a diminished efficacy of tamoxifen because one of its most important active metabolites-endoxifen-is not sufficiently available. Therefore, combination of tamoxifen and terbinafine should be avoided. In conclusion, the number of substances which are able to cause clinically relevant interactions in case of simultaneously administration with terbinafine is clear and should be manageable in the dermatological office with adequate monitoring.

The DOD Humanitarian and Civic Assistance Program Concepts, Trends, Medical Challenges

DTIC Science & Technology

1997-03-01

program improvements; measuring program performance and effectiveness; and defining military roles relevant to training, long term benefits, and the...support conclusions relevant to trends, benefits, challenges, suggested improvements, and suggested areas for future research. 15. SUBJECT TERMS 16...a Long Term Medical Benefit ................ 28 CONCLUSION

In Defense of a Social Value Requirement for Clinical Research

PubMed Central

Wendler, David; Rid, Annette

2017-01-01

Many guidelines and commentators endorse the view that clinical research is ethically acceptable only when it has social value, in the sense of collecting data which might be used to improve health. A version of this social value requirement is included in the Declaration of Helsinki and the Nuremberg Code, and is codified in many national research regulations. At the same time, there have been no systematic analyses of why social value is an ethical requirement for clinical research. Recognizing this gap in the literature, recent articles by Alan Wertheimer and David Resnik argue that the extant justifications for the social value requirement are unpersuasive. Both authors conclude, contrary to almost all current guidelines and regulations, that it can be acceptable across a broad range of cases to conduct clinical research which is known prospectively to have no social value. The present paper assesses this conclusion by critically evaluating the ethical and policy considerations relevant to the claim that clinical research must have social value. This analysis supports the standard view that social value is an ethical requirement for the vast majority of clinical research studies and should be mandated by applicable guidelines and policies. PMID:28060427

In Defense of a Social Value Requirement for Clinical Research.

PubMed

Wendler, David; Rid, Annette

2017-02-01

Many guidelines and commentators endorse the view that clinical research is ethically acceptable only when it has social value, in the sense of collecting data which might be used to improve health. A version of this social value requirement is included in the Declaration of Helsinki and the Nuremberg Code, and is codified in many national research regulations. At the same time, there have been no systematic analyses of why social value is an ethical requirement for clinical research. Recognizing this gap in the literature, recent articles by Alan Wertheimer and David Resnik argue that the extant justifications for the social value requirement are unpersuasive. Both authors conclude, contrary to almost all current guidelines and regulations, that it can be acceptable across a broad range of cases to conduct clinical research which is known prospectively to have no social value. The present article assesses this conclusion by critically evaluating the ethical and policy considerations relevant to the claim that clinical research must have social value. This analysis supports the standard view that social value is an ethical requirement for the vast majority of clinical research studies and should be mandated by applicable guidelines and policies. © 2017 John Wiley & Sons Ltd.

Generalised joint hypermobility and neurodevelopmental traits in a non-clinical adult population

PubMed Central

Glans, Martin; Humble, Mats B.

2017-01-01

Background Generalised joint hypermobility (GJH) is reportedly overrepresented among clinical cases of attention deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and developmental coordination disorder (DCD). It is unknown if these associations are dimensional and, therefore, also relevant among non-clinical populations. Aims To investigate if GJH correlates with sub-syndromal neurodevelopmental symptoms in a normal population. Method Hakim-Grahame’s 5-part questionnaire (5PQ) on GJH, neuropsychiatric screening scales measuring ADHD and ASD traits, and a DCD-related question concerning clumsiness were distributed to a non-clinical, adult, Swedish population (n=1039). Results In total, 887 individuals met our entry criteria. We found no associations between GJH and sub-syndromal symptoms of ADHD, ASD or DCD. Conclusions Although GJH is overrepresented in clinical cases with neurodevelopmental disorders, such an association seems absent in a normal population. Thus, if GJH serves as a biomarker cutting across diagnostic boundaries, this association is presumably limited to clinical populations. Declaration of interest None. Copyright and usage © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license. PMID:28959454

Prenatal Antidepressant Exposure: Clinical and Preclinical Findings

PubMed Central

Bourke, Chase H.; Stowe, Zachary N.

2014-01-01

Pharmacological treatment of any maternal illness during pregnancy warrants consideration of the consequences of the illness and/or medication for both the mother and unborn child. In the case of major depressive disorder, which affects up to 10–20% of pregnant women, the deleterious effects of untreated depression on the offspring can be profound and long lasting. Progress has been made in our understanding of the mechanism(s) of action of antidepressants, fetal exposure to these medications, and serotonin’s role in development. New technologies and careful study designs have enabled the accurate sampling of maternal serum, breast milk, umbilical cord serum, and infant serum psychotropic medication concentrations to characterize the magnitude of placental transfer and exposure through human breast milk. Despite this progress, the extant clinical literature is largely composed of case series, population-based patient registry data that are reliant on nonobjective means and retrospective recall to determine both medication and maternal depression exposure, and limited inclusion of suitable control groups for maternal depression. Conclusions drawn from such studies often fail to incorporate embryology/neurotransmitter ontogeny, appropriate gestational windows, or a critical discussion of statistically versus clinically significant. Similarly, preclinical studies have predominantly relied on dosing models, leading to exposures that may not be clinically relevant. The elucidation of a defined teratological effect or mechanism, if any, has yet to be conclusively demonstrated. The extant literature indicates that, in many cases, the benefits of antidepressant use during pregnancy for a depressed pregnant woman may outweigh potential risks. PMID:24567054

The Traditional Chinese Medicine and Relevant Treatment for the Efficacy and Safety of Atopic Dermatitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

PubMed Central

Shi, Zhao-feng; Song, Tie-bing; Xie, Juan; Yan, Yi-quan

2017-01-01

Background Atopic dermatitis (AD) has become a common skin disease that requires systematic and comprehensive treatment to achieve adequate clinical control. Traditional Chinese medicines and related treatments have shown clinical effects for AD in many studies. But the systematic reviews and meta-analyses for them are lacking. Objective The systematic review and meta-analysis based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement were conducted to evaluate the efficacy and safety of traditional Chinese medicines and related treatments for AD treatment. Methods Randomized controlled trials (RCTs) were searched based on standardized searching rules in eight medical databases from the inception up to December 2016 and a total of 24 articles with 1,618 patients were enrolled in this meta-analysis. Results The results revealed that traditional Chinese medicines and related treatments did not show statistical differences in clinical effectiveness, SCORAD amelioration, and SSRI amelioration for AD treatment compared with control group. However, EASI amelioration of traditional Chinese medicines and related treatments for AD was superior to control group. Conclusion We need to make conclusion cautiously for the efficacy and safety of traditional Chinese medicine and related treatment on AD therapy. More standard, multicenter, double-blind randomized controlled trials (RCTs) of traditional Chinese medicine and related treatment for AD were required to be conducted for more clinical evidences providing in the future. PMID:28713436

Trustworthiness and relevance in web-based clinical question answering.

PubMed

Cruchet, Sarah; Boyer, Célia; van der Plas, Lonneke

2012-01-01

Question answering systems try to give precise answers to a user's question posed in natural language. It is of utmost importance that the answers returned are relevant to the user's question. For clinical QA, the trustworthiness of answers is another important issue. Limiting the document collection to certified websites helps to improve the trustworthiness of answers. On the other hand, limited document collections are known to harm the relevancy of answers. We show, however, in a comparative evaluation, that promoting trustworthiness has no negative effect on the relevance of the retrieved answers in our clinical QA system. On the contrary, the answers found are in general more relevant.

Development of a national audit tool for juvenile idiopathic arthritis: a BSPAR project funded by the Health Care Quality Improvement Partnership

PubMed Central

McErlane, Flora; Foster, Helen E; Armitt, Gillian; Bailey, Kathryn; Cobb, Joanna; Davidson, Joyce E; Douglas, Sharon; Fell, Andrew; Friswell, Mark; Pilkington, Clarissa; Strike, Helen; Smith, Nicola; Thomson, Wendy; Cleary, Gavin

2018-01-01

Abstract Objective Timely access to holistic multidisciplinary care is the core principle underpinning management of juvenile idiopathic arthritis (JIA). Data collected in national clinical audit programmes fundamentally aim to improve health outcomes of disease, ensuring clinical care is equitable, safe and patient-centred. The aim of this study was to develop a tool for national audit of JIA in the UK. Methods A staged and consultative methodology was used across a broad group of relevant stakeholders to develop a national audit tool, with reference to pre-existing standards of care for JIA. The tool comprises key service delivery quality measures assessed against two aspects of impact, namely disease-related outcome measures and patient/carer reported outcome and experience measures. Results Eleven service-related quality measures were identified, including those that map to current standards for commissioning of JIA clinical services in the UK. The three-variable Juvenile Arthritis Disease Activity Score and presence/absence of sacro-iliitis in patients with enthesitis-related arthritis were identified as the primary disease-related outcome measures, with presence/absence of uveitis a secondary outcome. Novel patient/carer reported outcomes and patient/carer reported experience measures were developed and face validity confirmed by relevant patient/carer groups. Conclusion A tool for national audit of JIA has been developed with the aim of benchmarking current clinical practice and setting future standards and targets for improvement. Staged implementation of this national audit tool should facilitate investigation of variability in levels of care and drive quality improvement. This will require engagement from patients and carers, clinical teams and commissioners of JIA services. PMID:29069424

Rapid Whole-Genome Sequencing for Investigation of a Neonatal MRSA Outbreak

PubMed Central

Köser, Claudio U.; Holden, Matthew T.G.; Ellington, Matthew J.; Cartwright, Edward J.P.; Brown, Nicholas M.; Ogilvy-Stuart, Amanda L.; Hsu, Li Yang; Chewapreecha, Claire; Croucher, Nicholas J.; Harris, Simon R.; Sanders, Mandy; Enright, Mark C.; Dougan, Gordon; Bentley, Stephen D.; Parkhill, Julian; Fraser, Louise J.; Betley, Jason R.; Schulz-Trieglaff, Ole B.; Smith, Geoffrey P.; Peacock, Sharon J.

2013-01-01

Background Isolates of methicillin-resistant Staphylococcus aureus (MRSA) belonging to a single lineage are often indistinguishable by means of current typing techniques. Whole-genome sequencing may provide improved resolution to define transmission pathways and characterize outbreaks. Methods We investigated a putative MRSA outbreak in a neonatal intensive care unit. By using rapid high-throughput sequencing technology with a clinically relevant turnaround time, we retrospectively sequenced the DNA from seven isolates associated with the outbreak and another seven MRSA isolates associated with carriage of MRSA or bacteremia in the same hospital. Results We constructed a phylogenetic tree by comparing single-nucleotide polymorphisms (SNPs) in the core genome to a reference genome (an epidemic MRSA clone, EMRSA-15 [sequence type 22]). This revealed a distinct cluster of outbreak isolates and clear separation between these and the nonoutbreak isolates. A previously missed transmission event was detected between two patients with bacteremia who were not part of the outbreak. We created an artificial “resistome” of antibiotic-resistance genes and demonstrated concordance between it and the results of phenotypic susceptibility testing; we also created a “toxome” consisting of toxin genes. One outbreak isolate had a hypermutator phenotype with a higher number of SNPs than the other outbreak isolates, highlighting the difficulty of imposing a simple threshold for the number of SNPs between isolates to decide whether they are part of a recent transmission chain. Conclusions Whole-genome sequencing can provide clinically relevant data within a time frame that can influence patient care. The need for automated data interpretation and the provision of clinically meaningful reports represent hurdles to clinical implementation. (Funded by the U.K. Clinical Research Collaboration Translational Infection Research Initiative and others.) PMID:22693998

Nutritional Management of Metabolic Endotoxemia: A Clinical Review.

PubMed

Brown, Benjamin I

2017-07-01

Context • Diet-induced, metabolic endotoxemia is emerging as an important contributory factor to the development of a wide range of chronic diseases, including cardiometabolic, autoimmune, psychiatric, and neurodegenerative illnesses. Emerging human clinical studies have demonstrated that diet and dietary components are potent modifiers of circulating endotoxins and can be used to reduce plasma levels significantly and improve metabolic health. Objective • The aim of the current study was to explore briefly the concept of metabolic endotoxemia and its relationship to disease development, to examine the influence of diet and dietary components on circulating endotoxins, and, finally, discuss the clinical relevance of nutritional interventions for management of metabolic endotoxemia. Design • The researcher performed a literature review of dietary and nutritional interactions with metabolic endotoxemia with a focus on studies relevant to clinical practice. Setting • The study took place at the UK College of Nutrition and Health (London, England). Results • Improving dietary quality, optimizing the intake of phytonutrient-rich foods, improving micronutrient status, consuming fermented foods, manipulating the gut microflora with prebiotics and probiotics, and using specific nutritional supplements, such as glutamine, lactoferrin, resveratrol, and berberine, have been shown to be effective in targeting metabolic endotoxemia. Conclusions • Diet, dietary components, and nutritional supplements, including prebiotics and probiotics, have demonstrated the ability to provide clinically important reductions in circulating endotoxins and improve related sequels, such as inflammation and other negative health markers. The development of personalized nutritional interventions for the management of metabolic endotoxemia is a promising area for future research due to the potential of such interventions to improve multiple aspects of human health and mitigate a wide range of chronic diseases.

Primary hip and knee replacement surgery: Ontario criteria for case selection and surgical priority.

PubMed Central

Naylor, C D; Williams, J I

1996-01-01

OBJECTIVES--To develop, from simple clinical factors, criteria to identify appropriate patients for referral to a surgeon for consideration for arthroplasty, and to rank them in the queue once surgery is agreed. DESIGN--Delphi process, with a panel including orthopaedic surgeons, rheumatologists, general practitioners, epidemiologists, and physiotherapists, who rated 120 case scenarios for appropriateness and 42 for waiting list priority. Scenarios incorporated combinations of relevant clinical factors. It was assumed that queues should be organised not simply by chronology but by clinical and social impact of delayed surgery. The panel focused on information obtained from clinical histories, to ensure the utility of the guidelines in practice. Relevant high quality research evidence was limited. SETTING--Ontario, Canada. MAIN MEASURES--Appropriateness ratings on a 7-point scale, and urgency rankings on a 4-point scale keyed to specific waiting times. RESULTS--Despite incomplete evidence panellists agreed on ratings in 92.5% of appropriateness and 73.8% of urgency scenarios versus 15% and 18% agreement expected by chance, respectively. Statistically validated algorithms in decision tree form, which should permit rapid estimation of urgency or appropriateness in practice, were compiled by recursive partitioning. Rating patterns and algorithms were also used to make brief written guidelines on how clinical factors affect appropriateness and urgency of surgery. A summary score was provided for each case scenario; scenarios could then be matched to chart audit results, with scoring for quality management. CONCLUSIONS--These algorithms and criteria can be used by managers or practitioners to assess appropriateness of referral for hip or knee replacement and relative rankings of patients in the queue for surgery. PMID:10157268

Dreams and Psychedelics: Neurophenomenological Comparison and Therapeutic Implications

PubMed Central

Kraehenmann, Rainer

2017-01-01

Background: A resurgence of neurobiological and clinical research is currently underway into the therapeutic potential of serotonergic or ‘classical’ psychedelics such as the prototypical psychedelic drug lysergic acid diethylamide (LSD) psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) and ayahuasca – a betacarboline- and dimethyltryptamine (DMT)-containing Amazonian beverage. The aim of this review is to introduce readers to the similarities and dissimilarities between psychedelic states and night dreams and to draw conclusions related to therapeutic applications of psychedelics in psychiatry. Methods: Research literature related to psychedelics and dreaming is reviewed and these two states of consciousness are systematically compared. Relevant conclusions with regard to psychedelic-assisted therapy will be provided. Results: Common features between psychedelic states and night dreams include perception mental imagery emotion activation fear memory extinction and sense of self and body. Differences between these two states are related to differential perceptual input from the environment clarity of consciousness and meta-cognitive abilities. Therefore psychedelic states are closest to lucid dreaming which is characterized by a mixed state of dreaming and waking consciousness Conclusion: The broad overlap between dreaming and psychedelic states supports the notion that psychedelics acutely induce dreamlike subjective experiences which may have long-term beneficial effects on psychosocial functioning and well-being. Future clinical studies should examine how therapeutic outcome is related to the acute dreamlike effects of psychedelics. PMID:28625125

Clinical Detection of Pre-Cataractous Lens Protein Changes using Dynamic Light Scattering

PubMed Central

Datiles, Manuel B.; Ansari, Rafat R.; Suh, Kwang I.; Vitale, Susan; Reed, George F.; Zigler, J. Samuel; Ferris., Frederick L.

2008-01-01

Purpose To use Dynamic Light Scattering (DLS) to clinically assess early pre-cataractous lens protein changes. Methods We performed a cross sectional study in 380 eyes of 235 subjects aged 7–86 years with AREDS clinical lens nuclear grades ranging from 0–3.8. A DLS device was used to assess α-crystallin, a molecular chaperone protein shown to bind other damaged lens proteins, preventing their aggregation. The outcome measure was the α-crystallin index (ACI), a measure of unbound α-crystallin in each lens. The association of ACI with increasing nuclear opacity and aging was determined. Results There was a significant decrease in ACI associated with increasing grades of lens nuclear opacity (p<0.0001). There are significant losses of α-crystallin even in clinically clear lenses associated with aging (p<0.0001). The standard error of measurement was 3%. Conclusions DLS clinically detects loss of α-crystallin proteins even in clinically clear lenses. ACI measurements may be useful in identifying patients at high risk for developing cataract, and as an outcome variable in clinical lens studies. Clinical Relevance Our studies suggest that the ACI may be a useful measure of the protective α-crystallin molecular chaperone reserve present in a lens, analogous to creatinine clearance in estimating renal function reserve. PMID:19064850

Application of Platelet-Rich Plasma to Disorders of the Knee Joint

PubMed Central

Mandelbaum, Bert R.; McIlwraith, C. Wayne

2013-01-01

Importance. The promising therapeutic potential and regenerative properties of platelet-rich plasma (PRP) have rapidly led to its widespread clinical use in musculoskeletal injury and disease. Although the basic scientific rationale surrounding PRP products is compelling, the clinical application has outpaced the research. Objective. The purpose of this article is to examine the current concepts around the basic science of PRP application, different preparation systems, and clinical application of PRP in disorders in the knee. Evidence Acquisition. A systematic search of PubMed for studies that evaluated the basic science, preparation and clinical application of platelet concentrates was performed. The search used terms, including platelet-rich plasma or PRP preparation, activation, use in the knee, cartilage, ligament, and meniscus. Studies found in the initial search and related studies were reviewed. Results. A comprehensive review of the literature supports the potential use of PRP both nonoperatively and intraoperatively, but highlights the absence of large clinical studies and the lack of standardization between method, product, and clinical efficacy. Conclusions and Relevance. In addition to the call for more randomized, controlled clinical studies to assess the clinical effect of PRP, at this point, it is necessary to investigate PRP product composition and eventually have the ability to tailor the therapeutic product for specific indications. PMID:26069674

A cross-country comparison of intensive care physicians’ beliefs about their transfusion behaviour: A qualitative study using the theoretical domains framework

PubMed Central

2012-01-01

Background Evidence of variations in red blood cell transfusion practices have been reported in a wide range of clinical settings. Parallel studies in Canada and the United Kingdom were designed to explore transfusion behaviour in intensive care physicians. The aim of this paper is three-fold: first, to explore beliefs that influence Canadian intensive care physicians’ transfusion behaviour; second, to systematically select relevant theories and models using the Theoretical Domains Framework (TDF) to inform a future predictive study; and third, to compare its results with the UK study. Methods Ten intensive care unit (ICU) physicians throughout Canada were interviewed. Physicians’ responses were coded into theoretical domains, and specific beliefs were generated for each response. Theoretical domains relevant to behaviour change were identified, and specific constructs from the relevant domains were used to select psychological theories. The results from Canada and the United Kingdom were compared. Results Seven theoretical domains populated by 31 specific beliefs were identified as relevant to the target behaviour. The domains Beliefs about capabilities (confident to not transfuse if patients’ clinical condition is stable), Beliefs about consequences (positive beliefs of reducing infection and saving resources and negative beliefs about risking patients’ clinical outcome and potentially more work), Social influences (transfusion decision is influenced by team members and patients’ relatives), and Behavioural regulation (wide range of approaches to encourage restrictive transfusion) that were identified in the UK study were also relevant in the Canadian context. Three additional domains, Knowledge (it requires more evidence to support restrictive transfusion), Social/professional role and identity (conflicting beliefs about not adhering to guidelines, referring to evidence, believing restrictive transfusion as professional standard, and believing that guideline is important for other professionals), and Motivation and goals (opposing beliefs about the importance of restrictive transfusion and compatibility with other goals), were also identified in this study. Similar to the UK study, the Theory of Planned Behaviour, Social Cognitive Theory, Operant Learning Theory, Action Planning, and Knowledge-Attitude-Behaviour model were identified as potentially relevant theories and models for further study. Personal project analysis was added to the Canadian study to explore the Motivation and goals domain in further detail. Conclusions A wide range of beliefs was identified by the Canadian ICU physicians as likely to influence their transfusion behaviour. We were able to demonstrate similar though not identical results in a cross-country comparison. Designing targeted behaviour-change interventions based on unique beliefs identified by physicians from two countries are more likely to encourage restrictive transfusion in ICU physicians in respective countries. This needs to be tested in future prospective clinical trials. PMID:22999460

Prediction of citation counts for clinical articles at two years using data available within three weeks of publication: retrospective cohort study

PubMed Central

2008-01-01

Objective To determine if citation counts at two years could be predicted for clinical articles that pass basic criteria for critical appraisal using data within three weeks of publication from external sources and an online article rating service. Design Retrospective cohort study. Setting Online rating service, Canada. Participants 1274 articles from 105 journals published from January to June 2005, randomly divided into a 60:40 split to provide derivation and validation datasets. Main outcome measures 20 article and journal features, including ratings of clinical relevance and newsworthiness, routinely collected by the McMaster online rating of evidence system, compared with citation counts at two years. Results The derivation analysis showed that the regression equation accounted for 60% of the variation (R2=0.60, 95% confidence interval 0.538 to 0.629). This model applied to the validation dataset gave a similar prediction (R2=0.56, 0.476 to 0.596, shrinkage 0.04; shrinkage measures how well the derived equation matches data from the validation dataset). Cited articles in the top half and top third were predicted with 83% and 61% sensitivity and 72% and 82% specificity. Higher citations were predicted by indexing in numerous databases; number of authors; abstraction in synoptic journals; clinical relevance scores; number of cited references; and original, multicentred, and therapy articles from journals with a greater proportion of articles abstracted. Conclusion Citation counts can be reliably predicted at two years using data within three weeks of publication. PMID:18292132

Diagnosis and Inflammatory Response of Patients with Candiduria

PubMed Central

Helbig, S.; Achkar, J. M.; Jain, N.; Wang, X.; Gialanella, P.; Levi, M; Fries, B.C.

2012-01-01

Summary Background Candiduria is common in hospitalized patients but the clinical relevance is still unclear. Objective This study was done to further our knowledge on detection of and host responses to candiduria. Patients Urines and clinical data from 136 patients in whom presence of yeast was diagnosed by microscopic urinalysis were collected. Diagnosis by standard urine culture methods on blood and MacConkey agar as well as on fungal culture medium (Sabouraud dextrose agar) was compared. Inflammatory parameters (IL-6 and IL-17, Ig) were quantified in the urine and compared to levels in control patients without candiduria. Results and Conclusions Standard urine culture methods detected only 37% of Candida spp. in urine. Sensitivity was especially low (23%) for C. glabrata and was independent of fungal burden. Candida specific IgG but not IgA was significantly elevated when compared to control patients (p<0.0001 and 0.07, respectively). In addition, urine levels of IL-6 and IL-17 were significantly higher in candiduric patients when compared to control patients (p<0.001). Multivariate analysis documented an independent association between an increased IgG (odds ratio (OR) 136.0, 95% confidence interval (CI) 25.7 to 719.2; p<0.0001), an increased IL-17 (OR 17.4, 95% CI 5.3–57.0; p<0.0001) and an increased IL-6 level (OR 4.9, 95% CI 1.9–12.4; p=0.001) and candiduria. In summary, our data indicate that clinical studies on candiduria should include fungal urine culture and that inflammatory parameters may be helpful to identify patients with clinically relevant candiduria. PMID:22574854

The role of tissue damage in whiplash associated disorders: Discussion paper 1

PubMed Central

Bogduk, Nikolai; Ivancic, Paul C.; McLean, Samuel A.; Siegmund, Gunter P.; Winkelstein, Beth

2011-01-01

STUDY DESIGN Non-systematic review of cervical spine lesions in whiplash-associated disorders (WAD). OBJECTIVE To describe whiplash injury models in terms of basic and clinical science, to summarize what can and cannot be explained by injury models, and to highlight future research areas to better understand the role of tissue damage in WAD. SUMMARY OF BACKGROUND DATA The frequent lack of detectable tissue damage has raised questions about whether tissue damage is necessary for WAD and what role it plays in the clinical context of WAD. METHODS Non-systematic review. RESULTS Lesions of various tissues have been documented by numerous investigations conducted in animals, cadavers, healthy volunteers and patients. Most lesions are undetected by imaging techniques. For zygapophysial (facet) joints, lesions have been predicted by bioengineering studies and validated through animal studies; for zygapophysial joint pain, a valid diagnostic test and a proven treatment are available. Lesions of dorsal root ganglia, discs, ligaments, muscles and vertebral artery have been documented in biomechanical and autopsy studies, but no valid diagnostic test is available to assess their clinical relevance. The proportion of WAD patients in whom a persistent lesion is the major determinant of ongoing symptoms is unknown. Psychosocial factors, stress reactions and generalized hyperalgesia have also been shown to predict WAD outcomes. CONCLUSION There is evidence supporting a lesion-based model in WAD. Lack of macroscopically identifiable tissue damage does not rule out the presence of painful lesions. The best available evidence concerns zygapophysial joint pain. The clinical relevance of other lesions needs to be addressed by future research. PMID:22020601

Electronic information and clinical decision support for prescribing: state of play in Australian general practice

PubMed Central

Robertson, Jane; Moxey, Annette J; Newby, David A; Gillies, Malcolm B; Williamson, Margaret; Pearson, Sallie-Anne

2011-01-01

Background. Investments in eHealth worldwide have been mirrored in Australia, with >90% of general practices computerized. Recent eHealth incentives promote the use of up to date electronic information sources relevant to general practice with flexibility in mode of access. Objective. To determine GPs’ access to and use of electronic information sources and computerized clinical decision support systems (CDSSs) for prescribing. Methods. Semi-structured interviews were conducted with 18 experienced GPs and nine GP trainees in New South Wales, Australia in 2008. A thematic analysis of interview transcripts was undertaken. Results. Information needs varied with clinical experience, and people resources (specialists, GP peers and supervisors for trainees) were often preferred over written formats. Experienced GPs used a small number of electronic resources and accessed them infrequently. Familiarity from training and early clinical practice and easy access were dominant influences on resource use. Practice time constraints meant relevant information needed to be readily accessible during consultations, requiring integration or direct access from prescribing software. Quality of electronic resource content was assumed and cost a barrier for some GPs. Conclusions. The current Australian practice incentives do not prescribe which information resources GPs should use. Without integration into practice computing systems, uptake and routine use seem unlikely. CDSS developments must recognize the time pressures of practice, preference for integration and cost concerns. Minimum standards are required to ensure that high-quality information resources are integrated and regularly updated. Without standards, the anticipated benefits of computerization on patient safety and health outcomes will be uncertain. PMID:21109619

Evidence for the use of parenteral nutrition in the pediatric intensive care unit.

PubMed

Fivez, Tom; Kerklaan, Dorian; Mesotten, Dieter; Verbruggen, Sascha; Joosten, Koen; Van den Berghe, Greet

2017-02-01

During hospitalization in a pediatric intensive care unit (PICU), critically ill children are fed artificially. Administered via the preferred enteral route, caloric targets are often not reached. Hence, parenteral nutrition is given to this patient population. In this review we analyzed the available evidence from randomized controlled trials (RCTs) that supports the use of parenteral nutrition in children during critical illness. A search strategy in Ovid MEDLINE and Ovid EMBASE was created and trial registries were screened to identify the relevant RCTs. Studies were included if they were randomized controlled trials, involved pediatric patients admitted to PICU, and compared different dosing/compositions of parenteral nutrition. Descriptive studies and reviews were excluded. Of the 584 articles identified by the search strategy, only 114 articles were retained after title screening. Further abstract and full text screening identified 6 small RCTs that compared two dosing/composition strategies of parenteral nutrition. These trials reported differences in surrogate endpoints without an effect on hard clinical endpoints. The RCTs observed improvements in these surrogate endpoints with the use of more calories or when parenteral glutamine or fish oil was added. The few RCTs suggest that surrogate endpoints can be affected by providing parenteral nutrition to critically ill children, but the studies were not statistically powered to draw meaningful clinical conclusions. Large RCTs with clinically relevant outcome measures are urgently needed to support the current nutritional guidelines that advise the use of parenteral nutrition in the PICU. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

The enteral vs parenteral nutrition debate revisited.

PubMed

Thomson, Andrew

2008-01-01

Many trials and several meta-analyses have been devoted to comparing enteral with parenteral nutrition support. In this review, these studies are subjected to critical analysis with particular emphasis on their methodology and clinical relevance. Evidence is produced to suggest that the heterogeneous patient populations of the studies and the rigid approach taken to comparing different nutrition therapies inter alia render their conclusions highly questionable and of very doubtful clinical significance. An alternative approach to nutrition research is suggested in which strategies of nutrition support rather than fixed menus are compared. It is suggested that objective measures of intestinal function be evaluated more fully in patients requiring nonvolitional nutrition support, and these are briefly reviewed. In addition, a more scientific approach to evaluating the physiological effects of nutrition support, including chemical tagging and evaluation of muscle function, is recommended.

14th International Congress on Antiphospholipid Antibodies Task Force. Report on antiphospholipid syndrome laboratory diagnostics and trends.

PubMed

Bertolaccini, Maria Laura; Amengual, Olga; Andreoli, Laura; Atsumi, Tatsuya; Chighizola, Cecilia B; Forastiero, Ricardo; de Groot, Philip; Lakos, Gabriella; Lambert, Marc; Meroni, Pierluigi; Ortel, Thomas L; Petri, Michelle; Rahman, Anisur; Roubey, Robert; Sciascia, Savino; Snyder, Melissa; Tebo, Anne E; Tincani, Angela; Willis, Rohan

2014-09-01

Current classification criteria for definite Antiphospholipid Syndrome (APS) require the use of three laboratory assays to detect antiphospholipid antibodies (aCL, anti-β2GPI and LA) in the presence of at least one of the two major clinical manifestations (i.e. thrombosis or pregnancy morbidity) of the syndrome. However, several other autoantibodies shown to be directed to other proteins or their complex with phospholipids have been proposed to be relevant to APS but their clinical utility and their diagnostic value remains elusive. This report summarizes the findings, conclusions and recommendations of the "APS Task Force 3-Laboratory Diagnostics and Trends" meeting that took place during the 14th International Congress on Antiphospholipid Antibodies (APLA 2013, September 18-21, Rio de Janeiro, RJ, Brazil). Copyright © 2014 Elsevier B.V. All rights reserved.

Clinical practice and self-awareness as determinants of empathy in undergraduate education: A qualitative short survey at three medical schools in Germany

PubMed Central

Ahrweiler, Florian; Scheffer, Christian; Roling, Gudrun; Goldblatt, Hadass; Hahn, Eckhart G.; Neumann, Melanie

2014-01-01

Study aim: Physician empathy constitutes an outcome-relevant aim of medical education. Yet, the factors promoting and inhibiting physician empathy have not yet been extensively researched, especially in Germany. In this study, we explored German medical students’ views of the factors promoting and inhibiting their empathy and how their experiences were related to their curricula. Methods: A qualitative short survey was conducted at three medical schools: Bochum University, the University of Cologne and Witten/Herdecke University. Students were invited to complete an anonymous written questionnaire comprised of open-ended questions inquiring about the educational content of and situations during their medical education that positively or negatively impacted their empathy. Data were analyzed through qualitative content analysis according to the methods of Green and Thorogood. Results: A total of 115 students participated in the survey. Respondents reported that practice-based education involving patient contact and teaching with reference to clinical practice and the patient’s perspective improved their empathy, while a lack of these inhibited it. Students’ internal reactions to patients, such as liking or disliking a patient, prejudice and other attitudes, were also considered to influence their empathy. Although each of the three schools takes a different approach to teaching interpersonal skills, no relevant differences were found in their students’ responses concerning the possible determinants of empathy. Conclusion: Providing more training in practice and more contact with patients may be effective ways of promoting student empathy. Students need support in establishing therapeutic relationships with patients and in dealing with their own feelings and attitudes. Such support could be provided in the form of reflective practice training in order to promote self-awareness. More research is needed to evaluate these hypothetical conclusions. PMID:25489346

Factors associated to clinical learning in nursing students in primary health care: an analytical cross-sectional study

PubMed Central

Serrano-Gallardo, Pilar; Martínez-Marcos, Mercedes; Espejo-Matorrales, Flora; Arakawa, Tiemi; Magnabosco, Gabriela Tavares; Pinto, Ione Carvalho

2016-01-01

ABSTRACT Objective: to identify the students' perception about the quality of clinical placements and asses the influence of the different tutoring processes in clinical learning. Methods: analytical cross-sectional study on second and third year nursing students (n=122) about clinical learning in primary health care. The Clinical Placement Evaluation Tool and a synthetic index of attitudes and skills were computed to give scores to the clinical learning (scale 0-10). Univariate, bivariate and multivariate (multiple linear regression) analyses were performed. Results: the response rate was 91.8%. The most commonly identified tutoring process was "preceptor-professor" (45.2%). The clinical placement was assessed as "optimal" by 55.1%, relationship with team-preceptor was considered good by 80.4% of the cases and the average grade for clinical learning was 7.89. The multiple linear regression model with more explanatory capacity included the variables "Academic year" (beta coefficient = 1.042 for third-year students), "Primary Health Care Area (PHC)" (beta coefficient = 0.308 for Area B) and "Clinical placement perception" (beta coefficient = - 0.204 for a suboptimal perception). Conclusions: timeframe within the academic program, location and clinical placement perception were associated with students' clinical learning. Students' perceptions of setting quality were positive and a good team-preceptor relationship is a matter of relevance. PMID:27627124

Reflections on relevance: Psychotherapy and Psychosomatics in 2004.

PubMed

Balon, Richard

2005-01-01

Relevance of an article is a highly desirable yet hardly predictable quality at the time of its publication. Article relevance is frequently measured by the impact factor of the journal where the article is published. Furthermore, impact factor, citation index and citation analysis are used as a measure of research progress and scientific wealth of a nation. The wisdom and significance of this approach to relevance is debatable and thus discussed here. In 2004, Psychotherapy and Psychosomatics published a variety of articles which, in the author's view, are clinically relevant. Several selected clinically relevant issues reviewed in this article include: the conceptualization of fibromyalgia as a stress disorder; the psychosocial impact and psychosocial interventions in cancer; the impact of alexithymia on patient care; the possible relationship between depression and nutrition (namely intake of folate and pyridoxal phosphate); the significance of hypercoagulability in panic-like anxiety; the questionable value of single isomer drugs, and the relevance and adequacy of clinimetrics versus psychometrics in clinical research. The reviewed issues seem to be relevant to clinical practice, research or both, but also to our critical thinking, and the critical review of the developments in psychiatry and psychology. Copyright 2005 S. Karger AG, Basel.

Interpersonal behaviors and socioemotional interaction of medical students in a virtual clinical encounter

PubMed Central

2014-01-01

Background The virtual clinical encounter (VCE) may function as an important support for medical students in or prior to clinical practice to train and ease communication and socioemotional interactions with patients. Few studies have however focused on the dynamics of interpersonal behaviors in clinical interviewing with a virtual patient (VP) and the affective responses evoked by such a learning experience. The study was designed to investigate the dynamics and congruence of interpersonal behaviors and socioemotional interaction exhibited during the learning experience in a VCE, and to evaluate which interaction design characteristics contribute most to the behavioral and affective engagement in medical students. Methods Thirty medical students (sixth semester) participated voluntarily in an exploratory observational study with a highly interactive VP case based on a trustworthy VP encounter with a natural and realistic dialogue interface. Students worked collaboratively in pairs. They were videotaped for further behavioral analysis and self-reported (in both a survey and an interview) their personal opinions, perceptions and attitudes about the VCE. A mixed methods approach was applied. Results All participants demonstrated an adequate, respectful and relevant clinical case management and to obtain psychosocial history. The collaborative workspace played its role and led to dynamic and engaged discussions fostering thus shared understanding. The results suggest that the VCE studied was perceived as a meaningful, intrinsically motivational and activating learning environment, and was found to socially and emotionally engage learners. We also found that VCEs have the potential to support the development of relevant and congruent interpersonal communication skills in trainees. Conclusions By taking advantage of socioemotional interaction, VCEs promote not only critical reflection skills or strategy-selection skills, but also to develop listening and nonverbal skills, induce self-awareness and target coping behaviours. We believe that, if applied in early medical education, this learning approach may facilitate clinical encounters at an early stage and contribute to responsible clinical decision making. PMID:24685070

Diagnostic value of clinical tests for degenerative rotator cuff disease in medical practice.

PubMed

Lasbleiz, S; Quintero, N; Ea, K; Petrover, D; Aout, M; Laredo, J D; Vicaut, E; Bardin, T; Orcel, P; Beaudreuil, J

2014-06-01

To assess the diagnostic value of clinical tests for degenerative rotator cuff disease (DRCD) in medical practice. Patients with DRCD were prospectively included. Eleven clinical tests of the rotator cuff have been done. One radiologist performed ultrasonography (US) of the shoulder. Results of US were expressed as normal tendon, tendinopathy or full-thickness tear (the reference). For each clinical test and each US criteria, sensitivity, specificity, negative predictive value and positive predictive value, accuracy, negative likelihood ratio (NLR) and positive likelihood ratio (PLR) were calculated. Clinical relevance was defined as PLR ≥2 and NLR ≤0.5. For 35 patients (39 shoulders), Jobe (PLR: 2.08, NLR: 0.31) and full-can (2, 0.5) test results were relevant for diagnosis of supraspinatus tears and resisted lateral rotation (2.42, 0.5) for infraspinatus tears, with weakness as response criteria. The lift-off test (8.50, 0.27) was relevant for subscapularis tears with lag sign as response criteria. Yergason's test (3.7, 0.41) was relevant for tendinopathy of the long head of the biceps with pain as a response criterion. There was no relevant clinical test for diagnosis of tendinopathy of supraspinatus, infraspinatus or subscapularis. Five of 11 clinical tests were relevant for degenerative rotator cuff disease. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Probing consciousness with event-related potentials in the vegetative state

PubMed Central

Faugeras, F.; Rohaut, B.; Weiss, N.; Bekinschtein, T.A.; Galanaud, D.; Puybasset, L.; Bolgert, F.; Sergent, C.; Cohen, L.; Dehaene, S.

2011-01-01

Objective: Probing consciousness in noncommunicating patients is a major medical and neuroscientific challenge. While standardized and expert behavioral assessment of patients constitutes a mandatory step, this clinical evaluation stage is often difficult and doubtful, and calls for complementary measures which may overcome its inherent limitations. Several functional brain imaging methods are currently being developed within this perspective, including fMRI and cognitive event-related potentials (ERPs). We recently designed an original rule extraction ERP test that is positive only in subjects who are conscious of the long-term regularity of auditory stimuli. Methods: In the present work, we report the results of this test in a population of 22 patients who met clinical criteria for vegetative state. Results: We identified 2 patients showing this neural signature of consciousness. Interestingly, these 2 patients showed unequivocal clinical signs of consciousness within the 3 to 4 days following ERP recording. Conclusions: Taken together, these results strengthen the relevance of bedside neurophysiological tools to improve diagnosis of consciousness in noncommunicating patients. PMID:21593438

Sharing all types of clinical data and harmonizing journal standards.

PubMed

Barbui, Corrado

2016-04-03

Despite recent efforts to enforce policies requiring the sharing of data underlying clinical findings, current policies of biomedical journals remain largely heterogeneous. As this heterogeneity does not optimally serve the cause of data sharing, a first step towards better harmonization would be the requirement of a data sharing statement for all clinical studies and not simply for randomized studies. Although the publication of a data sharing statement does not imply that all data is made readily available, such a policy would swiftly implement a cultural change in the definition of scientific outputs. Currently, a scientific output only corresponds to a study report published in a medical journal, while in the near future it might consist of all materials described in the manuscript, including all relevant raw data. When such a cultural shift has been achieved, the logical conclusion would be for biomedical journals to require authors to make all data fully available without restriction as a condition for publication.

Stress-related Clinical Pain and Mood in Women with Chronic Pain: Moderating Effects of Depression and Positive Mood Induction

PubMed Central

Davis, Mary C.; Thummala, Kirti; Zautra, Alex J.

2014-01-01

Background Chronic pain with co-morbid depression is characterized by poor mood regulation and stress-related pain. Purpose Compare depressed and non-depressed pain patients in mood and pain stress reactivity and recovery, and test whether a post-stress positive mood induction moderates pain recovery. Methods Women with fibromyalgia and/or osteoarthritis (N=110) underwent interpersonal stress and were then randomly assigned by pain condition and depression status, assessed via the Center for Epidemiological Studies-Depression scale, to positive versus neutral mood induction. Results Depression did not predict stress-related reactivity in despondency, joviality, or clinical pain. However, depression X mood condition predicted recovery in joviality and clinical pain; depressed women recovered only in the positive mood condition, whereas non-depressed women recovered in both mood conditions. Conclusions Depression does not alter pain and mood stress reactivity, but does impair recovery. Boosting post-stress jovial mood ameliorates pain recovery deficits in depressed patients, a finding relevant to chronic pain interventions. PMID:24532393

Biomarkers for Psychiatry: The Journey from Fantasy to Fact, a Report of the 2013 CINP Think Tank

PubMed Central

Millan, Mark J.; Bahn, Sabine; Bertolino, Alessandro; Turck, Christoph W.; Kapur, Shitij; Möller, Hans-Jürgen; Dean, Brian

2015-01-01

Background: A think tank sponsored by the Collegium Internationale Neuropsychopharmacologium (CINP) debated the status and prospects of biological markers for psychiatric disorders, focusing on schizophrenia and major depressive disorder. Methods: Discussions covered markers defining and predicting specific disorders or domains of dysfunction, as well as predicting and monitoring medication efficacy. Deliberations included clinically useful and viable biomarkers, why suitable markers are not available, and the need for tightly-controlled sample collection. Results: Different types of biomarkers, appropriate sensitivity, specificity, and broad-based exploitability were discussed. Whilst a number of candidates are in the discovery phases, all will require replication in larger, real-life cohorts. Clinical cost-effectiveness also needs to be established. Conclusions: Since a single measure is unlikely to suffice, multi-modal strategies look more promising, although they bring greater technical and implementation complexities. Identifying reproducible, robust biomarkers will probably require pre-competitive consortia to provide the resources needed to identify, validate, and develop the relevant clinical tests. PMID:25899066

Treatment of osteoporosis in men

PubMed Central

Kaufman, J.-M.; Reginster, J.-Y.; Boonen, S.; Brandi, M. L.; Cooper, C.; Dere, W.; Devogelaer, J.-P.; Diez-Perez, A.; Kanis, J. A.; McCloskey, E.; Mitlak, B.; Orwoll, E.; Ringe, J.D.; Weryha, G.; Rizzoli, R.

2013-01-01

Summary Aspects of osteoporosis in men, such as screening and identification strategies, definitions of diagnosis and intervention thresholds, and treatment options (both approved and in the pipeline) are discussed. Introduction Awareness of osteoporosis in men is improving, although it remains under-diagnosed and under-treated. A European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) workshop was convened to discuss osteoporosis in men and to provide a report by a panel of experts (the authors). Methods A debate with an expert panel on preselected topics was conducted. Results and Conclusions Although additional fracture data are needed to endorse the clinical care of osteoporosis in men, consensus views were reached on diagnostic criteria and intervention thresholds. Empirical data in men display similarities with data acquired in women, despite pathophysiological differences, which may not be clinically relevant. Men should receive treatment at a similar 10-year fracture probability as in women. The design of mixed studies may reduce the lag between comparable treatments for osteoporosis in women becoming available in men. PMID:23201268

Pharmacogenomics in type II diabetes mellitus management: Steps toward personalized medicine

PubMed Central

Avery, Peter; Mousa, Shaymaa S; Mousa, Shaker A

2009-01-01

Advances in genotype technology in the last decade have put the pharmacogenomics revolution at the forefront of future medicine in clinical practice. Discovery of novel gene variations in drug transporters, drug targets, effector proteins and metabolizing enzymes in the form of single-nucleotide polymorphisms (SNPs) continue to provide insight into the biological phenomena that govern drug efficacy and toxicity. To date, novel gene discoveries extracted from genome-wide association scans and candidate gene studies in at least four antidiabetic drug classes have helped illuminate possible causes of interindividual variability in response. Inadequate protocol guidelines for pharmacogenomics studies often leads to poorly designed studies, making it hard to formulate a definitive conclusion regarding the clinical relevance of the information at hand. These issues, along with the ethical, social, political, legislative, technological, and economic challenges associated with pharmacogenomics have only delayed its entry to mainstream clinical practice. On the other hand, these issues are being actively pursued and rapid progress is being made in each area which assures the possibility of gaining widespread acceptance in clinical practice. PMID:23226037

Topical Vitamin C and the Skin: Mechanisms of Action and Clinical Applications.

PubMed

Al-Niaimi, Firas; Chiang, Nicole Yi Zhen

2017-07-01

OBJECTIVE: This review article details the main mechanisms of action and clinical applications of topical vitamin C on the skin, including its antioxidative, photoprotective, antiaging, and antipigmentary effects. DESIGN: A PubMed search for the relevant articles on vitamin C and the skin was conducted using the following key words: "vitamin C," "ascorbic acid," "ascorbyl-6-palmitate,"and "magnesium ascorbyl phosphate." RESULTS: As one of the most powerful antioxidants in the skin, vitamin C has been shown to protect against photoaging, ultraviolet-induced immunosuppression, and photocarcinogenesis. It also has an antiaging effect by increasing collagen synthesis, stabilizing collagen fibers, and decreasing collagen degradation. It decreases melanin formation, thereby reducing pigmentation. Vitamin C is the primary replenisher of vitamin E and works synergistically with vitamin E in the protection against oxidative damage. CONCLUSION: Topical vitamin C has a wide range of clinical applications, from antiaging and antipigmentary to photoprotective. Currently, clinical studies on the efficacy of topical formulations of vitamin C remain limited, and the challenge lies in finding the most stable and permeable formulation in achieving the optimal results.

Retrieval of diagnostic and treatment studies for clinical use through PubMed and PubMed's Clinical Queries filters.

PubMed

Lokker, Cynthia; Haynes, R Brian; Wilczynski, Nancy L; McKibbon, K Ann; Walter, Stephen D

2011-01-01

Clinical Queries filters were developed to improve the retrieval of high-quality studies in searches on clinical matters. The study objective was to determine the yield of relevant citations and physician satisfaction while searching for diagnostic and treatment studies using the Clinical Queries page of PubMed compared with searching PubMed without these filters. Forty practicing physicians, presented with standardized treatment and diagnosis questions and one question of their choosing, entered search terms which were processed in a random, blinded fashion through PubMed alone and PubMed Clinical Queries. Participants rated search retrievals for applicability to the question at hand and satisfaction. For treatment, the primary outcome of retrieval of relevant articles was not significantly different between the groups, but a higher proportion of articles from the Clinical Queries searches met methodologic criteria (p=0.049), and more articles were published in core internal medicine journals (p=0.056). For diagnosis, the filtered results returned more relevant articles (p=0.031) and fewer irrelevant articles (overall retrieval less, p=0.023); participants needed to screen fewer articles before arriving at the first relevant citation (p<0.05). Relevance was also influenced by content terms used by participants in searching. Participants varied greatly in their search performance. Clinical Queries filtered searches returned more high-quality studies, though the retrieval of relevant articles was only statistically different between the groups for diagnosis questions. Retrieving clinically important research studies from Medline is a challenging task for physicians. Methodological search filters can improve search retrieval.

Neurogenic bowel dysfunction: Clinical management recommendations of the Neurologic Incontinence Committee of the Fifth International Consultation on Incontinence 2013.

PubMed

Cotterill, Nikki; Madersbacher, Helmut; Wyndaele, Jean J; Apostolidis, Apostolos; Drake, Marcus J; Gajewski, Jerzy; Heesakkers, John; Panicker, Jalesh; Radziszewski, Piotr; Sakakibara, Ryuji; Sievert, Karl-Dietrich; Hamid, Rizwan; Kessler, Thomas M; Emmanuel, Anton

2018-01-01

Evidence-based guidelines for the management of neurological disease and lower bowel dysfunction have been produced by the International Consultations on Incontinence (ICI). These are comprehensive guidelines, and were developed to have world-wide relevance. To update clinical management of neurogenic bowel dysfunction from the recommendations of the 4th ICI, 2009. A series of evidence reviews and updates were performed by members of the working group. The resulting guidelines were presented at the 2012 meeting of the European Association of Urology for consultation, and modifications applied to deliver evidence based conclusions and recommendations for the scientific report of the 5th edition of the ICI in 2013. The current review is a synthesis of the conclusions and recommendations, including the algorithms for initial and specialized management of neurogenic bowel dysfunction. The pathophysiology is described in terms of spinal cord injury, multiple sclerosis, and Parkinson's disease. Assessment requires detailed history and clinical assessment, general investigations, and specialized testing, if required. Treatment primarily focuses on optimizing stool consistency and regulating bowel evacuation to improve quality of life. Symptom management covers conservative and interventional measures to promote good habits and assist stool evacuation, along with prevention of incontinence. Education is essential to achieving optimal bowel management. The review offers a pragmatic approach to management in the context of complex pathophysiology and varied evidence base. © 2017 Wiley Periodicals, Inc.

Neurogenic lower urinary tract dysfunction: Clinical management recommendations of the Neurologic Incontinence committee of the fifth International Consultation on Incontinence 2013.

PubMed

Drake, Marcus John; Apostolidis, Apostolos; Cocci, Andrea; Emmanuel, Anton; Gajewski, Jerzy B; Harrison, Simon C W; Heesakkers, John P F A; Lemack, Gary E; Madersbacher, Helmut; Panicker, Jalesh N; Radziszewski, Piotr; Sakakibara, Ryuji; Wyndaele, Jean Jacques

2016-08-01

Evidence-based guidelines for the management of neurological disease and lower urinary tract dysfunction have been produced by the International Consultations on Incontinence (ICI). These are comprehensive guidelines, and were developed to have world-wide relevance. To update clinical management of neurogenic bladder dysfunction from the recommendations of the fourth ICI, 2009. A series of evidence reviews and updates were performed by members of the working group. The resulting guidelines were presented at the 2012 meeting of the European Association of Urology for consultation, and consequently amended to deliver evidence-based conclusions and recommendations in 2013. The current review is a synthesis of the conclusions and recommendations, including the algorithms for initial and specialized management of neurogenic lower urinary tract dysfunction. The pathophysiology is categorized according to the nature of onset of neurological disease and the part(s) of the nervous system affected. Assessment requires clinical evaluation, general investigations, and specialized testing. Treatment primarily focuses on ensuring safety of the patient and optimizing quality of life. Symptom management covers conservative and interventional measures to aid urine storage and bladder emptying, along with containment of incontinence. A multidisciplinary approach to management is essential. The review offers a pragmatic review of management in the context of complex pathophysiology and varied evidence base. Neurourol. Urodynam. 35:657-665, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Clinical relevance of diagnosing COPD by fixed ratio or lower limit of normal: a systematic review.

PubMed

van Dijk, Wouter D; Gupta, Nisha; Tan, Wan C; Bourbeau, Jean

2014-02-01

Different spirometric criteria in diagnosing COPD have been advocated by different groups, debilitating adequate diagnosis and treatment of COPD. We reviewed the clinical relevance of fixed ratio and lower limit of normal (LLN) in diagnosing COPD and explored if modifying factors may affect their clinical relevance. Two reviewers independently searched PubMed and Embase for papers that compared both criteria on any clinically relevant outcome, published before June 1st, 2012, without any language restriction. Two reviewers independently extracted the study characteristics, including study design, population characteristics and diagnostic criteria used, and summarized the results of clinical relevance. Study quality was assessed by scoring forms for bias and level of evidence. Of 394 studies retrieved, 11 studies were included, with a median of 1,258 participants. Although both criteria appeared related with various clinically relevant outcomes, we were unable to prefer one criterion over the other, with various performances of the criteria for different outcomes. Should the criteria disagree on diagnosis, an alternative diagnosis should be suspected, in particular in those (elderly) with less severe airflow limitation for whom the LLN appears a better criterion. The fixed ratio appears to perform better in subjects with more severe airflow limitation. In diagnosing COPD, severity of airflow limitation appears an important factor for choosing whether the fixed ratio or LLN. Disagreement between the criteria is suggestive for an alternative diagnosis. Future studies on clinical relevance should further reveal the criterion of choice, in order to improve adequate diagnosis and consequent treatments.

Insights from clinical research completed during the west Africa Ebola virus disease epidemic

PubMed Central

Rojek, Amanda; Horby, Peter; Dunning, Jake

2018-01-01

The west Africa Ebola virus disease (EVD) epidemic was extraordinary in scale. Now that the epidemic has ended, it is a relevant time to examine published studies with direct relevance to clinical care and, more broadly, to examine the implications of the clinical research response mounted. Clinically relevant research includes literature detailing risk factors for and clinical manifestations of EVD, laboratory and other investigation findings in patients, experimental vaccine and therapeutic clinical trials, and analyses of survivor syndrome. In this Review, we discuss new insights from patient-oriented research completed during the west Africa epidemic, identify ongoing knowledge gaps, and suggest priorities for future research. PMID:28461209

Frequency of Toxocariasis among Patients Clinically Suspected to Have Visceral Toxocariasis: A Retrospective Descriptive Study in Sri Lanka

PubMed Central

Iddawela, Devika; Ehambaram, Kiruthiha; Pethiyagoda, Kalyani; Bandara, Lakmalee

2017-01-01

Introduction Human toxocariasis is caused by several species of the nematode Toxocara. Two common clinical syndromes are ocular and visceral larva migrans. Objectives To determine the Toxocara antibody positivity in clinically suspected VLM patients and to describe demographic factors and clinical manifestations of seropositive patients. Methods 522 clinically suspected patients were studied between 1993 and 2014. Relevant data was gathered from referral letters. Serum samples were subjected to Toxocara antigen ELISA. Results Overall, seropositivity was 50.2% (262), of which 109 (40.8%) were positive at high level of Toxocara antibody carriage and 153 (58.4%) were positive at low levels. The seropositives ranged from 3 months to 70 years (mean = 7.8). Younger age group had higher levels of seropositivity and it was statistically significant. Majority of children under 5 years were seropositive (47.7%, n = 125). Seropositivity was common in males (55.3%, n = 145). Clinical manifestations of seropositives include lymphadenopathy (24.1%) skin rash (22.5%), dyspnoea (21.7%), fever (21%), hepatosplenomegaly (9.2%), and abdominal pain (3.8%). 197 (75.2%) seropositive cases had eosinophilia. These symptoms were not statistically significant. Conclusions This study confirms toxocariasis as an important cause of childhood ill health identifying common clinical symptoms recommending preventive measures to limit transmission. PMID:29362672

Using scenario-based training to promote information literacy among on-call consultant pediatricians

PubMed Central

Pettersson, Jonas; Bjorkander, Emil; Bark, Sirpa; Holmgren, Daniel; Wekell, Per

2017-01-01

Background Traditionally, teaching hospital staff to search for medical information relies heavily on educator-defined search methods. In contrast, the authors describe our experiences using real-time scenarios to teach on-call consultant pediatricians information literacy skills as part of a two-year continuing professional development program. Case Presentation Two information-searching workshops were held at Sahlgrenska University Hospital in Gothenburg, Sweden. During the workshops, pediatricians were presented with medical scenarios that were closely related to their clinical practice. Participants were initially encouraged to solve the problems using their own preferred search methods, followed by group discussions led by clinical educators and a medical librarian in which search problems were identified and overcome. The workshops were evaluated using questionnaires to assess participant satisfaction and the extent to which participants intended to implement changes in their clinical practice and reported actual change. Conclusions A scenario-based approach to teaching clinicians how to search for medical information is an attractive alternative to traditional lectures. The relevance of such an approach was supported by a high level of participant engagement during the workshops and high scores for participant satisfaction, intended changes to clinical practice, and reported benefits in actual clinical practice. PMID:28670215

Early investigational tubulin inhibitors as novel cancer therapeutics.

PubMed

Nepali, Kunal; Ojha, Ritu; Lee, Hsueh-Yun; Liou, Jing-Ping

2016-08-01

Microtubules represent one of the most logical and strategic molecular targets amongst the current targets for chemotherapy, alongside DNA. In the past decade, tubulin inhibitors as cancer therapeutics have been an area of focus due to the improved understanding and biological relevance of microtubules in cellular functions. Fueled by the objective of developing novel chemotherapeutics and with the aim of establishing the benefits of tubulin inhibition, several clinical trials have been conducted with others ongoing. At present, the antitubulin development pipeline contains an armful of agents under clinical investigation. This review focuses on novel tubulin inhibitors as cancer therapeutics. The article covers the agents which have completed the phase II studies along with the agents demonstrating promising results in phase I studies. Countless clinical trials evaluating the efficacy, safety and pharmacokinetics of novel tubulin inhibitors highlights the scientific efforts being paid to establish their candidature as cancer therapeutics. Colchicine binding site inhibitors as vascular disrupting agents (VDAs) and new taxanes appear to be the most likely agents for future clinical interest. Numerous agents have demonstrated clinical benefits in terms of efficacy and survival in phase I and II studies. However conclusive benefits can only be ascertained on the basis of phase III studies.

Teaching pediatric communication skills to medical students

PubMed Central

Frost, Katherine A; Metcalf, Elizabeth P; Brooks, Rachel; Kinnersley, Paul; Greenwood, Stephen R; Powell, Colin VE

2015-01-01

Background Delivering effective clinical pediatric communication skills training to undergraduate medical students is a distinct and important challenge. Pediatric-specific communication skills teaching is complex and under-researched. We report on the development of a scenario-based pediatric clinical communication skills program as well as students’ assessment of this module. Methods We designed a pediatric clinical communication skills program and delivered it five times during one academic year via small-group teaching. Students were asked to score the workshop in eight domains (learning objectives, complexity, interest, competencies, confidence, tutors, feedback, and discussion) using 5-point Likert scales, along with free text comments that were grouped and analyzed thematically, identifying both the strengths of the workshop and changes suggested to improve future delivery. Results Two hundred and twenty-one of 275 (80%) student feedback forms were returned. Ninety-six percent of students’ comments were positive or very positive, highlighting themes such as the timing of teaching, relevance, group sizes, and the use of actors, tutors, and clinical scenarios. Conclusion Scenario-based teaching of clinical communication skills is positively received by students. Studies need to demonstrate an impact on practice, performance, development, and sustainability of communications training. PMID:25653569

Comparison between refraction measured by Spot Vision ScreeningTM and subjective clinical refractometry

PubMed Central

de Jesus, Daniela Lima; Villela, Flávio Fernandes; Orlandin, Luis Fernando; Eiji, Fernando Naves; Dantas, Daniel Oliveira; Alves, Milton Ruiz

2016-01-01

OBJECTIVE: The purpose of this study was to evaluate the accuracy of Spot Vision ScreeningTM as an autorefractor by comparing refraction measurements to subjective clinical refractometry results in children and adult patients. METHODS: One-hundred and thirty-four eyes of 134 patients were submitted to refractometry by Spot and clinical refractometry under cycloplegia. Patients, students, physicians, staff and children of staff from the Hospital das Clínicas (School of Medicine, University of São Paulo) aged 7-50 years without signs of ocular disease were examined. Only right-eye refraction data were analyzed. The findings were converted in magnitude vectors for analysis. RESULTS: The difference between Spot Vision ScreeningTM and subjective clinical refractometry expressed in spherical equivalents was +0.66±0.56 diopters (D), +0.16±0.27 D for the vector projected on the 90 axis and +0.02±0.15 D for the oblique vector. CONCLUSIONS: Despite the statistical significance of the difference between the two methods, we consider the difference non-relevant in a clinical setting, supporting the use of Spot Vision ScreeningTM as an ancillary method for estimating refraction. PMID:26934234

Surrogate outcomes are associated with low methodological quality of studies of rheumatoid arthritis treated with antitumour necrosis factor agents: a systematic review.

PubMed

Nobre, Moacyr Roberto Cuce; da Costa, Frnanda Marques

2012-02-01

Surrogate endpoints may be used as substitutes for, but often do not predict clinically relevant events. Objective To assess the methodological quality of articles that present their conclusions based on clinically relevant or surrogate outcomes in a systematic review of randomised trials and cohort studies of patients with rheumatoid arthritis treated with antitumour necrosis factor (TNF) agents. PubMed, Embase and Cochrane databases were searched. The Jadad score, the percentage of Consolidated Standards Of Reporting Trials (CONSORT) statement items adequately reported and levels-of-evidence (Center for Evidence-based Medicine, Oxford) were used in a descriptive synthesis. Among 88 articles appraised, 27 had surrogate endpoints, mainly radiographic, and 44 were duplicate publications; 74% of articles with surrogate and 39% of articles with clinical endpoints (p=0.006). Fewer articles with surrogate endpoints represented a high level of evidence (Level 1b, 33% vs 62%, p=0.037) and the mean percentage of CONSORT statement items met was also lower for articles with surrogate endpoints (62.5 vs 70.7, p=0.026). Although fewer articles with surrogate endpoints were randomised trials (63% vs 74%, p=0.307) and articles with surrogate endpoints had lower Jadad scores (3.0 vs 3.2, p=0.538), these differences were not statistically significant. Studies of anti-TNF agents that report surrogate outcomes are of lesser methodological quality. As such, inclusion of such studies in evidence syntheses may bias results.

Quantitative Ultrasound Using Texture Analysis of Myofascial Pain Syndrome in the Trapezius.

PubMed

Kumbhare, Dinesh A; Ahmed, Sara; Behr, Michael G; Noseworthy, Michael D

2018-01-01

Objective-The objective of this study is to assess the discriminative ability of textural analyses to assist in the differentiation of the myofascial trigger point (MTrP) region from normal regions of skeletal muscle. Also, to measure the ability to reliably differentiate between three clinically relevant groups: healthy asymptomatic, latent MTrPs, and active MTrP. Methods-18 and 19 patients were identified with having active and latent MTrPs in the trapezius muscle, respectively. We included 24 healthy volunteers. Images were obtained by research personnel, who were blinded with respect to the clinical status of the study participant. Histograms provided first-order parameters associated with image grayscale. Haralick, Galloway, and histogram-related features were used in texture analysis. Blob analysis was conducted on the regions of interest (ROIs). Principal component analysis (PCA) was performed followed by multivariate analysis of variance (MANOVA) to determine the statistical significance of the features. Results-92 texture features were analyzed for factorability using Bartlett's test of sphericity, which was significant. The Kaiser-Meyer-Olkin measure of sampling adequacy was 0.94. PCA demonstrated rotated eigenvalues of the first eight components (each comprised of multiple texture features) explained 94.92% of the cumulative variance in the ultrasound image characteristics. The 24 features identified by PCA were included in the MANOVA as dependent variables, and the presence of a latent or active MTrP or healthy muscle were independent variables. Conclusion-Texture analysis techniques can discriminate between the three clinically relevant groups.

Comparative effectiveness research in hand surgery.

PubMed

Johnson, Shepard P; Chung, Kevin C

2014-08-01

Comparative effectiveness research (CER) is a concept initiated by the Institute of Medicine and financially supported by the federal government. The primary objective of CER is to improve decision making in medicine. This research is intended to evaluate the effectiveness, benefits, and harmful effects of alternative interventions. CER studies are commonly large, simple, observational, and conducted using electronic databases. To date, there is little comparative effectiveness evidence within hand surgery to guide therapeutic decisions. To draw conclusions on effectiveness through electronic health records, databases must contain clinical information and outcomes relevant to hand surgery interventions, such as patient-related outcomes. Copyright © 2014 Elsevier Inc. All rights reserved.

Symbrachydactyly

PubMed Central

Goodell, Parker B.; Bauer, Andrea S.; Sierra, Francisco J. A.; James, Michelle A.

2016-01-01

Background: Symbrachydactyly is a unilateral congenital hand malformation characterized by failure of formation of fingers and the presence of rudimentary digit nubbins. The management is variable and are investigated in this review. Methods: A detailed review of the literature was compiled into succinct clinically relevant categories. Results: Etiology, classification, non-surgical management, surgical intervention, and patient oriented outcomes are discussed. Conclusions: All interventions should prioritize realistic, evidence-supported appearance and functional gains. Studies of the baseline function and quality of life of children with symbrachydactyly would allow surgeons to better understand functional changes associated with various interventions and would help surgeons and parents to make the best treatment decisions. PMID:27698626

Panel 3: Genetics and Precision Medicine of Otitis Media.

PubMed

Lin, Jizhen; Hafrén, Hena; Kerschner, Joseph; Li, Jian-Dong; Brown, Steve; Zheng, Qing Y; Preciado, Diego; Nakamura, Yoshihisa; Huang, Qiuhong; Zhang, Yan

2017-04-01

Objective The objective is to perform a comprehensive review of the literature up to 2015 on the genetics and precision medicine relevant to otitis media. Data Sources PubMed database of the National Library of Medicine. Review Methods Two subpanels were formed comprising experts in the genetics and precision medicine of otitis media. Each of the panels reviewed the literature in their respective fields and wrote draft reviews. The reviews were shared with all panel members, and a merged draft was created. The entire panel met at the 18th International Symposium on Recent Advances in Otitis Media in June 2015 and discussed the review and refined the content. A final draft was made, circulated, and approved by the panel members. Conclusion Many genes relevant to otitis media have been identified in the last 4 years in advancing our knowledge regarding the predisposition of the middle ear mucosa to commensals and pathogens. Advances include mutant animal models and clinical studies. Many signaling pathways are involved in the predisposition of otitis media. Implications for Practice New knowledge on the genetic background relevant to otitis media forms a basis of novel potential interventions, including potential new ways to treat otitis media.

The relevance of non-human primate and rodent malaria models for humans

PubMed Central

2011-01-01

At the 2010 Keystone Symposium on "Malaria: new approaches to understanding Host-Parasite interactions", an extra scientific session to discuss animal models in malaria research was convened at the request of participants. This was prompted by the concern of investigators that skepticism in the malaria community about the use and relevance of animal models, particularly rodent models of severe malaria, has impacted on funding decisions and publication of research using animal models. Several speakers took the opportunity to demonstrate the similarities between findings in rodent models and human severe disease, as well as points of difference. The variety of malaria presentations in the different experimental models parallels the wide diversity of human malaria disease and, therefore, might be viewed as a strength. Many of the key features of human malaria can be replicated in a variety of nonhuman primate models, which are very under-utilized. The importance of animal models in the discovery of new anti-malarial drugs was emphasized. The major conclusions of the session were that experimental and human studies should be more closely linked so that they inform each other, and that there should be wider access to relevant clinical material. PMID:21288352

Concept mapping enhances learning of biochemistry

PubMed Central

Surapaneni, Krishna M.; Tekian, Ara

2013-01-01

Background Teaching basic science courses is challenging in undergraduate medical education because of the ubiquitous use of didactic lectures and reward for recall of factual information during examinations. The purpose of this study is to introduce concept maps with clinical cases (the innovative program) to improve learning of biochemistry course content. Methods Participants were first year medical students (n=150) from Saveetha Medical College and Hospital (India); they were randomly divided into two groups of 75, one group attending the traditional program, the other the innovative program. Student performance was measured using three written knowledge tests (each with a maximum score of 20). The students also evaluated the relevance of the learning process using a 12-item questionnaire. Results Students in the innovative program using concept mapping outperformed those in the traditional didactic program (means of 7.13–8.28 vs. 12.33–13.93, p<0.001). The students gave high positive ratings for the innovative course (93–100% agreement). Conclusion The new concept-mapping program resulted in higher academic performance compared to the traditional course and was perceived favorably by the students. They especially valued the use of concept mapping as learning tools to foster the relevance of biochemistry to clinical practice, and to enhance their reasoning and learning skills, as well as their deeper understanding for biochemistry. PMID:23464600

Clinical relevance of quantified fundus autofluorescence in diabetic macular oedema

PubMed Central

Yoshitake, S; Murakami, T; Uji, A; Unoki, N; Dodo, Y; Horii, T; Yoshimura, N

2015-01-01

Purpose To quantify the signal intensity of fundus autofluorescence (FAF) and evaluate its association with visual function and optical coherence tomography (OCT) findings in diabetic macular oedema (DMO). Methods We reviewed 103 eyes of 78 patients with DMO and 30 eyes of 22 patients without DMO. FAF images were acquired using Heidelberg Retina Angiograph 2, and the signal levels of FAF in the individual subfields of the Early Treatment Diabetic Retinopathy Study grid were measured. We evaluated the association between quantified FAF and the logMAR VA and OCT findings. Results One hundred and three eyes with DMO had lower FAF signal intensity levels in the parafoveal subfields compared with 30 eyes without DMO. The autofluorescence intensity in the parafoveal subfields was associated negatively with logMAR VA and the retinal thickness in the corresponding subfields. The autofluorescence levels in the parafoveal subfield, except the nasal subfield, were lower in eyes with autofluorescent cystoid spaces in the corresponding subfield than in those without autofluorescent cystoid spaces. The autofluorescence level in the central subfield was related to foveal cystoid spaces but not logMAR VA or retinal thickness in the corresponding area. Conclusions Quantified FAF in the parafovea has diagnostic significance and is clinically relevant in DMO. PMID:25771817

Detection Rate and Clinical Relevance of Ink Tattooing during Balloon-Assisted Enteroscopy

PubMed Central

Ebigbo, A.; Schrempf, M.; Messmann, H.; Gölder, S. K.

2017-01-01

Background and Aims Balloon-assisted enteroscopy (BAE) is a well-established tool in the diagnosis and therapy of small bowel diseases. Ink tattooing of the small bowel is used to mark pathologic lesions or the depth of small bowel insertion. The purpose of this study was to determine the safety, the detection rate, and the clinical relevance of ink tattooing during BAE. Methods We performed a retrospective analysis of all 81 patients who received an ink tattooing during BAE between 2010 and 2015. Results In all patients, ink tattooing was performed with no complications. 26 patients received a capsule endoscopy after BAE. The tattoo could be detected via capsule endoscopy in 19 of these 26 patients. The tattoo of the previous BAE could be detected via opposite BAE in 2 of 11 patients. In 9 patients, ink tattooing influenced the choice of approach for reenteroscopy. In 7 patients, the tattoo was used for intraoperative localization and in 3 patients for intraoperative localization as well as for reenteroscopy. The intraoperative detection rate of the tattoo was 100%. Conclusion Ink tattooing of the small intestine is a safe endoscopic procedure to mark the depth of scope insertion or a pathologic lesion during balloon-assisted enteroscopy. PMID:29230241

Diabetes Self-Management Care via Cell Phone: A Systematic Review

PubMed Central

Krishna, Santosh; Boren, Suzanne Austin

2008-01-01

Background The objective of this study was to evaluate the evidence on the impact of cell phone interventions for persons with diabetes and/or obesity in improving health outcomes and/or processes of care for persons with diabetes and/or obesity. Methods We searched Medline (1966–2007) and reviewed reference lists from included studies and relevant reviews to identify additional studies. We extracted descriptions of the study design, sample size, patient age, duration of study, technology, educational content and delivery environment, intervention and control groups, process and outcome measures, and statistical significance. Results In this review, we included 20 articles, representing 18 studies, evaluating the use of a cell phone for health information for persons with diabetes or obesity. Thirteen of 18 studies measured health outcomes and the remaining 5 studies evaluated processes of care. Outcomes were grouped into learning, behavior change, clinical improvement, and improved health status. Nine out of 10 studies that measured hemoglobin A1c reported significant improvement among those receiving education and care support. Cell phone and text message interventions increased patient–provider and parent–child communication and satisfaction with care. Conclusions Providing care and support with cell phones and text message interventions can improve clinically relevant diabetes-related health outcomes by increasing knowledge and self-efficacy to carry out self-management behaviors. PMID:19885219

The impact of patents on the development of genome-based clinical diagnostics: an analysis of case studies

PubMed Central

Pierce, Brandon L.; Carlson, Christopher S.; Kuszler, Patricia C.; Stanford, Janet L.; Austin, Melissa A.

2010-01-01

Purpose Fragmented ownership of diagnostic gene patents has the potential to create an ‘anticommons’ in the area of genomic diagnostics, making it difficult and expensive to assemble the patent rights necessary to develop a panel of genetic tests. The objectives of this study were to identify U.S. patents that protect existing panels of genetic tests, describe how (or if) test providers acquired rights to these patents, and determine if fragmented patent ownership has inhibited the commercialization of these panels. Methods As case studies, we selected four clinical applications of genetic testing (cystic fibrosis, maturity-onset diabetes of the young, long QT syndrome, and hereditary breast cancer) that utilize tests protected by ≥3 U.S. patents. We summarized publically available information on relevant patents, test providers, licenses, and litigation. Results For each case study, all tests of major genes/mutations were patented, and at least one party held the collective rights to conduct all relevant tests, often as a result of licensing agreements. Conclusions We did not find evidence that fragmentation of patent rights has inhibited commercialization of genetic testing services. However, as knowledge of genetic susceptibility increases, it will be important to consider the potential consequences of fragmented ownership of diagnostic gene patents. PMID:19367193

Neonatal morphine in extremely and very preterm neonates: its effect on the developing brain - a review.

PubMed

Schuurmans, Juliette; Benders, Manon; Lemmers, Petra; van Bel, Frank

2015-01-01

Preterm infants requiring intensive care experience a large number of stressful and painful procedures. Management of stress and pain is therefore an important issue. This review provides an overview of the research on the use of morphine and its neurodevelopmental effects on this vulnerable group of neonates. A structural literature search of both experimental and clinical data has been done using an electronic database (PubMed), but also relevant reference lists and related articles were used. A total of 39 sources were considered relevant for this review to elucidate the effects of morphine on the developing brain. The results showed that both animal experimental and clinical data displayed conflicting results on the effects of neonatal morphine on neurodevelopmental outcome. However, in contrast to specific short-term neurological outcomes long-term neurodevelopmental outcome does not seem to be adversely affected by morphine. After a careful review of the literature, no definite conclusions concerning the effects of neonatal morphine on the long-term neurodevelopmental outcome in extremely premature neonates can be drawn. More prospectively designed trials should be conducted using reliable and validated pain assessment scores to evaluate effects of morphine on long-term neurodevelopmental outcome to demonstrate a beneficial or adverse effect of morphine in preterm infants.

Current Concepts: Osteochondritis Dissecans of the Capitellum and the Role of Osteochondral Autograft Transplantation.

PubMed

Kirsch, Jacob M; Thomas, Jared; Bedi, Asheesh; Lawton, Jeffrey N

2016-12-01

Background: Osteochondritis dissecans (OCD) of the capitellum is a painful condition, which often affects young throwing athletes. Our current understanding regarding the etiology, risks factors, diagnosis, and efficacy of the available treatment options has expanded over recent years, however remains suboptimal. Recent data on patient-reported outcomes following osteochondral autograft transplantation (OAT) for the treatment of large osteochondral lesions of the capitellum have been promising but limited. This review seeks to critically analyze and summarize the available literature on the etiology, diagnosis, and reported outcomes associated with OCD of the capitellum and the use of OAT for its treatment. Methods: A comprehensive literature search was conducted. Unique and customized search strategies were formulated in PubMed, Embase, Scopus, Web of Science, and CENTRAL. Combinations of keywords and controlled vocabulary terms were utilized in order to cast a broad net. Relevant clinical, biomechanical, anatomic and imaging studies were reviewed along with recent review articles, and case series. Results: Forty-three articles from our initial literature search were found to be relevant for this review. The majority of these articles were either review articles, clinical studies, anatomic or imaging studies or biomechanical studies. Conclusions: Current evidence suggests that OAT may lead to better and more consistent outcomes than previously described methods for treating large OCD lesions of the capitellum.

Systematic reviews of complementary therapies – an annotated bibliography. Part 3: Homeopathy

PubMed Central

Linde, Klaus; Hondras, Maria; Vickers, Andrew; Riet, Gerben ter; Melchart, Dieter

2001-01-01

Background Complementary therapies are widespread but controversial. We aim to provide a comprehensive collection and a summary of systematic reviews of clinical trials in three major complementary therapies (acupuncture, herbal medicine, homeopathy). This article is dealing with homeopathy. Potentially relevant reviews were searched through the register of the Cochrane Complementary Medicine Field, the Cochrane Library, Medline, and bibliographies of articles and books. To be included articles had to review prospective clinical trials of homeopathy; had to describe review methods explicitly; had to be published; and had to focus on treatment effects. Information on conditions, interventions, methods, results and conclusions was extracted using a pretested form and summarized descriptively. Results Eighteen out of 22 potentially relevant reviews preselected in the screening process met the inclusion criteria. Six reviews addressed the question whether homeopathy is effective across conditions and interventions. The majority of available trials seem to report positive results but the evidence is not convincing. For isopathic nosodes for allergic conditions, oscillococcinum for influenza-like syndromes and galphimia for pollinosis the evidence is promising while in other areas reviewed the results are equivocal. Interpretation Reviews on homeopathy often address general questions. While the evidence is promising for some topics the findings of the available reviews are unlikely to end the controversy on this therapy. PMID:11527508

Clinical research data warehouse governance for distributed research networks in the USA: a systematic review of the literature

PubMed Central

Holmes, John H; Elliott, Thomas E; Brown, Jeffrey S; Raebel, Marsha A; Davidson, Arthur; Nelson, Andrew F; Chung, Annie; La Chance, Pierre; Steiner, John F

2014-01-01

Objective To review the published, peer-reviewed literature on clinical research data warehouse governance in distributed research networks (DRNs). Materials and methods Medline, PubMed, EMBASE, CINAHL, and INSPEC were searched for relevant documents published through July 31, 2013 using a systematic approach. Only documents relating to DRNs in the USA were included. Documents were analyzed using a classification framework consisting of 10 facets to identify themes. Results 6641 documents were retrieved. After screening for duplicates and relevance, 38 were included in the final review. A peer-reviewed literature on data warehouse governance is emerging, but is still sparse. Peer-reviewed publications on UK research network governance were more prevalent, although not reviewed for this analysis. All 10 classification facets were used, with some documents falling into two or more classifications. No document addressed costs associated with governance. Discussion Even though DRNs are emerging as vehicles for research and public health surveillance, understanding of DRN data governance policies and procedures is limited. This is expected to change as more DRN projects disseminate their governance approaches as publicly available toolkits and peer-reviewed publications. Conclusions While peer-reviewed, US-based DRN data warehouse governance publications have increased, DRN developers and administrators are encouraged to publish information about these programs. PMID:24682495

Reservations about the conclusions of the interdivisional (APA Divisions 12 & 29) task force on evidence-based therapy relationships: what do we know, what don't we know?

PubMed

Kazantzis, Nikolaos; Cronin, Timothy J; Norton, Peter J; Lai, Jerry; Hofmann, Stefan G

2015-05-01

We offer a critical and constructive appraisal of the conclusions provided by the Interdivisional (American Psychological Association [APA] Divisions 12 & 29) Task Force on Evidence-Based Therapy Relationships. We highlight problems in overlapping terminology and definitions, as well as problems in the conduct of its meta-analyses (i.e., duplication of studies between reviews, inappropriate study inclusion, and use of measures of specific constructs for the calculation of effects for multiple relationship elements). On this basis, we express reservation about the conclusions offered by the APA Task Force. This special issue explores whether there are other therapeutic relationship elements that warrant consideration and further study. We were particularly interested in those elements that showed promise based on empirical or theoretical grounds, and in each article, we asked for an account of how the case formulation would guide the methods of adaptation for each individual client, and how the element would contribute to clinically relevant changes. © 2015 Wiley Periodicals, Inc.

Does the choice of display system influence perception and visibility of clinically relevant features in digital pathology images?

NASA Astrophysics Data System (ADS)

Kimpe, Tom; Rostang, Johan; Avanaki, Ali; Espig, Kathryn; Xthona, Albert; Cocuranu, Ioan; Parwani, Anil V.; Pantanowitz, Liron

2014-03-01

Digital pathology systems typically consist of a slide scanner, processing software, visualization software, and finally a workstation with display for visualization of the digital slide images. This paper studies whether digital pathology images can look different when presenting them on different display systems, and whether these visual differences can result in different perceived contrast of clinically relevant features. By analyzing a set of four digital pathology images of different subspecialties on three different display systems, it was concluded that pathology images look different when visualized on different display systems. The importance of these visual differences is elucidated when they are located in areas of the digital slide that contain clinically relevant features. Based on a calculation of dE2000 differences between background and clinically relevant features, it was clear that perceived contrast of clinically relevant features is influenced by the choice of display system. Furthermore, it seems that the specific calibration target chosen for the display system has an important effect on the perceived contrast of clinically relevant features. Preliminary results suggest that calibrating to DICOM GSDF calibration performed slightly worse than sRGB, while a new experimental calibration target CSDF performed better than both DICOM GSDF and sRGB. This result is promising as it suggests that further research work could lead to better definition of an optimized calibration target for digital pathology images resulting in a positive effect on clinical performance.

Detecting clinically relevant new information in clinical notes across specialties and settings.

PubMed

Zhang, Rui; Pakhomov, Serguei V S; Arsoniadis, Elliot G; Lee, Janet T; Wang, Yan; Melton, Genevieve B

2017-07-05

Automated methods for identifying clinically relevant new versus redundant information in electronic health record (EHR) clinical notes is useful for clinicians and researchers involved in patient care and clinical research, respectively. We evaluated methods to automatically identify clinically relevant new information in clinical notes, and compared the quantity of redundant information across specialties and clinical settings. Statistical language models augmented with semantic similarity measures were evaluated as a means to detect and quantify clinically relevant new and redundant information over longitudinal clinical notes for a given patient. A corpus of 591 progress notes over 40 inpatient admissions was annotated for new information longitudinally by physicians to generate a reference standard. Note redundancy between various specialties was evaluated on 71,021 outpatient notes and 64,695 inpatient notes from 500 solid organ transplant patients (April 2015 through August 2015). Our best method achieved at best performance of 0.87 recall, 0.62 precision, and 0.72 F-measure. Addition of semantic similarity metrics compared to baseline improved recall but otherwise resulted in similar performance. While outpatient and inpatient notes had relatively similar levels of high redundancy (61% and 68%, respectively), redundancy differed by author specialty with mean redundancy of 75%, 66%, 57%, and 55% observed in pediatric, internal medicine, psychiatry and surgical notes, respectively. Automated techniques with statistical language models for detecting redundant versus clinically relevant new information in clinical notes do not improve with the addition of semantic similarity measures. While levels of redundancy seem relatively similar in the inpatient and ambulatory settings in the Fairview Health Services, clinical note redundancy appears to vary significantly with different medical specialties.

The Value of Decision Analytical Modeling in Surgical Research: An Example of Laparoscopic Versus Open Distal Pancreatectomy.

PubMed

Tax, Casper; Govaert, Paulien H M; Stommel, Martijn W J; Besselink, Marc G H; Gooszen, Hein G; Rovers, Maroeska M

2017-11-02

To illustrate how decision modeling may identify relevant uncertainty and can preclude or identify areas of future research in surgery. To optimize use of research resources, a tool is needed that assists in identifying relevant uncertainties and the added value of reducing these uncertainties. The clinical pathway for laparoscopic distal pancreatectomy (LDP) versus open (ODP) for nonmalignant lesions was modeled in a decision tree. Cost-effectiveness based on complications, hospital stay, costs, quality of life, and survival was analyzed. The effect of existing uncertainty on the cost-effectiveness was addressed, as well as the expected value of eliminating uncertainties. Based on 29 nonrandomized studies (3.701 patients) the model shows that LDP is more cost-effective compared with ODP. Scenarios in which LDP does not outperform ODP for cost-effectiveness seem unrealistic, e.g., a 30-day mortality rate of 1.79 times higher after LDP as compared with ODP, conversion in 62.2%, surgically repair of incisional hernias in 21% after LDP, or an average 2.3 days longer hospital stay after LDP than after ODP. Taking all uncertainty into account, LDP remained more cost-effective. Minimizing these uncertainties did not change the outcome. The results show how decision analytical modeling can help to identify relevant uncertainty and guide decisions for future research in surgery. Based on the current available evidence, a randomized clinical trial on complications, hospital stay, costs, quality of life, and survival is highly unlikely to change the conclusion that LDP is more cost-effective than ODP.

The Effects of Clinically Relevant Multiple-Choice Items on the Statistical Discrimination of Physician Clinical Competence.

ERIC Educational Resources Information Center

Downing, Steven M.; Maatsch, Jack L.

To test the effect of clinically relevant multiple-choice item content on the validity of statistical discriminations of physicians' clinical competence, data were collected from a field test of the Emergency Medicine Examination, test items for the certification of specialists in emergency medicine. Two 91-item multiple-choice subscales were…

Knowledge discovery for Deep Phenotyping serious mental illness from Electronic Mental Health records.

PubMed

Jackson, Richard; Patel, Rashmi; Velupillai, Sumithra; Gkotsis, George; Hoyle, David; Stewart, Robert

2018-01-01

Background: Deep Phenotyping is the precise and comprehensive analysis of phenotypic features in which the individual components of the phenotype are observed and described. In UK mental health clinical practice, most clinically relevant information is recorded as free text in the Electronic Health Record, and offers a granularity of information beyond what is expressed in most medical knowledge bases. The SNOMED CT nomenclature potentially offers the means to model such information at scale, yet given a sufficiently large body of clinical text collected over many years, it is difficult to identify the language that clinicians favour to express concepts. Methods: By utilising a large corpus of healthcare data, we sought to make use of semantic modelling and clustering techniques to represent the relationship between the clinical vocabulary of internationally recognised SMI symptoms and the preferred language used by clinicians within a care setting. We explore how such models can be used for discovering novel vocabulary relevant to the task of phenotyping Serious Mental Illness (SMI) with only a small amount of prior knowledge.  Results: 20 403 terms were derived and curated via a two stage methodology. The list was reduced to 557 putative concepts based on eliminating redundant information content. These were then organised into 9 distinct categories pertaining to different aspects of psychiatric assessment. 235 concepts were found to be expressions of putative clinical significance. Of these, 53 were identified having novel synonymy with existing SNOMED CT concepts. 106 had no mapping to SNOMED CT. Conclusions: We demonstrate a scalable approach to discovering new concepts of SMI symptomatology based on real-world clinical observation. Such approaches may offer the opportunity to consider broader manifestations of SMI symptomatology than is typically assessed via current diagnostic frameworks, and create the potential for enhancing nomenclatures such as SNOMED CT based on real-world expressions.

No Clinically Significant Difference Between Adult and Pediatric IKDC Subjective Knee Evaluation Scores in Adults

PubMed Central

Stegmeier, Nicole; Oak, Sameer R.; O’Rourke, Colin; Strnad, Greg; Spindler, Kurt P.; Jones, Morgan; Farrow, Lutul D.; Andrish, Jack; Saluan, Paul

2017-01-01

Background: Two versions of the International Knee Documentation Committee (IKDC) Subjective Knee Evaluation form currently exist: the original version (1999) and a recently modified pediatric-specific version (2011). Comparison of the pediatric IKDC with the adult version in the adult population may reveal that either version could be used longitudinally. Hypothesis: We hypothesize that the scores for the adult IKDC and pediatric IKDC will not be clinically different among adult patients aged 18 to 50 years. Study Design: Randomized crossover study design. Level of Evidence: Level 2. Methods: The study consisted of 100 participants, aged 18 to 50 years, who presented to orthopaedic outpatient clinics with knee problems. All participants completed both adult and pediatric versions of the IKDC in random order with a 10-minute break in between. We used a paired t test to test for a difference between the scores and a Welch’s 2-sample t test to test for equivalence. A least-squares regression model was used to model adult scores as a function of pediatric scores, and vice versa. Results: A paired t test revealed a statistically significant 1.6-point difference between the mean adult and pediatric scores. However, the 95% confidence interval (0.54-2.66) for this difference did not exceed our a priori threshold of 5 points, indicating that this difference was not clinically important. Equivalence testing with an equivalence region of 5 points further supported this finding. The adult and pediatric scores had a linear relationship and were highly correlated with an R2 of 92.6%. Conclusion: There is no clinically relevant difference between the scores of the adult and pediatric IKDC forms in adults, aged 18 to 50 years, with knee conditions. Clinical Relevance: Either form, adult or pediatric, of the IKDC can be used in this population for longitudinal studies. If the pediatric version is administered in adolescence, it can be used for follow-up into adulthood. PMID:28080306

Association of weight loss with improved disease activity in patients with rheumatoid arthritis: A retrospective analysis using electronic medical record data

PubMed Central

Kreps, David J.; Halperin, Florencia; Desai, Sonali P.; Zhang, Zhi Z.; Losina, Elena; Olson, Amber T.; Karlson, Elizabeth W.; Bermas, Bonnie L.; Sparks, Jeffrey A.

2018-01-01

Objective To evaluate the association between weight loss and rheumatoid arthritis (RA) disease activity. Methods We conducted a retrospective cohort study of RA patients seen at routine clinic visits at an academic medical center, 2012–2015. We included patients who had ≥2 clinical disease activity index (CDAI) measures. We identified visits during follow-up where the maximum and minimum weights occurred and defined weight change and CDAI change as the differences of these measures at these visits. We defined disease activity improvement as CDAI decrease of ≥5 and clinically relevant weight loss as ≥5 kg. We performed logistic regression analyses to establish the association between improved disease activity and weight loss and baseline BMI category (≥25 kg/m2 or <25 kg/m2). We built linear regression models to investigate the association between continuous weight loss and CDAI change among patients who were overweight/obese at baseline and who lost weight during follow-up. Results We analyzed data from 174 RA patients with a median follow-up of 1.9 years (IQR 1.3–2.4); 117 (67%) were overweight/obese at baseline, and 53 (31%) lost ≥5 kg during follow-up. Patients who were overweight/obese and lost ≥5 kg had three-fold increased odds of disease activity improvement compared to those who did not (OR 3.03, 95%CI 1.18–7.83). Among those who were overweight/obese at baseline, each kilogram weight loss was associated with CDAI improvement of 1.15 (95%CI 0.42–1.88). Our study was limited by using clinical data from a single center without fixed intervals for assessments. Conclusion Clinically relevant weight loss (≥5 kg) was associated with improved RA disease activity in the routine clinical setting. Further studies are needed for replication and to evaluate the effect of prospective weight loss interventions on RA disease activity. PMID:29606976

Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines

PubMed Central

Norris, Susan L.; Schulman, Sam; Hirsh, Jack; Eckman, Mark H.; Akl, Elie A.; Crowther, Mark; Vandvik, Per Olav; Eikelboom, John W.; McDonagh, Marian S.; Lewis, Sandra Zelman; Gutterman, David D.; Cook, Deborah J.; Schünemann, Holger J.

2012-01-01

Background: To develop the Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: ACCP Evidence-Based Clinical Practice Guidelines (AT9), the American College of Chest Physicians (ACCP) assembled a panel of clinical experts, information scientists, decision scientists, and systematic review and guideline methodologists. Methods: Clinical areas were designated as articles, and a methodologist without important intellectual or financial conflicts of interest led a panel for each article. Only panel members without significant conflicts of interest participated in making recommendations. Panelists specified the population, intervention and alternative, and outcomes for each clinical question and defined criteria for eligible studies. Panelists and an independent evidence-based practice center executed systematic searches for relevant studies and evaluated the evidence, and where resources and evidence permitted, they created standardized tables that present the quality of the evidence and key results in a transparent fashion. Results: One or more recommendations relate to each specific clinical question, and each recommendation is clearly linked to the underlying body of evidence. Judgments regarding the quality of evidence and strength of recommendations were based on approaches developed by the Grades of Recommendations, Assessment, Development, and Evaluation Working Group. Panel members constructed scenarios describing relevant health states and rated the disutility associated with these states based on an additional systematic review of evidence regarding patient values and preferences for antithrombotic therapy. These ratings guided value and preference decisions underlying the recommendations. Each topic panel identified questions in which resource allocation issues were particularly important and, for these issues, experts in economic analysis provided additional searches and guidance. Conclusions: AT9 methodology reflects the current science of evidence-based clinical practice guideline development, with reliance on high-quality systematic reviews, a standardized process for quality assessment of individual studies and the body of evidence, an explicit process for translating the evidence into recommendations, disclosure of financial as well as intellectual conflicts of interest followed by management of disclosed conflicts, and extensive peer review. PMID:22315256

Knowledge discovery for Deep Phenotyping serious mental illness from Electronic Mental Health records

PubMed Central

Jackson, Richard; Patel, Rashmi; Velupillai, Sumithra; Gkotsis, George; Hoyle, David; Stewart, Robert

2018-01-01

Background: Deep Phenotyping is the precise and comprehensive analysis of phenotypic features in which the individual components of the phenotype are observed and described. In UK mental health clinical practice, most clinically relevant information is recorded as free text in the Electronic Health Record, and offers a granularity of information beyond what is expressed in most medical knowledge bases. The SNOMED CT nomenclature potentially offers the means to model such information at scale, yet given a sufficiently large body of clinical text collected over many years, it is difficult to identify the language that clinicians favour to express concepts. Methods: By utilising a large corpus of healthcare data, we sought to make use of semantic modelling and clustering techniques to represent the relationship between the clinical vocabulary of internationally recognised SMI symptoms and the preferred language used by clinicians within a care setting. We explore how such models can be used for discovering novel vocabulary relevant to the task of phenotyping Serious Mental Illness (SMI) with only a small amount of prior knowledge.  Results: 20 403 terms were derived and curated via a two stage methodology. The list was reduced to 557 putative concepts based on eliminating redundant information content. These were then organised into 9 distinct categories pertaining to different aspects of psychiatric assessment. 235 concepts were found to be expressions of putative clinical significance. Of these, 53 were identified having novel synonymy with existing SNOMED CT concepts. 106 had no mapping to SNOMED CT. Conclusions: We demonstrate a scalable approach to discovering new concepts of SMI symptomatology based on real-world clinical observation. Such approaches may offer the opportunity to consider broader manifestations of SMI symptomatology than is typically assessed via current diagnostic frameworks, and create the potential for enhancing nomenclatures such as SNOMED CT based on real-world expressions. PMID:29899974

Measuring saccade peak velocity using a low-frequency sampling rate of 50 Hz.

PubMed

Wierts, Roel; Janssen, Maurice J A; Kingma, Herman

2008-12-01

During the last decades, small head-mounted video eye trackers have been developed in order to record eye movements. Real-time systems-with a low sampling frequency of 50/60 Hz-are used for clinical vestibular practice, but are generally considered not to be suited for measuring fast eye movements. In this paper, it is shown that saccadic eye movements, having an amplitude of at least 5 degrees, can, in good approximation, be considered to be bandwidth limited up to a frequency of 25-30 Hz. Using the Nyquist theorem to reconstruct saccadic eye movement signals at higher temporal resolutions, it is shown that accurate values for saccade peak velocities, recorded at 50 Hz, can be obtained, but saccade peak accelerations and decelerations cannot. In conclusion, video eye trackers sampling at 50/60 Hz are appropriate for detecting the clinical relevant saccade peak velocities in contrast to what has been stated up till now.

Time for a change to assess and evaluate body temperature in clinical practice.

PubMed

Sund-Levander, Märtha; Grodzinsky, Ewa

2009-08-01

The definition of normal body temperature as 37 degrees C still is considered the norm worldwide, but in practice there is a widespread confusion of the evaluation of body temperature, especially in elderly individuals. In this paper, we discuss the relevance of normal body temperature as 37 degrees C and consequences in clinical practice. Our conclusion is that body temperature should be evaluated in relation to the individual variability and that the best approach is to use the same site, and an unadjusted mode without adjustments to other sites. If the baseline value is not known, it is important to notice that frail elderly individuals are at risk of a low body temperature. In addition, what should be regarded as fever is closely related to what is considered as normal body temperature. That is, as normal body temperature shows individual variations, it is reasonable that the same should hold true for the febrile range.

Acute myeloid leukemia associated with t(10;17)(p13-15;q12-21) and phagocytic activity by leukemic blasts: a clinical study and review of the literature.

PubMed

Oh, Seung Hwan; Park, Tae Sung; Cho, Sun Young; Kim, Min Jin; Huh, Jungwon; Kim, Bomi; Song, Sae Am; Lee, Ja Young; Jun, Kyung Ran; Shin, Jeong Hwan; Kim, Hye Ran; Lee, Jeong Nyeo

2010-10-01

Translocation (10;17)(p13-15;q12-21) in acute leukemia is rarely reported in the literature. Here, we present both a novel t(10;17) case study and a review of relevant literature on t(10;17) in acute leukemia (10 cases). In summary, we came to the following preliminary conclusions: t(10;17) is associated with poorly differentiated acute leukemia subtype [90%; eight cases of acute myeloid leukemia (AML M0, M1) and one case of acute undifferentiated leukemia], phagocytic activity by blasts occurs (30%), and the survival time was short in three of the seven t(10;17) cases for whom follow-up data were available (median, 8 months). More clinical studies concerning the prognosis, treatment response, and survival of patients with t(10;17) are necessary. 2010 Elsevier Inc. All rights reserved.

One Year of Glaucoma Research in Review: 2013 to 2014

PubMed Central

Van Tassel, Sarah H.; Radcliffe, Nathan M.; Demetriades, Anna M.

2015-01-01

Purpose The purpose of this study was to provide the practicing clinical ophthalmologist with an update of relevant glaucoma literature published from 2013 to 2014. Design Literature review. Methods The authors conducted a 1-year (October 1, 2013, to September 30, 2014) English-language glaucoma literature search on PubMed of articles containing “glaucoma” or “glaucomatous” with title/abstract as a filter. Medical Subject Headings (MeSH) filtered searching was not performed because of the newness of the reviewed material. Results Literature review yielded 2,314 articles, after which we excluded reviews and letters to the editor. We highlighted articles featuring new or updated approaches to the pathophysiology, diagnosis, or treatment of glaucoma and gave preference to human research. Conclusions This review features literature that is of interest to ophthalmologists in practice and also highlights studies that may provide insight to future developments applicable to clinical ophthalmology. PMID:26197218

Foot care education in patients with diabetes at low risk of complications: a consensus statement

PubMed Central

McInnes, A; Jeffcoate, W; Vileikyte, L; Game, F; Lucas, K; Higson, N; Stuart, L; Church, A; Scanlan, J; Anders, J

2011-01-01

Aims To define and agree a practical educational framework for delivery by all healthcare professionals managing patients with diabetes, particularly those at low risk of developing foot complications. Methods A consensus meeting of a multidisciplinary expert panel. Prior to the meeting, relevant clinical papers were disseminated to the panel for review. The consensus was largely based upon the experts’ clinical experience and judgement. Results Four main health behaviours were identified for those at low risk of developing foot complications, namely:, control of blood glucose levels; attendance at annual foot screening examination; reporting of any changes in foot health immediately; and the engagement in a simple daily foot care routine. Conclusion There is currently little evidence-based literature to support specific foot care practices. Patients with diabetes at low risk of developing complications should be encouraged to undertake a basic foot care regimen to reduce their likelihood of developing complications. PMID:21219423

A study of an ethics education topic for undergraduate nursing students.

PubMed

Kalaitzidis, Evdokia; Schmitz, Karl

2012-01-01

The study aims to explore nursing students' perceptions of the relative value of various aspects of the ethical component of the undergraduate topic, 'Ethics and Law applied to Nursing' (topic NURS2104). To enable time for reflection on ethics in nursing, sampling occurred 1 year after successful completion of the above-mentioned topic and after successful completion of all but the final clinical experience components of the Bachelor of Nursing (BN) degree. A significant proportion of respondents perceived ethics education as relevant to professional practices. It is also noteworthy that the ethical decision-making strategies that had been incorporated into the topic (NURS2104) became transformed by the clinical experience of each particular student. While results of this study are not conclusive, they nevertheless provide important information for future nursing students on the evolutionary development of ethics education. Copyright © 2011 Elsevier Ltd. All rights reserved.

Nanoengineered implant as a new platform for regenerative nanomedicine using 3D well-organized human cell spheroids

PubMed Central

Keller, Laetitia; Idoux-Gillet, Ysia; Wagner, Quentin; Eap, Sandy; Brasse, David; Schwinté, Pascale; Arruebo, Manuel; Benkirane-Jessel, Nadia

2017-01-01

In tissue engineering, it is still rare today to see clinically transferable strategies for tissue-engineered graft production that conclusively offer better tissue regeneration than the already existing technologies, decreased recovery times, and less risk of complications. Here a novel tissue-engineering concept is presented for the production of living bone implants combining 1) a nanofibrous and microporous implant as cell colonization matrix and 2) 3D bone cell spheroids. This combination, double 3D implants, shows clinical relevant thicknesses for the treatment of an early stage of bone lesions before the need of bone substitutes. The strategy presented here shows a complete closure of a defect in nude mice calvaria after only 31 days. As a novel strategy for bone regenerative nanomedicine, it holds great promises to enhance the therapeutic efficacy of living bone implants. PMID:28138241

Overtraining Syndrome

PubMed Central

Kreher, Jeffrey B.; Schwartz, Jennifer B.

2012-01-01

Context: Fatigue and underperformance are common in athletes. Understanding overtraining syndrome (OTS) is helpful in the evaluation, management, and education of athletes. Evidence Acquisition: Relevant articles in English were searched with OVID (1948-2011) and PubMed using the following keywords: overtraining syndrome, overtraining, overreaching, unexplained underperformance, staleness, pathophysiology, management, treatment, evaluation. Bibliographies were reviewed for additional resources. Results: OTS appears to be a maladapted response to excessive exercise without adequate rest, resulting in perturbations of multiple body systems (neurologic, endocrinologic, immunologic) coupled with mood changes. Many hypotheses of OTS pathogenesis are reviewed, and a clinical approach to athletes with possible OTS (including history, testing, and prevention) is presented. Conclusions: OTS remains a clinical diagnosis with arbitrary definitions per the European College of Sports Science’s position statement. History and, in most situations, limited serologies are helpful. However, much remains to be learned given that most past research has been on athletes with overreaching rather than OTS. PMID:23016079

Neuroprosthetic technology for individuals with spinal cord injury

PubMed Central

Collinger, Jennifer L.; Foldes, Stephen; Bruns, Tim M.; Wodlinger, Brian; Gaunt, Robert; Weber, Douglas J.

2013-01-01

Context Spinal cord injury (SCI) results in a loss of function and sensation below the level of the lesion. Neuroprosthetic technology has been developed to help restore motor and autonomic functions as well as to provide sensory feedback. Findings This paper provides an overview of neuroprosthetic technology that aims to address the priorities for functional restoration as defined by individuals with SCI. We describe neuroprostheses that are in various stages of preclinical development, clinical testing, and commercialization including functional electrical stimulators, epidural and intraspinal microstimulation, bladder neuroprosthesis, and cortical stimulation for restoring sensation. We also discuss neural recording technologies that may provide command or feedback signals for neuroprosthetic devices. Conclusion/clinical relevance Neuroprostheses have begun to address the priorities of individuals with SCI, although there remains room for improvement. In addition to continued technological improvements, closing the loop between the technology and the user may help provide intuitive device control with high levels of performance. PMID:23820142

Alleged biological father incest: a forensic approach.

PubMed

Gomes, Vânia; Jardim, Patrícia; Taveira, Francisco; Dinis-Oliveira, Ricardo J; Magalhães, Teresa

2014-01-01

Paternal incest is one of the most serious forms of intrafamilial sexual abuse with clinical, social, and legal relevance. A retrospective study was performed, based on forensic reports and judicial decisions of alleged cases of biological paternal incest of victims under 18 years old (n = 215) from 2003 to 2008. Results highlight that in a relevant number of cases: victims were female; the abuse begun at an early age with reiteration; the alleged perpetrator presented a history of sexual crimes against children; sexual practices were physically poorly intrusive, which associated with a forensic medical evaluation performed more than 72 h after the abuse, explain partially the absence of physical injuries or other evidence-these last aspects are different from extrafamilial cases. In conclusion, observations about paternal incest are likely to exacerbate the psychosocial consequences of the abuse and may explain the difficulty and delay in detect and disclose these cases. Few cases were legally prosecuted and convicted. © 2013 American Academy of Forensic Sciences.

Nutraceuticals for Skin Care: A Comprehensive Review of Human Clinical Studies.

PubMed

Pérez-Sánchez, Almudena; Barrajón-Catalán, Enrique; Herranz-López, María; Micol, Vicente

2018-03-24

The skin is the body's largest organ, it participates in sensitivity and offers protection against microorganisms, chemicals and ultraviolet (UV) radiation. Consequently, the skin may suffer alterations such as photo-ageing, immune dysfunction and inflammation which may significantly affect human health. Nutraceuticals represent a promising strategy for preventing, delaying, or minimising premature ageing of the skin and also to alleviate certain skin disorders. Among them, bioactive peptides and oligosaccharides, plant polyphenols, carotenoids, vitamins and polyunsaturated fatty acids are the most widely used ingredients. Supplementation with these products has shown evidence of having an effect on the signs of ageing and protection against UV radiation ageing in several human trials. In this review, the most relevant human studies on skin nutraceuticals are evaluated and the statistical resolution, biological relevance of their results, and, the trial protocols are discussed. In conclusion, quality and rigorousness of the trials must be improved to build credible scientific evidence for skin nutraceuticals and to establish a cause-effect relationship between the ingredients the beneficial effects for the skin.

Is the Internet a useful and relevant source for health and health care information retrieval for German cardiothoracic patients? First results from a prospective survey among 255 Patients at a German cardiothoracic surgical clinic

PubMed Central

Stoevesandt, Dietrich; Diez, Claudius

2006-01-01

Background It is not clear how prevalent Internet use among cardiopathic patients in Germany is and what impact it has on the health care utilisation. We measured the extent of Internet use among cardiopathic patients and examined the effects that Internet use has on users' knowledge about their cardiac disease, health care matters and their use of the health care system. Methods We conducted a prospective survey among 255 cardiopathic patients at a German university hospital. Results Forty seven respondents (18 %) used the internet and 8,8 % (n = 23) went online more than 20 hours per month. The most frequent reason for not using the internet was disinterest (52,3 %). Fourteen patients (5,4 %) searched for specific disease-related information and valued the retrieved information on an analogous scale (1 = not relevant, 5 = very relevant) on median with 4,0. Internet use is age and education dependent. Only 36 (14,1 %) respondents found the internet useful, whereas the vast majority would not use it. Electronic scheduling for ambulatory visits or postoperative telemedical monitoring were rather disapproved. Conclusion We conclude that Internet use is infrequent among our study population and the search for relevant health and disease related information is not well established. PMID:17054799

Clarity and strength of implications for practice in medical journal articles: an exploratory analysis

PubMed Central

Owens, Allessia P; Bartunek, Jean M

2011-01-01

Objective To examine how leading clinical journals report research findings, aiming to assess how they frame their implications for medical practice and to compare that literature's patterns with those of the management literature. Data Source Clinically relevant research articles from three leading clinical journals (N Engl J Med, JAMA, and Ann Intern Med). Methods Review of wording of a sequential sample from 2010, with categorisation, comparison among journals, and comparison with management literature. Results Clinical journals usually state that one approach did or did not differ from another approach (35 of 51 articles, 68.6%), but they recommended a specific course of action (‘therefore, x should be done’) in just 25.5%. One article gave instruction on how to implement the changes. Two-thirds of the reports called for further research. Half used tentative language. Management research articles nearly always specified who should use the information and drew from over 60 types of potential users, whereas the clinical literature named the audience in only 23.5% of clinicians. Conclusions Authors and editors of the clinical literature could test being more clear and direct in presenting implications of research findings for practice, including stating when the findings do not justify changes in practice. PMID:21450773

Comprehensive computerized diabetes registry. Serving the Cree of Eeyou Istchee (eastern James Bay).

PubMed Central

Dannenbaum, D.; Verronneau, M.; Torrie, J.; Smeja, H.; Robinson, E.; Dumont, C.; Kovitch, I.; Webster, T.

1999-01-01

PROBLEM BEING ADDRESSED: Diabetes is rapidly evolving as a major health concern in the Cree population of eastern James Bay (Eeyou Istchee). The Cree Board of Health and Social Services of James Bay (CBHSSJB) diabetes registry was the initial phase in the development of a comprehensive program for diabetes in this region. OBJECTIVE OF PROGRAM: The CBHSSJB diabetes registry was developed to provide a framework to track the prevalence of diabetes and the progression of diabetic complications. The database will also identify patients not receiving appropriate clinical and laboratory screening for diabetic complications, and will provide standardized clinical flow sheets for routine patient management. MAIN COMPONENTS OF PROGRAM: The CBHSSJB diabetes registry uses a system of paper registration forms and clinical flow sheets kept in the nine community clinics. Information from these sheets is entered into a computer database annually. The flow sheets serve as a guideline for appropriate management of patients with diabetes, and provide a one-page summary of relevant clinical and laboratory information. CONCLUSIONS: A diabetes registry is vital to follow the progression of diabetes and diabetic complications in the region served by the CBHSSJB. The registry system incorporates both a means for regional epidemiologic monitoring of diabetes mellitus and clinical tools for managing patients with the disease. PMID:10065310

How well are journal and clinical article characteristics associated with the journal impact factor? a retrospective cohort study

PubMed Central

Lokker, Cynthia; Haynes, R. Brian; Chu, Rong; McKibbon, K. Ann; Wilczynski, Nancy L; Walter, Stephen D

2012-01-01

Objective: Journal impact factor (JIF) is often used as a measure of journal quality. A retrospective cohort study determined the ability of clinical article and journal characteristics, including appraisal measures collected at the time of publication, to predict subsequent JIFs. Methods: Clinical research articles that passed methods quality criteria were included. Each article was rated for relevance and newsworthiness by 3 to 24 physicians from a panel of more than 4,000 practicing clinicians. The 1,267 articles (from 103 journals) were divided 60∶40 into derivation (760 articles) and validation sets (507 articles), representing 99 and 88 journals, respectively. A multiple regression model was produced determining the association of 10 journal and article measures with the 2007 JIF. Results: Four of the 10 measures were significant in the regression model: number of authors, number of databases indexing the journal, proportion of articles passing methods criteria, and mean clinical newsworthiness scores. With the number of disciplines rating the article, the 5 variables accounted for 61% of the variation in JIF (R2 = 0.607, 95% CI 0.444 to 0.706, P<0.001). Conclusion: For the clinical literature, measures of scientific quality and clinical newsworthiness available at the time of publication can predict JIFs with 60% accuracy. PMID:22272156

Impact of a novel teaching method based on feedback, activity, individuality and relevance on students' learning.

PubMed

Edafe, Ovie; Brooks, William S; Laskar, Simone N; Benjamin, Miles W; Chan, Philip

2016-03-20

This study examines the perceived impact of a novel clinical teaching method based on FAIR principles (feedback, activity, individuality and relevance) on students' learning on clinical placement. This was a qualitative research study. Participants were third year and final year medical students attached to one UK vascular firm over a four-year period (N=108). Students were asked to write a reflective essay on how FAIRness approach differs from previous clinical placement, and its advantages and disadvantages. Essays were thematically analysed and globally rated (positive, negative or neutral) by two independent researchers. Over 90% of essays reported positive experiences of feedback, activity, individuality and relevance model. The model provided multifaceted feedback; active participation; longitudinal improvement; relevance to stage of learning and future goals; structured teaching; professional development; safe learning environment; consultant involvement in teaching. Students perceived preparation for tutorials to be time intensive for tutors/students; a lack of teaching on medical sciences and direct observation of performance; more than once weekly sessions would be beneficial; some issues with peer and public feedback, relevance to upcoming exam and large group sizes. Students described negative experiences of "standard" clinical teaching. Progressive teaching programmes based on the FAIRness principles, feedback, activity, individuality and relevance, could be used as a model to improve current undergraduate clinical teaching.

Evidence-based practice in chiropractic practice: A survey of chiropractors' knowledge, skills, use of research literature and barriers to the use of research evidence.

PubMed

Walker, B F; Stomski, N J; Hebert, J J; French, S D

2014-04-01

Scant research has been undertaken regarding chiropractors' skills and knowledge associated with evidence-based practice (EBP), and their perceived barriers to EBP. These issues appear to have been examined in only one small qualitative study and one small study of chiropractors holding orthopaedic diplomas. The lack of research in this area suggests that additional studies are warranted to develop a better understanding of factors that affect chiropractors' use of research evidence in clinical practice. We used a modified online questionnaire that captured information regarding EBP skills and knowledge, and barriers to EBP. Its adaption was informed by the use of a content validity panel. The questionnaire was disseminated through email by Australian chiropractic professional organisations and the Chiropractic Board of Australia. Logistic regression analyses were conducted to examine univariate associations between responses to items measuring knowledge and skills with items measuring: age; years since registration; reading research literature; and use of research literature in clinical decision-making. 584 respondents returned questionnaires. About half of the respondents stated they had learned the foundations of EBP (56.6%) during their undergraduate training. Slightly more than two thirds of the respondents were confident in their ability to critically review literature (69.5%) and find relevant research to answer clinical questions (72.6%). The most common factors involved with reading more research, and increased use of research literature in clinical decision-making, were confidence in critical appraisal skills and confidence in finding relevant research literature. Conclusion Educational interventions should be implemented to enhance Australian chiropractors' fundamental EBP skills. Copyright © 2014 Elsevier Ltd. All rights reserved.

Plant extracts for the topical management of psoriasis: a systematic review and meta-analysis.

PubMed

Deng, S; May, B H; Zhang, A L; Lu, C; Xue, C C L

2013-10-01

Patients with psoriasis frequently use preparations of plant extracts. Physicians need to be aware of the current evidence concerning these products. This review evaluates the efficacy and safety of preparations of plant extracts used topically for psoriasis. Searches were conducted in PubMed, Embase, the Cochrane library, two Chinese databases and article reference lists. Randomized controlled trials investigating extracts of single plants were included. Preparations of multiple plants and combinations of plant extracts plus conventional therapies were excluded. Two authors conducted searches, extracted data and assessed risk of bias. Outcomes used in meta-analyses were: clinical efficacy, Psoriasis Area and Severity Index score, and quality of life and symptom scores. The 12 included studies investigated extracts of: Mahonia aquifolium (n = 5), Aloe vera (n = 3), indigo naturalis (n = 2), kukui nut oil (n = 1) and Camptotheca acuminata nut (n = 1). Methodological quality was variable. Six studies provided data suitable for meta-analysis of clinical efficacy, and five were vs. placebo (relative risk 3·37, 95% confidence interval 1·36-8·33). Experimental studies indicate components of indigo naturalis, Mahonia and Camptotheca have anti-inflammatory, antiproliferative and other actions of relevance to psoriasis. The clinical trial evidence provides limited support for preparations containing extracts of M. aquifolium, indigo naturalis and Aloe vera for the topical management of plaque psoriasis based on multiple studies. No serious adverse events were reported. Because of the small size of most studies and methodological weaknesses, strong conclusions cannot be made. The magnitudes of any effects cannot be measured with accuracy, so it is difficult to assess the clinical relevance of these preparations. © 2013 British Association of Dermatologists.

Assessing research impact in academic clinical medicine: a study using Research Excellence Framework pilot impact indicators

PubMed Central

2012-01-01

Background Funders of medical research the world over are increasingly seeking, in research assessment, to complement traditional output measures of scientific publications with more outcome-based indicators of societal and economic impact. In the United Kingdom, the Higher Education Funding Council for England (HEFCE) developed proposals for the Research Excellence Framework (REF) to allocate public research funding to higher education institutions, inter alia, on the basis of the social and economic impact of their research. In 2010, it conducted a pilot exercise to test these proposals and refine impact indicators and criteria. Methods The impact indicators proposed in the 2010 REF impact pilot exercise are critically reviewed and appraised using insights from the relevant literature and empirical data collected for the University of Oxford’s REF pilot submission in clinical medicine. The empirical data were gathered from existing administrative sources and an online administrative survey carried out by the university’s Medical Sciences Division among 289 clinical medicine faculty members (48.1% response rate). Results The feasibility and scope of measuring research impact in clinical medicine in a given university are assessed. Twenty impact indicators from seven categories proposed by HEFCE are presented; their strengths and limitations are discussed using insights from the relevant biomedical and research policy literature. Conclusions While the 2010 pilot exercise has confirmed that the majority of the proposed indicators have some validity, there are significant challenges in operationalising and measuring these indicators reliably, as well as in comparing evidence of research impact across different cases in a standardised manner. It is suggested that the public funding agencies, medical research charities, universities, and the wider medical research community work together to develop more robust methodologies for capturing and describing impact, including more valid and reliable impact indicators. PMID:23259467

Prediction of clinical response based on pharmacokinetic/pharmacodynamic models of 5-hydroxytryptamine reuptake inhibitors in mice

PubMed Central

Kreilgaard, M; Smith, D G; Brennum, L T; Sánchez, C

2008-01-01

Background and purpose: Bridging the gap between preclinical research and clinical trials is vital for drug development. Predicting clinically relevant steady-state drug concentrations (Css) in serum from preclinical animal models may facilitate this transition. Here we used a pharmacokinetic/pharmacodynamic (PK/PD) modelling approach to evaluate the predictive validity of 5-hydroxytryptamine (5-HT; serotonin) transporter (SERT) occupancy and 5-hydroxytryptophan (5-HTP)-potentiated behavioral syndrome induced by 5-HT reuptake inhibitor (SRI) antidepressants in mice. Experimental approach: Serum and whole brain drug concentrations, cortical SERT occupancy and 5-HTP-potentiated behavioral syndrome were measured over 6 h after a single subcutaneous injection of escitalopram, paroxetine or sertraline. [3H]2-(2-dimethylaminomethylphenylsulphanyl)-5-methyl-phenylamine ([3H]MADAM) was used to assess SERT occupancy. For PK/PD modelling, an effect-compartment model was applied to collapse the hysteresis and predict the steady-state relationship between drug exposure and PD response. Key results: The predicted Css for escitalopram, paroxetine and sertraline at 80% SERT occupancy in mice are 18 ng mL−1, 18 ng mL−1 and 24 ng mL−1, respectively, with corresponding responses in the 5-HTP behavioral model being between 20–40% of the maximum. Conclusions and implications: Therapeutically effective SERT occupancy for SRIs in depressed patients is approximately 80%, and the corresponding plasma Css are 6–21 ng mL−1, 21-95 ng mL−1 and 20–48 ng mL−1 for escitalopram, paroxetine and sertraline, respectively. Thus, PK/PD modelling using SERT occupancy and 5-HTP-potentiated behavioral syndrome as response markers in mice may be a useful tool to predict clinically relevant plasma Css values. PMID:18552871

Immediate and long-term clinical outcome after spinal cord stimulation for refractory stable angina pectoris.

PubMed

Di Pede, Francesco; Lanza, Gaetano Antonio; Zuin, Guerrino; Alfieri, Ottavio; Rapati, Massimo; Romanò, Massimo; Circo, Antonio; Cardano, Paola; Bellocci, Fulvio; Santini, Massimo; Maseri, Attilio

2003-04-15

The treatment of patients with angina pectoris refractory to medical therapy and unsuitable for revascularization procedures has yet not been well standardized. Previous retrospective studies and small prospective studies have suggested beneficial effects of spinal cord stimulation (SCS) in these patients. We created a Prospective Italian Registry of SCS to evaluate the short- and long-term clinical outcome of patients who underwent SCS device implantation because of severe refractory angina pectoris. Overall, 104 patients were enrolled in the registry (70 men, aged 68 +/- 17 years), most of whom (83%) had severe coronary artery disease. Average follow-up was 13.2 +/- 8 months. Overall, 17 patients (16%) died, 8 (8%) due to cardiac death. Among clinical variables, only age was found to be significantly associated both with total mortality (p = 0.04) and cardiac mortality (p = 0.02) on Cox regression analysis. A significant improvement of anginal symptoms (> or =50% reduction of weekly anginal episodes, compared with baseline) occurred in 73% of patients, and Canadian Cardiovascular Society angina class improved by > or =1 class in 80% and by > or =2 classes in 42% of patients, with a relevant reduction in the rate of hospital admission and days spent in the hospital because of angina (p <0.0001 for both). No life-threatening or clinically serious complications were observed. The most frequent side effect consisted of superficial infections, either at the site of puncture of electrode insertion or of the abdominal pocket, which occurred in 6 patients. In conclusion, our prospective data point out that SCS can be performed safely and is associated with a sustained improvement of anginal symptoms in a relevant number of patients with refractory stable angina pectoris.

RELATIONSHIP BETWEEN ISOMETRIC THIGH MUSCLE STRENGTH AND MINIMAL CLINICALLY IMPORTANT DIFFERENCES (MCIDS) IN KNEE FUNCTION IN OSTEOARTHRITIS – DATA FROM THE OSTEOARTHRITIS INITIATIVE

PubMed Central

Ruhdorfer, Anja; Wirth, Wolfgang; Eckstein, Felix

2014-01-01

Objective To determine the relationship between thigh muscle strength and clinically relevant differences in self-assessed lower limb function. Methods Isometric knee extensor and flexor strength of 4553 Osteoarthritis Initiative participants (2651 women/1902 men) was related to Western Ontario McMasters Universities (WOMAC) physical function scores by linear regression. Further, groups of Male and female participant strata with minimal clinically important differences (MCIDs) in WOMAC function scores (6/68) were compared across the full range of observed values, and to participants without functional deficits (WOMAC=0). The effect of WOMAC knee pain and body mass index on the above relationships was explored using stepwise regression. Results Per regression equations, a 3.7% reduction in extensor and a 4.0% reduction in flexor strength were associated with an MCID in WOMAC function in women, and a 3.6%/4.8% reduction in men. For strength divided by body weight, reductions were 5.2%/6.7% in women and 5.8%/6.7% in men. Comparing MCID strata across the full observed range of WOMAC function confirmed the above estimates and did not suggest non-linear relationships across the spectrum of observed values. WOMAC pain correlated strongly with WOMAC function, but extensor (and flexor) muscle strength contributed significant independent information. Conclusion Reductions of approximately 4% in isometric muscle strength and of 6% in strength/weight were related to a clinically relevant difference in WOMAC functional disability. Longitudinal studies will need to confirm these relationships within persons. Muscle extensor (and flexor) strength (per body weight) provided significant independent information in addition to pain in explaining variability in lower limb function. PMID:25303012

EULAR/ACR classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups: a methodology report

PubMed Central

Bottai, Matteo; Tjärnlund, Anna; Santoni, Giola; Werth, Victoria P; Pilkington, Clarissa; de Visser, Marianne; Alfredsson, Lars; Amato, Anthony A; Barohn, Richard J; Liang, Matthew H; Aggarwal, Rohit; Arnardottir, Snjolaug; Chinoy, Hector; Cooper, Robert G; Danko, Katalin; Dimachkie, Mazen M; Feldman, Brian M; García-De La Torre, Ignacio; Gordon, Patrick; Hayashi, Taichi; Katz, James D; Kohsaka, Hitoshi; Lachenbruch, Peter A; Lang, Bianca A; Li, Yuhui; Oddis, Chester V; Olesinka, Marzena; Reed, Ann M; Rutkowska-Sak, Lidia; Sanner, Helga; Selva-O’Callaghan, Albert; Wook Song, Yeong; Ytterberg, Steven R; Miller, Frederick W; Rider, Lisa G; Lundberg, Ingrid E; Amoruso, Maria

2017-01-01

Objective To describe the methodology used to develop new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIMs) and their major subgroups. Methods An international, multidisciplinary group of myositis experts produced a set of 93 potentially relevant variables to be tested for inclusion in the criteria. Rheumatology, dermatology, neurology and paediatric clinics worldwide collected data on 976 IIM cases (74% adults, 26% children) and 624 non-IIM comparator cases with mimicking conditions (82% adults, 18% children). The participating clinicians classified each case as IIM or non-IIM. Generally, the classification of any given patient was based on few variables, leaving remaining variables unmeasured. We investigated the strength of the association between all variables and between these and the disease status as determined by the physician. We considered three approaches: (1) a probability-score approach, (2) a sum-of-items approach criteria and (3) a classification-tree approach. Results The approaches yielded several candidate models that were scrutinised with respect to statistical performance and clinical relevance. The probability-score approach showed superior statistical performance and clinical practicability and was therefore preferred over the others. We developed a classification tree for subclassification of patients with IIM. A calculator for electronic devices, such as computers and smartphones, facilitates the use of the European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria. Conclusions The new EULAR/ACR classification criteria provide a patient’s probability of having IIM for use in clinical and research settings. The probability is based on a score obtained by summing the weights associated with a set of criteria items. PMID:29177080

Novel drug metabolism indices for pharmacogenetic functional status based on combinatory genotyping of CYP2C9, CYP2C19 and CYP2D6 genes

PubMed Central

Villagra, David; Goethe, John; Schwartz, Harold I; Szarek, Bonnie; Kocherla, Mohan; Gorowski, Krystyna; Windemuth, Andreas; Ruaño, Gualberto

2011-01-01

Aims We aim to demonstrate clinical relevance and utility of four novel drug-metabolism indices derived from a combinatory (multigene) approach to CYP2C9, CYP2C19 and CYP2D6 allele scoring. Each index considers all three genes as complementary components of a liver enzyme drug metabolism system and uniquely benchmarks innate hepatic drug metabolism reserve or alteration through CYP450 combinatory genotype scores. Methods A total of 1199 psychiatric referrals were genotyped for polymorphisms in the CYP2C9, CYP2C19 and CYP2D6 gene loci and were scored on each of the four indices. The data were used to create distributions and rankings of innate drug metabolism capacity to which individuals can be compared. Drug-specific indices are a combination of the drug metabolism indices with substrate-specific coefficients. Results The combinatory drug metabolism indices proved useful in positioning individuals relative to a population with regard to innate drug metabolism capacity prior to pharmacotherapy. Drug-specific indices generate pharmacogenetic guidance of immediate clinical relevance, and can be further modified to incorporate covariates in particular clinical cases. Conclusions We believe that this combinatory approach represents an improvement over the current gene-by-gene reporting by providing greater scope while still allowing for the resolution of a single-gene index when needed. This method will result in novel clinical and research applications, facilitating the translation from pharmacogenomics to personalized medicine, particularly in psychiatry where many drugs are metabolized or activated by multiple CYP450 isoenzymes. PMID:21861665

Self-reported indications for antidepressant use in a population-based cohort of middle-aged and elderly.

PubMed

Aarts, Nikkie; Noordam, Raymond; Hofman, Albert; Tiemeier, Henning; Stricker, Bruno H; Visser, Loes E

2016-10-01

Background Population-based studies investigating indications for antidepressant prescribing mostly rely on diagnoses from general practitioners. However, diagnostic codes might be incomplete and drugs may be prescribed 'off-label' for indications not investigated in clinical trials. Objective We aimed to study indications for antidepressant use based on self-report. Also, we studied the presence of depressive symptoms associated with the self-reported indications. Setting Our study population of antidepressant users was selected based on interview data between 1997 and 2013 from the prospective population-based Rotterdam Study cohort (age >45 years). Method Antidepressant use, self-reported indication for use, and presence of depressive symptoms (Center for Epidemiological Studies Depression Scale) were based on interview. Self-reported indications were categorized by the researchers into officially approved, clinically-accepted and commonly mentioned off-label indications. Main outcome measures A score of 16 and higher on the Center for Epidemiological Studies Depression Scale was considered as indicator for clinically-relevant depressive symptoms. Results The majority of 914 antidepressant users reported 'depression' (52.4 %) as indication for treatment. Furthermore, anxiety, stress and sleep disorders were reported in selective serotonin reuptake inhibitor and other antidepressant users (ranging from 5.9 to 13.3 %). The indication 'pain' was commonly mentioned by tricyclic antidepressant users (19.0 %). Indications were statistically significantly associated with higher depressive symptom scores when compared to non-users (n = 10,979). Conclusions Depression was the main indication for antidepressant treatment. However, our findings suggest that antidepressants are also used for off-label indications, subthreshold disorders and complex situations, which were all associated with clinically-relevant depressive symptoms in the middle-aged and elderly population.

Validation of the diagnosis of autism in general practitioner records

PubMed Central

Fombonne, Eric; Heavey, Lisa; Smeeth, Liam; Rodrigues, Laura C; Cook, Claire; Smith, Peter G; Meng, Linyan; Hall, Andrew J

2004-01-01

Background We report on the validity of the computerized diagnoses of autism in a large case-control study investigating the possible association between autism and the measles, mumps and rubella vaccine in the UK using the General Practitioner Research Database (GPRD). We examined anonymized copies of all relevant available clinical reports, including general practitioners' (GP) notes, consultant, speech therapy and educational psychologists reports, on 318 subjects born between 1973 and 1997 with a diagnosis of autism or a related disorder recorded in their electronic general practice record. Methods Data were abstracted to a case validation form allowing for the identification of developmental symptoms relevant to the diagnosis of pervasive developmental disorders (PDDs). Information on other background clinical and familial features was also abstracted. A subset of 50 notes was coded independently by 2 raters to derive reliability estimates for key clinical characteristics. Results For 294 subjects (92.5%) the diagnosis of PDD was confirmed after review of the records. Of these, 180 subjects (61.2%) fulfilled criteria for autistic disorder. The mean age at first recording of a PDD diagnosis in the GPRD database was 6.3 years (SD = 4.6). Consistent with previous estimates, the proportion of subjects experiencing regression in the course of their development was 19%. Inter-rater reliability for the presence of a PDD diagnosis was good (kappa = .73), and agreement on clinical features such as regression, age of parental recognition of first symptoms, language delay and presence of epilepsy was also good (kappas ranging from .56 to 1.0). Conclusions This study provides evidence that the positive predictive value of a diagnosis of autism recorded in the GPRD is high. PMID:15113435

A Multifactorial Weight Reduction Programme for Children with Overweight and Asthma: A Randomized Controlled Trial

PubMed Central

Willeboordse, Maartje; van de Kant, Kim D. G.; Tan, Frans E. S.; Mulkens, Sandra; Schellings, Julia; Crijns, Yvonne; van der Ploeg, Liesbeth; van Schayck, Constant P.; Dompeling, Edward

2016-01-01

Background There is increasing evidence that obesity is related to asthma development and severity. However, it is largely unknown whether weight reduction can influence asthma management, especially in children. Objective To determine the effects of a multifactorial weight reduction intervention on asthma management in overweight/obese children with (a high risk of developing) asthma. Methods An 18-month weight-reduction randomized controlled trial was conducted in 87 children with overweight/obesity and asthma. Every six months, measurements of anthropometry, lung function, lifestyle parameters and inflammatory markers were assessed. Analyses were performed with linear mixed models for longitudinal analyses. Results After 18 months, the body mass index-standard deviation score decreased by -0.14±0.29 points (p<0.01) in the intervention group and -0.12±0.34 points (p<0.01) in the control group. This change over time did not differ between groups (p>0.05). Asthma features (including asthma control and asthma-related quality of life) and lung function indices (static and dynamic) improved significantly over time in both groups. The FVC% predicted improved over time by 10.1 ± 8.7% in the intervention group (p<0.001), which was significantly greater than the 6.1 ± 8.4% in the control group (p<0.05). Conclusions & clinical relevance Clinically relevant improvements in body weight, lung function and asthma features were found in both the intervention and control group, although some effects were more pronounced in the intervention group (FVC, asthma control, and quality of life). This implies that a weight reduction intervention could be clinically beneficial for children with asthma. Trial Registration ClinicalTrials.gov NCT00998413 PMID:27294869

Critical Care Follow-up Clinics: A Scoping Review of Interventions and Outcomes

PubMed Central

Oles, Sylwia K.; Mundell, James; London, Susan; Khan, Babar

2016-01-01

Objective The purpose of this scoping review was to identify evidence describing benefits of interventions provided in ICU-survivor follow-up clinics. Background Advances in intensive care unit (ICU) treatments have increased the number of survivors who require specialized care for ICU-related sequelae. ICU survivor follow-up clinics exist yet little is known about the nature and impact of interventions provided in such clinics. A scoping review of publications about in-person post-ICU follow-up care was undertaken. Method Ten databases were searched yielding one-hundred eleven relevant unique publication titles and abstracts. Sample heterogeneity supported using a scoping review method. After excluding non-related publications, 33 reports were fully reviewed. Twenty international publications were included that described ICU follow-up clinic interventions and/or outcomes. Results Authors discussed very diverse interventions in 15 publications, and 9 reported some level of intervention effectiveness. Evidence was strongest that supported the use of prospective diaries as an intervention to prevent or improve psychological symptoms whereas evidence to support implementation of other interventions was weak. Conclusions Although ICU follow-up clinics exist, evidence for interventions and effectiveness of treatments in these clinics remains under-explored. Implications ICU survivor follow-up clinics provide a venue for further interdisciplinary intervention research that could lead to better health outcomes for ICU survivors. PMID:27309787

There's an App for That? Highlighting the Difficulty in Finding Clinically Relevant Smartphone Applications.

PubMed

Wiechmann, Warren; Kwan, Daniel; Bokarius, Andrew; Toohey, Shannon L

2016-03-01

The use of personal mobile devices in the medical field has grown quickly, and a large proportion of physicians use their mobile devices as an immediate resource for clinical decision-making, prescription information and other medical information. The iTunes App Store (Apple, Inc.) contains approximately 20,000 apps in its "Medical" category, providing a robust repository of resources for clinicians; however, this represents only 2% of the entire App Store. The App Store does not have strict criteria for identifying content specific to practicing physicians, making the identification of clinically relevant content difficult. The objective of this study is to quantify the characteristics of existing medical applications in the iTunes App Store that could be used by emergency physicians, residents, or medical students. We found applications related to emergency medicine (EM) by searching the iTunes App Store for 21 terms representing core content areas of EM, such as "emergency medicine," "critical care," "orthopedics," and "procedures." Two physicians independently reviewed descriptions of these applications in the App Store and categorized each as the following: Clinically Relevant, Book/Published Source, Non-English, Study Tools, or Not Relevant. A third physician reviewer resolved disagreements about categorization. Descriptive statistics were calculated. We found a total of 7,699 apps from the 21 search terms, of which 17.8% were clinical, 9.6% were based on a book or published source, 1.6% were non-English, 0.7% were clinically relevant patient education resources, and 4.8% were study tools. Most significantly, 64.9% were considered not relevant to medical professionals. Clinically relevant apps make up approximately 6.9% of the App Store's "Medical" Category and 0.1% of the overall App Store. Clinically relevant apps represent only a small percentage (6.9%) of the total App volume within the Medical section of the App Store. Without a structured search-and-evaluation strategy, it may be difficult for the casual user to identify this potentially useful content. Given the increasing adoption of devices in healthcare, national EM associations should consider curating these resources for their members.

A randomized trial comparing INR monitoring devices in patients with anticoagulation self-management: evaluation of a novel error-grid approach.

PubMed

Hemkens, Lars G; Hilden, Kristian M; Hartschen, Stephan; Kaiser, Thomas; Didjurgeit, Ulrike; Hansen, Roland; Bender, Ralf; Sawicki, Peter T

2008-08-01

In addition to the metrological quality of international normalized ratio (INR) monitoring devices used in patients' self-management of long-term anticoagulation, the effectiveness of self-monitoring with such devices has to be evaluated under real-life conditions with a focus on clinical implications. An approach to evaluate the clinical significance of inaccuracies is the error-grid analysis as already established in self-monitoring of blood glucose. Two anticoagulation monitors were compared in a real-life setting and a novel error-grid instrument for oral anticoagulation has been evaluated. In a randomized crossover study 16 patients performed self-management of anticoagulation using the INRatio and the CoaguChek S system. Main outcome measures were clinically relevant INR differences according to established criteria and to the error-grid approach. A lower rate of clinically relevant disagreements according to Anderson's criteria was found with CoaguChek S than with INRatio without statistical significance (10.77% vs. 12.90%; P = 0.787). Using the error-grid we found principally consistent results: More measurement pairs with discrepancies of no or low clinical relevance were found with CoaguChek S, whereas with INRatio we found more differences with a moderate clinical relevance. A high rate of patients' satisfaction with both of the point of care devices was found with only marginal differences. A principal appropriateness of the investigated point-of-care devices to adequately monitor the INR is shown. The error-grid is useful for comparing monitoring methods with a focus on clinical relevance under real-life conditions beyond assessing the pure metrological quality, but we emphasize that additional trials using this instrument with larger patient populations are needed to detect differences in clinically relevant disagreements.

Pharmacological guidelines for schizophrenia: a systematic review and comparison of recommendations for the first episode

PubMed Central

Keating, Dolores; McWilliams, Stephen; Schneider, Ian; Hynes, Caroline; Cousins, Gráinne; Strawbridge, Judith; Clarke, Mary

2017-01-01

Objectives Clinical practice guidelines (CPGs) support the translation of research evidence into clinical practice. Key health questions in CPGs ensure that recommendations will be applicable to the clinical context in which the guideline is used. The objectives of this study were to identify CPGs for the pharmacological treatment of first-episode schizophrenia; assess the quality of these guidelines using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument; and compare recommendations in relation to the key health questions that are relevant to the pharmacological treatment of first-episode schizophrenia. Methods A multidisciplinary group identified key health questions that are relevant to the pharmacological treatment of first-episode schizophrenia. The MEDLINE and EMBASE databases, websites of professional organisations and international guideline repositories, were searched for CPGs that met the inclusion criteria. The AGREE II instrument was applied by three raters and data were extracted from the guidelines in relation to the key health questions. Results In total, 3299 records were screened. 10 guidelines met the inclusion criteria. 3 guidelines scored well across all domains. Recommendations varied in specificity. Side effect concerns, rather than comparative efficacy benefits, were a key consideration in antipsychotic choice. Antipsychotic medication is recommended for maintenance of remission following a first episode of schizophrenia but there is a paucity of evidence to guide duration of treatment. Clozapine is universally regarded as the medication of choice for treatment resistance. There is less evidence to guide care for those who do not respond to clozapine. Conclusions An individual's experience of using antipsychotic medication for the initial treatment of first-episode schizophrenia may have implications for future engagement, adherence and outcome. While guidelines of good quality exist to assist in medicines optimisation, the evidence base required to answer key health questions relevant to the pharmacological treatment of first-episode schizophrenia is limited. PMID:28062471

Changes in Imaging and Cognition in Juvenile Rats After Whole-Brain Irradiation

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

Brown, Robert J.; Jun, Brandon J.; Advanced Imaging Laboratory, Department of Radiology, Children's Hospital Los Angeles, Los Angeles, California

Purpose: In pediatric cancer survivors treated with whole-brain irradiation (WBI), long-term cognitive deficits and morbidity develop that are poorly understood and for which there is no treatment. We describe similar cognitive defects in juvenile WBI rats and correlate them with alterations in diffusion tensor imaging and magnetic resonance spectroscopy (MRS) during brain development. Methods and Materials: Juvenile Fischer rats received clinically relevant fractionated doses of WBI or a high-dose exposure. Diffusion tensor imaging and MRS were performed at the time of WBI and during the subacute (3-month) and late (6-month) phases, before behavioral testing. Results: Fractional anisotropy in the spleniummore » of the corpus callosum increased steadily over the study period, reflecting brain development. WBI did not alter the subacute response, but thereafter there was no further increase in fractional anisotropy, especially in the high-dose group. Similarly, the ratios of various MRS metabolites to creatine increased over the study period, and in general, the most significant changes after WBI were during the late phase and with the higher dose. The most dramatic changes observed were in glutamine-creatine ratios that failed to increase normally between 3 and 6 months after either radiation dose. WBI did not affect the ambulatory response to novel open field testing in the subacute phase, but locomotor habituation was impaired and anxiety-like behaviors increased. As for cognitive measures, the most dramatic impairments were in novel object recognition late after either dose of WBI. Conclusions: The developing brains of juvenile rats given clinically relevant fractionated doses of WBI show few abnormalities in the subacute phase but marked late cognitive alterations that may be linked with perturbed MRS signals measured in the corpus callosum. This pathomimetic phenotype of clinically relevant cranial irradiation effects may be useful for modeling, mechanistic evaluations, and testing of mitigation approaches.« less

Mapping Systematic Reviews on Atopic Eczema—An Essential Resource for Dermatology Professionals and Researchers

PubMed Central

Futamura, Masaki; Thomas, Kim S.; Grindlay, Douglas J. C.; Doney, Elizabeth J.; Torley, Donna; Williams, Hywel C.

2013-01-01

Background Many research studies have been published on atopic eczema and these are often summarised in systematic reviews (SRs). Identifying SRs can be time-consuming for health professionals, and researchers. In order to facilitate the identification of important research, we have compiled an on-line resource that includes all relevant eczema reviews published since 2000. Methods SRs were searched for in MEDLINE (Ovid), EMBASE (Ovid), PubMed, the Cochrane Database of Systematic Reviews, DARE and NHS Evidence. Selected SRs were assessed against the pre-defined eligibility criteria and relevant articles were grouped by treatment category for the included interventions. All identified systematic reviews are included in the Global Resource of EczemA Trials (GREAT) database (www.greatdatabase.org.uk) and key clinical messages are summarised here. Results A total of 128 SRs reviews were identified, including three clinical guidelines. Of these, 46 (36%) were found in the Cochrane Library. No single database contained all of the SRs found. The number of SRs published per year has increased substantially over the last thirteen years, and reviews were published in a variety of clinical journals. Of the 128 SRs, 1 (1%) was on mechanism, 37 (29%) were on epidemiology, 40 (31%) were on eczema prevention, 29 (23%) were on topical treatments, 31 (24%) were on systemic treatments, and 24 (19%) were on other treatments. All SRs included searches of MEDLINE in their search methods. One hundred six SRs (83%) searched more than one electronic database. There were no language restrictions reported in the search methods of 52 of the SRs (41%). Conclusions This mapping of atopic eczema reviews is a valuable resource. It will help healthcare practitioners, guideline writers, information specialists, and researchers to quickly identify relevant up-to-date evidence in the field for improving patient care. PMID:23505516

The interaction of escitalopram and R-citalopram at the human serotonin transporter investigated in the mouse

PubMed Central

Jacobsen, Jacob P.R.; Plenge, Per; Sachs, Benjamin D.; Pehrson, Alan L.; Cajina, Manuel; Du, Yunzhi; Roberts, Wendy; Rudder, Meghan L.; Dalvi, Prachiti; Robinson, Taylor J.; O’Neill, Sharon P.; Khoo, King S.; Morillo, Connie Sanchez; Zhang, Xiaodong; Caron, Marc G.

2015-01-01

Rationale Escitalopram is a superior antidepressant to racemic citalopram. It has been hypothesized that binding of R-citalopram to the serotonin transporter (SERT) antagonizes escitalopram binding to and inhibition of the SERT, curtailing the elevation of extracellular 5-hydroxytryptamine (5-HTExt), and antidepressant efficacy. Further, it has been suggested that a putative allosteric binding site is important for binding of escitalopram to the primary, orthosteric, site, and for R-citalopram’s inhibition hereof. Objectives Primary: Investigate at the human (h)SERT, at clinical relevant doses, whether R-citalopram antagonizes escitalopram-induced 5-HTExt elevation. Secondary: Investigate whether abolishing the putative allosteric site affects escitalopram-induced 5-HTExt elevation and/or modulates the effect of R-citalopram. Methods Recombinant technology; in vivo microdialysis; receptor binding; pharmacokinetics; 5-HT sensitive behaviors (tail suspension, marble burying). Results We generated mice expressing either the wild-type human SERT (hSERTWT) or hSERT carrying amino acid substitutions (A505V, L506F, I507L, S574T and I575T) collectively abolishing the putative allosteric site (hSERTALI/VFL+SI/TT). One mg/kg escitalopram yielded clinical relevant plasma levels and brain levels consistent with therapeutic SERT occupancy. Importantly, escitalopram-induced 5-HTExt elevation was not decreased by R-citalopram co-treatment. Further, escitalopram-induced 5-HTExt elevation was not affected by loss of the allosteric site. The behavioral effects of the clinically relevant escitalopram dose were small, tending to be enhanced by R-citalopram co-administration. Conclusions We find no evidence that R-citalopram directly antagonizes escitalopram or that the putative allosteric site is important for hSERT inhibition by escitalopram. Our findings points to mechanisms for R-citalopram antagonism of escitalopram’s antidepressant action other than direct antagonistic binding interactions at the hSERT. PMID:24810106

SU-E-T-789: Validation of 3DVH Accuracy On Quantifying Delivery Errors Based On Clinical Relevant DVH Metrics

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

Ma, T; Kumaraswamy, L

Purpose: Detection of treatment delivery errors is important in radiation therapy. However, accurate quantification of delivery errors is also of great importance. This study aims to evaluate the 3DVH software’s ability to accurately quantify delivery errors. Methods: Three VMAT plans (prostate, H&N and brain) were randomly chosen for this study. First, we evaluated whether delivery errors could be detected by gamma evaluation. Conventional per-beam IMRT QA was performed with the ArcCHECK diode detector for the original plans and for the following modified plans: (1) induced dose difference error up to ±4.0% and (2) control point (CP) deletion (3 to 10more » CPs were deleted) (3) gantry angle shift error (3 degree uniformly shift). 2D and 3D gamma evaluation were performed for all plans through SNC Patient and 3DVH, respectively. Subsequently, we investigated the accuracy of 3DVH analysis for all cases. This part evaluated, using the Eclipse TPS plans as standard, whether 3DVH accurately can model the changes in clinically relevant metrics caused by the delivery errors. Results: 2D evaluation seemed to be more sensitive to delivery errors. The average differences between ECLIPSE predicted and 3DVH results for each pair of specific DVH constraints were within 2% for all three types of error-induced treatment plans, illustrating the fact that 3DVH is fairly accurate in quantifying the delivery errors. Another interesting observation was that even though the gamma pass rates for the error plans are high, the DVHs showed significant differences between original plan and error-induced plans in both Eclipse and 3DVH analysis. Conclusion: The 3DVH software is shown to accurately quantify the error in delivered dose based on clinically relevant DVH metrics, where a conventional gamma based pre-treatment QA might not necessarily detect.« less

Resected Brain Tissue, Seizure Onset Zone and Quantitative EEG Measures: Towards Prediction of Post-Surgical Seizure Control

PubMed Central

Andrzejak, Ralph G.; Hauf, Martinus; Pollo, Claudio; Müller, Markus; Weisstanner, Christian; Wiest, Roland; Schindler, Kaspar

2015-01-01

Background Epilepsy surgery is a potentially curative treatment option for pharmacoresistent patients. If non-invasive methods alone do not allow to delineate the epileptogenic brain areas the surgical candidates undergo long-term monitoring with intracranial EEG. Visual EEG analysis is then used to identify the seizure onset zone for targeted resection as a standard procedure. Methods Despite of its great potential to assess the epileptogenicty of brain tissue, quantitative EEG analysis has not yet found its way into routine clinical practice. To demonstrate that quantitative EEG may yield clinically highly relevant information we retrospectively investigated how post-operative seizure control is associated with four selected EEG measures evaluated in the resected brain tissue and the seizure onset zone. Importantly, the exact spatial location of the intracranial electrodes was determined by coregistration of pre-operative MRI and post-implantation CT and coregistration with post-resection MRI was used to delineate the extent of tissue resection. Using data-driven thresholding, quantitative EEG results were separated into normally contributing and salient channels. Results In patients with favorable post-surgical seizure control a significantly larger fraction of salient channels in three of the four quantitative EEG measures was resected than in patients with unfavorable outcome in terms of seizure control (median over the whole peri-ictal recordings). The same statistics revealed no association with post-operative seizure control when EEG channels contributing to the seizure onset zone were studied. Conclusions We conclude that quantitative EEG measures provide clinically relevant and objective markers of target tissue, which may be used to optimize epilepsy surgery. The finding that differentiation between favorable and unfavorable outcome was better for the fraction of salient values in the resected brain tissue than in the seizure onset zone is consistent with growing evidence that spatially extended networks might be more relevant for seizure generation, evolution and termination than a single highly localized brain region (i.e. a “focus”) where seizures start. PMID:26513359

Health measurement using the ICF: Test-retest reliability study of ICF codes and qualifiers in geriatric care

PubMed Central

Okochi, Jiro; Utsunomiya, Sakiko; Takahashi, Tai

2005-01-01

Background The International Classification of Functioning, Disability and Health (ICF) was published by the World Health Organization (WHO) to standardize descriptions of health and disability. Little is known about the reliability and clinical relevance of measurements using the ICF and its qualifiers. This study examines the test-retest reliability of ICF codes, and the rate of immeasurability in long-term care settings of the elderly to evaluate the clinical applicability of the ICF and its qualifiers, and the ICF checklist. Methods Reliability of 85 body function (BF) items and 152 activity and participation (AP) items of the ICF was studied using a test-retest procedure with a sample of 742 elderly persons from 59 institutional and at home care service centers. Test-retest reliability was estimated using the weighted kappa statistic. The clinical relevance of the ICF was estimated by calculating immeasurability rate. The effect of the measurement settings and evaluators' experience was analyzed by stratification of these variables. The properties of each item were evaluated using both the kappa statistic and immeasurability rate to assess the clinical applicability of WHO's ICF checklist in the elderly care setting. Results The median of the weighted kappa statistics of 85 BF and 152 AP items were 0.46 and 0.55 respectively. The reproducibility statistics improved when the measurements were performed by experienced evaluators. Some chapters such as genitourinary and reproductive functions in the BF domain and major life area in the AP domain contained more items with lower test-retest reliability measures and rated as immeasurable than in the other chapters. Some items in the ICF checklist were rated as unreliable and immeasurable. Conclusion The reliability of the ICF codes when measured with the current ICF qualifiers is relatively low. The result in increase in reliability according to evaluators' experience suggests proper education will have positive effects to raise the reliability. The ICF checklist contains some items that are difficult to be applied in the geriatric care settings. The improvements should be achieved by selecting the most relevant items for each measurement and by developing appropriate qualifiers for each code according to the interest of the users. PMID:16050960

Genome-wide analysis of pain-, nerve- and neurotrophin -related gene expression in the degenerating human annulus

PubMed Central

2012-01-01

Background In spite of its high clinical relevance, the relationship between disc degeneration and low back pain is still not well understood. Recent studies have shown that genome-wide gene expression studies utilizing ontology searches provide an efficient and valuable methodology for identification of clinically relevant genes. Here we use this approach in analysis of pain-, nerve-, and neurotrophin-related gene expression patterns in specimens of human disc tissue. Control, non-herniated clinical, and herniated clinical specimens of human annulus tissue were studied following Institutional Review Board approval. Results Analyses were performed on more generated (Thompson grade IV and V) discs vs. less degenerated discs (grades I-III), on surgically operated discs vs. control discs, and on herniated vs. control discs. Analyses of more degenerated vs. less degenerated discs identified significant upregulation of well-recognized pain-related genes (bradykinin receptor B1, calcitonin gene-related peptide and catechol-0-methyltransferase). Nerve growth factor was significantly upregulated in surgical vs. control and in herniated vs. control discs. All three analyses also found significant changes in numerous proinflammatory cytokine- and chemokine-related genes. Nerve, neurotrophin and pain-ontology searches identified many matrix, signaling and functional genes which have known importance in the disc. Immunohistochemistry was utilized to confirm the presence of calcitonin gene-related peptide, catechol-0-methyltransferase and bradykinin receptor B1 at the protein level in the human annulus. Conclusions Findings point to the utility of microarray analyses in identification of pain-, neurotrophin and nerve-related genes in the disc, and point to the importance of future work exploring functional interactions between nerve and disc cells in vitro and in vivo. Nerve, pain and neurotrophin ontology searches identified numerous changes in proinflammatory cytokines and chemokines which also have significant relevance to disc biology. Since the degenerating human disc is primarily an avascular tissue site into which disc cells have contributed high levels of proinflammatory cytokines, these substances are not cleared from the tissue and remain there over time. We hypothesize that as nerves grow into the human annulus, they encounter a proinflammatory cytokine-rich milieu which may sensitize nociceptors and exacerbate pain production. PMID:22963171

Sensitivity and predictive value of 15 PubMed search strategies to answer clinical questions rated against full systematic reviews.

PubMed

Agoritsas, Thomas; Merglen, Arnaud; Courvoisier, Delphine S; Combescure, Christophe; Garin, Nicolas; Perrier, Arnaud; Perneger, Thomas V

2012-06-12

Clinicians perform searches in PubMed daily, but retrieving relevant studies is challenging due to the rapid expansion of medical knowledge. Little is known about the performance of search strategies when they are applied to answer specific clinical questions. To compare the performance of 15 PubMed search strategies in retrieving relevant clinical trials on therapeutic interventions. We used Cochrane systematic reviews to identify relevant trials for 30 clinical questions. Search terms were extracted from the abstract using a predefined procedure based on the population, interventions, comparison, outcomes (PICO) framework and combined into queries. We tested 15 search strategies that varied in their query (PIC or PICO), use of PubMed's Clinical Queries therapeutic filters (broad or narrow), search limits, and PubMed links to related articles. We assessed sensitivity (recall) and positive predictive value (precision) of each strategy on the first 2 PubMed pages (40 articles) and on the complete search output. The performance of the search strategies varied widely according to the clinical question. Unfiltered searches and those using the broad filter of Clinical Queries produced large outputs and retrieved few relevant articles within the first 2 pages, resulting in a median sensitivity of only 10%-25%. In contrast, all searches using the narrow filter performed significantly better, with a median sensitivity of about 50% (all P < .001 compared with unfiltered queries) and positive predictive values of 20%-30% (P < .001 compared with unfiltered queries). This benefit was consistent for most clinical questions. Searches based on related articles retrieved about a third of the relevant studies. The Clinical Queries narrow filter, along with well-formulated queries based on the PICO framework, provided the greatest aid in retrieving relevant clinical trials within the 2 first PubMed pages. These results can help clinicians apply effective strategies to answer their questions at the point of care.

Structure-based approach for identification of novel phenylboronic acids as serine-β-lactamase inhibitors

NASA Astrophysics Data System (ADS)

Sgrignani, Jacopo; De Luca, Filomena; Torosyan, Hayarpi; Docquier, Jean-Denis; Duan, Da; Novati, Beatrice; Prati, Fabio; Colombo, Giorgio; Grazioso, Giovanni

2016-10-01

β-Lactamases are bacterial enzymes conferring resistance to β-lactam antibiotics in clinically-relevant pathogens, and represent relevant drug targets. Recently, the identification of new boronic acids (i.e. RPX7009) paved the way to the clinical application of these molecules as potential drugs. Here, we screened in silico a library of 1400 boronic acids as potential AmpC β-lactamase inhibitors. Six of the most promising candidates were evaluated in biochemical assays leading to the identification of potent inhibitors of clinically-relevant β-lactamases like AmpC, KPC-2 and CTX-M-15. One of the selected compounds showed nanomolar K i value with the clinically-relevant KPC-2 carbapenemase, while another one exhibited broad spectrum inhibition, being also active on Enterobacter AmpC and the OXA-48 class D carbapenemase.

Research standardization tools: pregnancy measures in the PhenX Toolkit.

PubMed

Malinowski, Ann Kinga; Ananth, Cande V; Catalano, Patrick; Hines, Erin P; Kirby, Russell S; Klebanoff, Mark A; Mulvihill, John J; Simhan, Hyagriv; Hamilton, Carol M; Hendershot, Tabitha P; Phillips, Michael J; Kilpatrick, Lisa A; Maiese, Deborah R; Ramos, Erin M; Wright, Rosalind J; Dolan, Siobhan M

2017-09-01

Only through concerted and well-executed research endeavors can we gain the requisite knowledge to advance pregnancy care and have a positive impact on maternal and newborn health. Yet the heterogeneity inherent in individual studies limits our ability to compare and synthesize study results, thus impeding the capacity to draw meaningful conclusions that can be trusted to inform clinical care. The PhenX Toolkit (http://www.phenxtoolkit.org), supported since 2007 by the National Institutes of Health, is a web-based catalog of standardized protocols for measuring phenotypes and exposures relevant for clinical research. In 2016, a working group of pregnancy experts recommended 15 measures for the PhenX Toolkit that are highly relevant to pregnancy research. The working group followed the established PhenX consensus process to recommend protocols that are broadly validated, well established, nonproprietary, and have a relatively low burden for investigators and participants. The working group considered input from the pregnancy experts and the broader research community and included measures addressing the mode of conception, gestational age, fetal growth assessment, prenatal care, the mode of delivery, gestational diabetes, behavioral and mental health, and environmental exposure biomarkers. These pregnancy measures complement the existing measures for other established domains in the PhenX Toolkit, including reproductive health, anthropometrics, demographic characteristics, and alcohol, tobacco, and other substances. The preceding domains influence a woman's health during pregnancy. For each measure, the PhenX Toolkit includes data dictionaries and data collection worksheets that facilitate incorporation of the protocol into new or existing studies. The measures within the pregnancy domain offer a valuable resource to investigators and clinicians and are well poised to facilitate collaborative pregnancy research with the goal to improve patient care. To achieve this aim, investigators whose work includes the perinatal population are encouraged to utilize the PhenX Toolkit in the design and implementation of their studies, thus potentially reducing heterogeneity in data measures across studies. Such an effort will enhance the overall impact of individual studies, increasing the ability to draw more meaningful conclusions that can then be translated into clinical practice. Copyright © 2017 Elsevier Inc. All rights reserved.

Association Between Deliberate Self-harm and Violent Criminality

PubMed Central

Kuja-Halkola, Ralf; Bjureberg, Johan; Lichtenstein, Paul; Molero, Yasmina; Rydell, Mina; Hedman, Erik; Runeson, Bo; Jokinen, Jussi; Ljótsson, Brjánn; Hellner, Clara

2017-01-01

Importance Individuals who self-harm may have an increased risk of aggression toward others, but this association has been insufficiently investigated. More conclusive evidence may affect assessment, treatment interventions, and clinical guidelines. Objective To investigate the association between nonfatal self-harm and violent crime. Design, Setting, and Participants This population-based longitudinal cohort study, conducted from January 1, 1997, through December 31, 2013, studied all Swedish citizens born between 1982 and 1998 who were 15 years and older (N = 1 850 252). Individuals who emigrated from Sweden before the age of 15 years (n = 104 051) or immigrated to Sweden after the age of 13 years (ie, <2 years before the beginning of the follow-up; n = 22 009) were excluded. Data analysis was performed from April 21, 2016, to June 4, 2016. Exposures Receipt of self-harm–associated clinical care. Main Outcomes and Measures Conviction of a violent crime according to the Swedish penal code. Results The study cohort consisted of 1 850 525 individuals (950 382 males and 900 143 females), and the mean (SD) follow-up time was 8.1 (4.7) years (range, 0-17.0 years; minimum age, 15 years; maximum age, 32 years). During a mean follow-up period of 8.1 years, 55 185 individuals (3.0%) received clinical care for self-harm. The crude hazard ratio was 4.9 (95% CI, 4.8-5.0) for violent crime conviction in exposed individuals compared with the unexposed group. Women who self-harm were at particularly high risk for expressing violent behaviors. After adjustment for relevant psychiatric comorbidities and socioeconomic status, an almost doubled hazard of violent offense remained (hazard ratio, 1.8; 95% CI, 1.8-1.9). Conclusions and Relevance Self-harm is associated with an increased risk of conviction for a violent offense in both sexes. The risk of violence, as well as the risk of suicide and self-harm, should be assessed among offending and self-harming individuals. PMID:28384711

Clinic Design and Continuity in Internal Medicine Resident Clinics: Findings of the Educational Innovations Project Ambulatory Collaborative

PubMed Central

Francis, Maureen D.; Wieland, Mark L.; Drake, Sean; Gwisdalla, Keri Lyn; Julian, Katherine A.; Nabors, Christopher; Pereira, Anne; Rosenblum, Michael; Smith, Amy; Sweet, David; Thomas, Kris; Varney, Andrew; Warm, Eric; Wininger, David; Francis, Mark L.

2015-01-01

Background Many internal medicine (IM) programs have reorganized their resident continuity clinics to improve trainees' ambulatory experience. Downstream effects on continuity of care and other clinical and educational metrics are unclear. Methods This multi-institutional, cross-sectional study included 713 IM residents from 12 programs. Continuity was measured using the usual provider of care method (UPC) and the continuity for physician method (PHY). Three clinic models (traditional, block, and combination) were compared using analysis of covariance. Multivariable linear regression analysis was used to analyze the effect of practice metrics and clinic model on continuity. Results UPC, reflecting continuity from the patient perspective, was significantly different, and was highest in the block model, midrange in combination model, and lowest in the traditional model programs. PHY, reflecting continuity from the perspective of the resident provider, was significantly lower in the block model than in combination and traditional programs. Panel size, ambulatory workload, utilization, number of clinics attended in the study period, and clinic model together accounted for 62% of the variation found in UPC and 26% of the variation found in PHY. Conclusions Clinic model appeared to have a significant effect on continuity measured from both the patient and resident perspectives. Continuity requires balance between provider availability and demand for services. Optimizing this balance to maximize resident education, and the health of the population served, will require consideration of relevant local factors and priorities in addition to the clinic model. PMID:26217420

A qualitative study on clinical research in Finland: fragmented governance and volume in the 2000s

PubMed Central

Hemminki, Elina; Veerus, Piret; Virtanen, Jorma; Lehto, Juhani

2013-01-01

Objectives Although concerns over clinical research have been expressed, the governance of clinical research has been little studied. The aim was to describe research policy, volume, funding and concerns over clinical research in Finland. Design A qualitative study and the data were collected from various sources, including documents, statistics and semistructured expert interviews. Setting Finland. Results We found no national policy for clinical research. Many actors were responsible for facilitating, directing, regulating and funding clinical research, but no actor had the main responsibility. Health professionals were the main drivers for clinical research. The role of the health ministry was small. The ministry distributed state money for clinical research in health services (EVO-money), but did not use it to direct research. Municipalities responsible for health services or national health insurance had little interest in clinical research. The Academy of Finland had had initiatives to promote clinical research, but they had not materialised in funding. Clinical research was common and internationally competitive, but its volume had declined relatively in the 2000s. Industry was an important private funder, mainly supporting drug trials made for licensing purposes. Drug trials without an outside sponsor (academic projects) declined between 2002 and 2010. The funding and its targeting and amount were no one's responsibility. Concerns over clinical research were similar as in other countries, but it had appeared late. Conclusions Our results suggest fragmented governance and funding in clinical research. The unsystematic research environment has not prevented clinical research from flourishing, but the public health relevance of the research carried out and its sustainability are unclear. PMID:23408074

Clinically relevant transmitted drug resistance to first line antiretroviral drugs and implications for recommendations.

PubMed

Monge, Susana; Guillot, Vicente; Alvarez, Marta; Chueca, Natalia; Stella, Natalia; Peña, Alejandro; Delgado, Rafael; Córdoba, Juan; Aguilera, Antonio; Vidal, Carmen; García, Federico

2014-01-01

The aim was to analyse trends in clinically relevant resistance to first-line antiretroviral drugs in Spain, applying the Stanford algorithm, and to compare these results with reported Transmitted Drug Resistance (TDR) defined by the 2009 update of the WHO SDRM list. We analysed 2781 sequences from ARV naive patients of the CoRIS cohort (Spain) between 2007-2011. Using the Stanford algorithm "Low-level resistance", "Intermediate resistance" and "High-level resistance" categories were considered as "Resistant". 70% of the TDR found using the WHO list were relevant for first-line treatment according to the Stanford algorithm. A total of 188 patients showed clinically relevant resistance to first-line ARVs [6.8% (95%Confidence Interval: 5.8-7.7)], and 221 harbored TDR using the WHO list [7.9% (6.9-9.0)]. Differences were due to a lower prevalence in clinically relevant resistance for NRTIs [2.3% (1.8-2.9) vs. 3.6% (2.9-4.3) by the WHO list] and PIs [0.8% (0.4-1.1) vs. 1.7% (1.2-2.2)], while it was higher for NNRTIs [4.6% (3.8-5.3) vs. 3.7% (3.0-4.7)]. While TDR remained stable throughout the study period, clinically relevant resistance to first line drugs showed a significant trend to a decline (p = 0.02). Prevalence of clinically relevant resistance to first line ARVs in Spain is decreasing, and lower than the one expected looking at TDR using the WHO list. Resistance to first-line PIs falls below 1%, so the recommendation of screening for TDR in the protease gene should be questioned in our setting. Cost-effectiveness studies need to be carried out to inform evidence-based recommendations.

Micrometastases in neuroblastoma: are they clinically important?

PubMed Central

Burchill, S A

2004-01-01

Despite advances in the treatment of neuroblastoma (NBL), recurrence and metastases continue to pose major problems in clinical management. The relation between micrometastases and the development of secondary disease is not fully understood. However, accurate methods to detect low numbers of tumour cells may allow the evaluation of their role in the disease process, and by implication the possible benefits of eliminating them. Although there is substantial evidence for the increased sensitivity of current molecular methods for the detection of NBL cells compared with more conventional cytology, the clinical relevance and usefulness of detecting this disease remain controversial. The primary goal of current translational research must be to evaluate the clinical relevance of micrometastatic disease detected by these methods in multicentre prospective clinical outcome studies. Only then can the clinical usefulness of these methods be defined so that they may be introduced into relevant clinical practice. PMID:14693828

Identifying clinically relevant drug resistance genes in drug-induced resistant cancer cell lines and post-chemotherapy tissues.

PubMed

Tong, Mengsha; Zheng, Weicheng; Lu, Xingrong; Ao, Lu; Li, Xiangyu; Guan, Qingzhou; Cai, Hao; Li, Mengyao; Yan, Haidan; Guo, You; Chi, Pan; Guo, Zheng

2015-12-01

Until recently, few molecular signatures of drug resistance identified in drug-induced resistant cancer cell models can be translated into clinical practice. Here, we defined differentially expressed genes (DEGs) between pre-chemotherapy colorectal cancer (CRC) tissue samples of non-responders and responders for 5-fluorouracil and oxaliplatin-based therapy as clinically relevant drug resistance genes (CRG5-FU/L-OHP). Taking CRG5-FU/L-OHP as reference, we evaluated the clinical relevance of several types of genes derived from HCT116 CRC cells with resistance to 5-fluorouracil and oxaliplatin, respectively. The results revealed that DEGs between parental and resistant cells, when both were treated with the corresponding drug for a certain time, were significantly consistent with the CRG5-FU/L-OHP as well as the DEGs between the post-chemotherapy CRC specimens of responders and non-responders. This study suggests a novel strategy to extract clinically relevant drug resistance genes from both drug-induced resistant cell models and post-chemotherapy cancer tissue specimens.

[The Probabilistic Efficiency Frontier: A Value Assessment of Treatment Options in Hepatitis C].

PubMed

Mühlbacher, Axel C; Sadler, Andrew

2017-06-19

Background The German Institute for Quality and Efficiency in Health Care (IQWiG) recommends the concept of the efficiency frontier to assess health care interventions. The efficiency frontier supports regulatory decisions on reimbursement prices for the appropriate allocation of health care resources. Until today this cost-benefit assessment framework has only been applied on the basis of individual patient-relevant endpoints. This contradicts the reality of a multi-dimensional patient benefit. Objective The objective of this study was to illustrate the operationalization of multi-dimensional benefit considering the uncertainty in clinical effects and preference data in order to calculate the efficiency of different treatment options for hepatitis C (HCV). This case study shows how methodological challenges could be overcome in order to use the efficiency frontier for economic analysis and health care decision-making. Method The operationalization of patient benefit was carried out on several patient-relevant endpoints. Preference data from a discrete choice experiment (DCE) study and clinical data based on clinical trials, which reflected the patient and the clinical perspective, respectively, were used for the aggregation of an overall benefit score. A probabilistic efficiency frontier was constructed in a Monte Carlo simulation with 10000 random draws. Patient-relevant endpoints were modeled with a beta distribution and preference data with a normal distribution. The assessment of overall benefit and costs provided information about the adequacy of the treatment prices. The parameter uncertainty was illustrated by the price-acceptability-curve and the net monetary benefit. Results Based on the clinical and preference data in Germany, the interferon-free treatment options proved to be efficient for the current price level. The interferon-free therapies of the latest generation achieved a positive net cost-benefit. Within the decision model, these therapies showed a maximum overall benefit. Due to their high additional benefit and approved prices, the therapies lie above of the extrapolated efficiency frontier, which suggests that these options have efficient reimbursement prices. Considering uncertainty, even a higher price would have resulted in a positive cost-benefit ratio. Conclusion IQWiG's efficiency frontier was used to assess the value of different treatment options in HCV. This study demonstrates that the probabilistic efficiency frontier, price-acceptability-curve and the net monetary benefit can contribute essential information to reimbursement decisions and price negotiations. © Georg Thieme Verlag KG Stuttgart · New York.

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.

Does a 3-week critical research appraisal course affect how students perceive their appraisal skills and the relevance of research for clinical practice? A repeated cross-sectional survey.

PubMed

Jelsness-Jørgensen, Lars-Petter

2015-01-01

Research utilisation is essential in developing evidence-based practices; although many students may be generally able to adopt such skills, there are reports of barriers related to critical appraisal skills. To explore how students perceive the relevance of research to future clinical practice and patients, and to what extent they read research (including reading pattern). Additionally, the objective was to explore whether a three-week intensive course in critical appraisal of research could affect these variables. A cross-sectional survey design, with a pre- and post-test. One large university college in Southeastern Norway. 196 multidisciplinary healthcare students at baseline and 147 after three weeks. A purposely-designed 21 item questionnaire was used to quantify students' attitudes towards using research and critical thinking. The questionnaire was based on themes emerging from prior focus group interviews with 10 nursing and social educator students as well as from the existing literature. At baseline, 6.1% and 7.1% of respondents perceived the research to be of little or very little importance for their future work and patients, respectively. Furthermore, 83.2% reported that they seldom or very seldom read scientific papers. At baseline, 40 different patterns of reading a scientific paper were identified. Additionally, 7.1% of respondents reported to read the introduction, methods and conclusion in combination. Significantly improved scores were found after completing the three-week course related to a) relevance of research for future work (p<0.01), b) self-perceived skills in critical appraisal (p<0.001), c) ability to find scientific papers (p≤0.01), and d) relevance of research for patients and users (p≤0.001). Teaching students' practical critical appraisal skills improved their view of the relevance of research for patients, future work as well as their own critical appraisal skills. Prospective studies are warranted to explore the effects of such teaching modules in the long-term. Copyright © 2014 Elsevier Ltd. All rights reserved.

Exploring e-readers to support clinical medical education: two case studies*†

PubMed Central

von Isenburg, Megan

2011-01-01

Question: Can e-readers loaded with medical textbooks and other relevant material benefit medical students, residents, and preceptors in clinical settings? Settings: The settings are North Carolina community clinics served by Duke University Medical Center and St. Joseph's Hospital in Bryan, Texas, and Scott and White Memorial Hospital in Temple, Texas. Methods: Duke University: Twenty second-year medical students and fourteen family medicine clerkship preceptors used Kindle e-readers in clinics during eight months of rotations. Students and preceptors provided feedback through an anonymous online survey. Texas A&M University: Nine fourth-year medical students in an elective compared medical textbooks in print, online, and on a Kindle. Six residents at a local hospital completed an anonymous online survey after a three-week loan of a Kindle loaded with medical textbooks. Results: The e-reader's major advantages in clinical settings are portability and searchability. The selected e-reader's limitations include connection speed, navigation, and display. User preferences varied, but online resources were preferred. Participants suggested additional uses for Kindles in medical education. Conclusions: The selected e-reader's limitations may be resolved with further development of the device. Investigation of other e-readers is needed. Criteria for evaluating e-readers in clinical settings should include portability, searchability, speed, navigation, and display. Research comparing e-readers and mobile devices in clinical education is also warranted. PMID:21464848

Translating U-500R Randomized Clinical Trial Evidence to the Practice Setting: A Diabetes Educator/Expert Prescriber Team Approach

PubMed Central

Bergen, Paula M.; Kruger, Davida F.; Taylor, April D.; Eid, Wael E.; Bhan, Arti; Jackson, Jeffrey A.

2017-01-01

Purpose The purpose of this article is to provide recommendations to the diabetes educator/expert prescriber team for the use of human regular U-500 insulin (U-500R) in patients with severely insulin-resistant type 2 diabetes, including its initiation and titration, by utilizing dosing charts and teaching materials translated from a recent U-500R clinical trial. Conclusions Clinically relevant recommendations and teaching materials for the optimal use and management of U-500R in clinical practice are provided based on the efficacy and safety results of and lessons learned from the U-500R clinical trial by Hood et al, current standards of practice, and the authors’ clinical expertise. This trial was the first robustly powered, randomized, titration-to-target trial to compare twice-daily and three-times-daily U-500R dosing regimens. Modifications were made to the initiation and titration dosing algorithms used in this trial to simplify dosing strategies for the clinical setting and align with current glycemic targets recommended by the American Diabetes Association. Leveraging the expertise, resources, and patient interactions of the diabetes educator who can provide diabetes self-management education and support in collaboration with the multidisciplinary diabetes team is strongly recommended to ensure patients treated with U-500R receive the timely and comprehensive care required to safely and effectively use this highly concentrated insulin. PMID:28427304

Translating U-500R Randomized Clinical Trial Evidence to the Practice Setting: A Diabetes Educator/Expert Prescriber Team Approach.

PubMed

Bergen, Paula M; Kruger, Davida F; Taylor, April D; Eid, Wael E; Bhan, Arti; Jackson, Jeffrey A

2017-06-01

Purpose The purpose of this article is to provide recommendations to the diabetes educator/expert prescriber team for the use of human regular U-500 insulin (U-500R) in patients with severely insulin-resistant type 2 diabetes, including its initiation and titration, by utilizing dosing charts and teaching materials translated from a recent U-500R clinical trial. Conclusions Clinically relevant recommendations and teaching materials for the optimal use and management of U-500R in clinical practice are provided based on the efficacy and safety results of and lessons learned from the U-500R clinical trial by Hood et al, current standards of practice, and the authors' clinical expertise. This trial was the first robustly powered, randomized, titration-to-target trial to compare twice-daily and three-times-daily U-500R dosing regimens. Modifications were made to the initiation and titration dosing algorithms used in this trial to simplify dosing strategies for the clinical setting and align with current glycemic targets recommended by the American Diabetes Association. Leveraging the expertise, resources, and patient interactions of the diabetes educator who can provide diabetes self-management education and support in collaboration with the multidisciplinary diabetes team is strongly recommended to ensure patients treated with U-500R receive the timely and comprehensive care required to safely and effectively use this highly concentrated insulin.

Epileptic spasms are a feature of DEPDC5 mTORopathy

PubMed Central

Carvill, Gemma L.; Crompton, Douglas E.; Regan, Brigid M.; McMahon, Jacinta M.; Saykally, Julia; Zemel, Matthew; Schneider, Amy L.; Dibbens, Leanne; Howell, Katherine B.; Mandelstam, Simone; Leventer, Richard J.; Harvey, A. Simon; Mullen, Saul A.; Berkovic, Samuel F.; Sullivan, Joseph; Scheffer, Ingrid E.

2015-01-01

Objective: To assess the presence of DEPDC5 mutations in a cohort of patients with epileptic spasms. Methods: We performed DEPDC5 resequencing in 130 patients with spasms, segregation analysis of variants of interest, and detailed clinical assessment of patients with possibly and likely pathogenic variants. Results: We identified 3 patients with variants in DEPDC5 in the cohort of 130 patients with spasms. We also describe 3 additional patients with DEPDC5 alterations and epileptic spasms: 2 from a previously described family and a third ascertained by clinical testing. Overall, we describe 6 patients from 5 families with spasms and DEPDC5 variants; 2 arose de novo and 3 were familial. Two individuals had focal cortical dysplasia. Clinical outcome was highly variable. Conclusions: While recent molecular findings in epileptic spasms emphasize the contribution of de novo mutations, we highlight the relevance of inherited mutations in the setting of a family history of focal epilepsies. We also illustrate the utility of clinical diagnostic testing and detailed phenotypic evaluation in characterizing the constellation of phenotypes associated with DEPDC5 alterations. We expand this phenotypic spectrum to include epileptic spasms, aligning DEPDC5 epilepsies more with the recognized features of other mTORopathies. PMID:27066554

The role of alprazolam for the treatment of panic disorder in Australia.

PubMed

Moylan, Steven; Giorlando, Francesco; Nordfjærn, Trond; Berk, Michael

2012-03-01

To investigate the potential impact of increasing prescription rates of alprazolam for the treatment of panic disorder (PD) in Australia through a review of efficacy, tolerability and adverse outcome literature. Data were sourced by a literature search using MEDLINE, Embase, PsycINFO and a manual search of scientific journals to identify relevant articles. Clinical practice guidelines from the American Psychiatric Association, National Institute of Clinical Excellence, Royal Australian and New Zealand College of Psychiatrists and World Federation of Societies of Biological Psychiatry were sourced. Prescription data were sourced from Australian governmental sources. Alprazolam has shown efficacy for control of PD symptoms, particularly in short-term controlled clinical trials, but is no longer recommended as a first-line pharmacological treatment due to concerns about the risks of developing tolerance, dependence and abuse potential. Almost no evidence is available comparing alprazolam to current first-line pharmacological treatment. Despite this, prescription rates are increasing. A number of potential issues including use in overdose and impact on car accidents are noted. conclusion: Although effective for PD symptoms in clinical trials, a number of potential issues may exist with use. Consideration of its future place in PD treatment in Australia may be warranted.

Current and Emerging Technology Approaches in Genomics

PubMed Central

Conley, Yvette P.; Biesecker, Leslie G.; Gonsalves, Stephen; Merkle, Carrie J.; Kirk, Maggie; Aouizerat, Bradley E.

2013-01-01

Purpose To introduce current and emerging approaches that are being utilized in the field of genomics so the reader can conceptually evaluate the literature and appreciate how these approaches are advancing our understanding of health-related issues. Organizing Construct Each approach is described and includes information related to how it is advancing research, its potential clinical utility, exemplars of current uses, challenges related to technologies used for these approaches, and when appropriate information related to understanding the evidence base for clinical utilization of each approach is provided. Web-based resources are included for the reader who would like more in-depth information and to provide opportunity to stay up to date with these approaches and their utility. Conclusions The chosen approaches– genome sequencing, genome-wide association studies, epigenomics, and gene expression– are extremely valuable approaches for collecting research data to help us better understand the pathophysiology of a variety of health-related conditions, but they are also gaining in utility for clinical assessment and testing purposes. Clinical Relevance Our increased understanding of the molecular underpinnings of disease will assist with better development of screening tests, diagnostic tests, tests that allow us to prognosticate, tests that allow for individualized treatments, and tests to facilitate post-treatment surveillance. PMID:23294727

Varying ethics rules in clinical research and routine patient care – research ethics committee chairpersons’ views in Finland

PubMed Central

2014-01-01

Background To present empirical data on how the variation in regulating clinical research and patient care was perceived in Finland between 2009 and 2012. Methods Notes of interviews with 22 research ethics committee (REC) chairpersons were analyzed to identify whether differences in the regulation of clinical research and patient care were addressed. REC chairpersons’ opinions on three imaginary cases of clinical research projects challenging current research ethics rules (vignettes) were requested with a questionnaire; 18 of the 22 interviewed chairpersons responded. Results Based on REC chairpersons’ interviews, the differences between care and research regulation were not considered important issues in Finland. In the vignettes, REC chairpersons’ assumptions on how their REC would decide varied in regard to allowing research without informed consent, while solutions that are not allowed by current law were even anticipated. Mostly, but not always, the chairpersons’ own personal view agreed with their REC. Conclusions The distinction between care and research regulation has not been publicly challenged by Finnish RECs, even though it is a challenge when research relevant to health care is carried out. There is a need for debate and changes in laws and practices. PMID:24666735

Topical Vitamin C and the Skin: Mechanisms of Action and Clinical Applications

PubMed Central

Al-Niaimi, Firas

2017-01-01

OBJECTIVE: This review article details the main mechanisms of action and clinical applications of topical vitamin C on the skin, including its antioxidative, photoprotective, antiaging, and antipigmentary effects. DESIGN: A PubMed search for the relevant articles on vitamin C and the skin was conducted using the following key words: “vitamin C,” “ascorbic acid,” “ascorbyl-6-palmitate,”and “magnesium ascorbyl phosphate.” RESULTS: As one of the most powerful antioxidants in the skin, vitamin C has been shown to protect against photoaging, ultraviolet-induced immunosuppression, and photocarcinogenesis. It also has an antiaging effect by increasing collagen synthesis, stabilizing collagen fibers, and decreasing collagen degradation. It decreases melanin formation, thereby reducing pigmentation. Vitamin C is the primary replenisher of vitamin E and works synergistically with vitamin E in the protection against oxidative damage. CONCLUSION: Topical vitamin C has a wide range of clinical applications, from antiaging and antipigmentary to photoprotective. Currently, clinical studies on the efficacy of topical formulations of vitamin C remain limited, and the challenge lies in finding the most stable and permeable formulation in achieving the optimal results. PMID:29104718

Clinical Efficacy of Acupuncture on Rheumatoid Arthritis and Associated Mechanisms: A Systemic Review.

PubMed

Chou, Pei-Chi; Chu, Heng-Yi

2018-01-01

The objective of this review is to investigate the detailed existing scientific information about the clinical efficacy of acupuncture on rheumatoid arthritis (RA) conditions and to reveal the proposed mechanisms. We searched the PubMed, EMBASE, Cochrane, AMED (Allied and Complementary Medicine), NCCAM (The National Center for Complementary and Alternative Medicine), and CNKI (China National Knowledge Infrastructure) databases to identify relevant monographs and related references from 1974 to 2018. Chinese journals and theses/dissertations were hand searched. 43 studies were recruited. Each research was analyzed for study design, subject characteristics, intervention, selected acupoints, assessment parameters, proposed mechanisms, and results/conclusions. In our review, we concluded that acupuncture alone or combined with other treatment modalities is beneficial to the clinical conditions of RA without adverse effects reported and can improve function and quality of life and is worth trying. Several important possible mechanisms were summarized including anti-inflammatory effect, antioxidative effect, and regulation of immune system function. However, there is still inconsistency regarding the clinical efficacy and lack of well-designed human/animal double-blinded RCTs. Future discussion for further agreement on taking traditional Chinese medicine (TCM) theory into consideration as much as possible is a top priority.

Assessing Research Interest and Capacity in Community Health Centers

PubMed Central

Bhuiya, Nazmim; Pernice, Joan; Khan, Sami M.; Sequist, Thomas D.; Tendulkar, Shalini A.

2013-01-01

Abstract Objective Community health centers (CHCs) have great potential to participate in the development of evidence‐based primary care but face obstacles to engagement in clinical translational research. Methods To understand factors associated with CHC interest in building research infrastructure, Harvard Catalyst and the Massachusetts League of Community Health Centers conducted an online survey of medical directors in all 50 Massachusetts CHC networks. Results Thirty‐two (64%) medical directors completed the survey representing 126 clinical sites. Over 80% reported that their primary care providers (PCPs) were slightly to very interested in future clinical research and that they were interested in building research infrastructure at their CHC. Frequently cited barriers to participation in research included financial issues, lack of research skills, and lack of research infrastructure. In bivariate analyses, PCP interest in future clinical research and a belief that involvement in research contributed to PCP retention were significantly associated with interest in building research infrastructure. Conclusion CHCs critical role in caring for vulnerable populations ideally positions them to raise relevant research questions and translate evidence into practice. Our findings suggest a high interest in engagement in research among CHC leadership. CTSAs have a unique opportunity to support local CHCs in this endeavor. PMID:24127928

Biophysical Technologies for Management of Wound Bioburden

PubMed Central

Korzendorfer, Holly; Hettrick, Heather

2014-01-01

Significance: Chronic wounds commonly have high levels of bioburden and antibiotic-resistant pathogens. This review article focuses on findings from current literature related to four biophysical technologies (ultrasound, electrical stimulation, phototherapy, and negative pressure wound therapy) believed to be beneficial for managing wound bioburden and support healing. Recent Advances and Critical Issues: Recent advances for each modality are provided as a basic synopsis of the technology followed by brief overviews of the most recent literature addressing its effectiveness for managing wound bioburden, and critical issues for each modality are provided as conclusions. Future Directions: This review highlights the need for further clinically relevant studies examining bacterial levels in addition to healing progression for each technology. PMID:25493207

[Doubting the twirling angle of filiform needle in Science of Acupuncture and Moxibustion textbooks and National Standards].

PubMed

Tian, Kaiyu

2016-07-12

In National Standards (GB) as well as the textbooks used in TCM universities, the twirling angles of acupuncture manipulation vary a lot. By reviewing the previous editions of textbooks from 3 publication houses and comparing the relevant contents, the author calculated the arc lengths of various twirling angles based on the specification of filiform needle in National Standards (GB) and International Standards (ISO). The conclusion is that the twirling angles mentioned in National Standards (GB) and textbooks are too small and not in compliance with the clinical practice. Hence, it is not advisable to propose a rigid specific provision of twirling angle in acupuncture manipulation.

Gliomatosis cerebri: A consensus summary report from the First International Gliomatosis cerebri Group Meeting, March 26-27, 2015, Paris, France.

PubMed

Greenfield, Jeffrey P; Castañeda Heredia, Alicia; George, Emilie; Kieran, Mark W; Morales La Madrid, Andres

2016-12-01

Gliomatosis cerebri (GC) is a universally fatal extensive and diffuse infiltration of brain parenchyma by a glial tumor. Many aspects of this phenomenon remain unknown. The First International Gliomatosis cerebri Group Meeting had the following goals: refine the clinical and radiologic diagnostic criteria for GC, suggest appropriate diagnostic procedures, standardize tissue manipulation for histologic and molecular characterization, and prioritize relevant preclinical projects. Also, general treatment recommendations were outlined for the pediatric population. Importantly, this meeting was the starting point for meaningful collaborative international research projects. This review is a consensus summary of discussions shared and conclusions derived from this meeting. © 2016 Wiley Periodicals, Inc.

A misleading review of response bias: comment on McGrath, Mitchell, Kim, and Hough (2010).

PubMed

Rohling, Martin L; Larrabee, Glenn J; Greiffenstein, Manfred F; Ben-Porath, Yossef S; Lees-Haley, Paul; Green, Paul; Greve, Kevin W

2011-07-01

In the May 2010 issue of Psychological Bulletin, R. E. McGrath, M. Mitchell, B. H. Kim, and L. Hough published an article entitled "Evidence for Response Bias as a Source of Error Variance in Applied Assessment" (pp. 450-470). They argued that response bias indicators used in a variety of settings typically have insufficient data to support such use in everyday clinical practice. Furthermore, they claimed that despite 100 years of research into the use of response bias indicators, "a sufficient justification for [their] use… in applied settings remains elusive" (p. 450). We disagree with McGrath et al.'s conclusions. In fact, we assert that the relevant and voluminous literature that has addressed the issues of response bias substantiates validity of these indicators. In addition, we believe that response bias measures should be used in clinical and research settings on a regular basis. Finally, the empirical evidence for the use of response bias measures is strongest in clinical neuropsychology. We argue that McGrath et al.'s erroneous perspective on response bias measures is a result of 3 errors in their research methodology: (a) inclusion criteria for relevant studies that are too narrow; (b) errors in interpreting results of the empirical research they did include; (c) evidence of a confirmatory bias in selectively citing the literature, as evidence of moderation appears to have been overlooked. Finally, their acknowledging experts in the field who might have highlighted these errors prior to publication may have prevented critiques during the review process.

Functional Validation and Comparison Framework for EIT Lung Imaging

PubMed Central

Meybohm, Patrick; Weiler, Norbert; Frerichs, Inéz; Adler, Andy

2014-01-01

Introduction Electrical impedance tomography (EIT) is an emerging clinical tool for monitoring ventilation distribution in mechanically ventilated patients, for which many image reconstruction algorithms have been suggested. We propose an experimental framework to assess such algorithms with respect to their ability to correctly represent well-defined physiological changes. We defined a set of clinically relevant ventilation conditions and induced them experimentally in 8 pigs by controlling three ventilator settings (tidal volume, positive end-expiratory pressure and the fraction of inspired oxygen). In this way, large and discrete shifts in global and regional lung air content were elicited. Methods We use the framework to compare twelve 2D EIT reconstruction algorithms, including backprojection (the original and still most frequently used algorithm), GREIT (a more recent consensus algorithm for lung imaging), truncated singular value decomposition (TSVD), several variants of the one-step Gauss-Newton approach and two iterative algorithms. We consider the effects of using a 3D finite element model, assuming non-uniform background conductivity, noise modeling, reconstructing for electrode movement, total variation (TV) reconstruction, robust error norms, smoothing priors, and using difference vs. normalized difference data. Results and Conclusions Our results indicate that, while variation in appearance of images reconstructed from the same data is not negligible, clinically relevant parameters do not vary considerably among the advanced algorithms. Among the analysed algorithms, several advanced algorithms perform well, while some others are significantly worse. Given its vintage and ad-hoc formulation backprojection works surprisingly well, supporting the validity of previous studies in lung EIT. PMID:25110887

The effect of normobaric oxygen in patients with acute stroke: a systematic review and meta-analysis.

PubMed

Ding, Jiayue; Zhou, Da; Sui, Meng; Meng, Ran; Chandra, Ankush; Han, Jie; Ding, Yuchuan; Ji, Xunming

2018-03-30

Background Normobaric oxygen (NBO) has received considerable attention due to controversial data in brain protection in patients with acute stroke. This study aims to analyze current data of NBO on brain protection as used in the clinic. Methods We searched for and reviewed relevant articles and references from Pubmed, Medline, Embase, Cochrane, and Clincialtrials.gov that were published prior to October 2017. Data from prospective studies were processed using RevMan5.0 software, provided by Cochrane collaboration and transformed using relevant formulas. Results A total of 11 prospective RCT studies including 6366 patients with acute stroke (NBO group, 3207; control group, 3159) were enrolled in this analysis. △NIHSS represented the values of NIHSS at 4, 24 h, or 7 days post-stroke minus baseline NIHSS. Compared to controls, there was a minor trend toward NBO benefits in short-term prognostic indices, as indicated by decreased ΔNIHSS at our defined time points. By contrast, NBO decreased Barthel Index scores between 3 and 7 months, and increased death rates at 3, 6 months, and 1 year, whereas, modified Rankin Scale scores between 3 and 6 months were unchanged. Conclusions The existing trends toward benefits revealed in this meta-analysis help us appreciate the promising value of NBO, although current evidence of NBO on improving clinical outcomes of stroke is insufficient. Well-designed multi-center clinical trials are encouraged and urgently needed to further explore the efficacy of NBO on brain protection.

Tibiofemoral Compression Force Differences Using Laxity- and Force-Based Initial Graft Tensioning Techniques in the ACL-Reconstructed Knee

PubMed Central

Fleming, Braden C.; Brady, Mark F.; Bradley, Michael P.; Banerjee, Rahul; Hulstyn, Michael J.; Fadale, Paul D.

2008-01-01

Purpose To document the tibiofemoral (TF) compression forces produced during clinical initial graft tension protocols. Methods An image analysis system was used to track the position of the tibia relative to the femur in 11 cadaver knees. TF compression forces were quantified using thin-film pressure sensors. Prior to performing ACL reconstructions with patellar tendon grafts, measurements of TF compression force were obtained from the ACL-intact knee with knee flexion. ACL reconstructions were then performed using “force-based” and “laxity-based” graft tension approaches. Within each approach, high- and low-tension conditions were compared to the ACL-intact condition over the range of knee flexion angles. Results The TF compression forces for all initial graft tension conditions were significantly greater than that of the normal knee when the knee was in full extension (0°). The TF compression forces when using the laxity-based approach were greater than those produced with the force-based approach. However the laxity-based approach was necessary to restore normal laxity at the time of surgery. Conclusions The initial graft tension conditions produce different TF compressive force profiles at the time of surgery. A compromise must be made between restoring knee laxity or TF compressive forces when reconstructing the ACL with patellar tendon graft. Clinical Relevance The TF compression forces were greater in the ACL-reconstructed knee for all the initial graft tension conditions when compared to the ACL-intact knee, and that clinically relevant initial graft tension conditions produce different TF compressive forces. PMID:18760214

Prenatal exposure to escitalopram and/or stress in rats: a prenatal stress model of maternal depression and its treatment

PubMed Central

Bourke, Chase H.; Capello, Catherine F.; Rogers, Swati M.; Yu, Megan L.; Boss-Williams, Katherine A.; Weiss, Jay M.; Stowe, Zachary N.; Owens, Michael J.

2014-01-01

Rationale A rigorously investigated model of stress and antidepressant administration during pregnancy is needed to evaluate possible effects on the mother. Objective The objective of this study was to develop a model of clinically relevant prenatal exposure to an antidepressant and stress during pregnancy to evaluate the effects on maternal care behavior. Results Female rats implanted with 28 day osmotic minipumps delivering the SSRI escitalopram throughout pregnancy had serum escitalopram concentrations in a clinically observed range (17-65 ng/mL). A separate cohort of pregnant females exposed to a chronic unpredictable mild stress paradigm on gestational days 10-20 showed elevated baseline (305 ng/mL), and acute stress-induced (463 ng/mL), plasma corticosterone concentrations compared to unstressed controls (109 ng/mL). A final cohort of pregnant dams were exposed to saline (control), escitalopram, stress, or stress and escitalopram to determine the effects on maternal care. Maternal behavior was continuously monitored over the first 10 days post parturition. A reduction of 35% in maternal contact and 11% in nursing behavior was observed due to stress during the light cycle. Licking and grooming behavior was unaffected by stress or drug exposure in either the light or dark cycle. Conclusions These data indicate that: 1) clinically relevant antidepressant treatment during human pregnancy can be modeled in rats using escitalopram; 2) chronic mild stress can be delivered in a manner that does not compromise fetal viability; and 3) neither of these prenatal treatments substantially altered maternal care post parturition. PMID:23436130

Panic disorder and its subtypes: a comprehensive analysis of panic symptom heterogeneity using epidemiological and treatment seeking samples

PubMed Central

Roberson-Nay, R.; Kendler, K. S.

2014-01-01

Background Panic disorder (PD) is a heterogeneous syndrome that can present with a variety of symptom profiles that potentially reflect distinct etiologic pathways. The present study represents the most comprehensive examination of phenotypic variance in PD with and without agoraphobia for the purpose of identifying clinically relevant and etiologically meaningful subtypes. Method Latent class (LC) and factor mixture analysis were used to examine panic symptom data ascertained from three national epidemiologic surveys [Epidemiological Catchment Area (ECA), National Comorbidity Study (NCS), National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), Wave 1], a twin study [Virginia Adult Twin Study of Psychiatric and Substance Use Disorders (VATSPSUD)] and a clinical trial (Cross-National Collaborative Panic Study [CNCPS]). Results Factor mixture models (versus LC) generally provided better fit to panic symptom data and suggested two panic classes for the ECA, VATSPSUD and CNCPS, with one class typified by prominent respiratory symptoms. The NCS yielded two classes, but suggested both qualitative and quantitative differences. The more contemporary NESARC sample supported a two and three class model, with the three class model suggesting two variants of respiratory panic. The NESARC’s three class model continued to provide the best fit when the model was restricted to a more severe form of PD/panic disorder with agoraphobia. Conclusions Results from epidemiologic and clinical samples suggest two panic subtypes, with one subtype characterized by a respiratory component and a second class typified by general somatic symptoms. Results are discussed in light of their relevance to the etiopathogenesis of PD. PMID:21557895

Pre-Operative Diet Impacts the Adipose Tissue Response to Surgical Trauma

PubMed Central

Nguyen, Binh; Tao, Ming; Yu, Peng; Mauro, Christine; Seidman, Michael A.; Wang, Yaoyu E.; Mitchell, James; Ozaki, C. Keith

2012-01-01

Background Short-term changes in pre-operative nutrition can have profound effects on surgery related outcomes such as ischemia reperfusions injury in pre-clinical models. Dietary interventions that lend protection against stress in animal models (e.g. fasting, dietary restriction [DR]) impact adipose tissue quality/quantity. Adipose tissue holds high surgical relevance due to its anatomic location and high tissue volume, and it is ubiquitously traumatized during surgery. Yet the response of adipose tissue to trauma under clinically relevant circumstances including dietary status remains poorly defined. We hypothesized that pre-operative diet alters the adipose tissue response to surgical trauma. Methods A novel mouse model of adipose tissue surgical trauma was employed. Dietary conditions (diet induced obesity [DIO], pre-operative DR) were modulated prior to application of surgical adipose tissue trauma in the context of clinically common scenarios (different ages, simulated bacterial wound contamination). Local/distant adipose tissue phenotypic responses were measured as represented by gene expression of inflammatory, tissue remodeling/growth, and metabolic markers. Results Surgical trauma had a profound effect on adipose tissue phenotype at the site of trauma. Milder but significant distal effects on non-traumatized adipose tissue were also observed. DIO exacerbated the inflammatory aspects of this response, and pre-operative DR tended to reverse these changes. Age and LPS-simulated bacterial contamination also impacted the adipose tissue response to trauma, with young adult animals and LPS treatment exacerbating the proinflammatory response. Conclusions Surgical trauma dramatically impacts both local and distal adipose tissue biology. Short-term pre-operative DR may offer a strategy to attenuate this response. PMID:23274098

Even High Doses of Oral Cannabidiol Do Not Cause THC-Like Effects in Humans: Comment on Merrick et al. Cannabis and Cannabinoid Research 2016;1(1):102–112; DOI: 10.1089/can.2015.0004

PubMed Central

Grotenhermen, Franjo; Russo, Ethan; Zuardi, Antonio Waldo

2017-01-01

Abstract This short communication examines the question whether the experimental data presented in a study by Merrick et al. are of clinical relevance. These authors found that cannabidiol (CBD), a major cannabinoid of the cannabis plant devoid of psychotropic effects and of great interest for therapeutic use in several medical conditions, may be converted in gastric fluid into the psychoactive cannabinoids delta-8-THC and delta-9-THC to a relevant degree. They concluded that “the acidic environment during normal gastrointestinal transit can expose orally CBD-treated patients to levels of THC and other psychoactive cannabinoids that may exceed the threshold for a positive physiological response.” They issued a warning concerning oral use of CBD and recommend the development of other delivery methods. However, the available clinical data do not support this conclusion and recommendation, since even high doses of oral CBD do not cause psychological, psychomotor, cognitive, or physical effects that are characteristic for THC or cannabis rich in THC. On the contrary, in the past decades and by several groups, high doses of oral CBD were consistently shown to cause opposite effects to those of THC in clinical studies. In addition, administration of CBD did not result in detectable THC blood concentrations. Thus, there is no reason to avoid oral use of CBD, which has been demonstrated to be a safe means of administration of CBD, even at very high doses. PMID:28861499

Monoclonal antibodies for chronic pain: A practical review of mechanisms and clinical applications

PubMed Central

Yeh, Ju-Fen; Akinci, Aysen; Al Shaker, Mohammed; Chang, Ming Hong; Danilov, Andrei; Guillen, Rocio; Johnson, Kirk W; Kim, Yong-Chul; Skljarevski, Vladimir; Dueñas, Héctor J; Tassanawipas, Warat

2017-01-01

Context Monoclonal antibodies are being investigated for chronic pain to overcome the shortcomings of current treatment options. Objective To provide a practical overview of monoclonal antibodies in clinical development for use in chronic pain conditions, with a focus on mechanisms of action and relevance to specific classes. Methods Qualitative review using a systematic strategy to search for randomized controlled trials, systematic and nonsystematic (narrative) reviews, observational studies, nonclinical studies, and case reports for inclusion. Studies were identified via relevant search terms using an electronic search of MEDLINE via PubMed (1990 to June 2017) in addition to hand-searching reference lists of retrieved systematic and nonsystematic reviews. Results Monoclonal antibodies targeting nerve growth factor, calcitonin gene-related peptide pathways, various ion channels, tumor necrosis factor-α, and epidermal growth factor receptor are in different stages of development. Mechanisms of action are dependent on specific signaling pathways, which commonly involve those related to peripheral neurogenic inflammation. In clinical studies, there has been a mixed response to different monoclonal antibodies in several chronic pain conditions, including migraine, neuropathic pain conditions (e.g., diabetic peripheral neuropathy), osteoarthritis, chronic back pain, ankylosing spondylitis, and cancer. Adverse events observed to date have generally been mild, although further studies are needed to ensure safety of monoclonal antibodies in early stages of development, especially where there is an overlap with non-pain-related pathways. High acquisition cost remains another treatment limitation. Conclusion Monoclonal antibodies for chronic pain have the potential to overcome the limitations of current treatment options, but strategies to ensure their appropriate use need to be determined. PMID:29056066

Acute Stress Symptoms in Children: Results From an International Data Archive

PubMed Central

Kassam-Adams, Nancy; Palmieri, Patrick A.; Rork, Kristine; Delahanty, Douglas L.; Kenardy, Justin; Kohser, Kristen L.; Landolt, Markus A.; Le Brocque, Robyne; Marsac, Meghan L.; Meiser-Stedman, Richard; Nixon, Reginald D. V.; Bui, Eric; McGrath, Caitlin

2012-01-01

Objective To describe the prevalence of acute stress disorder (ASD) symptoms and examine proposed DSM-5 symptom criteria in relation to concurrent functional impairment in children. Method From an international archive, datasets were identified which included assessment of acute traumatic stress reactions and concurrent impairment in children age 5 to 17. Data came from 15 studies conducted in the US, UK, Australia, and Switzerland with 1645 children. Dichotomized items were created to indicate the presence or absence of each of the 14 proposed ASD symptoms and functional impairment. The performance of a proposed diagnostic criterion (number of ASD symptoms required) was examined as a predictor of concurrent impairment. Results Each ASD symptom was endorsed by 14% to 51% of children; 41% reported clinically-relevant impairment. Children reported from 0 to 13 symptoms (mean = 3.6). Individual ASD symptoms were associated with greater likelihood of functional impairment. The DSM-5 proposed 8-symptom requirement was met by 202 (12.3%) children, and had low sensitivity (.25) in predicting concurrent clinically-relevant impairment. Requiring fewer symptoms (three to four) greatly improved sensitivity while maintaining moderate specificity. Conclusions This group of symptoms appears to capture aspects of traumatic stress reactions that can create distress and interfere with children’s ability to function in the acute post-trauma phase. Results provide a benchmark for comparison with adult samples; a smaller proportion of children met the 8-symptom criterion than reported for adults. Symptom requirements for the ASD diagnosis may need to be lowered to optimally identify children whose acute distress warrants clinical attention. PMID:22840552

Evaluating beneficial drug effects in a non‐interventional setting: a review of effectiveness studies based on Swedish Prescribed Drug Register data

PubMed Central

Hoffmann, Mikael

2017-01-01

Aims To describe and assess current effectiveness studies published up to 2014 using Swedish Prescribed Drug Register (SPDR) data. Methods Study characteristics were extracted. Each study was assessed concerning the clinical relevance of the research question, the risk of bias according to a structured checklist, and as to whether its findings contributed to new knowledge. The biases encountered and ways of handling these were retrieved. Results A total of 24 effectiveness studies were included in the review, the majority on cardiovascular or psychiatric disease (n = 17; 71%). The articles linked data from four (interquartile range: three to four) registers, and were published in 21 different journals with an impact factor ranging from 1.58 to 51.66. All articles had a clinically relevant research question. According to the systematic quality assessments, the overall risk of bias was low in one (4%), moderate in eight (33%) and high in 15 (62%) studies. Overall, two (8%) studies were assessed as contributing to new knowledge. Frequently occurring problems were selection bias making the comparison groups incomparable, treatment bias with suboptimal handling of drug exposure and an intention‐to‐treat approach, and assessment bias including immortal time bias. Good examples of how to handle bias problems included propensity score matching and sensitivity analyses. Conclusion Although this review illustrates that effectiveness studies based on dispensed drug register data can contribute to new evidence of intended effects of drug treatment in clinical practice, the expectations of such data to provide valuable information need to be tempered due to methodological issues. PMID:27928842

Electronic case report forms and electronic data capture within clinical trials and pharmacoepidemiology

PubMed Central

Flynn, Robert W. V.; Grieve, Kerr; Doney, Alexander; Mackenzie, Isla; MacDonald, Thomas M.; Rogers, Amy

2017-01-01

Aims Researchers in clinical and pharmacoepidemiology fields have adopted information technology (IT) and electronic data capture, but these remain underused despite the benefits. This review discusses electronic case report forms and electronic data capture, specifically within pharmacoepidemiology and clinical research. Methods The review used PubMed and the Institute of Electrical and Electronic Engineers library. Search terms used were agreed by the authors and documented. PubMed is medical and health based, whereas Institute of Electrical and Electronic Engineers is technology based. The review focuses on electronic case report forms and electronic data capture, but briefly considers other relevant topics; consent, ethics and security. Results There were 1126 papers found using the search terms. Manual filtering and reviewing of abstracts further condensed this number to 136 relevant manuscripts. The papers were further categorized: 17 contained study data; 40 observational data; 27 anecdotal data; 47 covering methodology or design of systems; one case study; one literature review; two feasibility studies; and one cost analysis. Conclusion Electronic case report forms, electronic data capture and IT in general are viewed with enthusiasm and are seen as a cost‐effective means of improving research efficiency, educating participants and improving trial recruitment, provided concerns about how data will be protected from misuse can be addressed. Clear operational guidelines and best practises are key for healthcare providers, and researchers adopting IT, and further work is needed on improving integration of new technologies with current systems. A robust method of evaluation for technical innovation is required. PMID:28276585

18F-FDG uptake and its clinical relevance in primary gastric lymphoma.

PubMed

Yi, Jun Ho; Kim, Seok Jin; Choi, Joon Young; Ko, Young Hyeh; Kim, Byung-Tae; Kim, Won Seog

2010-06-01

We studied the clinical relevance of (18)F-fluorodeoxyglucose ((18)F-FDG) uptake in patients with primary gastric lymphoma underwent positron emission tomography (PET)/ computed tomography (CT) scan. Forty-two patients with primary gastric lymphoma were analysed: 32 diffuse large B-cell lymphomas (DLBCL) and 10 extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT lymphomas). The PET/CT scans were compared with clinical and pathologic features, and the results of CT and endoscopy. Nine patients were up-staged based on the results of their PET/CT scan compared to CT (seven DLBCLs, two MALT lymphomas) while six patients were down-staged by the PET/CT scan. The standard uptake value (SUV) was used as an indicator of a lesion with a high metabolic rate. The high SUVmax group, defined as an SUVmax >or= median value, was significantly associated with an advanced Lugano stage (p < 0.001). Three patients with DLBCL, who showed an initially high SUVmax, died of disease progression. Among 24 patients for whom follow-up PET/CT scan with endoscopy was performed, 11 patients with ulcerative or mucosal lesions showed residual (18)F-FDG uptake. All of these gastric lesions were grossly and pathologically benign lesions without evidence of lymphoma cells. In conclusion, PET/CT scan can be used in staging patients with primary gastric lymphoma; however, the residual (18)F-FDG uptake observed during follow-up should be interpreted cautiously and should be combined with endoscopy and multiple biopsies of the stomach. (c) 2009 John Wiley & Sons, Ltd.

Allergy Diagnosis in Children and Adults: Performance of a New Point-of-Care Device, ImmunoCAP Rapid

PubMed Central

2009-01-01

Background Allergy is a serious problem affecting approximately 1 of 4 individuals. The symptoms with and without allergy etiology are often difficult to distinguish from each other without using an IgE antibody test. The aim of this study was to investigate the performance of a new point-of-care (POC) test for IgE antibodies to relevant allergens in Europe. Methods IgE antibodies from children and adults with allergies recruited from allergy clinics in Sweden and Spain were analyzed for 10 allergens, suitable for the age groups, using the new POC test and ImmunoCAP laboratory test. The IgE antibody level best discriminating between positive and negative results (the cutoff point) for the different allergens of the POC test and the efficacy of the POC and the ImmunoCAP laboratory tests for diagnosing allergy compared with that of clinical diagnosis were investigated. Results The estimated cutoffs for the different allergens in the POC test ranged from 0.70 to 2.56 kUA/L. Taking into account all positive allergen results in a given patient, the POC test could identify 95% of the patients with allergies. Seventy-eight percent of the allergen-specific physicians' diagnoses were identified and 97% of the negative ones. Most allergens exhibited good performance, identifying about 80% of clinically relevant cases. However, dog, mugwort, and wall pellitory would benefit from improvement. Conclusions The POC test will be a valuable adjunct in the identification or exclusion of patients with allergies and their most likely offending allergens, both in specialist and general care settings. PMID:23283063

Even High Doses of Oral Cannabidol Do Not Cause THC-Like Effects in Humans: Comment on Merrick et al. Cannabis and Cannabinoid Research 2016;1(1):102-112; DOI: 10.1089/can.2015.0004.

PubMed

Grotenhermen, Franjo; Russo, Ethan; Zuardi, Antonio Waldo

2017-01-01

This short communication examines the question whether the experimental data presented in a study by Merrick et al. are of clinical relevance. These authors found that cannabidiol (CBD), a major cannabinoid of the cannabis plant devoid of psychotropic effects and of great interest for therapeutic use in several medical conditions, may be converted in gastric fluid into the psychoactive cannabinoids delta-8-THC and delta-9-THC to a relevant degree. They concluded that "the acidic environment during normal gastrointestinal transit can expose orally CBD-treated patients to levels of THC and other psychoactive cannabinoids that may exceed the threshold for a positive physiological response." They issued a warning concerning oral use of CBD and recommend the development of other delivery methods. However, the available clinical data do not support this conclusion and recommendation, since even high doses of oral CBD do not cause psychological, psychomotor, cognitive, or physical effects that are characteristic for THC or cannabis rich in THC. On the contrary, in the past decades and by several groups, high doses of oral CBD were consistently shown to cause opposite effects to those of THC in clinical studies. In addition, administration of CBD did not result in detectable THC blood concentrations. Thus, there is no reason to avoid oral use of CBD, which has been demonstrated to be a safe means of administration of CBD, even at very high doses.

National evaluation of the benefits and risks of greater structuring and coding of the electronic health record: exploratory qualitative investigation

PubMed Central

Morrison, Zoe; Fernando, Bernard; Kalra, Dipak; Cresswell, Kathrin; Sheikh, Aziz

2014-01-01

Objective We aimed to explore stakeholder views, attitudes, needs, and expectations regarding likely benefits and risks resulting from increased structuring and coding of clinical information within electronic health records (EHRs). Materials and methods Qualitative investigation in primary and secondary care and research settings throughout the UK. Data were derived from interviews, expert discussion groups, observations, and relevant documents. Participants (n=70) included patients, healthcare professionals, health service commissioners, policy makers, managers, administrators, systems developers, researchers, and academics. Results Four main themes arose from our data: variations in documentation practice; patient care benefits; secondary uses of information; and informing and involving patients. We observed a lack of guidelines, co-ordination, and dissemination of best practice relating to the design and use of information structures. While we identified immediate benefits for direct care and secondary analysis, many healthcare professionals did not see the relevance of structured and/or coded data to clinical practice. The potential for structured information to increase patient understanding of their diagnosis and treatment contrasted with concerns regarding the appropriateness of coded information for patients. Conclusions The design and development of EHRs requires the capture of narrative information to reflect patient/clinician communication and computable data for administration and research purposes. Increased structuring and/or coding of EHRs therefore offers both benefits and risks. Documentation standards within clinical guidelines are likely to encourage comprehensive, accurate processing of data. As data structures may impact upon clinician/patient interactions, new models of documentation may be necessary if EHRs are to be read and authored by patients. PMID:24186957

Rectal and sublingual administration of tacrolimus: a single-dose pharmacokinetic study in healthy volunteers

PubMed Central

Stifft, Frank; Vanmolkot, Floris; Scheffers, Ingrid; van Bortel, Luc; Neef, Cees; Christiaans, Maarten

2014-01-01

Aims The immunosuppressant tacrolimus is usually administered orally. When this is not feasible, other routes of administration may be useful. Previous research suggested that tacrolimus may be applied sublingually or rectally. Pharmacokinetic data are sparse. The aim of this study was to investigate and compare the pharmacokinetics of these alternative formulations with orally administered tacrolimus. Methods Three single, fixed-dose formulations of tacrolimus were administered in a random sequence in 18 healthy subjects, using a cross-over study design. For sublingual administration, 3 mg of powder obtained from oral capsules was applied under the tongue for a period of 15 min without swallowing, with mouth rinsing afterwards. For rectal administration, a suppository containing 15 mg of the oral powder was used. Oral administration consisted of 7 mg of instant-release tacrolimus capsules (Prograf). Main pharmacokinetic outcome parameters were compared by anova. Results Sublingual administration showed no clinically significant exposure, contrary to rectal administration, where all subjects had clinically relevant exposure, with a lower relative bioavailability (78%), a lower maximal blood concentration and a later time of maximal blood concentration compared with oral administration. Conclusions Sublingual administration of a single dose of tacrolimus does not result in systemic exposure if care is taken not to swallow saliva and to rinse the oral cavity afterwards. Rectal administration of tacrolimus results in clinically relevant systemic exposure and might represent an alternative formulation in case oral administration is not feasible. When used as a topical agent, systemic side-effects should be considered. PMID:24809233

Home cage wheel running is an objective and clinically relevant method to assess inflammatory pain in male and female rats

PubMed Central

Kandasamy, Ram; Calsbeek, Jonas J.; Morgan, Michael M.

2016-01-01

Background The assessment of nociception in preclinical studies is undergoing a transformation from pain-evoked to pain-depressed tests to more closely mimic the effects of clinical pain. Many inflammatory pain-depressed behaviors (reward seeking, locomotion) have been examined, but these tests are limited because of confounds such as stress and difficulties in quantifying behavior. New Method The present study evaluates home cage wheel running as an objective method to assess the magnitude and duration of inflammatory pain in male and female rats. Results Injection of Complete Freund’s Adjuvant (CFA) into the right hindpaw to induce inflammatory pain almost completely inhibited wheel running for 2 days in males and females. Wheel running gradually returned to baseline levels within 12 days despite persistent mechanical hypersensitivity (von Frey test). Comparison with Existing Methods Continuously monitoring home cage wheel running improves on previous studies examining inflammatory pain-depressed wheel running because it is more sensitive to noxious stimuli, avoids the stress of removing the rat from its cage for testing, and provides a complete analysis of the time course for changes in nociception. Conclusions The present data indicate that home cage wheel running is a clinically relevant method to assess inflammatory pain in the rat. The decrease in activity caused by inflammatory pain and subsequent gradual recovery mimics the changes in activity caused by pain in humans. The tendency for pain-depressed wheel running to be greater in female than male rats is consistent with the tendency for women to be at greater risk of chronic pain than men. PMID:26891874

Clinically Relevant Outcome Measures Following Limb Osseointegration; Systematic Review of the Literature.

PubMed

Al Muderis, Munjed M; Lu, William Y; Li, Jiao Jiao; Kaufman, Kenton; Orendurff, Michael; Highsmith, M Jason; Lunseth, Paul A; Kahle, Jason T

2018-02-01

The current standard of care for an amputee is a socket-based prostheses. An osseointegrated implant (OI) is an alternative for prosthetic attachment. Osseointegration addresses reported problems related to wearing a socket interface, such as skin issues, discomfort, diminished function, quality of life, prosthetic use, and abandonment. The purpose of this report is to systematically review current literature regarding OI to identify and categorize the reported clinically relevant outcome measures, rate the quality of available evidence, and synthesize the findings. A multidisciplinary team used PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) methods. Search methodology was based on identifying clinically relevant articles. Three databases were searched: PubMed, CINAHL, and Web of Science. Clinical studies with aggregated data reporting at least 1 clinically relevant outcome measure were included. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criterion was used for critical appraisal and recommendations. This review identified 21 clinically relevant observational studies. Outcome measures were categorized into the following 9 categories: vibratory stimulation, complications, biomechanics, economics, patient-reported outcome measures, electromyography, x-ray, physical functional performance, and energy consumption. This systematic review consisted of Level III and IV observational studies. Homogeneous outcome measures with strong psychometric properties across prospective studies do not exist to date. Higher-level, prospective, randomized, long-term, clinically relevant trials are needed to prove efficacy of OI compared with socket prosthetic attachment. Osseointegration was at least equivalent to sockets in most studies. In some cases, it was superior. Osseointegration represents a promising alternative to socket prosthetic attachments for extremity amputees. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

DNA Repair in Prostate Cancer: Biology and Clinical Implications.

PubMed

Mateo, Joaquin; Boysen, Gunther; Barbieri, Christopher E; Bryant, Helen E; Castro, Elena; Nelson, Pete S; Olmos, David; Pritchard, Colin C; Rubin, Mark A; de Bono, Johann S

2017-03-01

For more precise, personalized care in prostate cancer (PC), a new classification based on molecular features relevant for prognostication and treatment stratification is needed. Genomic aberrations in the DNA damage repair pathway are common in PC, particularly in late-stage disease, and may be relevant for treatment stratification. To review current knowledge on the prevalence and clinical significance of aberrations in DNA repair genes in PC, particularly in metastatic disease. A literature search up to July 2016 was conducted, including clinical trials and preclinical basic research studies. Keywords included DNA repair, BRCA, ATM, CRPC, prostate cancer, PARP, platinum, predictive biomarkers, and hereditary cancer. We review how the DNA repair pathway is relevant to prostate carcinogenesis and progression. Data on how this may be relevant to hereditary cancer and genetic counseling are included, as well as data from clinical trials of PARP inhibitors and platinum therapeutics in PC. Relevant studies have identified genomic defects in DNA repair in PCs in 20-30% of advanced castration-resistant PC cases, a proportion of which are germline aberrations and heritable. Phase 1/2 clinical trial data, and other supporting clinical data, support the development of PARP inhibitors and DNA-damaging agents in this molecularly defined subgroup of PC following success in other cancer types. These studies may be an opportunity to improve patient care with personalized therapeutic strategies. Key literature on how genomic defects in the DNA damage repair pathway are relevant for prostate cancer biology and clinical management is reviewed. Potential implications for future changes in patient care are discussed. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

A Planetary Defense Gateway for Smart Discovery of relevant Information for Decision Support

NASA Technical Reports Server (NTRS)

Bambacus, Myra; Yang, Chaowei Phil; Leung, Ronald Y.; Barbee, Brent; Nuth, Joseph A.; Seery, Bernard; Jiang, Yongyao; Qin, Han; Li, Yun; Yu, Manzhu;

Practical aspects of NGS-based pathways analysis for personalized cancer science and medicine

PubMed Central

Paleeva, Anna; Kremenetskaya, Olga; Vinogradov, Dmitriy

2016-01-01

Nowadays, the personalized approach to health care and cancer care in particular is becoming more and more popular and is taking an important place in the translational medicine paradigm. In some cases, detection of the patient-specific individual mutations that point to a targeted therapy has already become a routine practice for clinical oncologists. Wider panels of genetic markers are also on the market which cover a greater number of possible oncogenes including those with lower reliability of resulting medical conclusions. In light of the large availability of high-throughput technologies, it is very tempting to use complete patient-specific New Generation Sequencing (NGS) or other “omics” data for cancer treatment guidance. However, there are still no gold standard methods and protocols to evaluate them. Here we will discuss the clinical utility of each of the data types and describe a systems biology approach adapted for single patient measurements. We will try to summarize the current state of the field focusing on the clinically relevant case-studies and practical aspects of data processing. PMID:27191992

Grading the quality of evidence and the strength of recommendations in clinical dentistry: a critical review of 2 prominent approaches.

PubMed

Faggion, Clovis Mariano

2010-06-01

The objective of this article was to critically review 2 prominent approaches used to grade the quality of evidence and the strength of recommendations. Every year much information becomes available as a result of publication of scientific papers, and clinicians should be able to assess current evidence so they, along with their patients, can make the most appropriate clinical decisions. This is particularly important when there is little or no high-quality evidence available about the subject of interest. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) and the Strength of Recommendation Taxonomy (SORT) were evaluated. Strengths and weaknesses of these 2 systems are discussed, mainly on the basis of their relevance to clinical dentistry. The conclusion was that use of a system for grading the quality of evidence and the strength of recommendations is urgently required because of the great heterogeneity of the quality and type of evidence relating to many dental procedures. Use of such a system will enable clinicians and their patients to make more informed decisions.

The value of fine needle aspiration cytology in the clinical management of rare salivary gland tumors

PubMed Central

Mezei, Tibor; Mocan, Simona; Ormenisan, Alina; Baróti, Beáta; Iacob, Alina

2018-01-01

Abstract Salivary gland tumors are relatively rare neoplasms, mostly located in the parotid gland, and few are malignant. Preoperative evaluation of salivary gland tumors includes fine needle aspiration cytology (FNAC). Objective The purpose of this study was to determine the importance of FNAC in the evaluation of rare salivary gland neoplasms. Material and Methods Four cases of rare salivary gland tumors were included, which were preoperatively assessed by clinical investigation, computed tomography, and FNAC. Results The presented cases include myoepithelial carcinoma, oncocytic carcinoma, undifferentiated lymphoepithelial carcinoma, and marginal zone lymphoma. Conclusion FNAC is a reliable diagnostic tool for common salivary gland neoplasms; however, rare tumors often represent diagnostic challenges. Clinical relevance In such rare tumors, the role of aspiration cytology may be limited to establishing the dignity of the lesion (benign/malignant). This knowledge enables the surgeon to choose the most appropriate therapeutic procedure. A definitive diagnosis of rare tumors (either epithelial or nonepithelial) is obtained by histological examination; cytology is limited in this regard due to overlapping features. PMID:29489937

PubMed Central

Côté, L.; Clavet, D.; St-Hilaire, S.; Vaillancourt, C.; Blondeau, F.; Martineau, B.

1999-01-01

PROBLEM ADDRESSED: In addition to clinical instruction, residents need "people" skills that will enable them to deal with all sorts of patients in difficult clinical situations. We planned a series of 12 seminars to teach these skills to first-year residents. OBJECTIVES OF PROGRAM: To ask relevant questions typical of the patient-centred approach; with empathy and respect, to encourage patients to express their emotions; to become more aware of one's own emotions and reactions in one's work as a physician; to negotiate with patients, taking into account both the patient's agenda and one's own. MAIN COMPONENTS OF PROGRAM: Clinical problems drawn from a list of situations likely to involve difficult contact with patients were used to achieve program objectives. Various teaching methods (discussion, brief presentation, practical demonstration, role play) were used during the four stages of skills development: information, demonstration, practice, and feedback. Various tools were used to test the program. CONCLUSION: Proper planning requires ongoing exploration of objectives, content, teaching methods, and evaluation. This discussion of the teaching principles applied in planning our seminars might inspire others to develop similar programs. PMID:10349069

N of 1, two contemporary arm, randomised controlled clinical trial for bilateral epicondylitis: a new study design

PubMed Central

Fante, Claudia Del; Perotti, Cesare; Pavesi, Claudio Francesco; Coscia, Davide; Scotti, Valeria; Tinelli, Carmine

2011-01-01

Objective To investigate the use of a novel study design in analysis of bilateral elbow pain. Design N of 1, two contemporary arm, open label, randomised controlled clinical trial. Setting A clinical epidemiologist at a university hospital in Pavia, Italy. Participants Two elbows with epicondylitis. Interventions Autologous platelet lysate versus “wait and see” strategy. Main outcome measures Visual analogue scale for pain on elbow extension and resisted wrist extension. Results Over six months’ follow-up, the patient experienced bilateral improvement in pain, but higher in the treated arm, with a drop in visual analogue scale for pain from 28 to 4 for right (control) arm (drop of 24 points) and from 67 to 10.5 for left (treated) arm (drop of 56.5 points). Conclusions Platelet lysate might (or might not) work. Competing interests and lack of blinding might be relevant issues in the interpretation of trial results. However, the new study design can be applied to a number of conditions such as bilateral sport or trauma injuries, bilateral otitis, or any condition affecting chiral organs or limbs. PMID:22187187

[Pelargonium sidoides in acute bronchitis - Health-related quality of life and patient-reported outcome in adults receiving EPs 7630 treatment].

PubMed

Matthys, Heinrich; Lizogub, Victor G; Funk, Petra; Malek, Fathi A

2010-12-01

Health-related quality of life (HRQL) and patient-reported outcome (PRO) have become important outcome parameters for the evaluation of medical treatment within clinical trials and, furthermore, to evaluate efficiency in clinical practice. We therefore report further exploratory results of an already reported dose-finding study with EPs 7630 tablets, now focussing on HRQL and PRO. A total of 406 adults with acute bronchitis were randomly assigned to one of four parallel treatment groups (placebo, 30 mg, 60 mg or 90 mg EPs 7630 daily). HRQL and PRO were assessed by questionnaires as secondary outcome measures at each study visit or daily in the patient's diary. At day 7, the patient-reported outcome measures were significantly more improved in all the three EPs 7630 groups compared to placebo (EQ-5D and EQ VAS, SF-12: physical score, impact of patient's sickness, duration of activity limitation, patient-reported treatment outcome, satisfaction with treatment). In conclusion, a statistically significant and clinically relevant improvement of HRQL/PRO compared to placebo was shown in all the three EPs 7630 groups.

The Full Spectrum of Clinical Ethical Issues in Kidney Failure. Findings of a Systematic Qualitative Review

PubMed Central

Kahrass, Hannes; Strech, Daniel; Mertz, Marcel

2016-01-01

Background When treating patients with kidney failure, unavoidable ethical issues often arise. Current clinical practice guidelines some of them, but lack comprehensive information about the full range of relevant ethical issues in kidney failure. A systematic literature review of such ethical issues supports medical professionalism in nephrology, and offers a solid evidential base for efforts that aim to improve ethical conduct in health care. Aim To identify the full spectrum of clinical ethical issues that can arise for patients with kidney failure in a systematic and transparent manner. Method A systematic review in Medline (publications in English or German between 2000 and 2014) and Google Books (with no restrictions) was conducted. Ethical issues were identified by qualitative text analysis and normative analysis. Results The literature review retrieved 106 references that together mentioned 27 ethical issues in clinical care of kidney failure. This set of ethical issues was structured into a matrix consisting of seven major categories and further first and second-order categories. Conclusions The systematically-derived matrix helps raise awareness and understanding of the complexity of ethical issues in kidney failure. It can be used to identify ethical issues that should be addressed in specific training programs for clinicians, clinical practice guidelines, or other types of policies dealing with kidney failure. PMID:26938863

Bioprosthetic Tissue Matrices in Complex Abdominal Wall Reconstruction

PubMed Central

Broyles, Justin M.; Abt, Nicholas B.; Sacks, Justin M.

2013-01-01

Background: Complex abdominal defects are difficult problems encountered by surgeons in multiple specialties. Although current evidence supports the primary repair of these defects with mesh reinforcement, it is unclear which mesh is superior for any given clinical scenario. The purpose of this review was to explore the characteristics of and clinical relevance behind bioprosthetic tissue matrices in an effort to better clarify their role in abdominal wall reconstruction. Methods: We reviewed the peer-reviewed literature on the use of bioprosthetic mesh in human subjects. Basic science articles and large retrospective and prospective reviews were included in author’s analysis. The clinical performance and characteristics of 13 bioprosthetic tissue matrices were evaluated. Results: The majority of the products evaluated perform well in contaminated fields, where the risk of wound-healing difficulties is high. Clinical outcomes, which included infection, reherniation, and bulge formation, were variable, and the majority of the studies had a mean follow-up of less than 24 months. Conclusions: Although bioprosthetic matrix has a multitude of indications within the growing field of abdominal wall reconstruction, the functionality, regenerative capacity, and long-term fate of these products have yet to be fully established. Furthermore, the clinical performance, indications, and contraindications for each type of matrix need to be fully evaluated in long-term outcome studies. PMID:25289285

Use of Clinical Anatomy Resources by Musculoskeletal Outpatient Physiotherapists in Australian Public Hospitals: A Cross-Sectional Study

PubMed Central

Davies, Tilman M.; Cornwall, Jon

2015-01-01

ABSTRACT Purpose: To investigate how musculoskeletal outpatient physiotherapists in public hospitals interact with and perceive clinical anatomy resources in the workplace. Method: This cross-sectional study used a postal survey sent to musculoskeletal outpatient physiotherapists in 64 Australian public hospitals. Survey questions examined demographics, qualifications, experience, types of resources used, whether resources meet requirements, and what improvements could be made to current resources. Results: A total of 193 physiotherapists responded (75% response rate; 60% female), of whom 49% were age 35 years or younger; 67% had only an undergraduate qualification, and 37% had practised for 5 years or less. More experienced physiotherapists used resources significantly less frequently ([odds ratio]=1.35; 95% CI, 1.17–1.57), and we found no significant associations between preference for online versus printed resources and age, sex, qualifications, or experience. Trends included less experienced physiotherapists identifying the absence of online access as a barrier to resource use and provision of improved online facilities as necessary to improve access to clinical anatomy resources. Conclusion: Results indicate distinct trends in physiotherapists' use of clinical anatomy resources, including a desire for improved online resource access on the part of less experienced physiotherapists. The findings are relevant to hospital outpatient clinics, particularly those that employ less experienced physiotherapists. PMID:26839457

Treatment of medial shoulder joint instability in dogs by extracapsular stabilization with a prosthetic ligament: 39 cases (2008-2013).

PubMed

O'Donnell, Erica M; Canapp, Sherman O; Cook, James L; Pike, Fred

2017-11-01

OBJECTIVE To investigate clinical outcomes for dogs surgically treated for medial shoulder joint instability (MSI) by extracapsular stabilization with a prosthetic ligament. DESIGN Retrospective multicenter case series. ANIMALS 39 client-owned dogs. PROCEDURES Medical records of 3 veterinary medical centers were searched to identify dogs with MSI diagnosed by clinical examination and arthroscopic assessment and treated by extracapsular stabilization with a prosthetic ligament. A minimum 6-month follow-up period was required for study inclusion. Signalment, function or use of the dog, duration of clinical signs, clinical and diagnostic imaging data, MSI grade (1 [mild] to 4 [complete luxation]), follow-up duration, complications, and outcome data were recorded. RESULTS All grades of MSI were represented. Implants were placed successfully in all dogs. Complications (4 major and 2 minor) were recorded for 6 of 39 (15%) dogs; all were treated successfully. Function at the time of last follow-up (6 to 68 months) was deemed full in 30 of 39 (77%) dogs and acceptable in 9 (23%). CONCLUSIONS AND CLINICAL RELEVANCE Surgical treatment of MSI in dogs by extracapsular stabilization with a prosthetic ligament was associated with a complication rate considered acceptable for orthopedic procedures. All patient outcomes were considered successful.

Serious gaming in women's health care.

PubMed

de Wit-Zuurendonk, L D; Oei, S G

2011-11-01

Computer-based (serious) gaming is a new field in medical education, which has the potential to become an important tool for healthcare professionals for learning a range of clinical skills. To evaluate the current status of serious gaming in medicine, we performed a systematic literature review. In June 2011, we undertook a search in PubMed and Embase databases with the MeSH terms video games, education, training, gaming and healthcare. Thirty relevant papers were identified, reviewed and summarised. The studies showed that serious gaming is a stimulating learning method and that students are enthusiastic about its use. Studies have shown that previous recreational gaming is associated with greater surgical skill, especially for laparoscopy. In addition to surgical skills, serious gaming is potentially a good method for learning clinical decision-making and patient interaction. Games are already being developed for teaching specific clinical skills, for example in cardiology and orthopaedics for example. Initial studies suggest that serious gaming is likely to be an effective training method; however, there is a paucity of studies showing the conclusive clinical benefit of serious gaming. Future studies should focus on demonstrating the clinical effectiveness of serious gaming on skills used in patient care. © 2011 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2011 RCOG.

Gene expression profiling of immunomagnetically separated cells directly from stabilized whole blood for multicenter clinical trials

PubMed Central

2014-01-01

Background Clinically useful biomarkers for patient stratification and monitoring of disease progression and drug response are in big demand in drug development and for addressing potential safety concerns. Many diseases influence the frequency and phenotype of cells found in the peripheral blood and the transcriptome of blood cells. Changes in cell type composition influence whole blood gene expression analysis results and thus the discovery of true transcript level changes remains a challenge. We propose a robust and reproducible procedure, which includes whole transcriptome gene expression profiling of major subsets of immune cell cells directly sorted from whole blood. Methods Target cells were enriched using magnetic microbeads and an autoMACS® Pro Separator (Miltenyi Biotec). Flow cytometric analysis for purity was performed before and after magnetic cell sorting. Total RNA was hybridized on HGU133 Plus 2.0 expression microarrays (Affymetrix, USA). CEL files signal intensity values were condensed using RMA and a custom CDF file (EntrezGene-based). Results Positive selection by use of MACS® Technology coupled to transcriptomics was assessed for eight different peripheral blood cell types, CD14+ monocytes, CD3+, CD4+, or CD8+ T cells, CD15+ granulocytes, CD19+ B cells, CD56+ NK cells, and CD45+ pan leukocytes. RNA quality from enriched cells was above a RIN of eight. GeneChip analysis confirmed cell type specific transcriptome profiles. Storing whole blood collected in an EDTA Vacutainer® tube at 4°C followed by MACS does not activate sorted cells. Gene expression analysis supports cell enrichment measurements by MACS. Conclusions The proposed workflow generates reproducible cell-type specific transcriptome data which can be translated to clinical settings and used to identify clinically relevant gene expression biomarkers from whole blood samples. This procedure enables the integration of transcriptomics of relevant immune cell subsets sorted directly from whole blood in clinical trial protocols. PMID:25984272

Intravenous anaesthetics inhibit nicotinic acetylcholine receptor-mediated currents and Ca2+ transients in rat intracardiac ganglion neurons

PubMed Central

Weber, Martin; Motin, Leonid; Gaul, Simon; Beker, Friederike; Fink, Rainer H A; Adams, David J

2004-01-01

The effects of intravenous (i.v.) anaesthetics on nicotinic acetylcholine receptor (nAChR)-induced transients in intracellular free Ca2+ concentration ([Ca2+]i) and membrane currents were investigated in neonatal rat intracardiac neurons. In fura-2-loaded neurons, nAChR activation evoked a transient increase in [Ca2+]I, which was inhibited reversibly and selectively by clinically relevant concentrations of thiopental. The half-maximal concentration for thiopental inhibition of nAChR-induced [Ca2+]i transients was 28 μM, close to the estimated clinical EC50 (clinically relevant (half-maximal) effective concentration) of thiopental. In fura-2-loaded neurons, voltage clamped at −60 mV to eliminate any contribution of voltage-gated Ca2+ channels, thiopental (25 μM) simultaneously inhibited nAChR-induced increases in [Ca2+]i and peak current amplitudes. Thiopental inhibited nAChR-induced peak current amplitudes in dialysed whole-cell recordings by ∼ 40% at −120, −80 and −40 mV holding potential, indicating that the inhibition is voltage independent. The barbiturate, pentobarbital and the dissociative anaesthetic, ketamine, used at clinical EC50 were also shown to inhibit nAChR-induced increases in [Ca2+]i by ∼40%. Thiopental (25 μM) did not inhibit caffeine-, muscarine- or ATP-evoked increases in [Ca2+]i, indicating that inhibition of Ca2+ release from internal stores via either ryanodine receptor or inositol-1,4,5-trisphosphate receptor channels is unlikely. Depolarization-activated Ca2+ channel currents were unaffected in the presence of thiopental (25 μM), pentobarbital (50 μM) and ketamine (10 μM). In conclusion, i.v. anaesthetics inhibit nAChR-induced currents and [Ca2+]i transients in intracardiac neurons by binding to nAChRs and thereby may contribute to changes in heart rate and cardiac output under clinical conditions. PMID:15644873

Pregnancy-Associated Changes in Pharmacokinetics: A Systematic Review

PubMed Central

Leibson, Tom; Carls, Alexandra; Ito, Shinya; Koren, Gideon

2016-01-01

Background Women are commonly prescribed a variety of medications during pregnancy. As most organ systems are affected by the substantial anatomical and physiological changes that occur during pregnancy, it is expected that pharmacokinetics (PK) (absorption, distribution, metabolism, and excretion of drugs) would also be affected in ways that may necessitate changes in dosing schedules. The objective of this study was to systematically identify existing clinically relevant evidence on PK changes during pregnancy. Methods and Findings Systematic searches were conducted in MEDLINE (Ovid), Embase (Ovid), Cochrane Central Register of Controlled Trials (Ovid), and Web of Science (Thomson Reuters), from database inception to August 31, 2015. An update of the search from September 1, 2015, to May 20, 2016, was performed, and relevant data were added to the present review. No language or date restrictions were applied. All publications of clinical PK studies involving a group of pregnant women with a comparison to nonpregnant participants or nonpregnant population data were eligible to be included in this review. A total of 198 studies involving 121 different medications fulfilled the inclusion criteria. In these studies, commonly investigated drug classes included antiretrovirals (54 studies), antiepileptic drugs (27 studies), antibiotics (23 studies), antimalarial drugs (22 studies), and cardiovascular drugs (17 studies). Overall, pregnancy-associated changes in PK parameters were often observed as consistent findings among many studies, particularly enhanced drug elimination and decreased exposure to total drugs (bound and unbound to plasma proteins) at a given dose. However, associated alterations in clinical responses and outcomes, or lack thereof, remain largely unknown. Conclusion This systematic review of pregnancy-associated PK changes identifies a significant gap between the accumulating knowledge of PK changes in pregnant women and our understanding of their clinical impact for both mother and fetus. It is essential for clinicians to be aware of these unique pregnancy-related changes in PK, and to critically examine their clinical implications. PMID:27802281

Adolescent idiopathic scoliosis screening for school, community, and clinical health promotion practice utilizing the PRECEDE-PROCEED model

PubMed Central

Mirtz, Timothy A; Thompson, Mark A; Greene, Leon; Wyatt, Lawrence A; Akagi, Cynthia G

2005-01-01

Background Screening for adolescent idiopathic scoliosis (AIS) is a commonly performed procedure for school children during the high risk years. The PRECEDE-PROCEDE (PP) model is a health promotion planning model that has not been utilized for the clinical diagnosis of AIS. The purpose of this research is to study AIS in the school age population using the PP model and its relevance for community, school, and clinical health promotion. Methods MEDLINE was utilized to locate AIS data. Studies were screened for relevance and applicability under the auspices of the PP model. Where data was unavailable, expert opinion was utilized based on consensus. Results The social assessment of quality of life is limited with few studies approaching the long-term effects of AIS. Epidemiologically, AIS is the most common form of scoliosis and leading orthopedic problem in children. Behavioral/environmental studies focus on discovering etiologic relationships yet this data is confounded because AIS is not a behavioral. Illness and parenting health behaviors can be appreciated. The educational diagnosis is confounded because AIS is an orthopedic disorder and not behavioral. The administration/policy diagnosis is hindered in that scoliosis screening programs are not considered cost-effective. Policies are determined in some schools because 26 states mandate school scoliosis screening. There exists potential error with the Adam's test. The most widely used measure in the PP model, the Health Belief Model, has not been utilized in any AIS research. Conclusion The PP model is a useful tool for a comprehensive study of a particular health concern. This research showed where gaps in AIS research exist suggesting that there may be problems to the implementation of school screening. Until research disparities are filled, implementation of AIS screening by school, community, and clinical health promotion will be compromised. Lack of data and perceived importance by school/community health planners may influence clinical health promotion practices. PMID:16318632

Automatic Term Class Construction Using Relevance--A Summary of Work in Automatic Pseudoclassification.

ERIC Educational Resources Information Center

Salton, G.

1980-01-01

Summarizes studies of pseudoclassification, a process of utilizing user relevance assessments of certain documents with respect to certain queries to build term classes designed to retrieve relevant documents. Conclusions are reached concerning the effectiveness and feasibility of constructing term classifications based on human relevance…

Mechanisms and disease relevance of neutrophil extracellular trap formation.

PubMed

Van Avondt, Kristof; Hartl, Dominik

2018-03-15

While the microscopic appearance of neutrophil extracellular traps (NETs) has fascinated basic researchers since its discovery, the (patho)physiological mechanisms triggering NET release, the disease relevance and clinical translatability of this unconventional cellular mechanism remained poorly understood. Here, we summarize and discuss current concepts of the mechanisms and disease relevance of NET formation. © 2018 Stichting European Society for Clinical Investigation Journal Foundation.

Clinical Relevance of IgE to Profilin and/or Polcalcin in Pollen-Sensitized Patients.

PubMed

San Nicoló, Marion; Braun, Thomas; Eder, Katharina; Berghaus, Alexander; Gröger, Moritz

2016-01-01

Component-resolved diagnostics is gaining importance in allergy diagnostics. Allergen extracts contain components with different rates of prevalence and clinical relevance, which can be subdivided at molecular level into major and minor allergens. Clinical complaints are usually triggered by major allergens, while the role of sensitization to the panallergens profilin and polcalcin still remains unclear. Eighty-six patients from southern Bavaria with sensitization to the panallergens profilin (Bet v 2/Phl p 12) and/or polcalcin (Bet v 4/Phl p 7) were examined in regard to their sensitization to the 4 main botanic denominations Betulaceae, Oleaceae, Poaceae and Asteraceae by skin prick test and measurement of specific immunoglobulin E antibodies to natural allergen extracts as well as major allergen components rPhl p 1/5, rBet v 1, rOle e 1 and nArt v 1. Sensitization was rated as clinically relevant or irrelevant depending on anamnesis or intranasal allergen challenge. Regarding the 4 botanic denominations, there was no significant difference in the incidence of sensitization to the panallergens profilin, polcalcin or both. The sensitization pattern does not alter when subdividing the cohort into clinically relevant and silent sensitization. We did not find clinically symptomatic sensitization to panallergens without cosensitization to a major allergen. Our results suggest that sole sensitization to panallergens seems to have no clinical relevance in allergic rhinoconjunctivitis. Clinical complaints seem to be triggered manly by major allergens. Thus, component-resolved allergy diagnostics is crucial in the diagnosis and treatment of polysensitized patients. © 2016 S. Karger AG, Basel.

Automated identification of molecular effects of drugs (AIMED)

PubMed Central

Fathiamini, Safa; Johnson, Amber M; Zeng, Jia; Araya, Alejandro; Holla, Vijaykumar; Bailey, Ann M; Litzenburger, Beate C; Sanchez, Nora S; Khotskaya, Yekaterina; Xu, Hua; Meric-Bernstam, Funda; Bernstam, Elmer V

2016-01-01

Introduction Genomic profiling information is frequently available to oncologists, enabling targeted cancer therapy. Because clinically relevant information is rapidly emerging in the literature and elsewhere, there is a need for informatics technologies to support targeted therapies. To this end, we have developed a system for Automated Identification of Molecular Effects of Drugs, to help biomedical scientists curate this literature to facilitate decision support. Objectives To create an automated system to identify assertions in the literature concerning drugs targeting genes with therapeutic implications and characterize the challenges inherent in automating this process in rapidly evolving domains. Methods We used subject-predicate-object triples (semantic predications) and co-occurrence relations generated by applying the SemRep Natural Language Processing system to MEDLINE abstracts and ClinicalTrials.gov descriptions. We applied customized semantic queries to find drugs targeting genes of interest. The results were manually reviewed by a team of experts. Results Compared to a manually curated set of relationships, recall, precision, and F2 were 0.39, 0.21, and 0.33, respectively, which represents a 3- to 4-fold improvement over a publically available set of predications (SemMedDB) alone. Upon review of ostensibly false positive results, 26% were considered relevant additions to the reference set, and an additional 61% were considered to be relevant for review. Adding co-occurrence data improved results for drugs in early development, but not their better-established counterparts. Conclusions Precision medicine poses unique challenges for biomedical informatics systems that help domain experts find answers to their research questions. Further research is required to improve the performance of such systems, particularly for drugs in development. PMID:27107438

Outcome assessment for spasticity management in the patient with traumatic brain injury: the state of the art.

PubMed

Elovic, Elie P; Simone, Lisa K; Zafonte, Ross

2004-01-01

The objective of this article was to (1) review the engineering and medical literature to structure the available information concerning the assessment of spasticity in the neurological population; (2) to discuss the strengths and weaknesses of the different methods currently in use in spasticity assessment; and (3) make recommendations for future efforts in spasticity outcome assessment. Spasticity textbooks, Web sites, and OVID, IEEE, and Medline searches from 1966 through 2003 of spasticity, quantitative measure, or outcome assessment in the rehabilitation population were used as data sources. Over 500 articles were reviewed. Articles that discussed outcome measures used to assess interventions and evaluation of spasticity were included. Authors reviewed the articles looking at inclusion criteria, data collection, methodology, assessment methods, and conclusions for validity and relevance to this article. Issues such as clinical relevance, real-world function and lack of objectivity, and time consumed during performance are important issues for spasticity assessment. Some measures such as the Ashworth Scale remain in common use secondary to ease of use despite their obvious functional limitations. More functional outcome goals are plagued by being more time consuming and a general inability to demonstrate changes after an intervention. This may be secondary to the other factors that combine with spasticity to cause dysfunction at that level. Quantitative metrics can provide more objective measurements but their clinical relevance is sometimes problematic. The assessment of spasticity outcome is still somewhat problematic. Further work is necessary to develop measures that have real-world functional significance to both the individuals being treated and the clinicians. A lack of objectivity is still a problem. In the future it is important for clinicians and the engineers to work together in the development of better outcome measures.

Prevalence of cagA and vacA among Helicobacter pylori-infected patients in Iran: a systematic review and meta-analysis.

PubMed

Sayehmiri, Fatemeh; Kiani, Faezeh; Sayehmiri, Kourosh; Soroush, Setareh; Asadollahi, Khairollah; Alikhani, Mohammad Yousef; Delpisheh, Ali; Emaneini, Mohammad; Bogdanović, Lidija; Varzi, Ali Mohammad; Zarrilli, Raffaele; Taherikalani, Morovat

2015-07-30

The varieties of infections caused by Helicobacter pylori may be due to differences in bacterial genotypes and virulence factors as well as environmental and host-related factors. This study aimed to investigate the prevalence of cagA and vacA genes among H. pylori-infected patients in Iran and analyze their relevance to the disease status between two clinical groups via a meta-analysis method. Different databases including PubMed, ISI, Scopus, SID, Magiran, Science Direct, and Medlib were investigated, and 23 relevant articles from the period between 2001 and 2012 were finally analyzed. The relevant data obtained from these papers were analyzed by a random-effects model. Data were analyzed using R software and STATA. The prevalence of cagA and vacA genes among H. pylori-infected patients was 70% (95% CI, 64-75) and 41% (95% CI, 24.3-57.7), respectively. The prevalence of duodenal ulcers, peptic ulcers, and gastritis among cagA+ individuals was 53% (95% CI, 20-86), 65% (95% CI, 34-97), and 71% (95% CI, 59-84), respectively. Odds ratio (OR) between cagA-positive compared with cagA-negative patients showed a 1.89 (95% CI, 1.38-2.57) risk of ulcers. In conclusion, the frequency of cagA gene among H. pylori strains is elevated in Iran and it seems to be more frequently associated with gastritis. Therefore, any information about cagA and vacA prevalence among different H. pylori-infected clinical groups in the country can help public health authorities to plan preventive policies to reduce the prevalence of diseases associated with H. pylori infection.

Molecular Subtypes of Glioblastoma Are Relevant to Lower Grade Glioma

PubMed Central

Sloan, Andrew E.; Chen, Yanwen; Brat, Daniel J.; O’Neill, Brian Patrick; de Groot, John; Yust-Katz, Shlomit; Yung, Wai-Kwan Alfred; Cohen, Mark L.; Aldape, Kenneth D.; Rosenfeld, Steven; Verhaak, Roeland G. W.; Barnholtz-Sloan, Jill S.

2014-01-01

Background Gliomas are the most common primary malignant brain tumors in adults with great heterogeneity in histopathology and clinical course. The intent was to evaluate the relevance of known glioblastoma (GBM) expression and methylation based subtypes to grade II and III gliomas (ie. lower grade gliomas). Methods Gene expression array, single nucleotide polymorphism (SNP) array and clinical data were obtained for 228 GBMs and 176 grade II/II gliomas (GII/III) from the publically available Rembrandt dataset. Two additional datasets with IDH1 mutation status were utilized as validation datasets (one publicly available dataset and one newly generated dataset from MD Anderson). Unsupervised clustering was performed and compared to gene expression subtypes assigned using the Verhaak et al 840-gene classifier. The glioma-CpG Island Methylator Phenotype (G-CIMP) was assigned using prediction models by Fine et al. Results Unsupervised clustering by gene expression aligned with the Verhaak 840-gene subtype group assignments. GII/IIIs were preferentially assigned to the proneural subtype with IDH1 mutation and G-CIMP. GBMs were evenly distributed among the four subtypes. Proneural, IDH1 mutant, G-CIMP GII/III s had significantly better survival than other molecular subtypes. Only 6% of GBMs were proneural and had either IDH1 mutation or G-CIMP but these tumors had significantly better survival than other GBMs. Copy number changes in chromosomes 1p and 19q were associated with GII/IIIs, while these changes in CDKN2A, PTEN and EGFR were more commonly associated with GBMs. Conclusions GBM gene-expression and methylation based subtypes are relevant for GII/III s and associate with overall survival differences. A better understanding of the association between these subtypes and GII/IIIs could further knowledge regarding prognosis and mechanisms of glioma progression. PMID:24614622

Xenosurveillance: A Novel Mosquito-Based Approach for Examining the Human-Pathogen Landscape

PubMed Central

Grubaugh, Nathan D.; Sharma, Supriya; Krajacich, Benjamin J.; Fakoli III, Lawrence S.; Bolay, Fatorma K.; Diclaro II, Joe W.; Johnson, W. Evan; Ebel, Gregory D.; Foy, Brian D.; Brackney, Doug E.

2015-01-01

Background Globally, regions at the highest risk for emerging infectious diseases are often the ones with the fewest resources. As a result, implementing sustainable infectious disease surveillance systems in these regions is challenging. The cost of these programs and difficulties associated with collecting, storing and transporting relevant samples have hindered them in the regions where they are most needed. Therefore, we tested the sensitivity and feasibility of a novel surveillance technique called xenosurveillance. This approach utilizes the host feeding preferences and behaviors of Anopheles gambiae, which are highly anthropophilic and rest indoors after feeding, to sample viruses in human beings. We hypothesized that mosquito bloodmeals could be used to detect vertebrate viral pathogens within realistic field collection timeframes and clinically relevant concentrations. Methodology/Principal Findings To validate this approach, we examined variables influencing virus detection such as the duration between mosquito blood feeding and mosquito processing, the pathogen nucleic acid stability in the mosquito gut and the pathogen load present in the host’s blood at the time of bloodmeal ingestion using our laboratory model. Our findings revealed that viral nucleic acids, at clinically relevant concentrations, could be detected from engorged mosquitoes for up to 24 hours post feeding by qRT-PCR. Subsequently, we tested this approach in the field by examining blood from engorged mosquitoes from two field sites in Liberia. Using next-generation sequencing and PCR we were able to detect the genetic signatures of multiple viral pathogens including Epstein-Barr virus and canine distemper virus. Conclusions/Significance Together, these data demonstrate the feasibility of xenosurveillance and in doing so validated a simple and non-invasive surveillance tool that could be used to complement current biosurveillance efforts. PMID:25775236

Interviews with children about their mental health problems: The congruence and validity of information that children report.

PubMed

Macleod, Emily; Woolford, June; Hobbs, Linda; Gross, Julien; Hayne, Harlene; Patterson, Tess

2017-04-01

To obtain a child's perspective during a mental health assessment, he or she is usually interviewed. Although researchers and clinicians generally agree that it is beneficial to hear a child's account of his or her presenting issues, there is debate about whether children provide reliable or valid clinical information during these interviews. Here, we examined whether children provide clinically and diagnostically relevant information in a clinical setting. In all, 31 children aged 5-12-years undergoing mental health assessments were asked open-ended questions about their presenting problems during a semi-structured interview. We coded the information that children reported to determine whether it was clinically relevant and could be used to diagnose their problems and to formulate and plan treatment. We also coded children's information to determine whether it was congruent with the children's presenting problems and their eventual clinical diagnoses. Most of the information that children reported was clinically relevant and included information about behaviour, affect, temporal details, thoughts, people, the environment, and the child's physical experiences. The information that children reported was also clinically valid; it was congruent with the problems that were discussed (84%) and also with the eventual diagnosis that the child received after a complete assessment (74%). We conclude that children can contribute relevant, clinically useful, valid information during clinical psychological assessments.

Estrogen receptor alpha gene amplification in breast cancer: 25 years of debate

PubMed Central

Holst, Frederik

2016-01-01

Twenty-five years ago, Nembrot and colleagues reported amplification of the estrogen receptor alpha gene (ESR1) in breast cancer, initiating a broad and still ongoing scientific debate on the prevalence and clinical significance of this genetic aberration, which affects one of the most important genes in breast cancer. Since then, a multitude of studies on this topic has been published, covering a wide range of divergent results and arguments. The reported prevalence of this alteration in breast cancer ranges from 0% to 75%, suggesting that ESR1 copy number analysis is hampered by technical and interpreter issues. To date, two major issues related to ESR1 amplification remain to be conclusively addressed: (1) The extent to which abundant amounts of messenger RNA can mimic amplification in standard fluorescence in situ hybridization assays in the analysis of strongly expressed genes like ESR1, and (2) the clinical relevance of ESR1 amplification: Such relevance is strongly disputed, with data showing predictive value for response as well as for resistance of the cancer to anti-estrogen therapies, or for subsequent development of cancers in the case of precursor lesions that display amplification of ESR1. This review provides a comprehensive summary of the various views on ESR1 amplification, and highlights explanations for the contradictions and conflicting data that could inform future ESR1 research. PMID:27081639

Effect of food on the bioavailability of lesogaberan given as an oral solution or as modified-release capsules in healthy male volunteers.

PubMed

Fransson, Bo; Silberg, Debra G; Niazi, Mohammad; Miller, Frank; Ruth, Magnus; Holmberg, Ann Aurell

2012-04-01

The novel Type B gamma-aminobutyric acid (GABAB)-receptor agonist lesogaberan (AZD3355) has been evaluated as an add-on to proton pump inhibitor treatment for gastroesophageal reflux disease, but the effect of food on the bioavailability of this compound has not been assessed. In this openlabel crossover study, healthy males received single 100 mg doses of lesogaberan (oral solution (A) or oral modified release (MR) capsules with a dissolution rate of 50% (B) or 100% (C) over 4 h) with and without food. Blood plasma concentrations of lesogaberan were assessed over 48 h. A log-transformed geometric mean Cmax and AUC ratio within the 90% confidence interval (CI) range (0.80 - 1.25) was defined as excluding a clinically relevant food effect. Overall, 57 subjects completed the study. Only the oral lesogaberan solution had a fed/fasting Cmax ratio outside the 90% CI range (Cmax ratio: 0.76). AUC ratios were within the 90% CI limits for all three lesogaberan formulations. The only substantial change in tmax associated with food intake was observed for the oral solution (1.0 h without food, 1.8 h with food). In conclusion, a clinically relevant food effect could be excluded for the lesogaberan MR formulations, but not for the oral lesogaberan solution.

Functional assessment and performance evaluation for assistive robotic manipulators: Literature review

PubMed Central

Chung, Cheng-Shiu; Wang, Hongwu; Cooper, Rory A.

2013-01-01

Context The user interface development of assistive robotic manipulators can be traced back to the 1960s. Studies include kinematic designs, cost-efficiency, user experience involvements, and performance evaluation. This paper is to review studies conducted with clinical trials using activities of daily living (ADLs) tasks to evaluate performance categorized using the International Classification of Functioning, Disability, and Health (ICF) frameworks, in order to give the scope of current research and provide suggestions for future studies. Methods We conducted a literature search of assistive robotic manipulators from 1970 to 2012 in PubMed, Google Scholar, and University of Pittsburgh Library System – PITTCat. Results Twenty relevant studies were identified. Conclusion Studies were separated into two broad categories: user task preferences and user-interface performance measurements of commercialized and developing assistive robotic manipulators. The outcome measures and ICF codes associated with the performance evaluations are reported. Suggestions for the future studies include (1) standardized ADL tasks for the quantitative and qualitative evaluation of task efficiency and performance to build comparable measures between research groups, (2) studies relevant to the tasks from user priority lists and ICF codes, and (3) appropriate clinical functional assessment tests with consideration of constraints in assistive robotic manipulator user interfaces. In addition, these outcome measures will help physicians and therapists build standardized tools while prescribing and assessing assistive robotic manipulators. PMID:23820143

Efficacy of febuxostat in hyperuricemic patients with mild-to-moderate chronic kidney disease: a meta-analysis of randomized clinical trials

PubMed Central

Zeng, Xiang Xia; Tang, Yunliang; Hu, Kaixiang; Zhou, Xi; Wang, Jiao; Zhu, Lingyan; Liu, Jianying; Xu, Jixiong

2018-01-01

Abstract Background: To investigate the efficacy of febuxostat in hyperuricemic patients with chronic kidney disease (CKD), relevant randomized clinical trials (RCTs) were analyzed. Methods: We used PubMed, Medline, ISI Web of Science, CBMdisc, and Cochrane Library databases to conduct a systematic literature research. A fixed-effects model was used to evaluate the standardized mean differences (SMDs) with 95% confidence intervals (CIs). We conducted subgroup analysis, sensitivity analysis, and analyzed publication bias, to comprehensively estimate the renoprotective effects of febuxostat in hyperuricemic patients with CKD. Results: Among 296 retrieved studies, 5 relevant RCTs were included in the meta-analysis. The result showed that serum estimated glomerular filtration rate (eGFR) was improved after febuxostat treatment in hyperuricemic patients with CKD, with an SMD (95% CI) of 0.24 [−0.17 to 0.43] and P = .67 (fixed-effects model). No heterogeneity was observed across studies (I2 = 0% and P = .67). Subgroup analysis suggested that treatment-related reductions in serum eGFR levels were not related to drug doses, intervention times, or region. Conclusions: The present meta-analysis suggests that febuxostat may slow the progression of mild-to-moderate CKD. Given the limited number of included studies, additional large sample-size RCTs are required to determine the long-term renoprotective effects of febuxostat in hyperuricemic patients with CKD. PMID:29595642

Flowable Resin Composites: A Systematic Review and Clinical Considerations

PubMed Central

Rodrigues, Jean C.

2015-01-01

Background Little is known about flowable composite materials. Most literature mentions conventional composite materials at large, giving minimal emphasis to flowables in particular. This paper briefly gives an in depth insight to the multiple facets of this versatile material. Aim To exclusively review the most salient features of flowable composite materials in comparison to conventional composites and to give clinicians a detailed understanding of the advantages, drawbacks, indications and contraindications based on composition and physical/mechanical properties. Methodology Data Sources: A thorough literature search from the year 1996 up to January 2015 was done on PubMed Central, The Cochrane Library, Science Direct, Wiley Online Library, and Google Scholar. Grey literature (pending patents, technical reports etc.) was also screened. The search terms used were “dental flowable resin composites”. Search Strategy After omitting the duplicates/repetitions, a total of 491 full text articles were assessed. As including all articles were out of the scope of this paper. Only relevant articles that fulfilled the reviewer’s objectives {mentioning indications, contraindications, applications, assessment of physical/mechanical/biological properties (in vitro/ in vivo /ex vivo)} were considered. A total of 92 full text articles were selected. Conclusion Flowable composites exhibit a variable composition and consequently variable mechanical/ physical properties. Clinicians must be aware of this aspect to make a proper material selection based on specific properties and indications of each material relevant to a particular clinical situation. PMID:26266238

Characterization of blunt chest trauma in a long-term porcine model of severe multiple trauma

PubMed Central

Horst, K.; Simon, T. P.; Pfeifer, R.; Teuben, M.; Almahmoud, K.; Zhi, Q.; Santos, S. Aguiar; Wembers, C. Castelar; Leonhardt, S.; Heussen, N.; Störmann, P.; Auner, B.; Relja, B.; Marzi, I.; Haug, A. T.; van Griensven, M.; Kalbitz, M.; Huber-Lang, M.; Tolba, R.; Reiss, L. K.; Uhlig, S.; Marx, G.; Pape, H. C.; Hildebrand, F.

2016-01-01

Chest trauma has a significant relevance on outcome after severe trauma. Clinically, impaired lung function typically occurs within 72 hours after trauma. However, the underlying pathophysiological mechanisms are still not fully elucidated. Therefore, we aimed to establish an experimental long-term model to investigate physiological, morphologic and inflammatory changes, after severe trauma. Male pigs (sus scrofa) sustained severe trauma (including unilateral chest trauma, femur fracture, liver laceration and hemorrhagic shock). Additionally, non-injured animals served as sham controls. Chest trauma resulted in severe lung damage on both CT and histological analyses. Furthermore, severe inflammation with a systemic increase of IL-6 (p = 0.0305) and a local increase of IL-8 in BAL (p = 0.0009) was observed. The pO2/FiO2 ratio in trauma animals decreased over the observation period (p < 0.0001) but not in the sham group (p = 0.2967). Electrical Impedance Tomography (EIT) revealed differences between the traumatized and healthy lung (p < 0.0001). In conclusion, a clinically relevant, long-term model of blunt chest trauma with concomitant injuries has been developed. This reproducible model allows to examine local and systemic consequences of trauma and is valid for investigation of potential diagnostic or therapeutic options. In this context, EIT might represent a radiation-free method for bedside diagnostics. PMID:28000769

Chronic fatigue in Hodgkin lymphoma survivors and associations with anxiety, depression and comorbidity

PubMed Central

Daniëls, L A; Oerlemans, S; Krol, A D G; Creutzberg, C L; van de Poll-Franse, L V

2014-01-01

Background: Fatigue is a frequent and persistent problem among Hodgkin lymphoma (HL) survivors. We investigated the prevalence of clinically relevant fatigue in HL survivors and the relation between fatigue and anxiety and depression. Methods: Fatigue was measured through the generic European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) and Fatigue Assessment Scale (FAS). Anxiety and depression were measured with the Hospital Anxiety and Depression Scale. Questionnaires were mailed to 267 HL survivors. Results were compared with a Dutch age-matched normative population. Results: Response rate was 68% (median age 46 years, mean time since diagnosis 4.6 years). Prevalence of fatigue was significantly higher among HL survivors than in the norm population (FAS 41% vs 23%, QLQ-C30 43% vs 28%), as were fatigue levels. There was a significant association between fatigue, anxiety and depression. Of the HL survivors with high symptom levels of depression, 97% also reported fatigue. In multivariate analysis, depression was strongly associated with high levels of fatigue and, to a lesser extent, anxiety and comorbidity. Conclusions: Prevalence rates of fatigue are significantly higher in HL survivors than in the general population and differences are clinically relevant. Depression and anxiety were strongly associated with high levels of fatigue. Reducing fatigue levels by treatment of depression and anxiety should be further explored. PMID:24434433

Direct effects of diazepam on emotional processing in healthy volunteers

PubMed Central

Murphy, S. E.; Downham, C.; Cowen, P. J.

2008-01-01

Rationale Pharmacological agents used in the treatment of anxiety have been reported to decrease threat relevant processing in patients and healthy controls, suggesting a potentially relevant mechanism of action. However, the effects of the anxiolytic diazepam have typically been examined at sedative doses, which do not allow the direct actions on emotional processing to be fully separated from global effects of the drug on cognition and alertness. Objectives The aim of this study was to investigate the effect of a lower, but still clinically effective, dose of diazepam on emotional processing in healthy volunteers. Materials and methods Twenty-four participants were randomised to receive a single dose of diazepam (5 mg) or placebo. Sixty minutes later, participants completed a battery of psychological tests, including measures of non-emotional cognitive performance (reaction time and sustained attention) and emotional processing (affective modulation of the startle reflex, attentional dot probe, facial expression recognition, and emotional memory). Mood and subjective experience were also measured. Results Diazepam significantly modulated attentional vigilance to masked emotional faces and significantly decreased overall startle reactivity. Diazepam did not significantly affect mood, alertness, response times, facial expression recognition, or sustained attention. Conclusions At non-sedating doses, diazepam produces effects on attentional vigilance and startle responsivity that are consistent with its anxiolytic action. This may be an underlying mechanism through which benzodiazepines exert their therapeutic effects in clinical anxiety. PMID:18581100

Human Adipose Mesenchymal Cells Inhibit Melanocyte Differentiation and the Pigmentation of Human Skin via Increased Expression of TGF-β1.

PubMed

Klar, Agnes S; Biedermann, Thomas; Michalak, Katarzyna; Michalczyk, Teresa; Meuli-Simmen, Claudia; Scherberich, Arnaud; Meuli, Martin; Reichmann, Ernst

2017-12-01

There is accumulating evidence that interactions between epidermal melanocytes and stromal cells play an important role in the regulation of skin pigmentation. In this study we established a pigmented dermo-epidermal skin model, melDESS, of human origin to investigate the effects of distinct stromal cells on melanogenesis. melDESS is a complex, clinically relevant skin equivalent composed of an epidermis containing both melanocytes and keratinocytes. Its dermal compartment consists either of adipose tissue-derived stromal cells, dermal fibroblasts (Fbs), or a mixture of both cell types. These skin substitutes were transplanted for 5 weeks on the backs of immuno-incompetent rats and analyzed. Gene expression and Western blot analyses showed a significantly higher expression of transforming growth factor-β1 by adipose tissue-derived stromal cells compared with dermal Fbs. In addition, we showed that melanocytes responded to the increased levels of transforming growth factor-β1 by down-regulating the expression of key melanogenic enzymes such as tyrosinase. This caused decreased melanin synthesis and, consequently, greatly reduced pigmentation of melDESS. The conclusions are of utmost clinical relevance, namely that adipose tissue-derived stromal cells derived from the hypodermis fail to appropriately interact with epidermal melanocytes, thus preventing the sustainable restoration of the patient's native skin color in bioengineered skin grafts. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Interactive decision support in hepatic surgery

PubMed Central

Dugas, Martin; Schauer, Rolf; Volk, Andreas; Rau, Horst

2002-01-01

Background Hepatic surgery is characterized by complicated operations with a significant peri- and postoperative risk for the patient. We developed a web-based, high-granular research database for comprehensive documentation of all relevant variables to evaluate new surgical techniques. Methods To integrate this research system into the clinical setting, we designed an interactive decision support component. The objective is to provide relevant information for the surgeon and the patient to assess preoperatively the risk of a specific surgical procedure. Based on five established predictors of patient outcomes, the risk assessment tool searches for similar cases in the database and aggregates the information to estimate the risk for an individual patient. Results The physician can verify the analysis and exclude manually non-matching cases according to his expertise. The analysis is visualized by means of a Kaplan-Meier plot. To evaluate the decision support component we analyzed data on 165 patients diagnosed with hepatocellular carcinoma (period 1996–2000). The similarity search provides a two-peak distribution indicating there are groups of similar patients and singular cases which are quite different to the average. The results of the risk estimation are consistent with the observed survival data, but must be interpreted with caution because of the limited number of matching reference cases. Conclusion Critical issues for the decision support system are clinical integration, a transparent and reliable knowledge base and user feedback. PMID:12003639

Identification of clinically relevant viridans streptococci by an oligonucleotide array.

PubMed

Chen, Chao Chien; Teng, Lee Jene; Kaiung, Seng; Chang, Tsung Chain

2005-04-01

Viridans streptococci (VS) are common etiologic agents of subacute infective endocarditis and are capable of causing a variety of pyogenic infections. Many species of VS are difficult to differentiate by phenotypic traits. An oligonucleotide array based on 16S-23S rRNA gene intergenic spacer (ITS) sequences was developed to identify 11 clinically relevant VS. These 11 species were Streptococcus anginosus, S. constellatus, S. gordonii, S. intermedius, S. mitis, S. mutans, S. oralis, S. parasanguinis, S. salivarius, S. sanguinis, and S. uberis. The method consisted of PCR amplification of the ITS regions by using a pair of universal primers, followed by hybridization of the digoxigenin-labeled PCR products to a panel of species-specific oligonucleotides immobilized on a nylon membrane. After 120 strains of the 11 species of VG and 91 strains of other bacteria were tested, the sensitivity and specificity of the oligonucleotide array were found to be 100% (120 of 120 strains) and 95.6% (87 of 91 strains), respectively. S. pneumoniae cross-hybridized to the probes used for the identification of S. mitis, and simple biochemical tests such as optochin susceptibility or bile solubility should be used to differentiate S. pneumoniae from S. mitis. In conclusion, identification of species of VS by use of the present oligonucleotide array is accurate and could be used as an alternative reliable method for species identification of strains of VS.

Systematic Review of Vitamin D and Hypertensive Disorders of Pregnancy

PubMed Central

O’Callaghan, Karen M.

2018-01-01

This narrative systematic review evaluates growing evidence of an association between low maternal vitamin D status and increased risk of hypertensive disorders. The inclusion of interventional, observational, and dietary studies on vitamin D and all hypertensive disorders of pregnancy is a novel aspect of this review, providing a unique contribution to an intensively-researched area that still lacks a definitive conclusion. To date, trial evidence supports a protective effect of combined vitamin D and calcium supplementation against preeclampsia. Conflicting data for an association of vitamin D with gestational hypertensive disorders in observational studies arises from a number of sources, including large heterogeneity between study designs, lack of adherence to standardized perinatal outcome definitions, variable quality of analytical data for 25-hydroxyvitamin D (25(OH)D), and inconsistent data reporting of vitamin D status. While evidence does appear to lean towards an increased risk of gestational hypertensive disorders at 25(OH)D concentrations <50 nmol/L, caution should be exercised with dosing in trials, given the lack of data on long-term safety. The possibility that a fairly narrow target range for circulating 25(OH)D for achievement of clinically-relevant improvements requires further exploration. As hypertension alone, and not preeclampsia specifically, limits intrauterine growth, evaluation of the relationship between vitamin D status and all terms of hypertension in pregnancy is a clinically relevant area for research and should be prioritised in future randomised trials. PMID:29494538

Systematic Review of Vitamin D and Hypertensive Disorders of Pregnancy.

PubMed

O'Callaghan, Karen M; Kiely, Mairead

2018-03-01

This narrative systematic review evaluates growing evidence of an association between low maternal vitamin D status and increased risk of hypertensive disorders. The inclusion of interventional, observational, and dietary studies on vitamin D and all hypertensive disorders of pregnancy is a novel aspect of this review, providing a unique contribution to an intensively-researched area that still lacks a definitive conclusion. To date, trial evidence supports a protective effect of combined vitamin D and calcium supplementation against preeclampsia. Conflicting data for an association of vitamin D with gestational hypertensive disorders in observational studies arises from a number of sources, including large heterogeneity between study designs, lack of adherence to standardized perinatal outcome definitions, variable quality of analytical data for 25-hydroxyvitamin D (25(OH)D), and inconsistent data reporting of vitamin D status. While evidence does appear to lean towards an increased risk of gestational hypertensive disorders at 25(OH)D concentrations <50 nmol/L, caution should be exercised with dosing in trials, given the lack of data on long-term safety. The possibility that a fairly narrow target range for circulating 25(OH)D for achievement of clinically-relevant improvements requires further exploration. As hypertension alone, and not preeclampsia specifically, limits intrauterine growth, evaluation of the relationship between vitamin D status and all terms of hypertension in pregnancy is a clinically relevant area for research and should be prioritised in future randomised trials.

A simple measure of cognitive reserve is relevant for cognitive performance in MS patients.

PubMed

Della Corte, Marida; Santangelo, Gabriella; Bisecco, Alvino; Sacco, Rosaria; Siciliano, Mattia; d'Ambrosio, Alessandro; Docimo, Renato; Cuomo, Teresa; Lavorgna, Luigi; Bonavita, Simona; Tedeschi, Gioacchino; Gallo, Antonio

2018-05-04

Cognitive reserve (CR) contributes to preserve cognition despite brain damage. This theory has been applied to multiple sclerosis (MS) to explain the partial relationship between cognition and MRI markers of brain pathology. Our aim was to determine the relationship between two measures of CR and cognition in MS. One hundred and forty-seven MS patients were enrolled. Cognition was assessed using the Rao's Brief Repeatable Battery and the Stroop Test. CR was measured as the vocabulary subtest of the WAIS-R score (VOC) and the number of years of formal education (EDU). Regression analysis included raw score data on each neuropsychological (NP) test as dependent variables and demographic/clinical parameters, VOC, and EDU as independent predictors. A binary logistic regression analysis including clinical/CR parameters as covariates and absence/presence of cognitive deficits as dependent variables was performed too. VOC, but not EDU, was strongly correlated with performances at all ten NP tests. EDU was correlated with executive performances. The binary logistic regression showed that only the Expanded Disability Status Scale (EDSS) and VOC were independently correlated with the presence/absence of CD. The lower the VOC and/or the higher the EDSS, the higher the frequency of CD. In conclusion, our study supports the relevance of CR in subtending cognitive performances and the presence of CD in MS patients.

Interference of Antibacterial Agents with Phagocyte Functions: Immunomodulation or “Immuno-Fairy Tales”?

PubMed Central

Labro, Marie-Thérése

2000-01-01

Professional phagocytes (polymorphonuclear neutrophils and monocytes/macrophages) are a main component of the immune system. These cells are involved in both host defenses and various pathological settings characterized by excessive inflammation. Accordingly, they are key targets for immunomodulatory drugs, among which antibacterial agents are promising candidates. The basic and historical concepts of immunomodulation will first be briefly reviewed. Phagocyte complexity will then be unravelled (at least in terms of what we know about the origin, subsets, ambivalent roles, functional capacities, and transductional pathways of this cell and how to explore them). The core subject of this review will be the many possible interactions between antibacterial agents and phagocytes, classified according to demonstrated or potential clinical relevance (e.g., neutropenia, intracellular accumulation, and modulation of bacterial virulence). A detailed review of direct in vitro effects will be provided for the various antibacterial drug families, followed by a discussion of the clinical relevance of these effects in two particular settings: immune deficiency and inflammatory diseases. The prophylactic and therapeutic use of immunomodulatory antibiotics will be considered before conclusions are drawn about the emerging (optimistic) vision of future therapeutic prospects to deal with largely unknown new diseases and new pathogens by using new agents, new techniques, and a better understanding of the phagocyte in particular and the immune system in general. PMID:11023961

Drug-induced QT interval prolongation: does ethnicity of the thorough QT study population matter?

PubMed Central

Shah, Rashmi R

2013-01-01

Inter-ethnic differences in drug responses have been well documented. Drug-induced QT interval prolongation is a major safety concern and therefore, regulatory authorities recommend a clinical thorough QT study (TQT) to investigate new drugs for their QT-prolonging potential. A positive study, determined by breach of a preset regulatory threshold, significantly influences late phase clinical trials by requiring intense ECG monitoring. A few studies that are currently available, although not statistically conclusive at present, question the assumption that ethnicity of the study population may not influence the outcome of a TQT study. Collective consideration of available pharmacogenetic and clinical information suggests that there may be inter-ethnic differences in QT-prolonging effects of drugs and that Caucasians may be more sensitive than other populations. The information also suggest s that (a) these differences may depend on the QT-prolonging potency of the drug and (b) exposure–response (E–R) analysis may be more sensitive than simple changes in QTc interval in unmasking this difference. If the QT response in Caucasians is generally found to be more intense than in non-Caucasians, there may be significant regulatory implications for domestic acceptance of data from a TQT study conducted in foreign populations. However, each drug will warrant an individual consideration when extrapolating the results of a TQT studyfrom one ethnic population to another and the ultimate clinical relevance of any difference. Further adequately designed and powered studies, investigating the pharmacologic properties and E–R relationships of additional drugs with different potencies, are needed in Caucasians, Oriental/Asian and African populations before firm conclusions can be drawn. PMID:22882246

Locating relevant patient information in electronic health record data using representations of clinical concepts and database structures.

PubMed

Pan, Xuequn; Cimino, James J

2014-01-01

Clinicians and clinical researchers often seek information in electronic health records (EHRs) that are relevant to some concept of interest, such as a disease or finding. The heterogeneous nature of EHRs can complicate retrieval, risking incomplete results. We frame this problem as the presence of two gaps: 1) a gap between clinical concepts and their representations in EHR data and 2) a gap between data representations and their locations within EHR data structures. We bridge these gaps with a knowledge structure that comprises relationships among clinical concepts (including concepts of interest and concepts that may be instantiated in EHR data) and relationships between clinical concepts and the database structures. We make use of available knowledge resources to develop a reproducible, scalable process for creating a knowledge base that can support automated query expansion from a clinical concept to all relevant EHR data.

When doubting begins: exploring inductive reasoning in obsessive-compulsive disorder.

PubMed

Pélissier, Marie-Claude; O'Connor, Kieron P; Dupuis, Gilles

2009-03-01

The objective of this study was to test the hypothesis that inductive reasoning plays a role in obsessional doubting by comparing an OCD sample with a non-OCD control group in performance of an inductive reasoning task. The 'Reasoning with Inductive Arguments Task' (RIAT) measures inductive performance using arguments drawn from both given vs. self-generated sources and containing neutral vs. OCD-related content. Both an OCD group recruited from clinical referrals and a control group recruited from the general population were compared on performance of the RIAT. People with OCD tended to doubt an initial conclusion much more than controls in the light of subsequent alternative conclusions given by the experimenter. There were no significant differences between the two groups in the self-generated condition. The OCD group doubted more regardless of whether the items were OCD-relevant or neutral. The control group also doubted the initial conclusions but not to the same extent as the OCD group in the 'given' condition and their degree of doubting did not differ between self-generated or given items. People with OCD may create doubt because they are giving too much credit to mental models given from external sources.

The ethical implications of Paul Meehl's work on comparing clinical versus actuarial prediction methods.

PubMed

Dawes, Robyn M

2005-10-01

Paul E. Meehl's work comparing statistical versus actuarial prediction-and the large body of research that followed by others on the same topic-was mainly theoretical and empirical. Meehl also suggested that this work led to a "practical" conclusion, which was quite strong. The author argues that, in addition, it leads to an ethical conclusion, equally strong. Whether the scientific findings are combined with an overarching ethical principle that the best predictions possible should be made for clients, or whether these findings are framed as delineating what can be done for clients-and that clinicians ought not to attempt to do what they cannot-the conclusion is the same. Whenever statistical prediction rules (SPR's) are available for making a relevant prediction, they should be used in preference to intuition. Any modification of these rules should be systematic and subject to the same type of evaluation originally used to assess the SPR's themselves. It is even possible to develop near-optimal rules in new situations. Providing service that assumes that clinicians "can do better" simply based on self-confidence or plausibility in the absence of evidence that they can actually do so is simply unethical. 2005 Wiley Periodicals, Inc.

Selecting relevant and feasible measurement instruments for the revised Dutch clinical practice guideline for physical therapy in patients after stroke.

PubMed

Otterman, Nicoline; Veerbeek, Janne; Schiemanck, Sven; van der Wees, Philip; Nollet, Frans; Kwakkel, Gert

2017-07-01

To select relevant and feasible instruments for the revision of the Dutch clinical practice guideline for physical therapy in patients with stroke. In this implementation study a comprehensive proposal for ICF categories and matching instruments was developed, based on reliability and validity. Relevant instruments were then selected in a consensus round by 11 knowledge brokers who were responsible for the implementation of the selected instruments. The feasibility of the selected instruments was tested by 36 physical therapists at different work settings within stroke services. Finally, instruments that were deemed relevant and feasible were included in the revised guideline. A total of 28 instruments were recommended for inclusion in the revised guideline. Nineteen instruments were retained from the previous guideline. Ten new instruments were tested in clinical practice, seven of which were found feasible. Two more instruments were added after critical appraisal of the set of the measurement instruments. The revised guideline contains 28 relevant and feasible instrument selected and tested in clinical practice by physical therapists. Further education and implementation is needed to integrate instruments in clinical practice. Further research is proposed for developing and implementing a core set of measurement instruments to be used at fixed time points to establish data registries that allow for continuous improvement of rehabilitation for stroke patients. Implications for Rehabilitation The revised Dutch Stroke Physical Therapy Guideline recommends a total of 28 instruments, that are relevant and feasible for clinical practice of physical therapist in the different settings of stroke rehabilitation. The selection of instrument in daily practice should be part of the clinical reasoning process of PTs and be tailored to individual patients' needs and the degree of priority of the affected ICF category. Suggested education strategies for further integration of instruments in of the daily practice of PTs in Stroke Rehabilitation are: 'Training on the job' and 'peer assessment in clinical situations'.

Direct-to-consumer advertising of success rates for medically assisted reproduction: a review of national clinic websites

PubMed Central

Vail, Andy; Roberts, Stephen A

2017-01-01

Objectives To establish how medically assisted reproduction (MAR) clinics report success rates on their websites. Setting Websites of private and NHS clinics offering in vitro fertilisation (IVF) in the UK. Participants We identified clinics offering IVF using the Choose a Fertility Clinic facility on the website of the Human Fertilisation and Embryology Authority (HFEA). Of 81 clinics identified, a website could not be found for 2, leaving 79 for inclusion in the analysis. Primary and secondary outcome measures Outcome measures reported by clinic websites. The numerator and denominator included in the outcome measure were of interest. Results 53 (67%) websites reported their performance using 51 different outcome measures. It was most common to report pregnancy (83% of these clinics) or live birth rates (51%). 31 different ways of reporting pregnancy and 9 different ways of reporting live birth were identified. 11 (21%) reported multiple birth or pregnancy rates. 1 clinic provided information on adverse events. It was usual for clinics to present results without relevant contextual information such as sample size, reporting period, the characteristics of patients and particular details of treatments. Conclusions Many combinations of numerator and denominator are available for the purpose of reporting success rates for MAR. The range of reporting options available to clinics is further increased by the possibility of presenting results for subgroups of patients and for different time periods. Given the status of these websites as advertisements to patients, the risk of selective reporting is considerable. Binding guidance is required to ensure consistent, informative reporting. PMID:28082363

The Genomic Landscape and Clinical Relevance of A-to-I RNA Editing in Human Cancers | Office of Cancer Genomics

Cancer.gov

Adenosine-to-inosine (A-to-I) RNA editing is a widespread post-transcriptional mechanism, but its genomic landscape and clinical relevance in cancer have not been investigated systematically. We characterized the global A-to-I RNA editing profiles of 6,236 patient samples of 17 cancer types from The Cancer Genome Atlas and revealed a striking diversity of altered RNA-editing patterns in tumors relative to normal tissues. We identified an appreciable number of clinically relevant editing events, many of which are in noncoding regions.

Twitter: A Novel Tool for Studying the Health and Social Needs of Transgender Communities

PubMed Central

Young, Sean D

2015-01-01

Background Limited research has examined the health and social needs of transgender and gender nonconforming populations. Due to high levels of stigma, transgender individuals may avoid disclosing their identities to researchers, hindering this type of work. Further, researchers have traditionally relied on clinic-based sampling methods, which may mask the true heterogeneity of transgender and gender nonconforming communities. Online social networking websites present a novel platform for studying this diverse, difficult-to-reach population. Objective The objective of this study was to attempt to examine the perceived health and social needs of transgender and gender nonconforming communities by examining messages posted to the popular microblogging platform, Twitter. Methods Tweets were collected from 13 transgender-related hashtags on July 11, 2014. They were read and coded according to general themes addressed, and a content analysis was performed. Qualitative and descriptive statistics are presented. Results There were 1135 tweets that were collected in total. Both “positive” and “negative” events were discussed, in both personal and social contexts. Violence, discrimination, suicide, and sexual risk behavior were discussed. There were 34.36% (390/1135) of tweets that addressed transgender-relevant current events, and 60.79% (690/1135) provided a link to a relevant news article or resource. Conclusions This study found that transgender individuals and allies use Twitter to discuss health and social needs relevant to the population. Real-time social media sites like Twitter can be used to study issues relevant to transgender communities. PMID:26082941

Setting priorities for comparative effectiveness research on management of primary angle closure: a survey of Asia-Pacific clinicians.

PubMed

Yu, Tsung; Li, Tianjing; Lee, Kinbo J; Friedman, David S; Dickersin, Kay; Puhan, Milo A

2015-01-01

To set priorities for new systematic reviews (SRs) and randomized clinical trials on the management of primary angle closure (PAC) using clinical practice guidelines and a survey of Asia-Pacific clinicians. We restated the American Academy of Ophthalmology's Preferred Practice Patterns recommendations for management of PAC into answerable clinical questions. We asked participants at the Asia-Pacific Joint Glaucoma Congress 2010 in Taipei to rate the importance of having an answer to each question for providing effective patient care, using a Likert-type scale and scoring from 0 (not important at all) to 10 (highly important). We identified relevant SRs and mapped the evidence to clinical questions to identify evidence gaps. We generated 42 clinical questions. One hundred seventy-five individuals agreed to participate in the survey, 132 responded (75.4% response rate) and 96 completed the questionnaire (54.9% usable response rate). Questions rated important include laser iridotomy for the prevention of angle closure in primary angle-closure suspects, further therapies in eyes with plateau iris syndrome after laser iridotomy, and evaluation of the fellow eye in acute angle-closure patients for improving prognosis. Up-to-date and conclusive SR evidence was not available for any of the 42 clinical questions. We identified high priority clinical questions on the management of PAC, none of which had reliable SR evidence available. New SRs and randomized clinical trials can be initiated to address these evidence gaps.

Infliximab is superior to other biological agents for treatment of active ulcerative colitis: A meta-analysis

PubMed Central

Mei, Wei-Qun; Hu, Hui-Zhen; Liu, Ying; Li, Zhi-Chen; Wang, Wei-Guo

2015-01-01

AIM: To compare the efficacy and safety of biological agents for the treatment of active ulcerative colitis (UC). METHODS: PubMed, MEDLINE, EMBASE and the Cochrane library were searched to screen relevant articles from January 1996 to August 2014. The mixed treatment comparison meta-analysis within a Bayesian framework was performed using WinBUGS14 software. The proportions of patients reaching clinical response, clinical remission and mucosal healing in induction and maintenance phases were analyzed as efficacy indicators. Serious adverse events in maintenance phase were analyzed as safety indicators. RESULTS: The meta-analysis results showed that biological agents achieved better clinical response, clinical remission and mucosal healing than placebo. Indirect comparison indicated that in induction phase, infliximab was more effective than adalimumab in inducing clinical response (OR = 0.41, 95%CI: 0.29-0.57), clinical remission (OR = 0.33, 95%CI: 0.19-0.56) and mucosal healing (OR = 0.33, 95%CI: 0.19-0.56), and golimumab in inducing clinical response (OR = 0.66, 95%CI: 0.39-2.33) and mucosal healing (OR = 2.15, 95%CI: 1.18-4.22). No significant difference was found between placebo and biological agents regarding their safety. CONCLUSION: All biological agents were superior to placebo for UC treatment in both induction and maintenance phases with a similar safety profile, and infliximab had a better clinical effect than the other biological agents. PMID:26019471

Tools in the assessment of sarcopenia

PubMed Central

Cooper, C; Fielding, R; Visser, M; van Loon, LJ; Rolland, Y; Orwoll, E; Reid, K; Boonen, S; Dere, W; Epstein, S; Mitlak, B; Tsouderos, Y; Sayer, AA; Rizzoli, R; Reginster, JY; Kanis, JA

2013-01-01

Summary This review provides a framework for development of an operational definition of sarcopenia and of the potential endpoints that might be adopted in clinical trials among older adults. Introduction While the clinical relevance of sarcopenia is widely recognized, there is currently no universally accepted definition of the disorder. The development of interventions to alter the natural history of sarcopenia also requires consensus on the most appropriate endpoints for determining outcomes of clinical importance which might be utilised in intervention studies. Methods and results We review current approaches to the definition of sarcopenia, and the methods used for the assessment of various aspects of physical function in older people. The potential endpoints of muscle mass, muscle strength, muscle power and muscle fatigue, as well as the relationships between them, are explored with reference to the availability and practicality of the available methods for measuring these endpoints in clinical trials. Conclusions Based on current evidence, none of the four potential outcomes in question is sufficiently comprehensive to recommend as a uniform single outcome in randomised clinical trials. We propose that sarcopenia may be optimally defined (for the purposes of clinical trial inclusion criteria, as well as epidemiological studies) using a combination of measures of muscle mass and physical performance. The choice of outcome measures for clinical trials in sarcopenia is more difficult; co-primary outcomes, tailored to the specific intervention in question, may be the best way forward in this difficult but clinically important area. PMID:23842964

Assessment of the skin sensitising potency of the lower alkyl methacrylate esters.

PubMed

Kimber, Ian; Pemberton, Mark A

2014-10-01

There is continued interest in, and imperatives for, the classification of contact allergens according to their relative skin sensitising potency. However, achieving that end can prove problematic, not least when there is an apparent lack of concordance between experimental assessments of potency and the prevalence allergic contact dermatitis as judged by clinical experience. For the purpose of exploring this issue, and illustrating the important considerations that are required to reach sound judgements about potency categorisation, the lower alkyl methacrylate esters (LAM) have been employed here as a case study. Although the sensitising potential of methyl methacrylate (MMA) has been reviewed previously, there is available new information that is relevant for assessment of skin sensitising potency. Moreover, for the purposes of this article, analyses have been extended to include also other LAM for which relevant data are available: ethyl methacrylate (EMA), n-butyl methacrylate (nBMA), isobutyl methacrylate (iBMA), and 2-ethylhexyl methacrylate (EHMA). In addressing the skin sensitising activity of these chemicals and in drawing conclusions regarding relative potency, a number of sources of information has been considered, including estimates of potency derived from local lymph node assay (LLNA) data, the results of guinea pig assays, and data derived from in silico methods and from recently developed in vitro approaches. Moreover, clinical experience of skin sensitisation of humans by LAM has also been evaluated. The conclusion drawn is that MMA and other LAM are contact allergens, but that none of these chemicals has any more than weak skin sensitising potency. We have also explored here the possible bases for this modest sensitising activity. Finally, the nature of exposure to LAM has been reviewed briefly and on the basis of that information, together with an understanding of skin sensitising potency, a risk assessment has been prepared. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Retrieving clinical evidence: a comparison of PubMed and Google Scholar for quick clinical searches.

PubMed

Shariff, Salimah Z; Bejaimal, Shayna Ad; Sontrop, Jessica M; Iansavichus, Arthur V; Haynes, R Brian; Weir, Matthew A; Garg, Amit X

2013-08-15

Physicians frequently search PubMed for information to guide patient care. More recently, Google Scholar has gained popularity as another freely accessible bibliographic database. To compare the performance of searches in PubMed and Google Scholar. We surveyed nephrologists (kidney specialists) and provided each with a unique clinical question derived from 100 renal therapy systematic reviews. Each physician provided the search terms they would type into a bibliographic database to locate evidence to answer the clinical question. We executed each of these searches in PubMed and Google Scholar and compared results for the first 40 records retrieved (equivalent to 2 default search pages in PubMed). We evaluated the recall (proportion of relevant articles found) and precision (ratio of relevant to nonrelevant articles) of the searches performed in PubMed and Google Scholar. Primary studies included in the systematic reviews served as the reference standard for relevant articles. We further documented whether relevant articles were available as free full-texts. Compared with PubMed, the average search in Google Scholar retrieved twice as many relevant articles (PubMed: 11%; Google Scholar: 22%; P<.001). Precision was similar in both databases (PubMed: 6%; Google Scholar: 8%; P=.07). Google Scholar provided significantly greater access to free full-text publications (PubMed: 5%; Google Scholar: 14%; P<.001). For quick clinical searches, Google Scholar returns twice as many relevant articles as PubMed and provides greater access to free full-text articles.

Assessment of the Incorporation of Patient-Centric Outcomes in Studies of Minimally Invasive Glaucoma Surgical Devices

PubMed Central

Le, Jimmy T.; Viswanathan, Shilpa; Tarver, Michelle E.; Eydelman, Malvina; Li, Tianjing

2017-01-01

IMPORTANCE Minimally invasive glaucoma surgical (MIGS) devices are one option for lowering intraocular pressure in patients with glaucoma. OBJECTIVE To examine how often existing clinical studies of MIGS devices registered on ClinicalTrials.gov measure patient-centric outcomes that patients value directly. DESIGN, SETTING, AND PARTICIPANTS We searched ClinicalTrials.gov, a registry of publicly and privately supported clinical studies, on February 20, 2015, for records of MIGS device studies involving patients with glaucoma. Two investigators independently abstracted study design and outcome details from eligible records. We classified outcomes as patient-centric or not patient-centric using a prespecified definition. MAIN OUTCOMES AND MEASURES Proportion of patient-centric and nonpatient-centric outcomes registered on ClinicalTrials.gov. RESULTS We identified 51 eligible studies specifying 127 outcomes. Reduction in intraocular pressure was the most frequent outcome specified (78/127; 61%) and a primary outcome in 41 studies. Patient-centric outcomes—such as adverse events (n = 19; 15%), topical medication use (n = 16; 13%), visual acuity (n = 4; 3%), and health-related quality of life (n = 1; 1%)—were less frequently specified (n = 40; 32%) and a primary outcome in only 12 studies. CONCLUSION AND RELEVANCE Patient-centric outcomes that provide insight into the relative desirability and acceptability of the benefits and risks of MIGS devices are not well represented in current clinical studies. PMID:27389667

Identifying clinically relevant drug resistance genes in drug-induced resistant cancer cell lines and post- chemotherapy tissues

PubMed Central

Tong, Mengsha; Zheng, Weicheng; Lu, Xingrong; Ao, Lu; Li, Xiangyu; Guan, Qingzhou; Cai, Hao; Li, Mengyao; Yan, Haidan; Guo, You; Chi, Pan; Guo, Zheng

2015-01-01

Until recently, few molecular signatures of drug resistance identified in drug-induced resistant cancer cell models can be translated into clinical practice. Here, we defined differentially expressed genes (DEGs) between pre-chemotherapy colorectal cancer (CRC) tissue samples of non-responders and responders for 5-fluorouracil and oxaliplatin-based therapy as clinically relevant drug resistance genes (CRG5-FU/L-OHP). Taking CRG5-FU/L-OHP as reference, we evaluated the clinical relevance of several types of genes derived from HCT116 CRC cells with resistance to 5-fluorouracil and oxaliplatin, respectively. The results revealed that DEGs between parental and resistant cells, when both were treated with the corresponding drug for a certain time, were significantly consistent with the CRG5-FU/L-OHP as well as the DEGs between the post-chemotherapy CRC specimens of responders and non-responders. This study suggests a novel strategy to extract clinically relevant drug resistance genes from both drug-induced resistant cell models and post-chemotherapy cancer tissue specimens. PMID:26515599

The clinical trial landscape in oncology and connectivity of somatic mutational profiles to targeted therapies.

PubMed

Patterson, Sara E; Liu, Rangjiao; Statz, Cara M; Durkin, Daniel; Lakshminarayana, Anuradha; Mockus, Susan M

2016-01-16

Precision medicine in oncology relies on rapid associations between patient-specific variations and targeted therapeutic efficacy. Due to the advancement of genomic analysis, a vast literature characterizing cancer-associated molecular aberrations and relative therapeutic relevance has been published. However, data are not uniformly reported or readily available, and accessing relevant information in a clinically acceptable time-frame is a daunting proposition, hampering connections between patients and appropriate therapeutic options. One important therapeutic avenue for oncology patients is through clinical trials. Accordingly, a global view into the availability of targeted clinical trials would provide insight into strengths and weaknesses and potentially enable research focus. However, data regarding the landscape of clinical trials in oncology is not readily available, and as a result, a comprehensive understanding of clinical trial availability is difficult. To support clinical decision-making, we have developed a data loader and mapper that connects sequence information from oncology patients to data stored in an in-house database, the JAX Clinical Knowledgebase (JAX-CKB), which can be queried readily to access comprehensive data for clinical reporting via customized reporting queries. JAX-CKB functions as a repository to house expertly curated clinically relevant data surrounding our 358-gene panel, the JAX Cancer Treatment Profile (JAX CTP), and supports annotation of functional significance of molecular variants. Through queries of data housed in JAX-CKB, we have analyzed the landscape of clinical trials relevant to our 358-gene targeted sequencing panel to evaluate strengths and weaknesses in current molecular targeting in oncology. Through this analysis, we have identified patient indications, molecular aberrations, and targeted therapy classes that have strong or weak representation in clinical trials. Here, we describe the development and disseminate system methods for associating patient genomic sequence data with clinically relevant information, facilitating interpretation and providing a mechanism for informing therapeutic decision-making. Additionally, through customized queries, we have the capability to rapidly analyze the landscape of targeted therapies in clinical trials, enabling a unique view into current therapeutic availability in oncology.

Urokinase-receptor (u-PAR): an essential player in multiple games of cancer: a review on its role in tumor progression, invasion, metastasis, proliferation/dormancy, clinical outcome and minimal residual disease.

PubMed

Laufs, Stephanie; Schumacher, Jens; Allgayer, Heike

2006-08-01

The relevance of the u-PA system in mediating tumor-associated proteolysis, invasion and metastasis, amongst other phenomena associated with tumor progression, has been clearly demonstrated in diverse cancer entities. This review will update on the biological and clinical relevance of the urokinase-receptor (u-PAR). Specifically, the article focuses on the potential importance of u-PAR for the development of minimal residual disease in solid cancer, and in this context reviews the biological relevance of the u-PAR for tumor cell dormancy. Furthermore, transcriptional mechanisms regulating u-PAR in vitro and in vivo, and their potential clinical and therapeutic relevance in gastrointestinal cancers, are elucidated.

A Vietnamese man with selective mutism: the relevance of multiple interacting 'cultures' in clinical psychiatry.

PubMed

Hollifield, Michael; Geppert, Cynthia; Johnson, Yuam; Fryer, Carol

2003-09-01

Multiple cultural variables have effects on the psychobiology and behavioral manifestations of illness, as do patient and physician perceptions of illness. The interaction among these variables is at the heart of clinical psychiatry. This case of a Vietnamese man with selective mutism underscores the relevance of the 'cultures' of medicine, psychiatry, and war and trauma on the manifestations of illness and illness perceptions by patient and physician. The discussion focuses on how these cultures interact and play a crucial role in formulating diagnosis and treatment planning. Suggestions are given for shifts in medical education that will encourage relevant cultural paradigms to make their way into educational and clinical systems, which in turn should improve cultural competence in clinical psychiatry.

77 FR 32975 - AHRQ Workgroups on ICD-10-CM/PCS Conversion of Quality Indicators (QIs)

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-04

... relevant clinical expertise (e.g., cardiovascular disease, neurologic disease, orthopedic and musculoskeletal disease, obstetrics and gynecologic disease, surgery, critical care and pulmonary disease... measurement using administrative data in specific, relevant clinical domains (e.g., cardiovascular disease...

Barriers to retrieving patient information from electronic health record data: failure analysis from the TREC Medical Records Track.

PubMed

Edinger, Tracy; Cohen, Aaron M; Bedrick, Steven; Ambert, Kyle; Hersh, William

2012-01-01

Secondary use of electronic health record (EHR) data relies on the ability to retrieve accurate and complete information about desired patient populations. The Text Retrieval Conference (TREC) 2011 Medical Records Track was a challenge evaluation allowing comparison of systems and algorithms to retrieve patients eligible for clinical studies from a corpus of de-identified medical records, grouped by patient visit. Participants retrieved cohorts of patients relevant to 35 different clinical topics, and visits were judged for relevance to each topic. This study identified the most common barriers to identifying specific clinic populations in the test collection. Using the runs from track participants and judged visits, we analyzed the five non-relevant visits most often retrieved and the five relevant visits most often overlooked. Categories were developed iteratively to group the reasons for incorrect retrieval for each of the 35 topics. Reasons fell into nine categories for non-relevant visits and five categories for relevant visits. Non-relevant visits were most often retrieved because they contained a non-relevant reference to the topic terms. Relevant visits were most often infrequently retrieved because they used a synonym for a topic term. This failure analysis provides insight into areas for future improvement in EHR-based retrieval with techniques such as more widespread and complete use of standardized terminology in retrieval and data entry systems.

Cross-reactivity of steroid hormone immunoassays: clinical significance and two-dimensional molecular similarity prediction

PubMed Central

2014-01-01

Background Immunoassays are widely used in clinical laboratories for measurement of plasma/serum concentrations of steroid hormones such as cortisol and testosterone. Immunoassays can be performed on a variety of standard clinical chemistry analyzers, thus allowing even small clinical laboratories to do analysis on-site. One limitation of steroid hormone immunoassays is interference caused by compounds with structural similarity to the target steroid of the assay. Interfering molecules include structurally related endogenous compounds and their metabolites as well as drugs such as anabolic steroids and synthetic glucocorticoids. Methods Cross-reactivity of a structurally diverse set of compounds were determined for the Roche Diagnostics Elecsys assays for cortisol, dehydroepiandrosterone (DHEA) sulfate, estradiol, progesterone, and testosterone. These data were compared and contrasted to package insert data and published cross-reactivity studies for other marketed steroid hormone immunoassays. Cross-reactivity was computationally predicted using the technique of two-dimensional molecular similarity. Results The Roche Elecsys Cortisol and Testosterone II assays showed a wider range of cross-reactivity than the DHEA sulfate, Estradiol II, and Progesterone II assays. 6-Methylprednisolone and prednisolone showed high cross-reactivity for the cortisol assay, with high likelihood of clinically significant effect for patients administered these drugs. In addition, 21-deoxycortisol likely produces clinically relevant cross-reactivity for cortisol in patients with 21-hydroxylase deficiency, while 11-deoxycortisol may produce clinically relevant cross-reactivity in 11β-hydroxylase deficiency or following metyrapone challenge. Several anabolic steroids may produce clinically significant false positives on the testosterone assay, although interpretation is limited by sparse pharmacokinetic data for some of these drugs. Norethindrone therapy may impact immunoassay measurement of testosterone in women. Using two-dimensional similarity calculations, all compounds with high cross-reactivity also showed a high degree of similarity to the target molecule of the immunoassay. Conclusions Compounds producing cross-reactivity in steroid hormone immunoassays generally have a high degree of structural similarity to the target hormone. Clinically significant interactions can occur with structurally similar drugs (e.g., prednisolone and cortisol immunoassays; methyltestosterone and testosterone immunoassays) or with endogenous compounds such as 21-deoxycortisol that can accumulate to very high concentrations in certain disease conditions. Simple similarity calculations can help triage compounds for future testing of assay cross-reactivity. PMID:25071417

Assessing clinically meaningful treatment effects in controlled trials: chronic migraine as an example.

PubMed

Dodick, David W; Turkel, Catherine C; DeGryse, Ronald E; Diener, Hans-Christoph; Lipton, Richard B; Aurora, Sheena K; Nolan, Marissa E; Silberstein, Stephen D

2015-02-01

In addition to headache, persons with chronic migraine (CM) experience multiple symptoms, both ictal and interictal, that may contribute to their suffering. Translating clinical trial results into practice requires assessment of the results' clinical meaningfulness. When examining treatment benefit in this disabled patient population, multiple headache-symptom measures should be considered to fully reflect clinical relevance. Currently, only onabotulinumtoxinA is approved specifically for headache prophylaxis in adults with CM. Topiramate is the only other therapeutic agent with double-blind, placebo-controlled evidence in this population. Herein we evaluate the clinical meaningfulness of onabotulinumtoxinA and topiramate as headache prophylaxis in CM by comparing primary endpoints from the placebo-controlled, double-blind phase of the Phase 3 REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical program and the topiramate clinical trial (frequency of headache days [primary endpoint in PREEMPT; secondary in topiramate trial] and migraine/migrainous days [primary in topiramate trial, or "migraine/probable-migraine days"; secondary in PREEMPT]). Additionally, outcome measures such as responder rates, health-related quality of life, discontinuation rates, safety, and tolerability profiles are important clinical considerations. The clinical data indicate that statistically significant, clinically relevant treatment benefits exist for both onabotulinumtoxinA and topiramate. These data support these treatments as meaningful headache prophylaxis in adults with CM. CM is a chronic pain condition. We sought to determine the clinical relevance of recent trials in this disabled population. Clinical data indicate that statistically significant, clinically relevant treatment benefits exist for both onabotulinumtoxinA and topiramate, and support use of these treatments as meaningful headache prophylaxis in CM. Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.

Attitudes of small animal practitioners toward participation in veterinary clinical trials

PubMed Central

Gruen, Margaret E.; Griffith, Emily H.; Caney, Sarah M. A.; Rishniw, Mark; Lascelles, B. Duncan X.

2017-01-01

OBJECTIVE To determine attitudes of small animal practitioners toward veterinary clinical trials and variables influencing their likelihood of participating in such trials. DESIGN Cross-sectional survey. SAMPLE Small animal practitioners with membership in 1 of 2 online veterinary communities (n = 163 and 652). PROCEDURES An online survey was developed for each of 2 veterinary communities, and invitations to participate were sent via email. Each survey included questions designed to collect information on the respondents’ willingness to enroll their patients in clinical trials and to recommend participation to clients for their pets. RESULTS More than 80% of respondents to each survey indicated that they spend no time in clinical research. A high proportion of respondents were likely or extremely likely to recommend clinical trial participation to clients for their pets when those trials involved treatments licensed in other countries, novel treatments, respected investigators, or sponsoring by academic institutions, among other reasons. Reasons for not recommending participation included distance, time restrictions, and lack of awareness of ongoing clinical trials; 28% of respondents indicated that they did not usually learn about such clinical trials. Most respondents (79% to 92%) rated their recommendation of a trial as important to their client’s willingness to participate. CONCLUSIONS AND CLINICAL RELEVANCE Participation in veterinary clinical trials by small animal practitioners and their clients and patients appeared low. Efforts should be increased to raise practitioner awareness of clinical trials for which patients might qualify. Specific elements of trial design were identified that could be modified to increase participation. PMID:28001115

A new approach to identify, classify and count drugrelated events

PubMed Central

Bürkle, Thomas; Müller, Fabian; Patapovas, Andrius; Sonst, Anja; Pfistermeister, Barbara; Plank-Kiegele, Bettina; Dormann, Harald; Maas, Renke

2013-01-01

Aims The incidence of clinical events related to medication errors and/or adverse drug reactions reported in the literature varies by a degree that cannot solely be explained by the clinical setting, the varying scrutiny of investigators or varying definitions of drug-related events. Our hypothesis was that the individual complexity of many clinical cases may pose relevant limitations for current definitions and algorithms used to identify, classify and count adverse drug-related events. Methods Based on clinical cases derived from an observational study we identified and classified common clinical problems that cannot be adequately characterized by the currently used definitions and algorithms. Results It appears that some key models currently used to describe the relation of medication errors (MEs), adverse drug reactions (ADRs) and adverse drug events (ADEs) can easily be misinterpreted or contain logical inconsistencies that limit their accurate use to all but the simplest clinical cases. A key limitation of current models is the inability to deal with complex interactions such as one drug causing two clinically distinct side effects or multiple drugs contributing to a single clinical event. Using a large set of clinical cases we developed a revised model of the interdependence between MEs, ADEs and ADRs and extended current event definitions when multiple medications cause multiple types of problems. We propose algorithms that may help to improve the identification, classification and counting of drug-related events. Conclusions The new model may help to overcome some of the limitations that complex clinical cases pose to current paper- or software-based drug therapy safety. PMID:24007453

Impact of Hypertension on Cognitive Function

PubMed Central

Iadecola, Costantino; Yaffe, Kristine; Biller, José; Bratzke, Lisa C.; Faraci, Frank M.; Gorelick, Philip B.; Gulati, Martha; Kamel, Hooman; Knopman, David S.; Launer, Lenore J.; Saczynski, Jane S.; Seshadri, Sudha; Zeki Al Hazzouri, Adina

2017-01-01

Background Age-related dementia, most commonly caused by Alzheimer disease or cerebrovascular factors (vascular dementia), is a major public health threat. Chronic arterial hypertension is a well-established risk factor for both types of dementia, but the link between hypertension and its treatment and cognition remains poorly understood. In this scientific statement, a multidisciplinary team of experts examines the impact of hypertension on cognition to assess the state of the knowledge, to identify gaps, and to provide future directions. Methods Authors with relevant expertise were selected to contribute to this statement in accordance with the American Heart Association conflict-of-interest management policy. Panel members were assigned topics relevant to their areas of expertise, reviewed the literature, and summarized the available data. Results Hypertension disrupts the structure and function of cerebral blood vessels, leads to ischemic damage of white matter regions critical for cognitive function, and may promote Alzheimer pathology. There is strong evidence of a deleterious influence of midlife hypertension on late-life cognitive function, but the cognitive impact of late-life hypertension is less clear. Observational studies demonstrated a cumulative effect of hypertension on cerebrovascular damage, but evidence from clinical trials that antihypertensive treatment improves cognition is not conclusive. Conclusions After carefully reviewing the literature, the group concluded that there were insufficient data to make evidence-based recommendations. However, judicious treatment of hypertension, taking into account goals of care and individual characteristics (eg, age and comorbidities), seems justified to safeguard vascular health and, as a consequence, brain health. PMID:27977393

What Is New for an Old Molecule? Systematic Review and Recommendations on the Use of Resveratrol

PubMed Central

Vang, Ole; Ahmad, Nihal; Baile, Clifton A.; Baur, Joseph A.; Brown, Karen; Csiszar, Anna; Das, Dipak K.; Delmas, Dominique; Gottfried, Carmem; Lin, Hung-Yun; Ma, Qing-Yong; Mukhopadhyay, Partha; Nalini, Namasivayam; Pezzuto, John M.; Richard, Tristan; Shukla, Yogeshwer; Surh, Young-Joon; Szekeres, Thomas; Szkudelski, Tomasz; Walle, Thomas; Wu, Joseph M.

2011-01-01

Background Resveratrol is a natural compound suggested to have beneficial health effects. However, people are consuming resveratrol for this reason without having the adequate scientific evidence for its effects in humans. Therefore, scientific valid recommendations concerning the human intake of resveratrol based on available published scientific data are necessary. Such recommendations were formulated after the Resveratrol 2010 conference, held in September 2010 in Helsingør, Denmark. Methodology Literature search in databases as PubMed and ISI Web of Science in combination with manual search was used to answer the following five questions: 1Can resveratrol be recommended in the prevention or treatment of human diseases?; 2Are there observed “side effects” caused by the intake of resveratrol in humans?; 3What is the relevant dose of resveratrol?; 4What valid data are available regarding an effect in various species of experimental animals?; 5Which relevant (overall) mechanisms of action of resveratrol have been documented? Conclusions/Significance The overall conclusion is that the published evidence is not sufficiently strong to justify a recommendation for the administration of resveratrol to humans, beyond the dose which can be obtained from dietary sources. On the other hand, animal data are promising in prevention of various cancer types, coronary heart diseases and diabetes which strongly indicate the need for human clinical trials. Finally, we suggest directions for future research in resveratrol regarding its mechanism of action and its safety and toxicology in human subjects. PMID:21698226

Using mixed methods to identify and answer clinically relevant research questions.

PubMed

Shneerson, Catherine L; Gale, Nicola K

2015-06-01

The need for mixed methods research in answering health care questions is becoming increasingly recognized because of the complexity of factors that affect health outcomes. In this article, we argue for the value of using a qualitatively driven mixed method approach for identifying and answering clinically relevant research questions. This argument is illustrated by findings from a study on the self-management practices of cancer survivors and the exploration of one particular clinically relevant finding about higher uptake of self-management in cancer survivors who had received chemotherapy treatment compared with those who have not. A cross-sectional study generated findings that formed the basis for the qualitative study, by informing the purposive sampling strategy and generating new qualitative research questions. Using a quantitative research component to supplement a qualitative study can enhance the generalizability and clinical relevance of the findings and produce detailed, contextualized, and rich answers to research questions that would be unachievable through quantitative or qualitative methods alone. © The Author(s) 2015.

Musculoskeletal injuries and pain in dancers: a systematic review.

PubMed

Hincapié, Cesar A; Morton, Emily J; Cassidy, J David

2008-09-01

To assemble and synthesize the best evidence on the epidemiology, diagnosis, prognosis, treatment, and prevention of musculoskeletal injuries and pain in dancers. Medline, CINAHL, PsycINFO, Embase, and other electronic databases were searched from 1966 to 2004 using key words such as dance, dancer, dancing, athletic injuries, occupational injuries, sprains and strains, and musculoskeletal diseases. In addition, the reference lists of relevant studies were examined, specialized journals were hand-searched, and the websites of major dance associations were scanned for relevant information. Citations were screened for relevance using a priori criteria, and relevant studies were critically reviewed for scientific merit by the best evidence synthesis method. After 1865 abstracts were screened, 103 articles were reviewed, and 32 (31%) of these were accepted as scientifically admissible (representing 29 unique studies). Data from accepted studies were abstracted into evidence tables relating to the prevalence and associated factors, incidence and risk factors, diagnosis, treatment, economic costs, and prevention of musculoskeletal injuries and pain in dancers. The scientifically admissible studies consisted of 15 (52%) cohort studies, 13 (45%) cross-sectional studies, and 1 (3%) validation study of a diagnostic assessment tool. There is a high prevalence and incidence of lower extremity and back injuries, with soft tissue and overuse injuries predominating. For example, lifetime prevalence estimates for injury in professional ballet dancers ranged between 40% and 84%, while the point prevalence of minor injury in a diverse group of university and professional ballet and modern dancers was 74%. Several potential risk factors for injury are suggested by the literature, but conclusive evidence for any of these is lacking. There is preliminary evidence that comprehensive injury prevention and management strategies may help decrease the incidence of future injury. The dance medicine literature is young and heterogeneous, limiting our ability to draw consistent conclusions. Nonetheless, the best available evidence suggests that musculoskeletal injury is an important health issue for dancers at all skill levels. Better quality research is needed in this specialized area. Future research would benefit from clear and relevant research questions being addressed with appropriate study designs, use of conceptually valid and clinically meaningful case definitions of injury and pain, and better reporting of studies in line with current scientific standards.

Nutraceuticals for Skin Care: A Comprehensive Review of Human Clinical Studies

PubMed Central

Pérez-Sánchez, Almudena; Micol, Vicente

2018-01-01

The skin is the body’s largest organ, it participates in sensitivity and offers protection against microorganisms, chemicals and ultraviolet (UV) radiation. Consequently, the skin may suffer alterations such as photo-ageing, immune dysfunction and inflammation which may significantly affect human health. Nutraceuticals represent a promising strategy for preventing, delaying, or minimising premature ageing of the skin and also to alleviate certain skin disorders. Among them, bioactive peptides and oligosaccharides, plant polyphenols, carotenoids, vitamins and polyunsaturated fatty acids are the most widely used ingredients. Supplementation with these products has shown evidence of having an effect on the signs of ageing and protection against UV radiation ageing in several human trials. In this review, the most relevant human studies on skin nutraceuticals are evaluated and the statistical resolution, biological relevance of their results, and, the trial protocols are discussed. In conclusion, quality and rigorousness of the trials must be improved to build credible scientific evidence for skin nutraceuticals and to establish a cause-effect relationship between the ingredients the beneficial effects for the skin. PMID:29587342

Circulating microparticles: square the circle

PubMed Central

2013-01-01

Background The present review summarizes current knowledge about microparticles (MPs) and provides a systematic overview of last 20 years of research on circulating MPs, with particular focus on their clinical relevance. Results MPs are a heterogeneous population of cell-derived vesicles, with sizes ranging between 50 and 1000 nm. MPs are capable of transferring peptides, proteins, lipid components, microRNA, mRNA, and DNA from one cell to another without direct cell-to-cell contact. Growing evidence suggests that MPs present in peripheral blood and body fluids contribute to the development and progression of cancer, and are of pathophysiological relevance for autoimmune, inflammatory, infectious, cardiovascular, hematological, and other diseases. MPs have large diagnostic potential as biomarkers; however, due to current technological limitations in purification of MPs and an absence of standardized methods of MP detection, challenges remain in validating the potential of MPs as a non-invasive and early diagnostic platform. Conclusions Improvements in the effective deciphering of MP molecular signatures will be critical not only for diagnostics, but also for the evaluation of treatment regimens and predicting disease outcomes. PMID:23607880

Comparison of lower limb muscle activation with ballet movements (releve and demi-plie) and general movements (heel rise and squat) in healthy adults.

PubMed

Kim, Min-Ju; Kim, Joong-Hwi

2016-01-01

[Purpose] The aim of this study was to demonstrate therapeutic grounds for rehabilitation exercise approach by comparing and analyzing muscular activities of Ballet movements: the releve movement (RM) and the demi-plie movement (DM). [Methods] Four types of movements such as RM vs. heel rise (HM) and DM vs. squat movement (SM) were randomized and applied in 30 healthy male and female individuals while measuring 10-s lower limb muscular activities (gluteus maximus [GMa], gluteus medius [GMe], rectus femoris [RF], adductor longus [AL], medial gastrocnemius [MG], and lateral gastrocnemius [LG]) by using surface electromyography (EMG). [Results] Significant differences were found in GMa, GMe, AL and MG activities for DM and in all of the six muscles for RM, in particular when the two groups were compared (RM vs HM and DM vs SM). [Conclusion] The RM and DM have a greater effect on lower limb muscular force activities compared to HM and SM and could be recommended as clinical therapeutic exercises for lower limb muscle enhancement.

Comparison of lower limb muscle activation with ballet movements (releve and demi-plie) and general movements (heel rise and squat) in healthy adults

PubMed Central

Kim, Min-Ju; Kim, Joong-Hwi

2016-01-01

[Purpose] The aim of this study was to demonstrate therapeutic grounds for rehabilitation exercise approach by comparing and analyzing muscular activities of Ballet movements: the releve movement (RM) and the demi-plie movement (DM). [Methods] Four types of movements such as RM vs. heel rise (HM) and DM vs. squat movement (SM) were randomized and applied in 30 healthy male and female individuals while measuring 10-s lower limb muscular activities (gluteus maximus [GMa], gluteus medius [GMe], rectus femoris [RF], adductor longus [AL], medial gastrocnemius [MG], and lateral gastrocnemius [LG]) by using surface electromyography (EMG). [Results] Significant differences were found in GMa, GMe, AL and MG activities for DM and in all of the six muscles for RM, in particular when the two groups were compared (RM vs HM and DM vs SM). [Conclusion] The RM and DM have a greater effect on lower limb muscular force activities compared to HM and SM and could be recommended as clinical therapeutic exercises for lower limb muscle enhancement. PMID:26957762

Models and mechanisms of anxiety: evidence from startle studies

PubMed Central

Grillon, Christian

2009-01-01

Rationale Preclinical data indicates that threat stimuli elicit two classes of defensive behaviors, those that are associated with imminent danger and are characterized by avoidance or fight (fear), and those that are associated with temporally uncertain danger and are characterized by sustained apprehension and hypervigilance (anxiety). Objective To 1) review evidence for a distinction between fear and anxiety in animal and human experimental models using the startle reflex as an operational measure of aversive states, 2) describe experimental models of anxiety, as opposed to fear, in humans, 3) examine the relevance of these models to clinical anxiety. Results The distinction between phasic fear to imminent threat and sustained anxiety to temporally uncertain danger is suggested by psychopharmacological and behavioral evidence from ethological studies and can be traced back to distinct neuroanatomical systems, the amygdala and the bed nucleus of the stria terminalis. Experimental models of anxiety, not fear, are relevant to non-phobic anxiety disorders. Conclusions Progress in our understanding of normal and abnormal anxiety is critically dependent on our ability to model sustained aversive states to temporally uncertain threat. PMID:18058089

Power Calculations and Placebo Effect for Future Clinical Trials in Progressive Supranuclear Palsy

PubMed Central

Stamelou, Maria; Schöpe, Jakob; Wagenpfeil, Stefan; Ser, Teodoro Del; Bang, Jee; Lobach, Iryna Y.; Luong, Phi; Respondek, Gesine; Oertel, Wolfgang H.; Boxer, Adam L.; Höglinger, Günter U.

2016-01-01

Background Two recent randomized, placebo-controlled trials of putative disease-modifying agents (davunetide, tideglusib) in progressive supranuclear palsy (PSP) failed to show efficacy, but generated data relevant for future trials. Methods We provide sample size calculations based on data collected in 187 PSP patients assigned to placebo in these trials. A placebo effect was calculated. Results The total PSP-Rating Scale required the least number of patients per group (N = 51) to detect a 50% change in the 1-year progression and 39 when including patients with ≤ 5 years disease duration. The Schwab and England Activities of Daily Living required 70 patients per group and was highly correlated with the PSP-Rating Scale. A placebo effect was not detected in these scales. Conclusions We propose the 1-year PSP-Rating Scale score change as the single primary readout in clinical neuroprotective or disease-modifying trials. The Schwab and England Activities of Daily Living could be used as a secondary outcome. PMID:26948290

Intra-dialytic hypertension is associated with high mortality in hemodialysis patients

PubMed Central

Yoon, Kyu Tae; Gil, Hyo Wook; Hong, Sae Yong

2017-01-01

Background Intra-dialytic hypertension (IDH) is emerging as an important issue in hemodialysis patients. Its risk factors and clinical outcomes are unclear. Methods A total of 73 prevalent hemodialysis patients were enrolled. They included 14 (19.2%) patients with baseline IDH and 59 patients without IDH. Their clinical parameters, laboratory parameters, and mortality were investigated over 78 months. Results The risks factor of IDH included low serum potassium levels, low ultrafiltration, and low arm muscle area. Lower median survival was evident in the IDH group compared to the non-IDH group, but was not significantly different. After adjusting for relevant confounders for age, the IDH group displayed 2.846 times higher mortality rate than the non-IDH Group (adjusted hazard ratio: 2.846; 95% confidence interval: 1.081–7.490; P = 0.034). Conclusion IDH is associated with high mortality in hemodialysis patients. Clinicians should be aware of the risk factors. Future research studies are needed to explore the mechanisms involved in the association between IDH and mortality. PMID:28742805

Halitosis

PubMed Central

2014-01-01

Introduction Halitosis can be caused by oral disease or by respiratory tract conditions such as sinusitis, tonsillitis, and bronchiectasis, but an estimated 40% of affected individuals have no underlying organic disease. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments in people with physiological halitosis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 2013 (Clinical evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 11 studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review, we present information relating to the effectiveness and safety of the following interventions: artificial saliva; cleaning, brushing, or scraping the tongue; regular use of mouthwash; sugar-free chewing gums; and zinc toothpastes. PMID:25234037

Contractualist reasoning, HIV cure clinical trials, and the moral (ir)relevance of the risk/benefit ratio

PubMed Central

Kumar, Rahul

2017-01-01

Institutional review boards (IRB) normally require of a morally defensible clinical trial that any trial participant will benefit from the inquiry, or at least not be exposed to a significant risk of having their prospects worsened by participating. Stage 1 HIV cure trials tend not to meet this requirement. Does that show them to be morally indefensible? Utilitarian thinking about this question supports a negative answer. But one might reasonably expect a Kantian moral theory to support the conclusion that exposing trial participants to a significant risk of their prospects being worsened by their participation to be morally indefensible, on grounds that this would be a clear case of using a person as a mere means. In this paper, I argue, drawing on Kantian contractualist thinking, that requiring the risk/benefit ratio for participants be positive if a trial is to be morally defensible does not in fact gain any support from Kantian thinking about morality. PMID:27590492

Ankle sprain

PubMed Central

2010-01-01

Introduction Injury of the lateral ligament complex of the ankle joint occurs in about one in 10,000 people a day, accounting for a quarter of all sports injuries. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatment strategies for acute ankle ligament ruptures? We searched: Medline, Embase, The Cochrane Library, and other important databases up to November 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 38 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: cold treatment, diathermy, functional treatment, homeopathic ointment, immobilisation, physiotherapy, surgery, and ultrasound. PMID:21718566

Recent Advances and Future of Gene Therapy for Bone Regeneration.

PubMed

Shapiro, Galina; Lieber, Raphael; Gazit, Dan; Pelled, Gadi

2018-06-16

The purpose of this review is to discuss the recent advances in gene therapy as a treatment for bone regeneration. While most fractures heal spontaneously, patients who present with fracture nonunion suffer from prolonged pain, disability, and often require additional operations to regain musculoskeletal function. In the last few years, BMP gene delivery by means of electroporation and sonoporation resulted in repair of nonunion bone defects in mice, rats, and minipigs. Ex vivo transfection of porcine mesenchymal stem cells (MSCs) resulted in bone regeneration following implantation in vertebral defects of minipigs. Sustained release of VEGF gene from a collagen-hydroxyapatite scaffold to the mandible of a human patient was shown to be safe and osteoinductive. In conclusion, gene therapy methods for bone regeneration are systematically becoming more efficient and show proof-of-concept in clinically relevant animal models. Yet, on the pathway to clinical use, more investigation is needed to determine the safety aspects of the various techniques in terms of biodistribution, toxicity, and tumorigenicity.

Increasing clinical presence of mobile communication technology: avoiding the pitfalls.

PubMed

Visvanathan, Akila; Gibb, Alan P; Brady, Richard R W

2011-10-01

Mobile communication technologies are employed in many diverse areas of healthcare delivery to provide improved quality and efficiency of communication and facilitate increased rapidity of data or information transfer. Mobile phones enable healthcare professionals to possess a portable platform from which to provide many healthcare-related applications and are a popular means to directly communicate with colleagues and patients. As involvement of mobile communication technology in healthcare delivery continues to rapidly expand, there are also important considerations of relevance to patient safety and security as a result. Here, we review the previous evidence of reported clinical risks associated with mobile communication technology, such as electromagnetic interference, confidentiality and data security, distraction/noise, infection control, and cross contamination. In conclusion, although mobile phones provide much putative potential improvement to healthcare delivery, further evaluation and research are required to both inform and protect health professionals and users of such technology in the healthcare environment and provide the evidence base to support the provision of clear and comprehensive guidelines.

Burning mouth syndrome

PubMed Central

2008-01-01

Introduction Burning mouth syndrome mainly affects women, particularly after the menopause, when its prevalence may be 18-33%. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for burning mouth syndrome? We searched: Medline, Embase, The Cochrane Library, and other important databases up to February 2007 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 12 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: anaesthetics (local), antidepressants, benzodiazepines (topical clonazepam), benzydamine hydrochloride, cognitive behavioural therapy (CBT), dietary supplements, and hormone replacement therapy (HRT) in postmenopausal women. PMID:19450321

Integrating Query of Relational and Textual Data in Clinical Databases: A Case Study

PubMed Central

Fisk, John M.; Mutalik, Pradeep; Levin, Forrest W.; Erdos, Joseph; Taylor, Caroline; Nadkarni, Prakash

2003-01-01

Objectives: The authors designed and implemented a clinical data mart composed of an integrated information retrieval (IR) and relational database management system (RDBMS). Design: Using commodity software, which supports interactive, attribute-centric text and relational searches, the mart houses 2.8 million documents that span a five-year period and supports basic IR features such as Boolean searches, stemming, and proximity and fuzzy searching. Measurements: Results are relevance-ranked using either “total documents per patient” or “report type weighting.” Results: Non-curated medical text has a significant degree of malformation with respect to spelling and punctuation, which creates difficulties for text indexing and searching. Presently, the IR facilities of RDBMS packages lack the features necessary to handle such malformed text adequately. Conclusion: A robust IR+RDBMS system can be developed, but it requires integrating RDBMSs with third-party IR software. RDBMS vendors need to make their IR offerings more accessible to non-programmers. PMID:12509355

Are obsessive-compulsive symptoms impulsive, compulsive or both?

PubMed Central

Chamberlain, Samuel R; Leppink, Eric W.; Redden, Sarah A.; Grant, Jon E.

2017-01-01

Background The relationships between obsessive-compulsive symptoms and distinct forms of impulsivity and compulsivity are unclear. Such examination would be relevant in terms of how best to classify psychiatric disorders and in understanding candidate ‘latent traits’ that extend across a continuum between normalcy and clinical disorders. Method 515 young adults (aged 18-29 years) completed the Padua Inventory and undertook detailed clinical and neurocognitive assessments. Relationships between obsessive-compulsive symptoms and distinct types of impulsivity and compulsivity were evaluated using linear regression modelling. Results Obsessive-compulsive symptoms were significantly predicted by female gender, lower quality of life, psychiatric disorders in general (but not impulse control disorders), and worse extra-dimensional set-shifting. Obsessive-compulsive symptoms were not significantly predicted by alcohol/nicotine consumption, stop-signal reaction times, or decision-making abilities. Conclusion These data indicate that obsessive-compulsive symptoms are more related to certain forms of compulsivity than to impulsivity. These findings have important implications for diagnostic conceptualizations and neurobiological models. PMID:27234191

Economic impact of ovarian stimulation with corifollitropin alfa versus conventional daily gonadotropins in oocyte donors: a randomized study.

PubMed

Cruz, María; Alamá, Pilar; Muñoz, Manuel; Collado, Diana; Blanes, Carlos; Solbes, Enrique; Requena, Antonio

2017-06-01

Assisted reproductive technologies are well-established treatments for many types of subfertility representing substantial economic and healthcare implications for patients, healthcare providers and society as a whole. In order to optimize outcomes according to the type of gonadotrophins within an oocyte donor programme, we performed an economic evaluation based on data collected in a multicentre, prospective, randomized study within three private clinics belonging to the IVI Group. Results showed no relevant between-group differences in the clinical variables. According to the economic analysis, ovarian stimulation with corifollitropin alfa increased the overall cost of the treatment as well as the cost per retrieved and effective oocyte, although the differences were not statistically significant. In conclusion, cost savings can be achieved using cheaper gonadotrophins during ovarian stimulation. The cost of corifollitropin alfa compared with recombinant FSH and highly purified human menopausal gonadotrophin should be considered when making treatment decisions. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.