Identifying and preparing the next generation of part-time clinical teachers from dental practice.

PubMed

Radford, D R; Hellyer, P; Meakin, N; Jones, K A

2015-10-09

Part-time general dental practitioners (GDPs) and dental care professionals (DCPs) working in practice are being increasingly utilised to deliver undergraduate clinical dental education to both dental and hygiene/therapy students. As such, there is a need for appropriate recruitment processes and ongoing staff development in the different and complex role of the clinical teacher. Recently a group of experienced dental practitioners, making a journey from GDP to part-time clinical teacher, identified common themes, experiences, challenges and realisations. These were: 'what is clinical dental education?'; 'me as a clinical teacher'; and 'specific teaching issues'. The themes highlighted the complexity of dental education and the different environment of the teaching clinic from general practice. Some of the themes identified could be a starting point for the induction process to facilitate an easier transition from experienced GDP to clinical teacher. With the current demands from both students and patients alike, the 'three way dynamic of patient, student and teacher' needs to be supported if dental schools are to attract and develop the highest quality clinical teachers. It is of critical importance to give an exceptional experience to students in their clinical education as well as to patients in terms of excellent and appropriate treatment. The challenge for deans and directors of education is to find the resources to properly fund teacher recruitment, induction and the development of part-time GDPs in order to produce the expert teachers of tomorrow.

Cancer in silico drug discovery: a systems biology tool for identifying candidate drugs to target specific molecular tumor subtypes.

PubMed

San Lucas, F Anthony; Fowler, Jerry; Chang, Kyle; Kopetz, Scott; Vilar, Eduardo; Scheet, Paul

2014-12-01

Large-scale cancer datasets such as The Cancer Genome Atlas (TCGA) allow researchers to profile tumors based on a wide range of clinical and molecular characteristics. Subsequently, TCGA-derived gene expression profiles can be analyzed with the Connectivity Map (CMap) to find candidate drugs to target tumors with specific clinical phenotypes or molecular characteristics. This represents a powerful computational approach for candidate drug identification, but due to the complexity of TCGA and technology differences between CMap and TCGA experiments, such analyses are challenging to conduct and reproduce. We present Cancer in silico Drug Discovery (CiDD; scheet.org/software), a computational drug discovery platform that addresses these challenges. CiDD integrates data from TCGA, CMap, and Cancer Cell Line Encyclopedia (CCLE) to perform computational drug discovery experiments, generating hypotheses for the following three general problems: (i) determining whether specific clinical phenotypes or molecular characteristics are associated with unique gene expression signatures; (ii) finding candidate drugs to repress these expression signatures; and (iii) identifying cell lines that resemble the tumors being studied for subsequent in vitro experiments. The primary input to CiDD is a clinical or molecular characteristic. The output is a biologically annotated list of candidate drugs and a list of cell lines for in vitro experimentation. We applied CiDD to identify candidate drugs to treat colorectal cancers harboring mutations in BRAF. CiDD identified EGFR and proteasome inhibitors, while proposing five cell lines for in vitro testing. CiDD facilitates phenotype-driven, systematic drug discovery based on clinical and molecular data from TCGA. ©2014 American Association for Cancer Research.

Electrochemical sensors for identifying pyocyanin production in clinical Pseudomonas aeruginosa isolates.

PubMed

Sismaet, Hunter J; Pinto, Ameet J; Goluch, Edgar D

2017-11-15

In clinical practice, delays in obtaining culture results impact patient care and the ability to tailor antibiotic therapy. Despite the advancement of rapid molecular diagnostics, the use of plate cultures inoculated from swab samples continues to be the standard practice in clinical care. Because the inoculation culture process can take between 24 and 48h before a positive identification test can be run, there is an unmet need to develop rapid throughput methods for bacterial identification. Previous work has shown that pyocyanin can be used as a rapid, redox-active biomarker for identifying Pseudomonas aeruginosa in clinical infections. However, further validation is needed to confirm pyocyanin production occurs in all clinical strains of P. aeruginosa. Here, we validate this electrochemical detection strategy using clinical isolates obtained from patients with hospital-acquired infections or with cystic fibrosis. Square-wave voltammetric scans of 94 different clinical P. aeruginosa isolates were taken to measure the concentration of pyocyanin. The results showed that all isolates produced measureable concentrations of pyocyanin with production rates correlated with patient symptoms and comorbidity. Further bioinformatics analysis confirmed that 1649 genetically sequenced strains (99.9%) of P. aeruginosa possess the two genes (PhzM and PhzS) necessary to produce pyocyanin, supporting the specificity of this biomarker. Confirming the production of pyocyanin by all clinically-relevant strains of P. aeruginosa is a significant step towards validating this strategy for rapid, point-of-care diagnostics. Copyright © 2017 Elsevier B.V. All rights reserved.

Sub-grouping patients with non-specific low back pain based on cluster analysis of discriminatory clinical items.

PubMed

Billis, Evdokia; McCarthy, Christopher J; Roberts, Chris; Gliatis, John; Papandreou, Maria; Gioftsos, George; Oldham, Jacqueline A

2013-02-01

To identify potential subgroups amongst patients with non-specific low back pain based on a consensus list of potentially discriminatory examination items. Exploratory study. A convenience sample of 106 patients with non-specific low back pain (43 males, 63 females, mean age 36 years, standard deviation 15.9 years) and 7 physiotherapists. Based on 3 focus groups and a two-round Delphi involving 23 health professionals and a random stratified sample of 150 physiotherapists, respectively, a comprehensive examination list comprising the most "discriminatory" items was compiled. Following reliability analysis, the most reliable clinical items were assessed with a sample of patients with non-specific low back pain. K-means cluster analysis was conducted for 2-, 3- and 4-cluster options to explore for meaningful homogenous subgroups. The most clinically meaningful cluster was a two-subgroup option, comprising a small group (n = 24) with more severe clinical presentation (i.e. more widespread pain, functional and sleeping problems, other symptoms, increased investigations undertaken, more severe clinical signs, etc.) and a larger less dysfunctional group (n = 80). A number of potentially discriminatory clinical items were identified by health professionals and sub-classified, based on a sample of patients with non-specific low back pain, into two subgroups. However, further work is needed to validate this classification process.

Clinical and Public Health Considerations in Urine Drug Testing to Identify and Treat Substance Use.

PubMed

Barthwell, Andrea G

2016-05-11

To expand appropriate use of substance use testing, practitioners must increase their knowledge of the appropriate methodology, scope, and frequency. Yet, there is a current lack of accepted guidelines on clinical testing to identify and treat substance use. This article (1) conveys the importance of substance use testing as a clinical and public health response to trends of prescription drug abuse and increased access to medical and commercialized marijuana; (2) summarizes central features of the rapidly evolving science and the practice of patient-centered substance use testing in a clinical setting; and (3) provides recommendations that balance costs and benefits and serve as a starting point for appropriate testing to prevent, identify, and treat substance use disorders. The author conducted a search of peer-reviewed and government-supported articles and books in electronic databases and used her own knowledge and clinical experience. The author makes recommendations for determining the methodology, scope, and frequency of testing in each stage of care based on clinical considerations and methodological factors. Conclusion/Importance: Integrating sensible substance use testing broadly into clinical health care to identify substance use, diagnose substance use disorders, and guide patients into treatment can improve health outcomes and reduce the costs of substance use and addiction. No single testing regimen is suitable for all clinical scenarios; rather, a multitude of options, as discussed herein, can be adapted to meet a patient's unique needs. Ultimately, the practitioner must combine patient-specific information with knowledge of test technologies, capabilities, limitations, and costs.

Genome-wide association study of clinically defined gout identifies multiple risk loci and its association with clinical subtypes.

PubMed

Matsuo, Hirotaka; Yamamoto, Ken; Nakaoka, Hirofumi; Nakayama, Akiyoshi; Sakiyama, Masayuki; Chiba, Toshinori; Takahashi, Atsushi; Nakamura, Takahiro; Nakashima, Hiroshi; Takada, Yuzo; Danjoh, Inaho; Shimizu, Seiko; Abe, Junko; Kawamura, Yusuke; Terashige, Sho; Ogata, Hiraku; Tatsukawa, Seishiro; Yin, Guang; Okada, Rieko; Morita, Emi; Naito, Mariko; Tokumasu, Atsumi; Onoue, Hiroyuki; Iwaya, Keiichi; Ito, Toshimitsu; Takada, Tappei; Inoue, Katsuhisa; Kato, Yukio; Nakamura, Yukio; Sakurai, Yutaka; Suzuki, Hiroshi; Kanai, Yoshikatsu; Hosoya, Tatsuo; Hamajima, Nobuyuki; Inoue, Ituro; Kubo, Michiaki; Ichida, Kimiyoshi; Ooyama, Hiroshi; Shimizu, Toru; Shinomiya, Nariyoshi

2016-04-01

Gout, caused by hyperuricaemia, is a multifactorial disease. Although genome-wide association studies (GWASs) of gout have been reported, they included self-reported gout cases in which clinical information was insufficient. Therefore, the relationship between genetic variation and clinical subtypes of gout remains unclear. Here, we first performed a GWAS of clinically defined gout cases only. A GWAS was conducted with 945 patients with clinically defined gout and 1213 controls in a Japanese male population, followed by replication study of 1048 clinically defined cases and 1334 controls. Five gout susceptibility loci were identified at the genome-wide significance level (p<5.0×10(-8)), which contained well-known urate transporter genes (ABCG2 and SLC2A9) and additional genes: rs1260326 (p=1.9×10(-12); OR=1.36) of GCKR (a gene for glucose and lipid metabolism), rs2188380 (p=1.6×10(-23); OR=1.75) of MYL2-CUX2 (genes associated with cholesterol and diabetes mellitus) and rs4073582 (p=6.4×10(-9); OR=1.66) of CNIH-2 (a gene for regulation of glutamate signalling). The latter two are identified as novel gout loci. Furthermore, among the identified single-nucleotide polymorphisms (SNPs), we demonstrated that the SNPs of ABCG2 and SLC2A9 were differentially associated with types of gout and clinical parameters underlying specific subtypes (renal underexcretion type and renal overload type). The effect of the risk allele of each SNP on clinical parameters showed significant linear relationships with the ratio of the case-control ORs for two distinct types of gout (r=0.96 [p=4.8×10(-4)] for urate clearance and r=0.96 [p=5.0×10(-4)] for urinary urate excretion). Our findings provide clues to better understand the pathogenesis of gout and will be useful for development of companion diagnostics. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

ContextD: an algorithm to identify contextual properties of medical terms in a Dutch clinical corpus.

PubMed

Afzal, Zubair; Pons, Ewoud; Kang, Ning; Sturkenboom, Miriam C J M; Schuemie, Martijn J; Kors, Jan A

2014-11-29

In order to extract meaningful information from electronic medical records, such as signs and symptoms, diagnoses, and treatments, it is important to take into account the contextual properties of the identified information: negation, temporality, and experiencer. Most work on automatic identification of these contextual properties has been done on English clinical text. This study presents ContextD, an adaptation of the English ConText algorithm to the Dutch language, and a Dutch clinical corpus. We created a Dutch clinical corpus containing four types of anonymized clinical documents: entries from general practitioners, specialists' letters, radiology reports, and discharge letters. Using a Dutch list of medical terms extracted from the Unified Medical Language System, we identified medical terms in the corpus with exact matching. The identified terms were annotated for negation, temporality, and experiencer properties. To adapt the ConText algorithm, we translated English trigger terms to Dutch and added several general and document specific enhancements, such as negation rules for general practitioners' entries and a regular expression based temporality module. The ContextD algorithm utilized 41 unique triggers to identify the contextual properties in the clinical corpus. For the negation property, the algorithm obtained an F-score from 87% to 93% for the different document types. For the experiencer property, the F-score was 99% to 100%. For the historical and hypothetical values of the temporality property, F-scores ranged from 26% to 54% and from 13% to 44%, respectively. The ContextD showed good performance in identifying negation and experiencer property values across all Dutch clinical document types. Accurate identification of the temporality property proved to be difficult and requires further work. The anonymized and annotated Dutch clinical corpus can serve as a useful resource for further algorithm development.

Clinical significance of specific autoantibodies in juvenile dermatomyositis.

PubMed

Feldman, B M; Reichlin, M; Laxer, R M; Targoff, I N; Stein, L D; Silverman, E D

1996-10-01

To determine the prevalence and clinical association of myositis specific antibodies in an unselected group of patients with juvenile dermatomyositis (DM). The sera of 42 subjects, representing an unselected group of patients from a single center, with juvenile DM and 7 others with idiopathic inflammatory myopathy (IIM) were examined for the presence of myositis specific antibodies by immunodiffusion against calf thymus extract and immunoprecipitation with HeLa extract. Of the subjects with juvenile DM, only 2 had evidence of antibodies specific to myositis (anti-Mi2). Three other patients with juvenile DM had defined autoantibodies not usually considered to be specific to myositis. Two of the 3 subjects had anti-PM-Scl; both developed features of scleroderma after the juvenile DM remitted. The 5 subjects with defined autoantibodies did not differ clinically from the remainder of the subjects with the exception of the late development of scleroderma features in 2. Fourteen other subjects with juvenile DM had unidentified bands on immunoprecipitation, which may represent as yet undiscovered myositis specific antibodies. No myositis specific antibodies were detected in any of the 7 subjects with other IIM syndromes. Based on our findings, we do not recommend routine clinical testing for these antibodies in children with typical juvenile DM. Further study of the unidentified bands seen in our subjects may lead to better understanding of the clinical groupings and etiopathogenesis of childhood myositis.

Identifying influenza-like illness presentation from unstructured general practice clinical narrative using a text classifier rule-based expert system versus a clinical expert.

PubMed

MacRae, Jayden; Love, Tom; Baker, Michael G; Dowell, Anthony; Carnachan, Matthew; Stubbe, Maria; McBain, Lynn

2015-10-06

We designed and validated a rule-based expert system to identify influenza like illness (ILI) from routinely recorded general practice clinical narrative to aid a larger retrospective research study into the impact of the 2009 influenza pandemic in New Zealand. Rules were assessed using pattern matching heuristics on routine clinical narrative. The system was trained using data from 623 clinical encounters and validated using a clinical expert as a gold standard against a mutually exclusive set of 901 records. We calculated a 98.2 % specificity and 90.2 % sensitivity across an ILI incidence of 12.4 % measured against clinical expert classification. Peak problem list identification of ILI by clinical coding in any month was 9.2 % of all detected ILI presentations. Our system addressed an unusual problem domain for clinical narrative classification; using notational, unstructured, clinician entered information in a community care setting. It performed well compared with other approaches and domains. It has potential applications in real-time surveillance of disease, and in assisted problem list coding for clinicians. Our system identified ILI presentation with sufficient accuracy for use at a population level in the wider research study. The peak coding of 9.2 % illustrated the need for automated coding of unstructured narrative in our study.

Inferring Gene Family Histories in Yeast Identifies Lineage Specific Expansions

PubMed Central

Ames, Ryan M.; Money, Daniel; Lovell, Simon C.

2014-01-01

The complement of genes found in the genome is a balance between gene gain and gene loss. Knowledge of the specific genes that are gained and lost over evolutionary time allows an understanding of the evolution of biological functions. Here we use new evolutionary models to infer gene family histories across complete yeast genomes; these models allow us to estimate the relative genome-wide rates of gene birth, death, innovation and extinction (loss of an entire family) for the first time. We show that the rates of gene family evolution vary both between gene families and between species. We are also able to identify those families that have experienced rapid lineage specific expansion/contraction and show that these families are enriched for specific functions. Moreover, we find that families with specific functions are repeatedly expanded in multiple species, suggesting the presence of common adaptations and that these family expansions/contractions are not random. Additionally, we identify potential specialisations, unique to specific species, in the functions of lineage specific expanded families. These results suggest that an important mechanism in the evolution of genome content is the presence of lineage-specific gene family changes. PMID:24921666

Strategies to design clinical studies to identify predictive biomarkers in cancer research.

PubMed

Perez-Gracia, Jose Luis; Sanmamed, Miguel F; Bosch, Ana; Patiño-Garcia, Ana; Schalper, Kurt A; Segura, Victor; Bellmunt, Joaquim; Tabernero, Josep; Sweeney, Christopher J; Choueiri, Toni K; Martín, Miguel; Fusco, Juan Pablo; Rodriguez-Ruiz, Maria Esperanza; Calvo, Alfonso; Prior, Celia; Paz-Ares, Luis; Pio, Ruben; Gonzalez-Billalabeitia, Enrique; Gonzalez Hernandez, Alvaro; Páez, David; Piulats, Jose María; Gurpide, Alfonso; Andueza, Mapi; de Velasco, Guillermo; Pazo, Roberto; Grande, Enrique; Nicolas, Pilar; Abad-Santos, Francisco; Garcia-Donas, Jesus; Castellano, Daniel; Pajares, María J; Suarez, Cristina; Colomer, Ramon; Montuenga, Luis M; Melero, Ignacio

2017-02-01

The discovery of reliable biomarkers to predict efficacy and toxicity of anticancer drugs remains one of the key challenges in cancer research. Despite its relevance, no efficient study designs to identify promising candidate biomarkers have been established. This has led to the proliferation of a myriad of exploratory studies using dissimilar strategies, most of which fail to identify any promising targets and are seldom validated. The lack of a proper methodology also determines that many anti-cancer drugs are developed below their potential, due to failure to identify predictive biomarkers. While some drugs will be systematically administered to many patients who will not benefit from them, leading to unnecessary toxicities and costs, others will never reach registration due to our inability to identify the specific patient population in which they are active. Despite these drawbacks, a limited number of outstanding predictive biomarkers have been successfully identified and validated, and have changed the standard practice of oncology. In this manuscript, a multidisciplinary panel reviews how those key biomarkers were identified and, based on those experiences, proposes a methodological framework-the DESIGN guidelines-to standardize the clinical design of biomarker identification studies and to develop future research in this pivotal field. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Combinatorial Drug Screening Identifies Ewing Sarcoma-specific Sensitivities.

PubMed

Radic-Sarikas, Branka; Tsafou, Kalliopi P; Emdal, Kristina B; Papamarkou, Theodore; Huber, Kilian V M; Mutz, Cornelia; Toretsky, Jeffrey A; Bennett, Keiryn L; Olsen, Jesper V; Brunak, Søren; Kovar, Heinrich; Superti-Furga, Giulio

2017-01-01

Improvements in survival for Ewing sarcoma pediatric and adolescent patients have been modest over the past 20 years. Combinations of anticancer agents endure as an option to overcome resistance to single treatments caused by compensatory pathways. Moreover, combinations are thought to lessen any associated adverse side effects through reduced dosing, which is particularly important in childhood tumors. Using a parallel phenotypic combinatorial screening approach of cells derived from three pediatric tumor types, we identified Ewing sarcoma-specific interactions of a diverse set of targeted agents including approved drugs. We were able to retrieve highly synergistic drug combinations specific for Ewing sarcoma and identified signaling processes important for Ewing sarcoma cell proliferation determined by EWS-FLI1 We generated a molecular target profile of PKC412, a multikinase inhibitor with strong synergistic propensity in Ewing sarcoma, revealing its targets in critical Ewing sarcoma signaling routes. Using a multilevel experimental approach including quantitative phosphoproteomics, we analyzed the molecular rationale behind the disease-specific synergistic effect of simultaneous application of PKC412 and IGF1R inhibitors. The mechanism of the drug synergy between these inhibitors is different from the sum of the mechanisms of the single agents. The combination effectively inhibited pathway crosstalk and averted feedback loop repression, in EWS-FLI1-dependent manner. Mol Cancer Ther; 16(1); 88-101. ©2016 AACR. ©2016 American Association for Cancer Research.

TH-B-BRC-01: How to Identify and Resolve Potential Clinical Errors

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

Das, I.

2016-06-15

Radiation treatment consists of a chain of events influenced by the quality of machine operation, beam data commissioning, machine calibration, patient specific data, simulation, treatment planning, imaging and treatment delivery. There is always a chance that the clinical medical physicist may make or fail to detect an error in one of the events that may impact on the patient’s treatment. In the clinical scenario, errors may be systematic and, without peer review, may have a low detectability because they are not part of routine QA procedures. During treatment, there might be errors on machine that needs attention. External reviews ofmore » some of the treatment delivery components by independent reviewers, like IROC, can detect errors, but may not be timely. The goal of this session is to help junior clinical physicists identify potential errors as well as the approach of quality assurance to perform a root cause analysis to find and eliminate an error and to continually monitor for errors. A compilation of potential errors will be presented by examples of the thought process required to spot the error and determine the root cause. Examples may include unusual machine operation, erratic electrometer reading, consistent lower electron output, variation in photon output, body parts inadvertently left in beam, unusual treatment plan, poor normalization, hot spots etc. Awareness of the possibility and detection of error in any link of the treatment process chain will help improve the safe and accurate delivery of radiation to patients. Four experts will discuss how to identify errors in four areas of clinical treatment. D. Followill, NIH grant CA 180803.« less

Method To Identify Specific Inhibiutors Of Imp Dehydrogenase

DOEpatents

Collart, Frank R.; Huberman, Eliezer

2000-11-28

This invention relates to methods to identify specific inhibitors of the purine nucleotide synthesis enzyme, IMP dehydrogenase (IMPDH). IMPDH is an essential enzyme found in all free-living organisms from humans to bacteria and is an important therapeutic target. The invention allows the identification of specific inhibitors of any IMPDH enzyme which can be expressed in a functional form in a recombinant host cell. A variety of eukaryotic or prokaryotic host systems commonly used for the expression of recombinant proteins are suitable for the practice of the invention. The methods are amenable to high throughput systems for the screening of inhibitors generated by combinatorial chemistry or other methods such as antisense molecule production. Utilization of exogenous guanosine as a control component of the methods allows for the identification of inhibitors specific for IMPDH rather than other causes of decreased cell proliferation.

Challenges of Identifying Clinically Actionable Genetic Variants for Precision Medicine

PubMed Central

2016-01-01

Advances in genomic medicine have the potential to change the way we treat human disease, but translating these advances into reality for improving healthcare outcomes depends essentially on our ability to discover disease- and/or drug-associated clinically actionable genetic mutations. Integration and manipulation of diverse genomic data and comprehensive electronic health records (EHRs) on a big data infrastructure can provide an efficient and effective way to identify clinically actionable genetic variants for personalized treatments and reduce healthcare costs. We review bioinformatics processing of next-generation sequencing (NGS) data, bioinformatics infrastructures for implementing precision medicine, and bioinformatics approaches for identifying clinically actionable genetic variants using high-throughput NGS data and EHRs. PMID:27195526

Clinical expression of haemochromatosis in Irish C282Y homozygotes identified through family screening.

PubMed

Gleeson, F; Ryan, E; Barrett, S; Crowe, J

2004-09-01

In Ireland, the homozygote frequency of the C282Y mutation in the HFE gene is 1/83. The biochemical expression of this mutation is high in haemochromatosis (HH) individuals identified through family screening, but the clinical expression of the mutation in Irish HH subjects to date has not been investigated fully. To determine the clinical, biochemical and histological penetrance of the C282Y mutation in Irish C282Y homozygotes identified through family screening. Two hundred and nine C282Y homozygous individuals comprising of 172 first-degree relatives, 31 second-degree relatives and four unrelated individuals were identified following HFE mutation analysis of 167 families. The following variables were analysed: age at identification, gender, fasting transferrin saturation, fasting serum ferritin, liver enzymes, clinical symptomatology, liver histopathology and histochemical iron staining. An elevated transferrin saturation in combination with an elevated ferritin was present in 43.4% of males and 23.3% of females. Abnormal liver enzymes were found in 32.3% of males. Diabetes, a haemochromatosis-specific association, was noted in 2.8% of males. Of those individuals requiring liver histopathology evaluation, 38% had moderate-to-severe iron staining, and 42% had fibrosis; 2.8% of the biopsied cohort had cirrhosis. Thus, HH cirrhotics were identified in less than 1% of the screened population. Although the homozygote frequency in Ireland is very high, the prevalence of advanced liver disease was less than 1% of the family members screened. Nevertheless, 42% of biopsied patients had histological evidence of iron overload-related architectural change and 2.8% had cirrhosis. This cohort of young people had previously unrecognized biochemical iron overload and histopathological change. This emphasizes the importance and value of both genetic and biochemical screening in first-degree relatives of identified homozygotes.

Movement of Genetic Counselors from Clinical to Non-clinical Positions: Identifying Driving Forces.

PubMed

Cohen, Stephanie A; Tucker, Megan E

2018-03-05

A previous study of genetic counselors (GCs) in the state of Indiana identified movement out of clinical positions within the past 2 years. The aims of this study were to determine if this trend is nationwide and identify reasons why GCs are leaving their positions and factors that might help employers attract and retain GCs. An email was sent to members of the American Board of Genetic Counseling with a link to an online confidential survey. There were 939 responses (23.5% response rate). Overall, 52% of GCs report being highly satisfied in their current position, although almost two thirds think about leaving and one third had changed jobs within the past 2 years. Of those who had changed jobs (n = 295), 74.9% had been working in a hospital/clinic setting but only 46.3% currently do, demonstrating a major shift out of the clinic (p < 0.001). The top three reasons cited for leaving a position were work environment/institutional climate, salary/benefits, and a lack of feeling valued/recognized as a professional. These results confirm that GCs are moving out of clinical positions and document elements of job satisfaction. We suggest points for employers to consider when trying to recruit or retain GCs.

Clinical staff nurse leadership: Identifying gaps in competency development.

PubMed

Franks-Meeks, Sherron

2018-01-01

To date, there has been no development of a complete, applicable inventory of clinical staff nurse (CSN) leadership role competencies through a valid and reliable methodology. Further, the CSN has not been invited to engage in the identification, definition, or development of their own leadership competencies. Compare existing leadership competencies to identify and highlight gaps in clinical staff nurse leadership role competency development and validation. Literature review. The CSN has not participated in the development of CSN leadership role competencies, nor have the currently identified CSN leadership role competencies been scientifically validated through research. Finally, CSN leadership role competencies are incomplete and do not reflect the CSN perspective. © 2017 Wiley Periodicals, Inc.

GSK's antigen-specific cancer immunotherapy programme: pilot results leading to Phase III clinical development.

PubMed

Brichard, Vincent G; Lejeune, Diane

2007-09-27

From the first evidence that the immune system could recognize tumors, different types of tumor antigens have been identified and deeply characterized. Several different approaches aimed at targeting these antigens have already been the subject of clinical studies. In this field, the GSK Biologicals' approach relying on recombinant proteins combined with an immunological Adjuvant System in a specific clinical setting, has entertained hopes of developing a new class of well tolerated anti-cancer therapy. This methodology led to promising advances with MAGE-A3 immunotherapy in NSCLC and has the potential to be applied to all tumor types.

Cluster Analysis of Clinical Data Identifies Fibromyalgia Subgroups

PubMed Central

Docampo, Elisa; Collado, Antonio; Escaramís, Geòrgia; Carbonell, Jordi; Rivera, Javier; Vidal, Javier; Alegre, José

2013-01-01

Introduction Fibromyalgia (FM) is mainly characterized by widespread pain and multiple accompanying symptoms, which hinder FM assessment and management. In order to reduce FM heterogeneity we classified clinical data into simplified dimensions that were used to define FM subgroups. Material and Methods 48 variables were evaluated in 1,446 Spanish FM cases fulfilling 1990 ACR FM criteria. A partitioning analysis was performed to find groups of variables similar to each other. Similarities between variables were identified and the variables were grouped into dimensions. This was performed in a subset of 559 patients, and cross-validated in the remaining 887 patients. For each sample and dimension, a composite index was obtained based on the weights of the variables included in the dimension. Finally, a clustering procedure was applied to the indexes, resulting in FM subgroups. Results Variables clustered into three independent dimensions: “symptomatology”, “comorbidities” and “clinical scales”. Only the two first dimensions were considered for the construction of FM subgroups. Resulting scores classified FM samples into three subgroups: low symptomatology and comorbidities (Cluster 1), high symptomatology and comorbidities (Cluster 2), and high symptomatology but low comorbidities (Cluster 3), showing differences in measures of disease severity. Conclusions We have identified three subgroups of FM samples in a large cohort of FM by clustering clinical data. Our analysis stresses the importance of family and personal history of FM comorbidities. Also, the resulting patient clusters could indicate different forms of the disease, relevant to future research, and might have an impact on clinical assessment. PMID:24098674

Clinical and pathological tools for identifying microsatellite instability in colorectal cancer

PubMed Central

Krivokapić, Zoran; Marković, Srdjan; Antić, Jadranka; Dimitrijević, Ivan; Bojić, Daniela; Svorcan, Petar; Jojić, Njegica; Damjanović, Svetozar

2012-01-01

Aim To assess practical accuracy of revised Bethesda criteria (BGrev), pathological predictive model (MsPath), and histopathological parameters for detection of high-frequency of microsatellite instability (MSI-H) phenotype in patients with colorectal carcinoma (CRC). Method Tumors from 150 patients with CRC were analyzed for MSI using a fluorescence-based pentaplex polymerase chain reaction technique. For all patients, we evaluated age, sex, family history of cancer, localization, tumor differentiation, mucin production, lymphocytic infiltration (TIL), and Union for International Cancer Control stage. Patients were classified according to the BGrev, and the groups were compared. The utility of the BGrev, MsPath, and clinical and histopathological parameters for predicting microsatellite tumor status were assessed by univariate logistic regression analysis and by calculating the sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values. Results Fifteen out of 45 patients who met and 4 of 105 patients who did not meet the BGrev criteria had MSI-H CRC. Sensitivity, specificity, PPV, and NPV for BGrev were 78.9%, 77%, 30%, and 70%, respectively. MSI histology (the third BGrev criterion without age limit) was as sensitive as BGrev, but more specific. MsPath model was more sensitive than BGrev (86%), with similar specificity. Any BGrev criterion fulfillment, mucinous differentiation, and right-sided CRC were singled out as independent factors to identify MSI-H colorectal cancer. Conclusion The BGrev, MsPath model, and MSI histology are useful tools for selecting patients for MSI testing. PMID:22911525

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

Persistent fatigue in young athletes: measuring the clinical course and identifying variables affecting clinical recovery.

PubMed

Locke, S; Osborne, M; O'Rourke, P

2011-02-01

The objective of this paper is to measure the clinical course (months) in young athletes with persistent fatigue and to identify any covariates affecting the duration of recovery. This was a prospective longitudinal study of 68 athletes; 87% were elite (42 males, 26 females), aged 20.5±3.74 years (SD), who presented with the symptom of persistent fatigue. The collective duration to full clinical recovery was estimated using Kaplan-Meier product-limit curves, and covariates associated with prolonging recovery were identified from Cox proportional hazard models. The median recovery was 5 months (range 1-60 months). The range of presenting symptom duration was 0.5-36 months. The covariates identified were an increased duration of presenting symptoms [hazard ratio (HR), 1.06; 95% confidence interval (CI), 1.02-1.12; P=0.005] and the response of serum cortisol concentration to a standard exercise challenge (HR, 1.92; 95% CI, 1.09-3.38; P=0.03). Delay in recovery was not associated with categories of fatigue that included medical, training-related diagnoses, or other causes. In conclusion, the fatigued athlete represents a significant clinical problem with a median recovery of 5 months, whose collective clinical course to recovery can be estimated by Kaplan-Meier curves and appears to be a continuum. © 2009 John Wiley & Sons A/S.

Clinically Identified Postpartum Depression in Asian American Mothers

PubMed Central

Goyal, Deepika; Wang, Elsie J.; Shen, Jeremy; Wong, Eric C.; Palaniappan, Latha P.

2015-01-01

Objective To identify the clinical diagnosis rate of postpartum depression (PPD) in Asian American subgroups (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese) compared to non-Hispanic Whites. Design Cross-sectional study using electronic health records (EHR). Setting A large, outpatient, multiservice clinic in Northern California. Participants A diverse clinical population of non-Hispanic White (N = 4582), Asian Indian (N = 1264), Chinese (N = 1160), Filipino (N = 347), Japanese (N = 124), Korean (N = 183), and Vietnamese (N = 147) mothers. Methods Cases of PPD were identified from EHRs using physician diagnosis codes, medication usage, and age standardized for comparison. The relationship between PPD and other demographic variables (race/ethnicity, maternal age, delivery type, marital status, and infant gender) were examined in a multivariate logistic regression model. Results The PPD diagnosis rate for all Asian American mothers in aggregate was significantly lower than the diagnosis rate in non-Hispanic White mothers. Moreover, of the six Asian American subgroups, PPD diagnosis rates for Asian Indian, Chinese, and Filipino mothers were significantly lower than non-Hispanic White mothers. In multivariate analyses, race/ethnicity, age, and cesarean were significant predictors of PPD. Conclusion In this insured population, PPD diagnosis rates were lower among Asian Americans, with variability in rates across the individual Asian American subgroups. It is unclear whether these lower rates are due to underreporting, underdiagnosis, or underutilization of mental health care in this setting. PMID:22536783

Identifying randomized clinical trials in Spanish-language dermatology journals.

PubMed

Sanclemente, G; Pardo, H; Sánchez, S; Bonfill, X

2015-06-01

The necessary foundation for good clinical practice lies in knowledge derived from clinical research. Evidence from randomized clinical trials (RCTs) is the pillar on which decisions about therapy are based. To search exhaustively and rigorously to identify RCTs in dermatology journals published in Spanish. We located dermatology journals through the following search engines and indexes: PubMed, LILACS, SciELO, Periódica, Latindex, Índice Médico Español, C-17, IBECS, EMBASE, and IMBIOMED. We also sought information through dermatology associations and dermatologists in countries where Spanish was the usual language of publication, and we searched the Internet (Google). Afterwards we searched the journals electronically and manually to identify RCTs in all available volumes and issues, checking from the year publication started through 2012. Of 28 journals identified, we included 21 in the search. We found a total of 144 RCTs published since 1969; 78 (54%) were in Latin American journals and 66 (46%) were in Spanish journals. The most frequent disease contexts for RCTs in Spanish journals were psoriasis, mycoses, and acne vulgaris. In Latin American journals, the most frequent disease contexts were common warts, mycoses, acne vulgaris, and skin ulcers on the lower limbs. Manual searches identified more RCTs than electronic searches. Manual searches found a larger number of RCTs. Relatively fewer RCTs are published in Spanish and Latin American journals than in English-language journals. Internet facilitated access to full texts published by many journals; however, free open access to these texts is still unavailable and a large number of journal issues are still not posted online. Copyright © 2014 Elsevier España, S.L.U. and AEDV. All rights reserved.

Instruments to identify prescription medication misuse, abuse, and related events in clinical trials: an ACTTION systematic review

PubMed Central

Smith, Shannon M.; Paillard, Florence; McKeown, Andrew; Burke, Laurie B.; Edwards, Robert R.; Katz, Nathaniel P.; Papadopoulos, Elektra J.; Rappaport, Bob A.; Slagle, Ashley; Strain, Eric C.; Wasan, Ajay D.; Turk, Dennis C.; Dworkin, Robert H.

2017-01-01

Measurement of inappropriate medication use events (e.g., abuse, misuse) in clinical trials is important in characterizing a medication’s abuse potential. However, no “gold standard” assessment of inappropriate use events in clinical trials has been identified. In this systematic review, we examine the measurement properties (i.e., content validity, cross-sectional reliability and construct validity, longitudinal construct validity, ability to detect change, and responder definitions) of instruments assessing inappropriate use of opioid and non-opioid prescription medications to identify any that meet U.S. and European regulatory agencies’ rigorous standards for outcome measures in clinical trials. Sixteen published instruments were identified, most of which were not designed for the selected concept of interest and context of use. For this reason, many instruments were found to lack adequate content validity (or documentation of content validity) to evaluate current inappropriate medication use events; for example, evaluating inappropriate use across the lifespan rather than current use, including items that did not directly assess inappropriate use (e.g., questions about anger), or failing to capture information pertinent to inappropriate use events (e.g., intention, route of administration). In addition, the psychometric data across all instruments were generally limited in scope. A further limitation is the heterogeneous, non-standardized use of inappropriate medication use terminology. These observations suggest that available instruments are not well suited for assessing current inappropriate medication use within the specific context of clinical trials. Further effort is needed to develop reliable and valid instruments to measure current inappropriate medication use events in clinical trials. PMID:25660826

Sparse Feature Selection Identifies H2A.Z as a Novel, Pattern-Specific Biomarker for Asymmetrically Self-Renewing Distributed Stem Cells

PubMed Central

Huh, Yang Hoon; Noh, Minsoo; Burden, Frank R.; Chen, Jennifer C.; Winkler, David A.; Sherley, James L.

2015-01-01

There is a long-standing unmet clinical need for biomarkers with high specificity for distributed stem cells (DSCs) in tissues, or for use in diagnostic and therapeutic cell preparations (e.g., bone marrow). Although DSCs are essential for tissue maintenance and repair, accurate determination of their numbers for medical applications has been problematic. Previous searches for biomarkers expressed specifically in DSCs were hampered by difficulty obtaining pure DSCs and by the challenges in mining complex molecular expression data. To identify DSC such useful and specific biomarkers, we combined a novel sparse feature selection method with combinatorial molecular expression data focused on asymmetric self-renewal, a conspicuous property of DSCs. The analysis identified reduced expression of the histone H2A variant H2A.Z as a superior molecular discriminator for DSC asymmetric self-renewal. Subsequent molecular expression studies showed H2A.Z to be a novel “pattern-specific biomarker” for asymmetrically self-renewing cells with sufficient specificity to count asymmetrically self-renewing DSCs in vitro and potentially in situ. PMID:25636161

Clinically identified postpartum depression in Asian American mothers.

PubMed

Goyal, Deepika; Wang, Elsie J; Shen, Jeremy; Wong, Eric C; Palaniappan, Latha P

2012-01-01

To identify the clinical diagnosis rate of postpartum depression (PPD) in Asian American subgroups (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese) compared to non-Hispanic Whites. Cross-sectional study using electronic health records (EHR). A large, outpatient, multiservice clinic in Northern California. A diverse clinical population of non-Hispanic White (N = 4582), Asian Indian (N = 1264), Chinese (N = 1160), Filipino (N = 347), Japanese (N = 124), Korean (N = 183), and Vietnamese (N = 147) mothers. Cases of PPD were identified from EHRs using physician diagnosis codes, medication usage, and age standardized for comparison. The relationship between PPD and other demographic variables (race/ethnicity, maternal age, delivery type, marital status, and infant gender) were examined in a multivariate logistic regression model. The PPD diagnosis rate for all Asian American mothers in aggregate was significantly lower than the diagnosis rate in non-Hispanic White mothers. Moreover, of the six Asian American subgroups, PPD diagnosis rates for Asian Indian, Chinese, and Filipino mothers were significantly lower than non-Hispanic White mothers. In multivariate analyses, race/ethnicity, age, and cesarean were significant predictors of PPD. In this insured population, PPD diagnosis rates were lower among Asian Americans, with variability in rates across the individual Asian American subgroups. It is unclear whether these lower rates are due to underreporting, underdiagnosis, or underutilization of mental health care in this setting. © 2012 AWHONN, the Association of Women's Health, Obstetric and Neonatal Nurses.

Identifying protein phosphorylation sites with kinase substrate specificity on human viruses.

PubMed

Bretaña, Neil Arvin; Lu, Cheng-Tsung; Chiang, Chiu-Yun; Su, Min-Gang; Huang, Kai-Yao; Lee, Tzong-Yi; Weng, Shun-Long

2012-01-01

Viruses infect humans and progress inside the body leading to various diseases and complications. The phosphorylation of viral proteins catalyzed by host kinases plays crucial regulatory roles in enhancing replication and inhibition of normal host-cell functions. Due to its biological importance, there is a desire to identify the protein phosphorylation sites on human viruses. However, the use of mass spectrometry-based experiments is proven to be expensive and labor-intensive. Furthermore, previous studies which have identified phosphorylation sites in human viruses do not include the investigation of the responsible kinases. Thus, we are motivated to propose a new method to identify protein phosphorylation sites with its kinase substrate specificity on human viruses. The experimentally verified phosphorylation data were extracted from virPTM--a database containing 301 experimentally verified phosphorylation data on 104 human kinase-phosphorylated virus proteins. In an attempt to investigate kinase substrate specificities in viral protein phosphorylation sites, maximal dependence decomposition (MDD) is employed to cluster a large set of phosphorylation data into subgroups containing significantly conserved motifs. The experimental human phosphorylation sites are collected from Phospho.ELM, grouped according to its kinase annotation, and compared with the virus MDD clusters. This investigation identifies human kinases such as CK2, PKB, CDK, and MAPK as potential kinases for catalyzing virus protein substrates as confirmed by published literature. Profile hidden Markov model is then applied to learn a predictive model for each subgroup. A five-fold cross validation evaluation on the MDD-clustered HMMs yields an average accuracy of 84.93% for Serine, and 78.05% for Threonine. Furthermore, an independent testing data collected from UniProtKB and Phospho.ELM is used to make a comparison of predictive performance on three popular kinase-specific phosphorylation site

CardioClassifier: disease- and gene-specific computational decision support for clinical genome interpretation.

PubMed

Whiffin, Nicola; Walsh, Roddy; Govind, Risha; Edwards, Matthew; Ahmad, Mian; Zhang, Xiaolei; Tayal, Upasana; Buchan, Rachel; Midwinter, William; Wilk, Alicja E; Najgebauer, Hanna; Francis, Catherine; Wilkinson, Sam; Monk, Thomas; Brett, Laura; O'Regan, Declan P; Prasad, Sanjay K; Morris-Rosendahl, Deborah J; Barton, Paul J R; Edwards, Elizabeth; Ware, James S; Cook, Stuart A

2018-01-25

PurposeInternationally adopted variant interpretation guidelines from the American College of Medical Genetics and Genomics (ACMG) are generic and require disease-specific refinement. Here we developed CardioClassifier (http://www.cardioclassifier.org), a semiautomated decision-support tool for inherited cardiac conditions (ICCs).MethodsCardioClassifier integrates data retrieved from multiple sources with user-input case-specific information, through an interactive interface, to support variant interpretation. Combining disease- and gene-specific knowledge with variant observations in large cohorts of cases and controls, we refined 14 computational ACMG criteria and created three ICC-specific rules.ResultsWe benchmarked CardioClassifier on 57 expertly curated variants and show full retrieval of all computational data, concordantly activating 87.3% of rules. A generic annotation tool identified fewer than half as many clinically actionable variants (64/219 vs. 156/219, Fisher's P = 1.1  ×  10 -18 ), with important false positives, illustrating the critical importance of disease and gene-specific annotations. CardioClassifier identified putatively disease-causing variants in 33.7% of 327 cardiomyopathy cases, comparable with leading ICC laboratories. Through addition of manually curated data, variants found in over 40% of cardiomyopathy cases are fully annotated, without requiring additional user-input data.ConclusionCardioClassifier is an ICC-specific decision-support tool that integrates expertly curated computational annotations with case-specific data to generate fast, reproducible, and interactive variant pathogenicity reports, according to best practice guidelines.GENETICS in MEDICINE advance online publication, 25 January 2018; doi:10.1038/gim.2017.258.

Identifying mortality risks in patients with opioid use disorder using brief screening assessment: Secondary mental health clinical records analysis.

PubMed

Bogdanowicz, Karolina Magda; Stewart, Robert; Chang, Chin-Kuo; Downs, Johnny; Khondoker, Mizanur; Shetty, Hitesh; Strang, John; Hayes, Richard Derek

2016-07-01

Risk assessments are widely used, but their ability to predict outcomes in opioid use disorder (OUD) treatment remains unclear. Therefore, the aim was to investigate if addiction-specific brief risk screening is effective in identifying high mortality risk groups and if subsequent clinical actions following risk assessment impacts on mortality levels. Opioid use disorder (OUD) patients were identified in the South London and Maudsley Case Register. Deaths were identified through database linkage to the national mortality dataset. Cox and competing-risk regression were used to model associations between brief risk assessment domains and all-cause and overdose mortality in 4488 OUD patients, with up-to 6-year follow-up time where 227 deaths were registered. Data were stratified by admission to general mental health services. All-cause mortality was significantly associated with unsafe injecting (HR 1.53, 95% CI 1.10-2.11) and clinically appraised likelihood of accidental overdose (HR 1.48, 95% CI 1.00-2.19). Overdose-mortality was significantly associated with unsafe injecting (SHR 2.52, 95% CI 1.11-5.70) and clinically appraised suicidality (SHR 2.89, 95% CI 1.38-6.03). Suicidality was associated with a twofold increase in mortality risk among OUD patients who were not admitted to mental health services within 2 months of their risk assessment (HR 2.03, 95% CI 1.67-3.24). Diagnosis-specific brief risk screening can identify OUD patient subgroups at increased risk of all-cause and overdose mortality. OUD patients, where suicidality is evident, who are not admitted into services are particularly vulnerable. Copyright © 2016 The Author(s). Published by Elsevier Ireland Ltd.. All rights reserved.

Modeling Clinical Information Needs in the Context of a Specific Patient

PubMed Central

Price, Susan L.

2000-01-01

Investigators have tried various approaches to link clinical information directly to information sources that may contain answers to clinical questions. Developing a model of clinical information needs that may arise in the context of viewing information about a specific patient is a preliminary step to finding an efficient, useful solution to the information retrieval problem. This poster illustrates a method of modeling clinical information needs in the context of a specific patient that that is adapted from entity-relationship models used in database design.

Characteristics of effective clinical teachers identified by dental students: a qualitative study.

PubMed

Jahangiri, L; McAndrew, M; Muzaffar, A; Mucciolo, T W

2013-02-01

This qualitative research study identified criteria for clinical teacher quality preferences as perceived by dental students. Third and fourth year dental students at New York University College of Dentistry were given a two question, open-ended survey asking what qualities they liked most and least in a clinical teacher. Responses were collected until data saturation was achieved. A total of 157 respondents provided a total of 995 written comments. Descriptive words within the responses were coded and grouped into key words, according to similar relationships, and further refined into 17 defined categories. Three core themes, Character, Competence and Communication, emerged from these 17 categories, which were validated according to specific references found in the existing educational literature. 'Character' comprised nine of the 17 defined categories: (caring, motivation, empathy, patience, professionalism, available, fairness, happiness, patient-centred) and yielded 59.1% of total student responses; 'Competence' consisted of five categories: knowledgeable, expertise, efficient, skilful, effective (29.2%); and 'Communication' represented the remaining three categories: feedback, approachable and interpersonal communication (11.7%). Positive and negative responses related to the defined category of caring were cited by 59.2% of all students. Motivation was the next highest category, cited by 45.9% of students. Non-cognitive attributes, especially those in the Character theme, comprised the majority of student comments. Because students' perceptions are so critical to understanding clinical teaching effectiveness in dental education, these findings can be used to develop assessments to measure clinical teaching effectiveness, to create criteria for the hiring and promotion of clinical faculty and to plan faculty development programming. © 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

[Technical specification for clinical application of critical ultrasonography].

PubMed

Yin, M G; Wang, X T; Liu, D W; Chao, Y G; Guan, X D; Kang, Y; Yan, J; Ma, X C; Tang, Y Q; Hu, Z J; Yu, K J; Chen, D C; Ai, Y H; Zhang, L N; Zhang, H M; Wu, J; Liu, L X; Zhu, R; He, W; Zhang, Q; Ding, X; Li, L; Li, Y; Liu, H T; Zeng, Q B; Si, X; Chen, H; Zhang, J W; Xu, Q H; Chen, W J; Chen, X K; Huang, D Z; Cai, S H; Shang, X L; Guan, J; Du, J; Zhao, L; Wang, M J; Cui, S; Wang, X M; Zhou, R; Zeng, X Y; Wang, Y P; Lyu, L W; Zhu, W H; Zhu, Y; Duan, J; Yang, J; Yang, H

2018-06-01

Critical ultrasonography(CUS) is different from the traditional diagnostic ultrasound, the examiner and interpreter of the image are critical care medicine physicians. The core content of CUS is to evaluate the pathophysiological changes of organs and systems and etiology changes. With the idea of critical care medicine as the soul, it can integrate the above information and clinical information, bedside real-time diagnosis and titration treatment, and evaluate the therapeutic effect so as to improve the outcome. CUS is a traditional technique which is applied as a new application method. The consensus of experts on critical ultrasonography in China released in 2016 put forward consensus suggestions on the concept, implementation and application of CUS. It should be further emphasized that the accurate and objective assessment and implementation of CUS requires the standardization of ultrasound image acquisition and the need to establish a CUS procedure. At the same time, the standardized training for CUS accepted by critical care medicine physicians requires the application of technical specifications, and the establishment of technical specifications is the basis for the quality control and continuous improvement of CUS. Chinese Critical Ultrasound Study Group and Critical Hemodynamic Therapy Collabration Group, based on the rich experience of clinical practice in critical care and research, combined with the essence of CUS, to learn the traditional ultrasonic essence, established the clinical application technical specifications of CUS, including in five parts: basic view and relevant indicators to obtain in CUS; basic norms for viscera organ assessment and special assessment; standardized processes and systematic inspection programs; examples of CUS applications; CUS training and the application of qualification certification. The establishment of applied technology standard is helpful for standardized training and clinical correct implementation. It is helpful

Culling a clinical terminology: a systematic approach to identifying problematic content.

PubMed Central

Sable, J. H.; Nash, S. K.; Wang, A. Y.

2001-01-01

The College of American Pathologists and the National Health Service (NHS) in the United Kingdom are merging their respective clinical terminologies, SNOMED RT and Clinical Terms Version 3, into a new terminology, SNOMED CT. This requires mapping concept descriptions between the two existing terminologies. During the mapping process, many descriptions were identified as being potentially problematic. They require further review by the SNOMED editorial process before either (1) being incorporated into SNOMED CT, or (2) retired from active use. This article presents data on the concept descriptions that were identified as needing further review during the early phases of SNOMED CT development. Based on this work, we describe fourteen types of problematic terminology content. Identifying problematic terminology content can be approached in a systematic manner. PMID:11825253

A clinical test of stepping and change of direction to identify multiple falling older adults.

PubMed

Dite, Wayne; Temple, Viviene A

2002-11-01

To establish the reliability and validity of a new clinical test of dynamic standing balance, the Four Square Step Test (FSST), to evaluate its sensitivity, specificity, and predictive value in identifying subjects who fall, and to compare it with 3 established balance and mobility tests. A 3-group comparison performed by using 3 validated tests and 1 new test. A rehabilitation center and university medical school in Australia. Eighty-one community-dwelling adults over the age of 65 years. Subjects were age- and gender-matched to form 3 groups: multiple fallers, nonmultiple fallers, and healthy comparisons. Not applicable. Time to complete the FSST and Timed Up and Go test and the number of steps to complete the Step Test and Functional Reach Test distance. High reliability was found for interrater (n=30, intraclass correlation coefficient [ICC]=.99) and retest reliability (n=20, ICC=.98). Evidence for validity was found through correlation with other existing balance tests. Validity was supported, with the FSST showing significantly better performance scores (P<.01) for each of the healthier and less impaired groups. The FSST also revealed a sensitivity of 85%, a specificity of 88% to 100%, and a positive predictive value of 86%. As a clinical test, the FSST is reliable, valid, easy to score, quick to administer, requires little space, and needs no special equipment. It is unique in that it involves stepping over low objects (2.5cm) and movement in 4 directions. The FSST had higher combined sensitivity and specificity for identifying differences between groups in the selected sample population of older adults than the 3 tests with which it was compared. Copyright 2002 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation

Interactive cervical motion kinematics: sensitivity, specificity and clinically significant values for identifying kinematic impairments in patients with chronic neck pain.

PubMed

Sarig Bahat, Hilla; Chen, Xiaoqi; Reznik, David; Kodesh, Einat; Treleaven, Julia

2015-04-01

Chronic neck pain has been consistently shown to be associated with impaired kinematic control including reduced range, velocity and smoothness of cervical motion, that seem relevant to daily function as in quick neck motion in response to surrounding stimuli. The objectives of this study were: to compare interactive cervical kinematics in patients with neck pain and controls; to explore the new measures of cervical motion accuracy; and to find the sensitivity, specificity, and optimal cutoff values for defining impaired kinematics in those with neck pain. In this cross-section study, 33 patients with chronic neck pain and 22 asymptomatic controls were assessed for their cervical kinematic control using interactive virtual reality hardware and customized software utilizing a head mounted display with built-in head tracking. Outcome measures included peak and mean velocity, smoothness (represented by number of velocity peaks (NVP)), symmetry (represented by time to peak velocity percentage (TTPP)), and accuracy of cervical motion. Results demonstrated significant and strong effect-size differences in peak and mean velocities, NVP and TTPP in all directions excluding TTPP in left rotation, and good effect-size group differences in 5/8 accuracy measures. Regression results emphasized the high clinical value of neck motion velocity, with very high sensitivity and specificity (85%-100%), followed by motion smoothness, symmetry and accuracy. These finding suggest cervical kinematics should be evaluated clinically, and screened by the provided cut off values for identification of relevant impairments in those with neck pain. Such identification of presence or absence of kinematic impairments may direct treatment strategies and additional evaluation when needed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Using an International Clinical Registry of Regional Anesthesia to Identify Targets for Quality Improvement

PubMed Central

Sites, Brian D.; Barrington, Michael J.; Davis, Matthew

2014-01-01

Background Despite the widespread use of regional anesthesia, limited information on clinical performance exists. Institutions, therefore, have little knowledge of how they are performing in regards to both safety and effectiveness. In this study, we demonstrate how a medical institution (or physician/physician group) may use data from a multi-center clinical registry of regional anesthesia to inform quality improvement strategies. Methods We analyzed data from the International Registry of Regional Anesthesia that includes prospective data on peripheral regional anesthesia procedures from 19 centers located around the world. Using data from the clinical registry, we present summary statistics of the overall safety and effectiveness of regional anesthesia. Furthermore, we demonstrate, using a variety of performance measures, how these data can be used by hospitals to identify areas for quality improvement. To do so, we compare the performance of one member institution (a United States medical center in New Hampshire) to that of the other 18 member institutions of the clinical registry. Results The clinical registry contained information on 23,271 blocks that were performed between June 1, 2011, and May 1, 2014, on 16,725 patients. The overall success rate was 96.7%, immediate complication rate was 2.2%, and the all-cause 60-day rate of neurological sequelae was 8.3 (95% CI, 7.2–9.7) per 10,000. Registry wide major hospital events included 7 wrong site blocks, 3 seizures, 1 complete heart block, 1 retroperitoneal hematoma, and 3 pneumothoraces. For our reference medical center, we identified areas meriting quality improvement. Specifically, after accounting for differences in the age, sex, and health status of patient populations, the reference medical center appeared to rely more heavily on opioids for post procedure management, had higher patient pain scores, and experienced delayed discharge when compared with other member institutions. Conclusions To our

Treating reading comprehension deficits in sub-acute brain injury rehabilitation: Identifying clinical practice and management.

PubMed

Watter, Kerrin; Copley, Anna; Finch, Emma

There is limited evidence for cognitive-communication reading comprehension (CCRC) interventions for adults following acquired brain injury (ABI), particularly during sub-acute rehabilitation. The purpose of this study was to investigate the clinical practice of speech-language pathologists (SLPs) with CCRC deficits during sub-acute ABI rehabilitation and compare it to the best available evidence. An electronic survey was used to gather information from clinicians across Australia regarding clinical practice in the areas of assessment, intervention, treatment hierarchies and service delivery; survey questions were developed from an extensive review of the literature and expert clinician opinion. Survey findings were then compared with the literature in the form of a systematic review. Surveyed clinicians provided multiple interventions for CCRC rehabilitation, including impairment based (94.7%), activity based (94.7%) and reading strategy interventions (100.0%). Five strategies were used by >94% of SLPs (highlighting, identifying main points/wh- questioning, re-reading, summarising, reducing visual load). When compared with the literature, strong similarities were found for strategy-based interventions and individual service delivery, with broad similarities for functional and impairment-based interventions, and impairment based treatment hierarchies. Strong differences in assessment were identified. Strategy use reported in clinical practice (100.0% SLPs) was higher than in the literature. Further investigation into the effectiveness of specific reading strategies for people with ABI is warranted. Copyright © 2016 Elsevier Inc. All rights reserved.

Instruments to Identify Prescription Medication Misuse, Abuse, and Related Events in Clinical Trials: An ACTTION Systematic Review.

PubMed

Smith, Shannon M; Paillard, Florence; McKeown, Andrew; Burke, Laurie B; Edwards, Robert R; Katz, Nathaniel P; Papadopoulos, Elektra J; Rappaport, Bob A; Slagle, Ashley; Strain, Eric C; Wasan, Ajay D; Turk, Dennis C; Dworkin, Robert H

2015-05-01

Measurement of inappropriate medication use events (eg, abuse or misuse) in clinical trials is important in characterizing a medication's abuse potential. However, no gold standard assessment of inappropriate use events in clinical trials has been identified. In this systematic review, we examine the measurement properties (ie, content validity, cross-sectional reliability and construct validity, longitudinal construct validity, ability to detect change, and responder definitions) of instruments assessing inappropriate use of opioid and nonopioid prescription medications to identify any that meet U.S. and European regulatory agencies' rigorous standards for outcome measures in clinical trials. Sixteen published instruments were identified, most of which were not designed for the selected concept of interest and context of use. For this reason, many instruments were found to lack adequate content validity (or documentation of content validity) to evaluate current inappropriate medication use events; for example, evaluating inappropriate use across the life span rather than current use, including items that did not directly assess inappropriate use (eg, questions about anger), or failing to capture information pertinent to inappropriate use events (eg, intention and route of administration). In addition, the psychometric data across all instruments were generally limited in scope. A further limitation is the heterogeneous, nonstandardized use of inappropriate medication use terminology. These observations suggest that available instruments are not well suited for assessing current inappropriate medication use within the specific context of clinical trials. Further effort is needed to develop reliable and valid instruments to measure current inappropriate medication use events in clinical trials. This systematic review evaluates the measurement properties of inappropriate medication use (eg, abuse or misuse) instruments to determine whether any meet regulatory

Machine-learning identifies substance-specific behavioral markers for opiate and stimulant dependence.

PubMed

Ahn, Woo-Young; Vassileva, Jasmin

2016-04-01

Recent animal and human studies reveal distinct cognitive and neurobiological differences between opiate and stimulant addictions; however, our understanding of the common and specific effects of these two classes of drugs remains limited due to the high rates of polysubstance-dependence among drug users. The goal of the current study was to identify multivariate substance-specific markers classifying heroin dependence (HD) and amphetamine dependence (AD), by using machine-learning approaches. Participants included 39 amphetamine mono-dependent, 44 heroin mono-dependent, 58 polysubstance dependent, and 81 non-substance dependent individuals. The majority of substance dependent participants were in protracted abstinence. We used demographic, personality (trait impulsivity, trait psychopathy, aggression, sensation seeking), psychiatric (attention deficit hyperactivity disorder, conduct disorder, antisocial personality disorder, psychopathy, anxiety, depression), and neurocognitive impulsivity measures (Delay Discounting, Go/No-Go, Stop Signal, Immediate Memory, Balloon Analogue Risk, Cambridge Gambling, and Iowa Gambling tasks) as predictors in a machine-learning algorithm. The machine-learning approach revealed substance-specific multivariate profiles that classified HD and AD in new samples with high degree of accuracy. Out of 54 predictors, psychopathy was the only classifier common to both types of addiction. Important dissociations emerged between factors classifying HD and AD, which often showed opposite patterns among individuals with HD and AD. These results suggest that different mechanisms may underlie HD and AD, challenging the unitary account of drug addiction. This line of work may shed light on the development of standardized and cost-efficient clinical diagnostic tests and facilitate the development of individualized prevention and intervention programs for HD and AD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Machine-learning identifies substance-specific behavioral markers for opiate and stimulant dependence

PubMed Central

Ahn, Woo-Young; Vassileva, Jasmin

2016-01-01

Background Recent animal and human studies reveal distinct cognitive and neurobiological differences between opiate and stimulant addictions; however, our understanding of the common and specific effects of these two classes of drugs remains limited due to the high rates of polysubstance-dependence among drug users. Methods The goal of the current study was to identify multivariate substance-specific markers classifying heroin dependence (HD) and amphetamine dependence (AD), by using machine-learning approaches. Participants included 39 amphetamine mono-dependent, 44 heroin mono-dependent, 58 polysubstance dependent, and 81 non-substance dependent individuals. The majority of substance dependent participants were in protracted abstinence. We used demographic, personality (trait impulsivity, trait psychopathy, aggression, sensation seeking), psychiatric (attention deficit hyperactivity disorder, conduct disorder, antisocial personality disorder, psychopathy, anxiety, depression), and neurocognitive impulsivity measures (Delay Discounting, Go/No-Go, Stop Signal, Immediate Memory, Balloon Analogue Risk, Cambridge Gambling, and Iowa Gambling tasks) as predictors in a machine-learning algorithm. Results The machine-learning approach revealed substance-specific multivariate profiles that classified HD and AD in new samples with high degree of accuracy. Out of 54 predictors, psychopathy was the only classifier common to both types of addiction. Important dissociations emerged between factors classifying HD and AD, which often showed opposite patterns among individuals with HD and AD. Conclusions These results suggest that different mechanisms may underlie HD and AD, challenging the unitary account of drug addiction. This line of work may shed light on the development of standardized and cost-efficient clinical diagnostic tests and facilitate the development of individualized prevention and intervention programs for HD and AD. PMID:26905209

Hypocretin neuron-specific transcriptome profiling identifies the sleep modulator Kcnh4a.

PubMed

Yelin-Bekerman, Laura; Elbaz, Idan; Diber, Alex; Dahary, Dvir; Gibbs-Bar, Liron; Alon, Shahar; Lerer-Goldshtein, Tali; Appelbaum, Lior

2015-10-01

Sleep has been conserved throughout evolution; however, the molecular and neuronal mechanisms of sleep are largely unknown. The hypothalamic hypocretin/orexin (Hcrt) neurons regulate sleep\\wake states, feeding, stress, and reward. To elucidate the mechanism that enables these various functions and to identify sleep regulators, we combined fluorescence cell sorting and RNA-seq in hcrt:EGFP zebrafish. Dozens of Hcrt-neuron-specific transcripts were identified and comprehensive high-resolution imaging revealed gene-specific localization in all or subsets of Hcrt neurons. Clusters of Hcrt-neuron-specific genes are predicted to be regulated by shared transcription factors. These findings show that Hcrt neurons are heterogeneous and that integrative molecular mechanisms orchestrate their diverse functions. The voltage-gated potassium channel Kcnh4a, which is expressed in all Hcrt neurons, was silenced by the CRISPR-mediated gene inactivation system. The mutant kcnh4a (kcnh4a(-/-)) larvae showed reduced sleep time and consolidation, specifically during the night, suggesting that Kcnh4a regulates sleep.

Instruments to assess the perception of physicians in the decision-making process of specific clinical encounters: a systematic review

PubMed Central

Légaré, France; Moher, David; Elwyn, Glyn; LeBlanc, Annie; Gravel, Karine

2007-01-01

Background The measurement of processes and outcomes that reflect the complexity of the decision-making process within specific clinical encounters is an important area of research to pursue. A systematic review was conducted to identify instruments that assess the perception physicians have of the decision-making process within specific clinical encounters. Methods For every year available up until April 2007, PubMed, PsycINFO, Current Contents, Dissertation Abstracts and Sociological Abstracts were searched for original studies in English or French. Reference lists from retrieved studies were also consulted. Studies were included if they reported a self-administered instrument evaluating physicians' perceptions of the decision-making process within specific clinical encounters, contained sufficient description to permit critical appraisal and presented quantitative results based on administering the instrument. Two individuals independently assessed the eligibility of the instruments and abstracted information on their conceptual underpinnings, main evaluation domain, development, format, reliability, validity and responsiveness. They also assessed the quality of the studies that reported on the development of the instruments with a modified version of STARD. Results Out of 3431 records identified and screened for evaluation, 26 potentially relevant instruments were assessed; 11 met the inclusion criteria. Five instruments were published before 1995. Among those published after 1995, five offered a corresponding patient version. Overall, the main evaluation domains were: satisfaction with the clinical encounter (n = 2), mutual understanding between health professional and patient (n = 2), mental workload (n = 1), frustration with the clinical encounter (n = 1), nurse-physician collaboration (n = 1), perceptions of communication competence (n = 2), degree of comfort with a decision (n = 1) and information on medication (n = 1). For most instruments (n = 10), some

A methodology for evaluation of a markup-based specification of clinical guidelines.

PubMed

Shalom, Erez; Shahar, Yuval; Taieb-Maimon, Meirav; Lunenfeld, Eitan

2008-11-06

We introduce a three-phase, nine-step methodology for specification of clinical guidelines (GLs) by expert physicians, clinical editors, and knowledge engineers, and for quantitative evaluation of the specification's quality. We applied this methodology to a particular framework for incremental GL structuring (mark-up) and to GLs in three clinical domains with encouraging results.

What should we teach the teachers? Identifying the learning priorities of clinical supervisors.

PubMed

Bearman, Margaret; Tai, Joanna; Kent, Fiona; Edouard, Vicki; Nestel, Debra; Molloy, Elizabeth

2018-03-01

Clinicians who teach are essential for the health workforce but require faculty development to improve their educational skills. Curricula for faculty development programs are often based on expert frameworks without consideration of the learning priorities as defined by clinical supervisors themselves. We sought to inform these curricula by highlighting clinical supervisors own requirements through answering the research question: what do clinical supervisors identify as relative strengths and areas for improvement in their teaching practice? This mixed methods study employed a modified version of the Maastricht Clinical Teaching Questionnaire (mMCTQ) which included free-text reflections. Descriptive statistics were calculated and content analysis was conducted on textual comments. 481 (49%) of 978 clinical supervisors submitted their mMCTQs and associated reflections for the research study. Clinical supervisors self-identified relatively strong capability with interpersonal skills or attributes and indicated least capability with assisting learners to explore strengths, weaknesses and learning goals. The qualitative category 'establishing relationships' was the most reported strength with 224 responses. The qualitative category 'feedback' was the most reported area for improvement, with 151 responses. Key areas for curricular focus include: improving feedback practices; stimulating reflective and agentic learning; and managing the logistics of a clinical education environment. Clinical supervisors' self-identified needs provide a foundation for designing engaging and relevant faculty development programs.

Identifying psychotic defenses in a clinical interview.

PubMed

Berney, Sylvie; de Roten, Yves; Beretta, Véronique; Kramer, Ueli; Despland, Jean-Nicolas

2014-05-01

The Defense Mechanisms Rating Scales (DMRS), one of the most widely used and validated instruments in the study of defense mechanisms, does not include psychotic defenses. The Psychotic-DMRS (P-DMRS) has been developed to include 6 psychotic defense mechanisms: psychotic denial, autistic withdrawal, distortion, delusional projection, fragmentation, and concretization. We discuss psychotic defenses, including the difference between psychotic defenses and psychotic symptoms. Six clinical illustrations demonstrate how the 6 P-DMRS defenses can be identified in patients' narratives selected from the transcripts of dynamic interviews. Implications with respect to patient evaluation and treatment are discussed. © 2014 Wiley Periodicals, Inc.

SMM-system: A mining tool to identify specific markers in Salmonella enterica.

PubMed

Yu, Shuijing; Liu, Weibing; Shi, Chunlei; Wang, Dapeng; Dan, Xianlong; Li, Xiao; Shi, Xianming

2011-03-01

This report presents SMM-system, a software package that implements various personalized pre- and post-BLASTN tasks for mining specific markers of microbial pathogens. The main functionalities of SMM-system are summarized as follows: (i) converting multi-FASTA file, (ii) cutting interesting genomic sequence, (iii) automatic high-throughput BLASTN searches, and (iv) screening target sequences. The utility of SMM-system was demonstrated by using it to identify 214 Salmonella enterica-specific protein-coding sequences (CDSs). Eighteen primer pairs were designed based on eighteen S. enterica-specific CDSs, respectively. Seven of these primer pairs were validated with PCR assay, which showed 100% inclusivity for the 101 S. enterica genomes and 100% exclusivity of 30 non-S. enterica genomes. Three specific primer pairs were chosen to develop a multiplex PCR assay, which generated specific amplicons with a size of 180bp (SC1286), 238bp (SC1598) and 405bp (SC4361), respectively. This study demonstrates that SMM-system is a high-throughput specific marker generation tool that can be used to identify genus-, species-, serogroup- and even serovar-specific DNA sequences of microbial pathogens, which has a potential to be applied in food industries, diagnostics and taxonomic studies. SMM-system is freely available and can be downloaded from http://foodsafety.sjtu.edu.cn/SMM-system.html. Copyright © 2011 Elsevier B.V. All rights reserved.

Data sharing platforms for de-identified data from human clinical trials.

PubMed

Huser, Vojtech; Shmueli-Blumberg, Dikla

2018-04-01

Data sharing of de-identified individual participant data is being adopted by an increasing number of sponsors of human clinical trials. In addition to standardizing data syntax for shared trial data, semantic integration of various data elements is the focus of several initiatives that define research common data elements. This perspective article, in the first part, compares several data sharing platforms for de-identified clinical research data in terms of their size, policies and supported features. In the second part, we use a case study approach to describe in greater detail one data sharing platform (Data Share from National Institute of Drug Abuse). We present data on the past use of the platform, data formats offered, data de-identification approaches and its use of research common data elements. We conclude with a summary of current and expected future trends that facilitate secondary research use of data from completed human clinical trials.

The Cancer Genome Atlas Clinical Explorer: a web and mobile interface for identifying clinical-genomic driver associations.

PubMed

Lee, HoJoon; Palm, Jennifer; Grimes, Susan M; Ji, Hanlee P

2015-10-27

The Cancer Genome Atlas (TCGA) project has generated genomic data sets covering over 20 malignancies. These data provide valuable insights into the underlying genetic and genomic basis of cancer. However, exploring the relationship among TCGA genomic results and clinical phenotype remains a challenge, particularly for individuals lacking formal bioinformatics training. Overcoming this hurdle is an important step toward the wider clinical translation of cancer genomic/proteomic data and implementation of precision cancer medicine. Several websites such as the cBio portal or University of California Santa Cruz genome browser make TCGA data accessible but lack interactive features for querying clinically relevant phenotypic associations with cancer drivers. To enable exploration of the clinical-genomic driver associations from TCGA data, we developed the Cancer Genome Atlas Clinical Explorer. The Cancer Genome Atlas Clinical Explorer interface provides a straightforward platform to query TCGA data using one of the following methods: (1) searching for clinically relevant genes, micro RNAs, and proteins by name, cancer types, or clinical parameters; (2) searching for genomic/proteomic profile changes by clinical parameters in a cancer type; or (3) testing two-hit hypotheses. SQL queries run in the background and results are displayed on our portal in an easy-to-navigate interface according to user's input. To derive these associations, we relied on elastic-net estimates of optimal multiple linear regularized regression and clinical parameters in the space of multiple genomic/proteomic features provided by TCGA data. Moreover, we identified and ranked gene/micro RNA/protein predictors of each clinical parameter for each cancer. The robustness of the results was estimated by bootstrapping. Overall, we identify associations of potential clinical relevance among genes/micro RNAs/proteins using our statistical analysis from 25 cancer types and 18 clinical parameters that

Articular dysfunction patterns in patients with mechanical neck pain: a clinical algorithm to guide specific mobilization and manipulation techniques.

PubMed

Dewitte, Vincent; Beernaert, Axel; Vanthillo, Bart; Barbe, Tom; Danneels, Lieven; Cagnie, Barbara

2014-02-01

In view of a didactical approach for teaching cervical mobilization and manipulation techniques to students as well as their use in daily practice, it is mandatory to acquire sound clinical reasoning to optimally apply advanced technical skills. The aim of this Masterclass is to present a clinical algorithm to guide (novice) therapists in their clinical reasoning to identify patients who are likely to respond to mobilization and/or manipulation. The presented clinical reasoning process is situated within the context of pain mechanisms and is narrowed to and applicable in patients with a dominant input pain mechanism. Based on key features in subjective and clinical examination, patients with mechanical nociceptive pain probably arising from articular structures can be categorized into specific articular dysfunction patterns. Pending on these patterns, specific mobilization and manipulation techniques are warranted. The proposed patterns are illustrated in 3 case studies. This clinical algorithm is the corollary of empirical expertise and is complemented by in-depth discussions and knowledge exchange with international colleagues. Consequently, it is intended that a carefully targeted approach contributes to an increase in specificity and safety in the use of cervical mobilizations and manipulation techniques as valuable adjuncts to other manual therapy modalities. Copyright © 2013 Elsevier Ltd. All rights reserved.

Identifying uncontrolled asthma in young children: clinical scores or objective variables?

PubMed

Leung, T F; Ko, F W S; Sy, H Y; Wong, E; Li, C Y; Yung, E; Hui, D S C; Wong, G W K; Lai, C K W

2009-03-01

Several international asthma guidelines emphasize the importance of assessing asthma control. However, there is limited data on the usefulness of available assessment tools in indicating disease control in young asthmatics. This study investigated the ability of Chinese version of Childhood Asthma Control Test (C-ACT) and other disease-related factors in identifying uncontrolled asthma (UA) in young children. During the same clinic visit, asthma patients 4 to 11 years of age completed C-ACT and underwent exhaled nitric oxide and spirometric measurements. Blinded to these results, the same investigator assigned Disease Severity Score (DSS) and rated asthma control according to Global Initiative for Asthma. The mean (SD) age of 113 recruited patients was 9.1 (2.0) years, and 35% of them had UA. C-ACT, DSS and forced expiratory volume in 1 second (FEV(1)) differed among patients with different control status (p < 0.001 for C-ACT and DSS; p = 0.014 for FEV(1)). Logistic regression confirmed that UA was associated with DSS (p < 0.001), PEF (p = 0.002), C-ACT (p = 0.011), and FEV(1) (p = 0.012). By ROC analysis, C-ACT and DSS were the best predictors for UA (p < 0.001), followed by PEF (p = 0.006) and FEV(1) (p = 0.007). When analyzed by the Classification and Regression Tree (CART) approach, the sequential use of DSS and C-ACT had 77% sensitivity and 84% specificity in identifying UA. C-ACT is better than objective parameters in identifying young Chinese children with UA.

Clinically Practical Magnetic Resonance Protocol for Improved Specificity in Breast Cancer Diagnosis

DTIC Science & Technology

2007-06-01

Protocol for Improved Specificity in Breast Cancer Diagnosis PRINCIPAL INVESTIGATOR: Luminita Alina Tudorica, Ph.D. CONTRACTING...TITLE AND SUBTITLE 5a. CONTRACT NUMBER Clinically Practical Magnetic Resonance Protocol for Improved Specificity in Breast Cancer Diagnosis 5b... breast cancer study in a clinical setting. This study aims to improve specificity of breast cancer detection by using a combined MRI/MRS protocol. In

TnSeq of Mycobacterium tuberculosis clinical isolates reveals strain-specific antibiotic liabilities

PubMed Central

Carey, Allison F.; Rock, Jeremy M.; Krieger, Inna V.; Gagneux, Sebastien; Sacchettini, James C.; Fortune, Sarah M.

2018-01-01

Once considered a phenotypically monomorphic bacterium, there is a growing body of work demonstrating heterogeneity among Mycobacterium tuberculosis (Mtb) strains in clinically relevant characteristics, including virulence and response to antibiotics. However, the genetic and molecular basis for most phenotypic differences among Mtb strains remains unknown. To investigate the basis of strain variation in Mtb, we performed genome-wide transposon mutagenesis coupled with next-generation sequencing (TnSeq) for a panel of Mtb clinical isolates and the reference strain H37Rv to compare genetic requirements for in vitro growth across these strains. We developed an analytic approach to identify quantitative differences in genetic requirements between these genetically diverse strains, which vary in genomic structure and gene content. Using this methodology, we found differences between strains in their requirements for genes involved in fundamental cellular processes, including redox homeostasis and central carbon metabolism. Among the genes with differential requirements were katG, which encodes the activator of the first-line antitubercular agent isoniazid, and glcB, which encodes malate synthase, the target of a novel small-molecule inhibitor. Differences among strains in their requirement for katG and glcB predicted differences in their response to these antimicrobial agents. Importantly, these strain-specific differences in antibiotic response could not be predicted by genetic variants identified through whole genome sequencing or by gene expression analysis. Our results provide novel insight into the basis of variation among Mtb strains and demonstrate that TnSeq is a scalable method to predict clinically important phenotypic differences among Mtb strains. PMID:29505613

Performance specifications and six sigma theory: Clinical chemistry and industry compared.

PubMed

Oosterhuis, W P; Severens, M J M J

2018-04-11

Analytical performance specifications are crucial in test development and quality control. Although consensus has been reached on the use of biological variation to derive these specifications, no consensus has been reached which model should be preferred. The Six Sigma concept is widely applied in industry for quality specifications of products and can well be compared with Six Sigma models in clinical chemistry. However, the models for measurement specifications differ considerably between both fields: where the sigma metric is used in clinical chemistry, in industry the Number of Distinct Categories is used instead. In this study the models in both fields are compared and discussed. Copyright © 2018. Published by Elsevier Inc.

Sensitivity and Specificity of Cetuximab-IRDye800CW to Identify Regional Metastatic Disease in Head and Neck Cancer.

PubMed

Rosenthal, Eben L; Moore, Lindsay S; Tipirneni, Kiranya; de Boer, Esther; Stevens, Todd M; Hartman, Yolanda E; Carroll, William R; Zinn, Kurt R; Warram, Jason M

2017-08-15

Purpose: Comprehensive cervical lymphadenectomy can be associated with significant morbidity and poor quality of life. This study evaluated the sensitivity and specificity of cetuximab-IRDye800CW to identify metastatic disease in patients with head and neck cancer. Experimental Design: Consenting patients scheduled for curative resection were enrolled in a clinical trial to evaluate the safety and specificity of cetuximab-IRDye800CW. Patients ( n = 12) received escalating doses of the study drug. Where indicated, cervical lymphadenectomy accompanied primary tumor resection, which occurred 3 to 7 days following intravenous infusion of cetuximab-IRDye800CW. All 471 dissected lymph nodes were imaged with a closed-field, near-infrared imaging device during gross processing of the fresh specimens. Intraoperative imaging of exposed neck levels was performed with an open-field fluorescence imaging device. Blinded assessments of the fluorescence data were compared to histopathology to calculate sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). Results: Of the 35 nodes diagnosed pathologically positive, 34 were correctly identified with fluorescence imaging, yielding a sensitivity of 97.2%. Of the 435 pathologically negative nodes, 401 were correctly assessed using fluorescence imaging, yielding a specificity of 92.7%. The NPV was determined to be 99.7%, and the PPV was 50.7%. When 37 fluorescently false-positive nodes were sectioned deeper (1 mm) into their respective blocks, metastatic cancer was found in 8.1% of the recut nodal specimens, which altered staging in two of those cases. Conclusions: Fluorescence imaging of lymph nodes after systemic cetuximab-IRDye800CW administration demonstrated high sensitivity and was capable of identifying additional positive nodes on deep sectioning. Clin Cancer Res; 23(16); 4744-52. ©2017 AACR . ©2017 American Association for Cancer Research.

High Sensitivity and Specificity of Clinical Microscopy in Rural Health Facilities in Western Kenya Under an External Quality Assurance Program

PubMed Central

Wafula, Rebeccah; Sang, Edna; Cheruiyot, Olympia; Aboto, Angeline; Menya, Diana; O'Meara, Wendy Prudhomme

2014-01-01

Microscopic diagnosis of malaria is a well-established and inexpensive technique that has the potential to provide accurate diagnosis of malaria infection. However, it requires both training and experience. Although it is considered the gold standard in research settings, the sensitivity and specificity of routine microscopy for clinical care in the primary care setting has been reported to be unacceptably low. We established a monthly external quality assurance program to monitor the performance of clinical microscopy in 17 rural health centers in western Kenya. The average sensitivity over the 12-month period was 96% and the average specificity was 88%. We identified specific contextual factors that contributed to inadequate performance. Maintaining high-quality malaria diagnosis in high-volume, resource-constrained health facilities is possible. PMID:24935953

Genome-wide Association Study Identifies Peanut Allergy-Specific Loci and Evidence of Epigenetic Mediation in U.S. Children

PubMed Central

Hong, Xiumei; Hao, Ke; Ladd-Acosta, Christine; Hansen, Kasper D; Tsai, Hui-Ju; Liu, Xin; Xu, Xin; Thornton, Timothy A.; Caruso, Deanna; Keet, Corinne A; Sun, Yifei; Wang, Guoying; Luo, Wei; Kumar, Rajesh; Fuleihan, Ramsay; Singh, Anne Marie; Kim, Jennifer S; Story, Rachel E; Gupta, Ruchi S; Gao, Peisong; Chen, Zhu; Walker, Sheila O.; Bartell, Tami R; Beaty, Terri H; Fallin, M Daniele; Schleimer, Robert; Holt, Patrick G; Nadeau, Kari Christine; Wood, Robert A; Pongracic, Jacqueline A; Weeks, Daniel E; Wang, Xiaobin

2015-01-01

Food allergy (FA) affects 2–10% of U.S. children and is a growing clinical and public health problem. Here we conduct the first genome-wide association study of well-defined FA, including specific subtypes (peanut, milk, and egg) in 2,759 U.S. participants (1,315 children; 1,444 parents) from the Chicago Food Allergy Study; and identify peanut allergy (PA)-specific loci in the HLA-DR and -DQ gene region at 6p21.32, tagged by rs7192 (p=5.5×10−8) and rs9275596 (p=6.8×10−10), in 2,197 participants of European ancestry. We replicate these associations in an independent sample of European ancestry. These associations are further supported by meta-analyses across the discovery and replication samples. Both single-nucleotide polymorphisms (SNPs) are associated with differential DNA methylation levels at multiple CpG sites (p<5×10−8); and differential DNA methylation of the HLA-DQB1 and HLA-DRB1 genes partially mediate the identified SNP-PA associations. This study suggests that the HLA-DR and -DQ gene region likely poses significant genetic risk for PA. PMID:25710614

Assessment of clinical analytical sensitivity and specificity of next-generation sequencing for detection of simple and complex mutations.

PubMed

Chin, Ephrem L H; da Silva, Cristina; Hegde, Madhuri

2013-02-19

Detecting mutations in disease genes by full gene sequence analysis is common in clinical diagnostic laboratories. Sanger dideoxy terminator sequencing allows for rapid development and implementation of sequencing assays in the clinical laboratory, but it has limited throughput, and due to cost constraints, only allows analysis of one or at most a few genes in a patient. Next-generation sequencing (NGS), on the other hand, has evolved rapidly, although to date it has mainly been used for large-scale genome sequencing projects and is beginning to be used in the clinical diagnostic testing. One advantage of NGS is that many genes can be analyzed easily at the same time, allowing for mutation detection when there are many possible causative genes for a specific phenotype. In addition, regions of a gene typically not tested for mutations, like deep intronic and promoter mutations, can also be detected. Here we use 20 previously characterized Sanger-sequenced positive controls in disease-causing genes to demonstrate the utility of NGS in a clinical setting using standard PCR based amplification to assess the analytical sensitivity and specificity of the technology for detecting all previously characterized changes (mutations and benign SNPs). The positive controls chosen for validation range from simple substitution mutations to complex deletion and insertion mutations occurring in autosomal dominant and recessive disorders. The NGS data was 100% concordant with the Sanger sequencing data identifying all 119 previously identified changes in the 20 samples. We have demonstrated that NGS technology is ready to be deployed in clinical laboratories. However, NGS and associated technologies are evolving, and clinical laboratories will need to invest significantly in staff and infrastructure to build the necessary foundation for success.

[Myositis-specific autoantibodies].

PubMed

Gran, Jan Tore; Molberg, Øyvind; Dobloug, Gerd Cecilie; Andersson, Helena; Taraldsrud, Eli; Scheie, David

2009-08-27

Myositis-specific antibodies (MSA) are autoantibodies that are almost exclusively detected in idiopathic inflammatory myopathies (IIM). This article provides an overview of these autoantibodies and how they can be used clinically to identify subgroups of IIM. The article is based on a non-systematic literature review and our own experience. MSA can be detected in up to 50 % of patients with IIM. Patients with anti-synthetase antibodies have a constellation of clinical findings termed "the anti-synthetase syndrome", in which interstitial lung disease dominates the clinical picture. Anti-Mi2 antibodies is another myositis-specific antibody. Patients with anti-Mi2 antibodies often have classical dermatomyositis, while the anti-SRP antibody identifies patients with severe myopathy, poor response to treatment with corticosteroids and histological findings of muscle cell necrosis - often lacking inflammatory infiltrates. The newly detected anti-CADMp140 appears to be associated with amyopathic or hypomyopathic dermatomyositis, previously called dermatomyositis sine myositis. Anti-p155 antibodies are most often found in patients who also have cancer. Myositis-specific antibodies may be useful for identification of clinical subgroups of IIM and can thereby affect the choice of medical treatment.

The sensitivity and specificity of clinical measures of sport concussion: three tests are better than one.

PubMed

Resch, Jacob E; Brown, Cathleen N; Schmidt, Julianne; Macciocchi, Stephen N; Blueitt, Damond; Cullum, C Munro; Ferrara, Michael S

2016-01-01

A battery of clinical measures of neurocognition, balance and symptoms has been recommended for the management of sport concussion (SC) but is based on variable evidence. To examine the sensitivity and specificity of a battery of tests to assess SC in college athletes. Cross-sectional. Research laboratory. Division 1 athletes diagnosed with a SC (n=40) who were 20.2±1.60 years of age and 180.5±11.12 cm tall and healthy athletes (n=40) who were 19.0±0.93 years of age and 179.1±11.39 cm tall were enrolled. Participants were administered Immediate Postconcussion Assessment and Cognitive Test (ImPACT), the Sensory Organization Test (SOT) and the Revised Head Injury Scale (HIS-r) prior to and up to 24 h following injury between the 2004 and 2014 sport seasons. Sensitivity and specificity were calculated using predictive discriminant analyses (PDA) and clinical interpretation guidelines. Outcome measures included baseline and postinjury ImPACT, SOT and HIS-r composite scores. Using PDA, each clinical measure's sensitivity ranged from 55.0% to 77.5% and specificity ranged from 52.5% to 100%. The test battery possessed a sensitivity and specificity of 80.0% and 100%, respectively. Using clinical interpretation guidelines, sensitivity ranged from 55% to 97.5% individually, and 100% when combined. Our results support a multidimensional approach to assess SC in college athletes which correctly identified 80-100% of concussed participants as injured. When each test was evaluated separately, up to 47.5% of our sample was misclassified. Caution is warranted when using singular measures to manage SC.

NADiA ProsVue prostate-specific antigen slope is an independent prognostic marker for identifying men at reduced risk of clinical recurrence of prostate cancer after radical prostatectomy.

PubMed

Moul, Judd W; Lilja, Hans; Semmes, O John; Lance, Raymond S; Vessella, Robert L; Fleisher, Martin; Mazzola, Clarisse; Sarno, Mark J; Stevens, Barbara; Klem, Robert E; McDermed, Jonathan E; Triebell, Melissa T; Adams, Thomas H

2012-12-01

To validate the hypothesis that men displaying serum prostate-specific antigen (PSA) slopes ≤ 2.0 pg/mL/mo after prostatectomy, measured using a new immuno-polymerase chain reaction diagnostic test (NADiA ProsVue), have a reduced risk of clinical recurrence as determined by positive biopsy, imaging findings, or death from prostate cancer. From 4 clinical sites, we selected a cohort of 304 men who had been followed up for 17.6 years after prostatectomy for clinical recurrence. We assessed the prognostic value of a PSA slope cutpoint of 2.0 pg/mL/mo against established risk factors to identify men at low risk of clinical recurrence using uni- and multivariate Cox proportional hazards regression and Kaplan-Meier analyses. The univariate hazard ratio of a PSA slope >2.0 pg/mL/mo was 18.3 (95% confidence interval 10.6-31.8) compared with a slope ≤ 2.0 pg/mL/mo (P <.0001). The median disease-free survival interval was 4.8 years vs >10 years in the 2 groups (P <.0001). The multivariate hazard ratio for PSA slope with the covariates of preprostatectomy PSA, pathologic stage, and Gleason score was 9.8 (95% confidence interval 5.4-17.8), an 89.8% risk reduction for men with PSA slopes ≤ 2.0 pg/mL/mo (P <.0001). The Gleason score (<7 vs ≥ 7) was the only other significant predictor (hazard ratio 5.4, 95% confidence interval 2.1-13.8, P = .0004). Clinical recurrence after radical prostatectomy is difficult to predict using established risk factors. We have demonstrated that a NADiA ProsVue PSA slope of ≤ 2.0 pg/mL/mo after prostatectomy is prognostic for a reduced risk of prostate cancer recurrence and adds predictive power to the established risk factors. Copyright © 2012 Elsevier Inc. All rights reserved.

Gambogic acid identifies an isoform-specific druggable pocket in the middle domain of Hsp90β

PubMed Central

Yim, Kendrick H.; Prince, Thomas L.; Qu, Shiwei; Bai, Fang; Jennings, Patricia A.; Onuchic, José N.; Theodorakis, Emmanuel A.; Neckers, Leonard

2016-01-01

Because of their importance in maintaining protein homeostasis, molecular chaperones, including heat-shock protein 90 (Hsp90), represent attractive drug targets. Although a number of Hsp90 inhibitors are in preclinical/clinical development, none strongly differentiate between constitutively expressed Hsp90β and stress-induced Hsp90α, the two cytosolic paralogs of this molecular chaperone. Thus, the importance of inhibiting one or the other paralog in different disease states remains unknown. We show that the natural product, gambogic acid (GBA), binds selectively to a site in the middle domain of Hsp90β, identifying GBA as an Hsp90β-specific Hsp90 inhibitor. Furthermore, using computational and medicinal chemistry, we identified a GBA analog, referred to as DAP-19, which binds potently and selectively to Hsp90β. Because of its unprecedented selectivity for Hsp90β among all Hsp90 paralogs, GBA thus provides a new chemical tool to study the unique biological role of this abundantly expressed molecular chaperone in health and disease. PMID:27466407

A Domain-Specific Terminology for Retinopathy of Prematurity and Its Applications in Clinical Settings.

PubMed

Zhang, Yinsheng; Zhang, Guoming

2018-01-01

A terminology (or coding system) is a formal set of controlled vocabulary in a specific domain. With a well-defined terminology, each concept in the target domain is assigned with a unique code, which can be identified and processed across different medical systems in an unambiguous way. Though there are lots of well-known biomedical terminologies, there is currently no domain-specific terminology for ROP (retinopathy of prematurity). Based on a collection of historical ROP patients' data in the electronic medical record system, we extracted the most frequent terms in the domain and organized them into a hierarchical coding system-ROP Minimal Standard Terminology, which contains 62 core concepts in 4 categories. This terminology has been successfully used to provide highly structured and semantic-rich clinical data in several ROP-related applications.

Prostate-specific antigen screening impacts on biochemical recurrence in patients with clinically localized prostate cancer.

PubMed

Hashimoto, Takeshi; Ohori, Makoto; Shimodaira, Kenji; Kaburaki, Naoto; Hirasawa, Yosuke; Satake, Naoya; Gondo, Tatsuo; Nakagami, Yoshihiro; Namiki, Kazunori; Ohno, Yoshio

2018-06-01

To clarify the impact of prostate-specific antigen screening on surgical outcomes of prostate cancer. Patients who underwent radical prostatectomy were divided into two groups according to prostate-specific antigen testing opportunity (group 1, prostate-specific antigen screening; group 2, non-prostate-specific antigen screening). Perioperative clinical characteristics were compared using the Wilcoxon rank-sum and χ 2 -tests. Cox proportional hazards models were used to identify independent predictors of postoperative biochemical recurrence-free survival. In total, 798 patients (63.2%) and 464 patients (36.8%) were categorized into groups 1 and 2, respectively. Group 2 patients were more likely to have a higher prostate-specific antigen level and age at diagnosis and larger prostate volume. Clinical T stage, percentage of positive cores and pathological Gleason score did not differ between the groups. The 5-year biochemical recurrence-free survival rate was 83.9% for group 1 and 71.0% for group 2 (P < 0.001). On multivariate analysis, prostate-specific antigen testing opportunity (hazard ratio 2.530; P < 0.001) was an independent predictive factor for biochemical recurrence after surgery, as well as pathological T stage, pathological Gleason score, positive surgical margin and lymphovascular invasion. Additional analyses showed that prostate-specific antigen screening had a greater impact on biochemical recurrence in a younger patients, patients with a high prostate-specific antigen level, large prostate volume and D'Amico high risk, and patients meeting the exclusion criteria of the Prostate Cancer Research International Active Surveillance study. Detection by screening results in favorable outcomes after surgery. Prostate-specific antigen screening might contribute to reducing biochemical recurrence in patients with localized prostate cancer. © 2018 The Japanese Urological Association.

High sensitivity and specificity of clinical microscopy in rural health facilities in western Kenya under an external quality assurance program.

PubMed

Wafula, Rebeccah; Sang, Edna; Cheruiyot, Olympia; Aboto, Angeline; Menya, Diana; O'Meara, Wendy Prudhomme

2014-09-01

Microscopic diagnosis of malaria is a well-established and inexpensive technique that has the potential to provide accurate diagnosis of malaria infection. However, it requires both training and experience. Although it is considered the gold standard in research settings, the sensitivity and specificity of routine microscopy for clinical care in the primary care setting has been reported to be unacceptably low. We established a monthly external quality assurance program to monitor the performance of clinical microscopy in 17 rural health centers in western Kenya. The average sensitivity over the 12-month period was 96% and the average specificity was 88%. We identified specific contextual factors that contributed to inadequate performance. Maintaining high-quality malaria diagnosis in high-volume, resource-constrained health facilities is possible. © The American Society of Tropical Medicine and Hygiene.

Evaluating the validity of clinical codes to identify cataract and glaucoma in the UK Clinical Practice Research Datalink.

PubMed

Kang, Elizabeth M; Pinheiro, Simone P; Hammad, Tarek A; Abou-Ali, Adel

2015-01-01

The aim of this study is to determine (i) the positive predictive value (PPV) of an algorithm using clinical codes to identify incident glaucoma and cataract events in the Clinical Practice Research Datalink (CPRD) and (ii) the ability to capture the correct timing of these clinical events. A total of 21,339 and 5349 potential cataract and glaucoma cases, respectively, were identified in CPRD between 1 January 1990 and 31 December 2010. Questionnaires were sent to the general practitioners (GP) of 1169 (5.5%) cataract and 1163 (21.7%) glaucoma cases for validation. GPs were asked to verify the diagnosis and the timing of the diagnosis and to provide other supporting information. A total of 986 (84.3%) valid cataract questionnaires and 863 (74.2%) glaucoma questionnaires were completed. 92.1% and 92.4% of these used information beyond EMR to verify the diagnosis. Cataract and glaucoma diagnoses were confirmed in the large majority of the cases. The PPV (95% CI) of the cataract and glaucoma Read code algorithm were 92.0% (90.3-93.7%) and 84.1% (81.7-86.6%), respectively. However, timing of diagnosis was incorrect for a substantial proportion of the cases (20.3% and 32.8% of the cataract and glaucoma cases, respectively) among whom 30.4% and 49.2% had discrepancies in diagnosis timing greater than 1 year. High PPV suggests that the algorithms based on the clinical Read codes are sufficient to identify the cataract and glaucoma cases in CPRD. However, these codes alone may not be able to accurately identify the timing of the diagnosis of these eye disorders. Ltd. Copyright © 2014 John Wiley & Sons, Ltd.

Distinguishing between demoralization and specific personality traits in clinical assessment with the NEO-PI-R.

PubMed

Noordhof, Arjen; Sellbom, Martin; Eigenhuis, Annemarie; Kamphuis, Jan H

2015-06-01

Demoralization, a nonspecific unpleasant state that is common in clinical practice, has been identified as a potential source of nonspecificity in the assessment of personality and psychopathology. The aim of this research was to distinguish between Demoralization and specific personality traits in a widely used measure of personality: the Neuroticism-Extraversion-Openness Personality Inventory-Revised (NEO-PI-R). NEO-PI-R and Minnesota Multiphasic Personality Inventory-2 questionnaires were completed by 278 patients of a specialized clinic for personality disorders in The Netherlands. Furthermore, a replication sample was used consisting of 405 patients from the same institution who completed NEO-PI-R questionnaires, as well. A measure of Demoralization was derived (NEOdem, a NEO-PI-R-based Demoralization scale) using factor analytic techniques. Results indicated that the Demoralization Scale scores were reliable and showed expected patterns of convergence and divergence with conceptually relevant Minnesota Multiphasic Personality Inventory-2-RF scales. When items contributing to Demoralization-related variance were removed from the NEO-PI-R scales, increased specificity was notable with regard to external correlates. These results provide supportive evidence for the validity and heuristic potential of distinguishing between Demoralization and specific personality traits within the NEO-PI-R. (c) 2015 APA, all rights reserved).

The sensitivity and specificity of clinical measures of sport concussion: three tests are better than one

PubMed Central

Resch, Jacob E; Brown, Cathleen N; Schmidt, Julianne; Macciocchi, Stephen N; Blueitt, Damond; Cullum, C Munro; Ferrara, Michael S

2016-01-01

Context A battery of clinical measures of neurocognition, balance and symptoms has been recommended for the management of sport concussion (SC) but is based on variable evidence. Objective To examine the sensitivity and specificity of a battery of tests to assess SC in college athletes. Design Cross-sectional. Setting Research laboratory. Patients or other participants Division 1 athletes diagnosed with a SC (n=40) who were 20.2±1.60 years of age and 180.5±11.12 cm tall and healthy athletes (n=40) who were 19.0±0.93 years of age and 179.1±11.39 cm tall were enrolled. Intervention(s) Participants were administered Immediate Postconcussion Assessment and Cognitive Test (ImPACT), the Sensory Organization Test (SOT) and the Revised Head Injury Scale (HIS-r) prior to and up to 24 h following injury between the 2004 and 2014 sport seasons. Sensitivity and specificity were calculated using predictive discriminant analyses (PDA) and clinical interpretation guidelines. Main outcome measures Outcome measures included baseline and postinjury ImPACT, SOT and HIS-r composite scores. Results Using PDA, each clinical measure's sensitivity ranged from 55.0% to 77.5% and specificity ranged from 52.5% to 100%. The test battery possessed a sensitivity and specificity of 80.0% and 100%, respectively. Using clinical interpretation guidelines, sensitivity ranged from 55% to 97.5% individually, and 100% when combined. Conclusions Our results support a multidimensional approach to assess SC in college athletes which correctly identified 80–100% of concussed participants as injured. When each test was evaluated separately, up to 47.5% of our sample was misclassified. Caution is warranted when using singular measures to manage SC. PMID:27900145

Clinical Potential of Prefusion RSV F-specific Antibodies.

PubMed

Rossey, Iebe; McLellan, Jason S; Saelens, Xavier; Schepens, Bert

2018-03-01

Human respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in the very young. The RSV fusion protein (F) is essential for virus entry because it mediates viral and host membrane fusion. During this fusion process F is converted from a metastable prefusion conformation into an energetically favored postfusion state. Antibodies that target F can prevent viral entry and reduce disease caused by RSV. During recent years, many prefusion F-specific antibodies have been described. These antibodies typically have stronger RSV-neutralizing activity compared to those that also bind F in the postfusion conformation. Here, we describe how F-specific antibodies protect against RSV and why specifically targeting prefusion F could have great clinical potential. Copyright © 2017 Elsevier Ltd. All rights reserved.

Genus Level Identification of Mycobacteria from Clinical Specimens by Using an Easy-To-Handle Mycobacterium-Specific PCR Assay

PubMed Central

Stauffer, Fritz; Haber, Heinrich; Rieger, Armin; Mutschlechner, Robert; Hasenberger, Petra; Tevere, Vincent J.; Young, Karen K. Y.

1998-01-01

An easy-to-handle Mycobacterium-specific PCR assay for detection of the presence of a wide range of mycobacterial species in clinical samples was evaluated. The performance of the genus probe was compared with the performance of probes specific for Mycobacterium tuberculosis and Mycobacterium avium and with that of standard culture. In addition, the utility of an internal control in monitoring amplification inhibitors was studied. Of 545 respiratory and 325 nonrespiratory specimens (a total of 870 specimens), 58 (6.7%) showed the presence of amplification inhibitors, as determined by a negative result for the internal control. Of these 58 specimens, 31 (53%) were stool specimens; other material, even citrate blood after lysis of erythrocytes, did not pose a problem with regard to inhibition of PCR amplification. Eighty-one of the remaining 812 specimens had a positive Mycobacterium culture result. Of these culture-positive specimens, 58 (71.6%) showed a positive result with the Mycobacterium genus-specific probe. Seventy-two samples had a positive result with the Mycobacterium-specific probe but a negative culture result. Of these 72 samples, 26 samples were regarded as true positive, either because the M. tuberculosis- or M. avium-specific probe was also positive at the same time or because other specimens from the same patient taken at the same time were culture positive. The sensitivity of the Mycobacterium-specific probe was 78.5% and the specificity was 93.5%. This study showed that pretesting of clinical specimens for mycobacteria to the genus level with a Mycobacterium-specific probe offers the routine clinical laboratory the possibility of detecting tuberculous and nontuberculous mycobacteria with one test. Furthermore, specimens testing positive with the genus-specific probe can be immediately identified with species-specific probes. PMID:9508282

Functional measures developed for clinical populations identified impairment among active workers with upper extremity disorders

PubMed Central

Gardner, Bethany T.; Dale, Ann Marie; Buckner-Petty, Skye; Rachford, Robert; Strickland, Jaime; Kaskutas, Vicki; Evanoff, Bradley

2017-01-01

Purpose Few studies have explored measures of function across a range of health outcomes in a general working population. Using four upper extremity (UE) case definitions from the scientific literature, we described the performance of functional measures of work, activities of daily living, and overall health. Methods A sample of 573 workers completed several functional measures: modified recall versions of the QuickDASH, Levine Functional Status Scale (FSS), DASH Work module (DASH-W), and standard SF-8 physical component score. We determined case status based on four UE case definitions: 1) UE symptoms, 2) UE musculoskeletal disorders (MSD), 3) carpal tunnel syndrome (CTS), and 4) work limitations due to UE symptoms. We calculated effect sizes for each case definition to show the magnitude of the differences that were detected between cases and non-cases for each case definition on each functional measure. Sensitivity and specificity analyses showed how well each measure identified functional impairments across the UE case definitions. Results All measures discriminated between cases and non-cases for each case definition with the largest effect sizes for CTS and work limitations, particularly for the modified FSS and DASH-W measures. Specificity was high and sensitivity was low for outcomes of UE symptoms and UE MSD in all measures. Sensitivity was high for CTS and work limitations. Conclusions Functional measures developed specifically for use in clinical, treatment-seeking populations may identify mild levels of impairment in relatively healthy, active working populations, but measures performed better among workers with CTS or those reporting limitations at work. PMID:26091980

Elbow-specific clinical rating systems: extent of established validity, reliability, and responsiveness.

PubMed

The, Bertram; Reininga, Inge H F; El Moumni, Mostafa; Eygendaal, Denise

2013-10-01

The modern standard of evaluating treatment results includes the use of rating systems. Elbow-specific rating systems are frequently used in studies aiming at elbow-specific pathology. However, proper validation studies seem to be relatively sparse. In addition, these scoring systems might not always be used for appropriate populations of interest. Both of these issues might give rise to invalid conclusions being reported in the literature. Our aim was to investigate the extent to which the available elbow-specific outcome measurement tools have been validated and the quality of the validation itself. We also aimed to provide characteristics of the populations used for validation of these scales to enable clinicians to use them appropriately. A literature search identified 17 studies of 12 different elbow-specific scoring systems. These were assessed for validity, reliability, and responsiveness characteristics. The quality of these assessments was rated according to the Consensus Based Standards for the Selection of Health Measurement Instruments (COSMIN) checklist criteria, a standardized and validated tool developed specifically for this purpose. Currently, the only elbow-specific rating system that is validated using high-quality methodology is the Oxford Elbow Score, a patient-administered outcome measure tool that has been validated on heterogeneous study populations. Other rating systems still have to be proven in the future to be as good as the Oxford Elbow Score for clinical or research purposes. Additional validation studies are needed. Copyright © 2013 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.

Chimeric Antigen Receptor (CAR)-Specific Monoclonal Antibody to Detect CD19-Specific T Cells in Clinical Trials

PubMed Central

Jena, Bipulendu; Maiti, Sourindra; Huls, Helen; Singh, Harjeet; Lee, Dean A.; Champlin, Richard E.; Cooper, Laurence J. N.

2013-01-01

Clinical trials targeting CD19 on B-cell malignancies are underway with encouraging anti-tumor responses. Most infuse T cells genetically modified to express a chimeric antigen receptor (CAR) with specificity derived from the scFv region of a CD19-specific mouse monoclonal antibody (mAb, clone FMC63). We describe a novel anti-idiotype monoclonal antibody (mAb) to detect CD19-specific CAR+ T cells before and after their adoptive transfer. This mouse mAb was generated by immunizing with a cellular vaccine expressing the antigen-recognition domain of FMC63. The specificity of the mAb (clone no. 136.20.1) was confined to the scFv region of the CAR as validated by inhibiting CAR-dependent lysis of CD19+ tumor targets. This clone can be used to detect CD19-specific CAR+ T cells in peripheral blood mononuclear cells at a sensitivity of 1∶1,000. In clinical settings the mAb is used to inform on the immunophenotype and persistence of administered CD19-specific T cells. Thus, our CD19-specific CAR mAb (clone no. 136.20.1) will be useful to investigators implementing CD19-specific CAR+ T cells to treat B-lineage malignancies. The methodology described to develop a CAR-specific anti-idiotypic mAb could be extended to other gene therapy trials targeting different tumor associated antigens in the context of CAR-based adoptive T-cell therapy. PMID:23469246

Genome-wide association studies identify four ER negative-specific breast cancer risk loci.

PubMed

Garcia-Closas, Montserrat; Couch, Fergus J; Lindstrom, Sara; Michailidou, Kyriaki; Schmidt, Marjanka K; Brook, Mark N; Orr, Nick; Rhie, Suhn Kyong; Riboli, Elio; Feigelson, Heather S; Le Marchand, Loic; Buring, Julie E; Eccles, Diana; Miron, Penelope; Fasching, Peter A; Brauch, Hiltrud; Chang-Claude, Jenny; Carpenter, Jane; Godwin, Andrew K; Nevanlinna, Heli; Giles, Graham G; Cox, Angela; Hopper, John L; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Dicks, Ed; Howat, Will J; Schoof, Nils; Bojesen, Stig E; Lambrechts, Diether; Broeks, Annegien; Andrulis, Irene L; Guénel, Pascal; Burwinkel, Barbara; Sawyer, Elinor J; Hollestelle, Antoinette; Fletcher, Olivia; Winqvist, Robert; Brenner, Hermann; Mannermaa, Arto; Hamann, Ute; Meindl, Alfons; Lindblom, Annika; Zheng, Wei; Devillee, Peter; Goldberg, Mark S; Lubinski, Jan; Kristensen, Vessela; Swerdlow, Anthony; Anton-Culver, Hoda; Dörk, Thilo; Muir, Kenneth; Matsuo, Keitaro; Wu, Anna H; Radice, Paolo; Teo, Soo Hwang; Shu, Xiao-Ou; Blot, William; Kang, Daehee; Hartman, Mikael; Sangrajrang, Suleeporn; Shen, Chen-Yang; Southey, Melissa C; Park, Daniel J; Hammet, Fleur; Stone, Jennifer; Veer, Laura J Van't; Rutgers, Emiel J; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Peto, Julian; Schrauder, Michael G; Ekici, Arif B; Beckmann, Matthias W; Dos Santos Silva, Isabel; Johnson, Nichola; Warren, Helen; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Marme, Federick; Schneeweiss, Andreas; Sohn, Christof; Truong, Therese; Laurent-Puig, Pierre; Kerbrat, Pierre; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Milne, Roger L; Perez, Jose Ignacio Arias; Menéndez, Primitiva; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Lichtner, Peter; Lochmann, Magdalena; Justenhoven, Christina; Ko, Yon-Dschun; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Greco, Dario; Heikkinen, Tuomas; Ito, Hidemi; Iwata, Hiroji; Yatabe, Yasushi; Antonenkova, Natalia N; Margolin, Sara; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Balleine, Rosemary; Tseng, Chiu-Chen; Berg, David Van Den; Stram, Daniel O; Neven, Patrick; Dieudonné, Anne-Sophie; Leunen, Karin; Rudolph, Anja; Nickels, Stefan; Flesch-Janys, Dieter; Peterlongo, Paolo; Peissel, Bernard; Bernard, Loris; Olson, Janet E; Wang, Xianshu; Stevens, Kristen; Severi, Gianluca; Baglietto, Laura; McLean, Catriona; Coetzee, Gerhard A; Feng, Ye; Henderson, Brian E; Schumacher, Fredrick; Bogdanova, Natalia V; Labrèche, France; Dumont, Martine; Yip, Cheng Har; Taib, Nur Aishah Mohd; Cheng, Ching-Yu; Shrubsole, Martha; Long, Jirong; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Tollenaar, Robertus A E M; Seynaeve, Caroline M; Kriege, Mieke; Hooning, Maartje J; van den Ouweland, Ans M W; van Deurzen, Carolien H M; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Balasubramanian, Sabapathy P; Cross, Simon S; Reed, Malcolm W R; Signorello, Lisa; Cai, Qiuyin; Shah, Mitul; Miao, Hui; Chan, Ching Wan; Chia, Kee Seng; Jakubowska, Anna; Jaworska, Katarzyna; Durda, Katarzyna; Hsiung, Chia-Ni; Wu, Pei-Ei; Yu, Jyh-Cherng; Ashworth, Alan; Jones, Michael; Tessier, Daniel C; González-Neira, Anna; Pita, Guillermo; Alonso, M Rosario; Vincent, Daniel; Bacot, Francois; Ambrosone, Christine B; Bandera, Elisa V; John, Esther M; Chen, Gary K; Hu, Jennifer J; Rodriguez-Gil, Jorge L; Bernstein, Leslie; Press, Michael F; Ziegler, Regina G; Millikan, Robert M; Deming-Halverson, Sandra L; Nyante, Sarah; Ingles, Sue A; Waisfisz, Quinten; Tsimiklis, Helen; Makalic, Enes; Schmidt, Daniel; Bui, Minh; Gibson, Lorna; Müller-Myhsok, Bertram; Schmutzler, Rita K; Hein, Rebecca; Dahmen, Norbert; Beckmann, Lars; Aaltonen, Kirsimari; Czene, Kamila; Irwanto, Astrid; Liu, Jianjun; Turnbull, Clare; Rahman, Nazneen; Meijers-Heijboer, Hanne; Uitterlinden, Andre G; Rivadeneira, Fernando; Olswold, Curtis; Slager, Susan; Pilarski, Robert; Ademuyiwa, Foluso; Konstantopoulou, Irene; Martin, Nicholas G; Montgomery, Grant W; Slamon, Dennis J; Rauh, Claudia; Lux, Michael P; Jud, Sebastian M; Bruning, Thomas; Weaver, Joellen; Sharma, Priyanka; Pathak, Harsh; Tapper, Will; Gerty, Sue; Durcan, Lorraine; Trichopoulos, Dimitrios; Tumino, Rosario; Peeters, Petra H; Kaaks, Rudolf; Campa, Daniele; Canzian, Federico; Weiderpass, Elisabete; Johansson, Mattias; Khaw, Kay-Tee; Travis, Ruth; Clavel-Chapelon, Françoise; Kolonel, Laurence N; Chen, Constance; Beck, Andy; Hankinson, Susan E; Berg, Christine D; Hoover, Robert N; Lissowska, Jolanta; Figueroa, Jonine D; Chasman, Daniel I; Gaudet, Mia M; Diver, W Ryan; Willett, Walter C; Hunter, David J; Simard, Jacques; Benitez, Javier; Dunning, Alison M; Sherman, Mark E; Chenevix-Trench, Georgia; Chanock, Stephen J; Hall, Per; Pharoah, Paul D P; Vachon, Celine; Easton, Douglas F; Haiman, Christopher A; Kraft, Peter

2013-04-01

Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P = 2.1 × 10(-12) and LGR6, P = 1.4 × 10(-8)), 2p24.1 (P = 4.6 × 10(-8)) and 16q12.2 (FTO, P = 4.0 × 10(-8)), were associated with ER-negative but not ER-positive breast cancer (P > 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers.

40 CFR 148.18 - Waste specific prohibitions-newly listed and identified wastes.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Waste specific prohibitions-newly listed and identified wastes. 148.18 Section 148.18 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) HAZARDOUS WASTE INJECTION RESTRICTIONS Prohibitions on...

Development of Specific Sequence-Characterized Amplified Region Markers for Detecting Histoplasma capsulatum in Clinical and Environmental Samples

PubMed Central

Frías De León, María Guadalupe; Arenas López, Gabina; Taylor, Maria Lucia; Acosta Altamirano, Gustavo

2012-01-01

Sequence-characterized amplified region (SCAR) markers, generated by randomly amplified polymorphic DNA (RAPD)-PCR, were developed to detect Histoplasma capsulatum selectively in clinical and environmental samples. A 1,200-bp RAPD-PCR-specific band produced with the 1281-1283 primers was cloned, sequenced, and used to design two SCAR markers, 1281-1283220 and 1281-1283230. The specificity of these markers was confirmed by Southern hybridization. To evaluate the relevance of the SCAR markers for the diagnosis of histoplasmosis, another molecular marker (M antigen probe) was used for comparison. To validate 1281-1283220 and 1281-1283230 as new tools for the identification of H. capsulatum, the specificity and sensitivity of these markers were assessed for the detection of the pathogen in 36 clinical (17 humans, as well as 9 experimentally and 10 naturally infected nonhuman mammals) and 20 environmental (10 contaminated soil and 10 guano) samples. Although the two SCAR markers and the M antigen probe identified H. capsulatum isolates from different geographic origins in America, the 1281-1283220 SCAR marker was the most specific and detected the pathogen in all samples tested. In contrast, the 1281-1283230 SCAR marker and the M antigen probe also amplified DNA from Aspergillus niger and Cryptococcus neoformans, respectively. Both SCAR markers detected as little as 0.001 ng of H. capsulatum DNA, while the M antigen probe detected 0.5 ng of fungal DNA. The SCAR markers revealed the fungal presence better than the M antigen probe in contaminated soil and guano samples. Based on our results, the 1281-1283220 marker can be used to detect and identify H. capsulatum in samples from different sources. PMID:22189121

Automatically identifying health- and clinical-related content in wikipedia.

PubMed

Liu, Feifan; Moosavinasab, Soheil; Agarwal, Shashank; Bennett, Andrew S; Yu, Hong

2013-01-01

Physicians are increasingly using the Internet for finding medical information related to patient care. Wikipedia is a valuable online medical resource to be integrated into existing clinical question answering (QA) systems. On the other hand, Wikipedia contains a full spectrum of world's knowledge and therefore comprises a large partition of non-health-related content, which makes disambiguation more challenging and consequently leads to large overhead for existing systems to effectively filter irrelevant information. To overcome this, we have developed both unsupervised and supervised approaches to identify health-related articles as well as clinically relevant articles. Furthermore, we explored novel features by extracting health related hierarchy from the Wikipedia category network, from which a variety of features were derived and evaluated. Our experiments show promising results and also demonstrate that employing the category hierarchy can effectively improve the system performance.

Characteristics and treatment response of self-identified problematic Internet users in a behavioral addiction outpatient clinic.

PubMed

Thorens, Gabriel; Achab, Sophia; Billieux, Joël; Khazaal, Yasser; Khan, Riaz; Pivin, Edward; Gupta, Vishal; Zullino, Daniel

2014-03-01

Controversies remain about the validity of the diagnosis of problematic Internet use. This might be due in part to the lack of longitudinal naturalistic studies that have followed a cohort of patients who self-identify as having Internet-related problems. This retrospective study included 57 patients who consulted the Geneva Addiction Outpatient Clinic from January 1, 2007, to January 1, 2010. Patients underwent an initial clinical psychiatric evaluation that included collection of data on socio-demographics, method of referral, specific Internet usage, psychiatric diagnosis, and Internet Addiction Test (IAT) and Clinical Global Impression Scale (CGI) scores. Treatment consisted of individual psychotherapeutic sessions. Of these patients, 98% were male and 37% were 18 years or younger. Most patients were online gamers (46% playing massively multiplayer online role-playing games). The mean IAT score was 52.9 (range 20-90). Sixty-eight percent of patients had a co-morbid psychiatric diagnosis, with social phobia being the most prevalent (17.8%). Patients who remained in treatment (dropout rate 24%) showed an overall improvement of symptoms: 38.6% showed significant or average improvement on their CGI score, 26.3% showed minimal improvement, and 14% showed no change. Our results support the hypothesis that there are specific types of Internet use, with online gaming mainly affecting young male patients. As Internet addiction is not yet an official diagnosis, better instruments are needed to screen patients and to avoid false-negative and false-positive diagnoses. Successful care should integrate the treatment of co-morbid symptoms and involve families and relatives in the therapeutic process.

Effects of personal identifier resynthesis on clinical text de-identification.

PubMed

Yeniterzi, Reyyan; Aberdeen, John; Bayer, Samuel; Wellner, Ben; Hirschman, Lynette; Malin, Bradley

2010-01-01

De-identified medical records are critical to biomedical research. Text de-identification software exists, including "resynthesis" components that replace real identifiers with synthetic identifiers. The goal of this research is to evaluate the effectiveness and examine possible bias introduced by resynthesis on de-identification software. We evaluated the open-source MITRE Identification Scrubber Toolkit, which includes a resynthesis capability, with clinical text from Vanderbilt University Medical Center patient records. We investigated four record classes from over 500 patients' files, including laboratory reports, medication orders, discharge summaries and clinical notes. We trained and tested the de-identification tool on real and resynthesized records. We measured performance in terms of precision, recall, F-measure and accuracy for the detection of protected health identifiers as designated by the HIPAA Safe Harbor Rule. The de-identification tool was trained and tested on a collection of real and resynthesized Vanderbilt records. Results for training and testing on the real records were 0.990 accuracy and 0.960 F-measure. The results improved when trained and tested on resynthesized records with 0.998 accuracy and 0.980 F-measure but deteriorated moderately when trained on real records and tested on resynthesized records with 0.989 accuracy 0.862 F-measure. Moreover, the results declined significantly when trained on resynthesized records and tested on real records with 0.942 accuracy and 0.728 F-measure. The de-identification tool achieves high accuracy when training and test sets are homogeneous (ie, both real or resynthesized records). The resynthesis component regularizes the data to make them less "realistic," resulting in loss of performance particularly when training on resynthesized data and testing on real data.

Global population-specific variation in miRNA associated with cancer risk and clinical biomarkers.

PubMed

Rawlings-Goss, Renata A; Campbell, Michael C; Tishkoff, Sarah A

2014-08-28

MiRNA expression profiling is being actively investigated as a clinical biomarker and diagnostic tool to detect multiple cancer types and stages as well as other complex diseases. Initial investigations, however, have not comprehensively taken into account genetic variability affecting miRNA expression and/or function in populations of different ethnic backgrounds. Therefore, more complete surveys of miRNA genetic variability are needed to assess global patterns of miRNA variation within and between diverse human populations and their effect on clinically relevant miRNA genes. Genetic variation in 1524 miRNA genes was examined using whole genome sequencing (60x coverage) in a panel of 69 unrelated individuals from 14 global populations, including European, Asian and African populations. We identified 33 previously undescribed miRNA variants, and 31 miRNA containing variants that are globally population-differentiated in frequency between African and non-African populations (PD-miRNA). The top 1% of PD-miRNA were significantly enriched for regulation of genes involved in glucose/insulin metabolism and cell division (p < 10(-7)), most significantly the mitosis pathway, which is strongly linked to cancer onset. Overall, we identify 7 PD-miRNAs that are currently implicated as cancer biomarkers or diagnostics: hsa-mir-202, hsa-mir-423, hsa-mir-196a-2, hsa-mir-520h, hsa-mir-647, hsa-mir-943, and hsa-mir-1908. Notably, hsa-mir-202, a potential breast cancer biomarker, was found to show significantly high allele frequency differentiation at SNP rs12355840, which is known to affect miRNA expression levels in vivo and subsequently breast cancer mortality. MiRNA expression profiles represent a promising new category of disease biomarkers. However, population specific genetic variation can affect the prevalence and baseline expression of these miRNAs in diverse populations. Consequently, miRNA genetic and expression level variation among ethnic groups may be contributing in

[Identifying the specific causes of kidney allograft loss: A population-based study].

PubMed

Lohéac, Charlotte; Aubert, Olivier; Loupy, Alexandre; Legendre, Christophe

2018-04-01

Results of kidney transplantation have been improving but long-term allograft survival remains disappointing. The objective of the present study was to identify the specific causes of renal allograft loss, to assess their incidence and long-term outcomes. A total of 4783 patients from four French centres, transplanted between January 2004 and January 2014 were prospectively included. A total of 9959 kidney biopsies (protocol and for cause) performed between January 2004 and March 2015 were included. Donor and recipient clinical and biological parameters as well as anti-HLA antibody directed against the donor were included. The main outcome was the long-term kidney allograft survival, including the study of the associated causes of graft loss, the delay of graft loss according to their causes and the determinants of graft loss. There were 732 graft losses during the follow-up period (median time: 4.51 years) with an identified cause in 95.08 %. Kidney allograft survival at 9 years post-transplant was 78 %. The causes of allograft loss were: antibody-mediated rejection (31.69 %), thrombosis (25.55 %), medical intercurrent disease (14.62 %), recurrence of primary renal disease (7.1 %), BK- or CMV-associated nephropathy (n=35, 4.78 %), T cell-mediated rejection (4.78 %), urological disease (2.46 %) and calcineurin inhibitor nephrotoxicity (1.09 %). The main causes of allograft loss were antibody-mediated rejection and thrombosis. These results encourage efforts to prevent and detect these complications earlier in order to improve allograft survival. Copyright © 2018 Association Société de néphrologie. Published by Elsevier Masson SAS. All rights reserved.

Rheumatoid arthritis (RA)-specific autoantibodies in patients with interstitial lung disease and absence of clinically apparent articular RA.

PubMed

Gizinski, Alison M; Mascolo, Margherita; Loucks, Jennifer L; Kervitsky, Alma; Meehan, Richard T; Brown, Kevin K; Holers, V Michael; Deane, Kevin D

2009-05-01

The purpose of this study was to identify rheumatoid arthritis (RA)-related autoantibodies in subjects with interstitial lung disease (ILD) and no articular findings of RA, supporting the hypothesis that RA-related autoimmunity may be generated in non-articular sites, such as the lung. This was a retrospective chart review utilizing clinic databases of patients with ILD to identify cases with lung disease, RA-related autoantibody positivity, and no clinical evidence of articular RA. Four patients with ILD, RF, and anti-CCP positivity and no articular findings of RA were identified. All four patients were male with a mean age at time of diagnosis of ILD of 70 years old. All had a history of smoking. Three patients died within 2 years of diagnosis of ILD and never developed articular symptoms consistent with RA; the final case met full criteria for articular RA several months after stopping immunosuppressive treatment for ILD. RF and anti-CCP can be present in smokers with ILD without clinical evidence of articular RA and in one case symptomatic ILD and autoantibody positivity preceded the development of articular RA. These findings suggest that RA-specific autoimmunity may be generated due to immunologic interactions in the lung and may be related to environmental factors such as smoking.

The value of structured data elements from electronic health records for identifying subjects for primary care clinical trials.

PubMed

Ateya, Mohammad B; Delaney, Brendan C; Speedie, Stuart M

2016-01-11

An increasing number of clinical trials are conducted in primary care settings. Making better use of existing data in the electronic health records to identify eligible subjects can improve efficiency of such studies. Our study aims to quantify the proportion of eligibility criteria that can be addressed with data in electronic health records and to compare the content of eligibility criteria in primary care with previous work. Eligibility criteria were extracted from primary care studies downloaded from the UK Clinical Research Network Study Portfolio. Criteria were broken into elemental statements. Two expert independent raters classified each statement based on whether or not structured data items in the electronic health record can be used to determine if the statement was true for a specific patient. Disagreements in classification were discussed until 100 % agreement was reached. Statements were also classified based on content and the percentages of each category were compared to two similar studies reported in the literature. Eligibility criteria were retrieved from 228 studies and decomposed into 2619 criteria elemental statements. 74 % of the criteria elemental statements were considered likely associated with structured data in an electronic health record. 79 % of the studies had at least 60 % of their criteria statements addressable with structured data likely to be present in an electronic health record. Based on clinical content, most frequent categories were: "disease, symptom, and sign", "therapy or surgery", and "medication" (36 %, 13 %, and 10 % of total criteria statements respectively). We also identified new criteria categories related to provider and caregiver attributes (2.6 % and 1 % of total criteria statements respectively). Electronic health records readily contain much of the data needed to assess patients' eligibility for clinical trials enrollment. Eligibility criteria content categories identified by our study can be

Analysis of the Human Prostate-Specific Proteome Defined by Transcriptomics and Antibody-Based Profiling Identifies TMEM79 and ACOXL as Two Putative, Diagnostic Markers in Prostate Cancer

PubMed Central

O'Hurley, Gillian; Busch, Christer; Fagerberg, Linn; Hallström, Björn M.; Stadler, Charlotte; Tolf, Anna; Lundberg, Emma; Schwenk, Jochen M.; Jirström, Karin; Bjartell, Anders; Gallagher, William M.; Uhlén, Mathias; Pontén, Fredrik

2015-01-01

To better understand prostate function and disease, it is important to define and explore the molecular constituents that signify the prostate gland. The aim of this study was to define the prostate specific transcriptome and proteome, in comparison to 26 other human tissues. Deep sequencing of mRNA (RNA-seq) and immunohistochemistry-based protein profiling were combined to identify prostate specific gene expression patterns and to explore tissue biomarkers for potential clinical use in prostate cancer diagnostics. We identified 203 genes with elevated expression in the prostate, 22 of which showed more than five-fold higher expression levels compared to all other tissue types. In addition to previously well-known proteins we identified two poorly characterized proteins, TMEM79 and ACOXL, with potential to differentiate between benign and cancerous prostatic glands in tissue biopsies. In conclusion, we have applied a genome-wide analysis to identify the prostate specific proteome using transcriptomics and antibody-based protein profiling to identify genes with elevated expression in the prostate. Our data provides a starting point for further functional studies to explore the molecular repertoire of normal and diseased prostate including potential prostate cancer markers such as TMEM79 and ACOXL. PMID:26237329

Subgroup analyses in confirmatory clinical trials: time to be specific about their purposes.

PubMed

Tanniou, Julien; van der Tweel, Ingeborg; Teerenstra, Steven; Roes, Kit C B

2016-02-18

It is well recognized that treatment effects may not be homogeneous across the study population. Subgroup analyses constitute a fundamental step in the assessment of evidence from confirmatory (Phase III) clinical trials, where conclusions for the overall study population might not hold. Subgroup analyses can have different and distinct purposes, requiring specific design and analysis solutions. It is relevant to evaluate methodological developments in subgroup analyses against these purposes to guide health care professionals and regulators as well as to identify gaps in current methodology. We defined four purposes for subgroup analyses: (1) Investigate the consistency of treatment effects across subgroups of clinical importance, (2) Explore the treatment effect across different subgroups within an overall non-significant trial, (3) Evaluate safety profiles limited to one or a few subgroup(s), (4) Establish efficacy in the targeted subgroup when included in a confirmatory testing strategy of a single trial. We reviewed the methodology in line with this "purpose-based" framework. The review covered papers published between January 2005 and April 2015 and aimed to classify them in none, one or more of the aforementioned purposes. In total 1857 potentially eligible papers were identified. Forty-eight papers were selected and 20 additional relevant papers were identified from their references, leading to 68 papers in total. Nineteen were dedicated to purpose 1, 16 to purpose 4, one to purpose 2 and none to purpose 3. Seven papers were dedicated to more than one purpose, the 25 remaining could not be classified unambiguously. Purposes of the methods were often not specifically indicated, methods for subgroup analysis for safety purposes were almost absent and a multitude of diverse methods were developed for purpose (1). It is important that researchers developing methodology for subgroup analysis explicitly clarify the objectives of their methods in terms that can be

Diagnostic accuracy of clinical examination features for identifying large rotator cuff tears in primary health care

PubMed Central

Cadogan, Angela; McNair, Peter; Laslett, Mark; Hing, Wayne; Taylor, Stephen

2013-01-01

Objectives: Rotator cuff tears are a common and disabling complaint. The early diagnosis of medium and large size rotator cuff tears can enhance the prognosis of the patient. The aim of this study was to identify clinical features with the strongest ability to accurately predict the presence of a medium, large or multitendon (MLM) rotator cuff tear in a primary care cohort. Methods: Participants were consecutively recruited from primary health care practices (n = 203). All participants underwent a standardized history and physical examination, followed by a standardized X-ray series and diagnostic ultrasound scan. Clinical features associated with the presence of a MLM rotator cuff tear were identified (P<0.200), a logistic multiple regression model was derived for identifying a MLM rotator cuff tear and thereafter diagnostic accuracy was calculated. Results: A MLM rotator cuff tear was identified in 24 participants (11.8%). Constant pain and a painful arc in abduction were the strongest predictors of a MLM tear (adjusted odds ratio 3.04 and 13.97 respectively). Combinations of ten history and physical examination variables demonstrated highest levels of sensitivity when five or fewer were positive [100%, 95% confidence interval (CI): 0.86–1.00; negative likelihood ratio: 0.00, 95% CI: 0.00–0.28], and highest specificity when eight or more were positive (0.91, 95% CI: 0.86–0.95; positive likelihood ratio 4.66, 95% CI: 2.34–8.74). Discussion: Combinations of patient history and physical examination findings were able to accurately detect the presence of a MLM rotator cuff tear. These findings may aid the primary care clinician in more efficient and accurate identification of rotator cuff tears that may require further investigation or orthopedic consultation. PMID:24421626

Specific barriers to the conduct of randomised clinical trials on medical devices.

PubMed

Neugebauer, Edmund A M; Rath, Ana; Antoine, Sunya-Lee; Eikermann, Michaela; Seidel, Doerthe; Koenen, Carsten; Jacobs, Esther; Pieper, Dawid; Laville, Martine; Pitel, Séverine; Martinho, Cecilia; Djurisic, Snezana; Demotes-Mainard, Jacques; Kubiak, Christine; Bertele, Vittorio; Jakobsen, Janus C; Garattini, Silvio; Gluud, Christian

2017-09-13

Medical devices play an important role in the diagnosis, prevention, treatment and care of diseases. However, compared to pharmaceuticals, there is no rigorous formal regulation for demonstration of benefits and exclusion of harms to patients. The medical device industry argues that the classical evidence hierarchy cannot be applied for medical devices, as randomised clinical trials are impossible to perform. This article aims to identify the barriers for randomised clinical trials on medical devices. Systematic literature searches without meta-analysis and internal European Clinical Research Infrastructure Network (ECRIN) communications taking place during face-to-face meetings and telephone conferences from 2013 to 2017 within the context of the ECRIN Integrating Activity (ECRIN-IA) project. In addition to the barriers that exist for all trials, we identified three major barriers for randomised clinical trials on medical devices, namely: (1) randomisation, including timing of assessment, acceptability, blinding, choice of the comparator group and considerations on the learning curve; (2) difficulties in determining appropriate outcomes; and (3) the lack of scientific advice, regulations and transparency. The present review offers potential solutions to break down the barriers identified, and argues for applying the randomised clinical trial design when assessing the benefits and harms of medical devices.

Measures That Identify Prescription Medication Misuse, Abuse, and Related Events in Clinical Trials: ACTTION Critique and Recommended Considerations.

PubMed

Smith, Shannon M; Jones, Judith K; Katz, Nathaniel P; Roland, Carl L; Setnik, Beatrice; Trudeau, Jeremiah J; Wright, Stephen; Burke, Laurie B; Comer, Sandra D; Dart, Richard C; Dionne, Raymond; Haddox, J David; Jaffe, Jerome H; Kopecky, Ernest A; Martell, Bridget A; Montoya, Ivan D; Stanton, Marsha; Wasan, Ajay D; Turk, Dennis C; Dworkin, Robert H

2017-11-01

Accurate assessment of inappropriate medication use events (ie, misuse, abuse, and related events) occurring in clinical trials is an important component in evaluating a medication's abuse potential. A meeting was convened to review all instruments measuring such events in clinical trials according to previously published standardized terminology and definitions. Only 2 approaches have been reported that are specifically designed to identify and classify misuse, abuse, and related events occurring in clinical trials, rather than to measure an individual's risk of using a medication inappropriately: the Self-Reported Misuse, Abuse, and Diversion (SR-MAD) instrument and the Misuse, Abuse, and Diversion Drug Event Reporting System (MADDERS). The conceptual basis, strengths, and limitations of these methods are discussed. To our knowledge, MADDERS is the only system available to comprehensively evaluate inappropriate medication use events prospectively to determine the underlying intent. MADDERS can also be applied retrospectively to completed trial data. SR-MAD can be used prospectively; additional development may be required to standardize its implementation and fully appraise the intent of inappropriate use events. Additional research is needed to further demonstrate the validity and utility of MADDERS as well as SR-MAD. Identifying a medication's abuse potential requires assessing inappropriate medication use events in clinical trials on the basis of a standardized event classification system. The strengths and limitations of the 2 published methods designed to evaluate inappropriate medication use events are reviewed, with recommended considerations for further development and current implementation. Copyright © 2017 American Pain Society. Published by Elsevier Inc. All rights reserved.

Identifying States along the Hematopoietic Stem Cell Differentiation Hierarchy with Single Cell Specificity via Raman Spectroscopy.

PubMed

Ilin, Yelena; Choi, Ji Sun; Harley, Brendan A C; Kraft, Mary L

2015-11-17

A major challenge for expanding specific types of hematopoietic cells ex vivo for the treatment of blood cell pathologies is identifying the combinations of cellular and matrix cues that direct hematopoietic stem cells (HSC) to self-renew or differentiate into cell populations ex vivo. Microscale screening platforms enable minimizing the number of rare HSCs required to screen the effects of numerous cues on HSC fate decisions. These platforms create a strong demand for label-free methods that accurately identify the fate decisions of individual hematopoietic cells at specific locations on the platform. We demonstrate the capacity to identify discrete cells along the HSC differentiation hierarchy via multivariate analysis of Raman spectra. Notably, cell state identification is accurate for individual cells and independent of the biophysical properties of the functionalized polyacrylamide gels upon which these cells are cultured. We report partial least-squares discriminant analysis (PLS-DA) models of single cell Raman spectra enable identifying four dissimilar hematopoietic cell populations across the HSC lineage specification. Successful discrimination was obtained for a population enriched for long-term repopulating HSCs (LT-HSCs) versus their more differentiated progeny, including closely related short-term repopulating HSCs (ST-HSCs) and fully differentiated lymphoid (B cells) and myeloid (granulocytes) cells. The lineage-specific differentiation states of cells from these four subpopulations were accurately identified independent of the stiffness of the underlying biomaterial substrate, indicating subtle spectral variations that discriminated these populations were not masked by features from the culture substrate. This approach enables identifying the lineage-specific differentiation stages of hematopoietic cells on biomaterial substrates of differing composition and may facilitate correlating hematopoietic cell fate decisions with the extrinsic cues that

Mining the Immune Cell Proteome to Identify Ovarian Cancer-Specific Biomarkers

DTIC Science & Technology

2012-03-01

data and are in the process of identifying gene signatures that can be used as biomarkers for the identification of ovarian cancer-specific biomarkers...groups. The groups showed significant difference in age as well as gestational age, which is expected when considering the disease process . Isolation of...MUC4 in intracellular signaling.32 Oligosaccharides attached to the extracellular domains of mucins have also been shown to interact with different

Comparative Transcriptional Profiling of the Axolotl Limb Identifies a Tripartite Regeneration-Specific Gene Program

PubMed Central

Knapp, Dunja; Schulz, Herbert; Rascon, Cynthia Alexander; Volkmer, Michael; Scholz, Juliane; Nacu, Eugen; Le, Mu; Novozhilov, Sergey; Tazaki, Akira; Protze, Stephanie; Jacob, Tina; Hubner, Norbert; Habermann, Bianca; Tanaka, Elly M.

2013-01-01

Understanding how the limb blastema is established after the initial wound healing response is an important aspect of regeneration research. Here we performed parallel expression profile time courses of healing lateral wounds versus amputated limbs in axolotl. This comparison between wound healing and regeneration allowed us to identify amputation-specific genes. By clustering the expression profiles of these samples, we could detect three distinguishable phases of gene expression – early wound healing followed by a transition-phase leading to establishment of the limb development program, which correspond to the three phases of limb regeneration that had been defined by morphological criteria. By focusing on the transition-phase, we identified 93 strictly amputation-associated genes many of which are implicated in oxidative-stress response, chromatin modification, epithelial development or limb development. We further classified the genes based on whether they were or were not significantly expressed in the developing limb bud. The specific localization of 53 selected candidates within the blastema was investigated by in situ hybridization. In summary, we identified a set of genes that are expressed specifically during regeneration and are therefore, likely candidates for the regulation of blastema formation. PMID:23658691

Hydrograph Separations can Identify Contaminant-Specific Pathways for Conservation Targeting in a Tile-Drained Watershed

USDA-ARS?s Scientific Manuscript database

Water quality issues continue to vex agriculture. Understanding contaminant-specific pathways could help clarify effective water quality management strategies in watersheds. Hypothesis: If conducted at nested scales, hydrograph separation techniques can identify contaminant-specific pathways that co...

Characteristics and treatment response of self-identified problematic Internet users in a behavioral addiction outpatient clinic

PubMed Central

Thorens, Gabriel; Achab, Sophia; Billieux, Joël; Khazaal, Yasser; Khan, Riaz; Pivin, Edward; Gupta, Vishal; Zullino, Daniel

2014-01-01

Aims: Controversies remain about the validity of the diagnosis of problematic Internet use. This might be due in part to the lack of longitudinal naturalistic studies that have followed a cohort of patients who self-identify as having Internet-related problems. Methods: This retrospective study included 57 patients who consulted the Geneva Addiction Outpatient Clinic from January 1, 2007, to January 1, 2010. Patients underwent an initial clinical psychiatric evaluation that included collection of data on socio-demographics, method of referral, specific Internet usage, psychiatric diagnosis, and Internet Addiction Test (IAT) and Clinical Global Impression Scale (CGI) scores. Treatment consisted of individual psychotherapeutic sessions. Results: Of these patients, 98% were male and 37% were 18 years or younger. Most patients were online gamers (46% playing massively multiplayer online role-playing games). The mean IAT score was 52.9 (range 20–90). Sixty-eight percent of patients had a co-morbid psychiatric diagnosis, with social phobia being the most prevalent (17.8%). Patients who remained in treatment (dropout rate 24%) showed an overall improvement of symptoms: 38.6% showed significant or average improvement on their CGI score, 26.3% showed minimal improvement, and 14% showed no change. Conclusions: Our results support the hypothesis that there are specific types of Internet use, with online gaming mainly affecting young male patients. As Internet addiction is not yet an official diagnosis, better instruments are needed to screen patients and to avoid false-negative and false-positive diagnoses. Successful care should integrate the treatment of co-morbid symptoms and involve families and relatives in the therapeutic process. PMID:25215217

Evaluation of the Sensitivity and Specificity of the New Clinical Diagnostic and Classification Criteria for Kashin-Beck Disease, an Endemic Osteoarthritis, in China.

PubMed

Yu, Fang Fang; Ping, Zhi Guang; Yao, Chong; Wang, Zhi Wen; Wang, Fu Qi; Guo, Xiong

2017-02-01

This study aimed to evaluate the sensitivity and specificity of the new clinical diagnostic and classification criteria for Kashin-Beck disease (KBD) using six clinical markers: flexion of the distal part of fingers, deformed fingers, enlarged finger joints, shortened fingers, squat down, and dwarfism. One-third of the total population in Linyou County was sampled by stratified random sampling. The survey included baseline characteristics and clinical diagnoses, and the sensitivity and specificity of the new criteria was evaluated. We identified 3,459 KBD patients, of which 69 had early stage KBD, 1,952 had stage I, 1,132 had stage II, and 306 had stage III. A screening test classified enlarged finger joints as stage I KBD, with a sensitivity and specificity of 0.978 and 0.045, respectively. Shortened fingers were classified as stage II KBD, with a sensitivity and specificity of 0.969 and 0.844, respectively, and dwarfism was classified as stage III KBD with a sensitivity and specificity of 0.951 and 0.992, respectively. Serial screening test revealed that the new clinical classification of KBD classified stages I, II, and III KBD with sensitivities of 0.949, 0.945, and 0.925 and specificities of 0.967, 0.970, and 0.993, respectively. The screening tests revealed that enlarged finger joints, shortened fingers, and dwarfism were appropriate markers for the clinical diagnosis and classification of KBD with high sensitivity and specificity. Copyright © 2017 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Genome-wide association studies identify four ER negative–specific breast cancer risk loci

PubMed Central

Garcia-Closas, Montserrat; Couch, Fergus J; Lindstrom, Sara; Michailidou, Kyriaki; Schmidt, Marjanka K; Brook, Mark N; orr, Nick; Rhie, Suhn Kyong; Riboli, Elio; Feigelson, Heather s; Le Marchand, Loic; Buring, Julie E; Eccles, Diana; Miron, Penelope; Fasching, Peter A; Brauch, Hiltrud; Chang-Claude, Jenny; Carpenter, Jane; Godwin, Andrew K; Nevanlinna, Heli; Giles, Graham G; Cox, Angela; Hopper, John L; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Dicks, Ed; Howat, Will J; Schoof, Nils; Bojesen, Stig E; Lambrechts, Diether; Broeks, Annegien; Andrulis, Irene L; Guénel, Pascal; Burwinkel, Barbara; Sawyer, Elinor J; Hollestelle, Antoinette; Fletcher, Olivia; Winqvist, Robert; Brenner, Hermann; Mannermaa, Arto; Hamann, Ute; Meindl, Alfons; Lindblom, Annika; Zheng, Wei; Devillee, Peter; Goldberg, Mark S; Lubinski, Jan; Kristensen, Vessela; Swerdlow, Anthony; Anton-Culver, Hoda; Dörk, Thilo; Muir, Kenneth; Matsuo, Keitaro; Wu, Anna H; Radice, Paolo; Teo, Soo Hwang; Shu, Xiao-Ou; Blot, William; Kang, Daehee; Hartman, Mikael; Sangrajrang, Suleeporn; Shen, Chen-Yang; Southey, Melissa C; Park, Daniel J; Hammet, Fleur; Stone, Jennifer; Veer, Laura J Van’t; Rutgers, Emiel J; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Peto, Julian; Schrauder, Michael G; Ekici, Arif B; Beckmann, Matthias W; Silva, Isabel dos Santos; Johnson, Nichola; Warren, Helen; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Marme, Federick; Schneeweiss, Andreas; Sohn, Christof; Truong, Therese; Laurent-Puig, Pierre; Kerbrat, Pierre; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Milne, Roger L; Perez, Jose Ignacio Arias; Menéndez, Primitiva; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Lichtner, Peter; Lochmann, Magdalena; Justenhoven, Christina; Ko, Yon-Dschun; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Greco, Dario; Heikkinen, Tuomas; Ito, Hidemi; Iwata, Hiroji; Yatabe, Yasushi; Antonenkova, Natalia N; Margolin, Sara; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Balleine, Rosemary; Tseng, Chiu-Chen; Van Den Berg, David; Stram, Daniel O; Neven, Patrick; Dieudonné, Anne-Sophie; Leunen, Karin; Rudolph, Anja; Nickels, Stefan; Flesch-Janys, Dieter; Peterlongo, Paolo; Peissel, Bernard; Bernard, Loris; Olson, Janet E; Wang, Xianshu; Stevens, Kristen; Severi, Gianluca; Baglietto, Laura; Mclean, Catriona; Coetzee, Gerhard A; Feng, Ye; Henderson, Brian E; Schumacher, Fredrick; Bogdanova, Natalia V; Labrèche, France; Dumont, Martine; Yip, Cheng Har; Taib, Nur Aishah Mohd; Cheng, Ching-Yu; Shrubsole, Martha; Long, Jirong; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Tollenaar, Robertus A E M; Seynaeve, Caroline M; Kriege, Mieke; Hooning, Maartje J; Van den Ouweland, Ans M W; Van Deurzen, Carolien H M; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Balasubramanian, Sabapathy P; Cross, Simon S; Reed, Malcolm W R; Signorello, Lisa; Cai, Qiuyin; Shah, Mitul; Miao, Hui; Chan, Ching Wan; Chia, Kee Seng; Jakubowska, Anna; Jaworska, Katarzyna; Durda, Katarzyna; Hsiung, Chia-Ni; Wu, Pei-Ei; Yu, Jyh-Cherng; Ashworth, Alan; Jones, Michael; Tessier, Daniel C; González-Neira, Anna; Pita, Guillermo; Alonso, M Rosario; Vincent, Daniel; Bacot, Francois; Ambrosone, Christine B; Bandera, Elisa V; John, Esther M; Chen, Gary K; Hu, Jennifer J; Rodriguez-gil, Jorge L; Bernstein, Leslie; Press, Michael F; Ziegler, Regina G; Millikan, Robert M; Deming-Halverson, Sandra L; Nyante, Sarah; Ingles, Sue A; Waisfisz, Quinten; Tsimiklis, Helen; Makalic, Enes; Schmidt, Daniel; Bui, Minh; Gibson, Lorna; Müller-Myhsok, Bertram; Schmutzler, Rita K; Hein, Rebecca; Dahmen, Norbert; Beckmann, Lars; Aaltonen, Kirsimari; Czene, Kamila; Irwanto, Astrid; Liu, Jianjun; Turnbull, Clare; Rahman, Nazneen; Meijers-Heijboer, Hanne; Uitterlinden, Andre G; Rivadeneira, Fernando; Olswold, Curtis; Slager, Susan; Pilarski, Robert; Ademuyiwa, Foluso; Konstantopoulou, Irene; Martin, Nicholas G; Montgomery, Grant W; Slamon, Dennis J; Rauh, Claudia; Lux, Michael P; Jud, Sebastian M; Bruning, Thomas; Weaver, Joellen; Sharma, Priyanka; Pathak, Harsh; Tapper, Will; Gerty, Sue; Durcan, Lorraine; Trichopoulos, Dimitrios; Tumino, Rosario; Peeters, Petra H; Kaaks, Rudolf; Campa, Daniele; Canzian, Federico; Weiderpass, Elisabete; Johansson, Mattias; Khaw, Kay-Tee; Travis, Ruth; Clavel-Chapelon, Françoise; Kolonel, Laurence N; Chen, Constance; Beck, Andy; Hankinson, Susan E; Berg, Christine D; Hoover, Robert N; Lissowska, Jolanta; Figueroa, Jonine D; Chasman, Daniel I; Gaudet, Mia M; Diver, W Ryan; Willett, Walter C; Hunter, David J; Simard, Jacques; Benitez, Javier; Dunning, Alison M; Sherman, Mark E; Chenevix-Trench, Georgia; Chanock, Stephen J; Hall, Per; Pharoah, Paul D P; Vachon, Celine; Easton, Douglas F; Haiman, Christopher A; Kraft, Peter

2013-01-01

Estrogen receptor (ER)-negative tumors represent 20–30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry1. The etiology2 and clinical behavior3 of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition4. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P = 2.1 × 10−12 and LGR6, P = 1.4 × 10−8), 2p24.1 (P = 4.6 × 10−8) and 16q12.2 (FTO, P = 4.0 × 10−8), were associated with ER-negative but not ER-positive breast cancer (P > 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers. PMID:23535733

40 CFR 148.18 - Waste specific prohibitions-newly listed and identified wastes.

Code of Federal Regulations, 2012 CFR

2012-07-01

.... (e) On July 8, 1996, the wastes specified in 40 CFR 261.32 as EPA Hazardous waste numbers K156-K161... 40 Protection of Environment 24 2012-07-01 2012-07-01 false Waste specific prohibitions-newly listed and identified wastes. 148.18 Section 148.18 Protection of Environment ENVIRONMENTAL PROTECTION...

40 CFR 148.18 - Waste specific prohibitions-newly listed and identified wastes.

Code of Federal Regulations, 2011 CFR

2011-07-01

.... (e) On July 8, 1996, the wastes specified in 40 CFR 261.32 as EPA Hazardous waste numbers K156-K161... 40 Protection of Environment 23 2011-07-01 2011-07-01 false Waste specific prohibitions-newly listed and identified wastes. 148.18 Section 148.18 Protection of Environment ENVIRONMENTAL PROTECTION...

40 CFR 148.18 - Waste specific prohibitions-newly listed and identified wastes.

Code of Federal Regulations, 2013 CFR

2013-07-01

.... (e) On July 8, 1996, the wastes specified in 40 CFR 261.32 as EPA Hazardous waste numbers K156-K161... 40 Protection of Environment 24 2013-07-01 2013-07-01 false Waste specific prohibitions-newly listed and identified wastes. 148.18 Section 148.18 Protection of Environment ENVIRONMENTAL PROTECTION...

40 CFR 148.18 - Waste specific prohibitions-newly listed and identified wastes.

Code of Federal Regulations, 2014 CFR

2014-07-01

.... (e) On July 8, 1996, the wastes specified in 40 CFR 261.32 as EPA Hazardous waste numbers K156-K161... 40 Protection of Environment 23 2014-07-01 2014-07-01 false Waste specific prohibitions-newly listed and identified wastes. 148.18 Section 148.18 Protection of Environment ENVIRONMENTAL PROTECTION...

Toward a Framework for Benefit-Risk Assessment in Diagnostic Imaging: Identifying Scenario-specific Criteria.

PubMed

Agapova, Maria; Bresnahan, Brian W; Linnau, Ken F; Garrison, Louis P; Higashi, Mitchell; Kessler, Larry; Devine, Beth

2017-05-01

Diagnostic imaging has many effects and there is no common definition of value in diagnostic radiology. As benefit-risk trade-offs are rarely made explicit, it is not clear which framework is used in clinical guideline development. We describe initial steps toward the creation of a benefit-risk framework for diagnostic radiology. We performed a literature search and an online survey of physicians to identify and collect benefit-risk criteria (BRC) relevant to diagnostic imaging tests. We operationalized a process for selection of BRC with the use of four clinical use case scenarios that vary by diagnostic alternatives and clinical indication. Respondent BRC selections were compared across clinical scenarios and between radiologists and nonradiologists. Thirty-six BRC were identified and organized into three domains: (1) those that account for differences attributable only to the test or device (n = 17); (2) those that account for clinical management and provider experiences (n = 12); and (3) those that capture patient experience (n = 7). Forty-eight survey participants selected 22 criteria from the initial list in the survey (9-11 per case). Engaging ordering physicians increased the number of criteria selected in each of the four clinical scenarios presented. We developed a process for standardizing selection of BRC in guideline development. These results suggest that a process relying on elements of comparative effectiveness and the use of standardized BRC may ensure consistent examination of differences among alternatives by way of making explicit implicit trade-offs that otherwise enter the decision-making space and detract from consistency and transparency. These findings also highlight the need for multidisciplinary teams that include input from ordering physicians. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Clinical Characteristics of Exacerbation-Prone Adult Asthmatics Identified by Cluster Analysis.

PubMed

Kim, Mi Ae; Shin, Seung Woo; Park, Jong Sook; Uh, Soo Taek; Chang, Hun Soo; Bae, Da Jeong; Cho, You Sook; Park, Hae Sim; Yoon, Ho Joo; Choi, Byoung Whui; Kim, Yong Hoon; Park, Choon Sik

2017-11-01

Asthma is a heterogeneous disease characterized by various types of airway inflammation and obstruction. Therefore, it is classified into several subphenotypes, such as early-onset atopic, obese non-eosinophilic, benign, and eosinophilic asthma, using cluster analysis. A number of asthmatics frequently experience exacerbation over a long-term follow-up period, but the exacerbation-prone subphenotype has rarely been evaluated by cluster analysis. This prompted us to identify clusters reflecting asthma exacerbation. A uniform cluster analysis method was applied to 259 adult asthmatics who were regularly followed-up for over 1 year using 12 variables, selected on the basis of their contribution to asthma phenotypes. After clustering, clinical profiles and exacerbation rates during follow-up were compared among the clusters. Four subphenotypes were identified: cluster 1 was comprised of patients with early-onset atopic asthma with preserved lung function, cluster 2 late-onset non-atopic asthma with impaired lung function, cluster 3 early-onset atopic asthma with severely impaired lung function, and cluster 4 late-onset non-atopic asthma with well-preserved lung function. The patients in clusters 2 and 3 were identified as exacerbation-prone asthmatics, showing a higher risk of asthma exacerbation. Two different phenotypes of exacerbation-prone asthma were identified among Korean asthmatics using cluster analysis; both were characterized by impaired lung function, but the age at asthma onset and atopic status were different between the two. Copyright © 2017 The Korean Academy of Asthma, Allergy and Clinical Immunology · The Korean Academy of Pediatric Allergy and Respiratory Disease

USING FORMATIVE RESEARCH TO DEVELOP A CONTEXT-SPECIFIC APPROACH TO INFORMED CONSENT FOR CLINICAL TRIALS

PubMed Central

Corneli, Amy L.; Bentley, Margaret E.; Sorenson, James R.; Henderson, Gail E.; van der Horst, Charles; Moses, Agnes; Nkhoma, Jacqueline; Tenthani, Lyson; Ahmed, Yusuf; Heilig, Charles M.; Jamieson, Denise J.

2009-01-01

Participant understanding is of particular concern when obtaining informed consent. Recommendations for improving understanding include disclosing information using culturally appropriate and innovative approaches. To increase the effectiveness of the consent process for a clinical trial in Malawi on interventions to prevent mother-to-child transmission of HIV during breastfeeding, formative research was conducted to explore the community’s understanding of medical research as well as how to explain research through local terms and meanings. Contextual analogies and other approaches were identified to explain consent information. Guided by theory, strategies for developing culturally appropriate interventions, and recommendations from the literature, we demonstrate how the formative data were used to develop culturally appropriate counseling cards specifically for the trial in Malawi. With appropriate contextual modifications, the steps outlined here could be applied in other clinical trials conducted elsewhere, as well as in other types of research. PMID:19385837

40 CFR 268.38 - Waste specific prohibitions-newly identified organic toxicity characteristic wastes and newly...

Code of Federal Regulations, 2010 CFR

2010-07-01

... identified organic toxicity characteristic wastes and newly listed coke by-product and chlorotoluene... specific prohibitions—newly identified organic toxicity characteristic wastes and newly listed coke by-product and chlorotoluene production wastes. (a) Effective December 19, 1994, the wastes specified in 40...

Drug-related problems identified during medication review before and after the introduction of a clinical decision support system.

PubMed

Verdoorn, S; Kwint, H F; Hoogland, P; Gussekloo, J; Bouvy, M L

2018-04-01

To facilitate the identification of drug-related problems (DRPs) during medication review, several tools have been developed. Explicit criteria, like Beers criteria or STOPP (Screening Tool of Older Peoples' Prescriptions) and START (Screening Tool to Alert doctors to Right Treatment) criteria, can easily be integrated into a clinical decision support system (CDSS). The aim of this study was to investigate the effect of adding a CDSS to medication review software on identifying and solving DRPs in daily pharmacy practice. Pre- to post-analysis of clinical medication reviews (CMRs) performed by 121 pharmacies in 2012 and 2013, before and after the introduction of CDSS into medication review software. Mean number of DRPs per patient, type of DRPs and their resolution rates were compared in the pharmacies pre- and post-CDSS using paired t tests. In total, 9151 DRPs were identified in 3100 patients pre-CDSS and 15 268 DRPs were identified in 4303 patients post-CDSS. The mean number of identified DRPs per patient (aggregated per pharmacy) was higher after the introduction of CDSS (3.2 vs 3.6 P < .01). The resolution rate was lower post-CDSS (50% vs 44%; P < .01), which overall resulted in 1.6 resolved DRPs per patient in both groups (P = .93). After the introduction of CDSS, 41% of DRPs were detected by the CDSS. The resolution rate of DRPs generated by CDSS was lower than of DRPs identified without the help of CDSS (29% vs 55%; P < .01). The two most prevalent DRP types were "Overtreatment" and "Suboptimal therapy" in both groups. The prevalence of "Overtreatment" was equal in both groups (mean DRPs per patient: 0.84 vs 0.77; P = .22), and "Suboptimal therapy" was more frequently identified post-CDSS (mean DRPs per patient: 0.54 vs 1.1; P < .01). The introduction of CDSS to medication review software generated additional DRPs with a lower resolution rate. Structural assessment including a patient interview elicited the most relevant DRPs. Further

Articular dysfunction patterns in patients with mechanical low back pain: A clinical algorithm to guide specific mobilization and manipulation techniques.

PubMed

Dewitte, V; Cagnie, B; Barbe, T; Beernaert, A; Vanthillo, B; Danneels, L

2015-06-01

Recent systematic reviews have demonstrated reasonable evidence that lumbar mobilization and manipulation techniques are beneficial. However, knowledge on optimal techniques and doses, and its clinical reasoning is currently lacking. To address this, a clinical algorithm is presented so as to guide therapists in their clinical reasoning to identify patients who are likely to respond to lumbar mobilization and/or manipulation and to direct appropriate technique selection. Key features in subjective and clinical examination suggestive of mechanical nociceptive pain probably arising from articular structures, can categorize patients into distinct articular dysfunction patterns. Based on these patterns, specific mobilization and manipulation techniques are suggested. This clinical algorithm is merely based on empirical clinical expertise and complemented through knowledge exchange between international colleagues. The added value of the proposed articular dysfunction patterns should be considered within a broader perspective. Copyright © 2014 Elsevier Ltd. All rights reserved.

Identifying clinically important difference on the Epworth Sleepiness Scale: results from a narcolepsy clinical trial of JZP-110.

PubMed

Scrima, Lawrence; Emsellem, Helene A; Becker, Philip M; Ruoff, Chad; Lankford, Alan; Bream, Gary; Khayrallah, Moise; Lu, Yuan; Black, Jed

2017-10-01

While scores ≤10 on the Epworth Sleepiness Scale (ESS) are within the normal range, the reduction in elevated ESS score that is clinically meaningful in patients with narcolepsy has not been established. This post hoc analysis of a clinical trial of patients with narcolepsy evaluated correlations between Patient Global Impression of Change (PGI-C) and ESS. Data of adult patients with narcolepsy from a double-blind, 12-week placebo-controlled study of JZP-110, a wake-promoting agent, were used in this analysis. Descriptive statistics and receiver operating characteristic (ROC) analysis compared PGI-C (anchor measure) to percent change from baseline in ESS to establish the responder criterion from patients taking either placebo or JZP-110 (treatments). At week 12, patients (n = 10) who reported being "very much improved" on the PGI-C had a mean 76.7% reduction in ESS score, and patients (n = 33) who reported being "much improved" on the PGI-C had a mean 49.1% reduction in ESS score. ROC analysis showed that patients who improved were almost exclusively from JZP-110 treatment group, with an area-under-the-curve of 0.9, and revealed that a 25% reduction in ESS (sensitivity, 81.4%; specificity, 80.9%) may be an appropriate threshold for defining a meaningful patient response to JZP-110 and placebo. A ≥25% reduction in patients' subjective ESS score may be useful as a threshold to identify patients with narcolepsy who respond to JZP-110 treatment. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Reliable change, sensitivity, and specificity of a multidimensional concussion assessment battery: implications for caution in clinical practice.

PubMed

Register-Mihalik, Johna K; Guskiewicz, Kevin M; Mihalik, Jason P; Schmidt, Julianne D; Kerr, Zachary Y; McCrea, Michael A

2013-01-01

To provide reliable change confidence intervals for common clinical concussion measures using a healthy sample of collegiate athletes and to apply these reliable change parameters to a sample of concussed collegiate athletes. Two independent samples were included in the study and evaluated on common clinical measures of concussion. The healthy sample included male, collegiate football student-athletes (n = 38) assessed at 2 time points. The concussed sample included college-aged student-athletes (n = 132) evaluated before and after a concussion. Outcome measures included symptom severity scores, Automated Neuropsychological Assessment Metrics throughput scores, and Sensory Organization Test composite scores. Application of the reliable change parameters suggests that a small percentage of concussed participants were impaired on each measure. We identified a low sensitivity of the entire battery (all measures combined) of 50% but high specificity of 96%. Clinicians should be trained in understanding clinical concussion measures and should be aware of evidence suggesting the multifaceted battery is more sensitive than any single measure. Clinicians should be cautioned that sensitivity to balance and neurocognitive impairments was low for each individual measure. Applying the confidence intervals to our injured sample suggests that these measures do not adequately identify postconcussion impairments when used in isolation.

Identifying patients for clinical trials using fuzzy ternary logic expressions on HL7 messages.

PubMed

Majeed, Raphael W; Röhrig, Rainer

2011-01-01

Identifying eligible patients is one of the most critical parts of any clinical trial. The process of recruiting patients for the third phase of any clinical trial is usually done manually, informing relevant physicians or putting notes on bulletin boards. While most necessary information is already available in electronic hospital information systems, required data still has to be looked up individually. Most university hospitals make use of a dedicated communication server to distribute information from independent information systems, e.g. laboratory information systems, electronic health records, surgery planning systems. Thus, a theoretical model is developed to formally describe inclusion and exclusion criteria for each clinical trial using a fuzzy ternary logic expression. These expressions will then be used to process HL7 messages from a communication server in order to identify eligible patients.

Development of a PubMed Based Search Tool for Identifying Sex and Gender Specific Health Literature.

PubMed

Song, Michael M; Simonsen, Cheryl K; Wilson, Joanna D; Jenkins, Marjorie R

2016-02-01

An effective literature search strategy is critical to achieving the aims of Sex and Gender Specific Health (SGSH): to understand sex and gender differences through research and to effectively incorporate the new knowledge into the clinical decision making process to benefit both male and female patients. The goal of this project was to develop and validate an SGSH literature search tool that is readily and freely available to clinical researchers and practitioners. PubMed, a freely available search engine for the Medline database, was selected as the platform to build the SGSH literature search tool. Combinations of Medical Subject Heading terms, text words, and title words were evaluated for optimal specificity and sensitivity. The search tool was then validated against reference bases compiled for two disease states, diabetes and stroke. Key sex and gender terms and limits were bundled to create a search tool to facilitate PubMed SGSH literature searches. During validation, the search tool retrieved 50 of 94 (53.2%) stroke and 62 of 95 (65.3%) diabetes reference articles selected for validation. A general keyword search of stroke or diabetes combined with sex difference retrieved 33 of 94 (35.1%) stroke and 22 of 95 (23.2%) diabetes reference base articles, with lower sensitivity and specificity for SGSH content. The Texas Tech University Health Sciences Center SGSH PubMed Search Tool provides higher sensitivity and specificity to sex and gender specific health literature. The tool will facilitate research, clinical decision-making, and guideline development relevant to SGSH.

Development of a PubMed Based Search Tool for Identifying Sex and Gender Specific Health Literature

PubMed Central

Song, Michael M.; Simonsen, Cheryl K.; Wilson, Joanna D.

2016-01-01

Abstract Background: An effective literature search strategy is critical to achieving the aims of Sex and Gender Specific Health (SGSH): to understand sex and gender differences through research and to effectively incorporate the new knowledge into the clinical decision making process to benefit both male and female patients. The goal of this project was to develop and validate an SGSH literature search tool that is readily and freely available to clinical researchers and practitioners. Methods: PubMed, a freely available search engine for the Medline database, was selected as the platform to build the SGSH literature search tool. Combinations of Medical Subject Heading terms, text words, and title words were evaluated for optimal specificity and sensitivity. The search tool was then validated against reference bases compiled for two disease states, diabetes and stroke. Results: Key sex and gender terms and limits were bundled to create a search tool to facilitate PubMed SGSH literature searches. During validation, the search tool retrieved 50 of 94 (53.2%) stroke and 62 of 95 (65.3%) diabetes reference articles selected for validation. A general keyword search of stroke or diabetes combined with sex difference retrieved 33 of 94 (35.1%) stroke and 22 of 95 (23.2%) diabetes reference base articles, with lower sensitivity and specificity for SGSH content. Conclusions: The Texas Tech University Health Sciences Center SGSH PubMed Search Tool provides higher sensitivity and specificity to sex and gender specific health literature. The tool will facilitate research, clinical decision-making, and guideline development relevant to SGSH. PMID:26555409

Clinical Scales Do Not Reliably Identify Acute Ischemic Stroke Patients With Large-Artery Occlusion.

PubMed

Turc, Guillaume; Maïer, Benjamin; Naggara, Olivier; Seners, Pierre; Isabel, Clothilde; Tisserand, Marie; Raynouard, Igor; Edjlali, Myriam; Calvet, David; Baron, Jean-Claude; Mas, Jean-Louis; Oppenheim, Catherine

2016-06-01

It remains debated whether clinical scores can help identify acute ischemic stroke patients with large-artery occlusion and hence improve triage in the era of thrombectomy. We aimed to determine the accuracy of published clinical scores to predict large-artery occlusion. We assessed the performance of 13 clinical scores to predict large-artery occlusion in consecutive patients with acute ischemic stroke undergoing clinical examination and magnetic resonance or computed tomographic angiography ≤6 hours of symptom onset. When no cutoff was published, we used the cutoff maximizing the sum of sensitivity and specificity in our cohort. We also determined, for each score, the cutoff associated with a false-negative rate ≤10%. Of 1004 patients (median National Institute of Health Stroke Scale score, 7; range, 0-40), 328 (32.7%) had an occlusion of the internal carotid artery, M1 segment of the middle cerebral artery, or basilar artery. The highest accuracy (79%; 95% confidence interval, 77-82) was observed for National Institute of Health Stroke Scale score ≥11 and Rapid Arterial Occlusion Evaluation Scale score ≥5. However, these cutoffs were associated with false-negative rates >25%. Cutoffs associated with an false-negative rate ≤10% were 5, 1, and 0 for National Institute of Health Stroke Scale, Rapid Arterial Occlusion Evaluation Scale, and Cincinnati Prehospital Stroke Severity Scale, respectively. Using published cutoffs for triage would result in a loss of opportunity for ≥20% of patients with large-artery occlusion who would be inappropriately sent to a center lacking neurointerventional facilities. Conversely, using cutoffs reducing the false-negative rate to 10% would result in sending almost every patient to a comprehensive stroke center. Our findings, therefore, suggest that intracranial arterial imaging should be performed in all patients with acute ischemic stroke presenting within 6 hours of symptom onset. © 2016 American Heart Association

Identifying Balance Measures Most Likely to Identify Recent Falls.

PubMed

Criter, Robin E; Honaker, Julie A

2016-01-01

Falls sustained by older adults are an increasing health care issue. Early identification of those at risk for falling can lead to successful prevention of falls. Balance complaints are common among individuals who fall or are at risk for falling. The purpose of this study was to evaluate the clinical utility of a multifaceted balance protocol used for fall risk screening, with the hypothesis that this protocol would successfully identify individuals who had a recent fall (within the previous 12 months). This is a retrospective review of 30 individuals who self-referred for a free fall risk screening. Measures included case history, Activities-Specific Balance Confidence Scale, modified Clinical Test of Sensory Interaction on Balance, Timed Up and Go test, and Dynamic Visual Acuity. Statistical analyses were focused on the ability of the test protocol to identify a fall within the past 12 months and included descriptive statistics, clinical utility indices, logistic regression, receiver operating characteristic curve, area under the curve analysis, effect size (Cohen d), and Spearman correlation coefficients. All individuals who self-referred for this free screening had current imbalance complaints, and were typically women (70%), had a mean age of 77.2 years, and had a fear of falling (70%). Almost half (46.7%) reported at least 1 lifetime fall and 40.0% within the past 12 months. Regression analysis suggested that the Timed Up and Go test was the most important indicator of a recent fall. A cutoff score of 12 or more seconds was optimal (sensitivity: 83.3%; specificity: 61.1%). Older adults with current complaints of imbalance have a higher rate of falls, fall-related injury, and fear of falling than the general community-dwelling public. The Timed Up and Go test is useful for determining recent fall history in individuals with imbalance.

Preformed Frequencies of Cytomegalovirus (CMV)–Specific Memory T and B Cells Identify Protected CMV-Sensitized Individuals Among Seronegative Kidney Transplant Recipients

PubMed Central

Lúcia, Marc; Crespo, Elena; Melilli, Edoardo; Cruzado, Josep M.; Luque, Sergi; Llaudó, Inés; Niubó, Jordi; Torras, Joan; Fernandez, Núria; Grinyó, Josep M.; Bestard, Oriol

2014-01-01

Background. Cytomegalovirus (CMV) infection remains a major complication after kidney transplantation. Baseline CMV risk is typically determined by the serological presence of preformed CMV-specific immunoglobulin (Ig) G antibodies, even though T-cell responses to major viral antigens are crucial when controlling viral replication. Some IgG-seronegative patients who receive an IgG-seropositive allograft do not develop CMV infection despite not receiving prophylaxis. We hypothesized that a more precise evaluation of pretransplant CMV-specific immune-sensitization using the B and T-cell enzyme-linked immunospot assays may identify CMV-sensitized individuals more accurately, regardless of serological evidence of CMV-specific IgG titers. Methods. We compared the presence of preformed CMV-specific memory B and T cells in kidney transplant recipients between 43 CMV IgG–seronegative (sR−) and 86 CMV IgG–seropositive (sR+) patients. Clinical outcome was evaluated in both groups. Results. All sR+ patients showed a wide range of CMV-specific memory T- and B-cell responses. High memory T- and B-cell frequencies were also clearly detected in 30% of sR− patients, and those with high CMV-specific T-cell frequencies had a significantly lower incidence of late CMV infection after prophylactic therapy. Receiver operating characteristic curve analysis for predicting CMV viremia and disease showed a high area under the receiver operating characteristic curve (>0.8), which translated into a high sensitivity and negative predictive value of the test. Conclusions. Assessment of CMV-specific memory T- and B-cell responses before kidney transplantation among sR− recipients may help identify immunized individuals more precisely, being ultimately at lower risk for CMV infection. PMID:25048845

Signatures from Tissue-specific MPSS Libraries Identify Transcripts Preferentially Expressed in the Mouse Inner Ear

PubMed Central

Peters, Linda M.; Belyantseva, Inna A.; Lagziel, Ayala; Battey, James F.; Friedman, Thomas B.; Morell, Robert J.

2007-01-01

Specialization in cell function and morphology is influenced by the differential expression of mRNAs, many of which are expressed at low abundance and restricted to certain cell types. Detecting such transcripts in cDNA libraries may require sequencing millions of clones. Massively parallel signature sequencing (MPSS) is well-suited for identifying transcripts that are expressed in discrete cell types and in low abundance. We have made MPSS libraries from microdissections of three inner ear tissues. By comparing these MPSS libraries to those of 87 other tissues included in the Mouse Reference Transcriptome (MRT) online resource, we have identified genes that are highly enriched in, or specific to, the inner ear. We show by RT-PCR and in situ hybridization that signatures unique to the inner ear libraries identify transcripts with highly specific cell-type localizations. These transcripts serve to illustrate the utility of a resource that is available to the research community. Utilization of these resources will increase the number of known transcription units and expand our knowledge of the tissue-specific regulation of the transcriptome. PMID:17049805

High-Throughput Screening to Identify Regulators of Meiosis-Specific Gene Expression in Saccharomyces cerevisiae.

PubMed

Kassir, Yona

2017-01-01

Meiosis and gamete formation are processes that are essential for sexual reproduction in all eukaryotic organisms. Multiple intracellular and extracellular signals feed into pathways that converge on transcription factors that induce the expression of meiosis-specific genes. Once triggered the meiosis-specific gene expression program proceeds in a cascade that drives progress through the events of meiosis and gamete formation. Meiosis-specific gene expression is tightly controlled by a balance of positive and negative regulatory factors that respond to a plethora of signaling pathways. The budding yeast Saccharomyces cerevisiae has proven to be an outstanding model for the dissection of gametogenesis owing to the sophisticated genetic manipulations that can be performed with the cells. It is possible to use a variety selection and screening methods to identify genes and their functions. High-throughput screening technology has been developed to allow an array of all viable yeast gene deletion mutants to be screened for phenotypes and for regulators of gene expression. This chapter describes a protocol that has been used to screen a library of homozygous diploid yeast deletion strains to identify regulators of the meiosis-specific IME1 gene.

A business planning model to identify new safety net clinic locations.

PubMed

Langabeer, James; Helton, Jeffrey; DelliFraine, Jami; Dotson, Ebbin; Watts, Carolyn; Love, Karen

2014-01-01

Community health clinics serving the poor and underserved are geographically expanding due to changes in U.S. health care policy. This paper describes the experience of a collaborative alliance of health care providers in a large metropolitan area who develop a conceptual and mathematical decision model to guide decisions on expanding its network of community health clinics. Community stakeholders participated in a collaborative process that defined constructs they deemed important in guiding decisions on the location of community health clinics. This collaboration also defined key variables within each construct. Scores for variables within each construct were then totaled and weighted into a community-specific optimal space planning equation. This analysis relied entirely on secondary data available from published sources. The model built from this collaboration revolved around the constructs of demand, sustainability, and competition. It used publicly available data defining variables within each construct to arrive at an optimal location that maximized demand and sustainability and minimized competition. This is a model that safety net clinic planners and community stakeholders can use to analyze demographic and utilization data to optimize capacity expansion to serve uninsured and Medicaid populations. Communities can use this innovative model to develop a locally relevant clinic location-planning framework.

A computational approach to identify cellular heterogeneity and tissue-specific gene regulatory networks.

PubMed

Jambusaria, Ankit; Klomp, Jeff; Hong, Zhigang; Rafii, Shahin; Dai, Yang; Malik, Asrar B; Rehman, Jalees

2018-06-07

The heterogeneity of cells across tissue types represents a major challenge for studying biological mechanisms as well as for therapeutic targeting of distinct tissues. Computational prediction of tissue-specific gene regulatory networks may provide important insights into the mechanisms underlying the cellular heterogeneity of cells in distinct organs and tissues. Using three pathway analysis techniques, gene set enrichment analysis (GSEA), parametric analysis of gene set enrichment (PGSEA), alongside our novel model (HeteroPath), which assesses heterogeneously upregulated and downregulated genes within the context of pathways, we generated distinct tissue-specific gene regulatory networks. We analyzed gene expression data derived from freshly isolated heart, brain, and lung endothelial cells and populations of neurons in the hippocampus, cingulate cortex, and amygdala. In both datasets, we found that HeteroPath segregated the distinct cellular populations by identifying regulatory pathways that were not identified by GSEA or PGSEA. Using simulated datasets, HeteroPath demonstrated robustness that was comparable to what was seen using existing gene set enrichment methods. Furthermore, we generated tissue-specific gene regulatory networks involved in vascular heterogeneity and neuronal heterogeneity by performing motif enrichment of the heterogeneous genes identified by HeteroPath and linking the enriched motifs to regulatory transcription factors in the ENCODE database. HeteroPath assesses contextual bidirectional gene expression within pathways and thus allows for transcriptomic assessment of cellular heterogeneity. Unraveling tissue-specific heterogeneity of gene expression can lead to a better understanding of the molecular underpinnings of tissue-specific phenotypes.

Identifying novel phenotypes of acute heart failure using cluster analysis of clinical variables.

PubMed

Horiuchi, Yu; Tanimoto, Shuzou; Latif, A H M Mahbub; Urayama, Kevin Y; Aoki, Jiro; Yahagi, Kazuyuki; Okuno, Taishi; Sato, Yu; Tanaka, Tetsu; Koseki, Keita; Komiyama, Kota; Nakajima, Hiroyoshi; Hara, Kazuhiro; Tanabe, Kengo

2018-07-01

Acute heart failure (AHF) is a heterogeneous disease caused by various cardiovascular (CV) pathophysiology and multiple non-CV comorbidities. We aimed to identify clinically important subgroups to improve our understanding of the pathophysiology of AHF and inform clinical decision-making. We evaluated detailed clinical data of 345 consecutive AHF patients using non-hierarchical cluster analysis of 77 variables, including age, sex, HF etiology, comorbidities, physical findings, laboratory data, electrocardiogram, echocardiogram and treatment during hospitalization. Cox proportional hazards regression analysis was performed to estimate the association between the clusters and clinical outcomes. Three clusters were identified. Cluster 1 (n=108) represented "vascular failure". This cluster had the highest average systolic blood pressure at admission and lung congestion with type 2 respiratory failure. Cluster 2 (n=89) represented "cardiac and renal failure". They had the lowest ejection fraction (EF) and worst renal function. Cluster 3 (n=148) comprised mostly older patients and had the highest prevalence of atrial fibrillation and preserved EF. Death or HF hospitalization within 12-month occurred in 23% of Cluster 1, 36% of Cluster 2 and 36% of Cluster 3 (p=0.034). Compared with Cluster 1, risk of death or HF hospitalization was 1.74 (95% CI, 1.03-2.95, p=0.037) for Cluster 2 and 1.82 (95% CI, 1.13-2.93, p=0.014) for Cluster 3. Cluster analysis may be effective in producing clinically relevant categories of AHF, and may suggest underlying pathophysiology and potential utility in predicting clinical outcomes. Copyright © 2018 Elsevier B.V. All rights reserved.

Empirical Methods for Identifying Specific Peptide-protein Interactions for Smart Reagent Development

DTIC Science & Technology

2012-09-01

orientated immobilization of proteins,” Biotechnology Progress, 22(2), 401-405 ( 2006 ). [26] J. M. Kogot, D. A. Sarkes , I. Val-Addo et al...Empirical Methods for Identifying Specific Peptide-protein Interactions for Smart Reagent Development by Joshua M. Kogot, Deborah A. Sarkes ...Peptide-protein Interactions for Smart Reagent Development Joshua M. Kogot, Deborah A. Sarkes , Dimitra N. Stratis-Cullum, and Paul M

Assessment of a brain-tumour-specific Patient Concerns Inventory in the neuro-oncology clinic.

PubMed

Rooney, Alasdair G; Netten, Anouk; McNamara, Shanne; Erridge, Sara; Peoples, Sharon; Whittle, Ian; Hacking, Belinda; Grant, Robin

2014-04-01

Brain tumour patients may struggle to express their concerns in the outpatient clinic, creating a physician-focused rather than a shared agenda. We created a simple, practical brain-tumour-specific holistic needs assessment (HNA) tool for use in the neuro-oncology outpatient clinic. We posted the brain tumour Patient Concerns Inventory (PCI) to a consecutive sample of adult brain tumour attendees to a neuro-oncology outpatient clinic. Participants brought the completed PCI to their clinic consultation. Patients and staff provided feedback. Seventy seven patients were eligible and 53 participated (response rate = 68%). The PCI captured many problems absent from general cancer checklists. The five most frequent concerns were fatigue, fear of tumour coming back, memory, concentration, and low mood. Respondents used the PCI to formulate 105 specific questions, usually about the meaning of physical or psychological symptoms. Patients and staff found the PCI to be useful, and satisfaction with the instrument was high. This study demonstrates the clinical utility of the brain tumour PCI in a neuro-oncology clinic. The combination of a brain-tumour-specific concerns checklist and an intervention to focus patient agenda creates a simple and efficient HNA tool.

Treatment selection in a randomized clinical trial via covariate-specific treatment effect curves.

PubMed

Ma, Yunbei; Zhou, Xiao-Hua

2017-02-01

For time-to-event data in a randomized clinical trial, we proposed two new methods for selecting an optimal treatment for a patient based on the covariate-specific treatment effect curve, which is used to represent the clinical utility of a predictive biomarker. To select an optimal treatment for a patient with a specific biomarker value, we proposed pointwise confidence intervals for each covariate-specific treatment effect curve and the difference between covariate-specific treatment effect curves of two treatments. Furthermore, to select an optimal treatment for a future biomarker-defined subpopulation of patients, we proposed confidence bands for each covariate-specific treatment effect curve and the difference between each pair of covariate-specific treatment effect curve over a fixed interval of biomarker values. We constructed the confidence bands based on a resampling technique. We also conducted simulation studies to evaluate finite-sample properties of the proposed estimation methods. Finally, we illustrated the application of the proposed method in a real-world data set.

Novel target for high-risk neuroblastoma identified in pre-clinical research | Center for Cancer Research

Cancer.gov

Pre-clinical research by investigators at the Center for Cancer Research and their colleagues have identified a number of novel epigenetic targets for high-risk neuroblastoma and validated a promising new targeted inhibitor in pre-clinical models.  Read more...

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.

GWAS of clinically defined gout and subtypes identifies multiple susceptibility loci that include urate transporter genes

PubMed Central

Nakayama, Akiyoshi; Nakaoka, Hirofumi; Yamamoto, Ken; Sakiyama, Masayuki; Shaukat, Amara; Toyoda, Yu; Okada, Yukinori; Kamatani, Yoichiro; Nakamura, Takahiro; Takada, Tappei; Inoue, Katsuhisa; Yasujima, Tomoya; Yuasa, Hiroaki; Shirahama, Yuko; Nakashima, Hiroshi; Shimizu, Seiko; Higashino, Toshihide; Kawamura, Yusuke; Ogata, Hiraku; Kawaguchi, Makoto; Ohkawa, Yasuyuki; Danjoh, Inaho; Tokumasu, Atsumi; Ooyama, Keiko; Ito, Toshimitsu; Kondo, Takaaki; Wakai, Kenji; Stiburkova, Blanka; Pavelka, Karel; Stamp, Lisa K; Dalbeth, Nicola; Sakurai, Yutaka; Suzuki, Hiroshi; Hosoyamada, Makoto; Fujimori, Shin; Yokoo, Takashi; Hosoya, Tatsuo; Inoue, Ituro; Takahashi, Atsushi; Kubo, Michiaki; Ooyama, Hiroshi; Shimizu, Toru; Ichida, Kimiyoshi; Shinomiya, Nariyoshi; Merriman, Tony R; Matsuo, Hirotaka

2017-01-01

Objective A genome-wide association study (GWAS) of gout and its subtypes was performed to identify novel gout loci, including those that are subtype-specific. Methods Putative causal association signals from a GWAS of 945 clinically defined gout cases and 1213 controls from Japanese males were replicated with 1396 cases and 1268 controls using a custom chip of 1961 single nucleotide polymorphisms (SNPs). We also first conducted GWASs of gout subtypes. Replication with Caucasian and New Zealand Polynesian samples was done to further validate the loci identified in this study. Results In addition to the five loci we reported previously, further susceptibility loci were identified at a genome-wide significance level (p<5.0×10−8): urate transporter genes (SLC22A12 and SLC17A1) and HIST1H2BF-HIST1H4E for all gout cases, and NIPAL1 and FAM35A for the renal underexcretion gout subtype. While NIPAL1 encodes a magnesium transporter, functional analysis did not detect urate transport via NIPAL1, suggesting an indirect association with urate handling. Localisation analysis in the human kidney revealed expression of NIPAL1 and FAM35A mainly in the distal tubules, which suggests the involvement of the distal nephron in urate handling in humans. Clinically ascertained male patients with gout and controls of Caucasian and Polynesian ancestries were also genotyped, and FAM35A was associated with gout in all cases. A meta-analysis of the three populations revealed FAM35A to be associated with gout at a genome-wide level of significance (pmeta=3.58×10−8). Conclusions Our findings including novel gout risk loci provide further understanding of the molecular pathogenesis of gout and lead to a novel concept for the therapeutic target of gout/hyperuricaemia. PMID:27899376

Identifying tagging SNPs for African specific genetic variation from the African Diaspora Genome

PubMed Central

Johnston, Henry Richard; Hu, Yi-Juan; Gao, Jingjing; O’Connor, Timothy D.; Abecasis, Gonçalo R.; Wojcik, Genevieve L; Gignoux, Christopher R.; Gourraud, Pierre-Antoine; Lizee, Antoine; Hansen, Mark; Genuario, Rob; Bullis, Dave; Lawley, Cindy; Kenny, Eimear E.; Bustamante, Carlos; Beaty, Terri H.; Mathias, Rasika A.; Barnes, Kathleen C.; Qin, Zhaohui S.; Preethi Boorgula, Meher; Campbell, Monica; Chavan, Sameer; Ford, Jean G.; Foster, Cassandra; Gao, Li; Hansel, Nadia N.; Horowitz, Edward; Huang, Lili; Ortiz, Romina; Potee, Joseph; Rafaels, Nicholas; Ruczinski, Ingo; Scott, Alan F.; Taub, Margaret A.; Vergara, Candelaria; Levin, Albert M.; Padhukasahasram, Badri; Williams, L. Keoki; Dunston, Georgia M.; Faruque, Mezbah U.; Gietzen, Kimberly; Deshpande, Aniket; Grus, Wendy E.; Locke, Devin P.; Foreman, Marilyn G.; Avila, Pedro C.; Grammer, Leslie; Kim, Kwang-Youn A.; Kumar, Rajesh; Schleimer, Robert; De La Vega, Francisco M.; Shringarpure, Suyash S.; Musharoff, Shaila; Burchard, Esteban G.; Eng, Celeste; Hernandez, Ryan D.; Pino-Yanes, Maria; Torgerson, Dara G.; Szpiech, Zachary A.; Torres, Raul; Nicolae, Dan L.; Ober, Carole; Olopade, Christopher O; Olopade, Olufunmilayo; Oluwole, Oluwafemi; Arinola, Ganiyu; Song, Wei; Correa, Adolfo; Musani, Solomon; Wilson, James G.; Lange, Leslie A.; Akey, Joshua; Bamshad, Michael; Chong, Jessica; Fu, Wenqing; Nickerson, Deborah; Reiner, Alexander; Hartert, Tina; Ware, Lorraine B.; Bleecker, Eugene; Meyers, Deborah; Ortega, Victor E.; Maul, Pissamai; Maul, Trevor; Watson, Harold; Ilma Araujo, Maria; Riccio Oliveira, Ricardo; Caraballo, Luis; Marrugo, Javier; Martinez, Beatriz; Meza, Catherine; Ayestas, Gerardo; Francisco Herrera-Paz, Edwin; Landaverde-Torres, Pamela; Erazo, Said Omar Leiva; Martinez, Rosella; Mayorga, Alvaro; Mayorga, Luis F.; Mejia-Mejia, Delmy-Aracely; Ramos, Hector; Saenz, Allan; Varela, Gloria; Marina Vasquez, Olga; Ferguson, Trevor; Knight-Madden, Jennifer; Samms-Vaughan, Maureen; Wilks, Rainford J.; Adegnika, Akim; Ateba-Ngoa, Ulysse; Yazdanbakhsh, Maria

2017-01-01

A primary goal of The Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA) is to develop an ‘African Diaspora Power Chip’ (ADPC), a genotyping array consisting of tagging SNPs, useful in comprehensively identifying African specific genetic variation. This array is designed based on the novel variation identified in 642 CAAPA samples of African ancestry with high coverage whole genome sequence data (~30× depth). This novel variation extends the pattern of variation catalogued in the 1000 Genomes and Exome Sequencing Projects to a spectrum of populations representing the wide range of West African genomic diversity. These individuals from CAAPA also comprise a large swath of the African Diaspora population and incorporate historical genetic diversity covering nearly the entire Atlantic coast of the Americas. Here we show the results of designing and producing such a microchip array. This novel array covers African specific variation far better than other commercially available arrays, and will enable better GWAS analyses for researchers with individuals of African descent in their study populations. A recent study cataloging variation in continental African populations suggests this type of African-specific genotyping array is both necessary and valuable for facilitating large-scale GWAS in populations of African ancestry. PMID:28429804

Association of Immunological Cell Profiles with Specific Clinical Phenotypes of Scleroderma Disease

PubMed Central

Calzada, David; Mayayo, Teodoro; González-Rodríguez, María Luisa; Rabasco, Antonio María; Lahoz, Carlos

2014-01-01

This study aimed to search the correlation among immunological profiles and clinical phenotypes of scleroderma in well-characterized groups of scleroderma patients, comparing forty-nine scleroderma patients stratified according to specific clinical phenotypes with forty-nine healthy controls. Five immunological cell subpopulations (B, CD4+ and CD8+ T-cells, NK, and monocytes) and their respective stages of apoptosis and activation were analyzed by flow cytometry, in samples of peripheral blood mononuclear cells (PBMCs). Analyses of results were stratified according to disease stage, time since the diagnosis, and visceral damage (pulmonary fibrosis, pulmonary hypertension, and cardiac affliction) and by time of treatment with corticosteroids. An increase in the percentages of monocytes and a decrease in the B cells were mainly related to the disease progression. A general apoptosis decrease was found in all phenotypes studied, except in localized scleroderma. An increase of B and NK cells activation was found in patients diagnosed more than 10 years ago. Specific cell populations like monocytes, NK, and B cells were associated with the type of affected organ. This study shows how, in a heterogeneous disease, proper patient's stratification according to clinical phenotypes allows finding specific cellular profiles. Our data may lead to improvements in the knowledge of prognosis factors and to aid in the analysis of future specific therapies. PMID:24818126

Comparative genome analysis identifies novel nucleic acid diagnostic targets for use in the specific detection of Haemophilus influenzae.

PubMed

Coughlan, Helena; Reddington, Kate; Tuite, Nina; Boo, Teck Wee; Cormican, Martin; Barrett, Louise; Smith, Terry J; Clancy, Eoin; Barry, Thomas

2015-10-01

Haemophilus influenzae is recognised as an important human pathogen associated with invasive infections, including bloodstream infection and meningitis. Currently used molecular-based diagnostic assays lack specificity in correctly detecting and identifying H. influenzae. As such, there is a need to develop novel diagnostic assays for the specific identification of H. influenzae. Whole genome comparative analysis was performed to identify putative diagnostic targets, which are unique in nucleotide sequence to H. influenzae. From this analysis, we identified 2H. influenzae putative diagnostic targets, phoB and pstA, for use in real-time PCR diagnostic assays. Real-time PCR diagnostic assays using these targets were designed and optimised to specifically detect and identify all 55H. influenzae strains tested. These novel rapid assays can be applied to the specific detection and identification of H. influenzae for use in epidemiological studies and could also enable improved monitoring of invasive disease caused by these bacteria. Copyright © 2015 Elsevier Inc. All rights reserved.

[Abnormal vaginal secretion: sensitivity, specificity and concordance between clinical and cytological diagnosis].

PubMed

de Camargo, Kélvia Cristina; Alves, Rosane Ribeiro Figueiredo; Baylão, Luciano Augusto; Ribeiro, Andrea Alves; Araujo, Nadja Lindany Alves de Souza; Tavares, Suelene Brito do Nascimento; dos Santos, Sílvia Helena Rabelo

2015-05-01

To estimate the prevalence of bacterial vaginosis (BV), candidiasis and trichomoniasis and compare the findings of physical examination of the vaginal secretion with the microbiological diagnosis obtained by cytology study of a vaginal smear using the Papanicolaou method. A cross-sectional study of 302 women aged 20 to 87 years, interviewed and submitted to a gynecology test for the evaluation of vaginal secretion and collection of a cytology smear, from June 2012 to May 2013. Sensitivity analyses were carried out and specificity, positive predictive value (PPV) and negative predictive value (NPV) with their respective 95%CI were determined to assess the accuracy of the characteristics of vaginal secretion in relation to the microbiological diagnosis of the cytology smear . The kappa index (k) was used to assess the degree of agreement between the clinical features of vaginal secretion and the microbiological findings obtained by cytology. RESULTS The prevalence of BV, candidiasis and trichomoniasis was 25.5, 9.3 and 2.0%, respectively. The sensitivity, specificity, PPV and NPV of the clinical characteristics of vaginal secretion for the cytological diagnosis of BV were 74, 78.6, 54.3 and 89.9%, respectively. The sensitivity, specificity, PPV and the NPV of the clinical characteristics of vaginal secretion for the cytological diagnosis of candidiasis were 46.4, 86.2, 25.5 and 94%, respectively. The correlation between the clinical evaluation of vaginal secretion and the microbiological diagnosis of BV, candidiasis and trichomoniasis, assessed by the kappa index, was 0.47, 0.23 and 0.28, respectively. CONCLUSION The most common cause of abnormal vaginal secretion was BV. The clinical evaluation of vaginal secretion presented amoderate to weak agreement with the microbiological diagnosis, indicating the need for complementary investigation of the clinical findings of abnormal vaginal secretion.

A Real-Time PCR Assay to Identify and Discriminate Among Wild-Type and Vaccine Strains of Varicella-Zoster Virus and Herpes Simplex Virus in Clinical Specimens, and Comparison With the Clinical Diagnoses

PubMed Central

Harbecke, Ruth; Oxman, Michael N.; Arnold, Beth A.; Ip, Charlotte; Johnson, Gary R.; Levin, Myron J.; Gelb, Lawrence D.; Schmader, Kenneth E.; Straus, Stephen E.; Wang, Hui; Wright, Peter F.; Pachucki, Constance T.; Gershon, Anne A.; Arbeit, Robert D.; Davis, Larry E.; Simberkoff, Michael S.; Weinberg, Adriana; Williams, Heather M.; Cheney, Carol; Petrukhin, Luba; Abraham, Katalin G.; Shaw, Alan; Manoff, Susan; Antonello, Joseph M.; Green, Tina; Wang, Yue; Tan, Charles; Keller, Paul M.

2014-01-01

A real-time PCR assay was developed to identify varicella-zoster virus (VZV) and herpes simplex virus (HSV) DNA in clinical specimens from subjects with suspected herpes zoster (HZ; shingles). Three sets of primers and probes were used in separate PCR reactions to detect and discriminate among wild-type VZV (VZV-WT), Oka vaccine strain VZV (VZV-Oka), and HSV DNA, and the reaction for each virus DNA was multiplexed with primers and probe specific for the human β-globin gene to assess specimen adequacy. Discrimination of all VZV-WT strains, including Japanese isolates and the Oka parent strain, from VZV-Oka was based upon a single nucleotide polymorphism at position 106262 in ORF 62, resulting in preferential amplification by the homologous primer pair. The assay was highly sensitive and specific for the target virus DNA, and no cross-reactions were detected with any other infectious agent. With the PCR assay as the gold standard, the sensitivity of virus culture was 53% for VZV and 77% for HSV. There was 92% agreement between the clinical diagnosis of HZ by the Clinical Evaluation Committee and the PCR assay results. PMID:19475609

Measures that identify prescription medication misuse, abuse, and related events in clinical trials: ACTTION critique and recommended considerations

PubMed Central

Smith, Shannon M.; Jones, Judith K.; Katz, Nathaniel P.; Roland, Carl L.; Setnik, Beatrice; Trudeau, Jeremiah J.; Wright, Stephen; Burke, Laurie B.; Comer, Sandra D.; Dart, Richard C.; Dionne, Raymond; Haddox, J. David; Jaffe, Jerome H.; Kopecky, Ernest A.; Martell, Bridget A.; Montoya, Ivan D.; Stanton, Marsha; Wasan, Ajay D.; Turk, Dennis C.; Dworkin, Robert H.

2017-01-01

Accurate assessment of inappropriate medication use events (i.e., misuse, abuse, and related events [MAREs]) occurring in clinical trials is an important component in evaluating a medication’s abuse potential. A meeting was convened to review all instruments measuring such events in clinical trials according to previously published standardized terminology and definitions [27]. Only 2 approaches have been reported that are specifically designed to identify and classify MAREs occurring in clinical trials, rather than to measure an individual’s risk of using a medication inappropriately: the Self-Reported Misuse, Abuse, and Diversion [SR-MAD] instrument and the Misuse, Abuse, and Diversion Drug Event Reporting System [MADDERS]. The conceptual basis, strengths, and limitations of these methods are discussed. To our knowledge, MADDERS is the only system available to comprehensively evaluate inappropriate medication use events prospectively in order to determine the underlying intent. MADDERS can also be applied retrospectively to completed trial data. SR-MAD can be used prospectively; additional development may be required to standardize its implementation and fully appraise the intent of inappropriate use events. Additional research is needed to further demonstrate the validity and utility of both MADDERS and SR-MAD. PMID:28479207

Identifying complications of interventional procedures from UK routine healthcare databases: a systematic search for methods using clinical codes.

PubMed

Keltie, Kim; Cole, Helen; Arber, Mick; Patrick, Hannah; Powell, John; Campbell, Bruce; Sims, Andrew

2014-11-28

Several authors have developed and applied methods to routine data sets to identify the nature and rate of complications following interventional procedures. But, to date, there has been no systematic search for such methods. The objective of this article was to find, classify and appraise published methods, based on analysis of clinical codes, which used routine healthcare databases in a United Kingdom setting to identify complications resulting from interventional procedures. A literature search strategy was developed to identify published studies that referred, in the title or abstract, to the name or acronym of a known routine healthcare database and to complications from procedures or devices. The following data sources were searched in February and March 2013: Cochrane Methods Register, Conference Proceedings Citation Index - Science, Econlit, EMBASE, Health Management Information Consortium, Health Technology Assessment database, MathSciNet, MEDLINE, MEDLINE in-process, OAIster, OpenGrey, Science Citation Index Expanded and ScienceDirect. Of the eligible papers, those which reported methods using clinical coding were classified and summarised in tabular form using the following headings: routine healthcare database; medical speciality; method for identifying complications; length of follow-up; method of recording comorbidity. The benefits and limitations of each approach were assessed. From 3688 papers identified from the literature search, 44 reported the use of clinical codes to identify complications, from which four distinct methods were identified: 1) searching the index admission for specified clinical codes, 2) searching a sequence of admissions for specified clinical codes, 3) searching for specified clinical codes for complications from procedures and devices within the International Classification of Diseases 10th revision (ICD-10) coding scheme which is the methodology recommended by NHS Classification Service, and 4) conducting manual clinical

TU-A-201-02: Treatment Site-Specific Considerations for Clinical IGRT

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

Wijesooriya, K.

2016-06-15

Recent years have seen a widespread proliferation of available in-room image guidance systems for radiation therapy target localization with many centers having multiple in-room options. In this session, available imaging systems for in-room IGRT will be reviewed highlighting the main differences in workflow efficiency, targeting accuracy and image quality as it relates to target visualization. Decision-making strategies for integrating these tools into clinical image guidance protocols that are tailored to specific disease sites like H&N, lung, pelvis, and spine SBRT will be discussed. Learning Objectives: Major system characteristics of a wide range of available in-room imaging systems for IGRT. Advantagesmore » / disadvantages of different systems for site-specific IGRT considerations. Concepts of targeting accuracy and time efficiency in designing clinical imaging protocols.« less

Non-coding cancer driver candidates identified with a sample- and position-specific model of the somatic mutation rate

PubMed Central

Juul, Malene; Bertl, Johanna; Guo, Qianyun; Nielsen, Morten Muhlig; Świtnicki, Michał; Hornshøj, Henrik; Madsen, Tobias; Hobolth, Asger; Pedersen, Jakob Skou

2017-01-01

Non-coding mutations may drive cancer development. Statistical detection of non-coding driver regions is challenged by a varying mutation rate and uncertainty of functional impact. Here, we develop a statistically founded non-coding driver-detection method, ncdDetect, which includes sample-specific mutational signatures, long-range mutation rate variation, and position-specific impact measures. Using ncdDetect, we screened non-coding regulatory regions of protein-coding genes across a pan-cancer set of whole-genomes (n = 505), which top-ranked known drivers and identified new candidates. For individual candidates, presence of non-coding mutations associates with altered expression or decreased patient survival across an independent pan-cancer sample set (n = 5454). This includes an antigen-presenting gene (CD1A), where 5’UTR mutations correlate significantly with decreased survival in melanoma. Additionally, mutations in a base-excision-repair gene (SMUG1) correlate with a C-to-T mutational-signature. Overall, we find that a rich model of mutational heterogeneity facilitates non-coding driver identification and integrative analysis points to candidates of potential clinical relevance. DOI: http://dx.doi.org/10.7554/eLife.21778.001 PMID:28362259

[Identifying clinical risk factors in recurrent idiopathic deep venous thrombosis].

PubMed

Del Río Solá, M Lourdes; González Fajardo, José Antonio; Vaquero Puerta, Carlos

2016-03-18

Oral anticoagulant therapy for more than 6 months in patients with an episode of idiopathic thromboembolic disease is controversial. The objective was to determine predictive clinical signs that identify patients at increased risk of thromboembolic recurrence after stopping anticoagulant therapy for 6 months after an episode of idiopathic deep vein thrombosis (DVT). A prospective study which included 306 consecutive patients with a first episode of idiopathic DVT from June 2012 to June 2014. Predictor variables of recurrent thromboembolic disease and episodes of recurrence during follow-up of the patients (28.42 months) were collected. We performed a multivariate analysis to analyze possible predictors (P<.20) and an analysis of Kaplan-Meier to establish mean recurrence-free survival. We identified 91 episodes of residual vein thrombosis on follow-up of the patients (37.5% men and 20.3% women) (OR 1.84; 95% CI 1.25-2.71). In the Cox regression analysis stratified by gender, variables showed significant presence of hyperechoic thrombus (P=.001) in males, and persistence of residual thrombus in women (P=.046). The mean recurrence-free survival was shorter in both groups. The presence of echogenic thrombus in men and the existence of residual DVT in women were 2 clinical signs associated with increased risk of thromboembolic recurrence after stopping anticoagulant therapy for 6 months after an episode of idiopathic DVT in our study. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

40 CFR 268.38 - Waste specific prohibitions-newly identified organic toxicity characteristic wastes and newly...

Code of Federal Regulations, 2014 CFR

2014-07-01

... identified organic toxicity characteristic wastes and newly listed coke by-product and chlorotoluene... specific prohibitions—newly identified organic toxicity characteristic wastes and newly listed coke by... numbers F037, F038, K107-K112, K117, K118, K123-K126, K131, K132, K136, U328, U353, U359, and soil and...

40 CFR 268.38 - Waste specific prohibitions-newly identified organic toxicity characteristic wastes and newly...

Code of Federal Regulations, 2013 CFR

2013-07-01

... identified organic toxicity characteristic wastes and newly listed coke by-product and chlorotoluene... specific prohibitions—newly identified organic toxicity characteristic wastes and newly listed coke by... numbers F037, F038, K107-K112, K117, K118, K123-K126, K131, K132, K136, U328, U353, U359, and soil and...

40 CFR 268.38 - Waste specific prohibitions-newly identified organic toxicity characteristic wastes and newly...

Code of Federal Regulations, 2012 CFR

2012-07-01

... identified organic toxicity characteristic wastes and newly listed coke by-product and chlorotoluene... specific prohibitions—newly identified organic toxicity characteristic wastes and newly listed coke by... numbers F037, F038, K107-K112, K117, K118, K123-K126, K131, K132, K136, U328, U353, U359, and soil and...

40 CFR 268.38 - Waste specific prohibitions-newly identified organic toxicity characteristic wastes and newly...

Code of Federal Regulations, 2011 CFR

2011-07-01

... identified organic toxicity characteristic wastes and newly listed coke by-product and chlorotoluene... specific prohibitions—newly identified organic toxicity characteristic wastes and newly listed coke by... numbers F037, F038, K107-K112, K117, K118, K123-K126, K131, K132, K136, U328, U353, U359, and soil and...

Use of the Menopause-Specific Quality of Life (MENQOL) questionnaire in research and clinical practice: a comprehensive scoping review.

PubMed

Sydora, Beate C; Fast, Hilary; Campbell, Sandy; Yuksel, Nese; Lewis, Jacqueline E; Ross, Sue

2016-09-01

The Menopause-Specific Quality of Life (MENQOL) questionnaire was developed as a validated research tool to measure condition-specific QOL in early postmenopausal women. We conducted a comprehensive scoping review to explore the extent of MENQOL's use in research and clinical practice to assess its value in providing effective, adequate, and comparable participant assessment information. Thirteen biomedical and clinical databases were systematically searched with "menqol" as a search term to find articles using MENQOL or its validated derivative MENQOL-Intervention as investigative or clinical tools from 1996 to November 2014 inclusive. Review articles, conference abstracts, proceedings, dissertations, and incomplete trials were excluded. Additional articles were collected from references within key articles. Three independent reviewers extracted data reflecting study design, intervention, sample characteristics, MENQOL questionnaire version, modifications and language, recall period, and analysis detail. Data analyses included categorization and descriptive statistics. The review included 220 eligible papers of various study designs, covering 39 countries worldwide and using MENQOL translated into more than 25 languages. A variety of modifications to the original questionnaire were identified, including omission or addition of items and alterations to the validated methodological analysis. No papers were found that described MENQOL's use in clinical practice. Our study found an extensive and steadily increasing use of MENQOL in clinical and epidemiological research over 18 years postpublication. Our results stress the importance of proper reporting and validation of translations and variations to ensure outcome comparison and transparency of MENQOL's use. The value of MENQOL in clinical practice remains unknown.

TH-B-BRC-00: How to Identify and Resolve Potential Clinical Errors Before They Impact Patients Treatment: Lessons Learned

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

NONE

2016-06-15

Radiation treatment consists of a chain of events influenced by the quality of machine operation, beam data commissioning, machine calibration, patient specific data, simulation, treatment planning, imaging and treatment delivery. There is always a chance that the clinical medical physicist may make or fail to detect an error in one of the events that may impact on the patient’s treatment. In the clinical scenario, errors may be systematic and, without peer review, may have a low detectability because they are not part of routine QA procedures. During treatment, there might be errors on machine that needs attention. External reviews ofmore » some of the treatment delivery components by independent reviewers, like IROC, can detect errors, but may not be timely. The goal of this session is to help junior clinical physicists identify potential errors as well as the approach of quality assurance to perform a root cause analysis to find and eliminate an error and to continually monitor for errors. A compilation of potential errors will be presented by examples of the thought process required to spot the error and determine the root cause. Examples may include unusual machine operation, erratic electrometer reading, consistent lower electron output, variation in photon output, body parts inadvertently left in beam, unusual treatment plan, poor normalization, hot spots etc. Awareness of the possibility and detection of error in any link of the treatment process chain will help improve the safe and accurate delivery of radiation to patients. Four experts will discuss how to identify errors in four areas of clinical treatment. D. Followill, NIH grant CA 180803.« less

Incidence rate of pathogen-specific clinical mastitis on conventional and organic Canadian dairy farms.

PubMed

Levison, L J; Miller-Cushon, E K; Tucker, A L; Bergeron, R; Leslie, K E; Barkema, H W; DeVries, T J

2016-02-01

Mastitis is a common and costly production disease on dairy farms. In Canada, the incidence rate of clinical mastitis (IRCM) has been determined for conventionally managed dairy farms; however, no studies to date have assessed rates in organically managed systems. The objectives of this observational study were (1) to determine the producer-reported IRCM and predominant pathogen types on conventional and organic dairy farms in Southern Ontario, Canada, and (2) to evaluate the association of both mean overall IRCM and pathogen-specific IRCM with management system, housing type, and pasture access. Data from 59 dairy farms in Southern Ontario, Canada, distributed across conventional (n=41) and organic management (n=18) systems, were collected from April 2011 to May 2012. In addition to management system, farms were categorized by housing method (loose or tie-stall) and pasture access for lactating cows. Participating producers identified and collected samples from 936 cases of clinical mastitis. The most frequently isolated mastitis pathogens were coagulase-negative staphylococci, Bacillus spp., Streptococcus spp., Staphylococcus aureus, and Escherichia coli. The IRCM was higher on conventional farms than organic (23.7 vs. 13.2 cases per 100 cow-years) and was not associated with housing type (loose or tie-stall), pasture access, or herd-average milk yield. Bulk tank somatic cell count tended to be lower on conventional farms than organic (222,000 vs. 272,000 cells/mL). Pathogen-specific IRCM attributed to Staph. aureus, Bacillus spp., and E. coli was greater on conventional than organic farms, but was not associated with housing or any other factors. In conclusion, organic management was associated with reduced overall and pathogen-specific IRCM. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Development and Validation of a Clinic-Based Prediction Tool to Identify Female Athletes at High Risk for Anterior Cruciate Ligament Injury

PubMed Central

Myer, Gregory D.; Ford, Kevin R.; Khoury, Jane; Succop, Paul; Hewett, Timothy E.

2012-01-01

Background Prospective measures of high knee abduction moment (KAM) during landing identify female athletes at high risk for anterior cruciate ligament injury. Laboratory-based measurements demonstrate 90% accuracy in prediction of high KAM. Clinic-based prediction algorithms that employ correlates derived from laboratory-based measurements also demonstrate high accuracy for prediction of high KAM mechanics during landing. Hypotheses Clinic-based measures derived from highly predictive laboratory-based models are valid for the accurate prediction of high KAM status, and simultaneous measurements using laboratory-based and clinic-based techniques highly correlate. Study Design Cohort study (diagnosis); Level of evidence, 2. Methods One hundred female athletes (basketball, soccer, volleyball players) were tested using laboratory-based measures to confirm the validity of identified laboratory-based correlate variables to clinic-based measures included in a prediction algorithm to determine high KAM status. To analyze selected clinic-based surrogate predictors, another cohort of 20 female athletes was simultaneously tested with both clinic-based and laboratory-based measures. Results The prediction model (odds ratio: 95% confidence interval), derived from laboratory-based surrogates including (1) knee valgus motion (1.59: 1.17-2.16 cm), (2) knee flexion range of motion (0.94: 0.89°-1.00°), (3) body mass (0.98: 0.94-1.03 kg), (4) tibia length (1.55: 1.20-2.07 cm), and (5) quadriceps-to-hamstrings ratio (1.70: 0.48%-6.0%), predicted high KAM status with 84% sensitivity and 67% specificity (P < .001). Clinic-based techniques that used a calibrated physician’s scale, a standard measuring tape, standard camcorder, ImageJ software, and an isokinetic dynamometer showed high correlation (knee valgus motion, r = .87; knee flexion range of motion, r = .95; and tibia length, r = .98) to simultaneous laboratory-based measurements. Body mass and quadriceps-to-hamstrings ratio

A deep-learning classifier identifies patients with clinical heart failure using whole-slide images of H&E tissue

PubMed Central

Peyster, Eliot G.; Frank, Renee; Margulies, Kenneth B.; Feldman, Michael D.

2018-01-01

Over 26 million people worldwide suffer from heart failure annually. When the cause of heart failure cannot be identified, endomyocardial biopsy (EMB) represents the gold-standard for the evaluation of disease. However, manual EMB interpretation has high inter-rater variability. Deep convolutional neural networks (CNNs) have been successfully applied to detect cancer, diabetic retinopathy, and dermatologic lesions from images. In this study, we develop a CNN classifier to detect clinical heart failure from H&E stained whole-slide images from a total of 209 patients, 104 patients were used for training and the remaining 105 patients for independent testing. The CNN was able to identify patients with heart failure or severe pathology with a 99% sensitivity and 94% specificity on the test set, outperforming conventional feature-engineering approaches. Importantly, the CNN outperformed two expert pathologists by nearly 20%. Our results suggest that deep learning analytics of EMB can be used to predict cardiac outcome. PMID:29614076

A deep-learning classifier identifies patients with clinical heart failure using whole-slide images of H&E tissue.

PubMed

Nirschl, Jeffrey J; Janowczyk, Andrew; Peyster, Eliot G; Frank, Renee; Margulies, Kenneth B; Feldman, Michael D; Madabhushi, Anant

2018-01-01

Over 26 million people worldwide suffer from heart failure annually. When the cause of heart failure cannot be identified, endomyocardial biopsy (EMB) represents the gold-standard for the evaluation of disease. However, manual EMB interpretation has high inter-rater variability. Deep convolutional neural networks (CNNs) have been successfully applied to detect cancer, diabetic retinopathy, and dermatologic lesions from images. In this study, we develop a CNN classifier to detect clinical heart failure from H&E stained whole-slide images from a total of 209 patients, 104 patients were used for training and the remaining 105 patients for independent testing. The CNN was able to identify patients with heart failure or severe pathology with a 99% sensitivity and 94% specificity on the test set, outperforming conventional feature-engineering approaches. Importantly, the CNN outperformed two expert pathologists by nearly 20%. Our results suggest that deep learning analytics of EMB can be used to predict cardiac outcome.

Identification of Clinical Markers of Specific Language Impairment in Adults

ERIC Educational Resources Information Center

Poll, Gerard H.; Betz, Stacy K.; Miller, Carol A.

2010-01-01

Purpose: To investigate the usefulness of 3 tasks known to be effective diagnostic clinical markers of specific language impairment (SLI) in children: (a) nonword repetition, (b) sentence repetition, and (c) grammaticality judgments of finiteness marking. Method: Two groups of young adults, 13 with SLI and 18 with typical language, completed 3…

Efficacy of ACL injury risk screening methods in identifying high-risk landing patterns during a sport-specific task.

PubMed

Fox, A S; Bonacci, J; McLean, S G; Saunders, N

2017-05-01

Screening methods sensitive to movement strategies that increase anterior cruciate ligament (ACL) loads are likely to be effective in identifying athletes at-risk of ACL injury. Current ACL injury risk screening methods are yet to be evaluated for their ability to identify athletes' who exhibit high-risk lower limb mechanics during sport-specific maneuvers associated with ACL injury occurrences. The purpose of this study was to examine the efficacy of two ACL injury risk screening methods in identifying high-risk lower limb mechanics during a sport-specific landing task. Thirty-two female athletes were screened using the Landing Error Scoring System (LESS) and Tuck Jump Assessment. Participants' also completed a sport-specific landing task, during which three-dimensional kinematic and kinetic data were collected. One-dimensional statistical parametric mapping was used to examine the relationships between screening method scores, and the three-dimensional hip and knee joint rotation and moment data from the sport-specific landing. Higher LESS scores were associated with reduced knee flexion from 30 to 57 ms after initial contact (P = 0.003) during the sport-specific landing; however, no additional relationships were found. These findings suggest the LESS and Tuck Jump Assessment may have minimal applicability in identifying athletes' who exhibit high-risk landing postures in the sport-specific task examined. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Retrospective evaluation of all recorded horse race starts in Switzerland during a four year period focusing on discipline-specific risk factors for clinical events.

PubMed

Schweizer, C; Ramseyer, A; Gerber, V; Christen, G; Burger, D; Wohlfender, F D

2016-11-01

Racetrack injuries are of welfare concern and the prevention of injuries is an important goal in many racing jurisdictions. Over the years this has led to more detailed recording of clinical events on racecourses. However, risk factor analyses of clinical events at race meetings have not been previously reported for Switzerland. To identify discipline-specific factors that influence the occurrence of clinical events during race meetings with the ultimate aim of improving the monitoring and safety of racetracks in Switzerland and optimising racehorse welfare. Retrospective study of horse race data collected by the Swiss horse racing association. All race starts (n = 17,670, including 6198 flat, 1257 obstacle and 10,215 trot race starts) recorded over a period of 4 years (2009-2012) were analysed in multivariable mixed effect logistic regression models including horse and racecourse related data. The models were designed to identify discipline-specific factors influencing the occurrence of clinical events on racecourses in Switzerland. Factors influencing the risk of clinical events during races were different for each discipline. The risk of a clinical event in trot racing was lower for racing on a Porphyre sand track than on grass tracks. Horses whose driver was also their trainer had an approximately 2-fold higher risk for clinical events. In obstacle races, longer distances (2401-3300 m and 3301-5400 m, respectively) had a protective effect compared with racing over shorter distances. In flat racing, 5 racecourses reported significantly fewer clinical events. In all 3 disciplines, finishing 8th place or later was associated with clinical events. Changes in management that aim to improve the safety and welfare of racehorses, such as racetrack adaptations, need to be individualised for each discipline. © 2015 EVJ Ltd.

Clinical and no-clinical setting specificities in first session short-term psychotherapy psychodrama group.

PubMed

Drakulić, Aleksandra Mindoljević

2011-03-01

Modern history of short-term group psychotherapy dates back to the late 1950-ies. From then to present day, this psychotherapeutic method has been used in various forms, from dynamic-oriented to cognitive behavioural psychotherapies. Although it has always been considered rather controversial, due its cost-effectiveness, it has been capturing more and more popularity. This paper presents the specificities of first session short-term psychotherapy psychodrama group through session work with two examined groups: a group of 20 adult women who suffer from mild or moderate forms of unipolar depression and a group of 20 students of the School of Medicine in Zagreb without any psychiatric symptomatology. The results indicate the high importance of having structure in first psychodrama session, of relating it with the previously thoroughly conducted, initial, clinical, interviews, and of the clarity and focus in terms of determining the goals of therapy, especially in a clinical context. This study also confirmed assumptions regarding the need for different approaches of warming-up in psychodrama, both in the clinical and in non-clinical samples. A psychodrama psychotherapist should have good time managing skills and capability to convert the time available into an opportunity for directly boosting the group energy and work on therapeutic alliance.

The clinical reasoning process in randomized clinical trials with patients with non-specific neck pain is incomplete: A systematic review.

PubMed

Maissan, Francois; Pool, Jan; de Raaij, Edwin; Mollema, Jürgen; Ostelo, Raymond; Wittink, Harriet

2018-06-01

Primarily to evaluate the completeness of the description of the clinical reasoning process in RCTs with patients with non-specific neck pain with an argued or diagnosed cause i.e. an impairment or activity limitation. Secondly, to determine the association between the completeness of the clinical reasoning process and the degree of risk of bias. Pubmed, Cinahl and PEDro were systematically searched from inception to July 2016. RCTs (n = 122) with patients with non-specific neck pain receiving physiotherapy treatment published in English were included. Data extraction included study characteristics and important features of the clinical reasoning process based on the Hypothesis-Oriented Algorithm for Clinicians II (HOAC II)]. Thirty-seven studies (30%) had a complete clinical reasoning process of which 8 (6%) had a 'diagnosed cause' and 29 (24%) had an 'argued cause'. The Spearmans rho association between the extent of the clinical reasoning process and the risk of bias was -0.2. In the majority of studies (70%) the described clinical reasoning process was incomplete. A very small proportion (6%) had a 'diagnosed cause'. Therefore, a better methodological quality does not necessarily imply a better described clinical reasoning process. Copyright © 2018 Elsevier Ltd. All rights reserved.

The Experiences of Parents with Adolescents Identified as Having a Specific Learning Disability

ERIC Educational Resources Information Center

Seals, Linda J.

2010-01-01

Of the 6.6 million children in the United States who were deemed in 2008 to have a disability that required special instruction, over 39% were classified as specific learning disabled (SLD). This figure translates into a high number of people who are parenting a child identified as having a SLD. Bronfenbrenner's theory of the ecology of human…

The Clinical Validation of the Athlete Sleep Screening Questionnaire: an Instrument to Identify Athletes that Need Further Sleep Assessment.

PubMed

Bender, Amy M; Lawson, Doug; Werthner, Penny; Samuels, Charles H

2018-06-04

Previous research has established that general sleep screening questionnaires are not valid and reliable in an athlete population. The Athlete Sleep Screening Questionnaire (ASSQ) was developed to address this need. While the initial validation of the ASSQ has been established, the clinical validity of the ASSQ has yet to be determined. The main objective of the current study was to evaluate the clinical validity of the ASSQ. Canadian National Team athletes (N = 199; mean age 24.0 ± 4.2 years, 62% females; from 23 sports) completed the ASSQ. A subset of athletes (N = 46) were randomized to the clinical validation sub-study which required subjects to complete an ASSQ at times 2 and 3 and to have a clinical sleep interview by a sleep medicine physician (SMP) who rated each subjects' category of clinical sleep problem and provided recommendations to improve sleep. To assess clinical validity, the SMP category of clinical sleep problem was compared to the ASSQ. The internal consistency (Cronbach's alpha = 0.74) and test-retest reliability (r = 0.86) of the ASSQ were acceptable. The ASSQ demonstrated good agreement with the SMP (Cohen's kappa = 0.84) which yielded a diagnostic sensitivity of 81%, specificity of 93%, positive predictive value of 87%, and negative predictive value of 90%. There were 25.1% of athletes identified to have clinically relevant sleep disturbances that required further clinical sleep assessment. Sleep improved from time 1 at baseline to after the recommendations at time 3. Sleep screening athletes with the ASSQ provides a method of accurately determining which athletes would benefit from preventative measures and which athletes suffer from clinically significant sleep problems. The process of sleep screening athletes and providing recommendations improves sleep and offers a clinical intervention output that is simple and efficient for teams and athletes to implement.

COMPETITIVE METAGENOMIC DNA HYBRIDIZATION IDENTIFIES HOST-SPECIFIC MICROBIAL GENETIC MARKERS IN COW FECAL SAMPLES

EPA Science Inventory

Several PCR methods have recently been developed to identify fecal contamination in surface waters. In all cases, researchers have relied on one gene or one microorganism for selection of host specific markers. Here, we describe the application of a genome fragment enrichment met...

COMPETITIVE METAGENOMIC DNA HYBRIDIZATION IDENTIFIES HOST-SPECIFIC GENETIC MARKERS IN CATTLE FECAL SAMPLES - ABSTRACT

EPA Science Inventory

Several PCR methods have recently been developed to identify fecal contamination in surface waters. In all cases, researchers have relied on one gene or one microorganism for selection of host specific markers. Here, we describe the application of a genome fragment enrichment met...

Presumptive specific clinical diagnosis of genital ulcer disease (GUD) in a primary health care setting in Nairobi.

PubMed

Ndinya-Achola, J O; Kihara, A N; Fisher, L D; Krone, M R; Plummer, F A; Ronald, A; Holmes, K K

1996-01-01

Of 22,274 patients 12 years of age or older attending a primary health care clinic in Nairobi, 1076 (4.8%) complained of symptoms suggesting a sexually transmitted disease (STD). Of these, 518 females and 462 males underwent complete clinical evaluation, and 78% had objective microbiologic or clinical evidence of STD, including 168 (17.1%) with genital ulcer disease (GUD). Presumptive specific clinical diagnoses on initial physical examination in cases of GUD were chancroid (131 patients), syphilis (25), genital herpes (15) and lymphogranuloma venereum (LGV) (1). Clinical diagnoses correlated only weakly with microbiological and serological diagnoses. Haemophilus ducreyi was isolated from 51 (41%) of the 125 with a clinical diagnosis of chancroid, and 4 (22%) of 18 with a diagnosis of syphilis, herpes, or LGV (P = 0.13). The rapid plasma reagin (RPR) test was reactive in 6 (24%) of 25 with a clinical diagnosis of syphilis, 18 (12.3%) of 146 with a diagnosis of chancroid or herpes, and 37 (4.7%) of 786 without a genital ulcer (P < 0.001, GUD vs no GUD). Sensitivity, specificity, and positive predictive value for presumptive clinical diagnosis of chancroid, relative to H. ducreyi isolation, were 93%, 16%, and 41%; and for diagnosis of syphilis, relative to reactive RPR, were 25%, 88% and 25%. Specific treatment based on presumptive specific clinical diagnosis frequently was inadequate for syphilis among patients with GUD and reactive RPR test. Syndromic treatment of GUD with antimicrobial combinations active against both chancroid and syphilis would be preferable to treatment with single drugs based on presumptive specific clinical diagnoses for this population.

An intelligent clinical decision support system for patient-specific predictions to improve cervical intraepithelial neoplasia detection.

PubMed

Bountris, Panagiotis; Haritou, Maria; Pouliakis, Abraham; Margari, Niki; Kyrgiou, Maria; Spathis, Aris; Pappas, Asimakis; Panayiotides, Ioannis; Paraskevaidis, Evangelos A; Karakitsos, Petros; Koutsouris, Dimitrios-Dionyssios

2014-01-01

Nowadays, there are molecular biology techniques providing information related to cervical cancer and its cause: the human Papillomavirus (HPV), including DNA microarrays identifying HPV subtypes, mRNA techniques such as nucleic acid based amplification or flow cytometry identifying E6/E7 oncogenes, and immunocytochemistry techniques such as overexpression of p16. Each one of these techniques has its own performance, limitations and advantages, thus a combinatorial approach via computational intelligence methods could exploit the benefits of each method and produce more accurate results. In this article we propose a clinical decision support system (CDSS), composed by artificial neural networks, intelligently combining the results of classic and ancillary techniques for diagnostic accuracy improvement. We evaluated this method on 740 cases with complete series of cytological assessment, molecular tests, and colposcopy examination. The CDSS demonstrated high sensitivity (89.4%), high specificity (97.1%), high positive predictive value (89.4%), and high negative predictive value (97.1%), for detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+). In comparison to the tests involved in this study and their combinations, the CDSS produced the most balanced results in terms of sensitivity, specificity, PPV, and NPV. The proposed system may reduce the referral rate for colposcopy and guide personalised management and therapeutic interventions.

An Intelligent Clinical Decision Support System for Patient-Specific Predictions to Improve Cervical Intraepithelial Neoplasia Detection

PubMed Central

Bountris, Panagiotis; Haritou, Maria; Pouliakis, Abraham; Margari, Niki; Kyrgiou, Maria; Spathis, Aris; Pappas, Asimakis; Panayiotides, Ioannis; Paraskevaidis, Evangelos A.; Karakitsos, Petros; Koutsouris, Dimitrios-Dionyssios

2014-01-01

Nowadays, there are molecular biology techniques providing information related to cervical cancer and its cause: the human Papillomavirus (HPV), including DNA microarrays identifying HPV subtypes, mRNA techniques such as nucleic acid based amplification or flow cytometry identifying E6/E7 oncogenes, and immunocytochemistry techniques such as overexpression of p16. Each one of these techniques has its own performance, limitations and advantages, thus a combinatorial approach via computational intelligence methods could exploit the benefits of each method and produce more accurate results. In this article we propose a clinical decision support system (CDSS), composed by artificial neural networks, intelligently combining the results of classic and ancillary techniques for diagnostic accuracy improvement. We evaluated this method on 740 cases with complete series of cytological assessment, molecular tests, and colposcopy examination. The CDSS demonstrated high sensitivity (89.4%), high specificity (97.1%), high positive predictive value (89.4%), and high negative predictive value (97.1%), for detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+). In comparison to the tests involved in this study and their combinations, the CDSS produced the most balanced results in terms of sensitivity, specificity, PPV, and NPV. The proposed system may reduce the referral rate for colposcopy and guide personalised management and therapeutic interventions. PMID:24812614

Sensitivity and specificity of the Eating Assessment Tool and the Volume-Viscosity Swallow Test for clinical evaluation of oropharyngeal dysphagia

PubMed Central

Rofes, L; Arreola, V; Mukherjee, R; Clavé, P

2014-01-01

Background Oropharyngeal dysphagia (OD) is an underdiagnosed digestive disorder that causes severe nutritional and respiratory complications. Our aim was to determine the accuracy of the Eating Assessment Tool (EAT-10) and the Volume-Viscosity Swallow Test (V-VST) for clinical evaluation of OD. Methods We studied 120 patients with swallowing difficulties and 14 healthy subjects. OD was evaluated by the 10-item screening questionnaire EAT-10 and the bedside method V-VST, videofluoroscopy (VFS) being the reference standard. The V-VST is an effort test that uses boluses of different volumes and viscosities to identify clinical signs of impaired efficacy (impaired labial seal, piecemeal deglutition, and residue) and impaired safety of swallow (cough, voice changes, and oxygen desaturation ≥3%). Discriminating ability was assessed by the AUC of the ROC curve and sensitivity and specificity values. Key Results According to VFS, prevalence of OD was 87%, 75.6% with impaired efficacy and 80.9% with impaired safety of swallow including 17.6% aspirations. The EAT-10 showed a ROC AUC of 0.89 for OD with an optimal cut-off at 2 (0.89 sensitivity and 0.82 specificity). The V-VST showed 0.94 sensitivity and 0.88 specificity for OD, 0.79 sensitivity and 0.75 specificity for impaired efficacy, 0.87 sensitivity and 0.81 specificity for impaired safety, and 0.91 sensitivity and 0.28 specificity for aspirations. Conclusions & Inferences Clinical methods for screening (EAT-10) and assessment (V-VST) of OD offer excellent psychometric proprieties that allow adequate management of OD. Their universal application among at-risk populations will improve the identification of patients with OD at risk for malnutrition and aspiration pneumonia. PMID:24909661

Sensitivity and specificity of the Eating Assessment Tool and the Volume-Viscosity Swallow Test for clinical evaluation of oropharyngeal dysphagia.

PubMed

Rofes, L; Arreola, V; Mukherjee, R; Clavé, P

2014-09-01

Oropharyngeal dysphagia (OD) is an underdiagnosed digestive disorder that causes severe nutritional and respiratory complications. Our aim was to determine the accuracy of the Eating Assessment Tool (EAT-10) and the Volume-Viscosity Swallow Test (V-VST) for clinical evaluation of OD. We studied 120 patients with swallowing difficulties and 14 healthy subjects. OD was evaluated by the 10-item screening questionnaire EAT-10 and the bedside method V-VST, videofluoroscopy (VFS) being the reference standard. The V-VST is an effort test that uses boluses of different volumes and viscosities to identify clinical signs of impaired efficacy (impaired labial seal, piecemeal deglutition, and residue) and impaired safety of swallow (cough, voice changes, and oxygen desaturation ≥3%). Discriminating ability was assessed by the AUC of the ROC curve and sensitivity and specificity values. According to VFS, prevalence of OD was 87%, 75.6% with impaired efficacy and 80.9% with impaired safety of swallow including 17.6% aspirations. The EAT-10 showed a ROC AUC of 0.89 for OD with an optimal cut-off at 2 (0.89 sensitivity and 0.82 specificity). The V-VST showed 0.94 sensitivity and 0.88 specificity for OD, 0.79 sensitivity and 0.75 specificity for impaired efficacy, 0.87 sensitivity and 0.81 specificity for impaired safety, and 0.91 sensitivity and 0.28 specificity for aspirations. Clinical methods for screening (EAT-10) and assessment (V-VST) of OD offer excellent psychometric proprieties that allow adequate management of OD. Their universal application among at-risk populations will improve the identification of patients with OD at risk for malnutrition and aspiration pneumonia. © 2014 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.

A Methodology for Validating Safety Heuristics Using Clinical Simulations: Identifying and Preventing Possible Technology-Induced Errors Related to Using Health Information Systems

PubMed Central

Borycki, Elizabeth; Kushniruk, Andre; Carvalho, Christopher

2013-01-01

Internationally, health information systems (HIS) safety has emerged as a significant concern for governments. Recently, research has emerged that has documented the ability of HIS to be implicated in the harm and death of patients. Researchers have attempted to develop methods that can be used to prevent or reduce technology-induced errors. Some researchers are developing methods that can be employed prior to systems release. These methods include the development of safety heuristics and clinical simulations. In this paper, we outline our methodology for developing safety heuristics specific to identifying the features or functions of a HIS user interface design that may lead to technology-induced errors. We follow this with a description of a methodological approach to validate these heuristics using clinical simulations. PMID:23606902

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

The clinical syndrome of specific antibody deficiency in children.

PubMed

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

2006-12-01

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

A scalable architecture for incremental specification and maintenance of procedural and declarative clinical decision-support knowledge.

PubMed

Hatsek, Avner; Shahar, Yuval; Taieb-Maimon, Meirav; Shalom, Erez; Klimov, Denis; Lunenfeld, Eitan

2010-01-01

Clinical guidelines have been shown to improve the quality of medical care and to reduce its costs. However, most guidelines exist in a free-text representation and, without automation, are not sufficiently accessible to clinicians at the point of care. A prerequisite for automated guideline application is a machine-comprehensible representation of the guidelines. In this study, we designed and implemented a scalable architecture to support medical experts and knowledge engineers in specifying and maintaining the procedural and declarative aspects of clinical guideline knowledge, resulting in a machine comprehensible representation. The new framework significantly extends our previous work on the Digital electronic Guidelines Library (DeGeL) The current study designed and implemented a graphical framework for specification of declarative and procedural clinical knowledge, Gesher. We performed three different experiments to evaluate the functionality and usability of the major aspects of the new framework: Specification of procedural clinical knowledge, specification of declarative clinical knowledge, and exploration of a given clinical guideline. The subjects included clinicians and knowledge engineers (overall, 27 participants). The evaluations indicated high levels of completeness and correctness of the guideline specification process by both the clinicians and the knowledge engineers, although the best results, in the case of declarative-knowledge specification, were achieved by teams including a clinician and a knowledge engineer. The usability scores were high as well, although the clinicians' assessment was significantly lower than the assessment of the knowledge engineers.

Defining thresholds of specific IgE levels to grass pollen and birch pollen allergens improves clinical interpretation.

PubMed

Van Hoeyveld, Erna; Nickmans, Silvie; Ceuppens, Jan L; Bossuyt, Xavier

2015-10-23

Cut-off values and predictive values are used for the clinical interpretation of specific IgE antibody results. However, cut-off levels are not well defined, and predictive values are dependent on the prevalence of disease. The objective of this study was to document clinically relevant diagnostic accuracy of specific IgE for inhalant allergens (grass pollen and birch pollen) based on test result interval-specific likelihood ratios. Likelihood ratios are independent of the prevalence and allow to provide diagnostic accuracy information for test result intervals. In a prospective study we included consecutive adult patients presenting at an allergy clinic with complaints of rhinitis or rhinoconjunctivitis. The standard for diagnosis was a suggestive clinical history of grass or birch pollen allergy and a positive skin test. Specific IgE was determined with the ImmunoCAP Fluorescence Enzyme Immuno-Assay. We established specific IgE test result interval related likelihood ratios for clinical allergy to inhalant allergens (grass pollen, rPhl p 1,5, birch pollen, rBet v 1). The likelihood ratios for allergy increased with increasing specific IgE antibody levels. The likelihood ratio was <0.03 for specific IgE <0.1 kU/L, between 0.1 and 1.4 for specific IgE between 0.1 kU/L and 0.35 kU/L, between 1.4 and 4.2 for specific IgE between 0.35 kU/L and 3.5 kU/L, >6.3 for specific IgE>0.7, and very high (∞) for specific IgE >3.5 kU/L. Test result interval specific likelihood ratios provide a useful tool for the interpretation of specific IgE test results for inhalant allergens. Copyright © 2015 Elsevier B.V. All rights reserved.

CloudNeo: a cloud pipeline for identifying patient-specific tumor neoantigens.

PubMed

Bais, Preeti; Namburi, Sandeep; Gatti, Daniel M; Zhang, Xinyu; Chuang, Jeffrey H

2017-10-01

We present CloudNeo, a cloud-based computational workflow for identifying patient-specific tumor neoantigens from next generation sequencing data. Tumor-specific mutant peptides can be detected by the immune system through their interactions with the human leukocyte antigen complex, and neoantigen presence has recently been shown to correlate with anti T-cell immunity and efficacy of checkpoint inhibitor therapy. However computing capabilities to identify neoantigens from genomic sequencing data are a limiting factor for understanding their role. This challenge has grown as cancer datasets become increasingly abundant, making them cumbersome to store and analyze on local servers. Our cloud-based pipeline provides scalable computation capabilities for neoantigen identification while eliminating the need to invest in local infrastructure for data transfer, storage or compute. The pipeline is a Common Workflow Language (CWL) implementation of human leukocyte antigen (HLA) typing using Polysolver or HLAminer combined with custom scripts for mutant peptide identification and NetMHCpan for neoantigen prediction. We have demonstrated the efficacy of these pipelines on Amazon cloud instances through the Seven Bridges Genomics implementation of the NCI Cancer Genomics Cloud, which provides graphical interfaces for running and editing, infrastructure for workflow sharing and version tracking, and access to TCGA data. The CWL implementation is at: https://github.com/TheJacksonLaboratory/CloudNeo. For users who have obtained licenses for all internal software, integrated versions in CWL and on the Seven Bridges Cancer Genomics Cloud platform (https://cgc.sbgenomics.com/, recommended version) can be obtained by contacting the authors. jeff.chuang@jax.org. Supplementary data are available at Bioinformatics online. © The Author(s) 2017. Published by Oxford University Press.

Identifying clinical and support-service resources and network practices for cancer patients and survivors in southern Puerto Rico

PubMed Central

Castro, Eida M.; Jiménez, Julio C.; Quinn, Gwendolyn; García, Myra; Colón, Yesenia; Ramos, Axel; Brandon, Thomas; Simmons, Vani; Gwede, Clement; Vadaparampil, Susan; Nazario, Cruz María

2015-01-01

Objective The objectives of this study were to identify cancer-related health care services and to explore the presence of inter-organizational interactions among clinical and support oncology services in southern Puerto Rico. Methods From January through July of 2010, a survey was completed by 54 health care organizations offering clinical, supportive, or both services to cancer patients/survivors (CPS) in southern PR. Survey data were compiled and descriptive analyses performed using the software Statistical Package for a Social Science (SPSS), version 18.0. Results The distribution of the primary services provided by the participating organizations was the following: 26 had clinical services, 16 had support services, and 12 offered a combination of clinical and support services. Only 24% of the surveyed organizations offered their services exclusively to patients diagnosed with cancer. In terms of referral practices, 61% of the responses were for medical specialists, 43% were for mental health services, and 37% were referrals for primary care services. The most common reason for interacting (n = 27) was to provide a given patient both an referral and information. Conclusion Findings suggest gaps in both the availability of oncology services and the delivery of integrated health care. Lack of communication among clinical and support organizations (for cancer patients, specifically) could negatively impact the quality of the services that they offer. Further network analysis studies are needed to confirm these gaps. Until systemic, structural changes occur, more efforts are needed to facilitate communication and collaboration among these kinds of organization. PMID:25249352

Newly identified bacteriolytic enzymes that target a wide range of clinical isolates of Clostridium difficile.

PubMed

Mehta, Krunal K; Paskaleva, Elena E; Wu, Xia; Grover, Navdeep; Mundra, Ruchir V; Chen, Kevin; Zhang, Yongrong; Yang, Zhiyong; Feng, Hanping; Dordick, Jonathan S; Kane, Ravi S

2016-12-01

Clostridium difficile has emerged as a major cause of infectious diarrhea in hospitalized patients, with increasing mortality rate and annual healthcare costs exceeding $3 billion. Since C. difficile infections are associated with the use of antibiotics, there is an urgent need to develop treatments that can inactivate the bacterium selectively without affecting commensal microflora. Lytic enzymes from bacteria and bacteriophages show promise as highly selective and effective antimicrobial agents. These enzymes often have a modular structure, consisting of a catalytic domain and a binding domain. In the current work, using consensus catalytic domain and cell-wall binding domain sequences as probes, we analyzed in silico the genome of C. difficile, as well as phages infecting C. difficile. We identified two genes encoding cell lytic enzymes with possible activity against C. difficile. We cloned the genes in a suitable expression vector, expressed and purified the protein products, and tested enzyme activity in vitro. These newly identified enzymes were found to be active against C. difficile cells in a dose-dependent manner. We achieved a more than 4-log reduction in the number of viable bacteria within 5 h of application. Moreover, we found that the enzymes were active against a wide range of C. difficile clinical isolates. We also characterized the biocatalytic mechanism by identifying the specific bonds cleaved by these enzymes within the cell wall peptidoglycan. These results suggest a new approach to combating the growing healthcare problem associated with C. difficile infections. Biotechnol. Bioeng. 2016;113: 2568-2576. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

The Introduction and Clinical Use of Cardiac-Specific Troponin Assays.

PubMed

Antman, Elliott M

2018-01-01

The earliest biomarkers introduced to diagnose myocardial infarction (MI) such as aspartate aminotransferase (AST) and lactic dehydrogenase (LDH) lacked cardiac specificity and were replaced by creatine kinase (CK), the CK-MB isoenzyme, and ultimately the cardiac-specific troponins (cTnT and cTnI). This has opened up the possibilities of ruling out MI more rapidly and also identifying patients with a chronic elevation of cTn and a poor prognosis in a range of cardiac conditions. © 2017 ASCPT.

Identifying Signs of Tinea Pedis: A Key to Understanding Clinical Variables.

PubMed

Canavan, Theresa N; Elewski, Boni E

2015-10-01

Tinea pedis is a frequently encountered dermatophytosis affecting the superficial skin of the feet, primarily of adults. The prevalence of tinea pedis has increased over the last several decades due to an increase in multiple risk factors. Infection from dermatophytes is most common, but infection from other fungi can also result in tinea pedis. Four distinct clinical presentations occur: interdigital, moccasin, vesicular, and acute ulcerative types. A variety of physical exam findings can help the clinician identify patients with tinea pedis.

GWAS of clinically defined gout and subtypes identifies multiple susceptibility loci that include urate transporter genes.

PubMed

Nakayama, Akiyoshi; Nakaoka, Hirofumi; Yamamoto, Ken; Sakiyama, Masayuki; Shaukat, Amara; Toyoda, Yu; Okada, Yukinori; Kamatani, Yoichiro; Nakamura, Takahiro; Takada, Tappei; Inoue, Katsuhisa; Yasujima, Tomoya; Yuasa, Hiroaki; Shirahama, Yuko; Nakashima, Hiroshi; Shimizu, Seiko; Higashino, Toshihide; Kawamura, Yusuke; Ogata, Hiraku; Kawaguchi, Makoto; Ohkawa, Yasuyuki; Danjoh, Inaho; Tokumasu, Atsumi; Ooyama, Keiko; Ito, Toshimitsu; Kondo, Takaaki; Wakai, Kenji; Stiburkova, Blanka; Pavelka, Karel; Stamp, Lisa K; Dalbeth, Nicola; Sakurai, Yutaka; Suzuki, Hiroshi; Hosoyamada, Makoto; Fujimori, Shin; Yokoo, Takashi; Hosoya, Tatsuo; Inoue, Ituro; Takahashi, Atsushi; Kubo, Michiaki; Ooyama, Hiroshi; Shimizu, Toru; Ichida, Kimiyoshi; Shinomiya, Nariyoshi; Merriman, Tony R; Matsuo, Hirotaka

2017-05-01

A genome-wide association study (GWAS) of gout and its subtypes was performed to identify novel gout loci, including those that are subtype-specific. Putative causal association signals from a GWAS of 945 clinically defined gout cases and 1213 controls from Japanese males were replicated with 1396 cases and 1268 controls using a custom chip of 1961 single nucleotide polymorphisms (SNPs). We also first conducted GWASs of gout subtypes. Replication with Caucasian and New Zealand Polynesian samples was done to further validate the loci identified in this study. In addition to the five loci we reported previously, further susceptibility loci were identified at a genome-wide significance level (p<5.0×10 -8 ): urate transporter genes ( SLC22A12 and SLC17A1 ) and HIST1H2BF-HIST1H4E for all gout cases, and NIPAL1 and FAM35A for the renal underexcretion gout subtype. While NIPAL1 encodes a magnesium transporter, functional analysis did not detect urate transport via NIPAL1, suggesting an indirect association with urate handling. Localisation analysis in the human kidney revealed expression of NIPAL1 and FAM35A mainly in the distal tubules, which suggests the involvement of the distal nephron in urate handling in humans. Clinically ascertained male patients with gout and controls of Caucasian and Polynesian ancestries were also genotyped, and FAM35A was associated with gout in all cases. A meta-analysis of the three populations revealed FAM35A to be associated with gout at a genome-wide level of significance (p meta =3.58×10 -8 ). Our findings including novel gout risk loci provide further understanding of the molecular pathogenesis of gout and lead to a novel concept for the therapeutic target of gout/hyperuricaemia. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Risk of Clinically Significant Prostate Cancer Associated With Prostate Imaging Reporting and Data System Category 3 (Equivocal) Lesions Identified on Multiparametric Prostate MRI.

PubMed

Sheridan, Alison D; Nath, Sameer K; Syed, Jamil S; Aneja, Sanjay; Sprenkle, Preston C; Weinreb, Jeffrey C; Spektor, Michael

2018-02-01

The objective of this study is to determine the frequency of clinically significant cancer (CSC) in Prostate Imaging Reporting and Data System (PI-RADS) category 3 (equivocal) lesions prospectively identified on multiparametric prostate MRI and to identify risk factors (RFs) for CSC that may aid in decision making. Between January 2015 and July 2016, a total of 977 consecutively seen men underwent multiparametric prostate MRI, and 342 underwent MRI-ultrasound (US) fusion targeted biopsy. A total of 474 lesions were retrospectively reviewed, and 111 were scored as PI-RADS category 3 and were visualized using a 3-T MRI scanner. Multiparametric prostate MR images were prospectively interpreted by body subspecialty radiologists trained to use PI-RADS version 2. CSC was defined as a Gleason score of at least 7 on targeted biopsy. A multivariate logistic regression model was constructed to identify the RFs associated with CSC. Of the 111 PI-RADS category 3 lesions, 81 (73.0%) were benign, 11 (9.9%) were clinically insignificant (Gleason score, 6), and 19 (17.1%) were clinically significant. On multivariate analysis, three RFs were identified as significant predictors of CSC: older patient age (odds ratio [OR], 1.13; p = 0.002), smaller prostate volume (OR, 0.94; p = 0.008), and abnormal digital rectal examination (DRE) findings (OR, 3.92; p = 0.03). For PI-RADS category 3 lesions associated with zero, one, two, or three RFs, the risk of CSC was 4%, 16%, 62%, and 100%, respectively. PI-RADS category 3 lesions for which two or more RFs were noted (e.g., age ≥ 70 years, gland size ≤ 36 mL, or abnormal DRE findings) had a CSC detection rate of 67% with a sensitivity of 53%, a specificity of 95%, a positive predictive value of 67%, and a negative predictive value of 91%. Incorporating clinical parameters into risk stratification algorithms may improve the ability to detect clinically significant disease among PI-RADS category 3 lesions and may aid in the decision to

The clinical examination of non-word repetition tasks in identifying Persian-speaking children with primary language impairment.

PubMed

Kazemi, Yalda; Saeednia, Soodeh

2017-02-01

This study aimed to examine the diagnostic accuracy of a non-word repetition (NWR) test in identifying Persian-speaking preschool children with specific/primary language impairment (PLI). Children with PLI show consistently poorer performance in non-word repetition tasks than their typically developing language (TDL) counterparts. It is assumed that the ability to repeat non-words triggers language skills and that the absence of this ability may be responsible for language impairment in PLI children. Twenty preschool children with PLI participated in this study and were compared with 31 peers whose language skills were developing typically. The TDL children were randomly selected from daycare centers, and the children with PLI were referred by qualified speech-language pathologists from speech therapy clinics. A Persian NWR test was administered and scored using two levels of scoring: item-level scoring and syllable-level scoring. Data were analyzed in two phases. The first phase aimed to determine any differences between the two groups of children in terms of NWR ability. The second phase examined the diagnostic measures of the test. The results of first phase documented that both scoring methods for the NWR test significantly differentiated between children with PLI and their normal peers. The second phase indicated that both scoring methods for the NWR test have good sensitivity and specificity in differentiating Persian-speaking children with PLI from their normal peers. Non-word repetition can be a reliable clinical marker of PLI in Persian-speaking preschool children. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Epidemiological study on the penicillin resistance of clinical Streptococcus pneumoniae isolates identified as the common sequence types.

PubMed

Gao, Wei; Shi, Wei; Chen, Chang-hui; Wen, De-nian; Tian, Jin; Yao, Kai-hu

2016-10-20

There were some limitation in the current interpretation about the penicillin resistance mechanism of clinical Streptococcus pneumoniae isolates at the strain level. To explore the possibilities of studying the mechanism based on the sequence types (ST) of this bacteria, 488 isolates collected in Beijing from 1997-2014 and 88 isolates collected in Youyang County, Chongqing and Zhongjiang County, Sichuan in 2015 were analyzed by penicillin minimum inhibitory concentration (MIC) distribution and annual distribution. The results showed that the penicillin MICs of the all isolates covering by the given ST in Beijing have a defined range, either <0.25 mg/L or≥0.25 mg/L, except for the ST342. The isolates with penicillin MIC <0.25 mg/L were mainly collected before 2001, after which the isolates with MIC≥0.25 mg/L occurred and became the major population gradually. This law of year distribution, however, was not obvious for any specific ST. The isolates covering by any given ST could be determined with different penicillin MICs in the first few years after it was identified. The penicillin MIC of isolates identified as common STs and collected in Youyang County, Chongqing and Sichuan Zhongjiang County, including the ST271, ST320 and ST81, was around 0.25~2 mg/L (≥0.25 mg/L). Our study revealed the epidemiological distribution of penicillin MICs of the given STs determined in clinical S. pneumoniae isolates, suggesting that it is reasonable to research the penicillin resistance mechanism based on the STs of this bacteria.

[Identifying indicators of good practice in clinical and healthcare management].

PubMed

Bermúdez Tamayo, C; Olry de Labry Lima, A; García Mochón, L

To identify good practices in order to develop and implement indicators of health outcomes for clinical and healthcare management, as well as the characteristics for an indicator to be considered adequate. A scoping review was performed, with the following phases: 1) Search and identification of bibliography. 2) Selection of relevant documents. Including those studies that discussed issues related to good practices for the use of health indicators in the management field. Those published in a language other than English or Spanish or before 2006 were excluded. 3) Analysis and extraction of information. 4) Consultation with stakeholders, using a qualitative methodology through Concept Mapping, with the participation of 40 experts (decision-makers, scientific societies, and health professionals). The data collection process included an inductive and structured procedure, with prioritisation of ideas grouped into clusters, according to feasibility and importance criteria (0-10 scale). Good practices identified 2 levels: 1) macro-management: Define a framework for the evaluation of indicators and establish a benchmark of indicators. 2) meso-management: Establish indicators according to evidence and expert consensus, taking into account priority areas and topics, testing before final use, and communicate results adequately. The characteristics of a suitable indicator are: 1) Approach of an important issue, 2) Scientific validity, 3) Possibility of measurement with reliable data, 4) Meaning of useful and applicable measurement, and 5) Wide scope. The best practices for the use of indicators in clinical and healthcare management can make it easier to monitor performance and accountability, as well as to support the decision-making addressed at the development of initiatives for quality improvement. Copyright © 2018 SECA. Publicado por Elsevier España, S.L.U. All rights reserved.

Identifying and applying psychological theory to setting and achieving rehabilitation goals.

PubMed

Scobbie, Lesley; Wyke, Sally; Dixon, Diane

2009-04-01

Goal setting is considered to be a fundamental part of rehabilitation; however, theories of behaviour change relevant to goal-setting practice have not been comprehensively reviewed. (i) To identify and discuss specific theories of behaviour change relevant to goal-setting practice in the rehabilitation setting. (ii) To identify 'candidate' theories that that offer most potential to inform clinical practice. The rehabilitation and self-management literature was systematically searched to identify review papers or empirical studies that proposed a specific theory of behaviour change relevant to setting and/or achieving goals in a clinical context. Data from included papers were extracted under the headings of: key constructs, clinical application and empirical support. Twenty-four papers were included in the review which proposed a total of five theories: (i) social cognitive theory, (ii) goal setting theory, (iii) health action process approach, (iv) proactive coping theory, and (v) the self-regulatory model of illness behaviour. The first three of these theories demonstrated most potential to inform clinical practice, on the basis of their capacity to inform interventions that resulted in improved patient outcomes. Social cognitive theory, goal setting theory and the health action process approach are theories of behaviour change that can inform clinicians in the process of setting and achieving goals in the rehabilitation setting. Overlapping constructs within these theories have been identified, and can be applied in clinical practice through the development and evaluation of a goal-setting practice framework.

The quality of clinical maternal and neonatal healthcare - a strategy for identifying 'routine care signal functions'.

PubMed

Brenner, Stephan; De Allegri, Manuela; Gabrysch, Sabine; Chinkhumba, Jobiba; Sarker, Malabika; Muula, Adamson S

2015-01-01

A variety of clinical process indicators exists to measure the quality of care provided by maternal and neonatal health (MNH) programs. To allow comparison across MNH programs in low- and middle-income countries (LMICs), a core set of essential process indicators is needed. Although such a core set is available for emergency obstetric care (EmOC), the 'EmOC signal functions', a similar approach is currently missing for MNH routine care evaluation. We describe a strategy for identifying core process indicators for routine care and illustrate their usefulness in a field example. We first developed an indicator selection strategy by combining epidemiological and programmatic aspects relevant to MNH in LMICs. We then identified routine care process indicators meeting our selection criteria by reviewing existing quality of care assessment protocols. We grouped these indicators into three categories based on their main function in addressing risk factors of maternal or neonatal complications. We then tested this indicator set in a study assessing MNH quality of clinical care in 33 health facilities in Malawi. Our strategy identified 51 routine care processes: 23 related to initial patient risk assessment, 17 to risk monitoring, 11 to risk prevention. During the clinical performance assessment a total of 82 cases were observed. Birth attendants' adherence to clinical standards was lowest in relation to risk monitoring processes. In relation to major complications, routine care processes addressing fetal and newborn distress were performed relatively consistently, but there were major gaps in the performance of routine care processes addressing bleeding, infection, and pre-eclampsia risks. The identified set of process indicators could identify major gaps in the quality of obstetric and neonatal care provided during the intra- and immediate postpartum period. We hope our suggested indicators for essential routine care processes will contribute to streamlining MNH program

Identifying factors which enhance capacity to engage in clinical education among podiatry practitioners: an action research project.

PubMed

Abey, Sally; Lea, Susan; Callaghan, Lynne; Shaw, Steve; Cotton, Debbie

2015-01-01

Health profession students develop practical skills whilst integrating theory with practice in a real world environment as an important component of their training. Research in the area of practice placements has identified challenges and barriers to the delivery of effective placement learning. However, there has been little research in podiatry and the question of which factors impact upon clinical educators' capacity to engage with the role remains an under-researched area. This paper presents the second phase of an action research project designed to determine the factors that impact upon clinical educators' capacity to engage with the mentorship role. An online survey was developed and podiatry clinical educators recruited through National Health Service (NHS) Trusts. The survey included socio-demographic items, and questions relating to the factors identified as possible variables influencing clinical educator capacity; the latter was assessed using the 'Clinical Educator Capacity to Engage' scale (CECE). Descriptive statistics were used to explore demographic data whilst the relationship between the CECE and socio-demographic factors were examined using inferential statistics in relation to academic profile, career profile and organisation of the placement. The survey response rate was 42 % (n = 66). Multiple linear regression identified four independent variables which explain a significant proportion of the variability of the dependent variable, 'capacity to engage with clinical education', with an adjusted R2 of 0.428. The four variables were: protected mentorship time, clinical educator relationship with university, sign-off responsibility, and volunteer status. The identification of factors that impact upon clinical educators' capacity to engage in mentoring of students has relevance for strategic planning and policy-making with the emphasis upon capacity-building at an individual level, so that the key attitudes and characteristics that are linked

ABPA diagnosis in cystic fibrosis patients: the clinical utility of IgE specific to recombinant Aspergillus fumigatus allergens.

PubMed

Almeida, Marina B; Bussamra, Maria Helena C F; Rodrigues, Joaquim C

2006-01-01

Allergic bronchopulmonary aspergillosis (ABPA) is a complicating factor of cystic fibrosis which can result in a devastating combination as lung disease progresses. The overlap between the signs and symptoms of the two conditions makes diagnosis problematic, even if standardized criteria are used. The objective of this study was to identify, in a group of cystic fibrosis patients, cases of ABPA by assaying IgE specific to recombinant Aspergillus fumigatus antigens and to compare the method with the Cystic Fibrosis Foundation diagnostic criteria. Fifty-four patients, aged 2 to 20 years, presenting characteristics that could occur with ABPA in isolation, were systematically assessed based on the following: clinical data, a chest CT scan, immediate hypersensitivity skin test for A. fumigatus, total serum IgE assay, RAST for A. fumigatus and serum IgE specific for the recombinant allergens Asp f1, f2, f3, f4 and f6. Thirty-nine patients were eligible for the study. Thirty-two of these were investigated. Sensitization to A. fumigatus was observed in 34%. Both the Cystic Fibrosis Foundation criteria and the recombinant antigen specific IgE assay defined three patients as suffering from ABPA; however, only two of these patients were diagnosed by both methods. The detection of A. fumigatus recombinant antigen specific IgE was a useful tool for the early detection of sensitization and diagnosis of ABPA. Nevertheless, diagnostic confirmation cannot be divorced from clinical findings, and before this method can be used for ABPA diagnosis, for detecting relapses and for defining cure criteria, longitudinal studies with larger numbers of patients are required.

Design of CT reconstruction kernel specifically for clinical lung imaging

NASA Astrophysics Data System (ADS)

Cody, Dianna D.; Hsieh, Jiang; Gladish, Gregory W.

2005-04-01

In this study we developed a new reconstruction kernel specifically for chest CT imaging. An experimental flat-panel CT scanner was used on large dogs to produce 'ground-truth" reference chest CT images. These dogs were also examined using a clinical 16-slice CT scanner. We concluded from the dog images acquired on the clinical scanner that the loss of subtle lung structures was due mostly to the presence of the background noise texture when using currently available reconstruction kernels. This qualitative evaluation of the dog CT images prompted the design of a new recon kernel. This new kernel consisted of the combination of a low-pass and a high-pass kernel to produce a new reconstruction kernel, called the 'Hybrid" kernel. The performance of this Hybrid kernel fell between the two kernels on which it was based, as expected. This Hybrid kernel was also applied to a set of 50 patient data sets; the analysis of these clinical images is underway. We are hopeful that this Hybrid kernel will produce clinical images with an acceptable tradeoff of lung detail, reliable HU, and image noise.

Identifying a Clinically Meaningful Threshold for Change in Uveitic Macular Edema Evaluated by Optical Coherence Tomography

PubMed Central

Sugar, Elizabeth A.; Jabs, Douglas A.; Altaweel, Michael M.; Lightman, Sue; Acharya, Nisha; Vitale, Albert T.; Thorne, Jennifer E.

2011-01-01

Purpose To identify a clinically meaningful threshold for change in retinal thickness measured by optical coherence tomography (OCT) for patients with uveitic macular edema, using correlation with change in visual acuity. Design Cross-sectional and longitudinal study. Methods 128 eyes (101 individuals) with macular edema enrolled in the Multicenter Uveitis Steroid Treatment (MUST) trial. At enrollment and after six months of follow-up, retinal thickness was measured at the central subfield with time domain OCT and visual acuity was measured with logarithmic (ETDRS) visual acuity charts. Participants were classified as having macular edema if the retinal thickness was ≥260μm. Results A threshold for change in retinal center subfield thickness of 20% balanced the percentage of false positives and negatives for predicting greater than 10-letter change in visual acuity with sensitivity of 77% and a specificity of 75%. The results were similar for greater than 5 or 15 or greater letter changes. Those with a 20% or greater reduction in retinal thickness had a mean 11.0 letter improvement (95% CI: 7.7 to 14.3) as compared to a -0.4 letter change (95% CI: -4.1 to 3.3) in visual acuity for those without a 20% reduction (p < 0.01). Conclusions In addition to being above the level of measurement uncertainty, a 20% change in retinal thickness in patients with macular edema appears to be optimal for clinically important changes in visual acuity and may be considered as an outcome for clinical trials of treatments for uveitic macular edema. PMID:21861971

A qualitative study examining methods of accessing and identifying research relevant to clinical practice among rehabilitation clinicians.

PubMed

Patel, Drasti; Koehmstedt, Christine; Jones, Rebecca; Coffey, Nathan T; Cai, Xinsheng; Garfinkel, Steven; Shaewitz, Dahlia M; Weinstein, Ali A

2017-01-01

Research examining the utilization of evidence-based practice (EBP) specifically among rehabilitation clinicians is limited. The objective of this study was to examine how various rehabilitative clinicians including physical therapists, occupational therapists, rehabilitation counselors, and physiatrists are gaining access to literature and whether they are able to implement the available research into practice. A total of 21 total clinicians were interviewed via telephone. Using NVivo, a qualitative analysis of the responses was performed. There were similarities found with respect to the information-seeking behaviors and translation of research across the different clinician types. Lack of time was reported to be a barrier for both access to literature and implementation of research across all clinician types. The majority of clinicians who reported having difficulty with utilizing the published literature indicated that the literature was not applicable to their practice, the research was not specific enough to be put into practice, or the research found was too outdated to be relevant. In addition, having a supportive work environment aided in the search and utilization of research through providing resources central to assisting clinicians in gaining access to health information. Our study identified several barriers that affect EBP for rehabilitation clinicians. The findings suggest the need for researchers to ensure that their work is applicable and specific to clinical practice for implementation to occur.

Clinical incidents involving students on placement: an analysis of incident reports to identify potential risk factors.

PubMed

Gaida, J E; Maloney, S; Lo, K; Morgan, P

2015-06-01

Students are sometimes involved in incidents during clinical training. To the authors' knowledge, no quantitative studies of incidents specifically involving physiotherapy students on clinical placement are available in the literature. A retrospective audit (2008 to 2011) of incident reports involving physiotherapy students was conducted to identify the nature and features of incidents. The study aimed to determine if injuries to a student or patient were more or less likely when the supervisor was in close proximity, and whether students with lower academic performance in their preclinical semester were more likely to be involved in an incident. There were 19 care-delivery-related and three equipment-related incidents. There were no incidents of violent, aggressive or demeaning behaviour towards students. The incident rate was 9.0/100,000 student-hours for third-year students and 6.8/100,000 student-hours for fourth-year students. The majority of incidents (55%) occurred from 11 am to 12-noon and from 3 pm to 3.30 pm. Incidents more often resulted in patient or student injury when the supervisor was not in close proximity (approximately 50% vs approximately 20%), although the difference was not significant (P=0.336). The academic results of students involved in incidents were equivalent to the whole cohort in their preclinical semester {mean 75 [standard deviation (SD) 6] vs 76 (SD 7); P=0.488}. The unexpected temporal clustering of incidents warrants further investigation. Student fatigue may warrant attention as a potential contributor; however, contextual factors, such as staff workload, along with organisational systems, structures and procedures may be more relevant. The potential relationship between supervisor proximity and injury also warrants further exploration. The findings of the present study should be integrated into clinical education curricula and communicated to clinical educators. Copyright © 2014 Chartered Society of Physiotherapy. Published by

Seeking informed consent to Phase I cancer clinical trials: identifying oncologists' communication strategies.

PubMed

Brown, Richard; Bylund, Carma L; Siminoff, Laura A; Slovin, Susan F

2011-04-01

Phase I clinical trials are the gateway to effective new cancer treatments. Many physicians have difficulty when discussing Phase I clinical trials. Research demonstrates evidence of suboptimal communication. Little is known about communication strategies used by oncologists when recruiting patients for Phase I trials. We analyzed audio recorded Phase I consultations to identify oncologists' communication strategies. Subjects were consecutive cancer patients from six medical oncologists attending one of three outpatient clinics at a major Cancer Center in the United States. Sixteen patients signed informed consent for audio recording of their consultations in which a Phase I study was discussed. These were transcribed in full and analyzed to identify communication strategies. Six communication themes emerged from the analysis: (1) orienting, (2) educating patients, (3) describing uncertainty and prognosis, (4) persuading, (5) decision making, and (6) making a treatment recommendation. As expected, although there was some common ground between communication in Phase I and the Phase II and III settings, there were distinct differences. Oncologists used persuasive communication, made explicit recommendations, or implicitly expressed a treatment preference and were choice limiting. This highlights the complexity of discussing Phase I trials and the need to develop strategies to aid oncologists and patients in these difficult conversations. Patient centered communication that values patient preferences while preserving the oncologist's agenda can be a helpful approach to these discussions. Copyright © 2010 John Wiley & Sons, Ltd.

Key clinical features to identify girls with CDKL5 mutations.

PubMed

Bahi-Buisson, Nadia; Nectoux, Juliette; Rosas-Vargas, Haydeé; Milh, Mathieu; Boddaert, Nathalie; Girard, Benoit; Cances, Claude; Ville, Dorothée; Afenjar, Alexandra; Rio, Marlène; Héron, Delphine; N'guyen Morel, Marie Ange; Arzimanoglou, Alexis; Philippe, Christophe; Jonveaux, Philippe; Chelly, Jamel; Bienvenu, Thierry

2008-10-01

Mutations in the human X-linked cyclin-dependent kinase-like 5 (CDKL5) gene have been shown to cause infantile spasms as well as Rett syndrome (RTT)-like phenotype. To date, less than 25 different mutations have been reported. So far, there are still little data on the key clinical diagnosis criteria and on the natural history of CDKL5-associated encephalopathy. We screened the entire coding region of CDKL5 for mutations in 183 females with encephalopathy with early seizures by denaturing high liquid performance chromatography and direct sequencing, and we identified in 20 unrelated girls, 18 different mutations including 7 novel mutations. These mutations were identified in eight patients with encephalopathy with RTT-like features, five with infantile spasms and seven with encephalopathy with refractory epilepsy. Early epilepsy with normal interictal EEG and severe hypotonia are the key clinical features in identifying patients likely to have CDKL5 mutations. Our study also indicates that these patients clearly exhibit some RTT features such as deceleration of head growth, stereotypies and hand apraxia and that these RTT features become more evident in older and ambulatory patients. However, some RTT signs are clearly absent such as the so called RTT disease profile (period of nearly normal development followed by regression with loss of acquired fine finger skill in early childhood and characteristic intensive eye communication) and the characteristic evolution of the RTT electroencephalogram. Interestingly, in addition to the overall stereotypical symptomatology (age of onset and evolution of the disease) resulting from CDKL5 mutations, atypical forms of CDKL5-related conditions have also been observed. Our data suggest that phenotypic heterogeneity does not correlate with the nature or the position of the mutations or with the pattern of X-chromosome inactivation, but most probably with the functional transcriptional and/or translational consequences of CDKL5

Patient-specific instrumentation does not improve radiographic alignment or clinical outcomes after total knee arthroplasty.

PubMed

Huijbregts, Henricus J T A M; Khan, Riaz J K; Sorensen, Emma; Fick, Daniel P; Haebich, Samantha

2016-08-01

Background and purpose - Patient-specific instrumentation (PSI) for total knee arthroplasty (TKA) has been introduced to improve alignment and reduce outliers, increase efficiency, and reduce operation time. In order to improve our understanding of the outcomes of patient-specific instrumentation, we conducted a meta-analysis. Patients and methods - We identified randomized and quasi-randomized controlled trials (RCTs) comparing patient-specific and conventional instrumentation in TKA. Weighted mean differences and risk ratios were determined for radiographic accuracy, operation time, hospital stay, blood loss, number of surgical trays required, and patient-reported outcome measures. Results - 21 RCTs involving 1,587 TKAs were included. Patient-specific instrumentation resulted in slightly more accurate hip-knee-ankle axis (0.3°), coronal femoral alignment (0.3°, femoral flexion (0.9°), tibial slope (0.7°), and femoral component rotation (0.5°). The risk ratio of a coronal plane outlier (> 3° deviation of chosen target) for the tibial component was statistically significantly increased in the PSI group (RR =1.64). No significance was found for other radiographic measures. Operation time, blood loss, and transfusion rate were similar. Hospital stay was significantly shortened, by approximately 8 h, and the number of surgical trays used decreased by 4 in the PSI group. Knee Society scores and Oxford knee scores were similar. Interpretation - Patient-specific instrumentation does not result in clinically meaningful improvement in alignment, fewer outliers, or better early patient-reported outcome measures. Efficiency is improved by reducing the number of trays used, but PSI does not reduce operation time.

Skin marker placement by technologist prior to knee MRI helps identify clinically relevant pathologies.

PubMed

Wadhwa, Vibhor; Weissman, Eric; Hayashi, Daichi; Xi, Yin; Chhabra, Avneesh

2017-12-15

Majority of musculoskeletal cross-sectional imaging requests have a non-revealing and non-specific clinical history of pain. However, the location of pain is very relevant towards arriving at a specific orthopedic diagnosis. The purpose of this research was to study the impact of skin marker placement and training of technologists prior to knee MRI in detection of clinically important findings. Total 200 consecutive left knee MRIs were evaluated before and after technologist training with regards to marker placement at the site of clinical symptoms or palpable finding. Marker location in relation to the knee was recorded and important findings were classified as correlated important finding, non-correlated important finding, other compartment important finding in non-correlated cases, and diffuse abnormality, i.e. tri-compartmental cartilage defects in both correlated and non-correlated cases. Differences among scans before and after technologist training were analyzed. The marker placement was observed in higher proportion of patients in post-training scans (78% vs 60%, p = 0.00). The most common location of the marker was in anterior or anterolateral knee (32% and 34% cases, respectively). The marker-important finding correlation was also higher post training, but not statistically significant (53% versus 38%, p = 0.57). Important findings correlated with the marker in more than 50% of the scans in the post-training set. Marker placement can aid in detection of clinically important imaging finding and technologist training aids in increased rates of marker placement and improved correlation.

Compendium of Immune Signatures Identifies Conserved and Species-Specific Biology in Response to Inflammation.

PubMed

Godec, Jernej; Tan, Yan; Liberzon, Arthur; Tamayo, Pablo; Bhattacharya, Sanchita; Butte, Atul J; Mesirov, Jill P; Haining, W Nicholas

2016-01-19

Gene-expression profiling has become a mainstay in immunology, but subtle changes in gene networks related to biological processes are hard to discern when comparing various datasets. For instance, conservation of the transcriptional response to sepsis in mouse models and human disease remains controversial. To improve transcriptional analysis in immunology, we created ImmuneSigDB: a manually annotated compendium of ∼5,000 gene-sets from diverse cell states, experimental manipulations, and genetic perturbations in immunology. Analysis using ImmuneSigDB identified signatures induced in activated myeloid cells and differentiating lymphocytes that were highly conserved between humans and mice. Sepsis triggered conserved patterns of gene expression in humans and mouse models. However, we also identified species-specific biological processes in the sepsis transcriptional response: although both species upregulated phagocytosis-related genes, a mitosis signature was specific to humans. ImmuneSigDB enables granular analysis of transcriptomic data to improve biological understanding of immune processes of the human and mouse immune systems. Copyright © 2016 Elsevier Inc. All rights reserved.

A microscopy-based screen employing multiplex genome sequencing identifies cargo-specific requirements for dynein velocity

PubMed Central

Tan, Kaeling; Roberts, Anthony J.; Chonofsky, Mark; Egan, Martin J.; Reck-Peterson, Samara L.

2014-01-01

The timely delivery of membranous organelles and macromolecules to specific locations within the majority of eukaryotic cells depends on microtubule-based transport. Here we describe a screening method to identify mutations that have a critical effect on intracellular transport and its regulation using mutagenesis, multicolor-fluorescence microscopy, and multiplex genome sequencing. This screen exploits the filamentous fungus Aspergillus nidulans, which has many of the advantages of yeast molecular genetics but uses long-range microtubule-based transport in a manner more similar to metazoan cells. Using this method, we identified seven mutants that represent novel alleles of components of the intracellular transport machinery: specifically, kinesin-1, cytoplasmic dynein, and the dynein regulators Lis1 and dynactin. The two dynein mutations identified in our screen map to dynein's AAA+ catalytic core. Single-molecule studies reveal that both mutations reduce dynein's velocity in vitro. In vivo these mutants severely impair the distribution and velocity of endosomes, a known dynein cargo. In contrast, another dynein cargo, the nucleus, is positioned normally in these mutants. These results reveal that different dynein functions have distinct stringencies for motor performance. PMID:24403603

Disease-specific clinical pathways - are they feasible in primary care? A mixed-methods study.

PubMed

Grimsmo, Anders; Løhre, Audhild; Røsstad, Tove; Gjerde, Ingunn; Heiberg, Ina; Steinsbekk, Aslak

2018-06-01

To explore the feasibility of disease-specific clinical pathways when used in primary care. A mixed-method sequential exploratory design was used. First, merging and exploring quality interview data across two cases of collaboration between the specialist care and primary care on the introduction of clinical pathways for four selected chronic diseases. Secondly, using quantitative data covering a population of 214,700 to validate and test hypothesis derived from the qualitative findings. Primary care and specialist care collaborating to manage care coordination. Primary-care representatives expressed that their patients often have complex health and social needs that clinical pathways guidelines seldom consider. The representatives experienced that COPD, heart failure, stroke and hip fracture, frequently seen in hospitals, appear in low numbers in primary care. The quantitative study confirmed the extensive complexity among home healthcare nursing patients and demonstrated that, for each of the four selected diagnoses, a homecare nurse on average is responsible for preparing reception of the patient at home after discharge from hospital, less often than every other year. The feasibility of disease-specific pathways in primary care is limited, both from a clinical and organisational perspective, for patients with complex needs. The low prevalence in primary care of patients with important chronic conditions, needing coordinated care after hospital discharge, constricts transferring tasks from specialist care. Generic clinical pathways are likely to be more feasible and efficient for patients in this setting. Key points Clinical pathways in hospitals apply to single-disease guidelines, while more than 90% of the patients discharged to community health care for follow-up have multimorbidity. Primary care has to manage the health care of the patient holistically, with all his or her complex needs. Patients most frequently admitted to hospitals, i.e. patients with COPD

Anti-MDA5 autoantibodies in juvenile dermatomyositis identify a distinct clinical phenotype: a prospective cohort study

PubMed Central

2014-01-01

Introduction The aim of this study was to define the frequency and associated clinical phenotype of anti-MDA5 autoantibodies in a large UK based, predominantly Caucasian, cohort of patients with juvenile dermatomyositis (JDM). Methods Serum samples and clinical data were obtained from 285 patients with JDM recruited to the UK Juvenile Dermatomyositis Cohort and Biomarker Study. The presence of anti-MDA5 antibodies was determined by immunoprecipitation and confirmed by ELISA using recombinant MDA5 protein. Results were compared with matched clinical data, muscle biopsies (scored by an experienced paediatric neuropathologist) and chest imaging (reviewed by an experienced paediatric radiologist). Results Anti-MDA5 antibodies were identified in 7.4% of JDM patients and were associated with a distinct clinical phenotype including skin ulceration (P = 0.03) oral ulceration (P = 0.01), arthritis (P <0.01) and milder muscle disease both clinically (as determined by Childhood Myositis Assessment Score (P = 0.03)) and histologically (as determined by a lower JDM muscle biopsy score (P <0.01)) than patients who did not have anti-MDA5 antibodies. A greater proportion of children with anti-MDA5 autoantibodies achieved disease inactivity at two years post-diagnosis according to PRINTO criteria (P = 0.02). A total of 4 out of 21 children with anti-MDA5 had interstitial lung disease; none had rapidly progressive interstitial lung disease. Conclusions Anti-MDA5 antibodies can be identified in a small but significant proportion of patients with JDM and identify a distinctive clinical sub-group. Screening for anti-MDA5 autoantibodies at diagnosis would be useful to guide further investigation for lung disease, inform on prognosis and potentially confirm the diagnosis, as subtle biopsy changes could otherwise be missed. PMID:24989778

Identifying Unmet Treatment Needs for Patients With Osteoporotic Fracture: Feasibility Study for an Electronic Clinical Surveillance System

PubMed Central

Shang, Rung Ji; Hsiao, Fei-Yuan; Lin, Mei-Shu; Hung, Kuan-Yu; Wang, Jui; Lin, Zhen-Fang; Lai, Feipei; Shen, Li-Jiuan

2018-01-01

Background Traditional clinical surveillance relied on the results from clinical trials and observational studies of administrative databases. However, these studies not only required many valuable resources but also faced a very long time lag. Objective This study aimed to illustrate a practical application of the National Taiwan University Hospital Clinical Surveillance System (NCSS) in the identification of patients with an osteoporotic fracture and to provide a high reusability infrastructure for longitudinal clinical data. Methods The NCSS integrates electronic medical records in the National Taiwan University Hospital (NTUH) with a data warehouse and is equipped with a user-friendly interface. The NCSS was developed using professional insight from multidisciplinary experts, including clinical practitioners, epidemiologists, and biomedical engineers. The practical example identifying the unmet treatment needs for patients encountering major osteoporotic fractures described herein was mainly achieved by adopting the computerized workflow in the NCSS. Results We developed the infrastructure of the NCSS, including an integrated data warehouse and an automatic surveillance workflow. By applying the NCSS, we efficiently identified 2193 patients who were newly diagnosed with a hip or vertebral fracture between 2010 and 2014 at NTUH. By adopting the filter function, we identified 1808 (1808/2193, 82.44%) patients who continued their follow-up at NTUH, and 464 (464/2193, 21.16%) patients who were prescribed anti-osteoporosis medications, within 3 and 12 months post the index date of their fracture, respectively. Conclusions The NCSS systems can integrate the workflow of cohort identification to accelerate the survey process of clinically relevant problems and provide decision support in the daily practice of clinical physicians, thereby making the benefit of evidence-based medicine a reality. PMID:29691201

Identifying Opportunities for Peer Learning: An Observational Study of Medical Students on Clinical Placements.

PubMed

Tai, Joanna H; Canny, Benedict J; Haines, Terry P; Molloy, Elizabeth K

2017-01-01

Phenomenon: Peer assisted learning (PAL) is frequently employed and researched in preclinical medical education. Fewer studies have examined PAL in the clinical context: These have focused mainly on the accuracy of peer assessment and potential benefits to learner communication and teamwork skills. Research has also examined the positive and negative effects of formal, structured PAL activities in the clinical setting. Given the prevalence of PAL activities during preclinical years, and the unstructured nature of clinical placements, it is likely that nonformal PAL activities are also undertaken. How PAL happens formally and informally and why students find PAL useful in this clinical setting remain poorly understood. This study aimed to describe PAL activities within the context of clinical placement learning and to explore students' perceptions of these activities. An ethnographic study was conducted to gather empirical data on engagement in clinical placement learning activities, including observations and interviews with students in their 1st clinical year, along with their supervising clinicians. Thematic analysis was used to interrogate the data. On average, students used PAL for 5.19 hours per week in a range of activities, of a total of 29.29 hours undertaking placements. PAL was recognized as a means of vicarious learning and had greater perceived value when an educator was present to guide or moderate the learning. Trust between students was seen as a requirement for PAL to be effective. Students found passive observation a barrier to PAL and were able to identify ways to adopt an active stance when observing peers interacting with patients. For example, learners reported that the expectation that they had to provide feedback to peers after task observation, resulted in them taking on a more critical gaze where they were encouraged to consider notions of good practice. Insights: Students use PAL in formal (i.e., tutorial) and nonformal (e.g., peer

Identifying cut points for biomarker defined subset effects in clinical trials with survival endpoints.

PubMed

He, Pei

2014-07-01

The advancements in biotechnology and genetics lead to an increasing research interest in personalized medicine, where a patient's genetic profile or biological traits contribute to choosing the most effective treatment for the patient. The process starts with finding a specific biomarker among all possible candidates that can best predict the treatment effect. After a biomarker is chosen, identifying a cut point of the biomarker value that splits the patients into treatment effective and non-effective subgroups becomes an important scientific problem. Numerous methods have been proposed to validate the predictive marker and select the appropriate cut points either prospectively or retrospectively using clinical trial data. In trials with survival outcomes, the current practice applies an interaction testing procedure and chooses the cut point that minimizes the p-values for the tests. Such method assumes independence between the baseline hazard and biomarker value. In reality, however, this assumption is often violated, as the chosen biomarker might also be prognostic in addition to its predictive nature for treatment effect. In this paper we propose a block-wise estimation and a sequential testing approach to identify the cut point in biomarkers that can group the patients into subsets based on their distinct treatment outcomes without assuming independence between the biomarker and baseline hazard. Numerical results based on simulated survival data show that the proposed method could pinpoint accurately the cut points in biomarker values that separate the patient subpopulations into subgroups with distinctive treatment outcomes. Copyright © 2014 Elsevier Inc. All rights reserved.

Cow-specific risk factors for clinical mastitis in Brazilian dairy cattle.

PubMed

Oliveira, C S F; Hogeveen, H; Botelho, A M; Maia, P V; Coelho, S G; Haddad, J P A

2015-10-01

Information related to mastitis risk factors is useful for the design and implementation of clinical mastitis (CM) control programs. The first objective of our study was to model the risk of CM under Brazilian conditions, using cow-specific risk factors. Our second objective was to explore which risk factors were associated with the occurrence of the most common pathogens involved in Brazilian CM infections. The analyses were based on 65 months of data from 9,789 dairy cows and 12,464 CM cases. Cow-specific risk factors that could easily be measured in standard Brazilian dairy farms were used in the statistical analyses, which included logistic regression and multinomial logistic regression. The first month of lactation, high somatic cell count, rainy season and history of clinical mastitis cases were factors associated with CM for both primiparous and multiparous cows. In addition, parity and breed were also associated risk factors for multiparous cows. Of all CM cases, 54% showed positive bacteriological culturing results from which 57% were classified as environmental pathogens, with a large percentage of coliforms (35%). Coagulase-negative Staphylococcus (16%), Streptococcus uberis (9%), Streptococcus agalactiae (7%) and other Streptococci (9%) were also common pathogens. Among the pathogens analyzed, the association of cow-specific risk factors, such as Zebu breed (OR=5.84, 95%CI 3.77-10.77) and accumulated history of SCC (1.76, 95%CI 1.37-2.27), was different for CM caused by Coagulase-negative Staphylococcus and S. agalactiae in comparison to CM caused by coliforms. Our results suggest that CM control programs in Brazil should specially consider the recent history of clinical mastitis cases and the beginning of the lactations, mainly during the rainy season as important risk factor for mastitis. Copyright © 2015 Elsevier B.V. All rights reserved.

Disease-specific dynamic biomarkers selected by integrating inflammatory mediators with clinical informatics in ARDS patients with severe pneumonia.

PubMed

Chen, Chengshui; Shi, Lin; Li, Yuping; Wang, Xiangdong; Yang, Shuanying

2016-06-01

Acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome that occurs as a result of various risk factors, including either direct or indirect lung injury, and systemic inflammation triggered also by severe pneumonia (SP). SP-ARDS-associated morbidity and mortality remains high also due to the lack of disease-specific biomarkers. The present study aimed at identifying disease-specific biomarkers in SP or SP-ARDS by integrating proteomic profiles of inflammatory mediators with clinical informatics. Plasma was sampled from the healthy as controls or patients with SP infected with bacteria or infection-associated SP-ARDS on the day of admission, day 3, and day 7. About 15 or 52 cytokines showed significant difference between SP and SP-ARDS patients with controls or 13 between SP-ARDS with SP alone and controls, including bone morphogenetic protein-15 (BMP-15), chemokine (C-X-C motif) ligand 16 (CXCL16), chemokine (C-X-C motif) receptor 3 (CXCR3), interleukin-6 (IL-6), protein NOV homolog (NOV/CCN3), glypican 3, insulin-like growth factor binding protein 4 (IGFBP-4), IL-5, IL-5 R alpha, IL-22 BP, leptin, MIP-1d, and orexin B with a significant correlation with Digital Evaluation Score System (DESS) scores. ARDS patients with overexpressed IL-6, CXCL16, or IGFBP-4 had significantly longer hospital stay and higher incidence of secondary infection. We also found higher levels of those mediators were associated with poor survival rates in patients with lung cancer and involved in the process of the epithelial mesenchymal transition of alveolar epithelial cells. Our preliminary study suggested that integration of proteomic profiles with clinical informatics as part of clinical bioinformatics is important to validate and optimize disease-specific and disease-staged biomarkers.

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

PubMed

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

2016-03-15

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. 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. All algorithms distinguished individual suicide attempters from non-attempters with prediction accuracy ranging between 65% and 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. 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. Copyright © 2015 Elsevier B.V. All rights reserved.

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

Identifying the educational needs of nursing staff: the role of the clinical nurse specialist in perinatal nursing.

PubMed

Millhaem, Toni Brown; Timm, Kathleen

2007-01-01

One of the priorities of the perinatal clinical nurse specialist is the identification of educational needs. This article describes the experience of 2 perinatal clinical nurse specialists and presents various methods for identifying the educational needs of perinatal nursing staff in the hospital setting.

A highly sensitive and specific combined clinical and sonographic score to diagnose appendicitis.

PubMed

Reddy, Swathi B; Kelleher, Michael; Bokhari, S A Jamal; Davis, Kimberly A; Schuster, Kevin M

2017-10-01

Computed tomography (CT) scanning reduces the negative appendectomy rate however it exposes the patient to ionizing radiation. Ultrasound (US) does not carry this risk but may be nondiagnostic. We hypothesized that a clinical-US scoring system would improve diagnostic accuracy. We conducted a retrospective review of all patients (age, >15 years) who presented through the emergency department with suspected appendicitis and underwent initial US. A US score was developed using odds ratios for appendicitis given appendiceal diameter, compressibility, hyperemia, free fluid, and focal or diffuse tenderness. The US score was then combined with the Alvarado score. Final diagnosis of appendicitis was assigned by pathology reports. Three hundred patients who underwent US as initial imaging were identified. Thirty-two patients with evident nonappendiceal pathology on US were excluded. In 114 (38%), the appendix was not visualized and partially visualized in 36 (12%). Fifty-seven (21.3%) had an appendectomy with 1 (1.7%) negative. Six nonvisualized appendicies underwent appendectomy, with no negative cases. Sensitivity and specificity for the sonographic score were 86% and 90%, respectively, at a score of 1.5. The combined score demonstrated 98% sensitivity and 82% specificity at 6.5, and 95% sensitivity, and 87% specificity at a score of 7.5. Sensitivity and specificity were confirmed by bootstrap resampling for validation. Area under receiver operating characteristic (ROC) curves for our new US score were similar to the ROC curve for the Alvarado score (91.9 and 91.1, p = 0.8). The combined US and Alvarado score yielded an area under the ROC curve of 97.1, significantly better than either score alone (p = 0.017 and p < 0.001, respectively). Our scoring system based entirely on US findings was highly sensitive and specific for appendicitis, and it significantly improved when combined with the Alvarado score. After prospective evaluation, the combined US-Alvarado score might

Clinical isolates of Enterococcus faecium exhibit strain-specific collagen binding mediated by Acm, a new member of the MSCRAMM family.

PubMed

Nallapareddy, Sreedhar R; Weinstock, George M; Murray, Barbara E

2003-03-01

A collagen-binding adhesin of Enterococcus faecium, Acm, was identified. Acm shows 62% similarity to the Staphylococcus aureus collagen adhesin Cna over the entire protein and is more similar to Cna (60% and 75% similarity with Cna A and B domains respectively) than to the Enterococcus faecalis collagen-binding adhesin, Ace, which shares homology with Acm only in the A domain. Despite the detection of acm in 32 out of 32 E. faecium isolates, only 11 of these (all clinical isolates, including four vancomycin-resistant endocarditis isolates and seven other isolates) exhibited binding to collagen type I (CI). Although acm from three CI-binding vancomycin-resistant E. faecium clinical isolates showed 100% identity, analysis of acm genes and their promoter regions from six non-CI-binding strains identified deletions or mutations that introduced stop codons and/or IS elements within the gene or the promoter region in five out of six strains, suggesting that the presence of an intact functional acm gene is necessary for binding of E. faecium strains to CI. Recombinant Acm A domain showed specific and concentration-dependent binding to collagen, and this protein competed with E. faecium binding to immobilized CI. Consistent with the adherence phenotype and sequence data, probing with Acm-specific IgGs purified from anti-recombinant Acm A polyclonal rabbit serum confirmed the surface expression of Acm in three out of three collagen-binding clinical isolates of E. faecium tested, but in none of the strains with a non-functional pseudo acm gene. Introduction of a functional acm gene into two non-CI-binding natural acm mutant strains conferred a CI-binding phenotype, further confirming that native Acm is sufficient for the binding of E. faecium to CI. These results demonstrate that acm, which encodes a potential virulence factor, is functional only in certain infection-derived clinical isolates of E. faecium, and suggest that Acm is the primary adhesin responsible for the

Antibodies to histones in systemic lupus erythematosus: prevalence, specificity, and relationship to clinical and laboratory features.

PubMed Central

Cohen, M G; Pollard, K M; Webb, J

1992-01-01

Antibodies to histones (AHA) are commonly found in patients with systemic lupus erythematosus (SLE). However, the full profile of AHA and their clinical associations remains unclear. A total of 111 patients with SLE were studied, including 13 patients in whom multiple serum samples were available over several years. IgM, IgG, and IgA antibodies to total core histones, histone complexes, and individual histones were determined by highly sensitive enzyme linked immunosorbent assays (ELISAs). Antibodies to histones were detected in 74% of serum samples, though only at low levels in half of these. Antibodies to each of the individual histones (H1, H2A, H2B, H3, H4) occurred with similar frequencies except for IgG and IgA antibodies to H4, which were uncommon. In contrast, antibodies to the histone complexes H2A-H2B and H3-H4 were detected in only two serum samples and thus do not appear to be a feature of SLE. All three major isotypes of AHA were common and usually occurred with similar frequencies to one another for the various histone specificities. There were few clinical or laboratory associations with AHA; the strongest was between IgG antibodies to total core histones and antibodies to native DNA. Similarly, there was no association between the presence of AHA and disease activity. However, for the patients as a group and in one patient alone, periods of SLE disease activity were associated with higher levels of AHA. Although the profile of antibodies to individual histones varied with time, no profile was identified that corresponded with any specific disease manifestations. It is concluded from this study that although AHA are common in patients with SLE, their clinical value in this syndrome must, at present, be considered limited. PMID:1540040

Whole transcriptome profiling of patient-derived xenograft models as a tool to identify both tumor and stromal specific biomarkers.

PubMed

Bradford, James R; Wappett, Mark; Beran, Garry; Logie, Armelle; Delpuech, Oona; Brown, Henry; Boros, Joanna; Camp, Nicola J; McEwen, Robert; Mazzola, Anne Marie; D'Cruz, Celina; Barry, Simon T

2016-04-12

The tumor microenvironment is emerging as a key regulator of cancer growth and progression, however the exact mechanisms of interaction with the tumor are poorly understood. Whilst the majority of genomic profiling efforts thus far have focused on the tumor, here we investigate RNA-Seq as a hypothesis-free tool to generate independent tumor and stromal biomarkers, and explore tumor-stroma interactions by exploiting the human-murine compartment specificity of patient-derived xenografts (PDX).Across a pan-cancer cohort of 79 PDX models, we determine that mouse stroma can be separated into distinct clusters, each corresponding to a specific stromal cell type. This implies heterogeneous recruitment of mouse stroma to the xenograft independent of tumor type. We then generate cross-species expression networks to recapitulate a known association between tumor epithelial cells and fibroblast activation, and propose a potentially novel relationship between two hypoxia-associated genes, human MIF and mouse Ddx6. Assessment of disease subtype also reveals MMP12 as a putative stromal marker of triple-negative breast cancer. Finally, we establish that our ability to dissect recruited stroma from trans-differentiated tumor cells is crucial to identifying stem-like poor-prognosis signatures in the tumor compartment.In conclusion, RNA-Seq is a powerful, cost-effective solution to global analysis of human tumor and mouse stroma simultaneously, providing new insights into mouse stromal heterogeneity and compartment-specific disease markers that are otherwise overlooked by alternative technologies. The study represents the first comprehensive analysis of its kind across multiple PDX models, and supports adoption of the approach in pre-clinical drug efficacy studies, and compartment-specific biomarker discovery.

Identifying a clinically meaningful threshold for change in uveitic macular edema evaluated by optical coherence tomography.

PubMed

Sugar, Elizabeth A; Jabs, Douglas A; Altaweel, Michael M; Lightman, Sue; Acharya, Nisha; Vitale, Albert T; Thorne, Jennifer E

2011-12-01

To identify a clinically meaningful threshold for change in retinal thickness measured by optical coherence tomography for patients with uveitic macular edema using correlation with change in visual acuity. Cross-sectional and longitudinal study. One hundred twenty-eight eyes (101 individuals) with macular edema enrolled in the Multicenter Uveitis Steroid Treatment (MUST) trial. At enrollment and after 6 months of follow-up, retinal thickness was measured at the central subfield with time-domain optical coherence tomography and visual acuity was measured with logarithmic (Early Treatment Diabetic Retinopathy Study) visual acuity charts. Participants were classified as having macular edema if the retinal thickness was 260 μm or more. A threshold for change in retinal center subfield thickness of 20% balanced the percentage of false positives and false negatives for predicting more than a 10-letter change in visual acuity with a sensitivity of 77% and a specificity of 75%. The results were similar for more than 5-letter changes and for 15-letter or more changes. Those with a 20% or more reduction in retinal thickness had a mean 11.0-letter improvement (95% confidence interval, 7.7 to 14.3) as compared with a -0.4-letter change (95% confidence interval, -4.1 to 3.3) in visual acuity for those without a 20% reduction (P < .01). In addition to being above the level of measurement uncertainty, a 20% change in retinal thickness in patients with macular edema seems to be optimal for clinically important changes in visual acuity and may be considered as an outcome for clinical trials of treatments for uveitic macular edema. Copyright © 2011 Elsevier Inc. All rights reserved.

Vibrio parahaemolyticus Strains of Pandemic Serotypes Identified from Clinical and Environmental Samples from Jiangsu, China

PubMed Central

Li, Jingjiao; Xue, Feng; Yang, Zhenquan; Zhang, Xiaoping; Zeng, Dexin; Chao, Guoxiang; Jiang, Yuan; Li, Baoguang

2016-01-01

Vibrio parahaemolyticus has emerged as a major foodborne pathogen in China, Japan, Thailand, and other Asian countries. In this study, 72 strains of V. parahaemolyticus were isolated from clinical and environmental samples between 2006 and 2014 in Jiangsu, China. The serotypes and six virulence genes including thermostable direct hemolysin (TDR) and TDR-related hemolysin (TRH) genes were assessed among the isolates. Twenty five serotypes were identified and O3:K6 was one of the dominant serotypes. The genetic diversity was assessed by multilocus sequence typing (MLST) analysis, and 48 sequence types (STs) were found, suggesting this V. parahaemolyticus group is widely dispersed and undergoing rapid evolution. A total of 25 strains of pandemic serotypes such as O3:K6, O5:K17, and O1:KUT were identified. It is worth noting that the pandemic serotypes were not exclusively identified from clinical samples, rather, nine strains were also isolated from environmental samples; and some of these strains harbored several virulence genes, which may render those strains pathogenicity potential. Therefore, the emergence of these “environmental” pandemic V. parahaemolyticus strains may poses a new threat to the public health in China. Furthermore, six novel serotypes and 34 novel STs were identified among the 72 isolates, indicating that V. parahaemolyticus were widely distributed and fast evolving in the environment in Jiangsu, China. The findings of this study provide new insight into the phylogenic relationship between V. parahaemolyticus strains of pandemic serotypes from clinical and environmental sources and enhance the MLST database; and our proposed possible O- and K- antigen evolving paths of V. parahaemolyticus may help understand how the serotypes of this dispersed bacterial population evolve. PMID:27303379

A putative biomarker signature for clinically effective AKT inhibition: correlation of in vitro, in vivo and clinical data identifies the importance of modulation of the mTORC1 pathway.

PubMed

Cheraghchi-Bashi, Azadeh; Parker, Christine A; Curry, Ed; Salazar, Jean-Frederic; Gungor, Hatice; Saleem, Azeem; Cunnea, Paula; Rama, Nona; Salinas, Cristian; Mills, Gordon B; Morris, Shannon R; Kumar, Rakesh; Gabra, Hani; Stronach, Euan A

2015-12-08

Our identification of dysregulation of the AKT pathway in ovarian cancer as a platinum resistance specific event led to a comprehensive analysis of in vitro, in vivo and clinical behaviour of the AKT inhibitor GSK2141795. Proteomic biomarker signatures correlating with effects of GSK2141795 were developed using in vitro and in vivo models, well characterised for related molecular, phenotypic and imaging endpoints. Signatures were validated in temporally paired biopsies from patients treated with GSK2141795 in a clinical study. GSK2141795 caused growth-arrest as single agent in vitro, enhanced cisplatin-induced apoptosis in vitro and reduced tumour volume in combination with platinum in vivo. GSK2141795 treatment in vitro and in vivo resulted in ~50-90% decrease in phospho-PRAS40 and 20-80% decrease in fluoro-deoxyglucose (FDG) uptake. Proteomic analysis of GSK2141795 in vitro and in vivo identified a signature of pathway inhibition including changes in AKT and p38 phosphorylation and total Bim, IGF1R, AR and YB1 levels. In patient biopsies, prior to treatment with GSK2141795 in a phase 1 clinical trial, this signature was predictive of post-treatment changes in the response marker CA125. Development of this signature represents an opportunity to demonstrate the clinical importance of AKT inhibition for re-sensitisation of platinum resistant ovarian cancer to platinum.

Clinical Reasoning Terms Included in Clinical Problem Solving Exercises?

PubMed Central

Musgrove, John L.; Morris, Jason; Estrada, Carlos A.; Kraemer, Ryan R.

2016-01-01

Background Published clinical problem solving exercises have emerged as a common tool to illustrate aspects of the clinical reasoning process. The specific clinical reasoning terms mentioned in such exercises is unknown. Objective We identified which clinical reasoning terms are mentioned in published clinical problem solving exercises and compared them to clinical reasoning terms given high priority by clinician educators. Methods A convenience sample of clinician educators prioritized a list of clinical reasoning terms (whether to include, weight percentage of top 20 terms). The authors then electronically searched the terms in the text of published reports of 4 internal medicine journals between January 2010 and May 2013. Results The top 5 clinical reasoning terms ranked by educators were dual-process thinking (weight percentage = 24%), problem representation (12%), illness scripts (9%), hypothesis generation (7%), and problem categorization (7%). The top clinical reasoning terms mentioned in the text of 79 published reports were context specificity (n = 20, 25%), bias (n = 13, 17%), dual-process thinking (n = 11, 14%), illness scripts (n = 11, 14%), and problem representation (n = 10, 13%). Context specificity and bias were not ranked highly by educators. Conclusions Some core concepts of modern clinical reasoning theory ranked highly by educators are mentioned explicitly in published clinical problem solving exercises. However, some highly ranked terms were not used, and some terms used were not ranked by the clinician educators. Effort to teach clinical reasoning to trainees may benefit from a common nomenclature of clinical reasoning terms. PMID:27168884

Clinical Reasoning Terms Included in Clinical Problem Solving Exercises?

PubMed

Musgrove, John L; Morris, Jason; Estrada, Carlos A; Kraemer, Ryan R

2016-05-01

Background Published clinical problem solving exercises have emerged as a common tool to illustrate aspects of the clinical reasoning process. The specific clinical reasoning terms mentioned in such exercises is unknown. Objective We identified which clinical reasoning terms are mentioned in published clinical problem solving exercises and compared them to clinical reasoning terms given high priority by clinician educators. Methods A convenience sample of clinician educators prioritized a list of clinical reasoning terms (whether to include, weight percentage of top 20 terms). The authors then electronically searched the terms in the text of published reports of 4 internal medicine journals between January 2010 and May 2013. Results The top 5 clinical reasoning terms ranked by educators were dual-process thinking (weight percentage = 24%), problem representation (12%), illness scripts (9%), hypothesis generation (7%), and problem categorization (7%). The top clinical reasoning terms mentioned in the text of 79 published reports were context specificity (n = 20, 25%), bias (n = 13, 17%), dual-process thinking (n = 11, 14%), illness scripts (n = 11, 14%), and problem representation (n = 10, 13%). Context specificity and bias were not ranked highly by educators. Conclusions Some core concepts of modern clinical reasoning theory ranked highly by educators are mentioned explicitly in published clinical problem solving exercises. However, some highly ranked terms were not used, and some terms used were not ranked by the clinician educators. Effort to teach clinical reasoning to trainees may benefit from a common nomenclature of clinical reasoning terms.

Identifying developmental features in students' clinical reasoning to inform teaching.

PubMed

Pinnock, Ralph; Anakin, Megan; Lawrence, Julie; Chignell, Helen; Wilkinson, Tim

2018-04-27

There is increasing evidence that students at different levels of training may benefit from different methods of learning clinical reasoning. Two of the common methods of teaching are the "whole - case" format and the "serial cue" approach. There is little empirical evidence to guide teachers as to which method to use and when to introduce them. We observed 23 students from different stages of training to examine how they were taking a history and how they were thinking whilst doing this. Each student interviewed a simulated patient who presented with a straightforward and a complex presentation. We inferred how students were reasoning from how they took a history and how they described their thinking while doing this. Early in their training students can only take a generic history. Only later in training are they able to take a focused history, remember the information they have gathered, use it to seek further specific information, compare and contrast possibilities and analyze their data as they are collecting it. Early in their training students are unable to analyze data during history taking. When they have started developing illness scripts, they are able to benefit from the "serial cue" approach of teaching clinical reasoning.

Four new type I restriction enzymes identified in Escherichia coli clinical isolates

PubMed Central

Kasarjian, Julie K. A.; Kodama, Yoshiaki; Iida, Masatake; Matsuda, Katsura; Ryu, Junichi

2005-01-01

Using a plasmid transformation method and the RM search computer program, four type I restriction enzymes with new recognition sites and two isoschizomers (EcoBI and Eco377I) were identified in a collection of clinical Escherichia coli isolates. These new enzymes were designated Eco394I, Eco826I, Eco851I and Eco912I. Their recognition sequences were determined to be GAC(5N)RTAAY, GCA(6N)CTGA, GTCA(6N)TGAY and CAC(5N)TGGC, respectively. A methylation sensitivity assay, using various synthetic oligonucleotides, was used to identify the adenines that prevent cleavage when methylated (underlined). These results suggest that type I enzymes are abundant in E.coli and many other bacteria, as has been inferred from bacterial genome sequencing projects. PMID:16040596

An HTS-compatible 3D colony formation assay to identify tumor-specific chemotherapeutics.

PubMed

Horman, Shane R; To, Jeremy; Orth, Anthony P

2013-12-01

There has been increasing interest in the development of cellular behavior models that take advantage of three-dimensional (3D) cell culture. To enable assessment of differential perturbagen impacts on cell growth in 2D and 3D, we have miniaturized and adapted for high-throughput screening (HTS) the soft agar colony formation assay, employing a laser-scanning cytometer to image and quantify multiple cell types simultaneously. The assay is HTS compatible, providing high-quality, image-based, replicable data for multiple, co-cultured cell types. As proof of concept, we subjected colorectal carcinoma colonies in 3D soft agar to a mini screen of 1528 natural product compounds. Hit compounds from the primary screen were rescreened in an HTS 3D co-culture matrix containing colon stromal cells and cancer cells. By combining tumor cells and normal, nontransformed colon epithelial cells in one primary screening assay, we were able to obtain differential IC50 data, thereby distinguishing tumor-specific compounds from general cytotoxic compounds. Moreover, we were able to identify compounds that antagonized tumor colony formation in 3D only, highlighting the importance of this assay in identifying agents that interfere with 3D tumor structural growth. This screening platform provides a fast, simple, and robust method for identification of tumor-specific agents in a biologically relevant microenvironment.

The Clinical Utility of ASRS-v1.1 for Identifying ADHD in Alcoholics Using PRISM as the Reference Standard.

PubMed

Reyes, Maria M; Schneekloth, Terry D; Hitschfeld, Mario J; Geske, Jennifer R; Atkinson, David L; Karpyak, Victor M

2016-05-02

The objective was to assess the clinical utility of the Adult ADHD Self-Report Scale (ASRS-v1.1) in identifying ADHD in alcoholics using the Psychiatric Research Interview for Substance and Mental Disorders (PRISM) as the diagnostic "gold standard." We performed a secondary analysis of data from 379 treatment-seeking alcoholics who completed the ASRS-v1.1 and the ADHD module of the PRISM. Data analysis included descriptive statistics. The prevalence of ADHD was 7.7% (95% CI = [5.4, 10.8]). The positive predictive value (PPV) of the ASRS-v1.1 was 18.1% (95% CI = [12.4, 25.7]) and the negative predictive value (NPV) was 97.6% (95% CI = [94.9, 98.9]). The ASRS-v1.1 demonstrated a sensitivity of 79.3% (95% CI = [61.6, 90.2]) and a specificity of 70.3% (95% CI = [65.3, 74.8]). The ASRS-v1.1 demonstrated acceptable sensitivity and specificity in a sample of treatment-seeking alcoholics when compared with the PRISM as the reference standard for ADHD diagnosis. © The Author(s) 2016.

A forward chemical screen in zebrafish identifies a retinoic acid derivative with receptor specificity.

PubMed

Das, Bhaskar C; McCartin, Kellie; Liu, Ting-Chun; Peterson, Randall T; Evans, Todd

2010-04-02

Retinoids regulate key developmental pathways throughout life, and have potential uses for differentiation therapy. It should be possible to identify novel retinoids by coupling new chemical reactions with screens using the zebrafish embryonic model. We synthesized novel retinoid analogues and derivatives by amide coupling, obtaining 80-92% yields. A small library of these compounds was screened for bioactivity in living zebrafish embryos. We found that several structurally related compounds significantly affect development. Distinct phenotypes are generated depending on time of exposure, and we characterize one compound (BT10) that produces specific cardiovascular defects when added 1 day post fertilization. When compared to retinoic acid (ATRA), BT10 shows similar but not identical changes in the expression pattern of embryonic genes that are known targets of the retinoid pathway. Reporter assays determined that BT10 interacts with all three RAR receptor sub-types, but has no activity for RXR receptors, at all concentrations tested. Our screen has identified a novel retinoid with specificity for retinoid receptors. This lead compound may be useful for manipulating components of retinoid signaling networks, and may be further derivatized for enhanced activity.

The Clinical Approach to Encephalitis.

PubMed

Piquet, Amanda L; Cho, Tracey A

2016-05-01

Encephalitis has various etiologies, but viral infections and autoimmune disorders are the most commonly identified. Clinical signs, geographical clues, and diagnostic testing-including cerebrospinal fluid abnormalities and magnetic resonance imaging abnormalities-can be helpful in identifying the cause. Certain forms of encephalitis have specific treatments; hence, establishing a diagnosis rapidly and accurately is crucial. Here, we describe the clinical approach to diagnosing several common etiologies of encephalitis as well as treatment strategies.

Functional genomics identifies specific vulnerabilities in PTEN-deficient breast cancer.

PubMed

Tang, Yew Chung; Ho, Szu-Chi; Tan, Elisabeth; Ng, Alvin Wei Tian; McPherson, John R; Goh, Germaine Yen Lin; Teh, Bin Tean; Bard, Frederic; Rozen, Steven G

2018-03-22

-SSL patterns of activity in a large proportion of PTEN-deficient breast cancer cell lines and are potential specific vulnerabilities in PTEN-deficient breast cancer. Furthermore, the NUAK1 PTEN-SSL vulnerability identified by RNA interference techniques can be recapitulated and exploited using the small molecule kinase inhibitor HTH-01-015. Thus, NUAK1 inhibition may be an effective strategy for precision treatment of PTEN-deficient breast tumors.

Genome-wide oxidative bisulfite sequencing identifies sex-specific methylation differences in the human placenta

PubMed Central

Johnson, Michelle D; Dopierala, Justyna

2018-01-01

ABSTRACT DNA methylation is an important regulator of gene function. Fetal sex is associated with the risk of several specific pregnancy complications related to placental function. However, the association between fetal sex and placental DNA methylation remains poorly understood. We carried out whole-genome oxidative bisulfite sequencing in the placentas of two healthy female and two healthy male pregnancies generating an average genome depth of coverage of 25x. Most highly ranked differentially methylated regions (DMRs) were located on the X chromosome but we identified a 225 kb sex-specific DMR in the body of the CUB and Sushi Multiple Domains 1 (CSMD1) gene on chromosome 8. The sex-specific differential methylation pattern observed in this region was validated in additional placentas using in-solution target capture. In a new RNA-seq data set from 64 female and 67 male placentas, CSMD1 mRNA was 1.8-fold higher in male than in female placentas (P value = 8.5 × 10−7, Mann-Whitney test). Exon-level quantification of CSMD1 mRNA from these 131 placentas suggested a likely placenta-specific CSMD1 isoform not detected in the 21 somatic tissues analyzed. We show that the gene body of an autosomal gene, CSMD1, is differentially methylated in a sex- and placental-specific manner, displaying sex-specific differences in placental transcript abundance. PMID:29376485

Clinical implications of prostate-specific antigen in men and women.

PubMed

Yu, H

2000-01-01

Prostate-specific antigen (PSA) is a valuable tumor marker for prostate cancer. Although it is indeed produced at an extremely high level by the prostate, PSA is also expressed in many female tissues, especially those regulated by sex steroid hormones. PSA is detected in both normal and abnormal breast tissue, as well as in various breast fluids, including milk, nipple aspirate, and cyst fluid. Clinical studies suggest that the presence of PSA in breast tissue may indicate a favorable prognosis for breast cancer patients. Levels of PSA in nipple aspirate fluid, however, may be indicative of breast cancer risk. Concentrations of PSA in serum are elevated in pregnant women as well as in women who have excess androgens. More studies are necessary to determine the clinical implications of the presence of PSA in amniotic fluid and female serum.

Identifying clinical features in primary care electronic health record studies: methods for codelist development.

PubMed

Watson, Jessica; Nicholson, Brian D; Hamilton, Willie; Price, Sarah

2017-11-22

Analysis of routinely collected electronic health record (EHR) data from primary care is reliant on the creation of codelists to define clinical features of interest. To improve scientific rigour, transparency and replicability, we describe and demonstrate a standardised reproducible methodology for clinical codelist development. We describe a three-stage process for developing clinical codelists. First, the clear definition a priori of the clinical feature of interest using reliable clinical resources. Second, development of a list of potential codes using statistical software to comprehensively search all available codes. Third, a modified Delphi process to reach consensus between primary care practitioners on the most relevant codes, including the generation of an 'uncertainty' variable to allow sensitivity analysis. These methods are illustrated by developing a codelist for shortness of breath in a primary care EHR sample, including modifiable syntax for commonly used statistical software. The codelist was used to estimate the frequency of shortness of breath in a cohort of 28 216 patients aged over 18 years who received an incident diagnosis of lung cancer between 1 January 2000 and 30 November 2016 in the Clinical Practice Research Datalink (CPRD). Of 78 candidate codes, 29 were excluded as inappropriate. Complete agreement was reached for 44 (90%) of the remaining codes, with partial disagreement over 5 (10%). 13 091 episodes of shortness of breath were identified in the cohort of 28 216 patients. Sensitivity analysis demonstrates that codes with the greatest uncertainty tend to be rarely used in clinical practice. Although initially time consuming, using a rigorous and reproducible method for codelist generation 'future-proofs' findings and an auditable, modifiable syntax for codelist generation enables sharing and replication of EHR studies. Published codelists should be badged by quality and report the methods of codelist generation including

Clinical validity of a disease-specific health status questionnaire: the peripheral artery questionnaire.

PubMed

Hoeks, Sanne E; Smolderen, Kim G; Scholte Op Reimer, Wilma J M; Verhagen, Hence J M; Spertus, John A; Poldermans, Don

2009-02-01

Measuring patient-centered outcomes is becoming increasingly important in patients with peripheral arterial disease (PAD), both as a means of determining the benefits of treatment and as an aid for disease management. In order to monitor health status in a reliable and sensitive way, the disease-specific measure Peripheral Artery Questionnaire (PAQ) was developed. However, to date, its correlation with traditional clinical indices is unknown. The primary aim of this study was to better establish the clinical validity of the PAQ by examining its association with functional indices related to PAD. Furthermore, we hypothesized that the clinical validity of this disease-specific measure is better as compared with the EuroQol-5-dimensional (EQ-5D), a standardized generic instrument. Data on 711 consecutive PAD patients undergoing surgery were collected from 11 Dutch hospitals in 2004. At 3-year follow-up, questionnaires including the PAQ, EQ-5D, and EuroQol-Visual Analogue Scale (EQ VAS) were completed in 84% of survivors. The PAQ was analyzed according to three domains, as established by a factor analyses in the Dutch population, and the summary score. Baseline clinical indices included the presence and severity of claudication intermittent (CI) and the Lee Cardiac Risk Index. All three PAQ domains (Physical Function, Perceived Disability, and Treatment Satisfaction) were significantly associated with CI symptoms (P values < .001-.008). Patients with claudication had significant lower PAQ summary scores as compared with asymptomatic patients (58.6 +/- 27.8 vs 68.6 +/- 27.8, P = < .001). Furthermore, the PAQ summary score and the subscale scores for Physical Functioning and Perceived Disability demonstrated a clear dose-response relation for walking distance and the Lee Risk Index (P values < .001-.031). With respect to the generic EQ-5D, the summary EQ-5D index was associated with CI (0.81 +/- 0.20 vs 0.76 +/- 0.24, P = .031) but not with walking distance (P = .128

Effects of Popular Diets without Specific Calorie Targets on Weight Loss Outcomes: Systematic Review of Findings from Clinical Trials

PubMed Central

Anton, Stephen D.; Hida, Azumi; Heekin, Kacey; Sowalsky, Kristen; Karabetian, Christy; Mutchie, Heather; Leeuwenburgh, Christiaan; Manini, Todd M.; Barnett, Tracey E.

2017-01-01

The present review examined the evidence base for current popular diets, as listed in the 2016 U.S. News & World Report, on short-term (≤six months) and long-term (≥one year) weight loss outcomes in overweight and obese adults. For the present review, all diets in the 2016 U.S. News & World Report Rankings for “Best Weight-Loss Diets”, which did not involve specific calorie targets, meal replacements, supplementation with commercial products, and/or were not categorized as “low-calorie” diets were examined. Of the 38 popular diets listed in the U.S. News & World Report, 20 met our pre-defined criteria. Literature searches were conducted through PubMed, Cochrane Library, and Web of Science using preset key terms to identify all relevant clinical trials for these 20 diets. A total of 16 articles were identified which reported findings of clinical trials for seven of these 20 diets: (1) Atkins; (2) Dietary Approaches to Stop Hypertension (DASH); (3) Glycemic-Index; (4) Mediterranean; (5) Ornish; (6) Paleolithic; and (7) Zone. Of the diets evaluated, the Atkins Diet showed the most evidence in producing clinically meaningful short-term (≤six months) and long-term (≥one-year) weight loss. Other popular diets may be equally or even more effective at producing weight loss, but this is unknown at the present time since there is a paucity of studies on these diets. PMID:28758964

Clinical Utility of Noninvasive Method to Measure Specific Gravity in the Pediatric Population.

PubMed

Hall, Jeanine E; Huynh, Pauline P; Mody, Ameer P; Wang, Vincent J

2018-04-01

Clinicians rely on any combination of signs and symptoms, clinical scores, or invasive procedures to assess the hydration status in children. Noninvasive tests to evaluate for dehydration in the pediatric population are appealing. The objective of our study is to assess the utility of measuring specific gravity of tears compared to specific gravity of urine and the clinical assessment of dehydration. We conducted a prospective cohort convenience sample study, in a pediatric emergency department at a tertiary care children's hospital. We approached parents/guardians of children aged 6 months to 4 years undergoing transurethral catheterization for evaluation of urinary tract infection for enrollment. We collected tears and urine for measurement of tear specific gravity (TSG) and urine specific gravity (USG), respectively. Treating physicians completed dehydration assessment forms to assess for hydration status. Among the 60 participants included, the mean TSG was 1.0183 (SD = 0.007); the mean USG was 1.0186 (SD = 0.0083). TSG and USG were positively correlated with each other (Pearson Correlation = 0.423, p = 0.001). Clinical dehydration scores ranged from 0 to 3, with 87% assigned a score of 0, by physician assessment. Mean number of episodes of vomiting and diarrhea in a 24-hour period were 2.2 (SD = 3.9) and 1.5 (SD = 3.2), respectively. Sixty-two percent of parents reported decreased oral intake. TSG measurements yielded similar results compared with USG. Further studies are needed to determine if TSG can be used as a noninvasive method of dehydration assessment in children. Copyright © 2017 Elsevier Inc. All rights reserved.

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

PubMed

Solovyova, M

2014-12-01

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

Recent advances in cross-cultural measurement in psychiatric epidemiology: utilizing 'what matters most' to identify culture-specific aspects of stigma.

PubMed

Yang, Lawrence Hsin; Thornicroft, Graham; Alvarado, Ruben; Vega, Eduardo; Link, Bruce George

2014-04-01

While stigma measurement across cultures has assumed growing importance in psychiatric epidemiology, it is unknown to what extent concepts arising from culture have been incorporated. We utilize a formulation of culture-as the everyday interactions that 'matter most' to individuals within a cultural group-to identify culturally-specific stigma dynamics relevant to measurement. A systematic literature review from January 1990 to September 2012 was conducted using PsycINFO, Medline and Google Scholar to identify articles studying: (i) mental health stigma-related concepts; (ii) ≥ 1 non-Western European cultural group. From 5292 abstracts, 196 empirical articles were located. The vast majority of studies (77%) utilized adaptations of existing Western-developed stigma measures to new cultural groups. Extremely few studies (2.0%) featured quantitative stigma measures derived within a non-Western European cultural group. A sizeable amount (16.8%) of studies employed qualitative methods to identify culture-specific stigma processes. The 'what matters most' perspective identified cultural ideals of the everyday activities that comprise 'personhood' of 'preserving lineage' among specific Asian groups, 'fighting hard to overcome problems and taking advantage of immigration opportunities' among specific Latino-American groups, and 'establishing trust among religious institutions due to institutional discrimination' among African-American groups. These essential cultural interactions shaped culture-specific stigma manifestations. Mixed method studies (3.6%) corroborated these qualitative results. Quantitatively-derived, culturally-specific stigma measures were lacking. Further, the vast majority of qualitative studies on stigma were conducted without using stigma-specific frameworks. We propose the 'what matters most' approach to address this key issue in future research.

Can physicians recognize their own patients in de-identified notes?

PubMed

Meystre, Stéphane; Shen, Shuying; Hofmann, Deborah; Gundlapalli, Adi

2014-01-01

The adoption of Electronic Health Records is growing at a fast pace, and this growth results in very large quantities of patient clinical information becoming available in electronic format, with tremendous potentials, but also equally growing concern for patient confidentiality breaches. De-identification of patient information has been proposed as a solution to both facilitate secondary uses of clinical information, and protect patient information confidentiality. Automated approaches based on Natural Language Processing have been implemented and evaluated, allowing for much faster text de-identification than manual approaches. A U.S. Veterans Affairs clinical text de-identification project focused on investigating the current state of the art of automatic clinical text de-identification, on developing a best-of-breed de-identification application for clinical documents, and on evaluating its impact on subsequent text uses and the risk for re-identification. To evaluate this risk, we de-identified discharge summaries from 86 patients using our 'best-of-breed' text de-identification application with resynthesis of the identifiers detected. We then asked physicians working in the ward the patients were hospitalized in if they could recognize these patients when reading the de-identified documents. Each document was examined by at least one resident and one attending physician, and with 4.65% of the documents, physicians thought they recognized the patient because of specific clinical information, but after verification, none was correctly re-identified.

Disease Specific Productivity of American Cancer Hospitals

PubMed Central

Goldstein, Jeffery A.; Prasad, Vinay

2015-01-01

Context Research-oriented cancer hospitals in the United States treat and study patients with a range of diseases. Measures of disease specific research productivity, and comparison to overall productivity, are currently lacking. Hypothesis Different institutions are specialized in research of particular diseases. Objective To report disease specific productivity of American cancer hospitals, and propose a summary measure. Method We conducted a retrospective observational survey of the 50 highest ranked cancer hospitals in the 2013 US News and World Report rankings. We performed an automated search of PubMed and Clinicaltrials.gov for published reports and registrations of clinical trials (respectively) addressing specific cancers between 2008 and 2013. We calculated the summed impact factor for the publications. We generated a summary measure of productivity based on the number of Phase II clinical trials registered and the impact factor of Phase II clinical trials published for each institution and disease pair. We generated rankings based on this summary measure. Results We identified 6076 registered trials and 6516 published trials with a combined impact factor of 44280.4, involving 32 different diseases over the 50 institutions. Using a summary measure based on registered and published clinical trails, we ranked institutions in specific diseases. As expected, different institutions were highly ranked in disease-specific productivity for different diseases. 43 institutions appeared in the top 10 ranks for at least 1 disease (vs 10 in the overall list), while 6 different institutions were ranked number 1 in at least 1 disease (vs 1 in the overall list). Conclusion Research productivity varies considerably among the sample. Overall cancer productivity conceals great variation between diseases. Disease specific rankings identify sites of high academic productivity, which may be of interest to physicians, patients and researchers. PMID:25781329

Disease specific productivity of american cancer hospitals.

PubMed

Goldstein, Jeffery A; Prasad, Vinay

2015-01-01

Research-oriented cancer hospitals in the United States treat and study patients with a range of diseases. Measures of disease specific research productivity, and comparison to overall productivity, are currently lacking. Different institutions are specialized in research of particular diseases. To report disease specific productivity of American cancer hospitals, and propose a summary measure. We conducted a retrospective observational survey of the 50 highest ranked cancer hospitals in the 2013 US News and World Report rankings. We performed an automated search of PubMed and Clinicaltrials.gov for published reports and registrations of clinical trials (respectively) addressing specific cancers between 2008 and 2013. We calculated the summed impact factor for the publications. We generated a summary measure of productivity based on the number of Phase II clinical trials registered and the impact factor of Phase II clinical trials published for each institution and disease pair. We generated rankings based on this summary measure. We identified 6076 registered trials and 6516 published trials with a combined impact factor of 44280.4, involving 32 different diseases over the 50 institutions. Using a summary measure based on registered and published clinical trails, we ranked institutions in specific diseases. As expected, different institutions were highly ranked in disease-specific productivity for different diseases. 43 institutions appeared in the top 10 ranks for at least 1 disease (vs 10 in the overall list), while 6 different institutions were ranked number 1 in at least 1 disease (vs 1 in the overall list). Research productivity varies considerably among the sample. Overall cancer productivity conceals great variation between diseases. Disease specific rankings identify sites of high academic productivity, which may be of interest to physicians, patients and researchers.

Chromosome 17 alterations identify good-risk and poor-risk tumors independently of clinical factors in medulloblastoma

PubMed Central

McCabe, Martin G.; Bäcklund, L. Magnus; Leong, Hui Sun; Ichimura, Koichi; Collins, V. Peter

2011-01-01

Current risk stratification schemas for medulloblastoma, based on combinations of clinical variables and histotype, fail to accurately identify particularly good- and poor-risk tumors. Attempts have been made to improve discriminatory power by combining clinical variables with cytogenetic data. We report here a pooled analysis of all previous reports of chromosomal copy number related to survival data in medulloblastoma. We collated data from previous reports that explicitly quoted survival data and chromosomal copy number in medulloblastoma. We analyzed the relative prognostic significance of currently used clinical risk stratifiers and the chromosomal aberrations previously reported to correlate with survival. In the pooled dataset metastatic disease, incomplete tumor resection and severe anaplasia were associated with poor outcome, while young age at presentation was not prognostically significant. Of the chromosomal variables studied, isolated 17p loss and gain of 1q correlated with poor survival. Gain of 17q without associated loss of 17p showed a trend to improved outcome. The most commonly reported alteration, isodicentric chromosome 17, was not prognostically significant. Sequential multivariate models identified isolated 17p loss, isolated 17q gain, and 1q gain as independent prognostic factors. In a historical dataset, we have identified isolated 17p loss as a marker of poor outcome and 17q gain as a novel putative marker of good prognosis. Biological markers of poor-risk and good-risk tumors will be critical in stratifying treatment in future trials. Our findings should be prospectively validated independently in future clinical studies. PMID:21292688

Clinical prediction model to identify vulnerable patients in ambulatory surgery: towards optimal medical decision-making.

PubMed

Mijderwijk, Herjan; Stolker, Robert Jan; Duivenvoorden, Hugo J; Klimek, Markus; Steyerberg, Ewout W

2016-09-01

Ambulatory surgery patients are at risk of adverse psychological outcomes such as anxiety, aggression, fatigue, and depression. We developed and validated a clinical prediction model to identify patients who were vulnerable to these psychological outcome parameters. We prospectively assessed 383 mixed ambulatory surgery patients for psychological vulnerability, defined as the presence of anxiety (state/trait), aggression (state/trait), fatigue, and depression seven days after surgery. Three psychological vulnerability categories were considered-i.e., none, one, or multiple poor scores, defined as a score exceeding one standard deviation above the mean for each single outcome according to normative data. The following determinants were assessed preoperatively: sociodemographic (age, sex, level of education, employment status, marital status, having children, religion, nationality), medical (heart rate and body mass index), and psychological variables (self-esteem and self-efficacy), in addition to anxiety, aggression, fatigue, and depression. A prediction model was constructed using ordinal polytomous logistic regression analysis, and bootstrapping was applied for internal validation. The ordinal c-index (ORC) quantified the discriminative ability of the model, in addition to measures for overall model performance (Nagelkerke's R (2) ). In this population, 137 (36%) patients were identified as being psychologically vulnerable after surgery for at least one of the psychological outcomes. The most parsimonious and optimal prediction model combined sociodemographic variables (level of education, having children, and nationality) with psychological variables (trait anxiety, state/trait aggression, fatigue, and depression). Model performance was promising: R (2)  = 30% and ORC = 0.76 after correction for optimism. This study identified a substantial group of vulnerable patients in ambulatory surgery. The proposed clinical prediction model could allow healthcare

An analysis of narratives to identify critical thinking contexts in psychiatric clinical practice.

PubMed

Mun, Mi Suk

2010-02-01

The development of students' critical thinking abilities is one of the greatest challenges facing contemporary nursing educators. Nursing educators should know about what kind of contents or situations need critical thinking. The research was undertaken to identify the critical thinking contexts that nursing students confront in psychiatric clinical practices. Students were asked to document their everyday experience. The narratives were analysed and interpreted from the philosophical notion of hermeneutics. Four themes emerged as critical thinking contexts: anxiety, conflict, hyper-awareness, dilemmas. Writing narratives appear to provide opportunities for reflection in addition to facilitating critical thinking and communicative skills in students. Also, for the instructor, students' clinical narratives could provide insight to understand how students are thinking and to share student's personal difficulties.

Real-time PCR for type-specific identification of herpes simplex in clinical samples: evaluation of type-specific results in the context of CNS diseases.

PubMed

Meylan, Sylvain; Robert, Daniel; Estrade, Christine; Grimbuehler, Valérie; Péter, Olivier; Meylan, Pascal R; Sahli, Roland

2008-02-01

HSV-1 and HSV-2 cause CNS infections of dissimilar clinico-pathological characteristics with prognostic and therapeutic implications. To validate a type-specific real-time PCR that uses MGB/LNA Taqman probes and to review the virologico-clinical data of 25 eligible patients with non-neonatal CNS infections. This real-time PCR was evaluated against conventional PCR (26 CSF and 20 quality controls), and LightCycler assay (51 mucocutaneous, 8 CSF and 32 quality controls) and culture/immunofluorescence (75 mucocutaneous) to assess typing with independent methods. Taqman real-time PCR detected 240 HSV genomes per ml CSF, a level appropriate for the management of patients, and provided unambiguous typing for the 104 positive (62 HSV-1 and 42 HSV-2) out the 160 independent clinical samples tested. HSV type diagnosed by Taqman real-time PCR predicted final diagnosis (meningitis versus encephalitis/meningoencephalitis, p<0.001) in 24/25 patients at time of presentation, in contrast to clinical evaluation. Our real-time PCR, as a sensitive and specific means for type-specific HSV diagnosis, provided rapid prognostic information for patient management.

Incorporating deep learning with convolutional neural networks and position specific scoring matrices for identifying electron transport proteins.

PubMed

Le, Nguyen-Quoc-Khanh; Ho, Quang-Thai; Ou, Yu-Yen

2017-09-05

In several years, deep learning is a modern machine learning technique using in a variety of fields with state-of-the-art performance. Therefore, utilization of deep learning to enhance performance is also an important solution for current bioinformatics field. In this study, we try to use deep learning via convolutional neural networks and position specific scoring matrices to identify electron transport proteins, which is an important molecular function in transmembrane proteins. Our deep learning method can approach a precise model for identifying of electron transport proteins with achieved sensitivity of 80.3%, specificity of 94.4%, and accuracy of 92.3%, with MCC of 0.71 for independent dataset. The proposed technique can serve as a powerful tool for identifying electron transport proteins and can help biologists understand the function of the electron transport proteins. Moreover, this study provides a basis for further research that can enrich a field of applying deep learning in bioinformatics. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Which ante mortem clinical features predict progressive supranuclear palsy pathology?

PubMed

Respondek, Gesine; Kurz, Carolin; Arzberger, Thomas; Compta, Yaroslau; Englund, Elisabet; Ferguson, Leslie W; Gelpi, Ellen; Giese, Armin; Irwin, David J; Meissner, Wassilios G; Nilsson, Christer; Pantelyat, Alexander; Rajput, Alex; van Swieten, John C; Troakes, Claire; Josephs, Keith A; Lang, Anthony E; Mollenhauer, Brit; Müller, Ulrich; Whitwell, Jennifer L; Antonini, Angelo; Bhatia, Kailash P; Bordelon, Yvette; Corvol, Jean-Christophe; Colosimo, Carlo; Dodel, Richard; Grossman, Murray; Kassubek, Jan; Krismer, Florian; Levin, Johannes; Lorenzl, Stefan; Morris, Huw; Nestor, Peter; Oertel, Wolfgang H; Rabinovici, Gil D; Rowe, James B; van Eimeren, Thilo; Wenning, Gregor K; Boxer, Adam; Golbe, Lawrence I; Litvan, Irene; Stamelou, Maria; Höglinger, Günter U

2017-07-01

Progressive supranuclear palsy (PSP) is a neuropathologically defined disease presenting with a broad spectrum of clinical phenotypes. To identify clinical features and investigations that predict or exclude PSP pathology during life, aiming at an optimization of the clinical diagnostic criteria for PSP. We performed a systematic review of the literature published since 1996 to identify clinical features and investigations that may predict or exclude PSP pathology. We then extracted standardized data from clinical charts of patients with pathologically diagnosed PSP and relevant disease controls and calculated the sensitivity, specificity, and positive predictive value of key clinical features for PSP in this cohort. Of 4166 articles identified by the database inquiry, 269 met predefined standards. The literature review identified clinical features predictive of PSP, including features of the following 4 functional domains: ocular motor dysfunction, postural instability, akinesia, and cognitive dysfunction. No biomarker or genetic feature was found reliably validated to predict definite PSP. High-quality original natural history data were available from 206 patients with pathologically diagnosed PSP and from 231 pathologically diagnosed disease controls (54 corticobasal degeneration, 51 multiple system atrophy with predominant parkinsonism, 53 Parkinson's disease, 73 behavioral variant frontotemporal dementia). We identified clinical features that predicted PSP pathology, including phenotypes other than Richardson's syndrome, with varying sensitivity and specificity. Our results highlight the clinical variability of PSP and the high prevalence of phenotypes other than Richardson's syndrome. The features of variant phenotypes with high specificity and sensitivity should serve to optimize clinical diagnosis of PSP. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

MYC Immunohistochemistry to Identify MYC-Driven B-Cell Lymphomas in Clinical Practice.

PubMed

Kluk, Michael J; Ho, Caleb; Yu, Hongbo; Chen, Benjamin J; Neuberg, Donna S; Dal Cin, Paola; Woda, Bruce A; Pinkus, Geraldine S; Rodig, Scott J

2016-02-01

Immunohistochemistry with anti-MYC antibody (MYC IHC) detects MYC protein in fixed samples of aggressive B-cell lymphomas and, according to the number of positive staining tumor nuclei, facilitates tumor subclassification, predicts underlying MYC rearrangements, and stratifies patient outcome. We aimed to determine the performance of MYC IHC in clinical practice. We reviewed MYC IHC performed on control specimens and 256 aggressive B-cell lymphomas and compared clinically reported IHC scores with experts' review. Control tissues showed less than 5% variation in daily IHC staining. Reported and expert IHC scores were well correlated (r = 0.86) with an SD of 14.2%. Reported IHC scores 30% or less and 70% or more were accurate (94.5%) compared with experts in categorizing tumors as "MYC IHC-Low" and "MYC IHC-High," respectively, but scores 40% to 60% were not (60.3%). The mean IHC score among lymphomas with MYC rearrangements was 80%, but with a large range of scores (20%-100%). There was no statistically significant association between IHC score and MYC copy number. Under optimal conditions, clinically reported MYC IHC scores are concordant with expert scores within 15%. MYC IHC does not capture all B-cell lymphomas with MYC rearrangements, however. MYC IHC and MYC fluorescence in situ hybridization are both recommended to identify MYC-driven B-cell lymphomas. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Identifying the culprit lesion in tumor induced hypophosphatemia, the solution of a clinical enigma.

PubMed

Slot-Steenks, Mathilde M Bruins; Hamdy, Neveen A T; van de Sande, Michiel A J; Vriens, Dennis; Cleven, Arjen H G; Appelman-Dijkstra, Natasha M

2016-12-01

Tumor-induced osteomalacia is a rare acquired metabolic bone disorder characterized by isolated renal phosphate wasting due to abnormal tumor production of fibroblast growth factor 23. We report the case of a 59 year old woman referred to our department with a long history of progressive diffuse muscle weakness and pain, generalized bone pains and multiple insufficiency fractures of heels, ankles and hips due to a hypophosphatemic osteomalacia. A fibroblast growth factor 23-producing phosphaturic mesenchymal tumor localized in the left quadriceps femoris muscle was identified 7 years after onset of symptoms. Excision of the tumor resulted in normalization of serum phosphate and fibroblast growth factor 23 levels and in complete resolution of the clinical picture with disappearance of all musculoskeletal symptoms. This case illustrates the diagnostic difficulties in establishing a diagnosis tumor-induced osteomalacia and in identifying the responsible tumor. Our case underscores the clinical need to investigate all patients with persistent musculoskeletal symptoms for hypophosphatemia. A systematic approach is of pivotal importance because early recognition and treatment of the metabolic abnormality can prevent deleterious effects of osteomalacia on the skeleton.

A Genotypic-Oriented View of CFTR Genetics Highlights Specific Mutational Patterns Underlying Clinical Macrocategories of Cystic Fibrosis

PubMed Central

Lucarelli, Marco; Bruno, Sabina Maria; Pierandrei, Silvia; Ferraguti, Giampiero; Stamato, Antonella; Narzi, Fabiana; Amato, Annalisa; Cimino, Giuseppe; Bertasi, Serenella; Quattrucci, Serena; Strom, Roberto

2015-01-01

Cystic fibrosis (CF) is a monogenic disease caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The genotype–phenotype relationship in this disease is still unclear, and diagnostic, prognostic and therapeutic challenges persist. We enrolled 610 patients with different forms of CF and studied them from a clinical, biochemical, microbiological and genetic point of view. Overall, there were 125 different mutated alleles (11 with novel mutations and 10 with complex mutations) and 225 genotypes. A strong correlation between mutational patterns at the genotypic level and phenotypic macrocategories emerged. This specificity appears to largely depend on rare and individual mutations, as well as on the varying prevalence of common alleles in different clinical macrocategories. However, 19 genotypes appeared to underlie different clinical forms of the disease. The dissection of the pathway from the CFTR mutated genotype to the clinical phenotype allowed to identify at least two components of the variability usually found in the genotype–phenotype relationship. One component seems to depend on the genetic variation of CFTR, the other component on the cumulative effect of variations in other genes and cellular pathways independent from CFTR. The experimental dissection of the overall biological CFTR pathway appears to be a powerful approach for a better comprehension of the genotype–phenotype relationship. However, a change from an allele-oriented to a genotypic-oriented view of CFTR genetics is mandatory, as well as a better assessment of sources of variability within the CFTR pathway. PMID:25910067

A Bottom-Up Proteomic Approach to Identify Substrate Specificity of Outer-Membrane Protease OmpT.

PubMed

Wood, Sarah E; Sinsinbar, Gaurav; Gudlur, Sushanth; Nallani, Madhavan; Huang, Che-Fan; Liedberg, Bo; Mrksich, Milan

2017-12-22

Identifying peptide substrates that are efficiently cleaved by proteases gives insights into substrate recognition and specificity, guides development of inhibitors, and improves assay sensitivity. Peptide arrays and SAMDI mass spectrometry were used to identify a tetrapeptide substrate exhibiting high activity for the bacterial outer-membrane protease (OmpT). Analysis of protease activity for the preferred residues at the cleavage site (P1, P1') and nearest-neighbor positions (P2, P2') and their positional interdependence revealed FRRV as the optimal peptide with the highest OmpT activity. Substituting FRRV into a fragment of LL37, a natural substrate of OmpT, led to a greater than 400-fold improvement in OmpT catalytic efficiency, with a k cat /K m value of 6.1×10 6  L mol -1  s -1 . Wild-type and mutant OmpT displayed significant differences in their substrate specificities, demonstrating that even modest mutants may not be suitable substitutes for the native enzyme. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Nephron segment specific microRNA biomarkers of pre-clinical drug-induced renal toxicity: Opportunities and challenges

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

Nassirpour, Rounak, E-mail: Rounak.nassirpour@pfiz

Drug-induced nephrotoxicity is a common drug development complication for pharmaceutical companies. Sensitive, specific, translatable and non-invasive biomarkers of renal toxicity are urgently needed to diagnose nephron segment specific injury. The currently available gold standard biomarkers for nephrotoxicity are not kidney-specific, lack sensitivity for early detection, and are not suitable for renal damage localization (glomerular vs tubulointerstitial injury). MicroRNAs (miRNAs) are increasingly gaining momentum as promising biomarkers of various organ toxicities, including drug induced renal injury. This is mostly due to their stability in easily accessible biofluids, ease of developing nucleic acids detection compared to protein detection assays, as well asmore » their interspecies translatability. Increasing concordance of miRNA findings by standardizing methodology most suitable for their detection and quantitation, as well as characterization of their expression pattern in a cell type specific manner, will accelerate progress toward validation of these miRNAs as biomarkers in pre-clinical, and clinical settings. This review aims to highlight the current pre-clinical findings surrounding miRNAs as biomarkers in two important segments of the nephron, the glomerulus and tubules. - Highlights: • miRNAs are promising biomarkers of drug-induced kidney injury. • Summarized pre-clinical miRNA biomarkers of drug-induced nephrotoxicity. • Described the strengths and challenges associated with miRNAs as biomarkers.« less

Identifying Unmet Treatment Needs for Patients With Osteoporotic Fracture: Feasibility Study for an Electronic Clinical Surveillance System.

PubMed

Lin, Fong-Ci; Wang, Chen-Yu; Shang, Rung Ji; Hsiao, Fei-Yuan; Lin, Mei-Shu; Hung, Kuan-Yu; Wang, Jui; Lin, Zhen-Fang; Lai, Feipei; Shen, Li-Jiuan; Huang, Chih-Fen

2018-04-24

Traditional clinical surveillance relied on the results from clinical trials and observational studies of administrative databases. However, these studies not only required many valuable resources but also faced a very long time lag. This study aimed to illustrate a practical application of the National Taiwan University Hospital Clinical Surveillance System (NCSS) in the identification of patients with an osteoporotic fracture and to provide a high reusability infrastructure for longitudinal clinical data. The NCSS integrates electronic medical records in the National Taiwan University Hospital (NTUH) with a data warehouse and is equipped with a user-friendly interface. The NCSS was developed using professional insight from multidisciplinary experts, including clinical practitioners, epidemiologists, and biomedical engineers. The practical example identifying the unmet treatment needs for patients encountering major osteoporotic fractures described herein was mainly achieved by adopting the computerized workflow in the NCSS. We developed the infrastructure of the NCSS, including an integrated data warehouse and an automatic surveillance workflow. By applying the NCSS, we efficiently identified 2193 patients who were newly diagnosed with a hip or vertebral fracture between 2010 and 2014 at NTUH. By adopting the filter function, we identified 1808 (1808/2193, 82.44%) patients who continued their follow-up at NTUH, and 464 (464/2193, 21.16%) patients who were prescribed anti-osteoporosis medications, within 3 and 12 months post the index date of their fracture, respectively. The NCSS systems can integrate the workflow of cohort identification to accelerate the survey process of clinically relevant problems and provide decision support in the daily practice of clinical physicians, thereby making the benefit of evidence-based medicine a reality. ©Fong-Ci Lin, Chen-Yu Wang, Rung Ji Shang, Fei-Yuan Hsiao, Mei-Shu Lin, Kuan-Yu Hung, Jui Wang, Zhen-Fang Lin, Feipei Lai

Clinical reasoning: concept analysis.

PubMed

Simmons, Barbara

2010-05-01

This paper is a report of a concept analysis of clinical reasoning in nursing. Clinical reasoning is an ambiguous term that is often used synonymously with decision-making and clinical judgment. Clinical reasoning has not been clearly defined in the literature. Healthcare settings are increasingly filled with uncertainty, risk and complexity due to increased patient acuity, multiple comorbidities, and enhanced use of technology, all of which require clinical reasoning. Data sources. Literature for this concept analysis was retrieved from several databases, including CINAHL, PubMed, PsycINFO, ERIC and OvidMEDLINE, for the years 1980 to 2008. Rodgers's evolutionary method of concept analysis was used because of its applicability to concepts that are still evolving. Multiple terms have been used synonymously to describe the thinking skills that nurses use. Research in the past 20 years has elucidated differences among these terms and identified the cognitive processes that precede judgment and decision-making. Our concept analysis defines one of these terms, 'clinical reasoning,' as a complex process that uses cognition, metacognition, and discipline-specific knowledge to gather and analyse patient information, evaluate its significance, and weigh alternative actions. This concept analysis provides a middle-range descriptive theory of clinical reasoning in nursing that helps clarify meaning and gives direction for future research. Appropriate instruments to operationalize the concept need to be developed. Research is needed to identify additional variables that have an impact on clinical reasoning and what are the consequences of clinical reasoning in specific situations.

Clinical and molecular characterization of a novel INS mutation identified in patients with MODY phenotype.

PubMed

Piccini, Barbara; Artuso, Rosangela; Lenzi, Lorenzo; Guasti, Monica; Braccesi, Giulia; Barni, Federica; Casalini, Emilio; Giglio, Sabrina; Toni, Sonia

2016-11-01

Correct diagnosis of Maturity-Onset Diabetes of the Young (MODY) is based on genetic tests requiring an appropriate subject selection by clinicians. Mutations in the insulin (INS) gene rarely occur in patients with MODY. This study is aimed at determining the genetic background and clinical phenotype in patients with suspected MODY. 34 patients with suspected MODY, negative for mutations in the GCK, HNF1α, HNF4α, HNF1β and PDX1 genes, were screened by next generation sequencing (NGS). A heterozygous INS mutation was identified in 4 members of the same family. First genetic tests performed identified two heterozygous silent nucleotide substitutions in MODY3/HNF1α gene. An ineffective attempt to suspend insulin therapy, administering repaglinide and sulphonylureas, was made. DNA was re-sequenced by NGS investigating a set of 102 genes. Genes implicated in the pathway of pancreatic β-cells, candidate genes for type 2 diabetes mellitus and genes causative of diabetes in mice were selected. A novel heterozygous variant in human preproinsulin INS gene (c.125T > C) was found in the affected family members. The new INS mutation broadens the spectrum of possible INS phenotypes. Screening for INS mutations is warranted not only in neonatal diabetes but also in MODYx patients and in selected patients with type 1 diabetes mellitus negative for autoantibodies. Subjects with complex diseases without a specific phenotype should be studied by NGS because Sanger sequencing is ineffective and time consuming in detecting rare variants. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Clinically actionable mutation profiles in patients with cancer identified by whole-genome sequencing

PubMed Central

Mizani, Tuba; Hamblin, Angela; Parton, Marina; Orosz, Zsolt; Athanasou, Nick; Hassan, Bass; Flanagan, Adrienne M.; Ahmed, Ahmed; Winter, Stuart; Harris, Adrian; Popitsch, Niko; Church, David; Taylor, Jenny C.

2018-01-01

Next-generation sequencing (NGS) efforts have established catalogs of mutations relevant to cancer development. However, the clinical utility of this information remains largely unexplored. Here, we present the results of the first eight patients recruited into a clinical whole-genome sequencing (WGS) program in the United Kingdom. We performed PCR-free WGS of fresh frozen tumors and germline DNA at 75× and 30×, respectively, using the HiSeq2500 HTv4. Subtracted tumor VCFs and paired germlines were subjected to comprehensive analysis of coding and noncoding regions, integration of germline with somatically acquired variants, and global mutation signatures and pathway analyses. Results were classified into tiers and presented to a multidisciplinary tumor board. WGS results helped to clarify an uncertain histopathological diagnosis in one case, led to informed or supported prognosis in two cases, leading to de-escalation of therapy in one, and indicated potential treatments in all eight. Overall 26 different tier 1 potentially clinically actionable findings were identified using WGS compared with six SNVs/indels using routine targeted NGS. These initial results demonstrate the potential of WGS to inform future diagnosis, prognosis, and treatment choice in cancer and justify the systematic evaluation of the clinical utility of WGS in larger cohorts of patients with cancer. PMID:29610388

Using language models to identify relevant new information in inpatient clinical notes.

PubMed

Zhang, Rui; Pakhomov, Serguei V; Lee, Janet T; Melton, Genevieve B

2014-01-01

Redundant information in clinical notes within electronic health record (EHR) systems is ubiquitous and may negatively impact the use of these notes by clinicians, and, potentially, the efficiency of patient care delivery. Automated methods to identify redundant versus relevant new information may provide a valuable tool for clinicians to better synthesize patient information and navigate to clinically important details. In this study, we investigated the use of language models for identification of new information in inpatient notes, and evaluated our methods using expert-derived reference standards. The best method achieved precision of 0.743, recall of 0.832 and F1-measure of 0.784. The average proportion of redundant information was similar between inpatient and outpatient progress notes (76.6% (SD=17.3%) and 76.7% (SD=14.0%), respectively). Advanced practice providers tended to have higher rates of redundancy in their notes compared to physicians. Future investigation includes the addition of semantic components and visualization of new information.

Using Language Models to Identify Relevant New Information in Inpatient Clinical Notes

PubMed Central

Zhang, Rui; Pakhomov, Serguei V.; Lee, Janet T.; Melton, Genevieve B.

2014-01-01

Redundant information in clinical notes within electronic health record (EHR) systems is ubiquitous and may negatively impact the use of these notes by clinicians, and, potentially, the efficiency of patient care delivery. Automated methods to identify redundant versus relevant new information may provide a valuable tool for clinicians to better synthesize patient information and navigate to clinically important details. In this study, we investigated the use of language models for identification of new information in inpatient notes, and evaluated our methods using expert-derived reference standards. The best method achieved precision of 0.743, recall of 0.832 and F1-measure of 0.784. The average proportion of redundant information was similar between inpatient and outpatient progress notes (76.6% (SD=17.3%) and 76.7% (SD=14.0%), respectively). Advanced practice providers tended to have higher rates of redundancy in their notes compared to physicians. Future investigation includes the addition of semantic components and visualization of new information. PMID:25954438

Clinical imaging guidelines part 4: challenges in identifying, engaging and collaborating with stakeholders.

PubMed

Bettmann, Michael A; Oikarinen, Helja; Rehani, Madan; Holmberg, Ola; del Rosario Perez, Maria; Naidoo, Anusha; Do, Kyung-Hyun; Dreyer, Keith; Ebdon-Jackson, Steve

2015-04-01

The effective development and use of clinical imaging guidelines requires an understanding of who the stakeholders are, what their interests in the process are, and what roles they should play. If the appropriate stakeholders are not engaged in the right roles, it is unlikely that clinical imaging guidelines will be successfully developed, relied on, and actually used. Some stakeholders are obvious: for the development of clinical imaging guidelines, both imagers and those who request examinations, such as general practitioners, internists, and medical specialists, must be involved. To gain acceptance, other relevant groups are stakeholders, including medical societies, other health care professionals, insurers, health IT experts and vendors, and patients. The role of stakeholders must be dictated by their specific interest. For some, involvement in the creation of guidelines is the right role. For others, such as regulators or insurers, reviews or invitations to comment are required, and for others, such as medical educators, it is probably sufficient to provide information and create awareness. Only through a careful consideration of who the stakeholders are and what are their interests are the successful development, acceptance, and use of clinical imaging guidelines likely to occur. Future efforts must focus on collaboration, particularly among groups that create clinical imaging guidelines and those that can support their use, and on regulatory roles and mandates. Copyright © 2015 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Building a Natural Language Processing Tool to Identify Patients With High Clinical Suspicion for Kawasaki Disease from Emergency Department Notes.

PubMed

Doan, Son; Maehara, Cleo K; Chaparro, Juan D; Lu, Sisi; Liu, Ruiling; Graham, Amanda; Berry, Erika; Hsu, Chun-Nan; Kanegaye, John T; Lloyd, David D; Ohno-Machado, Lucila; Burns, Jane C; Tremoulet, Adriana H

2016-05-01

Delayed diagnosis of Kawasaki disease (KD) may lead to serious cardiac complications. We sought to create and test the performance of a natural language processing (NLP) tool, the KD-NLP, in the identification of emergency department (ED) patients for whom the diagnosis of KD should be considered. We developed an NLP tool that recognizes the KD diagnostic criteria based on standard clinical terms and medical word usage using 22 pediatric ED notes augmented by Unified Medical Language System vocabulary. With high suspicion for KD defined as fever and three or more KD clinical signs, KD-NLP was applied to 253 ED notes from children ultimately diagnosed with either KD or another febrile illness. We evaluated KD-NLP performance against ED notes manually reviewed by clinicians and compared the results to a simple keyword search. KD-NLP identified high-suspicion patients with a sensitivity of 93.6% and specificity of 77.5% compared to notes manually reviewed by clinicians. The tool outperformed a simple keyword search (sensitivity = 41.0%; specificity = 76.3%). KD-NLP showed comparable performance to clinician manual chart review for identification of pediatric ED patients with a high suspicion for KD. This tool could be incorporated into the ED electronic health record system to alert providers to consider the diagnosis of KD. KD-NLP could serve as a model for decision support for other conditions in the ED. © 2016 by the Society for Academic Emergency Medicine.

Comparative analysis of four commercial on-farm culture methods to identify bacteria associated with clinical mastitis in dairy cattle.

PubMed

Ferreira, Jair C; Gomes, Marilia S; Bonsaglia, Erika C R; Canisso, Igor F; Garrett, Edgar F; Stewart, Jamie L; Zhou, Ziyao; Lima, Fabio S

2018-01-01

Several multiple-media culture systems have become commercially available for on-farm identification of mastitis-associated pathogens. However, the accuracy of these systems has not been thoroughly and independently validated against microbiological evaluations performed by referral laboratories. Therefore, the purpose of the present study was to evaluate the performance of commercially available culture plates (Accumast, Minnesota Easy System, SSGN and SSGNC Quad plates) to identify pathogens associated with clinical mastitis in dairy cows. Milk samples from the affected quarter with clinical mastitis were aerobically cultured with the on-farm culture systems and by two additional reference laboratories. Agreeing results from both standard laboratories were denoted as the reference standard (RS). Accuracy (Ac), sensitivity (Se), specificity (Sp), positive and negative predictive values (PPV and NPV, respectively) and Cohen's kappa coefficient (k) of on-farm plates were determined based on the RS culture of 211 milk samples. All four plate-systems correctly identified ≥ 84.9% of milk samples with no bacterial growth. Accumast had greater values for all overall predictive factors (Ac, Se, Sp, PPV and NPV) and a substantial agreement (k = 0.79) with RS. The inter-rater agreements of Minnesota, SSGN, and SSGNC with RS were moderate (0.45 ≤ k ≤ 0.55). The effectiveness to categorize bacterial colonies at the genus and species was numerically different amongst the commercial plates. Our findings suggest that Accumast was the most accurate on-farm culture system for identification of mastitis-associated pathogens of the four systems included in the analysis.

Comparative analysis of four commercial on-farm culture methods to identify bacteria associated with clinical mastitis in dairy cattle

PubMed Central

Ferreira, Jair C.; Gomes, Marilia S.; Bonsaglia, Erika C. R.; Canisso, Igor F.; Garrett, Edgar F.; Stewart, Jamie L.; Zhou, Ziyao

2018-01-01

Several multiple-media culture systems have become commercially available for on-farm identification of mastitis-associated pathogens. However, the accuracy of these systems has not been thoroughly and independently validated against microbiological evaluations performed by referral laboratories. Therefore, the purpose of the present study was to evaluate the performance of commercially available culture plates (Accumast, Minnesota Easy System, SSGN and SSGNC Quad plates) to identify pathogens associated with clinical mastitis in dairy cows. Milk samples from the affected quarter with clinical mastitis were aerobically cultured with the on-farm culture systems and by two additional reference laboratories. Agreeing results from both standard laboratories were denoted as the reference standard (RS). Accuracy (Ac), sensitivity (Se), specificity (Sp), positive and negative predictive values (PPV and NPV, respectively) and Cohen’s kappa coefficient (k) of on-farm plates were determined based on the RS culture of 211 milk samples. All four plate-systems correctly identified ≥ 84.9% of milk samples with no bacterial growth. Accumast had greater values for all overall predictive factors (Ac, Se, Sp, PPV and NPV) and a substantial agreement (k = 0.79) with RS. The inter-rater agreements of Minnesota, SSGN, and SSGNC with RS were moderate (0.45 ≤ k ≤ 0.55). The effectiveness to categorize bacterial colonies at the genus and species was numerically different amongst the commercial plates. Our findings suggest that Accumast was the most accurate on-farm culture system for identification of mastitis-associated pathogens of the four systems included in the analysis. PMID:29543852

Developing a questionnaire to identify perceived barriers for implementing the Dutch physical therapy COPD clinical practice guideline.

PubMed

van der Wees, Philip J; Zagers, Cor A M; de Die, Sara E; Hendriks, Erik J M; Nijhuis-van der Sanden, Maria W G; de Bie, Rob A

2013-05-01

Clinical practice guidelines have been developed to assist healthcare practitioners in clinical decision making. Publication of clinical practice guidelines does not automatically lead to their uptake and barrier identification has been recognized as an important step in implementation planning. This study aimed at developing a questionnaire to identify perceived barriers for implementing the Dutch COPD guideline for physical therapists and its recommended measurement instruments. An overall questionnaire, based on two existing questionnaires, was constructed to identify barriers and facilitators for implementing the COPD guideline. The construct of the questionnaire was assessed in a cross-sectional study among 246 chest physical therapists. Factor analysis was conducted to explore underlying dimensions. Psychometric properties were analyzed using Cronbach's alpha. Barriers and facilitators were assessed using descriptive statistics. Some 139 physical therapists (57%) responded. Factor analysis revealed 4-factor and 5-factor solutions with an explained variance of 36% and 39% respectively. Cronbach's alpha of the overall questionnaire was 0.90, and varied from 0.66 to 0.92 for the different factors. Underlying domains of the 5-factor solution were characterized as: attitude towards using measurement instruments, knowledge and skills of the physical therapist, applicability of the COPD guideline, required investment of time & money, and patient characteristics. Physical therapists showed a positive attitude toward using the COPD guideline. Main barriers for implementation were required time investment and financial constraints. The construct of the questionnaire revealed relevant underlying domains for the identification of barriers and facilitators for implementing the COPD guideline. The questionnaire allowed for tailoring to the target group and may be used across health care professionals as basis for in-depth analysis of barriers to specific recommendations in

Developing a questionnaire to identify perceived barriers for implementing the Dutch physical therapy COPD clinical practice guideline

PubMed Central

2013-01-01

Background Clinical practice guidelines have been developed to assist healthcare practitioners in clinical decision making. Publication of clinical practice guidelines does not automatically lead to their uptake and barrier identification has been recognized as an important step in implementation planning. This study aimed at developing a questionnaire to identify perceived barriers for implementing the Dutch COPD guideline for physical therapists and its recommended measurement instruments. Methods An overall questionnaire, based on two existing questionnaires, was constructed to identify barriers and facilitators for implementing the COPD guideline. The construct of the questionnaire was assessed in a cross-sectional study among 246 chest physical therapists. Factor analysis was conducted to explore underlying dimensions. Psychometric properties were analyzed using Cronbach’s alpha. Barriers and facilitators were assessed using descriptive statistics. Results Some 139 physical therapists (57%) responded. Factor analysis revealed 4-factor and 5-factor solutions with an explained variance of 36% and 39% respectively. Cronbach’s alpha of the overall questionnaire was 0.90, and varied from 0.66 to 0.92 for the different factors. Underlying domains of the 5-factor solution were characterized as: attitude towards using measurement instruments, knowledge and skills of the physical therapist, applicability of the COPD guideline, required investment of time & money, and patient characteristics. Physical therapists showed a positive attitude toward using the COPD guideline. Main barriers for implementation were required time investment and financial constraints. Conclusions The construct of the questionnaire revealed relevant underlying domains for the identification of barriers and facilitators for implementing the COPD guideline. The questionnaire allowed for tailoring to the target group and may be used across health care professionals as basis for in-depth analysis

Use of Digital Rectal Examination as an Adjunct to Prostate Specific Antigen in the Detection of Clinically Significant Prostate Cancer.

PubMed

Halpern, Joshua A; Oromendia, Clara; Shoag, Jonathan E; Mittal, Sameer; Cosiano, Michael F; Ballman, Karla V; Vickers, Andrew J; Hu, Jim C

2018-04-01

Guidelines from the NCCN ® (National Comprehensive Cancer Network®) advocate digital rectal examination screening only in men with elevated prostate specific antigen. We investigated the effect of prostate specific antigen on the association of digital rectal examination and clinically significant prostate cancer in a large American cohort. We evaluated the records of the 35,350 men who underwent digital rectal examination in the screening arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening trial for the development of clinically significant prostate cancer (Gleason 7 or greater). Followup was 343,273 person-years. The primary outcome was the rate of clinically significant prostate cancer among men with vs without suspicious digital rectal examination. We performed competing risks regression to evaluate the interaction between time varying suspicious digital rectal examination and prostate specific antigen. A total of 1,713 clinically significant prostate cancers were detected with a 10-year cumulative incidence of 5.9% (95% CI 5.6-6.2). Higher risk was seen for suspicious vs nonsuspicious digital rectal examination. Increases in absolute risk were small and clinically irrelevant for normal (less than 2 ng/ml) prostate specific antigen (1.5% vs 0.7% risk of clinically significant prostate cancer at 10 years), clinically relevant for elevated (3 ng/ml or greater) prostate specific antigen (23.0% vs 13.7%) and modestly clinically relevant for equivocal (2 to 3 ng/ml) prostate specific antigen (6.5% vs 3.5%). Digital rectal examination demonstrated prognostic usefulness when prostate specific antigen was greater than 3 ng/ml, limited usefulness for less than 2 ng/ml and marginal usefulness for 2 to 3 ng/ml. These findings support the restriction of digital rectal examination to men with higher prostate specific antigen as a reflex test to improve specificity. It should not be used as a primary screening modality to improve sensitivity. Copyright �

Identifying functional cancer-specific miRNA-mRNA interactions in testicular germ cell tumor.

PubMed

Sedaghat, Nafiseh; Fathy, Mahmood; Modarressi, Mohammad Hossein; Shojaie, Ali

2016-09-07

Testicular cancer is the most common cancer in men aged between 15 and 35 and more than 90% of testicular neoplasms are originated at germ cells. Recent research has shown the impact of microRNAs (miRNAs) in different types of cancer, including testicular germ cell tumor (TGCT). MicroRNAs are small non-coding RNAs which affect the development and progression of cancer cells by binding to mRNAs and regulating their expressions. The identification of functional miRNA-mRNA interactions in cancers, i.e. those that alter the expression of genes in cancer cells, can help delineate post-regulatory mechanisms and may lead to new treatments to control the progression of cancer. A number of sequence-based methods have been developed to predict miRNA-mRNA interactions based on the complementarity of sequences. While necessary, sequence complementarity is, however, not sufficient for presence of functional interactions. Alternative methods have thus been developed to refine the sequence-based interactions using concurrent expression profiles of miRNAs and mRNAs. This study aims to find functional cancer-specific miRNA-mRNA interactions in TGCT. To this end, the sequence-based predicted interactions are first refined using an ensemble learning method, based on two well-known methods of learning miRNA-mRNA interactions, namely, TaLasso and GenMiR++. Additional functional analyses were then used to identify a subset of interactions to be most likely functional and specific to TGCT. The final list of 13 miRNA-mRNA interactions can be potential targets for identifying TGCT-specific interactions and future laboratory experiments to develop new therapies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Plant food allergies: a suggested approach to allergen-resolved diagnosis in the clinical practice by identifying easily available sensitization markers.

PubMed

Asero, Riccardo

2005-09-01

Molecular biology techniques have led to the identification of a number of allergens in vegetable foods, but due to the lack of purified food proteins for routine diagnostic use, the detection of sensitizing allergens remains a nearly impossible task in most clinical settings. The allergen-resolved diagnosis of food allergy is essential because each plant-derived food may contain a number of different allergens showing different physical/chemical characteristics that strongly influence the clinical expression of allergy; moreover, many allergens may cross-react with homologue proteins present in botanically unrelated vegetable foods. Through a review of the available literature, this study aimed to detect "markers" of sensitization to specific plant food allergens that are easily accessible in the clinical practice. There are several "markers" of sensitization to different allergenic proteins in vegetable foods that can be helpful in the clinical practice. Specific algorithms for patients allergic to Rosaceae and to tree nuts were built. Clinical allergologists lacking the assistance of an advanced molecular biology lab may take advantage of some specific clinical data as well as of some "markers" in the difficult task of correctly diagnosing patients with plant food allergy and to provide them the best preventive advice. Copyright (c) 2005 S. Karger AG, Basel.

Identifying children with specific reading disabilities from listening and reading discrepancy scores.

PubMed

Spring, C; French, L

1990-01-01

A method of identifying children with specific reading disabilities by identifying discrepancies between their reading and listening comprehension scores was validated with disabled and nondisabled readers in Grades 4, 5, and 6. The method is based on a modification of the reading comprehension subtest of the Peabody Individual Achievement Test (Dunn & Markwardt, 1970). In this modification, even-numbered sentences are read by subjects, and odd-numbered sentences are read by the test administrator as subjects listen. The features of this test that reduce demands on working memory, thereby making it suitable for the detection of a discrepancy between reading and listening comprehension in readers with disabilities, are discussed. A significant group-by-modality interaction was obtained. Children with reading disabilities scored significantly lower on reading than on listening comprehension, while nondisabled readers scored slightly higher, but not significantly so, on reading than on listening comprehension. The appropriateness of this method as a substitute for the traditional method, which is based on the detection of a discrepancy between intelligence and reading and which has recently been proscribed in certain school districts, is discussed. Issues concerning the listening comprehension skills of disabled readers are also discussed.

Male specific genes from dioecious white campion identified by fluorescent differential display.

PubMed

Scutt, Charles P; Jenkins, Tom; Furuya, Masaki; Gilmartin, Philip M

2002-05-01

Fluorescent differential display (FDD) has been used to screen for cDNAs that are differentially up-regulated in male flowers of the dioecious plant Silene latifolia in which an X/Y chromosome system of sex determination operates. To adapt FDD to the cloning of large numbers of differential cDNAs, a novel method of confirming the differential expression of these has been devised. FDD gels were Southern electro-blotted and probed with mixtures of individual cDNA clones derived from different FDD product ligation reactions. These Southern blots were then stripped and re-probed with further mixtures of individual cloned FDD products to identify the maximum number of recombinant clones carrying the true differential amplification products. Of 135 differential bands identified by FDD, 56 differential amplification products were confirmed; these represent 23 unique differentially expressed genes as determined by virtual Northern analysis and two genes expressed at or below the level of detection by virtual Northern analysis. These two low expressed genes show bands of hybridization on genomic Southern blots that are specific to male plants, indicating that they are derived from, or closely related to, Y chromosome genes.

Sensitivity and specificity of administrative mortality data for identifying prescription opioid–related deaths

PubMed Central

Gladstone, Emilie; Smolina, Kate; Morgan, Steven G.; Fernandes, Kimberly A.; Martins, Diana; Gomes, Tara

2016-01-01

Background: Comprehensive systems for surveilling prescription opioid–related harms provide clear evidence that deaths from prescription opioids have increased dramatically in the United States. However, these harms are not systematically monitored in Canada. In light of a growing public health crisis, accessible, nationwide data sources to examine prescription opioid–related harms in Canada are needed. We sought to examine the performance of 5 algorithms to identify prescription opioid–related deaths from vital statistics data against data abstracted from the Office of the Chief Coroner of Ontario as a gold standard. Methods: We identified all prescription opioid–related deaths from Ontario coroners’ data that occurred between Jan. 31, 2003, and Dec. 31, 2010. We then used 5 different algorithms to identify prescription opioid–related deaths from vital statistics death data in 2010. We selected the algorithm with the highest sensitivity and a positive predictive value of more than 80% as the optimal algorithm for identifying prescription opioid–related deaths. Results: Four of the 5 algorithms had positive predictive values of more than 80%. The algorithm with the highest sensitivity (75%) in 2010 improved slightly in its predictive performance from 2003 to 2010. Interpretation: In the absence of specific systems for monitoring prescription opioid–related deaths in Canada, readily available national vital statistics data can be used to study prescription opioid–related mortality with considerable accuracy. Despite some limitations, these data may facilitate the implementation of national surveillance and monitoring strategies. PMID:26622006

Sensitivity and specificity of administrative mortality data for identifying prescription opioid-related deaths.

PubMed

Gladstone, Emilie; Smolina, Kate; Morgan, Steven G; Fernandes, Kimberly A; Martins, Diana; Gomes, Tara

2016-03-01

Comprehensive systems for surveilling prescription opioid-related harms provide clear evidence that deaths from prescription opioids have increased dramatically in the United States. However, these harms are not systematically monitored in Canada. In light of a growing public health crisis, accessible, nationwide data sources to examine prescription opioid-related harms in Canada are needed. We sought to examine the performance of 5 algorithms to identify prescription opioid-related deaths from vital statistics data against data abstracted from the Office of the Chief Coroner of Ontario as a gold standard. We identified all prescription opioid-related deaths from Ontario coroners' data that occurred between Jan. 31, 2003, and Dec. 31, 2010. We then used 5 different algorithms to identify prescription opioid-related deaths from vital statistics death data in 2010. We selected the algorithm with the highest sensitivity and a positive predictive value of more than 80% as the optimal algorithm for identifying prescription opioid-related deaths. Four of the 5 algorithms had positive predictive values of more than 80%. The algorithm with the highest sensitivity (75%) in 2010 improved slightly in its predictive performance from 2003 to 2010. In the absence of specific systems for monitoring prescription opioid-related deaths in Canada, readily available national vital statistics data can be used to study prescription opioid-related mortality with considerable accuracy. Despite some limitations, these data may facilitate the implementation of national surveillance and monitoring strategies. © 2016 Canadian Medical Association or its licensors.

Influenza-associated Encephalitis/Encephalopathy Identified by the Australian Childhood Encephalitis Study 2013-2015.

PubMed

Britton, Philip N; Dale, Russell C; Blyth, Christopher C; Macartney, Kristine; Crawford, Nigel W; Marshall, Helen; Clark, Julia E; Elliott, Elizabeth J; Webster, Richard I; Cheng, Allen C; Booy, Robert; Jones, Cheryl A

2017-11-01

Influenza-associated encephalitis/encephalopathy (IAE) is an important cause of acute encephalitis syndrome in children. IAE includes a series of clinicoradiologic syndromes or acute encephalopathy syndromes that have been infrequently reported outside East Asia. We aimed to describe cases of IAE identified by the Australian Childhood Encephalitis study. Children ≤ 14 years of age with suspected encephalitis were prospectively identified in 5 hospitals in Australia. Demographic, clinical, laboratory, imaging, and outcome at discharge data were reviewed by an expert panel and cases were categorized by using predetermined case definitions. We extracted cases associated with laboratory identification of influenza virus for this analysis; among these cases, specific IAE syndromes were identified where clinical and radiologic features were consistent with descriptions in the published literature. We identified 13 cases of IAE during 3 southern hemisphere influenza seasons at 5 tertiary children's hospitals in Australia; 8 children with specific acute encephalopathy syndromes including: acute necrotizing encephalopathy, acute encephalopathy with biphasic seizures and late diffusion restriction, mild encephalopathy with reversible splenial lesion, and hemiconvulsion-hemiplegia syndrome. Use of influenza-specific antiviral therapy and prior influenza vaccination were infrequent. In contrast, death or significant neurologic morbidity occurred in 7 of the 13 children (54%). The conditions comprising IAE are heterogeneous with varied clinical features, magnetic resonance imaging changes, and outcomes. Overall, outcome of IAE is poor emphasizing the need for optimized prevention, early recognition, and empiric management.

Cancer registries in Japan: National Clinical Database and site-specific cancer registries.

PubMed

Anazawa, Takayuki; Miyata, Hiroaki; Gotoh, Mitsukazu

2015-02-01

The cancer registry is an essential part of any rational program of evidence-based cancer control. The cancer control program is required to strategize in a systematic and impartial manner and efficiently utilize limited resources. In Japan, the National Clinical Database (NCD) was launched in 2010. It is a nationwide prospective registry linked to various types of board certification systems regarding surgery. The NCD is a nationally validated database using web-based data collection software; it is risk adjusted and outcome based to improve the quality of surgical care. The NCD generalizes site-specific cancer registries by taking advantage of their excellent organizing ability. Some site-specific cancer registries, including pancreatic, breast, and liver cancer registries have already been combined with the NCD. Cooperation between the NCD and site-specific cancer registries can establish a valuable platform to develop a cancer care plan in Japan. Furthermore, the prognosis information of cancer patients arranged using population-based and hospital-based cancer registries can help in efficient data accumulation on the NCD. International collaboration between Japan and the USA has recently started and is expected to provide global benchmarking and to allow a valuable comparison of cancer treatment practices between countries using nationwide cancer registries in the future. Clinical research and evidence-based policy recommendation based on accurate data from the nationwide database may positively impact the public.

Coupling genetics and proteomics to identify aphid proteins associated with vector-specific transmission of polerovirus (luteoviridae).

PubMed

Yang, Xiaolong; Thannhauser, T W; Burrows, Mary; Cox-Foster, Diana; Gildow, Fred E; Gray, Stewart M

2008-01-01

Cereal yellow dwarf virus-RPV (CYDV-RPV) is transmitted specifically by the aphids Rhopalosiphum padi and Schizaphis graminum in a circulative nonpropagative manner. The high level of vector specificity results from the vector aphids having the functional components of the receptor-mediated endocytotic pathways to allow virus to transverse the gut and salivary tissues. Studies of F(2) progeny from crosses of vector and nonvector genotypes of S. graminum showed that virus transmission efficiency is a heritable trait regulated by multiple genes acting in an additive fashion and that gut- and salivary gland-associated factors are not genetically linked. Utilizing two-dimensional difference gel electrophoresis to compare the proteomes of vector and nonvector parental and F(2) genotypes, four aphid proteins (S4, S8, S29, and S405) were specifically associated with the ability of S. graminum to transmit CYDV-RPV. The four proteins were coimmunoprecipitated with purified RPV, indicating that the aphid proteins are capable of binding to virus. Analysis by mass spectrometry identified S4 as a luciferase and S29 as a cyclophilin, both of which have been implicated in macromolecular transport. Proteins S8 and S405 were not identified from available databases. Study of this unique genetic system coupled with proteomic analysis indicated that these four virus-binding aphid proteins were specifically inherited and conserved in different generations of vector genotypes and suggests that they play a major role in regulating polerovirus transmission.

Clinical case definition for the diagnosis of acute intussusception.

PubMed

Bines, Julie E; Ivanoff, Bernard; Justice, Frances; Mulholland, Kim

2004-11-01

Because of the reported association between intussusception and a rotavirus vaccine, future clinical trials of rotavirus vaccines will need to include intussusception surveillance in the evaluation of vaccine safety. The aim of this study is to develop and validate a clinical case definition for the diagnosis of acute intussusception. A clinical case definition for the diagnosis of acute intussusception was developed by analysis of an extensive literature review that defined the clinical presentation of intussusception in 70 developed and developing countries. The clinical case definition was then assessed for sensitivity and specificity using a retrospective chart review of hospital admissions. Sensitivity of the clinical case definition was assessed in children diagnosed with intussusception over a 6.5-year period. Specificity was assessed in patients aged <2 years admitted with bowel obstruction and in patients aged <19 years presenting with symptoms that may occur in intussusception. The clinical case definition accurately identified 185 of 191 assessable cases as "probable" intussusception and six cases as "possible" intussusception (sensitivity, 97%). No case of radiologic or surgically proven intussusception failed to be identified by the clinical case definition. The specificity of the definition in correctly identifying patients who did not have intussusception ranged from 87% to 91%. The clinical case definition for intussusception may assist in the prompt identification of patients with intussusception and may provide an important tool for the future trials of enteric vaccines.

The Quality of Clinical Maternal and Neonatal Healthcare – A Strategy for Identifying ‘Routine Care Signal Functions’

PubMed Central

Brenner, Stephan; De Allegri, Manuela; Gabrysch, Sabine; Chinkhumba, Jobiba; Sarker, Malabika; Muula, Adamson S.

2015-01-01

Background A variety of clinical process indicators exists to measure the quality of care provided by maternal and neonatal health (MNH) programs. To allow comparison across MNH programs in low- and middle-income countries (LMICs), a core set of essential process indicators is needed. Although such a core set is available for emergency obstetric care (EmOC), the ‘EmOC signal functions’, a similar approach is currently missing for MNH routine care evaluation. We describe a strategy for identifying core process indicators for routine care and illustrate their usefulness in a field example. Methods We first developed an indicator selection strategy by combining epidemiological and programmatic aspects relevant to MNH in LMICs. We then identified routine care process indicators meeting our selection criteria by reviewing existing quality of care assessment protocols. We grouped these indicators into three categories based on their main function in addressing risk factors of maternal or neonatal complications. We then tested this indicator set in a study assessing MNH quality of clinical care in 33 health facilities in Malawi. Results Our strategy identified 51 routine care processes: 23 related to initial patient risk assessment, 17 to risk monitoring, 11 to risk prevention. During the clinical performance assessment a total of 82 cases were observed. Birth attendants’ adherence to clinical standards was lowest in relation to risk monitoring processes. In relation to major complications, routine care processes addressing fetal and newborn distress were performed relatively consistently, but there were major gaps in the performance of routine care processes addressing bleeding, infection, and pre-eclampsia risks. Conclusion The identified set of process indicators could identify major gaps in the quality of obstetric and neonatal care provided during the intra- and immediate postpartum period. We hope our suggested indicators for essential routine care processes

Identifying Military and Combat-Specific Risk Factors for Child Adjustment: Comparing High and Low Risk Military Families and Civilian Families

DTIC Science & Technology

2016-08-01

Award Number: W81XWH-12-2-0034 TITLE: Identifying Military and Combat-Specific Risk Factors for Child Adjustment: Comparing High and Low Risk...2. REPORT TYPE Final 3. DATES COVERED (From - To) 15May2012 - 31Aug2016 Identifying Military and Combat-Specific Risk Factors for Child Adjustment...deployment and has a child between the age of 3 and 7 and comparison groups of civilain single parent families (N=200) and civilian dual parent

Genome-wide methylomic and transcriptomic analyses identify subtype-specific epigenetic signatures commonly dysregulated in glioma stem cells and glioblastoma.

PubMed

Pangeni, Rajendra P; Zhang, Zhou; Alvarez, Angel A; Wan, Xuechao; Sastry, Namratha; Lu, Songjian; Shi, Taiping; Huang, Tianzhi; Lei, Charles X; James, C David; Kessler, John A; Brennan, Cameron W; Nakano, Ichiro; Lu, Xinghua; Hu, Bo; Zhang, Wei; Cheng, Shi-Yuan

2018-06-21

Glioma stem cells (GSCs), a subpopulation of tumor cells, contribute to tumor heterogeneity and therapy resistance. Gene expression profiling classified glioblastoma (GBM) and GSCs into four transcriptomically-defined subtypes. Here, we determined the DNA methylation signatures in transcriptomically pre-classified GSC and GBM bulk tumors subtypes. We hypothesized that these DNA methylation signatures correlate with gene expression and are uniquely associated either with only GSCs or only GBM bulk tumors. Additional methylation signatures may be commonly associated with both GSCs and GBM bulk tumors, i.e., common to non-stem-like and stem-like tumor cell populations and correlating with the clinical prognosis of glioma patients. We analyzed Illumina 450K methylation array and expression data from a panel of 23 patient-derived GSCs. We referenced these results with The Cancer Genome Atlas (TCGA) GBM datasets to generate methylomic and transcriptomic signatures for GSCs and GBM bulk tumors of each transcriptomically pre-defined tumor subtype. Survival analyses were carried out for these signature genes using publicly available datasets, including from TCGA. We report that DNA methylation signatures in proneural and mesenchymal tumor subtypes are either unique to GSCs, unique to GBM bulk tumors, or common to both. Further, dysregulated DNA methylation correlates with gene expression and clinical prognoses. Additionally, many previously identified transcriptionally-regulated markers are also dysregulated due to DNA methylation. The subtype-specific DNA methylation signatures described in this study could be useful for refining GBM sub-classification, improving prognostic accuracy, and making therapeutic decisions.

Aggregator: a machine learning approach to identifying MEDLINE articles that derive from the same underlying clinical trial.

PubMed

Shao, Weixiang; Adams, Clive E; Cohen, Aaron M; Davis, John M; McDonagh, Marian S; Thakurta, Sujata; Yu, Philip S; Smalheiser, Neil R

2015-03-01

It is important to identify separate publications that report outcomes from the same underlying clinical trial, in order to avoid over-counting these as independent pieces of evidence. We created positive and negative training sets (comprised of pairs of articles reporting on the same condition and intervention) that were, or were not, linked to the same clinicaltrials.gov trial registry number. Features were extracted from MEDLINE and PubMed metadata; pairwise similarity scores were modeled using logistic regression. Article pairs from the same trial were identified with high accuracy (F1 score=0.843). We also created a clustering tool, Aggregator, that takes as input a PubMed user query for RCTs on a given topic, and returns article clusters predicted to arise from the same clinical trial. Although painstaking examination of full-text may be needed to be conclusive, metadata are surprisingly accurate in predicting when two articles derive from the same underlying clinical trial. Copyright © 2014 Elsevier Inc. All rights reserved.

Precision Oncology Medicine: The Clinical Relevance of Patient-Specific Biomarkers Used to Optimize Cancer Treatment.

PubMed

Schmidt, Keith T; Chau, Cindy H; Price, Douglas K; Figg, William D

2016-12-01

Precision medicine in oncology is the result of an increasing awareness of patient-specific clinical features coupled with the development of genomic-based diagnostics and targeted therapeutics. Companion diagnostics designed for specific drug-target pairs were the first to widely utilize clinically applicable tumor biomarkers (eg, HER2, EGFR), directing treatment for patients whose tumors exhibit a mutation susceptible to an FDA-approved targeted therapy (eg, trastuzumab, erlotinib). Clinically relevant germline mutations in drug-metabolizing enzymes and transporters (eg, TPMT, DPYD) have been shown to impact drug response, providing a rationale for individualized dosing to optimize treatment. The use of multigene expression-based assays to analyze an array of prognostic biomarkers has been shown to help direct treatment decisions, especially in breast cancer (eg, Oncotype DX). More recently, the use of next-generation sequencing to detect many potential "actionable" cancer molecular alterations is further shifting the 1 gene-1 drug paradigm toward a more comprehensive, multigene approach. Currently, many clinical trials (eg, NCI-MATCH, NCI-MPACT) are assessing novel diagnostic tools with a combination of different targeted therapeutics while also examining tumor biomarkers that were previously unexplored in a variety of cancer histologies. Results from ongoing trials such as the NCI-MATCH will help determine the clinical utility and future development of the precision-medicine approach. © 2016, The American College of Clinical Pharmacology.

Identifying unmet clinical need in hypertrophic cardiomyopathy using national electronic health records.

PubMed

Pujades-Rodriguez, Mar; Guttmann, Oliver P; Gonzalez-Izquierdo, Arturo; Duyx, Bram; O'Mahony, Constantinos; Elliott, Perry; Hemingway, Harry

2018-01-01

To evaluate unmet clinical need in unselected hypertrophic cardiomyopathy (HCM) patients to determine the risk of a wide range of subsequent cardiovascular disease endpoints and safety endpoints relevant for trial design. Population based cohort (CALIBER, linked primary care, hospital and mortality records in England, period 1997-2010), all people diagnosed with HCM were identified and matched by age, sex and general practice with ten randomly selected people without HCM. Random-effects Poisson models were used to assess the associations between HCM and cardiovascular diseases and bleeding. Among 3,290,455 eligible people a diagnosis of hypertrophic cardiomyopathy was found in 4 per 10,000. Forty-one percent of the 1,160 individuals with hypertrophic cardiomyopathy were women and the median age was 57 years. The median follow-up was 4.0 years. Compared to general population controls, people with HCM had higher risk of ventricular arrhythmia (incidence rate ratio = 23.53, [95% confidence interval 12.67-43.72]), cardiac arrest or sudden cardiac death (6.33 [3.69-10.85]), heart failure (4.31, [3.30-5.62]), and atrial fibrillation (3.80 [3.04-4.75]). HCM was also associated with a higher incidence of myocardial infarction ([MI] 1.90 [1.27-2.84]) and coronary revascularisation (2.32 [1.46-3.69]).The absolute Kaplan-Meier risks at 3 years were 8.8% for the composite endpoint of cardiovascular death or heart failure, 8.4% for the composite of cardiovascular death, stroke or myocardial infarction, and 1.5% for major bleeding. Our study identified major unmet need in HCM and highlighted the importance of implementing improved cardiovascular prevention strategies to increase life-expectancy of the contemporary HCM population. They also show that national electronic health records provide an effective method for identifying outcomes and clinically relevant estimates of composite efficacy and safety endpoints essential for trial design in rare diseases.

Dlx1 and Rgs5 in the Ductus Arteriosus: Vessel-Specific Genes Identified by Transcriptional Profiling of Laser-Capture Microdissected Endothelial and Smooth Muscle Cells

PubMed Central

Bökenkamp, Regina; van Brempt, Ronald; van Munsteren, Jacoba Cornelia; van den Wijngaert, Ilse; de Hoogt, Ronald; Finos, Livio; Goeman, Jelle; Groot, Adriana Cornelia Gittenberger-de; Poelmann, Robert Eugen; Blom, Nicolaas Andreas; DeRuiter, Marcus Cornelis

2014-01-01

Closure of the ductus arteriosus (DA) is a crucial step in the transition from fetal to postnatal life. Patent DA is one of the most common cardiovascular anomalies in children with significant clinical consequences especially in premature infants. We aimed to identify genes that specify the DA in the fetus and differentiate it from the aorta. Comparative microarray analysis of laser-captured microdissected endothelial (ECs) and vascular smooth muscle cells (SMCs) from the DA and aorta of fetal rats (embryonic day 18 and 21) identified vessel-specific transcriptional profiles. We found a strong age-dependency of gene expression. Among the genes that were upregulated in the DA the regulator of the G-protein coupled receptor 5 (Rgs5) and the transcription factor distal-less homeobox 1 (Dlx1) exhibited the highest and most significant level of differential expression. The aorta showed a significant preferential expression of the Purkinje cell protein 4 (Pcp4) gene. The results of the microarray analysis were validated by real-time quantitative PCR and immunohistochemistry. Our study confirms vessel-specific transcriptional profiles in ECs and SMCs of rat DA and aorta. Rgs5 and Dlx1 represent novel molecular targets for the regulation of DA maturation and closure. PMID:24489801

Fecal level of calprotectin identifies histologic inflammation in patients with ulcerative colitis in clinical and endoscopic remission.

PubMed

Guardiola, Jordi; Lobatón, Triana; Rodríguez-Alonso, Lorena; Ruiz-Cerulla, Alexandra; Arajol, Claudia; Loayza, Carolina; Sanjuan, Xavier; Sánchez, Elena; Rodríguez-Moranta, Francisco

2014-11-01

Histologic recovery of patients with ulcerative colitis (UC) often is incomplete, even among those in clinical and endoscopic remission. Persistent active microscopic inflammation is associated with an increased risk of relapse and colorectal neoplasia. A high level of fecal calprotectin (FC) is a reliable marker of endoscopic lesions in patients with UC. We evaluated the accuracy of FC in identifying patients with UC in clinical and endoscopic remission who still have histologic features of inflammation. We performed a prospective observational study of 59 patients with UC in clinical and endoscopic remission undergoing colonoscopy. Several biopsy specimens were collected from each colonic segment. Endoscopic remission was defined as a Mayo endoscopic subscore with a grade of 0 or 1. Active histologic inflammation was defined by the presence of neutrophils infiltrating crypt epithelial cells. FC was determined by enzyme-linked immunosorbent assay analysis. Eighteen patients (30.5%) showed evidence of active histologic inflammation. Patients with active histologic inflammation had a significantly higher median level of FC (278 μg/g; interquartile range, 136-696 μg/g) than those without active histologic inflammation (68 μg/g; interquartile range, 30-172 μg/g) (P = .002). In multivariate analysis, the FC and Mayo endoscopic subscore (0 or 1) were each independent predictors of histologic inflammation. The level of FC identified active histologic inflammation in patients in clinical and endoscopic remission, with an area under the receiver operator characteristic curve value of 0.754. Histologic inflammation is common among patients with UC in clinical and endoscopic remission. Patients with histologic features of inflammation can be identified reliably based on their fecal level of calprotectin. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Specific autoantibodies in dermatomyositis: a helpful tool to classify different clinical subsets.

PubMed

Merlo, Giulia; Clapasson, Andrea; Cozzani, Emanuele; Sanna, Luigi; Pesce, Giampaola; Bagnasco, Marcello; Burlando, Martina; Parodi, Aurora

2017-03-01

Autoantibodies are important in the diagnosis of dermatomyositis. They can be divided in two different groups: myositis-associated autoantibodies (MAA) prevailing in overlap syndromes, and myositis-specific autoantibodies (MSA), with diagnostic specificity exceeding 90%. Our purpose was to detect retrospectively the prevalence of the most common MSAs in a group of 19 adult DM patients (13 women, 6 men). A severe DM (SDM), with extensive cutaneous and muscular manifestations, dysphagia, and sometimes pneumopathy, was detected in ten cases. Three patients had a mild DM (MDM), with little muscle and skin impairment, and a short course. Four patients suffered from amyopathic DM (ADM), two from paraneoplastic DM (PDM). Each serum was tested for ANA, ENA, MAAs, MSAs. Myositis-specific autoantibodies were detected in 15 cases. The most frequent was anti-TIF1γ, associated with SDM or PDM in four out of seven cases. Anti-MDA5 antibodies were recorded in a SDM and in a ADM with lung fibrosis. Anti-Mi2 and anti-SRP antibodies were both detected in a MDM and in a SDM, whereas anti-SAE1 in a amyopathic form. Other antibodies (anti-NXP2, -Jo1, -PL7, -PL12, -OJ) were found in single patients with SDM. Our series confirmed that specific autoantibodies could be helpful to classify different clinical subsets, particularly in the case of paraneoplastic forms or association with pneumopathy. Moreover, they can help in predicting the disease evolution and influence therapeutic strategies. A greater number of cases should be useful to highlight the clinical and pathogenic role of these antibodies, and develop a homogeneous protocol for diagnosis and treatment.

Use of clinical risk factors to identify postmenopausal women with vertebral fractures.

PubMed

Tobias, J H; Hutchinson, A P; Hunt, L P; McCloskey, E V; Stone, M D; Martin, J C; Thompson, P W; Palferman, T G; Bhalla, A K

2007-01-01

Previous studies have been unable to identify risk factors for prevalent vertebral fractures (VF), which are suitable for use in selection strategies intended to target high-risk sub-groups for diagnostic assessment. However, these studies generally consisted of large epidemiology surveys based on questionnaires and were only able to evaluate a limited number of risk factors. Here, we investigated whether a stronger relationship exists with prevalent VF when conventional risk factors are combined with additional information obtained from detailed one-to-one assessment. Women aged 65-75 registered at four geographically distinct GP practices were invited to participate (n=1,518), of whom 540 attended for assessment as follows: a questionnaire asking about risk factors for osteoporosis such as height loss compared to age 25 and history of non-vertebral fracture (NVF), the get-up-and-go test, Margolis back pain score, measurement of wall-tragus and rib-pelvis distances, and BMD as measured by the distal forearm BMD. A lateral thoraco-lumbar spine X-ray was obtained, which was subsequently scored for the presence of significant vertebral deformities. Of the 509 subjects who underwent spinal radiographs, 37 (7.3%) were found to have one or more VF. Following logistic regression analysis, the four most predictive clinical risk factors for prevalent VF were: height loss (P=0.006), past NVF (P=0.004), history of back pain (P=0.075) and age (P=0.05). BMD was also significantly associated with prevalent VF (P=0.002), but its inclusion did not affect associations with other variables. Factors elicited from detailed one-to-one assessment were not related to the risk of one or more prevalent VFs. The area under ROC curves derived from these regressions, which suggested that models for prevalent VF had modest predictive accuracy, were as follows: 0.68 (BMD), 0.74 (four clinical risk factors above) and 0.78 (clinical risk factors + BMD). Analyses were repeated in relation to the

Identifying Military and Combat Specific Risk Factors for Child Adjustment: Comparing High and Low Risk Military Families and Civilian Families

DTIC Science & Technology

2016-06-01

Award Number: W81XWH-12-2-0034 TITLE: Identifying Military and Combat-Specific Risk Factors for Child Adjustment: Comparing High and Low Risk...2. REPORT TYPE Annual 3. DATES COVERED (From - To) 15 May - 2013 - 14 May 2014. Identifying Military and Combat-Specific Risk Factors for Child ...parents (N=200) whose spouse/partner is currently in a “low perceived risk” deployment and has a child between the age of 3 and 7 and comparison

Formative evaluation of a patient-specific clinical knowledge summarization tool

PubMed Central

Del Fiol, Guilherme; Mostafa, Javed; Pu, Dongqiuye; Medlin, Richard; Slager, Stacey; Jonnalagadda, Siddhartha R.; Weir, Charlene R.

2015-01-01

Objective To iteratively design a prototype of a computerized clinical knowledge summarization (CKS) tool aimed at helping clinicians finding answers to their clinical questions; and to conduct a formative assessment of the usability, usefulness, efficiency, and impact of the CKS prototype on physicians’ perceived decision quality compared with standard search of UpToDate and PubMed. Materials and methods Mixed-methods observations of the interactions of 10 physicians with the CKS prototype vs. standard search in an effort to solve clinical problems posed as case vignettes. Results The CKS tool automatically summarizes patient-specific and actionable clinical recommendations from PubMed (high quality randomized controlled trials and systematic reviews) and UpToDate. Two thirds of the study participants completed 15 out of 17 usability tasks. The median time to task completion was less than 10 s for 12 of the 17 tasks. The difference in search time between the CKS and standard search was not significant (median = 4.9 vs. 4.5 min). Physician’s perceived decision quality was significantly higher with the CKS than with manual search (mean = 16.6 vs. 14.4; p = 0.036). Conclusions The CKS prototype was well-accepted by physicians both in terms of usability and usefulness. Physicians perceived better decision quality with the CKS prototype compared to standard search of PubMed and UpToDate within a similar search time. Due to the formative nature of this study and a small sample size, conclusions regarding efficiency and efficacy are exploratory. PMID:26612774

Formative evaluation of a patient-specific clinical knowledge summarization tool.

PubMed

Del Fiol, Guilherme; Mostafa, Javed; Pu, Dongqiuye; Medlin, Richard; Slager, Stacey; Jonnalagadda, Siddhartha R; Weir, Charlene R

2016-02-01

To iteratively design a prototype of a computerized clinical knowledge summarization (CKS) tool aimed at helping clinicians finding answers to their clinical questions; and to conduct a formative assessment of the usability, usefulness, efficiency, and impact of the CKS prototype on physicians' perceived decision quality compared with standard search of UpToDate and PubMed. Mixed-methods observations of the interactions of 10 physicians with the CKS prototype vs. standard search in an effort to solve clinical problems posed as case vignettes. The CKS tool automatically summarizes patient-specific and actionable clinical recommendations from PubMed (high quality randomized controlled trials and systematic reviews) and UpToDate. Two thirds of the study participants completed 15 out of 17 usability tasks. The median time to task completion was less than 10s for 12 of the 17 tasks. The difference in search time between the CKS and standard search was not significant (median=4.9 vs. 4.5m in). Physician's perceived decision quality was significantly higher with the CKS than with manual search (mean=16.6 vs. 14.4; p=0.036). The CKS prototype was well-accepted by physicians both in terms of usability and usefulness. Physicians perceived better decision quality with the CKS prototype compared to standard search of PubMed and UpToDate within a similar search time. Due to the formative nature of this study and a small sample size, conclusions regarding efficiency and efficacy are exploratory. Published by Elsevier Ireland Ltd.

Sensitivity and specificity of clinical, histologic, and immunologic features in the diagnosis of paraneoplastic pemphigus.

PubMed

Joly, P; Richard, C; Gilbert, D; Courville, P; Chosidow, O; Roujeau, J C; Beylot-Barry, M; D'incan, M; Martel, P; Lauret, P; Tron, F

2000-10-01

Paraneoplastic pemphigus (PNP) is an autoimmune blistering disease characterized by the production of autoantibodies mainly directed against proteins of the plakin family. An overlapping distribution of autoantibody specificities has been recently reported between PNP, pemphigus vulgaris (PV), and pemphigus foliaceus (PF), which suggests a relationship between the different types of pemphigus. Our purpose was to evaluate the sensitivity and the specificity of clinical, histologic, and immunologic features in the diagnosis of PNP. The clinical, histologic, and immunologic features of 22 PNP patients were retrospectively reviewed and compared with those of 81 PV and PF patients without neoplasia and of 8 PV and 4 PF patients with various neoplasms. One clinical and 2 biologic features had both high sensitivity (82%-86%) and high specificity (83%-100%) whatever the control group considered: (1) association with a lymphoproliferative disorder, (2) indirect immunofluorescence (IIF) labeling of rat bladder, and (3) recognition of the envoplakin and/or periplakin bands in immunoblotting. Two clinicopathologic and two biologic features had high specificity (87%-100%) but poor sensitivity (27%-59%): (1) clinical presentation associating erosive oral lesions with erythema multiforme-like, bullous pemphigoid-like, or lichen planus-like cutaneous lesions; (2) histologic picture of suprabasal acantholysis with keratinocyte necrosis, interface changes, or lichenoid infiltrate; (3) presence of both anti-epithelial cell surface and anti-basement membrane zone antibodies by IIF; and (4) recognition of the desmoplakin I and/or BPAG1 bands in immunoblotting. Interestingly, 45% of patients with PNP presented initially with isolated oral erosions that were undistinguishable from those seen in PV patients, and 27% had histologic findings of only suprabasal acantholysis, which was in accordance with the frequent detection of anti-desmoglein 3 antibodies in PNP sera. The association with

Constructing Patient Specific Clinical Trajectories from Electronic Healthcare Reimbursement Claims using Sequential Pattern Mining

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

Pullum, Laura L; Hobson, Tanner C

We examine the use of electronic healthcare reimbursement claims (EHRC) for analyzing healthcare delivery and practice patterns across the United States (US). By analyzing over 1 billion EHRCs, we track patterns of clinical procedures administered to patients with heart disease (HD) using sequential pattern mining algorithms. Our analyses reveal that the clinical procedures performed on HD patients are highly varied leading up to and after the primary diagnosis. The discovered clinical procedure sequences reveal significant differences in the overall costs incurred across different parts of the US, indicating significant heterogeneity in treating HD patients. We show that a data-driven approachmore » to understand patient specific clinical trajectories constructed from EHRC can provide quantitative insights into how to better manage and treat patients.« less

Transcriptome Analysis of Mycobacteria-Specific CD4+ T Cells Identified by Activation-Induced Expression of CD154.

PubMed

Kunnath-Velayudhan, Shajo; Goldberg, Michael F; Saini, Neeraj K; Johndrow, Christopher T; Ng, Tony W; Johnson, Alison J; Xu, Jiayong; Chan, John; Jacobs, William R; Porcelli, Steven A

2017-10-01

Analysis of Ag-specific CD4 + T cells in mycobacterial infections at the transcriptome level is informative but technically challenging. Although several methods exist for identifying Ag-specific T cells, including intracellular cytokine staining, cell surface cytokine-capture assays, and staining with peptide:MHC class II multimers, all of these have significant technical constraints that limit their usefulness. Measurement of activation-induced expression of CD154 has been reported to detect live Ag-specific CD4 + T cells, but this approach remains underexplored and, to our knowledge, has not previously been applied in mycobacteria-infected animals. In this article, we show that CD154 expression identifies adoptively transferred or endogenous Ag-specific CD4 + T cells induced by Mycobacterium bovis bacillus Calmette-Guérin vaccination. We confirmed that Ag-specific cytokine production was positively correlated with CD154 expression by CD4 + T cells from bacillus Calmette-Guérin-vaccinated mice and show that high-quality microarrays can be performed from RNA isolated from CD154 + cells purified by cell sorting. Analysis of microarray data demonstrated that the transcriptome of CD4 + CD154 + cells was distinct from that of CD154 - cells and showed major enrichment of transcripts encoding multiple cytokines and pathways of cellular activation. One notable finding was the identification of a previously unrecognized subset of mycobacteria-specific CD4 + T cells that is characterized by the production of IL-3. Our results support the use of CD154 expression as a practical and reliable method to isolate live Ag-specific CD4 + T cells for transcriptomic analysis and potentially for a range of other studies in infected or previously immunized hosts. Copyright © 2017 by The American Association of Immunologists, Inc.

The ability of clinical balance measures to identify falls risk in multiple sclerosis: a systematic review and meta-analysis.

PubMed

Quinn, Gillian; Comber, Laura; Galvin, Rose; Coote, Susan

2018-05-01

To determine the ability of clinical measures of balance to distinguish fallers from non-fallers and to determine their predictive validity in identifying those at risk of falls. AMED, CINAHL, Medline, Scopus, PubMed Central and Google Scholar. First search: July 2015. Final search: October 2017. Inclusion criteria were studies of adults with a definite multiple sclerosis diagnosis, a clinical balance assessment and method of falls recording. Data were extracted independently by two reviewers. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 scale and the modified Newcastle-Ottawa Quality Assessment Scale. Statistical analysis was conducted for the cross-sectional studies using Review Manager 5. The mean difference with 95% confidence interval in balance outcomes between fallers and non-fallers was used as the mode of analysis. We included 33 studies (19 cross-sectional, 5 randomised controlled trials, 9 prospective) with a total of 3901 participants, of which 1917 (49%) were classified as fallers. The balance measures most commonly reported were the Berg Balance Scale, Timed Up and Go and Falls Efficacy Scale International. Meta-analysis demonstrated fallers perform significantly worse than non-fallers on all measures analysed except the Timed Up and Go Cognitive ( p < 0.05), but discriminative ability of the measures is commonly not reported. Of those reported, the Activities-specific Balance Confidence Scale had the highest area under the receiver operating characteristic curve value (0.92), but without reporting corresponding measures of clinical utility. Clinical measures of balance differ significantly between fallers and non-fallers but have poor predictive ability for falls risk in people with multiple sclerosis.

The impact of case specificity and generalisable skills on clinical performance: a correlated traits-correlated methods approach.

PubMed

Wimmers, Paul F; Fung, Cha-Chi

2008-06-01

The finding of case or content specificity in medical problem solving moved the focus of research away from generalisable skills towards the importance of content knowledge. However, controversy about the content dependency of clinical performance and the generalisability of skills remains. This study aimed to explore the relative impact of both perspectives (case specificity and generalisable skills) on different components (history taking, physical examination, communication) of clinical performance within and across cases. Data from a clinical performance examination (CPX) taken by 350 Year 3 students were used in a correlated traits-correlated methods (CTCM) approach using confirmatory factor analysis, whereby 'traits' refers to generalisable skills and 'methods' to individual cases. The baseline CTCM model was analysed and compared with four nested models using structural equation modelling techniques. The CPX consisted of three skills components and five cases. Comparison of the four different models with the least-restricted baseline CTCM model revealed that a model with uncorrelated generalisable skills factors and correlated case-specific knowledge factors represented the data best. The generalisable processes found in history taking, physical examination and communication were responsible for half the explained variance, in comparison with the variance related to case specificity. Conclusions Pure knowledge-based and pure skill-based perspectives on clinical performance both seem too one-dimensional and new evidence supports the idea that a substantial amount of variance contributes to both aspects of performance. It could be concluded that generalisable skills and specialised knowledge go hand in hand: both are essential aspects of clinical performance.

Discordance between MTB/RIF and Real-Time Tuberculosis-Specific Polymerase Chain Reaction Assay in Bronchial Washing Specimen and Its Clinical Implications.

PubMed

Jo, Yong Suk; Park, Ju-Hee; Lee, Jung Kyu; Heo, Eun Young; Chung, Hee Soon; Kim, Deog Kyeom

2016-01-01

The prevalence and clinical implications of discordance between Xpert MTB/RIF assays and the AdvanSure TB/NTM real-time polymerase chain reaction (PCR) for bronchial washing specimens have not been studied in pulmonary TB (PTB) patients. The discordant proportion and its clinical impact were evaluated in 320 patients from the bronchoscopy registry whose bronchial washing specimens were tested simultaneously with Xpert MTB/RIF and the TB/NTM PCR assay for three years, and the accuracy of the assays, including the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), were studied. The clinical risk factors for discordance and false positivity of assays were also studied. Among 130 patients who were clinically diagnosed with PTB, 64 patients showed positive acid-fast bacilli culture results, 56 patients showed positive results in molecular methods and clinician diagnosed PTB without results of microbiology in 10 patients. The sensitivity, specificity, PPV, and NPV were 80.0%, 98.95%, 98.1%, and 87.9%, respectively, for Xpert MTB/RIF and 81.5%, 92.6%, 88.3%, and 88.0%, respectively, for TB/NTM PCR. The discordant proportion was 16.9% and was higher in culture-negative PTB compared to culture-confirmed PTB (24.3% vs. 9.4%, p = 0.024). However, there were no significant differences in the clinical characteristics, regardless of the discordance. The diagnostic yield increased with an additional assay (7.7% for Xpert MTB/RIF and 9.2% for TB/NTM PCR). False positivity was less common in patients tested with Xpert MTB/RIF (1.05% vs. 7.37%, p = 0.0035). No host-related risk factor for false positivity was identified. The Xpert MTB/RIF and TB/NTM PCR assay in bronchial washing specimens can improve the diagnostic yields for PTB, although there were considerable discordant results without any patient-related risk factors.

Clustering of self-organizing map identifies five distinct medulloblastoma subgroups.

PubMed

Cao, Changjun; Wang, Wei; Jiang, Pucha

2016-01-01

Medulloblastoma is one the most malignant paediatric brain tumours. Molecular subgrouping these medulloblastomas will not only help identify specific cohorts for certain treatment but also improve confidence in prognostic prediction. Currently, there is a consensus of the existences of four distinct subtypes of medulloblastoma. We proposed a novel bioinformatics method, clustering of self-organizing map, to determine the subgroups and their molecular diversity. Microarray expression profiles of 46 medulloblastoma samples were analysed and five clusters with distinct demographics, clinical outcome and transcriptional profiles were identified. The previously reported Wnt subgroup was identified as expected. Three other novel subgroups were proposed for later investigation. Our findings underscore the value of SOM clustering for discovering the medulloblastoma subgroups. When the suggested subdivision has been confirmed in large cohorts, this method should serve as a part of routine classification of clinical samples.

Sex-specific issues in eating disorders: a clinical and psychopathological investigation.

PubMed

Valente, Stefano; Di Girolamo, Giulia; Forlani, Martina; Biondini, Anna; Scudellari, Paolo; De Ronchi, Diana; Atti, Anna Rita

2017-12-01

To highlight the characteristics of eating disorders (ED) in males, with particular attention to sex-related clinical features and psychiatric co-morbidities. Out of 280 persons, referred to our outpatients ED clinic between January 2011 and June 2014, 267 with complete information were included in this retrospective observational study. The men/women ratio was one to five (male 16.5% vs female 83.5%) with an increasing proportion of male patients over the years. The most frequent ED in males was binge eating disorder, whereas in females anorexia nervosa and bulimia nervosa prevailed. Excessive exercising and fasting were the most common compensation behaviours in males; while self-induced vomiting and laxative-diuretic abuse were more typical in females. Among women, the most represented psychiatric co-morbidities were mood and somatoform disorders, whereas among men, anxiety and psychosis spectrum disorders were the most frequent ones. Borderline and histrionic personality disorders were prevalent in female ED, while narcissistic and antisocial personality disorders prevailed in males. ED in men is a growing phenomenon. Male ED, compared to female ED, show differences in clinical presentation, symptoms and co-morbidities. Despite the use of clinical and psychometric evaluating tools targeting female patients, sex differences do exist and additional studies are required to investigate male specific issues in ED. Level of Evidence Level V, cross-sectional descriptive study.

Identifying context-specific competencies required by community Australian Football sports trainers.

PubMed

Donaldson, Alex; Finch, Caroline F

2012-08-01

First-aid is a recommended injury prevention and risk management strategy in community sport; however, little is known about the sport-specific competencies required by first-aid providers. To achieve expert consensus on the competencies required by community Australian Football (community-AF) sports trainers. A three-round online Delphi process. Community-AF. 16 Australian sports first-aid and community-AF experts. Rating of competencies as either 'essential', 'expected', 'ideal' or 'not required'. Results After Round 3, 47 of the 77 (61%) competencies were endorsed as 'essential' or 'expected' for a sports trainer to effectively perform the activities required to the standards expected at a community-AF club by ≥75% of experts. These competencies covered: the role of the sports trainer; the responsibilities of the sports trainer; emergency management; injury and illness assessment and immediate management; taping; and injury prevention and risk management. Four competencies (5%) were endorsed as 'ideal' or 'not required' by ≥85% of experts and were excluded from further consideration. The 26 competencies where consensus was not reached were retained as second-tier, optional competencies. Sports trainers are important members of on-field first-aid teams, providing support to both injured players and other sports medicine professionals. The competencies identified in this study provide the basis of a proposed two-tiered community-AF-specific sports trainer education structure that can be implemented by the peak sports body. This includes six mandatory modules, relating to the 'required' competencies, and a further six optional modules covering competencies on which consensus was not reached.

MONKEY: Identifying conserved transcription-factor binding sitesin multiple alignments using a binding site-specific evolutionarymodel

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

Moses, Alan M.; Chiang, Derek Y.; Pollard, Daniel A.

2004-10-28

We introduce a method (MONKEY) to identify conserved transcription-factor binding sites in multispecies alignments. MONKEY employs probabilistic models of factor specificity and binding site evolution, on which basis we compute the likelihood that putative sites are conserved and assign statistical significance to each hit. Using genomes from the genus Saccharomyces, we illustrate how the significance of real sites increases with evolutionary distance and explore the relationship between conservation and function.

A systematic literature search to identify performance measure outcomes used in clinical studies of racehorses.

PubMed

Wylie, C E; Newton, J R

2018-05-01

Racing performance is often used as a measurable outcome variable in research studies investigating clinical diagnoses or interventions. However, the use of many different performance measures largely precludes conduct of meaningful comparative studies and, to date, those being used have not been collated. To systematically review the veterinary scientific literature for the use of racing performance as a measurable outcome variable in clinical studies of racehorses, collate and identify those most popular, and identify their advantages and disadvantages. Systematic literature search. The search criteria "((racing AND performance) AND (horses OR equidae))" were adapted for both MEDLINE and CAB Abstracts databases. Data were collected in standardised recording forms for binary, categorical and quantitative measures, and the use of performance indices. In total, 217 studies that described racing performance were identified, contributing 117 different performance measures. No one performance measure was used in all studies, despite 90.3% using more than one variable. Data regarding race starts and earnings were used most commonly, with 88.0% and 54.4% of studies including at least one measure of starts and earnings, respectively. Seventeen variables were used 10 times or more, with the top five comprising: 'return to racing', 'number of starts', 'days to first start', 'earnings per period of time' and 'earnings per start'. The search strategies may not have identified all relevant papers, introducing bias to the review. Performance indices have been developed to improve assessment of interventions; however, they are not widely adopted in the scientific literature. Use of the two most commonly identified measures, whether the horse returned to racing and number of starts over a defined period of time, would best facilitate future systematic reviews and meta-analyses in advance of the development of a gold-standard measure of race performance outcome. © 2017 EVJ Ltd.

IDO and galectin-3 hamper the ex vivo generation of clinical grade tumor-specific T cells for adoptive cell therapy in metastatic melanoma.

PubMed

Melief, Sara M; Visser, Marten; van der Burg, Sjoerd H; Verdegaal, Els M E

2017-07-01

Adoptive T cell transfer (ACT) with ex vivo-expanded tumor-reactive T cells proved to be successful for the treatment of metastatic melanoma patients. Mixed lymphocyte tumor cell cultures (MLTC) can be used to generate tumor-specific T cells for ACT; however, in a number of cases tumor-reactive T cell, expansion is far from optimal. We hypothesized that this is due to tumor intrinsic and extrinsic factors and aimed to identify and manipulate these factors so to optimize our clinical, GMP-compliant MLTC protocol. We found that the tumor cell produced IDO and/or galectin-3, and the accumulation of CD4 + CD25 hi FoxP3 + T cells suppressed the expansion of tumor-specific T cells in the MLTC. Strategies to eliminate CD4 + CD25 hi FoxP3 + T cells during culture required the depletion of the whole CD4 + T cell population and were found to be undesirable. Blocking of IDO and galectin-3 was feasible and resulted in improved efficiency of the MLTC. Implementation of these findings in clinical protocols for ex vivo expansion of tumor-reactive T cells holds promise for an increased therapeutic potential of adoptive cell transfer treatments with tumor-specific T cells.

Genome-wide meta-analysis identifies novel gender specific loci associated with thyroid antibodies level in Croatians.

PubMed

Matana, Antonela; Popović, Marijana; Boutin, Thibaud; Torlak, Vesela; Brdar, Dubravka; Gunjača, Ivana; Kolčić, Ivana; Boraska Perica, Vesna; Punda, Ante; Polašek, Ozren; Hayward, Caroline; Barbalić, Maja; Zemunik, Tatijana

2018-04-18

Autoimmune thyroid diseases (AITD) are multifactorial endocrine diseases most frequently accompanied by Tg and TPO autoantibodies. Both antibodies have a higher prevalence in females and act under a strong genetic influence. To identify novel variants underlying thyroid antibody levels, we performed GWAS meta-analysis on the plasma levels of TgAb and TPOAb in three Croatian cohorts, as well as gender specific GWAS and a bivariate analysis. No significant association was detected with the level of TgAb and TPOAb in the meta-analysis of GWAS or bivariate results for all individuals. The bivariate analysis in females only revealed a genome-wide significant association for the locus near GRIN3A (rs4457391, P = 7.76 × 10 -9 ). The same locus had borderline association with TPOAb levels in females (rs1935377, P = 8.58 × 10 -8 ). In conclusion, we identified a novel gender specific locus associated with TgAb and TPOAb levels. Our findings provide a novel insight into genetic and gender differences associated with thyroid antibodies. Copyright © 2018 Elsevier Inc. All rights reserved.

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

Binding specificity of anti-HNK-1 IgM M-protein in anti-MAG neuropathy: possible clinical relevance.

PubMed

Hamada, Yukihiro; Hirano, Makito; Kuwahara, Motoi; Samukawa, Makoto; Takada, Kazuo; Morise, Jyoji; Yabuno, Keiko; Oka, Shogo; Kusunoki, Susumu

2015-02-01

Anti-myelin-associated-glycoprotein (MAG) neuropathy is an intractable autoimmune polyneuropathy. The antigenic region of MAG is the human natural killer-1 (HNK-1) carbohydrate. We and others previously suggested that the extension of antibody reactivities to HNK-1-bearing proteins other than MAG was associated with treatment resistance, without statistical analyses. In this study, we established an ELISA method with recombinant proteins to test binding specificities of currently available monoclonal antibodies to MAG and another HNK-1-bearing protein, phosphacan. Using this system, we found the distinct binding specificities of anti-MAG antibody in 19 patients with anti-MAG neuropathy. Their clinical relevance was then determined retrospectively with the adjusted 10-points INCAT disability score (0 = normal and 10 = highly disable). The results showed that strong reactivities of anti-MAG antibodies to phosphacan were significantly associated with treatment resistance or progressive clinical courses, indicating a possible clinical relevance of the binding specificities. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

GSHSite: Exploiting an Iteratively Statistical Method to Identify S-Glutathionylation Sites with Substrate Specificity

PubMed Central

Chen, Yi-Ju; Lu, Cheng-Tsung; Huang, Kai-Yao; Wu, Hsin-Yi; Chen, Yu-Ju; Lee, Tzong-Yi

2015-01-01

S-glutathionylation, the covalent attachment of a glutathione (GSH) to the sulfur atom of cysteine, is a selective and reversible protein post-translational modification (PTM) that regulates protein activity, localization, and stability. Despite its implication in the regulation of protein functions and cell signaling, the substrate specificity of cysteine S-glutathionylation remains unknown. Based on a total of 1783 experimentally identified S-glutathionylation sites from mouse macrophages, this work presents an informatics investigation on S-glutathionylation sites including structural factors such as the flanking amino acids composition and the accessible surface area (ASA). TwoSampleLogo presents that positively charged amino acids flanking the S-glutathionylated cysteine may influence the formation of S-glutathionylation in closed three-dimensional environment. A statistical method is further applied to iteratively detect the conserved substrate motifs with statistical significance. Support vector machine (SVM) is then applied to generate predictive model considering the substrate motifs. According to five-fold cross-validation, the SVMs trained with substrate motifs could achieve an enhanced sensitivity, specificity, and accuracy, and provides a promising performance in an independent test set. The effectiveness of the proposed method is demonstrated by the correct identification of previously reported S-glutathionylation sites of mouse thioredoxin (TXN) and human protein tyrosine phosphatase 1b (PTP1B). Finally, the constructed models are adopted to implement an effective web-based tool, named GSHSite (http://csb.cse.yzu.edu.tw/GSHSite/), for identifying uncharacterized GSH substrate sites on the protein sequences. PMID:25849935

Use of mass spectrometry fingerprinting to identify urinary metabolites after consumption of specific foods.

PubMed

Lloyd, Amanda J; Favé, Gaëlle; Beckmann, Manfred; Lin, Wanchang; Tailliart, Kathleen; Xie, Long; Mathers, John C; Draper, John

2011-10-01

The lack of robust biological markers of dietary exposure hinders the quantitative understanding of causal relations between diet and health. We aimed to develop an efficient procedure to discover metabolites in urine that may have future potential as biomarkers of acute exposure to foods of high public health importance. Twenty-four participants were provided with a test breakfast in which the cereal component of a standardized breakfast was replaced by 1 of 4 foods of high public health importance; 1.5-, 3-, and 4.5-h postprandial urine samples were collected. Flow infusion electrospray-ionization mass spectrometry followed by supervised multivariate data analysis was used to discover signals resulting from consumption of each test food. Fasted-state urine samples provided a universal comparator for food biomarker lead discovery in postprandial urine. The filtering of data features associated with consumption of the common components of the standardized breakfast improved discrimination models and readily identified metabolites that showed consumption of specific test foods. A combination of trimethylamine-N-oxide and 1-methylhistidine was associated with salmon consumption. Novel ascorbate derivatives were discovered in urine after consumption of either broccoli or raspberries. Sulphonated caffeic acid and sulphonated methyl-epicatechin concentrations increased dramatically after consumption of raspberries. This biomarker lead discovery strategy can identify urinary metabolites associated with acute exposure to individual foods. Future studies are required to validate the specificity and utility of potential biomarkers in an epidemiologic context.

An in silico method to identify computer-based protocols worthy of clinical study: An insulin infusion protocol use case

PubMed Central

Wong, Anthony F; Pielmeier, Ulrike; Haug, Peter J; Andreassen, Steen

2016-01-01

Objective Develop an efficient non-clinical method for identifying promising computer-based protocols for clinical study. An in silico comparison can provide information that informs the decision to proceed to a clinical trial. The authors compared two existing computer-based insulin infusion protocols: eProtocol-insulin from Utah, USA, and Glucosafe from Denmark. Materials and Methods The authors used eProtocol-insulin to manage intensive care unit (ICU) hyperglycemia with intravenous (IV) insulin from 2004 to 2010. Recommendations accepted by the bedside clinicians directly link the subsequent blood glucose values to eProtocol-insulin recommendations and provide a unique clinical database. The authors retrospectively compared in silico 18 984 eProtocol-insulin continuous IV insulin infusion rate recommendations from 408 ICU patients with those of Glucosafe, the candidate computer-based protocol. The subsequent blood glucose measurement value (low, on target, high) was used to identify if the insulin recommendation was too high, on target, or too low. Results Glucosafe consistently provided more favorable continuous IV insulin infusion rate recommendations than eProtocol-insulin for on target (64% of comparisons), low (80% of comparisons), or high (70% of comparisons) blood glucose. Aggregated eProtocol-insulin and Glucosafe continuous IV insulin infusion rates were clinically similar though statistically significantly different (Wilcoxon signed rank test P = .01). In contrast, when stratified by low, on target, or high subsequent blood glucose measurement, insulin infusion rates from eProtocol-insulin and Glucosafe were statistically significantly different (Wilcoxon signed rank test, P < .001), and clinically different. Discussion This in silico comparison appears to be an efficient nonclinical method for identifying promising computer-based protocols. Conclusion Preclinical in silico comparison analytical framework allows rapid and inexpensive

Using Symptom and Interference Questionnaires to Identify Recovery Among Children With Anxiety Disorders

PubMed Central

2016-01-01

Questionnaires are widely used in routine clinical practice to assess treatment outcomes for children with anxiety disorders. This study was conducted to determine whether 2 widely used child and parent report questionnaires of child anxiety symptoms and interference (Spence Child Anxiety Scale [SCAS-C/P] and Child Anxiety Impact Scale [CAIS-C/P]) accurately identify recovery from common child anxiety disorder diagnoses as measured by a ‘gold-standard’ diagnostic interview. Three hundred thirty-seven children (7–12 years, 51% female) and their parents completed the ADIS-IV-C/P diagnostic interview and questionnaire measures (SCAS-C/P and CAIS-C/P) before (Time 1) and after (Time 2) treatment or wait-list. Time 2 parent reported interference (CAIS-P) was found to be a good predictor of absence of any diagnoses (area under the curve [AUC] = .81). In terms of specific diagnoses, Time 2 SCAS-C/P separation anxiety subscale (SCAS-C/P-SA) identified recovery from separation anxiety disorder well (SCAS-C-SA, AUC = .80; SCAS-P-SA, AUC = .82) as did the CAIS-P (AUC = .79). The CAIS-P also successfully identified recovery from social phobia (AUC = .78) and generalized anxiety disorder (AUC = .76). These AUC values were supported by moderate to good sensitivity (.70–.78) and specificity (.70–.73) at the best identified cut-off scores. None of the measures successfully identified recovery from specific phobia. The results suggest that questionnaire measures, particularly the CAIS-P, can be used to identify whether children have recovered from common anxiety disorders, with the exception of specific phobias. Cut-off scores have been identified that can guide the use of routine outcome measures in clinical practice. PMID:27845527

Using symptom and interference questionnaires to identify recovery among children with anxiety disorders.

PubMed

Evans, Rachel; Thirlwall, Kerstin; Cooper, Peter; Creswell, Cathy

2017-07-01

Questionnaires are widely used in routine clinical practice to assess treatment outcomes for children with anxiety disorders. This study was conducted to determine whether 2 widely used child and parent report questionnaires of child anxiety symptoms and interference (Spence Child Anxiety Scale [SCAS-C/P] and Child Anxiety Impact Scale [CAIS-C/P]) accurately identify recovery from common child anxiety disorder diagnoses as measured by a 'gold-standard' diagnostic interview. Three hundred thirty-seven children (7-12 years, 51% female) and their parents completed the ADIS-IV-C/P diagnostic interview and questionnaire measures (SCAS-C/P and CAIS-C/P) before (Time 1) and after (Time 2) treatment or wait-list. Time 2 parent reported interference (CAIS-P) was found to be a good predictor of absence of any diagnoses (area under the curve [AUC] = .81). In terms of specific diagnoses, Time 2 SCAS-C/P separation anxiety subscale (SCAS-C/P-SA) identified recovery from separation anxiety disorder well (SCAS-C-SA, AUC = .80; SCAS-P-SA, AUC = .82) as did the CAIS-P (AUC = .79). The CAIS-P also successfully identified recovery from social phobia (AUC = .78) and generalized anxiety disorder (AUC = .76). These AUC values were supported by moderate to good sensitivity (.70-.78) and specificity (.70-.73) at the best identified cut-off scores. None of the measures successfully identified recovery from specific phobia. The results suggest that questionnaire measures, particularly the CAIS-P, can be used to identify whether children have recovered from common anxiety disorders, with the exception of specific phobias. Cut-off scores have been identified that can guide the use of routine outcome measures in clinical practice. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Development of peptide-based lineage-specific serology for chronic Chagas disease: geographical and clinical distribution of epitope recognition.

PubMed

Bhattacharyya, Tapan; Falconar, Andrew K; Luquetti, Alejandro O; Costales, Jaime A; Grijalva, Mario J; Lewis, Michael D; Messenger, Louisa A; Tran, Trang T; Ramirez, Juan-David; Guhl, Felipe; Carrasco, Hernan J; Diosque, Patricio; Garcia, Lineth; Litvinov, Sergey V; Miles, Michael A

2014-05-01

Chagas disease, caused by infection with the protozoan Trypanosoma cruzi, remains a serious public health issue in Latin America. Genetically diverse, the species is sub-divided into six lineages, known as TcI-TcVI, which have disparate geographical and ecological distributions. TcII, TcV, and TcVI are associated with severe human disease in the Southern Cone countries, whereas TcI is associated with cardiomyopathy north of the Amazon. T. cruzi persists as a chronic infection, with cardiac and/or gastrointestinal symptoms developing years or decades after initial infection. Identifying an individual's history of T. cruzi lineage infection directly by genotyping of the parasite is complicated by the low parasitaemia and sequestration in the host tissues. We have applied here serology against lineage-specific epitopes of the T. cruzi surface antigen TSSA, as an indirect approach to allow identification of infecting lineage. Chagasic sera from chronic patients from a range of endemic countries were tested by ELISA against synthetic peptides representing lineage-specific TSSA epitopes bound to avidin-coated ELISA plates via a biotin labelled polyethylene glycol-glycine spacer to increase rotation and ensure each amino acid side chain could freely interact with their antibodies. 79/113 (70%) of samples from Brazil, Bolivia, and Argentina recognised the TSSA epitope common to lineages TcII/TcV/TcVI. Comparison with clinical information showed that a higher proportion of Brazilian TSSApep-II/V/VI responders had ECG abnormalities than non-responders (38% vs 17%; p<0.0001). Among northern chagasic sera 4/20 (20%) from Ecuador reacted with this peptide; 1/12 Venezuelan and 1/34 Colombian samples reacted with TSSApep-IV. In addition, a proposed TcI-specific epitope, described elsewhere, was demonstrated here to be highly conserved across lineages and therefore not applicable to lineage-specific serology. These results demonstrate the considerable potential for synthetic

Approach for Identifying Human Leukocyte Antigen (HLA)-DR Bound Peptides from Scarce Clinical Samples *

PubMed Central

Heyder, Tina; Kohler, Maxie; Tarasova, Nataliya K.; Haag, Sabrina; Rutishauser, Dorothea; Rivera, Natalia V.; Sandin, Charlotta; Mia, Sohel; Malmström, Vivianne; Wheelock, Åsa M.; Wahlström, Jan; Holmdahl, Rikard; Eklund, Anders; Zubarev, Roman A.; Grunewald, Johan; Ytterberg, A. Jimmy

2016-01-01

Immune-mediated diseases strongly associating with human leukocyte antigen (HLA) alleles are likely linked to specific antigens. These antigens are presented to T cells in the form of peptides bound to HLA molecules on antigen presenting cells, e.g. dendritic cells, macrophages or B cells. The identification of HLA-DR-bound peptides presents a valuable tool to investigate the human immunopeptidome. The lung is likely a key player in the activation of potentially auto-aggressive T cells prior to entering target tissues and inducing autoimmune disease. This makes the lung of exceptional interest and presents an ideal paradigm to study the human immunopeptidome and to identify antigenic peptides. Our previous investigation of HLA-DR peptide presentation in the lung required high numbers of cells (800 × 106 bronchoalveolar lavage (BAL) cells). Because BAL from healthy nonsmokers typically contains 10–15 × 106 cells, there is a need for a highly sensitive approach to study immunopeptides in the lungs of individual patients and controls. In this work, we analyzed the HLA-DR immunopeptidome in the lung by an optimized methodology to identify HLA-DR-bound peptides from low cell numbers. We used an Epstein-Barr Virus (EBV) immortalized B cell line and bronchoalveolar lavage (BAL) cells obtained from patients with sarcoidosis, an inflammatory T cell driven disease mainly occurring in the lung. Specifically, membrane complexes were isolated prior to immunoprecipitation, eluted peptides were identified by nanoLC-MS/MS and processed using the in-house developed ClusterMHCII software. With the optimized procedure we were able to identify peptides from 10 × 106 cells, which on average correspond to 10.9 peptides/million cells in EBV-B cells and 9.4 peptides/million cells in BAL cells. This work presents an optimized approach designed to identify HLA-DR-bound peptides from low numbers of cells, enabling the investigation of the BAL immunopeptidome from individual patients and

WE-D-204-01: Site-Specific Clinical Rotation: Into the Minds of the Radiation Oncologists

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

Hendrickson, K.

2016-06-15

Speakers in this session will present overview and details of a specific rotation or feature of their Medical Physics Residency Program that is particularly exceptional and noteworthy. The featured rotations include foundational topics executed with exceptional acumen and innovative educational rotations perhaps not commonly found in Medical Physics Residency Programs. A site-specific clinical rotation will be described, where the medical physics resident follows the physician and medical resident for two weeks into patient consultations, simulation sessions, target contouring sessions, planning meetings with dosimetry, patient follow up visits, and tumor boards, to gain insight into the thought processes of the radiationmore » oncologist. An incident learning rotation will be described where the residents learns about and practices evaluating clinical errors and investigates process improvements for the clinic. The residency environment at a Canadian medical physics residency program will be described, where the training and interactions with radiation oncology residents is integrated. And the first month rotation will be described, where the medical physics resident rotates through the clinical areas including simulation, dosimetry, and treatment units, gaining an overview of the clinical flow and meeting all the clinical staff to begin the residency program. This session will be of particular interest to residency programs who are interested in adopting or adapting these curricular ideas into their programs and to residency candidates who want to learn about programs already employing innovative practices. Learning Objectives: To learn about exceptional and innovative clinical rotations or program features within existing Medical Physics Residency Programs. To understand how to adopt/adapt innovative curricular designs into your own Medical Physics Residency Program, if appropriate.« less

Reduced Clostridium difficile Tests and Laboratory-Identified Events With a Computerized Clinical Decision Support Tool and Financial Incentive.

PubMed

Madden, Gregory R; German Mesner, Ian; Cox, Heather L; Mathers, Amy J; Lyman, Jason A; Sifri, Costi D; Enfield, Kyle B

2018-06-01

We hypothesized that a computerized clinical decision support tool for Clostridium difficile testing would reduce unnecessary inpatient tests, resulting in fewer laboratory-identified events. Census-adjusted interrupted time-series analyses demonstrated significant reductions of 41% fewer tests and 31% fewer hospital-onset C. difficile infection laboratory-identified events following this intervention.Infect Control Hosp Epidemiol 2018;39:737-740.

Identification of ssDNA aptamers specific to clinical isolates of Streptococcus mutans strains with different cariogenicity.

PubMed

Cui, Wei; Liu, Jiaojiao; Su, Donghua; Hu, Danyang; Hou, Shuai; Hu, Tongnan; Yang, Jiyong; Luo, Yanping; Xi, Qing; Chu, Bingfeng; Wang, Chenglong

2016-06-01

Streptococcus mutans, a Gram-positive facultative anaerobic bacterium, is considered to be a major etiological factor for dental caries. In this study, plaques from dental enamel surfaces of caries-active and caries-free individuals were obtained and cultivated for S. mutans isolation. Morphology examination, biochemical characterization, and polymerase chain reaction were performed to identify S. mutans The cariogenicity of S. mutans strains isolated from clinical specimens was evaluated by testing the acidogenicity, aciduricity, extracellular polysaccharide production, and adhesion ability of the bacteria. Finally, subtractive SELEX (systematic evolution of ligands by exponential enrichment) technology targeting whole intact cells was used to screen for ssDNA aptamers specific to the strains with high cariogenicity. After nine rounds of subtractive SELEX, sufficient pool enrichment was achieved as shown by radioactive isotope analysis. The enriched pool was cloned and sequenced randomly, followed by MEME online and RNA structure software analysis of the sequences. Results from the flow cytometry indicated that aptamers H1, H16, H4, L1, L10, and H19 could discriminate highly cariogenic S. mutans strains from poorly cariogenic strains. Among these, Aptamer H19 had the strongest binding capacity with cariogenic S. mutans strains with a dissociation constant of 69.45 ± 38.53 nM. In conclusion, ssDNA aptamers specific to highly cariogenic clinical S. mutans strains were successfully obtained. These ssDNA aptamers might be used for the early diagnosis and treatment of dental caries. © The Author 2016. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Using the Karolinska Sleep Questionnaire to identify obstructive sleep apnea syndrome in a sleep clinic population.

PubMed

Westerlund, Anna; Brandt, Lena; Harlid, Richard; Åkerstedt, Torbjörn; Lagerros, Ylva Trolle

2014-10-01

In Scandinavia, portable monitoring has virtually replaced standard polysomnography for diagnosis of obstructive sleep apnea syndrome (OSAS). Because waiting times for specialized OSAS care remain long, an accurate screening tool to exclude low-risk patients from diagnostic testing would be valuable. To examine the diagnostic accuracy of the Karolinska Sleep Questionnaire (KSQ) for OSAS. Consecutive patients, 30–66 years old, attending a large sleep clinic in Sweden for OSAS evaluation completed the KSQ and underwent in-home portable monitoring and medical history evaluation. OSAS was defined as apnea-hypopnea index ≥5 with symptoms of disease. We calculated sensitivity and specificity of apnea/snoring and sleepiness indices of the KSQ. Retrospectively, we combined six KSQ items (snoring, breathing cessations, disturbed sleep, etc.) and four clinical variables (age, sex, body mass index, smoking status) predictive of OSAS into a new instrument, which we also evaluated. Instrument score ranged between 0 and 21; a higher score indicated more severe symptoms. Of 103 patients, 62 were diagnosed with OSAS. Sensitivity and specificity of the indices were 0.56 and 0.68 (apnea/snoring), and 0.37 and 0.71 (sleepiness). The new instrument performed optimally at a score of 9. Sensitivity was 0.76 (95% confidence interval 0.63–0.86) and specificity 0.88 (0.74–0.96). Between 19.4% and 50.5% of patients were unaware of having apnea/snoring symptoms. Diagnostic accuracy of the apnea/snoring and sleepiness indices for OSAS was poor but could be improved by combining clinical and KSQ items. The usefulness of the apnea/snoring index and the combined instrument was questionable because of extensive symptom unawareness.

Coupling Genetics and Proteomics To Identify Aphid Proteins Associated with Vector-Specific Transmission of Polerovirus (Luteoviridae)▿

PubMed Central

Yang, Xiaolong; Thannhauser, T. W.; Burrows, Mary; Cox-Foster, Diana; Gildow, Fred E.; Gray, Stewart M.

2008-01-01

Cereal yellow dwarf virus-RPV (CYDV-RPV) is transmitted specifically by the aphids Rhopalosiphum padi and Schizaphis graminum in a circulative nonpropagative manner. The high level of vector specificity results from the vector aphids having the functional components of the receptor-mediated endocytotic pathways to allow virus to transverse the gut and salivary tissues. Studies of F2 progeny from crosses of vector and nonvector genotypes of S. graminum showed that virus transmission efficiency is a heritable trait regulated by multiple genes acting in an additive fashion and that gut- and salivary gland-associated factors are not genetically linked. Utilizing two-dimensional difference gel electrophoresis to compare the proteomes of vector and nonvector parental and F2 genotypes, four aphid proteins (S4, S8, S29, and S405) were specifically associated with the ability of S. graminum to transmit CYDV-RPV. The four proteins were coimmunoprecipitated with purified RPV, indicating that the aphid proteins are capable of binding to virus. Analysis by mass spectrometry identified S4 as a luciferase and S29 as a cyclophilin, both of which have been implicated in macromolecular transport. Proteins S8 and S405 were not identified from available databases. Study of this unique genetic system coupled with proteomic analysis indicated that these four virus-binding aphid proteins were specifically inherited and conserved in different generations of vector genotypes and suggests that they play a major role in regulating polerovirus transmission. PMID:17959668

Rare myositis-specific autoantibody associations among Hungarian patients with idiopathic inflammatory myopathy.

PubMed

Bodoki, L; Nagy-Vincze, M; Griger, Z; Betteridge, Z; Szöllősi, L; Jobanputra, R; Dankó, K

2015-01-01

Idiopathic inflammatory myopathies are systemic, chronic autoimmune diseases characterized by symmetrical, proximal muscle weakness. Homogeneous groups present with similar symptoms. The response to therapy and prognosis could be facilitated by myositis-specific autoantibodies, and in this way, give rise to immunoserological classification. The myositis-specific autoantibodies are directed against specific proteins found in the cytoplasm or in the nucleus of the cells. To date, literature suggests the rarity of the co-existence of two myositis-specific autoantibodies. In this study the authors highlight rare associations of myositis-specific autoantibodies. Three hundred and thirty-seven Hungarian patients with polymyositis or dermatomyositis were studied. Their clinical findings were noted retrospectively. Specific blood tests identified six patients with the rare co-existence of myositis-specific autoantibodies, anti-Jo-1 and anti-SRP, anti-Jo-1 and anti-Mi-2, anti-Mi-2 and anti-PL-12, anti-Mi-2 and anti-SRP, and anti-SRP and anti-PL-7, respectively. This case review aims to identify the clinical importance of these rare associations and their place within the immunoserological classification.

The clinical and immunological significance of GAD-specific autoantibody and T-cell responses in type 1 diabetes.

PubMed

Boettler, Tobias; Pagni, Philippe P; Jaffe, Rachel; Cheng, Yang; Zerhouni, Peter; von Herrath, Matthias

2013-08-01

Antigen-specific interventions are desirable approaches in Type 1 Diabetes (T1D) as they can alter islet-specific autoimmunity without systemic side effects. Glutamic acid decarboxylase of 65 kDa (GAD65) is a major autoantigen in type 1 diabetes (T1D) and GAD-specific autoimmunity is a common feature of T1D in humans but also in mouse models of the disease. In humans, administration of the GAD65 protein in an alum formulation has been shown to reduce C-peptide decline in recently diagnosed patients, however, these observations were not confirmed in subsequent phase II/III clinical trials. As GAD-based immune interventions in different formulations have successfully been employed to prevent the establishment of T1D in mouse models of T1D, we sought to analyze the efficacy of GAD-alum treatment and the effects on the GAD-specific immune response in two different mouse models of T1D. Consistent with the latest clinical trials, mice treated with GAD-alum were not protected from diabetes, although GAD-alum induced a GAD-specific Th2-deviated immune response in transgenic rat insulin promoter-glycoprotein (RIP-GP) mice. These observations underline the importance of a thorough, preclinical evaluation of potential drugs before the initiation of clinical trials. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Joint-specific DNA methylation and transcriptome signatures in rheumatoid arthritis identify distinct pathogenic processes

PubMed Central

Ai, Rizi; Hammaker, Deepa; Boyle, David L.; Morgan, Rachel; Walsh, Alice M.; Fan, Shicai; Firestein, Gary S.; Wang, Wei

2016-01-01

Stratifying patients on the basis of molecular signatures could facilitate development of therapeutics that target pathways specific to a particular disease or tissue location. Previous studies suggest that pathogenesis of rheumatoid arthritis (RA) is similar in all affected joints. Here we show that distinct DNA methylation and transcriptome signatures not only discriminate RA fibroblast-like synoviocytes (FLS) from osteoarthritis FLS, but also distinguish RA FLS isolated from knees and hips. Using genome-wide methods, we show differences between RA knee and hip FLS in the methylation of genes encoding biological pathways, such as IL-6 signalling via JAK-STAT pathway. Furthermore, differentially expressed genes are identified between knee and hip FLS using RNA-sequencing. Double-evidenced genes that are both differentially methylated and expressed include multiple HOX genes. Joint-specific DNA signatures suggest that RA disease mechanisms might vary from joint to joint, thus potentially explaining some of the diversity of drug responses in RA patients. PMID:27282753

Specification Reformulation During Specification Validation

NASA Technical Reports Server (NTRS)

Benner, Kevin M.

1992-01-01

The goal of the ARIES Simulation Component (ASC) is to uncover behavioral errors by 'running' a specification at the earliest possible points during the specification development process. The problems to be overcome are the obvious ones the specification may be large, incomplete, underconstrained, and/or uncompilable. This paper describes how specification reformulation is used to mitigate these problems. ASC begins by decomposing validation into specific validation questions. Next, the specification is reformulated to abstract out all those features unrelated to the identified validation question thus creating a new specialized specification. ASC relies on a precise statement of the validation question and a careful application of transformations so as to preserve the essential specification semantics in the resulting specialized specification. This technique is a win if the resulting specialized specification is small enough so the user my easily handle any remaining obstacles to execution. This paper will: (1) describe what a validation question is; (2) outline analysis techniques for identifying what concepts are and are not relevant to a validation question; and (3) identify and apply transformations which remove these less relevant concepts while preserving those which are relevant.

A novel assay to identify the trafficking proteins that bind to specific vesicle populations

PubMed Central

Bentley, Marvin; Banker, Gary

2016-01-01

Here we describe a method capable of identifying interactions between candidate trafficking proteins and a defined vesicle population in intact cells. The assay involves the expression of an FKBP12-rapamycin–binding domain (FRB)–tagged candidate vesicle-binding protein that can be inducibly linked to an FKBP-tagged molecular motor. If the FRB-tagged candidate protein binds the labeled vesicles, then linking the FRB and FKBP domains recruits motors to the vesicles and causes a predictable, highly distinctive change in vesicle trafficking. We describe two versions of the assay: a general protocol for use in cells with a typical microtubule-organizing center and a specialized protocol designed to detect protein-vesicle interactions in cultured neurons. We have successfully used this assay to identify kinesins and Rabs that bind to a variety of different vesicle populations. In principle, this assay could be used to investigate interactions between any category of vesicle trafficking proteins and any vesicle population that can be specifically labeled. PMID:26621371

Approaches for Establishing Clinically Relevant Dissolution Specifications for Immediate Release Solid Oral Dosage Forms.

PubMed

Hermans, Andre; Abend, Andreas M; Kesisoglou, Filippos; Flanagan, Talia; Cohen, Michael J; Diaz, Dorys A; Mao, Y; Zhang, Limin; Webster, Gregory K; Lin, Yiqing; Hahn, David A; Coutant, Carrie A; Grady, Haiyan

2017-11-01

This manuscript represents the perspective of the Dissolution Analytical Working Group of the IQ Consortium. The intent of this manuscript is to highlight the challenges of, and to provide a recommendation on, the development of clinically relevant dissolution specifications (CRS) for immediate release (IR) solid oral dosage forms. A roadmap toward the development of CRS for IR products containing active ingredients with a non-narrow therapeutic window is discussed, within the context of mechanistic dissolution understanding, supported by in-human pharmacokinetic (PK) data. Two case studies present potential outcomes of following the CRS roadmap and setting dissolution specifications. These cases reveal some benefits and challenges of pursuing CRS with additional PK data, in light of current regulatory positions, including that of the US Food and Drug Administration (FDA), who generally favor this approach, but with the understanding that both industry and regulatory agency perspectives are still evolving in this relatively new field. The CRS roadmap discussed in this manuscript also describes a way to develop clinically relevant dissolution specifications based primarily on dissolution data for batches used in pivotal clinical studies, acknowledging that not all IR product development efforts need to be supported by additional PK studies, albeit with the associated risk of potentially unnecessarily tight manufacturing controls. Recommendations are provided on what stages during the life cycle investment into in vivo studies may be valuable. Finally, the opportunities for CRS within the context of post-approval changes, Modeling and Simulation (M&S), and the application of biowaivers, are briefly discussed.

Beta Atomic Contacts: Identifying Critical Specific Contacts in Protein Binding Interfaces

PubMed Central

Liu, Qian; Kwoh, Chee Keong; Hoi, Steven C. H.

2013-01-01

Specific binding between proteins plays a crucial role in molecular functions and biological processes. Protein binding interfaces and their atomic contacts are typically defined by simple criteria, such as distance-based definitions that only use some threshold of spatial distance in previous studies. These definitions neglect the nearby atomic organization of contact atoms, and thus detect predominant contacts which are interrupted by other atoms. It is questionable whether such kinds of interrupted contacts are as important as other contacts in protein binding. To tackle this challenge, we propose a new definition called beta (β) atomic contacts. Our definition, founded on the β-skeletons in computational geometry, requires that there is no other atom in the contact spheres defined by two contact atoms; this sphere is similar to the van der Waals spheres of atoms. The statistical analysis on a large dataset shows that β contacts are only a small fraction of conventional distance-based contacts. To empirically quantify the importance of β contacts, we design βACV, an SVM classifier with β contacts as input, to classify homodimers from crystal packing. We found that our βACV is able to achieve the state-of-the-art classification performance superior to SVM classifiers with distance-based contacts as input. Our βACV also outperforms several existing methods when being evaluated on several datasets in previous works. The promising empirical performance suggests that β contacts can truly identify critical specific contacts in protein binding interfaces. β contacts thus provide a new model for more precise description of atomic organization in protein quaternary structures than distance-based contacts. PMID:23630569

Clinical manifestations of hemochromatosis in HFE C282Y homozygotes identified by screening.

PubMed

McLaren, Gordon D; McLaren, Christine E; Adams, Paul C; Barton, James C; Reboussin, David M; Gordeuk, Victor R; Acton, Ronald T; Harris, Emily L; Speechley, Mark R; Sholinsky, Phyliss; Dawkins, Fitzroy W; Snively, Beverly M; Vogt, Thomas M; Eckfeldt, John H

2008-11-01

Patients with hemochromatosis may suffer organ damage from iron overload, often with serious clinical consequences. To assess prevalences of self-reported symptoms and clinical signs and conditions in persons homozygous for the hemochromatosis gene (HFE) mutation (C282Y) identified by screening. Participants were adults 25 years of age or older enrolled in the Hemochromatosis and Iron Overload Screening (HEIRS) Study. C282Y homozygotes (n=282) were compared with control participants without the HFE C282Y or H63D alleles (ie, wild type/wild type; n=364). Previously diagnosed C282Y homozygotes and newly diagnosed homozygotes with elevated serum ferritin levels had higher prevalences of certain symptoms such as chronic fatigue (OR 2.8; 95% CI 1.34 to 5.95, and OR 2.0; 95% CI 1.07 to 3.75, respectively), and had more hyperpigmentation on physical examination (OR 4.7; 95% CI 1.50 to 15.06, and OR 3.7; 95% CI 1.10 to 12.16, respectively) and swelling or tenderness of the second and third metacarpophalangeal joints (OR 4.2; 95% CI 1.37 to 13.03, and OR 3.3; 95% CI 1.17 to 9.49, respectively) than control subjects. Joint stiffness was also more common among newly diagnosed C282Y homozygotes with elevated serum ferritin than among control subjects (OR 2.7; 95% CI 1.38 to 5.30). However, the sex- and age-adjusted prevalences of self-reported symptoms and signs of liver disease, heart disease, diabetes and most other major clinical manifestations of hemochromatosis were similar in C282Y homozygotes and control subjects. Some symptoms and conditions associated with hemochromatosis were more prevalent among C282Y homozygotes identified by screening than among control subjects, but prevalences of most outcomes were similar in C282Y homozygotes and controls in this primary care-based study.

Clinical manifestations of hemochromatosis in HFE C282Y homozygotes identified by screening

PubMed Central

McLaren, Gordon D; McLaren, Christine E; Adams, Paul C; Barton, James C; Reboussin, David M; Gordeuk, Victor R; Acton, Ronald T; Harris, Emily L; Speechley, Mark R; Sholinsky, Phyliss; Dawkins, Fitzroy W; Snively, Beverly M; Vogt, Thomas M; Eckfeldt, John H

2008-01-01

BACKGROUND: Patients with hemochromatosis may suffer organ damage from iron overload, often with serious clinical consequences. OBJECTIVE: To assess prevalences of self-reported symptoms and clinical signs and conditions in persons homozygous for the hemochromatosis gene (HFE) mutation (C282Y) identified by screening. METHODS: Participants were adults 25 years of age or older enrolled in the Hemochromatosis and Iron Overload Screening (HEIRS) Study. C282Y homozygotes (n=282) were compared with control participants without the HFE C282Y or H63D alleles (ie, wild type/wild type; n=364). RESULTS: Previously diagnosed C282Y homozygotes and newly diagnosed homozygotes with elevated serum ferritin levels had higher prevalences of certain symptoms such as chronic fatigue (OR 2.8; 95% CI 1.34 to 5.95, and OR 2.0; 95% CI 1.07 to 3.75, respectively), and had more hyperpigmentation on physical examination (OR 4.7; 95% CI 1.50 to 15.06, and OR 3.7; 95% CI 1.10 to 12.16, respectively) and swelling or tenderness of the second and third metacarpophalangeal joints (OR 4.2; 95% CI 1.37 to 13.03, and OR 3.3; 95% CI 1.17 to 9.49, respectively) than control subjects. Joint stiffness was also more common among newly diagnosed C282Y homozygotes with elevated serum ferritin than among control subjects (OR 2.7; 95% CI 1.38 to 5.30). However, the sex- and age-adjusted prevalences of self-reported symptoms and signs of liver disease, heart disease, diabetes and most other major clinical manifestations of hemochromatosis were similar in C282Y homozygotes and control subjects. CONCLUSIONS: Some symptoms and conditions associated with hemochromatosis were more prevalent among C282Y homozygotes identified by screening than among control subjects, but prevalences of most outcomes were similar in C282Y homozygotes and controls in this primary care-based study. PMID:19018338

Sensitivity and specificity of the World Health Organization pertussis clinical case definition.

PubMed

Ghanaie, Roxana Mansour; Karimi, Abdollah; Sadeghi, Hossein; Esteghamti, Abdolreza; Falah, Fateme; Armin, Shahnaz; Fahimzad, Alireza; Shamshiri, Ahmadreza; Kahbazi, Manige; Shiva, Faride

2010-12-01

Bordetella pertussis continues to circulate even in countries with good childhood vaccination coverage. This study was undertaken to define the relationship between documented disease and the clinical criteria proposed by the World Health Organization (WHO). Nasopharyngeal swab samples were collected from previously healthy 6-14-year-old school children in Tehran, presenting with persistent cough of at least 2- week duration. Specimens were examined for Bordetella pertussis and Bordetella parapertussis by culture and polymerase chain reaction (PCR). Out of 6601 students, 328 (5.0%) had been coughing for at least 2 weeks. Of these children with cough, 182 (55.5%) experienced whooping, 194 (59.1%) suffered a paroxysmal cough, and 73 (22.3%) had post-tussive vomiting. Twenty-one (6.4%) samples tested positive for B. pertussis and six (1.8%) for B. parapertussis by PCR. Culture of four (1.2%) specimens was positive for B. pertussis. In comparison to PCR, the sensitivity and the specificity of the WHO clinical criteria (year 2000) were 95.2% and 15.0%, respectively. Pertussis remains one of the etiologies of prolonged cough, even in communities with high immunization in children. The specificity of the WHO criteria is low in diagnosing pertussis compared with PCR. Copyright © 2010 International Society for Infectious Diseases. All rights reserved.

Identification of women at risk of depression in pregnancy: using women's accounts to understand the poor specificity of the Whooley and Arroll case finding questions in clinical practice.

PubMed

Darwin, Zoe; McGowan, Linda; Edozien, Leroy C

2016-02-01

Antenatal mental health assessment is increasingly common in high-income countries. Despite lacking evidence on validation or acceptability, the Whooley questions (modified PHQ-2) and Arroll 'help' question are used in the UK at booking (the first formal antenatal appointment) to identify possible cases of depression. This study investigated validation of the questions and women's views on assessment. Women (n = 191) booking at an inner-city hospital completed the Whooley and Arroll questions as part of their routine clinical care then completed a research questionnaire containing the Edinburgh postnatal depression scale (EPDS). A purposive subsample (n = 22) were subsequently interviewed. The Whooley questions 'missed' half the possible cases identified using the EPDS (EPDS threshold ≥ 10: sensitivity 45.7 %, specificity 92.1 %; ≥ 13: sensitivity 47.8 %, specificity 86.1 %), worsening to nine in ten when adopting the Arroll item (EPDS ≥ 10: sensitivity 9.1 %, specificity 98.2 %; ≥ 13: sensitivity 9.5 %, specificity 97.1 %). Women's accounts indicated that under-disclosure relates to the context of assessment and perceived relevance of depression to maternity services. Depression symptoms are under-identified in current local practice. While validated tools are needed that can be readily applied in routine maternity care, psychometric properties will be influenced by the context of disclosure when implemented in practice.

Classification, Identification, and Clinical Significance of Haemophilus and Aggregatibacter Species with Host Specificity for Humans

PubMed Central

2014-01-01

SUMMARY The aim of this review is to provide a comprehensive update on the current classification and identification of Haemophilus and Aggregatibacter species with exclusive or predominant host specificity for humans. Haemophilus influenzae and some of the other Haemophilus species are commonly encountered in the clinical microbiology laboratory and demonstrate a wide range of pathogenicity, from life-threatening invasive disease to respiratory infections to a nonpathogenic, commensal lifestyle. New species of Haemophilus have been described (Haemophilus pittmaniae and Haemophilus sputorum), and the new genus Aggregatibacter was created to accommodate some former Haemophilus and Actinobacillus species (Aggregatibacter aphrophilus, Aggregatibacter segnis, and Aggregatibacter actinomycetemcomitans). Aggregatibacter species are now a dominant etiology of infective endocarditis caused by fastidious organisms (HACEK endocarditis), and A. aphrophilus has emerged as an important cause of brain abscesses. Correct identification of Haemophilus and Aggregatibacter species based on phenotypic characterization can be challenging. It has become clear that 15 to 20% of presumptive H. influenzae isolates from the respiratory tracts of healthy individuals do not belong to this species but represent nonhemolytic variants of Haemophilus haemolyticus. Due to the limited pathogenicity of H. haemolyticus, the proportion of misidentified strains may be lower in clinical samples, but even among invasive strains, a misidentification rate of 0.5 to 2% can be found. Several methods have been investigated for differentiation of H. influenzae from its less pathogenic relatives, but a simple method for reliable discrimination is not available. With the implementation of identification by matrix-assisted laser desorption ionization–time of flight mass spectrometry, the more rarely encountered species of Haemophilus and Aggregatibacter will increasingly be identified in clinical microbiology

Medical student perspective: working toward specific and actionable clinical clerkship feedback.

PubMed

Moss, Haley A; Derman, Peter B; Clement, R Carter

2012-01-01

Feedback on the wards is an important component of medical student education. Medical schools have incorporated formalized feedback mechanisms such as clinical encounter cards and standardized patient encounters into clinical curricula. However, the system could be further improved as medical students frequently feel uncomfortable requesting feedback, and are often dissatisfied with the quality of the feedback they receive. This article explores the shortcomings of the existing medical student feedback system and examines the relevant literature in an effort to shed light on areas in which the system can be enhanced. The discussion focuses on resident-provided feedback but is broadly applicable to delivering feedback in general. A review of the organizational psychology and business administration literature on fostering effective feedback was performed. These insights were then applied to the setting of medical education. Providing effective feedback requires training and forethought. Feedback itself should be specific and actionable. Utilizing these strategies will help medical students and educators get the most out of existing feedback systems.

Evaluation of decision rules for identifying low bone density in postmenopausal African-American women.

PubMed Central

Wallace, Lorraine Silver; Ballard, Joyce E.; Holiday, David; Turner, Lori W.; Keenum, Amy J.; Pearman, Cynthia M.

2004-01-01

OBJECTIVE: While African-American women tend to have greater bone mineral density (BMD) than caucasian women, they are still at risk of developing osteoporosis later in life. Clinical decision rules (i.e., algorithms) have been developed to assist clinicians identify women at greatest risk of low BMD. However, such tools have only been validated in caucasian and Asian populations. Accordingly, the objective of this study was to compare the performance of five clinical decision rules in identifying postmenopausal African-American women at greatest risk for low femoral BMD. METHODOLOGY: One hundred-seventy-four (n=174) postmenopausal African-American women completed a valid and reliable oral questionnaire to assess lifestyle characteristics, and completed height and weight measures. BMD at the femoral neck was measured via dual energy x-ray absorptiometry (DXA). We calculated sensitivity, specificity, positive predictive value, and negative predictive value for identifying African-American women with low BMD (T-Score < or = -2.0 SD) using five clinical decision rules: Age, Body Size, No Estrogen (ABONE), Osteoporosis Risk Assessment Instrument (ORAI), Osteoporosis Self-Assessment Tool (OST), Simple Calculated Osteoporosis Risk Estimation (SCORE), and body weight less than 70 kg. RESULTS: Approximately 30% of African-American women had low BMD, half of whom had osteoporosis (BMD T-Score < or = -2.5 SD). Sensitivity for identifying women with a low BMD (T-Score < or = -2.0 SD) ranged from 65.57-83.61%, while specificity ranged from 53.85-78.85%. Positive predictive values ranged from 80.95-87.91%, while negative predictive values ranged from 48.44-58.33%. CONCLUSION: Our data suggest that the clinical decision rules analyzed in this study have some usefulness for identifying postmenopausal African-American women with low BMD. However, there is a need to establish cut-points for these clinical decision rules in a larger, more diverse sample of African-American women

Genome of the Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels

PubMed Central

van Leeuwen, Elisabeth M.; Karssen, Lennart C.; Deelen, Joris; Isaacs, Aaron; Medina-Gomez, Carolina; Mbarek, Hamdi; Kanterakis, Alexandros; Trompet, Stella; Postmus, Iris; Verweij, Niek; van Enckevort, David J.; Huffman, Jennifer E.; White, Charles C.; Feitosa, Mary F.; Bartz, Traci M.; Manichaikul, Ani; Joshi, Peter K.; Peloso, Gina M.; Deelen, Patrick; van Dijk, Freerk; Willemsen, Gonneke; de Geus, Eco J.; Milaneschi, Yuri; Penninx, Brenda W.J.H.; Francioli, Laurent C.; Menelaou, Androniki; Pulit, Sara L.; Rivadeneira, Fernando; Hofman, Albert; Oostra, Ben A.; Franco, Oscar H.; Leach, Irene Mateo; Beekman, Marian; de Craen, Anton J.M.; Uh, Hae-Won; Trochet, Holly; Hocking, Lynne J.; Porteous, David J.; Sattar, Naveed; Packard, Chris J.; Buckley, Brendan M.; Brody, Jennifer A.; Bis, Joshua C.; Rotter, Jerome I.; Mychaleckyj, Josyf C.; Campbell, Harry; Duan, Qing; Lange, Leslie A.; Wilson, James F.; Hayward, Caroline; Polasek, Ozren; Vitart, Veronique; Rudan, Igor; Wright, Alan F.; Rich, Stephen S.; Psaty, Bruce M.; Borecki, Ingrid B.; Kearney, Patricia M.; Stott, David J.; Adrienne Cupples, L.; Neerincx, Pieter B.T.; Elbers, Clara C.; Francesco Palamara, Pier; Pe'er, Itsik; Abdellaoui, Abdel; Kloosterman, Wigard P.; van Oven, Mannis; Vermaat, Martijn; Li, Mingkun; Laros, Jeroen F.J.; Stoneking, Mark; de Knijff, Peter; Kayser, Manfred; Veldink, Jan H.; van den Berg, Leonard H.; Byelas, Heorhiy; den Dunnen, Johan T.; Dijkstra, Martijn; Amin, Najaf; Joeri van der Velde, K.; van Setten, Jessica; Kattenberg, Mathijs; van Schaik, Barbera D.C.; Bot, Jan; Nijman, Isaäc J.; Mei, Hailiang; Koval, Vyacheslav; Ye, Kai; Lameijer, Eric-Wubbo; Moed, Matthijs H.; Hehir-Kwa, Jayne Y.; Handsaker, Robert E.; Sunyaev, Shamil R.; Sohail, Mashaal; Hormozdiari, Fereydoun; Marschall, Tobias; Schönhuth, Alexander; Guryev, Victor; Suchiman, H. Eka D.; Wolffenbuttel, Bruce H.; Platteel, Mathieu; Pitts, Steven J.; Potluri, Shobha; Cox, David R.; Li, Qibin; Li, Yingrui; Du, Yuanping; Chen, Ruoyan; Cao, Hongzhi; Li, Ning; Cao, Sujie; Wang, Jun; Bovenberg, Jasper A.; Jukema, J. Wouter; van der Harst, Pim; Sijbrands, Eric J.; Hottenga, Jouke-Jan; Uitterlinden, Andre G.; Swertz, Morris A.; van Ommen, Gert-Jan B.; de Bakker, Paul I.W.; Eline Slagboom, P.; Boomsma, Dorret I.; Wijmenga, Cisca; van Duijn, Cornelia M.

2015-01-01

Variants associated with blood lipid levels may be population-specific. To identify low-frequency variants associated with this phenotype, population-specific reference panels may be used. Here we impute nine large Dutch biobanks (~35,000 samples) with the population-specific reference panel created by the Genome of the Netherlands Project and perform association testing with blood lipid levels. We report the discovery of five novel associations at four loci (P value <6.61 × 10−4), including a rare missense variant in ABCA6 (rs77542162, p.Cys1359Arg, frequency 0.034), which is predicted to be deleterious. The frequency of this ABCA6 variant is 3.65-fold increased in the Dutch and its effect (βLDL-C=0.135, βTC=0.140) is estimated to be very similar to those observed for single variants in well-known lipid genes, such as LDLR. PMID:25751400

LC-QTOF-MS identification of porcine-specific peptide in heat treated pork identifies candidate markers for meat species determination.

PubMed

Sarah, S A; Faradalila, W N; Salwani, M S; Amin, I; Karsani, S A; Sazili, A Q

2016-05-15

The purpose of this study was to identify porcine-specific peptide markers from thermally processed meat that could differentiate pork from beef, chevon and chicken meat. In the initial stage, markers from tryptic digested protein of chilled, boiled and autoclaved pork were identified using LC-QTOF-MS. An MRM method was then established for verification. A thorough investigation of LC-QTOF-MS data showed that only seven porcine-specific peptides were consistently detected. Among these peptides, two were derived from lactate dehydrogenase, one from creatine kinase, and four from serum albumin protein. However, MRM could only detect four peptides (EVTEFAK, LVVITAGAR, FVIER and TVLGNFAAFVQK) that were consistently present in pork samples. In conclusion, meat species determination through a tandem mass spectrometry platform shows high potential in providing scientifically valid and reliable results even at peptide level. Besides, the specificity and selectivity offered by the proteomics approach also provide a robust platform for Halal authentication. Copyright © 2015 Elsevier Ltd. All rights reserved.

An Investigation to Validate the Grammar and Phonology Screening (GAPS) Test to Identify Children with Specific Language Impairment

PubMed Central

van der Lely, Heather K. J.; Payne, Elisabeth; McClelland, Alastair

2011-01-01

Background The extraordinarily high incidence of grammatical language impairments in developmental disorders suggests that this uniquely human cognitive function is “fragile”. Yet our understanding of the neurobiology of grammatical impairments is limited. Furthermore, there is no “gold-standard” to identify grammatical impairments and routine screening is not undertaken. An accurate screening test to identify grammatical abilities would serve the research, health and education communities, further our understanding of developmental disorders, and identify children who need remediation, many of whom are currently un-diagnosed. A potential realistic screening tool that could be widely administered is the Grammar and Phonology Screening (GAPS) test – a 10 minute test that can be administered by professionals and non-professionals alike. Here we provide a further step in evaluating the validity and accuracy (sensitivity and specificity) of the GAPS test in identifying children who have Specific Language Impairment (SLI). Methods and Findings We tested three groups of children; two groups aged 3;6–6:6, a typically developing (n = 30) group, and a group diagnosed with SLI: (n = 11) (Young (Y)-SLI), and a further group aged 6;9–8;11 with SLI (Older (O)-SLI) (n = 10) who were above the test age norms. We employed a battery of language assessments including the GAPS test to assess the children's language abilities. For Y-SLI children, analyses revealed a sensitivity and specificity at the 5th and 10th percentile of 1.00 and 0.98, respectively, and for O-SLI children at the 10th and 15th percentile .83 and .90, respectively. Conclusions The findings reveal that the GAPS is highly accurate in identifying impaired vs. non-impaired children up to 6;8 years, and has moderate-to-high accuracy up to 9 years. The results indicate that GAPS is a realistic tool for the early identification of grammatical abilities and impairment in young children. A larger

Detectable end of radiation prostate specific antigen assists in identifying men with unfavorable intermediate-risk prostate cancer at high risk of distant recurrence and cancer-specific mortality.

PubMed

Hayman, Jonathan; Phillips, Ryan; Chen, Di; Perin, Jamie; Narang, Amol K; Trieu, Janson; Radwan, Noura; Greco, Stephen; Deville, Curtiland; McNutt, Todd; Song, Daniel Y; DeWeese, Theodore L; Tran, Phuoc T

2018-06-01

Undetectable End of Radiation PSA (EOR-PSA) has been shown to predict improved survival in prostate cancer (PCa). While validating the unfavorable intermediate-risk (UIR) and favorable intermediate-risk (FIR) stratifications among Johns Hopkins PCa patients treated with radiotherapy, we examined whether EOR-PSA could further risk stratify UIR men for survival. A total of 302 IR patients were identified in the Johns Hopkins PCa database (178 UIR, 124 FIR). Kaplan-Meier curves and multivariable analysis was performed via Cox regression for biochemical recurrence free survival (bRFS), distant metastasis free survival (DMFS), and overall survival (OS), while a competing risks model was used for PCa specific survival (PCSS). Among the 235 patients with known EOR-PSA values, we then stratified by EOR-PSA and performed the aforementioned analysis. The median follow-up time was 11.5 years (138 months). UIR was predictive of worse DMFS and PCSS (P = 0.008 and P = 0.023) on multivariable analysis (MVA). Increased radiation dose was significant for improved DMFS (P = 0.016) on MVA. EOR-PSA was excluded from the models because it did not trend towards significance as a continuous or binary variable due to interaction with UIR, and we were unable to converge a multivariable model with a variable to control for this interaction. However, when stratifying by detectable versus undetectable EOR-PSA, UIR had worse DMFS and PCSS among detectable EOR-PSA patients, but not undetectable patients. UIR was significant on MVA among detectable EOR-PSA patients for DMFS (P = 0.021) and PCSS (P = 0.033), while RT dose also predicted PCSS (P = 0.013). EOR-PSA can assist in predicting DMFS and PCSS among UIR patients, suggesting a clinically meaningful time point for considering intensification of treatment in clinical trials of intermediate-risk men. © 2018 Wiley Periodicals, Inc.

Personality and Defense Styles: Clinical Specificities and Predictive Factors of Alcohol Use Disorder in Women.

PubMed

Ribadier, Aurélien; Dorard, Géraldine; Varescon, Isabelle

2016-01-01

This study investigated personality traits and defense styles in order to determine clinical specificities and predictive factors of alcohol use disorders (AUDs) in women. A female sample, composed of AUD outpatients (n = 48) and a control group (n = 50), completed a sociodemographic self-report and questionnaires assessing personality traits (BFI), defense mechanisms and defense styles (DSQ-40). Comparative and correlational analyses, as well as univariate and multivariate logistic regressions, were performed. AUD women presented with higher neuroticism and lower extraversion and conscientiousness. They used less mature and more neurotic and immature defense styles than the control group. Concerning personality traits, high neuroticism and lower conscientiousness were predictive of AUD, as well as low mature, high neurotic, and immature defense styles. Including personality traits and defense styles in a logistic model, high neuroticism was the only AUD predictive factor. AUD women presented clinical specificities and predictive factors in personality traits and defense styles that must be taken into account in AUD studies. Implications for specific treatment for women are discussed.

Comparative genome analysis of a large Dutch Legionella pneumophila strain collection identifies five markers highly correlated with clinical strains

PubMed Central

2010-01-01

Background Discrimination between clinical and environmental strains within many bacterial species is currently underexplored. Genomic analyses have clearly shown the enormous variability in genome composition between different strains of a bacterial species. In this study we have used Legionella pneumophila, the causative agent of Legionnaire's disease, to search for genomic markers related to pathogenicity. During a large surveillance study in The Netherlands well-characterized patient-derived strains and environmental strains were collected. We have used a mixed-genome microarray to perform comparative-genome analysis of 257 strains from this collection. Results Microarray analysis indicated that 480 DNA markers (out of in total 3360 markers) showed clear variation in presence between individual strains and these were therefore selected for further analysis. Unsupervised statistical analysis of these markers showed the enormous genomic variation within the species but did not show any correlation with a pathogenic phenotype. We therefore used supervised statistical analysis to identify discriminating markers. Genetic programming was used both to identify predictive markers and to define their interrelationships. A model consisting of five markers was developed that together correctly predicted 100% of the clinical strains and 69% of the environmental strains. Conclusions A novel approach for identifying predictive markers enabling discrimination between clinical and environmental isolates of L. pneumophila is presented. Out of over 3000 possible markers, five were selected that together enabled correct prediction of all the clinical strains included in this study. This novel approach for identifying predictive markers can be applied to all bacterial species, allowing for better discrimination between strains well equipped to cause human disease and relatively harmless strains. PMID:20630115

Measuring the Electronic Properties of DNA-Specific Schottky Diodes Towards Detecting and Identifying Basidiomycetes DNA

PubMed Central

Periasamy, Vengadesh; Rizan, Nastaran; Al-Ta’ii, Hassan Maktuff Jaber; Tan, Yee Shin; Tajuddin, Hairul Annuar; Iwamoto, Mitsumasa

2016-01-01

The discovery of semiconducting behavior of deoxyribonucleic acid (DNA) has resulted in a large number of literatures in the study of DNA electronics. Sequence-specific electronic response provides a platform towards understanding charge transfer mechanism and therefore the electronic properties of DNA. It is possible to utilize these characteristic properties to identify/detect DNA. In this current work, we demonstrate a novel method of DNA-based identification of basidiomycetes using current-voltage (I-V) profiles obtained from DNA-specific Schottky barrier diodes. Electronic properties such as ideality factor, barrier height, shunt resistance, series resistance, turn-on voltage, knee-voltage, breakdown voltage and breakdown current were calculated and used to quantify the identification process as compared to morphological and molecular characterization techniques. The use of these techniques is necessary in order to study biodiversity, but sometimes it can be misleading and unreliable and is not sufficiently useful for the identification of fungi genera. Many of these methods have failed when it comes to identification of closely related species of certain genus like Pleurotus. Our electronics profiles, both in the negative and positive bias regions were however found to be highly characteristic according to the base-pair sequences. We believe that this simple, low-cost and practical method could be useful towards identifying and detecting DNA in biotechnology and pathology. PMID:27435636

Measuring the Electronic Properties of DNA-Specific Schottky Diodes Towards Detecting and Identifying Basidiomycetes DNA

NASA Astrophysics Data System (ADS)

Periasamy, Vengadesh; Rizan, Nastaran; Al-Ta'Ii, Hassan Maktuff Jaber; Tan, Yee Shin; Tajuddin, Hairul Annuar; Iwamoto, Mitsumasa

2016-07-01

The discovery of semiconducting behavior of deoxyribonucleic acid (DNA) has resulted in a large number of literatures in the study of DNA electronics. Sequence-specific electronic response provides a platform towards understanding charge transfer mechanism and therefore the electronic properties of DNA. It is possible to utilize these characteristic properties to identify/detect DNA. In this current work, we demonstrate a novel method of DNA-based identification of basidiomycetes using current-voltage (I-V) profiles obtained from DNA-specific Schottky barrier diodes. Electronic properties such as ideality factor, barrier height, shunt resistance, series resistance, turn-on voltage, knee-voltage, breakdown voltage and breakdown current were calculated and used to quantify the identification process as compared to morphological and molecular characterization techniques. The use of these techniques is necessary in order to study biodiversity, but sometimes it can be misleading and unreliable and is not sufficiently useful for the identification of fungi genera. Many of these methods have failed when it comes to identification of closely related species of certain genus like Pleurotus. Our electronics profiles, both in the negative and positive bias regions were however found to be highly characteristic according to the base-pair sequences. We believe that this simple, low-cost and practical method could be useful towards identifying and detecting DNA in biotechnology and pathology.

Red blood cell antibodies in pregnancy and their clinical consequences: synergistic effects of multiple specificities.

PubMed

Nordvall, Maria; Dziegiel, Morten; Hegaard, Hanne Kristine; Bidstrup, Mogens; Jonsbo, Finn; Christensen, Birgit; Hedegaard, Morten

2009-10-01

The objective was to determine clinical consequences of various specificities for the infant/fetus. The population was patients referred between 1998 and 2005 to the tertiary center because of detected red blood cell (RBC) alloimmunization. Altogether 455 infants were delivered by 390 alloimmunized women. This was a retrospective cohort study. Data were obtained from the blood bank register and the obstetric and neonatal database. As indicators of hemolytic activity of the antibodies, the frequency of the therapeutic interventions intrauterine transfusion, exchange transfusion, and simple transfusion was used. Anti-D was the most common antibody (46.6%), followed by anti-K (15.4%). A combination of antibodies was detected in 27%. All three types of therapeutic intervention were significantly more frequent in women with anti-D plus an additional antibody than in women with anti-D as the sole antibody. The anti-D titer closely paralleled the clinical importance of the antibody. One case of anti-s with a titer of 512 required all three types of transfusion. Anti-D was the single most frequent and harmful specificity closely followed by anti-K. Combinations of antibody specificities were more harmful than single specificities, and a potentially synergistic effect should be considered.

Heterobivalent Imaging Agents for Simultaneous Targeting Prostate-Specific Membrane Antigen (PSMA) and Hepsin

DTIC Science & Technology

2011-04-01

specific membrane antigen (PSMA), showed promise in the clinic for identifying candidates for salvage radiotherapy. (4, 5) Because of the important...removed benzyl group to afford the Lys- Urea-Glu 14 in 85% yield. Compound 14 was conjugated with the suberic acid bis-(N- hydroxysuccinimide ( DSS ) in...directed against human and mouse prostate-specific membrane antigen. Prostate 2004; 61: 1-11. 4. Chang SS, Heston WD. The clinical role of prostate

CLINICAL PROGRESS IN INHERITED RETINAL DEGENERATIONS: GENE THERAPY CLINICAL TRIALS AND ADVANCES IN GENETIC SEQUENCING.

PubMed

Hafler, Brian P

2017-03-01

Inherited retinal dystrophies are a significant cause of vision loss and are characterized by the loss of photoreceptors and the retinal pigment epithelium (RPE). Mutations in approximately 250 genes cause inherited retinal degenerations with a high degree of genetic heterogeneity. New techniques in next-generation sequencing are allowing the comprehensive analysis of all retinal disease genes thus changing the approach to the molecular diagnosis of inherited retinal dystrophies. This review serves to analyze clinical progress in genetic diagnostic testing and implications for retinal gene therapy. A literature search of PubMed and OMIM was conducted to relevant articles in inherited retinal dystrophies. Next-generation genetic sequencing allows the simultaneous analysis of all the approximately 250 genes that cause inherited retinal dystrophies. Reported diagnostic rates range are high and range from 51% to 57%. These new sequencing tools are highly accurate with sensitivities of 97.9% and specificities of 100%. Retinal gene therapy clinical trials are underway for multiple genes including RPE65, ABCA4, CHM, RS1, MYO7A, CNGA3, CNGB3, ND4, and MERTK for which a molecular diagnosis may be beneficial for patients. Comprehensive next-generation genetic sequencing of all retinal dystrophy genes is changing the paradigm for how retinal specialists perform genetic testing for inherited retinal degenerations. Not only are high diagnostic yields obtained, but mutations in genes with novel clinical phenotypes are also identified. In the era of retinal gene therapy clinical trials, identifying specific genetic defects will increasingly be of use to identify patients who may enroll in clinical studies and benefit from novel therapies.

Identifying Health Information Technology Needs of Oncologists to Facilitate the Adoption of Genomic Medicine: Recommendations From the 2016 American Society of Clinical Oncology Omics and Precision Oncology Workshop.

PubMed

Hughes, Kevin S; Ambinder, Edward P; Hess, Gregory P; Yu, Peter Paul; Bernstam, Elmer V; Routbort, Mark J; Clemenceau, Jean Rene; Hamm, John T; Febbo, Phillip G; Domchek, Susan M; Chen, James L; Warner, Jeremy L

2017-09-20

At the ASCO Data Standards and Interoperability Summit held in May 2016, it was unanimously decided that four areas of current oncology clinical practice have serious, unmet health information technology needs. The following areas of need were identified: 1) omics and precision oncology, 2) advancing interoperability, 3) patient engagement, and 4) value-based oncology. To begin to address these issues, ASCO convened two complementary workshops: the Omics and Precision Oncology Workshop in October 2016 and the Advancing Interoperability Workshop in December 2016. A common goal was to address the complexity, enormity, and rapidly changing nature of genomic information, which existing electronic health records are ill equipped to manage. The subject matter experts invited to the Omics and Precision Oncology Workgroup were tasked with the responsibility of determining a specific, limited need that could be addressed by a software application (app) in the short-term future, using currently available genomic knowledge bases. Hence, the scope of this workshop was to determine the basic functionality of one app that could serve as a test case for app development. The goal of the second workshop, described separately, was to identify the specifications for such an app. This approach was chosen both to facilitate the development of a useful app and to help ASCO and oncologists better understand the mechanics, difficulties, and gaps in genomic clinical decision support tool development. In this article, we discuss the key challenges and recommendations identified by the workshop participants. Our hope is to narrow the gap between the practicing oncologist and ongoing national efforts to provide precision oncology and value-based care to cancer patients.

Parallel RNAi screens across different cell lines identify generic and cell type-specific regulators of actin organization and cell morphology.

PubMed

Liu, Tao; Sims, David; Baum, Buzz

2009-01-01

In recent years RNAi screening has proven a powerful tool for dissecting gene functions in animal cells in culture. However, to date, most RNAi screens have been performed in a single cell line, and results then extrapolated across cell types and systems. Here, to dissect generic and cell type-specific mechanisms underlying cell morphology, we have performed identical kinome RNAi screens in six different Drosophila cell lines, derived from two distinct tissues of origin. This analysis identified a core set of kinases required for normal cell morphology in all lines tested, together with a number of kinases with cell type-specific functions. Most significantly, the screen identified a role for minibrain (mnb/DYRK1A), a kinase associated with Down's syndrome, in the regulation of actin-based protrusions in CNS-derived cell lines. This cell type-specific requirement was not due to the peculiarities in the morphology of CNS-derived cells and could not be attributed to differences in mnb expression. Instead, it likely reflects differences in gene expression that constitute the cell type-specific functional context in which mnb/DYRK1A acts. Using parallel RNAi screens and gene expression analyses across cell types we have identified generic and cell type-specific regulators of cell morphology, which include mnb/DYRK1A in the regulation of protrusion morphology in CNS-derived cell lines. This analysis reveals the importance of using different cell types to gain a thorough understanding of gene function across the genome and, in the case of kinases, the difficulties of using the differential gene expression to predict function.

Patient-specific bone modeling and analysis: the role of integration and automation in clinical adoption.

PubMed

Zadpoor, Amir A; Weinans, Harrie

2015-03-18

Patient-specific analysis of bones is considered an important tool for diagnosis and treatment of skeletal diseases and for clinical research aimed at understanding the etiology of skeletal diseases and the effects of different types of treatment on their progress. In this article, we discuss how integration of several important components enables accurate and cost-effective patient-specific bone analysis, focusing primarily on patient-specific finite element (FE) modeling of bones. First, the different components are briefly reviewed. Then, two important aspects of patient-specific FE modeling, namely integration of modeling components and automation of modeling approaches, are discussed. We conclude with a section on validation of patient-specific modeling results, possible applications of patient-specific modeling procedures, current limitations of the modeling approaches, and possible areas for future research. Copyright © 2014 Elsevier Ltd. All rights reserved.

A concise guide to clinical reasoning.

PubMed

Daly, Patrick

2018-04-30

What constitutes clinical reasoning is a disputed subject regarding the processes underlying accurate diagnosis, the importance of patient-specific versus population-based data, and the relation between virtue and expertise in clinical practice. In this paper, I present a model of clinical reasoning that identifies and integrates the processes of diagnosis, prognosis, and therapeutic decision making. The model is based on the generalized empirical method of Bernard Lonergan, which approaches inquiry with equal attention to the subject who investigates and the object under investigation. After identifying the structured operations of knowing and doing and relating these to a self-correcting cycle of learning, I correlate levels of inquiry regarding what-is-going-on and what-to-do to the practical and theoretical elements of clinical reasoning. I conclude that this model provides a methodical way to study questions regarding the operations of clinical reasoning as well as what constitute significant clinical data, clinical expertise, and virtuous health care practice. © 2018 John Wiley & Sons, Ltd.

A comparison between the efficiency of the Xpert MTB/RIF assay and nested PCR in identifying Mycobacterium tuberculosis during routine clinical practice.

PubMed

Kim, Cheol-Hong; Woo, Heungjeong; Hyun, In Gyu; Kim, Changhwan; Choi, Jeong-Hee; Jang, Seung-Hun; Park, Sang Myeon; Kim, Dong-Gyu; Lee, Myung Goo; Jung, Ki-Suck; Hyun, Jeongwon; Kim, Hyun Soo

2014-06-01

Polymerase chain reaction (PCR) for the detection of Mycobacterium tuberculosis (MTB) is more sensitive, specific, and rapid than the conventional methods of acid-fast bacilli (AFB) smear and culture. The aim of this study was to determine if the Xpert MTB/rifampicin (RIF) assay had additional advantages over nested PCR for the detection of MTB in a geographical area with intermediate tuberculosis (TB) incidence. Between February and December 2013, the Xpert MTB/RIF assay and MTB nested PCR, as well as AFB smear and culture, were simultaneously performed on 198 clinical samples (160 pulmonary and 38 non-pulmonary specimens) collected from 171 patients hospitalized at Hallym University Medical Center for possible TB. The accuracy of the diagnosis of MTB culture-positive TB and the turnaround time of reporting laboratory results were calculated and compared. Rifampin resistance by the Xpert MTB/RIF assay was reviewed with that of conventional drug susceptibility testing (DST). The sensitivity, specificity, and positive and negative predictive values of the Xpert MTB/RIF assay and MTB nested PCR for diagnosis of MTB culture-positive pulmonary TB were 86.1% vs. 69.4% (P=0.1563), 97.8% vs. 94.1% (P=0.2173), 91.2% vs. 75.8% (P=0.1695), and 96.4% vs. 92.0% (P=0.2032), respectively. The median turnaround times of the Xpert MTB/RIF assay and MTB nested PCR were 0 [0-4] days and 4 [1-11] days, respectively (P<0.001). Two cases of rifampin resistance, as determined by the Xpert MTB/RIF assay, were found to be multi-drug resistant (MDR) pulmonary TB by DST. The Xpert MTB/RIF assay seemed to be sensitive, specific, and comparable to nested PCR for identifying MTB among clinically suspected TB patients, and the assay can be valuable in giving a timely identification of resistance to rifampin.

TargetLink, a new method for identifying the endogenous target set of a specific microRNA in intact living cells.

PubMed

Xu, Yan; Chen, Yan; Li, Daliang; Liu, Qing; Xuan, Zhenyu; Li, Wen-Hong

2017-02-01

MicroRNAs are small non-coding RNAs acting as posttranscriptional repressors of gene expression. Identifying mRNA targets of a given miRNA remains an outstanding challenge in the field. We have developed a new experimental approach, TargetLink, that applied locked nucleic acid (LNA) as the affinity probe to enrich target genes of a specific microRNA in intact cells. TargetLink also consists a rigorous and systematic data analysis pipeline to identify target genes by comparing LNA-enriched sequences between experimental and control samples. Using miR-21 as a test microRNA, we identified 12 target genes of miR-21 in a human colorectal cancer cell by this approach. The majority of the identified targets interacted with miR-21 via imperfect seed pairing. Target validation confirmed that miR-21 repressed the expression of the identified targets. The cellular abundance of the identified miR-21 target transcripts varied over a wide range, with some targets expressed at a rather low level, confirming that both abundant and rare transcripts are susceptible to regulation by microRNAs, and that TargetLink is an efficient approach for identifying the target set of a specific microRNA in intact cells. C20orf111, one of the novel targets identified by TargetLink, was found to reside in the nuclear speckle and to be reliably repressed by miR-21 through the interaction at its coding sequence.

Fabry Disease: prevalence of affected males and heterozygotes with pathogenic GLA mutations identified by screening renal, cardiac and stroke clinics, 1995-2017.

PubMed

Doheny, Dana; Srinivasan, Ram; Pagant, Silvere; Chen, Brenden; Yasuda, Makiko; Desnick, Robert J

2018-04-01

Fabry Disease (FD), an X linked lysosomal storage disease due to pathogenic α-galactosidase A ( GLA ) mutations, results in two major subtypes, the early-onset Type 1 'Classic' and the Type 2 'Later-Onset' phenotypes. To identify previously unrecognised patients, investigators screened cardiac, renal and stroke clinics by enzyme assays. However, some screening studies did not perform confirmatory GLA mutation analyses, and many included recently recognised 'benign/likely-benign' variants, thereby inflating prevalence estimates. Online databases were searched for all FD screening studies in high-risk clinics (1995-2017). Studies reporting GLA mutations were re-analysed for pathogenic mutations, sex and phenotype. Phenotype-specific and sex-specific prevalence rates were determined. Of 67 studies, 63 that screened 51363patients (33943M and 17420F) and provided GLA mutations were reanalysed for disease-causing mutations. Of reported GLA mutations, benign variants occurred in 47.9% of males and 74.1% of females. The following were the revised prevalence estimates: among 36820 (23954M and 12866F) haemodialysis screenees, 0.21% males and 0.15% females; among 3074 (2031M and 1043F) renal transplant screenees, 0.25% males and no females; among 5491 (4054M and 1437F) cardiac screenees, 0.94% males and 0.90% females; and among 5978 (3904M and 2074F) stroke screenees, 0.13% males and 0.14% females. Among male and female screenees with pathogenic mutations, the type 1 Classic phenotype was predominant (~60%), except more male cardiac patients (75%) had type 2 Later-Onset phenotype. Compared with previous findings, reanalysis of 63 studies increased the screenee numbers (~3.4-fold), eliminated 20 benign/likely benign variants, and provided more accurate sex-specific and phenotype-specific prevalence estimates, ranging from ~0.13% of stroke to ~0.9% of cardiac male or female screenees. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article

Pediatric Eosinophilic Esophagitis Symptom Scores (PEESS® v2.0) identify histologic and molecular correlates of the key clinical features of disease

PubMed Central

Martin, Lisa J.; Franciosi, James P.; Collins, Margaret H.; Abonia, J. Pablo; Lee, James J.; Hommel, Kevin A.; Varni, James W.; Grotjan, J. Tommie; Eby, Michael; He, Hua; Marsolo, Keith; Putnam, Philip E.; Garza, Jose M.; Kaul, Ajay; Wen, Ting; Rothenberg, Marc E.

2015-01-01

Background The Pediatric Eosinophilic Esophagitis Symptom Score (PEESS® v2.0) measures patient-relevant outcomes. However, whether patient-identified domains (dysphagia, gastrointestinal reflux disease (GERD), nausea/vomiting, and pain) align with clinical symptomology and histopathologic and molecular features of eosinophilic esophagitis (EoE) is unclear. Objective The purpose of this study was to determine if clinical features of EoE, measured through the PEESS® v2.0, associate with histopathologic and molecular features of EoE. This represents a novel approach for analysis of allergic diseases, given the availability of allergic tissue biopsy specimens. Methods We systematically recruited treated and untreated, pediatric patients with EoE (aged 2–18 years) and examined parent proxy–reported symptoms using the PEESS® v2.0. Clinical symptomology was collected by questionnaire. Esophageal biopsy samples were quantified for levels of eosinophils, eosinophil peroxidase (EPX) immunohistochemical staining, and mast cells. Molecular features were assessed by the EoE Diagnostic Panel (94 EoE-related gene transcripts). Associations between domain scores and clinical symptoms and biologic features were analyzed using Wilcoxon Rank Sum and Spearman correlation. Results The PEESS® v2.0 domains correlated to specific parent-reported symptoms: dysphagia (p = 0.0012), GERD (p = 0.0001), and nausea/vomiting (p < 0.0001). Pain correlated with multiple symptoms (p < 0.0005). Dysphagia correlated most strongly with overall histopathology, particularly in the proximal esophagus (p ≤ 0.0049). Markers of esophageal activity (EPX) were significantly associated with dysphagia (strongest r = .37; p = 0.02). Eosinophil levels were more associated with pain (r = 0.27; p=0.06) than for dysphagia (r = 0.24; p = 0.13). The dysphagia domain correlated the most with esophageal gene transcript levels, predominantly with mast cell–specific genes. Conclusion We have 1) established a

Tissue-enriched expression profiles in Aedes aegypti identify hemocyte-specific transcriptome responses to infection

PubMed Central

Choi, Young-Jun; Fuchs, Jeremy F.; Mayhew, George F.; Yu, Helen E.; Christensen, Bruce M.

2012-01-01

Hemocytes are integral components of mosquito immune mechanisms such as phagocytosis, melanization, and production of antimicrobial peptides. However, our understanding of hemocyte-specific molecular processes and their contribution to shaping the host immune response remains limited. To better understand the immunophysiological features distinctive of hemocytes, we conducted genome-wide analysis of hemocyte-enriched transcripts, and examined how tissue-enriched expression patterns change with the immune status of the host. Our microarray data indicate that the hemocyte-enriched trascriptome is dynamic and context-dependent. Analysis of transcripts enriched after bacterial challenge in circulating hemocytes with respect to carcass added a dimension to evaluating infection-responsive genes and immune-related gene families. We resolved patterns of transcriptional change unique to hemocytes from those that are likely shared by other immune responsive tissues, and identified clusters of genes preferentially induced in hemocytes, likely reflecting their involvement in cell type specific functions. In addition, the study revealed conserved hemocyte-enriched molecular repertoires which might be implicated in core hemocyte function by cross-species meta-analysis of microarray expression data from Anopheles gambiae and Drosophila melanogaster. PMID:22796331

Fall risk screening protocol for older hearing clinic patients.

PubMed

Criter, Robin E; Honaker, Julie A

2017-10-01

The primary purposes of this study were (1) to describe measures that may contrast audiology patients who fall from those who do not fall and (2) to evaluate the clinical performance of measures that could be easily used for fall risk screening in a mainstream audiology hearing clinic. Cross-sectional study Study sample: Thirty-six community-dwelling audiology patient participants and 27 community-dwelling non-audiology patients over 60 years of age. The Hearing Handicap Inventory for the Elderly (HHIE) most accurately identified patients with a recent fall (sensitivity: 76.0%), while the Dizziness Handicap Inventory (DHI) most accurately identified patients without a recent fall (specificity: 90.9%). A combination of measures used in a protocol-including HHIE, DHI, number of medications, and the Timed Up and Go test-resulted in good, accurate identification of patients with or without a recent history of falls (92.0% sensitivity, 100% specificity). This study reports good sensitivity and excellent specificity for identifying patients with and without a recent history of falls when measures were combined into a screening protocol. Despite previously reported barriers, effective fall risk screenings may be performed in hearing clinic settings with measures often readily accessible to audiologists.

Using Semantic Web technologies for the generation of domain-specific templates to support clinical study metadata standards.

PubMed

Jiang, Guoqian; Evans, Julie; Endle, Cory M; Solbrig, Harold R; Chute, Christopher G

2016-01-01

The Biomedical Research Integrated Domain Group (BRIDG) model is a formal domain analysis model for protocol-driven biomedical research, and serves as a semantic foundation for application and message development in the standards developing organizations (SDOs). The increasing sophistication and complexity of the BRIDG model requires new approaches to the management and utilization of the underlying semantics to harmonize domain-specific standards. The objective of this study is to develop and evaluate a Semantic Web-based approach that integrates the BRIDG model with ISO 21090 data types to generate domain-specific templates to support clinical study metadata standards development. We developed a template generation and visualization system based on an open source Resource Description Framework (RDF) store backend, a SmartGWT-based web user interface, and a "mind map" based tool for the visualization of generated domain-specific templates. We also developed a RESTful Web Service informed by the Clinical Information Modeling Initiative (CIMI) reference model for access to the generated domain-specific templates. A preliminary usability study is performed and all reviewers (n = 3) had very positive responses for the evaluation questions in terms of the usability and the capability of meeting the system requirements (with the average score of 4.6). Semantic Web technologies provide a scalable infrastructure and have great potential to enable computable semantic interoperability of models in the intersection of health care and clinical research.

Patient-specific cardiac phantom for clinical training and preprocedure surgical planning.

PubMed

Laing, Justin; Moore, John; Vassallo, Reid; Bainbridge, Daniel; Drangova, Maria; Peters, Terry

2018-04-01

Minimally invasive mitral valve repair procedures including MitraClip ® are becoming increasingly common. For cases of complex or diseased anatomy, clinicians may benefit from using a patient-specific cardiac phantom for training, surgical planning, and the validation of devices or techniques. An imaging compatible cardiac phantom was developed to simulate a MitraClip ® procedure. The phantom contained a patient-specific cardiac model manufactured using tissue mimicking materials. To evaluate accuracy, the patient-specific model was imaged using computed tomography (CT), segmented, and the resulting point cloud dataset was compared using absolute distance to the original patient data. The result, when comparing the molded model point cloud to the original dataset, resulted in a maximum Euclidean distance error of 7.7 mm, an average error of 0.98 mm, and a standard deviation of 0.91 mm. The phantom was validated using a MitraClip ® device to ensure anatomical features and tools are identifiable under image guidance. Patient-specific cardiac phantoms may allow for surgical complications to be accounted for preoperative planning. The information gained by clinicians involved in planning and performing the procedure should lead to shorter procedural times and better outcomes for patients.

Clinical Tests Combined with Color Doppler Versus Color Doppler Alone in Identifying Incompetent Perforator Veins of the Lower Limb: A Prospective Analytical Study.

PubMed

Sureshkumar, Sathasivam; Vignesh, Narayan; Venkatachalam, J; Vijayakumar, Chellappa; Sudharsanan, Sundaramurthi

2018-01-05

Background The color Doppler, a better investigation to identify the perforators objectively has replaced the clinical examination for the same. However, this has led to a significant number of negative explorations and cosmetic disfigurement. Objective To compare the efficacy of the clinical tests combined with the color Doppler versus color Doppler alone to identify the perforator incompetence during the surgery for primary varicose veins of the lower limb. Methods This was a prospective analytical study, including 61 lower limb varicose vein patients who belonged to the Clinical-Etiology-Anatomy-Pathophysiology (CEAP) class four-six, planned for the surgical treatment for perforator incompetence, excluding those requiring additional vascular or nonvascular procedure, recurrent varicose veins and those who had injection sclerotherapy prior to the surgery. The clinical tests, including Trendelenburg's test, multiple tourniquet tests and, the Fegan's tests were performed and incompetent perforators were marked on a template as 'C' to indicate the clinically positive perforator incompetence. The patients were then examined with the color Doppler ultrasound and the pathological incompetent perforators were marked as 'D'. The surgical management of the perforator incompetence was done by stab ligation. The incision was made in the color Doppler 'D' marked sites as it has been the standard protocol. The number of incompetent perforators identified during the surgical exploration were categorized as 'D' positive or 'C' and 'D' positive and were recorded in the specified proforma. Results It was found that the mean number of the perforator incompetence identified by the color Doppler alone was 8.2 whereas during the surgery, only a mean of six perforators was identified, leading to 20 unnecessary explorations per 10 patients (8.2 vs. 6; mean difference 2.229; P <0.001). The mean number of the perforator incompetence identified by the color Doppler combined with the

Clinical Tests Combined with Color Doppler Versus Color Doppler Alone in Identifying Incompetent Perforator Veins of the Lower Limb: A Prospective Analytical Study

PubMed Central

Vignesh, Narayan; Venkatachalam, J; Vijayakumar, Chellappa; Sudharsanan, Sundaramurthi

2018-01-01

Background The color Doppler, a better investigation to identify the perforators objectively has replaced the clinical examination for the same. However, this has led to a significant number of negative explorations and cosmetic disfigurement. Objective To compare the efficacy of the clinical tests combined with the color Doppler versus color Doppler alone to identify the perforator incompetence during the surgery for primary varicose veins of the lower limb. Methods This was a prospective analytical study, including 61 lower limb varicose vein patients who belonged to the Clinical-Etiology-Anatomy-Pathophysiology (CEAP) class four-six, planned for the surgical treatment for perforator incompetence, excluding those requiring additional vascular or nonvascular procedure, recurrent varicose veins and those who had injection sclerotherapy prior to the surgery. The clinical tests, including Trendelenburg’s test, multiple tourniquet tests and, the Fegan’s tests were performed and incompetent perforators were marked on a template as ‘C’ to indicate the clinically positive perforator incompetence. The patients were then examined with the color Doppler ultrasound and the pathological incompetent perforators were marked as ‘D’. The surgical management of the perforator incompetence was done by stab ligation. The incision was made in the color Doppler ‘D’ marked sites as it has been the standard protocol. The number of incompetent perforators identified during the surgical exploration were categorized as ‘D’ positive or ’C’ and ‘D’ positive and were recorded in the specified proforma. Results It was found that the mean number of the perforator incompetence identified by the color Doppler alone was 8.2 whereas during the surgery, only a mean of six perforators was identified, leading to 20 unnecessary explorations per 10 patients (8.2 vs. 6; mean difference 2.229; P <0.001). The mean number of the perforator incompetence identified by the color

Early-Onset Obsessive-Compulsive Disorder: A Subgroup with a Specific Clinical and Familial Pattern?

ERIC Educational Resources Information Center

Chabane, Nadia; Delorme, Richard; Millet, Bruno; Mouren, Marie-Christine; Leboyer, Marion; Pauls, David

2005-01-01

Background: The familial nature of obsessive-compulsive disorder (OCD) has been previously demonstrated. The identification of candidate symptoms such as age at onset may help to disentangle the clinical and genetic heterogeneity of the disorder. In this study, the specificity of early-onset OCD was investigated, focusing on the effect of gender,…

Strategies and methods to study female-specific cardiovascular health and disease: a guide for clinical scientists.

PubMed

Ouyang, Pamela; Wenger, Nanette K; Taylor, Doris; Rich-Edwards, Janet W; Steiner, Meir; Shaw, Leslee J; Berga, Sarah L; Miller, Virginia M; Merz, Noel Bairey

2016-01-01

In 2001, the Institute of Medicine's (IOM) report, "Exploring the Biological Contributions to Human Health: Does Sex Matter?" advocated for better understanding of the differences in human diseases between the sexes, with translation of these differences into clinical practice. Sex differences are well documented in the prevalence of cardiovascular (CV) risk factors, the clinical manifestation and incidence of cardiovascular disease (CVD), and the impact of risk factors on outcomes. There are also physiologic and psychosocial factors unique to women that may affect CVD risk, such as issues related to reproduction. The Society for Women's Health Research (SWHR) CV Network compiled an inventory of sex-specific strategies and methods for the study of women and CV health and disease across the lifespan. References for methods and strategy details are provided to gather and evaluate this information. Some items comprise robust measures; others are in development. To address female-specific CV health and disease in population, physiology, and clinical trial research, data should be collected on reproductive history, psychosocial variables, and other factors that disproportionately affect CVD in women. Variables related to reproductive health include the following: age of menarche, menstrual cycle regularity, hormone levels, oral contraceptive use, pregnancy history/complications, polycystic ovary syndrome (PCOS) components, menopause age, and use and type of menopausal hormone therapy. Other factors that differentially affect women's CV risk include diabetes mellitus, autoimmune inflammatory disease, and autonomic vasomotor control. Sex differences in aging as well as psychosocial variables such as depression and stress should also be considered. Women are frequently not included/enrolled in mixed-sex CVD studies; when they are included, information on these variables is generally not collected. These omissions limit the ability to determine the role of sex-specific

Capillary electrophoresis mass spectrometry-based saliva metabolomics identified oral, breast and pancreatic cancer-specific profiles.

PubMed

Sugimoto, Masahiro; Wong, David T; Hirayama, Akiyoshi; Soga, Tomoyoshi; Tomita, Masaru

2010-03-01

Saliva is a readily accessible and informative biofluid, making it ideal for the early detection of a wide range of diseases including cardiovascular, renal, and autoimmune diseases, viral and bacterial infections and, importantly, cancers. Saliva-based diagnostics, particularly those based on metabolomics technology, are emerging and offer a promising clinical strategy, characterizing the association between salivary analytes and a particular disease. Here, we conducted a comprehensive metabolite analysis of saliva samples obtained from 215 individuals (69 oral, 18 pancreatic and 30 breast cancer patients, 11 periodontal disease patients and 87 healthy controls) using capillary electrophoresis time-of-flight mass spectrometry (CE-TOF-MS). We identified 57 principal metabolites that can be used to accurately predict the probability of being affected by each individual disease. Although small but significant correlations were found between the known patient characteristics and the quantified metabolites, the profiles manifested relatively higher concentrations of most of the metabolites detected in all three cancers in comparison with those in people with periodontal disease and control subjects. This suggests that cancer-specific signatures are embedded in saliva metabolites. Multiple logistic regression models yielded high area under the receiver-operating characteristic curves (AUCs) to discriminate healthy controls from each disease. The AUCs were 0.865 for oral cancer, 0.973 for breast cancer, 0.993 for pancreatic cancer, and 0.969 for periodontal diseases. The accuracy of the models was also high, with cross-validation AUCs of 0.810, 0.881, 0.994, and 0.954, respectively. Quantitative information for these 57 metabolites and their combinations enable us to predict disease susceptibility. These metabolites are promising biomarkers for medical screening. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11306-009-0178-y

Sex-Specific Genetic Loci for Femoral Neck Bone Mass and Strength Identified in Inbred COP and DA Rats

PubMed Central

Alam, Imranul; Sun, Qiwei; Liu, Lixiang; Koller, Daniel L; Carr, Lucinda G; Econs, Michael J; Foroud, Tatiana; Turner, Charles H

2008-01-01

Introduction Hip fracture is the most devastating osteoporotic fracture type with significant morbidity and mortality. Several studies in humans identified chromosomal regions linked to hip size and bone mass. Animal models, particularly the inbred rat, serve as complementary approaches for studying the genetic influence on hip fragility. The purpose of this study is to identify sex-independent and sex-specific quantitative trait loci (QTLs) for femoral neck density, structure, and strength in inbred Copenhagen 2331 (COP) and Dark Agouti (DA) rats. Materials and Methods A total of 828 (405 males and 423 females) F2 progeny derived from the inbred COP and DA strains of rats were phenotyped for femoral neck volumetric BMD (vBMD), cross-sectional area, polar moment of inertia (Ip), neck width, ultimate force, and energy to break. A whole genome screen was performed using 93 microsatellite markers with an average intermarker distance of 20 cM. Recombination-based marker maps were generated using MAPMAKER/EXP from the COP × DA F2 data and compared with published Rat Genome Database (RGD) maps. These maps were used for genome-wide linkage analyses to detect sex-independent and sex-specific QTLs. Results Significant evidence of linkage (p < 0.01) for sex-independent QTLs were detected for (1) femoral neck vBMD on chromosomes (Chrs) 1, 6, 10, and 12, (2) femoral neck structure on Chrs 5, 7, 10, and 18, and (3) biomechanical properties on Chrs 1 and 4. Male-specific QTLs were discovered on Chrs 2, 9, and 18 for total vBMD, on Chr 17 for trabecular vBMD, on Chr 9 for total bone area, and on Chr 15 for ultimate force. A female-specific QTL was discovered on Chr 2 for ultimate force. The effect size of the individual QTL varied between 1% and 4%. Conclusions We detected evidence that sex-independent and sex-specific QTLs contribute to hip fragility in the inbred rat. Several QTLs regions identified in this study are homologous to human chromosomal regions previously linked to

Identifying predictive factors for long-term complications following button battery impactions: A case series and literature review.

PubMed

Eliason, Michael J; Melzer, Jonathan M; Winters, Jessica R; Gallagher, Thomas Q

2016-08-01

To complement a case series review of button battery impactions managed at our single military tertiary care center with a thorough literature review of laboratory research and clinical cases to develop a protocol to optimize patient care. Specifically, to identify predictive factors of long-term complications which can be used by the pediatric otolaryngologist to guide patient management after button battery impactions. A retrospective review of the Department of Defense's electronic medical record systems was conducted to identify patients with button battery ingestions and then characterize their treatment course. A thorough literature review complemented the lessons learned to identify potentially predictive clinical measures for long-term complications. Eight patients were identified as being treated for button battery impaction in the aerodigestive tract with two sustaining long-term complications. The median age of the patients treated was 33 months old and the median estimated time of impaction in the aerodigestive tract prior to removal was 10.5 h. Time of impaction, anatomic direction of the battery's negative pole, and identifying specific battery parameters were identified as factors that may be employed to predict sequelae. Based on case reviews, advancements in battery manufacturing, and laboratory research, there are distinct clinical factors that should be assessed at the time of initial therapy to guide follow-up management to minimize potential catastrophic sequelae of button battery ingestion. Published by Elsevier Ireland Ltd.

Autoantibody-producing plasmablasts after B cell depletion identified in muscle-specific kinase myasthenia gravis

PubMed Central

Stathopoulos, Panos; Kumar, Aditya; Nowak, Richard J.; O’Connor, Kevin C.

2017-01-01

Myasthenia gravis (MG) is a B cell–mediated autoimmune disorder of neuromuscular transmission. Pathogenic autoantibodies to muscle-specific tyrosine kinase (MuSK) can be found in patients with MG who do not have detectable antibodies to the acetylcholine receptor (AChR). MuSK MG includes immunological and clinical features that are generally distinct from AChR MG, particularly regarding responsiveness to therapy. B cell depletion has been shown to affect a decline in serum autoantibodies and to induce sustained clinical improvement in the majority of MuSK MG patients. However, the duration of this benefit may be limited, as we observed disease relapse in MuSK MG patients who had achieved rituximab-induced remission. We investigated the mechanisms of such relapses by exploring autoantibody production in the reemerging B cell compartment. Autoantibody-expressing CD27+ B cells were observed within the reconstituted repertoire during relapse but not during remission or in controls. Using two complementary approaches, which included production of 108 unique human monoclonal recombinant immunoglobulins, we demonstrated that antibody-secreting CD27hiCD38hi B cells (plasmablasts) contribute to the production of MuSK autoantibodies during relapse. The autoantibodies displayed hallmarks of antigen-driven affinity maturation. These collective findings introduce potential mechanisms for understanding both MuSK autoantibody production and disease relapse following B cell depletion. PMID:28878127

Exome chip meta-analysis identifies novel loci and East Asian-specific coding variants contributing to lipid levels and coronary artery disease

PubMed Central

Lu, Xiangfeng; Peloso, Gina M; Liu, Dajiang J.; Wu, Ying; Zhang, He; Zhou, Wei; Li, Jun; Tang, Clara Sze-man; Dorajoo, Rajkumar; Li, Huaixing; Long, Jirong; Guo, Xiuqing; Xu, Ming; Spracklen, Cassandra N.; Chen, Yang; Liu, Xuezhen; Zhang, Yan; Khor, Chiea Chuen; Liu, Jianjun; Sun, Liang; Wang, Laiyuan; Gao, Yu-Tang; Hu, Yao; Yu, Kuai; Wang, Yiqin; Cheung, Chloe Yu Yan; Wang, Feijie; Huang, Jianfeng; Fan, Qiao; Cai, Qiuyin; Chen, Shufeng; Shi, Jinxiu; Yang, Xueli; Zhao, Wanting; Sheu, Wayne H.-H.; Cherny, Stacey Shawn; He, Meian; Feranil, Alan B.; Adair, Linda S.; Gordon-Larsen, Penny; Du, Shufa; Varma, Rohit; da Chen, Yii-Der I; Shu, XiaoOu; Lam, Karen Siu Ling; Wong, Tien Yin; Ganesh, Santhi K.; Mo, Zengnan; Hveem, Kristian; Fritsche, Lars; Nielsen, Jonas Bille; Tse, Hung-fat; Huo, Yong; Cheng, Ching-Yu; Chen, Y. Eugene; Zheng, Wei; Tai, E Shyong; Gao, Wei; Lin, Xu; Huang, Wei; Abecasis, Goncalo; Consortium, GLGC; Kathiresan, Sekar; Mohlke, Karen L.; Wu, Tangchun; Sham, Pak Chung; Gu, Dongfeng; Willer, Cristen J

2017-01-01

Most genome-wide association studies have been conducted in European individuals, even though most genetic variation in humans is seen only in non-European samples. To search for novel loci associated with blood lipid levels and clarify the mechanism of action at previously identified lipid loci, we examined protein-coding genetic variants in 47,532 East Asian individuals using an exome array. We identified 255 variants at 41 loci reaching chip-wide significance, including 3 novel loci and 14 East Asian-specific coding variant associations. After meta-analysis with > 300,000 European samples, we identified an additional 9 novel loci. The same 16 genes were identified by the protein-altering variants in both East Asians and Europeans, likely pointing to the functional genes. Our data demonstrate that most of the low-frequency or rare coding variants associated with lipids are population-specific, and that examining genomic data across diverse ancestries may facilitate the identification of functional genes at associated loci. PMID:29083407

The registry case finding engine: an automated tool to identify cancer cases from unstructured, free-text pathology reports and clinical notes.

PubMed

Hanauer, David A; Miela, Gretchen; Chinnaiyan, Arul M; Chang, Alfred E; Blayney, Douglas W

2007-11-01

The American College of Surgeons mandates the maintenance of a cancer registry for hospitals seeking accreditation. At the University of Michigan Health System, more than 90% of all registry patients are identified by manual review, a method common to many institutions. We hypothesized that an automated computer system could accurately perform this time- and labor-intensive task. We created a tool to automatically scan free-text medical documents for terms relevant to cancer. We developed custom-made lists containing approximately 2,500 terms and phrases and 800 SNOMED codes. Text is processed by the Case Finding Engine (CaFE), and relevant terms are highlighted for review by a registrar and used to populate the registry database. We tested our system by comparing results from the CaFE to those by trained registrars who read through 2,200 pathology reports and marked relevant cases for the registry. The clinical documentation (eg, electronic chart notes) of an additional 476 patients was also reviewed by registrars and compared with the automated process by the CaFE. For pathology reports, the sensitivity for automated case identification was 100%, but specificity was 85.0%. For clinical documentation, sensitivity was 100% and specificity was 73.7%. Types of errors made by the CaFE were categorized to direct additional improvements. Use of the CaFE has resulted in a considerable increase in the number of cases added to the registry each month. The system has been well accepted by our registrars. CaFE can improve the accuracy and efficiency of tumor registry personnel and helps ensure that cancer cases are not overlooked.

Interactive Book Reading to Accelerate Word Learning by Kindergarten Children With Specific Language Impairment: Identifying an Adequate Intensity and Variation in Treatment Response.

PubMed

Storkel, Holly L; Voelmle, Krista; Fierro, Veronica; Flake, Kelsey; Fleming, Kandace K; Romine, Rebecca Swinburne

2017-01-01

This study sought to identify an adequate intensity of interactive book reading for new word learning by children with specific language impairment (SLI) and to examine variability in treatment response. An escalation design adapted from nontoxic drug trials (Hunsberger, Rubinstein, Dancey, & Korn, 2005) was used in this Phase I/II preliminary clinical trial. A total of 27 kindergarten children with SLI were randomized to 1 of 4 intensities of interactive book reading: 12, 24, 36, or 48 exposures. Word learning was monitored through a definition task and a naming task. An intensity response curve was examined to identify the adequate intensity. Correlations and classification accuracy were used to examine variation in response to treatment relative to pretreatment and early treatment measures. Response to treatment improved as intensity increased from 12 to 24 to 36 exposures, and then no further improvements were observed as intensity increased to 48 exposures. There was variability in treatment response: Children with poor phonological awareness, low vocabulary, and/or poor nonword repetition were less likely to respond to treatment. The adequate intensity for this version of interactive book reading was 36 exposures, but further development of the treatment is needed to increase the benefit for children with SLI.

Interactive Book Reading to Accelerate Word Learning by Kindergarten Children With Specific Language Impairment: Identifying an Adequate Intensity and Variation in Treatment Response

PubMed Central

Voelmle, Krista; Fierro, Veronica; Flake, Kelsey; Fleming, Kandace K.; Romine, Rebecca Swinburne

2017-01-01

Purpose This study sought to identify an adequate intensity of interactive book reading for new word learning by children with specific language impairment (SLI) and to examine variability in treatment response. Method An escalation design adapted from nontoxic drug trials (Hunsberger, Rubinstein, Dancey, & Korn, 2005) was used in this Phase I/II preliminary clinical trial. A total of 27 kindergarten children with SLI were randomized to 1 of 4 intensities of interactive book reading: 12, 24, 36, or 48 exposures. Word learning was monitored through a definition task and a naming task. An intensity response curve was examined to identify the adequate intensity. Correlations and classification accuracy were used to examine variation in response to treatment relative to pretreatment and early treatment measures. Results Response to treatment improved as intensity increased from 12 to 24 to 36 exposures, and then no further improvements were observed as intensity increased to 48 exposures. There was variability in treatment response: Children with poor phonological awareness, low vocabulary, and/or poor nonword repetition were less likely to respond to treatment. Conclusion The adequate intensity for this version of interactive book reading was 36 exposures, but further development of the treatment is needed to increase the benefit for children with SLI. PMID:28036410

Clinical evaluation of the new Roche platform of serological and molecular cytomegalovirus-specific assays in the diagnosis and prognosis of congenital cytomegalovirus infection.

PubMed

Chiereghin, Angela; Pavia, Claudia; Gabrielli, Liliana; Piccirilli, Giulia; Squarzoni, Diego; Turello, Gabriele; Gibertoni, Dino; Simonazzi, Giuliana; Capretti, Maria Grazia; Lanari, Marcello; Lazzarotto, Tiziana

2017-10-01

Clinical evaluation of the Elecsys ® CMV IgM, IgG, IgG Avidity and COBAS AmpliPrep/COBAS TaqMan CMV (COBAS CMV) assays (Roche Diagnostics AG) in the diagnosis and prognosis of congenital CMV infection was performed. In this study, 150 preselected clinical samples (50 primary infection sera, 50 amniotic fluid [AF] and 50 newborn urine) were processed using Roche serological/molecular CMV-specific tests. Results were compared with those obtained by routine assays (comparator assays). The Elecsys ® CMV IgM and IgG assays showed a perfect agreement (100%) with the comparator assays. Using the combination of the Elecsys ® CMV IgM and IgG Avidity assays results, a primary infection was identified in 100% of cases. Inappropriate avidity CMV IgG values in two samples with very low IgG values (<6 AU/mL) were observed. COBAS CMV assay showed an agreement equal to 98% and 100% with comparator assays by processing AF and urine samples, respectively. Among AF with quantitative results, Lin's concordance correlation was 0.933 and comparator-COBAS CMV assays gave CMV-DNA loads differing by <0.5 log 10 DNA. Finally, higher CMV-DNA levels in AF samples were associated with a symptomatic outcome (p=0.003). The Roche CMV-specific assays compared well with the comparator assays, thus providing to be suitable for clinical use. Copyright © 2017 Elsevier B.V. All rights reserved.

Clinical Ultrasound Is Safe and Highly Specific for Acute Appendicitis in Moderate to High Pre-test Probability Patients.

PubMed

Corson-Knowles, Daniel; Russell, Frances M

2018-05-01

Clinical ultrasound (CUS) is highly specific for the diagnosis of acute appendicitis but is operator-dependent. The goal of this study was to determine if a heterogeneous group of emergency physicians (EP) could diagnose acute appendicitis on CUS in patients with a moderate to high pre-test probability. This was a prospective, observational study of a convenience sample of adult and pediatric patients with suspected appendicitis. Sonographers received a structured, 20-minute CUS training on appendicitis prior to patient enrollment. The presence of a dilated (>6 mm diameter), non-compressible, blind-ending tubular structure was considered a positive study. Non-visualization or indeterminate studies were considered negative. We collected pre-test probability of acute appendicitis based on a 10-point visual analog scale (moderate to high was defined as >3), and confidence in CUS interpretation. The primary objective was measured by comparing CUS findings to surgical pathology and one week follow-up. We enrolled 105 patients; 76 had moderate to high pre-test probability. Of these, 24 were children. The rate of appendicitis was 36.8% in those with moderate to high pre-test probability. CUS were recorded by 33 different EPs. The sensitivity, specificity, and positive and negative likelihood ratios of EP-performed CUS in patients with moderate to high pre-test probability were 42.8% (95% confidence interval [CI] [25-62.5%]), 97.9% (95% CI [87.5-99.8%]), 20.7 (95% CI [2.8-149.9]) and 0.58 (95% CI [0.42-0.8]), respectively. The 16 false negative scans were all interpreted as indeterminate. There was one false positive CUS diagnosis; however, the sonographer reported low confidence of 2/10. A heterogeneous group of EP sonographers can safely identify acute appendicitis with high specificity in patients with moderate to high pre-test probability. This data adds support for surgical consultation without further imaging beyond CUS in the appropriate clinical setting.

Use of selected ambulatory dental services in Taiwan before and after global budgeting: a longitudinal study to identify trends in hospital and clinic-based services

PubMed Central

2012-01-01

Background The Taiwan government adopted National Health Insurance (NHI) in 1995, providing universal health care to all citizens. It was financed by mandatory premium contributions made by employers, employees, and the government. Since then, the government has faced increasing challenges to control NHI expenditures. The aim of this study was to determine trends in the provision of dental services in Taiwan after the implementation of global budgeting in 1998 and to identify areas of possible concern. Methods This longitudinal before/after study was based on data from the National Health Insurance Research Database from 1996 to 2001. These data were subjected to logistic regression analysis. Linear regression analysis was used to examine changes in delivery of specific services after global budgeting implementation. Utilization of hospital and clinic services was compared. Results Reimbursement for dental services increased significantly while the number of visits per patient remained steady in both hospitals and clinics. In hospitals, visits for root canal procedures, ionomer restoration, tooth extraction and tooth scaling increased significantly. In dental clinics, visits for amalgam restoration decreased significantly while those for ionomer restoration, tooth extraction, and tooth scaling increased significantly. After the adoption of global budgeting, expenditures for dental services increased dramatically while the number of visits per patient did not, indicating a possible shift in patients to hospital facilities that received additional National Health Insurance funding. Conclusions The identified trends indicate increased utilization of dental services and uneven distribution of care and dentists. These trends may be compromising the quality of dental care delivered in Taiwan. PMID:23009095

Use of selected ambulatory dental services in Taiwan before and after global budgeting: a longitudinal study to identify trends in hospital and clinic-based services.

PubMed

Lin, Chienhung; Chao, Hailun

2012-09-25

The Taiwan government adopted National Health Insurance (NHI) in 1995, providing universal health care to all citizens. It was financed by mandatory premium contributions made by employers, employees, and the government. Since then, the government has faced increasing challenges to control NHI expenditures. The aim of this study was to determine trends in the provision of dental services in Taiwan after the implementation of global budgeting in 1998 and to identify areas of possible concern. This longitudinal before/after study was based on data from the National Health Insurance Research Database from 1996 to 2001. These data were subjected to logistic regression analysis. Linear regression analysis was used to examine changes in delivery of specific services after global budgeting implementation. Utilization of hospital and clinic services was compared. Reimbursement for dental services increased significantly while the number of visits per patient remained steady in both hospitals and clinics. In hospitals, visits for root canal procedures, ionomer restoration, tooth extraction and tooth scaling increased significantly. In dental clinics, visits for amalgam restoration decreased significantly while those for ionomer restoration, tooth extraction, and tooth scaling increased significantly. After the adoption of global budgeting, expenditures for dental services increased dramatically while the number of visits per patient did not, indicating a possible shift in patients to hospital facilities that received additional National Health Insurance funding. The identified trends indicate increased utilization of dental services and uneven distribution of care and dentists. These trends may be compromising the quality of dental care delivered in Taiwan.

Nursing students in Iran identify the clinical environment stressors.

PubMed

Najafi Doulatabad, Shahla; Mohamadhosaini, Sima; Ghafarian Shirazi, Hamid Reza; Mohebbi, Zinat

2015-06-01

Stress at clinical environment is one of the cases that could affect the education quality among nursing students. The study aims to investigate Iranian nursing students' perceptions on the stressors in clinical environment in the South Western part of Iran. A cross-sectional descriptive study was conducted in 2010 to include 300 nursing students after their completion of second clinical nursing course in a hospital environment. Data were collected using a researcher-made questionnaire, with focus on the clinical environment stressors from personal, educational and training viewpoints. Data analysis was performed using SPSS software (IBM Corporation, Armonk, NY, USA) and descriptive statistics tests. Among the various stressors, the highest scores were given to the faculty (71 ± 19.77), followed by the students' personal characteristics (43.15 ± 21.79). Given that faculty-related factors provoked more stress in nursing students, nursing administration should diligently evaluate and improve communication skills among faculty to reduce student stress and enhance learning. © 2014 Wiley Publishing Asia Pty Ltd.

CLINICAL PROGRESS IN INHERITED RETINAL DEGENERATIONS: GENE THERAPY CLINICAL TRIALS AND ADVANCES IN GENETIC SEQUENCING

PubMed Central

HAFLER, BRIAN P.

2017-01-01

Purpose Inherited retinal dystrophies are a significant cause of vision loss and are characterized by the loss of photoreceptors and the retinal pigment epithelium (RPE). Mutations in approximately 250 genes cause inherited retinal degenerations with a high degree of genetic heterogeneity. New techniques in next-generation sequencing are allowing the comprehensive analysis of all retinal disease genes thus changing the approach to the molecular diagnosis of inherited retinal dystrophies. This review serves to analyze clinical progress in genetic diagnostic testing and implications for retinal gene therapy. Methods A literature search of PubMed and OMIM was conducted to relevant articles in inherited retinal dystrophies. Results Next-generation genetic sequencing allows the simultaneous analysis of all the approximately 250 genes that cause inherited retinal dystrophies. Reported diagnostic rates range are high and range from 51% to 57%. These new sequencing tools are highly accurate with sensitivities of 97.9% and specificities of 100%. Retinal gene therapy clinical trials are underway for multiple genes including RPE65, ABCA4, CHM, RS1, MYO7A, CNGA3, CNGB3, ND4, and MERTK for which a molecular diagnosis may be beneficial for patients. Conclusion Comprehensive next-generation genetic sequencing of all retinal dystrophy genes is changing the paradigm for how retinal specialists perform genetic testing for inherited retinal degenerations. Not only are high diagnostic yields obtained, but mutations in genes with novel clinical phenotypes are also identified. In the era of retinal gene therapy clinical trials, identifying specific genetic defects will increasingly be of use to identify patients who may enroll in clinical studies and benefit from novel therapies. PMID:27753762

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.

Sensitivity and specificity of FTDC criteria for behavioral variant frontotemporal dementia.

PubMed

Harris, Jennifer M; Gall, Claire; Thompson, Jennifer C; Richardson, Anna M T; Neary, David; du Plessis, Daniel; Pal, Piyali; Mann, David M A; Snowden, Julie S; Jones, Matthew

2013-05-14

We aimed to assess sensitivity and specificity of the updated criteria for behavioral variant frontotemporal dementia (bvFTD) based on a large autopsy-confirmed cohort of patients with dementia. Two hundred thirty-nine consecutive pathologically confirmed dementia patients, clinically assessed in a specialist cognitive unit were identified. Patients with predominant aphasia, motor disorders, or insufficient clinical information were excluded. Frontotemporal Dementia Consensus criteria were applied to anonymized clinical data taken from patients' initial assessment by raters who were blinded to clinical and pathologic diagnosis. The final study cohort comprised 156 patients with predominantly early-onset dementia. The updated criteria for possible bvFTD had a sensitivity of 95% and specificity of 82%. Probable bvFTD criteria had a sensitivity of 85% and specificity of 95%. False positives were predominantly patients with presenile Alzheimer disease. Revised diagnostic criteria show encouragingly high sensitivity and specificity when applied to patients with early-onset dementia. They therefore provide a useful tool both for specialist researchers and general clinicians. There is a need for further prospective studies of sensitivity and specificity involving a broader spectrum of patients with dementia.

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

PubMed

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

2015-04-21

Radiotherapy induces DNA damage and cell death, but recent data suggest that concomitant immune stimulation is an integral part of the therapeutic action of ionizing radiation. It is poorly understood how radiotherapy supports tumor-specific immunity. Here we report that radiotherapy induced tumor cell death and transiently activated complement both in murine and human tumors. The local production of pro-inflammatory anaphylatoxins C3a and C5a was crucial to the tumor response to radiotherapy and concomitant stimulation of tumor-specific immunity. Dexamethasone, a drug frequently given during radiotherapy, limited complement activation and the anti-tumor effects of the immune system. Overall, our findings indicate that anaphylatoxins are key players in radiotherapy-induced tumor-specific immunity and the ensuing clinical responses. Copyright © 2015 Elsevier Inc. All rights reserved.

An Evaluation of Algorithms for Identifying Metastatic Breast, Lung, or Colorectal Cancer in Administrative Claims Data.

PubMed

Whyte, Joanna L; Engel-Nitz, Nicole M; Teitelbaum, April; Gomez Rey, Gabriel; Kallich, Joel D

2015-07-01

Administrative health care claims data are used for epidemiologic, health services, and outcomes cancer research and thus play a significant role in policy. Cancer stage, which is often a major driver of cost and clinical outcomes, is not typically included in claims data. Evaluate algorithms used in a dataset of cancer patients to identify patients with metastatic breast (BC), lung (LC), or colorectal (CRC) cancer using claims data. Clinical data on BC, LC, or CRC patients (between January 1, 2007 and March 31, 2010) were linked to a health care claims database. Inclusion required health plan enrollment ≥3 months before initial cancer diagnosis date. Algorithms were used in the claims database to identify patients' disease status, which was compared with physician-reported metastases. Generic and tumor-specific algorithms were evaluated using ICD-9 codes, varying diagnosis time frames, and including/excluding other tumors. Positive and negative predictive values, sensitivity, and specificity were assessed. The linked databases included 14,480 patients; of whom, 32%, 17%, and 14.2% had metastatic BC, LC, and CRC, respectively, at diagnosis and met inclusion criteria. Nontumor-specific algorithms had lower specificity than tumor-specific algorithms. Tumor-specific algorithms' sensitivity and specificity were 53% and 99% for BC, 55% and 85% for LC, and 59% and 98% for CRC, respectively. Algorithms to distinguish metastatic BC, LC, and CRC from locally advanced disease should use tumor-specific primary cancer codes with 2 claims for the specific primary cancer >30-42 days apart to reduce misclassification. These performed best overall in specificity, positive predictive values, and overall accuracy to identify metastatic cancer in a health care claims database.

Psychometric properties of the Geriatric Anxiety Inventory (GAI) and its short-form (GAI-SF) in a clinical and non-clinical sample of older adults.

PubMed

Johnco, Carly; Knight, Ashleigh; Tadic, Dusanka; Wuthrich, Viviana M

2015-07-01

The Geriatric Anxiety Inventory is a 20-item geriatric-specific measure of anxiety severity. While studies suggest good internal consistency and convergent validity, divergent validity from measures of depression are weak. Clinical cutoffs have been developed that vary across studies due to the small clinical samples used. A six-item short form (GAI-SF) has been developed, and while this scale is promising, the research assessing the psychometrics of this scale is limited. This study examined the psychometric properties of GAI and GAI-SF in a large sample of 197 clinical geriatric participants with a comorbid anxiety and unipolar mood disorder, and a non-clinical control sample (N = 59). The internal consistency and convergent validity with other measures of anxiety was adequate for GAI and GAI-SF. Divergent validity from depressive symptoms was good in the clinical sample but weak in the total and non-clinical samples. Divergent validity from cognitive functioning was good in all samples. The one-factor structure was replicated for both measures. Receiver Operating Characteristic analyses indicated that the GAI is more accurate at identifying clinical status than the GAI-SF, although the sensitivity and specificity for the recommended cutoffs was adequate for both measures. Both GAI and GAI-SF show good psychometric properties for identifying geriatric anxiety. The GAI-SF may be a useful alternative screening measure for identifying anxiety in older adults.

Public clonotype usage identifies protective Gag-specific CD8+ T cell responses in SIV infection

PubMed Central

Asher, Tedi E.; Wilson, Nancy A.; Nason, Martha C.; Brenchley, Jason M.; Metzler, Ian S.; Venturi, Vanessa; Gostick, Emma; Chattopadhyay, Pratip K.; Roederer, Mario; Davenport, Miles P.; Watkins, David I.; Douek, Daniel C.

2009-01-01

Despite the pressing need for an AIDS vaccine, the determinants of protective immunity to HIV remain concealed within the complexity of adaptive immune responses. We dissected immunodominant virus-specific CD8+ T cell populations in Mamu-A*01+ rhesus macaques with primary SIV infection to elucidate the hallmarks of effective immunity at the level of individual constituent clonotypes, which were identified according to the expression of distinct T cell receptors (TCRs). The number of public clonotypes, defined as those that expressed identical TCR β-chain amino acid sequences and recurred in multiple individuals, contained within the acute phase CD8+ T cell population specific for the biologically constrained Gag CM9 (CTPYDINQM; residues 181–189) epitope correlated negatively with the virus load set point. This independent molecular signature of protection was confirmed in a prospective vaccine trial, in which clonotype engagement was governed by the nature of the antigen rather than the context of exposure and public clonotype usage was associated with enhanced recognition of epitope variants. Thus, the pattern of antigen-specific clonotype recruitment within a protective CD8+ T cell population is a prognostic indicator of vaccine efficacy and biological outcome in an AIDS virus infection. PMID:19349463

Prostate-specific antigen velocity is not better than total prostate-specific antigen in predicting prostate biopsy diagnosis.

PubMed

Gorday, William; Sadrzadeh, Hossein; de Koning, Lawrence; Naugler, Christopher T

2015-12-01

1.) Identify whether prostate-specific antigen velocity improves the ability to predict prostate biopsy diagnosis. 2.) Test whether there is an increase in the predictive capability of models when Gleason 7 prostate cancers are separated into a 3+4 and a 4+3 group. Calgary Laboratory Services' Clinical Laboratory Information System was searched for prostate biopsies reported between January 1, 2009 and December 31, 2013. Total prostate-specific antigen tests were recorded for each patient from January 1, 2007 to the most recent test before their recorded prostate biopsy. The data set was divided into the following three groups for comparison; benign, all prostate cancer and Gleason 7-10. The Gleason grade 7-10 group was further divided into 4+3 and 3+4 Gleason 7 prostate cancers. Prostate-specific antigen velocity was calculated using four different methods found in the literature. Receiver operator curves were used to assess operational characteristics of the tests. 4622 men between the ages of 40-89 with a prostate biopsy were included for analysis. Combining prostate-specific antigen velocity with total prostate-specific antigen (AUC=0.570-0.712) resulted in small non-statistically significant changes to the area under the curve compared to the area under the curve of total prostate-specific antigen alone (AUC=0.572-0.699). There were marked increases in the area under curves when 3+4 and 4+3 Gleason 7 cancers were separated. Prostate-specific antigen velocity does not add predictive value for prostate biopsy diagnosis. The clinical significance of the prostate specific antigen test can be improved by separating Gleason 7 prostate cancers into a 3+4 and 4+3 group. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Autobiographical memory specificity in response to verbal and pictorial cues in clinical depression.

PubMed

Ridout, Nathan; Dritschel, Barbara; Matthews, Keith; O'Carroll, Ronan

2016-06-01

Depressed individuals have been consistently shown to exhibit problems in accessing specific memories of events from their past and instead tend to retrieve categorical summaries of events. The majority of studies examining autobiographical memory changes associated with psychopathology have tended to use word cues, but only one study to date has used images (with PTSD patients). to determine if using images to cue autobiographical memories would reduce the memory specificity deficit exhibited by patients with depression in comparison to healthy controls. Twenty-five clinically depressed patients and twenty-five healthy controls were assessed on two versions of the autobiographical memory test; cued with emotional words and images. Depressed patients retrieved significantly fewer specific memories, and a greater number of categorical, than did the controls. Controls retrieved a greater proportion of specific memories to images compared to words, whereas depressed patients retrieved a similar proportion of specific memories to both images and words. no information about the presence and severity of past trauma was collected. results suggest that the overgeneral memory style in depression generalises from verbal to pictorial cues. This is important because retrieval to images may provide a more ecologically valid test of everyday memory experiences than word-cued retrieval.. Copyright © 2016 Elsevier Ltd. All rights reserved.

Identifying and treating codeine dependence: a systematic review.

PubMed

Nielsen, Suzanne; MacDonald, Tim; Johnson, Jacinta L

2018-06-04

Codeine dependence is a significant public health problem, motivating the recent rescheduling of codeine in Australia (1 February 2018). To provide information for informing clinical responses, we undertook a systematic review of what is known about identifying and treating codeine dependence. Articles published in English that described people who were codeine-dependent or a clinical approach to treating people who were codeine-dependent, without restriction on year of publication, were reviewed. Articles not including empirical data were excluded. One researcher screened each abstract; two researchers independently reviewed full text articles. Study quality was assessed, and data were extracted with standardised tools. MEDLINE and EMBASE were searched for relevant publications on 22 November 2016. The reference lists of eligible studies were searched to identify further relevant publications. 2150 articles were initially identified, of which 41 were eligible for inclusion in our analysis. Studies consistently reported specific characteristics associated with codeine dependence, including mental health comorbidity and escalation of codeine use attributed to psychiatric problems. Case reports and series described codeine dependence masked by complications associated with overusing simple analgesics and delayed detection. Ten studies described the treatment of codeine dependence. Three reports identified a role for behavioural therapy; the efficacy of CYP inhibitors in a small open label trial was not confirmed in a randomised controlled trial; four case series/chart reviews described opioid agonist therapy and medicated inpatient withdrawal; two qualitative studies identified barriers related to perceptions of codeine-dependent people and treatment providers, and confirmed positive perceptions and treatment outcomes achieved with opioid agonist treatments. Strategies for identifying problematic codeine use are needed. Identifying codeine dependence in clinical

Radiogenomics analysis identifies correlations of digital mammography with clinical molecular signatures in breast cancer.

PubMed

Tamez-Peña, Jose-Gerardo; Rodriguez-Rojas, Juan-Andrés; Gomez-Rueda, Hugo; Celaya-Padilla, Jose-Maria; Rivera-Prieto, Roxana-Alicia; Palacios-Corona, Rebeca; Garza-Montemayor, Margarita; Cardona-Huerta, Servando; Treviño, Victor

2018-01-01

In breast cancer, well-known gene expression subtypes have been related to a specific clinical outcome. However, their impact on the breast tissue phenotype has been poorly studied. Here, we investigate the association of imaging data of tumors to gene expression signatures from 71 patients with breast cancer that underwent pre-treatment digital mammograms and tumor biopsies. From digital mammograms, a semi-automated radiogenomics analysis generated 1,078 features describing the shape, signal distribution, and texture of tumors along their contralateral image used as control. From tumor biopsy, we estimated the OncotypeDX and PAM50 recurrence scores using gene expression microarrays. Then, we used multivariate analysis under stringent cross-validation to train models predicting recurrence scores. Few univariate features reached Spearman correlation coefficients above 0.4. Nevertheless, multivariate analysis yielded significantly correlated models for both signatures (correlation of OncotypeDX = 0.49 ± 0.07 and PAM50 = 0.32 ± 0.10 in stringent cross-validation and OncotypeDX = 0.83 and PAM50 = 0.78 for a unique model). Equivalent models trained from the unaffected contralateral breast were not correlated suggesting that the image signatures were tumor-specific and that overfitting was not a considerable issue. We also noted that models were improved by combining clinical information (triple negative status and progesterone receptor). The models used mostly wavelets and fractal features suggesting their importance to capture tumor information. Our results suggest that molecular-based recurrence risk and breast cancer subtypes have observable radiographic phenotypes. To our knowledge, this is the first study associating mammographic information to gene expression recurrence signatures.

Elastic light scattering for clinical pathogens identification: application to early screening of Staphylococcus aureus on specific medium

NASA Astrophysics Data System (ADS)

Schultz, E.; Genuer, V.; Marcoux, P.; Gal, O.; Belafdil, C.; Decq, D.; Maurin, Max; Morales, S.

2018-02-01

Elastic Light Scattering (ELS) is an innovative technique to identify bacterial pathogens directly on culture plates. Compelling results have already been reported for agri-food applications. Here, we have developed ELS for clinical diagnosis, starting with Staphylococcus aureus early screening. Our goal is to bring a result (positive/negative) after only 6 h of growth to fight surgical-site infections. The method starts with the acquisition of the scattering pattern arising from the interaction between a laser beam and a single bacterial colony growing on a culture medium. Then, the resulting image, considered as the bacterial species signature, is analyzed using statistical learning techniques. We present a custom optical setup able to target bacterial colonies with various sizes (30-500 microns). This system was used to collect a reference dataset of 38 strains of S. aureus and other Staphyloccocus species (5459 images) on ChromIDSAID/ MRSA bi-plates. A validation set from 20 patients has then been acquired and clinically-validated according to chromogenic enzymatic tests. The best correct-identification rate between S. aureus and S. non-aureus (94.7%) has been obtained using a support vector machine classifier trained on a combination of Fourier-Bessel moments and Local- Binary-Patterns extracted features. This statistical model applied to the validation set provided a sensitivity and a specificity of 90.0% and 56.9%, or alternatively, a positive predictive value of 47% and a negative predictive value of 93%. From a clinical point of view, the results head in the right direction and pave the way toward the WHO's requirements for rapid, low-cost, and automated diagnosis tools.

Clinical expression profiles of complex regional pain syndrome, fibromyalgia and a-specific repetitive strain injury: more common denominators than pain?

PubMed

Marinus, Johan; Van Hilten, Jacobus J

2006-03-30

To systematically evaluate and compare the clinical manifestations, disease course, risk factors and demographic characteristics of Complex Regional Pain Syndrome type 1 (CRPS), fibromyalgia (FM) and a-specific Repetitive Strain Injury (RSI). A literature search was performed using terms related to the aforementioned topics and diseases. Only original clinical studies that included at least 20 subjects were eligible. Fifty-nine studies on CRPS, 73 on FM and 7 on a-specific RSI were identified. The diseases show similarities in age distribution, male-female ratio, pain characteristics and sensory signs and symptoms. Motor, autonomic and trophic changes are frequently reported in CRPS, but only occasionally in FM and RSI. Systemic symptoms are found in patients with CRPS and FM, and in a subgroup of patients with RSI. In all three disorders, symptoms usually start locally, but may spread to other body regions later, which, in the case of FM, is a prerequisite for diagnosis. Disease onset is always, usually, or occasionally of traumatic origin in RSI, CRPS and FM, respectively. Anxiety and depression are more frequent in patients compared to controls, but probably not very different from patients with other pain conditions or chronic diseases. Apart from some obvious differences between CRPS, FM and RSI, the similarities are conspicuous. The common features of CRPS, FM and a-specific RSI may suggest that a common pathway is involved, but until patients with these type of symptoms are assessed with a uniform assessment procedure, a thorough comparison cannot be made. A systematic evaluation of patients with a suspected diagnosis of CRPS, FM or RSI, may lead to a better appreciation of the differences and similarities in these diseases and help to unravel the underlying mechanisms.

Identifying appropriate reference data models for comparative effectiveness research (CER) studies based on data from clinical information systems.

PubMed

Ogunyemi, Omolola I; Meeker, Daniella; Kim, Hyeon-Eui; Ashish, Naveen; Farzaneh, Seena; Boxwala, Aziz

2013-08-01

The need for a common format for electronic exchange of clinical data prompted federal endorsement of applicable standards. However, despite obvious similarities, a consensus standard has not yet been selected in the comparative effectiveness research (CER) community. Using qualitative metrics for data retrieval and information loss across a variety of CER topic areas, we compare several existing models from a representative sample of organizations associated with clinical research: the Observational Medical Outcomes Partnership (OMOP), Biomedical Research Integrated Domain Group, the Clinical Data Interchange Standards Consortium, and the US Food and Drug Administration. While the models examined captured a majority of the data elements that are useful for CER studies, data elements related to insurance benefit design and plans were most detailed in OMOP's CDM version 4.0. Standardized vocabularies that facilitate semantic interoperability were included in the OMOP and US Food and Drug Administration Mini-Sentinel data models, but are left to the discretion of the end-user in Biomedical Research Integrated Domain Group and Analysis Data Model, limiting reuse opportunities. Among the challenges we encountered was the need to model data specific to a local setting. This was handled by extending the standard data models. We found that the Common Data Model from the OMOP met the broadest complement of CER objectives. Minimal information loss occurred in mapping data from institution-specific data warehouses onto the data models from the standards we assessed. However, to support certain scenarios, we found a need to enhance existing data dictionaries with local, institution-specific information.

In vitro modeling to determine mutation specificity of EGFR tyrosine kinase inhibitors against clinically relevant EGFR mutants in non-small-cell lung cancer

PubMed Central

Yasuda, Hiroyuki; Hamamoto, Junko; Oashi, Ayano; Ishioka, Kota; Arai, Daisuke; Nukaga, Shigenari; Miyawaki, Masayoshi; Kawada, Ichiro; Naoki, Katsuhiko; Costa, Daniel B.; Kobayashi, Susumu S.; Betsuyaku, Tomoko; Soejima, Kenzo

2015-01-01

EGFR mutated lung cancer accounts for a significant subgroup of non-small-cell lung cancer (NSCLC). Over the last decade, multiple EGFR tyrosine kinase inhibitors (EGFR-TKIs) have been developed to target mutated EGFR. However, there is little information regarding mutation specific potency of EGFR-TKIs against various types of EGFR mutations. The purpose of this study is to establish an in vitro model to determine the “therapeutic window” of EGFR-TKIs against various types of EGFR mutations, including EGFR exon 20 insertion mutations. The potency of 1st (erlotinib), 2nd (afatinib) and 3rd (osimertinib and rociletinib) generation EGFR-TKIs was compared in vitro for human lung cancer cell lines and Ba/F3 cells, which exogenously express mutated or wild type EGFR. An in vitro model of mutation specificity was created by calculating the ratio of IC50 values between mutated and wild type EGFR. The in vitro model identified a wide therapeutic window of afatinib for exon 19 deletions and L858R and of osimertinib and rociletinib for T790M positive mutations. The results obtained with our models matched well with previously reported preclinical and clinical data. Interestingly, for EGFR exon 20 insertion mutations, most of which are known to be resistant to 1st and 2nd generation EGFR-TKIS, osimertinib was potent and presented a wide therapeutic window. To our knowledge, this is the first report that has identified the therapeutic window of osimertinib for EGFR exon 20 insertion mutations. In conclusion, this model will provide a preclinical rationale for proper selection of EGFR-TKIs against clinically-relevant EGFR mutations. PMID:26515464

The clinical phenotype associated with myositis-specific and associated autoantibodies: a meta-analysis revisiting the so-called antisynthetase syndrome.

PubMed

Lega, Jean-Christophe; Fabien, Nicole; Reynaud, Quitterie; Durieu, Isabelle; Durupt, Stéphane; Dutertre, Marine; Cordier, Jean-François; Cottin, Vincent

2014-09-01

To describe the clinical spectrum associated with aminoacyl-transfer RNA synthetase (ARS) autoantibodies in patients with idiopathic inflammatory myositis defined according to Peter and Bohan's criteria. Cohort studies were selected from MEDLINE and Embase up to August 2013. Two investigators independently extracted data on study design, patient characteristics, and clinical features (interstitial lung disease [ILD], fever, mechanic's hands [MH], Raynaud's phenomenon [RPh], arthralgia, sclerodactyly, cancer and dermatomyositis-specific rash) according to the presence of myositis-specific (anti-aminoacyl-transfer RNA synthetase [ARS], anti-signal recognition particle [anti-SRP] and anti-Mi2) and myositis-associated (anti-PM/Scl, anti-U1-RNP and anti-Ku) autoantibodies. 27 studies (3487 patients) were included in the meta-analysis. Arthralgia (75%, CI 67-81) and ILD (69%, CI 63-74) were the most prevalent clinical signs associated with anti-ARS autoantibodies. Anti-Mi2 and anti-SRP autoantibodies were associated with few extramuscular signs. ARS autoantibodies were identified in 13% of patients with cancer-associated myositis (5-25). Patients with non-anti-Jo1 ARS had greater odds of presenting fever (RR 0.63, CI 0.52-0.90) and ILD (RR 0.87, CI 0.81-0.93) compared to those with anti-Jo1 autoantibodies. The frequencies of myositis (RR 1.60, CI 1.38-1.85), arthralgia (RR 1.52, CI 1.32-1.76) and MH (RR 1.47, CI 1.11-1.94) were almost 50% higher in patients with anti-Jo1 compared to non-anti-Jo1 ARS autoantibodies. Patients with anti-PM/Scl differed from those with anti-ARS autoantibodies by a greater prevalence of RPh (RR 0.70, CI 0.53-0.94) and sclerodactyly (RR 0.47, CI 0.25-0.89). ILD was less frequent in patients with anti-U1-RNP autoantibodies (RR 3.35, CI 1.07-10.43). No difference was observed between anti-ARS and myositis-associated autoantibodies for other outcomes. The presence of anti-ARS autoantibodies delimits a heterogeneous subset of patients with a high

A review of biomarkers for predicting clinical reactivity to foods with a focus on specific immunoglobulin E antibodies.

PubMed

Sato, Sakura; Yanagida, Noriyuki; Ohtani, Kiyotaka; Koike, Yumi; Ebisawa, Motohiro

2015-06-01

The purpose of this study is to assess the latest studies that focus on specific immunoglobulin (Ig)E antibodies for predicting clinical reactivity to foods. Persistent hen's egg and cow's milk allergy patients have higher antigen-specific IgE levels at all ages than those who have outgrown these allergies. Recent studies on the natural histories of hen's egg and cow's milk allergies suggested that baseline antigen-specific IgEs are the most important predictors of tolerance. Oral immunotherapy (OIT), which is a novel therapeutic approach for food allergy, requires biomarkers for predicting outcomes after therapy. Several studies indicate that the initial antigen-specific IgE level may be a useful biomarker for the prognosis of OIT. Recently, component-resolved diagnostics (CRD) has been used for food allergy diagnosis. Current studies have suggested that Ara h 2, omega-5 gliadin and ovomucoid are good diagnostic markers for peanut, wheat and egg allergies, respectively. Antigen-specific IgE can be a useful biomarker for predicting clinical reactivity to food allergies. Monitoring hen's egg and cow's milk-specific IgE is useful for predicting prognosis, and baseline specific IgE levels may be associated with the outcome of OIT. The use of CRD provides us with a better tool for diagnosing food allergy.

Identifying Pediatric Severe Sepsis and Septic Shock: Accuracy of Diagnosis Codes.

PubMed

Balamuth, Fran; Weiss, Scott L; Hall, Matt; Neuman, Mark I; Scott, Halden; Brady, Patrick W; Paul, Raina; Farris, Reid W D; McClead, Richard; Centkowski, Sierra; Baumer-Mouradian, Shannon; Weiser, Jason; Hayes, Katie; Shah, Samir S; Alpern, Elizabeth R

2015-12-01

To evaluate accuracy of 2 established administrative methods of identifying children with sepsis using a medical record review reference standard. Multicenter retrospective study at 6 US children's hospitals. Subjects were children >60 days to <19 years of age and identified in 4 groups based on International Classification of Diseases, Ninth Revision, Clinical Modification codes: (1) severe sepsis/septic shock (sepsis codes); (2) infection plus organ dysfunction (combination codes); (3) subjects without codes for infection, organ dysfunction, or severe sepsis; and (4) infection but not severe sepsis or organ dysfunction. Combination codes were allowed, but not required within the sepsis codes group. We determined the presence of reference standard severe sepsis according to consensus criteria. Logistic regression was performed to determine whether addition of codes for sepsis therapies improved case identification. A total of 130 out of 432 subjects met reference SD of severe sepsis. Sepsis codes had sensitivity 73% (95% CI 70-86), specificity 92% (95% CI 87-95), and positive predictive value 79% (95% CI 70-86). Combination codes had sensitivity 15% (95% CI 9-22), specificity 71% (95% CI 65-76), and positive predictive value 18% (95% CI 11-27). Slight improvements in model characteristics were observed when codes for vasoactive medications and endotracheal intubation were added to sepsis codes (c-statistic 0.83 vs 0.87, P = .008). Sepsis specific International Classification of Diseases, Ninth Revision, Clinical Modification codes identify pediatric patients with severe sepsis in administrative data more accurately than a combination of codes for infection plus organ dysfunction. Copyright © 2015 Elsevier Inc. All rights reserved.

Single measure and gated screening approaches for identifying students at-risk for academic problems: Implications for sensitivity and specificity.

PubMed

Van Norman, Ethan R; Nelson, Peter M; Klingbeil, David A

2017-09-01

Educators need recommendations to improve screening practices without limiting students' instructional opportunities. Repurposing previous years' state test scores has shown promise in identifying at-risk students within multitiered systems of support. However, researchers have not directly compared the diagnostic accuracy of previous years' state test scores with data collected during fall screening periods to identify at-risk students. In addition, the benefit of using previous state test scores in conjunction with data from a separate measure to identify at-risk students has not been explored. The diagnostic accuracy of 3 types of screening approaches were tested to predict proficiency on end-of-year high-stakes assessments: state test data obtained during the previous year, data from a different measure administered in the fall, and both measures combined (i.e., a gated model). Extant reading and math data (N = 2,996) from 10 schools in the Midwest were analyzed. When used alone, both measures yielded similar sensitivity and specificity values. The gated model yielded superior specificity values compared with using either measure alone, at the expense of sensitivity. Implications, limitations, and ideas for future research are discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Clinical Growth: An Evolutionary Concept Analysis.

PubMed

Barkimer, Jessica

2016-01-01

Clinical growth is an essential component of nursing education, although challenging to evaluate. Considering the paradigm shift toward constructivism and student-centered learning, clinical growth requires an examination within contemporary practices. A concept analysis of clinical growth in nursing education produced defining attributes, antecedents, and consequences. Attributes included higher-level thinking, socialization, skill development, self-reflection, self-investment, interpersonal communication, and linking theory to practice. Identification of critical attributes allows educators to adapt to student-centered learning in the clinical environment. These findings allow educators to determine significant research questions, develop situation-specific theories, and identify strategies to enhance student learning in the clinical environment.

Using the Textpresso Site-Specific Recombinases Web server to identify Cre expressing mouse strains and floxed alleles.

PubMed

Condie, Brian G; Urbanski, William M

2014-01-01

Effective tools for searching the biomedical literature are essential for identifying reagents or mouse strains as well as for effective experimental design and informed interpretation of experimental results. We have built the Textpresso Site Specific Recombinases (Textpresso SSR) Web server to enable researchers who use mice to perform in-depth searches of a rapidly growing and complex part of the mouse literature. Our Textpresso Web server provides an interface for searching the full text of most of the peer-reviewed publications that report the characterization or use of mouse strains that express Cre or Flp recombinase. The database also contains most of the publications that describe the characterization or analysis of strains carrying conditional alleles or transgenes that can be inactivated or activated by site-specific recombinases such as Cre or Flp. Textpresso SSR complements the existing online databases that catalog Cre and Flp expression patterns by providing a unique online interface for the in-depth text mining of the site specific recombinase literature.

At-risk studies and clinical antecedents of psychosis, bipolar disorder and depression: a scoping review in the context of clinical staging.

PubMed

Hartmann, Jessica A; Nelson, Barnaby; Ratheesh, Aswin; Treen, Devi; McGorry, Patrick D

2018-06-04

Identifying young people at risk of developing serious mental illness and identifying predictors of onset of illness has been a focus of psychiatric prediction research, particularly in the field of psychosis. Work in this area has facilitated the adoption of the clinical staging model of early clinical phenotypes, ranging from at-risk mental states to chronic and severe mental illness. It has been a topic of debate if these staging models should be conceptualised as disorder-specific or transdiagnostic. In order to inform this debate and facilitate cross-diagnostic discourse, the present scoping review provides a broad overview of the body of literature of (a) longitudinal at-risk approaches and (b) identified antecedents of (homotypic) illness progression across three major mental disorders [psychosis, bipolar disorder (BD) and depression], and places these in the context of clinical staging. Stage 0 at-risk conceptualisations (i.e. familial high-risk approaches) were identified in all three disorders. However, formalised stage 1b conceptualisations (i.e. ultra-high-risk approaches) were only present in psychosis and marginally in BD. The presence of non-specific and overlapping antecedents in the three disorders may support a general staging model, at least in the early stages of severe psychotic or mood disorders.

Identifying clinical learning needs using structured group feedback: first year evaluation of pre-registration nursing and midwifery degree programmes.

PubMed

Frazer, Kate; Connolly, Michael; Naughton, Corina; Kow, Veronica

2014-07-01

Facilitating and supporting clinical learning for student nurses and midwives are essential within their practice environments. Clinical placements provide unique opportunities in preparation for future roles. Understanding the experiences of first year student nurses and midwives following clinical exposures and examining the clinical facilitators and barriers can assist in maintaining and developing clinical supports. The study used a structured group feedback approach with a convenience sample of 223 first year nursing and midwifery students in one Irish university in April 2011 to ascertain feedback on the clinical aspects of their degree programme. Approximately 200 students participated in the process. Two key clinical issues were identified by students: facilitating clinical learning and learning experiences and needs. Positive learning environments, supportive staff and increased opportunities for reflection were important issues for first year students. The role of supportive mentoring staff in clinical practice is essential to enhance student learning. Students value reflection in practice and require more opportunities to engage during placements. More collaborative approaches are required to ensure evolving and adapting practice environments can accommodate student learning. Copyright © 2014 Elsevier Ltd. All rights reserved.

A survey to identify the clinical coding and classification systems currently in use across Europe.

PubMed

de Lusignan, S; Minmagh, C; Kennedy, J; Zeimet, M; Bommezijn, H; Bryant, J

2001-01-01

This is a survey to identify what clinical coding systems are currently in use across the European Union, and the states seeking membership to it. We sought to identify what systems are currently used and to what extent they were subject to local adaptation. Clinical coding should facilitate identifying key medical events in a computerised medical record, and aggregating information across groups of records. The emerging new driver is as the enabler of the life-long computerised medical record. A prerequisite for this level of functionality is the transfer of information between different computer systems. This transfer can be facilitated either by working on the interoperability problems between disparate systems or by harmonising the underlying data. This paper examines the extent to which the latter has occurred across Europe. Literature and Internet search. Requests for information via electronic mail to pan-European mailing lists of health informatics professionals. Coding systems are now a de facto part of health information systems across Europe. There are relatively few coding systems in existence across Europe. ICD9 and ICD 10, ICPC and Read were the most established. However the local adaptation of these classification systems either on a by country or by computer software manufacturer basis; significantly reduces the ability for the meaning coded with patients computer records to be easily transferred from one medical record system to another. There is no longer any debate as to whether a coding or classification system should be used. Convergence of different classifications systems should be encouraged. Countries and computer manufacturers within the EU should be encouraged to stop making local modifications to coding and classification systems, as this practice risks significantly slowing progress towards easy transfer of records between computer systems.

Identifying neuropathic pain in patients with multiple sclerosis: a cross-sectional multicenter study using highly specific criteria.

PubMed

Solaro, Claudio; Cella, M; Signori, Alessio; Martinelli, Vittorio; Radaelli, Marta; Centonze, D; Sica, F; Grasso, M G; Clemenzi, A; Bonavita, S; Esposito, S; Patti, F; D'Amico, E; Cruccu, G; Truini, A

2018-04-01

Pain is a common and heterogeneous complication of multiple sclerosis (MS). In this multicenter, cross sectional study, we aimed at investigating the prevalence of pain in MS using highly specific criteria for distinguishing the different types of pain. After a structured interview, in patients with pain, clinical examination and DN4 questionnaire were used for distinguishing neuropathic and nociceptive pain. In subjects with neuropathic pain, the Neuropathic Pain Symptom Inventory was used for differentiating neuropathic pain symptoms. We enrolled 1249 participants (832 F, 417 M, mean age 33.9 years, mean disease duration 8 years, mean EDSS 3.2); based on clinical evaluation and DN4 score 429 patients (34.34%) were classified with pain (470 pain syndromes): 286 nociceptive pain syndromes and 184 neuropathic pain syndromes. Multivariate analysis showed that pain was associated with age, gender and disease severity and that neuropathic pain was distinctly associated with EDSS. Our study, providing definite information on the prevalence, characteristics and variables associated with neuropathic pain due to MS, shows that a more severe disease course is associated with a higher risk of neuropathic pain. Our findings might, therefore, provide a basis for improving the clinical management of this common MS complication.

Ancestry-specific and sex-specific risk alleles identified in a genome-wide gene-by-alcohol dependence interaction study of risky sexual behaviors.

PubMed

Polimanti, Renato; Zhao, Hongyu; Farrer, Lindsay A; Kranzler, Henry R; Gelernter, Joel

2017-12-01

We previously mapped loci for the genome-wide association studies (GWAS) and genome-wide gene-by-alcohol dependence interaction (GW-GxAD) analyses of risky sexual behaviors (RSB). This study extends those findings by analyzing the ancestry- and sex-specific AD-stratified effects on RSB. We examined the concordance of findings for the AD-stratified GWAS and the GW-GxAD analysis of RSB, with concordance defined as genome-wide significance in one analysis and at least nominal significance in the second analysis. A total of 2,173 African-American (AA) and 1,751 European-American (EA) subjects were investigated. Information regarding RSB (lifetime experiences of unprotected sex and multiple sexual partners) and DSM-IV diagnosis of lifetime AD were derived from the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA). In our ancestry- and sex-specific analyses, we identified four independent genome-wide significant (GWS) loci (p < 5*10 -8 ) and one suggestive locus (p < 6*10 -8 ). In men, we observed a GWS signal in FAM162A (rs2002594, p = 4.96*10 -8 ). In women, there was a suggestive locus in PLGRKT (rs3824435, p = 5.52*10 -8 ). In AAs, there was a GWS signal in GRK5 (rs1316543, p = 1.25*10 -9 ). In AA men, we observed an intergenic GWS signal (rs12898370, p = 4.49*10 -8 ) near LINGO1. In EA men, there was a GWS signal in CCSER1 (rs62313897; p = 7.93*10 -10 ). The loci identified in this GWAS implicate molecular mechanisms related to psychiatric illness and personality features, suggesting that the interplay between AD and RSB is mediated by alleles associated with behavioral traits. © 2017 Wiley Periodicals, Inc.

Utility of quantitative sensory testing and screening tools in identifying HIV-associated peripheral neuropathy in Western Kenya: pilot testing.

PubMed

Cettomai, Deanna; Kwasa, Judith; Kendi, Caroline; Birbeck, Gretchen L; Price, Richard W; Bukusi, Elizabeth A; Cohen, Craig R; Meyer, Ana-Claire

2010-12-08

Neuropathy is the most common neurologic complication of HIV but is widely under-diagnosed in resource-constrained settings. We aimed to identify tools that accurately distinguish individuals with moderate/severe peripheral neuropathy and can be administered by non-physician healthcare workers (HCW) in resource-constrained settings. We enrolled a convenience sample of 30 HIV-infected outpatients from a Kenyan HIV-care clinic. A HCW administered the Neuropathy Severity Score (NSS), Single Question Neuropathy Screen (Single-QNS), Subjective Peripheral Neuropathy Screen (Subjective-PNS), and Brief Peripheral Neuropathy Screen (Brief-PNS). Monofilament, graduated tuning fork, and two-point discrimination examinations were performed. Tools were validated against a neurologist's clinical assessment of moderate/severe neuropathy. The sample was 57% male, mean age 38.6 years, and mean CD4 count 324 cells/µL. Neurologist's assessment identified 20% (6/30) with moderate/severe neuropathy. Diagnostic utilities for moderate/severe neuropathy were: Single-QNS--83% sensitivity, 71% specificity; Subjective-PNS-total--83% sensitivity, 83% specificity; Subjective-PNS-max and NSS--67% sensitivity, 92% specificity; Brief-PNS--0% sensitivity, 92% specificity; monofilament--100% sensitivity, 88% specificity; graduated tuning fork--83% sensitivity, 88% specificity; two-point discrimination--75% sensitivity, 58% specificity. Pilot testing suggests Single-QNS, Subjective-PNS, and monofilament examination accurately identify HIV-infected patients with moderate/severe neuropathy and may be useful diagnostic tools in resource-constrained settings.

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

A consensus exercise identifying priorities for research into clinical effectiveness among children's orthopaedic surgeons in the United Kingdom.

PubMed

Perry, D C; Wright, J G; Cooke, S; Roposch, A; Gaston, M S; Nicolaou, N; Theologis, T

2018-05-01

Aims High-quality clinical research in children's orthopaedic surgery has lagged behind other surgical subspecialties. This study used a consensus-based approach to identify research priorities for clinical trials in children's orthopaedics. Methods A modified Delphi technique was used, which involved an initial scoping survey, a two-round Delphi process and an expert panel formed of members of the British Society of Children's Orthopaedic Surgery. The survey was conducted amongst orthopaedic surgeons treating children in the United Kingdom and Ireland. Results A total of 86 clinicians contributed to both rounds of the Delphi process, scoring priorities from one (low priority) to five (high priority). Elective topics were ranked higher than those relating to trauma, with the top ten elective research questions scoring higher than the top question for trauma. Ten elective, and five trauma research priorities were identified, with the three highest ranked questions relating to the treatment of slipped capital femoral epiphysis (mean score 4.6/ 5), Perthes' disease (4.5) and bone infection (4.5). Conclusion This consensus-based research agenda will guide surgeons, academics and funders to improve the evidence in children's orthopaedic surgery and encourage the development of multicentre clinical trials. Cite this article: Bone Joint J 2018;100-B:680-4.

What is a clinical pathway? Refinement of an operational definition to identify clinical pathway studies for a Cochrane systematic review.

PubMed

Lawal, Adegboyega K; Rotter, Thomas; Kinsman, Leigh; Machotta, Andreas; Ronellenfitsch, Ulrich; Scott, Shannon D; Goodridge, Donna; Plishka, Christopher; Groot, Gary

2016-02-23

Clinical pathways (CPWs) are a common component in the quest to improve the quality of health. CPWs are used to reduce variation, improve quality of care, and maximize the outcomes for specific groups of patients. An ongoing challenge is the operationalization of a definition of CPW in healthcare. This may be attributable to both the differences in definition and a lack of conceptualization in the field of clinical pathways. This correspondence article describes a process of refinement of an operational definition for CPW research and proposes an operational definition for the future syntheses of CPWs literature. Following the approach proposed by Kinsman et al. (BMC Medicine 8(1):31, 2010) and Wieland et al. (Alternative Therapies in Health and Medicine 17(2):50, 2011), we used a four-stage process to generate a five criteria checklist for the definition of CPWs. We refined the operational definition, through consensus, merging two of the checklist's criteria, leading to a more inclusive criterion for accommodating CPW studies conducted in various healthcare settings. The following four criteria for CPW operational definition, derived from the refinement process described above, are (1) the intervention was a structured multidisciplinary plan of care; (2) the intervention was used to translate guidelines or evidence into local structures; (3) the intervention detailed the steps in a course of treatment or care in a plan, pathway, algorithm, guideline, protocol or other 'inventory of actions' (i.e. the intervention had time-frames or criteria-based progression); and (4) the intervention aimed to standardize care for a specific population. An intervention meeting all four criteria was considered to be a CPW. The development of operational definitions for complex interventions is a useful approach to appraise and synthesize evidence for policy development and quality improvement.

Clinical pharmacology of analgesics assessed with human experimental pain models: bridging basic and clinical research

PubMed Central

Oertel, Bruno Georg; Lötsch, Jörn

2013-01-01

The medical impact of pain is such that much effort is being applied to develop novel analgesic drugs directed towards new targets and to investigate the analgesic efficacy of known drugs. Ongoing research requires cost-saving tools to translate basic science knowledge into clinically effective analgesic compounds. In this review we have re-examined the prediction of clinical analgesia by human experimental pain models as a basis for model selection in phase I studies. The overall prediction of analgesic efficacy or failure of a drug correlated well between experimental and clinical settings. However, correct model selection requires more detailed information about which model predicts a particular clinical pain condition. We hypothesized that if an analgesic drug was effective in an experimental pain model and also a specific clinical pain condition, then that model might be predictive for that particular condition and should be selected for development as an analgesic for that condition. The validity of the prediction increases with an increase in the numbers of analgesic drug classes for which this agreement was shown. From available evidence, only five clinical pain conditions were correctly predicted by seven different pain models for at least three different drugs. Most of these models combine a sensitization method. The analysis also identified several models with low impact with respect to their clinical translation. Thus, the presently identified agreements and non-agreements between analgesic effects on experimental and on clinical pain may serve as a solid basis to identify complex sets of human pain models that bridge basic science with clinical pain research. PMID:23082949

Radiogenomics analysis identifies correlations of digital mammography with clinical molecular signatures in breast cancer

PubMed Central

Tamez-Peña, Jose-Gerardo; Rodriguez-Rojas, Juan-Andrés; Gomez-Rueda, Hugo; Celaya-Padilla, Jose-Maria; Rivera-Prieto, Roxana-Alicia; Palacios-Corona, Rebeca; Garza-Montemayor, Margarita; Cardona-Huerta, Servando

2018-01-01

In breast cancer, well-known gene expression subtypes have been related to a specific clinical outcome. However, their impact on the breast tissue phenotype has been poorly studied. Here, we investigate the association of imaging data of tumors to gene expression signatures from 71 patients with breast cancer that underwent pre-treatment digital mammograms and tumor biopsies. From digital mammograms, a semi-automated radiogenomics analysis generated 1,078 features describing the shape, signal distribution, and texture of tumors along their contralateral image used as control. From tumor biopsy, we estimated the OncotypeDX and PAM50 recurrence scores using gene expression microarrays. Then, we used multivariate analysis under stringent cross-validation to train models predicting recurrence scores. Few univariate features reached Spearman correlation coefficients above 0.4. Nevertheless, multivariate analysis yielded significantly correlated models for both signatures (correlation of OncotypeDX = 0.49 ± 0.07 and PAM50 = 0.32 ± 0.10 in stringent cross-validation and OncotypeDX = 0.83 and PAM50 = 0.78 for a unique model). Equivalent models trained from the unaffected contralateral breast were not correlated suggesting that the image signatures were tumor-specific and that overfitting was not a considerable issue. We also noted that models were improved by combining clinical information (triple negative status and progesterone receptor). The models used mostly wavelets and fractal features suggesting their importance to capture tumor information. Our results suggest that molecular-based recurrence risk and breast cancer subtypes have observable radiographic phenotypes. To our knowledge, this is the first study associating mammographic information to gene expression recurrence signatures. PMID:29596496