Sample records for identifying clinically significant

  1. Use of electronic data and existing screening tools to identify clinically significant obstructive sleep apnea.

    PubMed

    Severson, Carl A; Pendharkar, Sachin R; Ronksley, Paul E; Tsai, Willis H

    2015-01-01

    To assess the ability of electronic health data and existing screening tools to identify clinically significant obstructive sleep apnea (OSA), as defined by symptomatic or severe OSA. The present retrospective cohort study of 1041 patients referred for sleep diagnostic testing was undertaken at a tertiary sleep centre in Calgary, Alberta. A diagnosis of clinically significant OSA or an alternative sleep diagnosis was assigned to each patient through blinded independent chart review by two sleep physicians. Predictive variables were identified from online questionnaire data, and diagnostic algorithms were developed. The performance of electronically derived algorithms for identifying patients with clinically significant OSA was determined. Diagnostic performance of these algorithms was compared with versions of the STOP-Bang questionnaire and adjusted neck circumference score (ANC) derived from electronic data. Electronic questionnaire data were highly sensitive (>95%) at identifying clinically significant OSA, but not specific. Sleep diagnostic testing-determined respiratory disturbance index was very specific (specificity ≥95%) for clinically relevant disease, but not sensitive (<35%). Derived algorithms had similar accuracy to the STOP-Bang or ANC, but required fewer questions and calculations. These data suggest that a two-step process using a small number of clinical variables (maximizing sensitivity) and objective diagnostic testing (maximizing specificity) is required to identify clinically significant OSA. When used in an online setting, simple algorithms can identify clinically relevant OSA with similar performance to existing decision rules such as the STOP-Bang or ANC.

  2. Needle Acupuncture for Substance Use Disorders: A Systematic Review

    DTIC Science & Technology

    2015-01-01

    RCTs). We did identify statistically significant, clinically medium effects in favor of acupuncture (as an adjunctive or monotherapy) versus any...statistically significant, clinically medium effects in favor of acupuncture (as an adjunctive or monotherapy) versus any comparator at...at postintervention. We did identify statistically significant, clinically medium effects in favor of acupuncture (as an adjunctive or monotherapy

  3. Cost-benefit value of microscopic examination of intervertebral discs.

    PubMed

    Grzybicki, D M; Callaghan, E J; Raab, S S

    1998-09-01

    Given the virtual absence of histologically detected, clinically unsuspected disease in intervertebral disc specimens, some authors have advocated that histological examination be discontinued. However, the examination of intervertebral disc specimens remains common practice in most pathology laboratories. No cost-benefit analysis of this practice has been made; therefore, the authors' goal in this study was perform such an analysis. Using the University of Iowa surgical pathology database, 1109 patients who had undergone a laminectomy were identified retrospectively. These cases were classified into four categories based on the patients' preoperative clinical diagnosis and final histopathological diagnosis: insignificant clinical diagnosis/insignificant pathological diagnosis (ICIP), significant clinical diagnosis/insignificant pathological diagnosis (SCIP), significant clinical diagnosis/significant pathological diagnosis (SCSP), and insignificant clinical diagnosis/significant pathological diagnosis (ICSP). A significant clinical diagnosis was defined as one other than a benign, noninfectious indication for laminectomy. A significant pathological diagnosis was a diagnosis other than degenerative changes. The cost-benefit value of performing a histological examination in cases with significant or insignificant clinical diagnoses was examined. The cases were classified as: 1068 ICIP, 17 SCIP, 21 SCSP, and three ICSP. On chart review, in all three cases of ICSP an epidural abscess was identified perioperatively and the subsequent histological diagnosis did not affect patient care. The costs per case of identifying a significant pathological diagnosis with a significant and an insignificant clinical diagnosis were $44.79 and $8811, respectively. Histological examination of intervertebral disc specimens is cost beneficial only if there is a significant preoperative clinical diagnosis.

  4. Identifying treatment responders and predictors of improvement after cognitive-behavioral therapy for juvenile fibromyalgia.

    PubMed

    Sil, Soumitri; Arnold, Lesley M; Lynch-Jordan, Anne; Ting, Tracy V; Peugh, James; Cunningham, Natoshia; Powers, Scott W; Lovell, Daniel J; Hashkes, Philip J; Passo, Murray; Schikler, Kenneth N; Kashikar-Zuck, Susmita

    2014-07-01

    The primary objective of this study was to estimate a clinically significant and quantifiable change in functional disability to identify treatment responders in a clinical trial of cognitive-behavioral therapy (CBT) for youth with juvenile fibromyalgia (JFM). The second objective was to examine whether baseline functional disability (Functional Disability Inventory), pain intensity, depressive symptoms (Children's Depression Inventory), coping self-efficacy (Pain Coping Questionnaire), and parental pain history predicted treatment response in disability at 6-month follow-up. Participants were 100 adolescents (11-18 years of age) with JFM enrolled in a recently published clinical trial comparing CBT to a fibromyalgia education (FE) intervention. Patients were identified as achieving a clinically significant change in disability (i.e., were considered treatment responders) if they achieved both a reliable magnitude of change (estimated as a > or = 7.8-point reduction on the FDI) using the Reliable Change Index, and a reduction in FDI disability grade based on established clinical reference points. Using this rigorous standard, 40% of patients who received CBT (20 of 50) were identified as treatment responders, compared to 28% who received FE (14 of 50). For CBT, patients with greater initial disability and higher coping efficacy were significantly more likely to achieve a clinically significant improvement in functioning. Pain intensity, depressive symptoms, and parent pain history did not significantly predict treatment response. Estimating clinically significant change for outcome measures in behavioral trials sets a high bar but is a potentially valuable approach to improve the quality of clinical trials, to enhance interpretability of treatment effects, and to challenge researchers to develop more potent and tailored interventions. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  5. Can CT imaging of the chest, abdomen, and pelvis identify all vertebral injuries of the thoracolumbar spine without dedicated reformatting?

    PubMed

    Imran, Jonathan B; Madni, Tarik D; Pruitt, Jeffrey H; Cornelius, Canon; Subramanian, Madhu; Clark, Audra T; Mokdad, Ali A; Rizk, Paul; Minei, Joseph P; Cripps, Michael W; Eastman, Alexander L

    2018-07-01

    The main objective of this study was to compare detection rates of clinically significant thoracolumbar spine (TLS) fracture between computed tomography (CT) imaging of the chest, abdomen, and spine (CT CAP) and CT for the thoracolumbar spine (CT TL). We retrospectively identified patients at our institution with a TLS fracture over a two-year period that had both CT CAP and reformatted CT TL imaging. The sensitivity of CT CAP to identify fracture was calculated for each fracture type. A total of 516 TLS fractures were identified in 125 patients using reformatted CT TL spine imaging. Overall, 69 of 512 fractures (13%) were missed on CT CAP that were identified on CT TL. Of those, there were no clinically significant missed fractures. CT CAP could potentially be used as a screening tool for clinically significant TLS injuries. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Pre-admission criteria and pre-clinical achievement: Can they predict medical students performance in the clinical phase?

    PubMed

    Salem, Raneem O; Al-Mously, Najwa; AlFadil, Sara; Baalash, Amal

    2016-01-01

    Various factors affect medical students' performance during clinical phase. Identifying these factors would help in mentoring weak students and help in selection process for residency programmes. Our study objective is to evaluate the impact of pre-admission criteria, and pre-clinical grade point average (GPA) on undergraduate medical students' performance during clinical phase. This study has a cross-sectional design that includes fifth- and sixth-year female medical students (71). Data of clinical and pre-clinical GPA in medical school and pre-admission to medical school tests scores were collected. A significant correlation between clinical GPA with the pre-clinical GPA was observed (p < 0.05). Such significant correlation was not seen with other variables under study. A regression analysis was performed, and the only significant predictor of students clinical performance was the pre-clinical GPA (p < 0.001). However, no significant difference between students' clinical and pre-clinical GPA for both cohorts was observed (p > 0.05). Pre-clinical GPA is strongly correlated with and can predict medical students' performance during clinical years. Our study highlighted the importance of evaluating the academic performances of students in pre-clinical years before they move into clinical years in order to identify weak students to mentor them and monitor their progress.

  7. The prevalence and clinical significance of maxillary sinus mucous retention cysts in a general clinic population.

    PubMed

    Rhodus, N L

    1990-02-01

    Previous studies have documented the occurrence and potential clinical significance of MSMR cysts. Studies also have alluded to a relationship between the MSMR cyst and certain signs or symptoms of disease. We determined the prevalence of MSMR cysts in a general clinic population and identified some important correlations with clinical signs and symptoms.

  8. A comparison between the clinical significance and growth mixture modelling early change methods at predicting negative outcomes.

    PubMed

    Flood, Nicola; Page, Andrew; Hooke, Geoff

    2018-05-03

    Routine outcome monitoring benefits treatment by identifying potential no change and deterioration. The present study compared two methods of identifying early change and their ability to predict negative outcomes on self-report symptom and wellbeing measures. 1467 voluntary day patients participated in a 10-day group Cognitive Behaviour Therapy (CBT) program and completed the symptom and wellbeing measures daily. Early change, as defined by (a) the clinical significance method and (b) longitudinal modelling, was compared on each measure. Early change, as defined by the simpler clinical significance method, was superior at predicting negative outcomes than longitudinal modelling. The longitudinal modelling method failed to detect a group of deteriorated patients, and agreement between the early change methods and the final unchanged outcome was higher for the clinical significance method. Therapists could use the clinical significance early change method during treatment to alert them of patients at risk for negative outcomes, which in turn could allow therapists to prevent those negative outcomes from occurring.

  9. High-resolution copy number variation analysis of schizophrenia in Japan.

    PubMed

    Kushima, I; Aleksic, B; Nakatochi, M; Shimamura, T; Shiino, T; Yoshimi, A; Kimura, H; Takasaki, Y; Wang, C; Xing, J; Ishizuka, K; Oya-Ito, T; Nakamura, Y; Arioka, Y; Maeda, T; Yamamoto, M; Yoshida, M; Noma, H; Hamada, S; Morikawa, M; Uno, Y; Okada, T; Iidaka, T; Iritani, S; Yamamoto, T; Miyashita, M; Kobori, A; Arai, M; Itokawa, M; Cheng, M-C; Chuang, Y-A; Chen, C-H; Suzuki, M; Takahashi, T; Hashimoto, R; Yamamori, H; Yasuda, Y; Watanabe, Y; Nunokawa, A; Someya, T; Ikeda, M; Toyota, T; Yoshikawa, T; Numata, S; Ohmori, T; Kunimoto, S; Mori, D; Iwata, N; Ozaki, N

    2017-03-01

    Recent schizophrenia (SCZ) studies have reported an increased burden of de novo copy number variants (CNVs) and identified specific high-risk CNVs, although with variable phenotype expressivity. However, the pathogenesis of SCZ has not been fully elucidated. Using array comparative genomic hybridization, we performed a high-resolution genome-wide CNV analysis on a mainly (92%) Japanese population (1699 SCZ cases and 824 controls) and identified 7066 rare CNVs, 70.0% of which were small (<100 kb). Clinically significant CNVs were significantly more frequent in cases than in controls (odds ratio=3.04, P=9.3 × 10 -9 , 9.0% of cases). We confirmed a significant association of X-chromosome aneuploidies with SCZ and identified 11 de novo CNVs (e.g., MBD5 deletion) in cases. In patients with clinically significant CNVs, 41.7% had a history of congenital/developmental phenotypes, and the rate of treatment resistance was significantly higher (odds ratio=2.79, P=0.0036). We found more severe clinical manifestations in patients with two clinically significant CNVs. Gene set analysis replicated previous findings (e.g., synapse, calcium signaling) and identified novel biological pathways including oxidative stress response, genomic integrity, kinase and small GTPase signaling. Furthermore, involvement of multiple SCZ candidate genes and biological pathways in the pathogenesis of SCZ was suggested in established SCZ-associated CNV loci. Our study shows the high genetic heterogeneity of SCZ and its clinical features and raises the possibility that genomic instability is involved in its pathogenesis, which may be related to the increased burden of de novo CNVs and variable expressivity of CNVs.

  10. Medication discrepancies associated with subsequent pharmacist-performed medication reconciliations in an ambulatory clinic.

    PubMed

    Philbrick, Ann M; Harris, Ila M; Schommer, Jon C; Fallert, Christopher J

    2015-01-01

    To describe the number of medication discrepancies associated with subsequent medication reconciliations by a clinical pharmacist in an ambulatory family medicine clinic and the proportion of subsequent medication reconciliation visits that were associated with hospital discharge, long-term anticoagulation management, or both. Data on medication reconciliations were collected over a 2-year time period in an ambulatory family medicine clinic for patients taking 10 or more medications. Medication reconciliation was performed 752 times for 500 patients. A total of 5,046 discrepancies were identified, with more than one-half deemed clinically important. A mean (± SD) of 6.7 ± 4.6 discrepancies per visit (3.5 ± 3.2 clinically important) were identified. The findings showed that the distribution of total discrepancies identified by pharmacist-performed medication reconciliation was significantly different over the course of subsequent medication reconciliations. However, the distribution of clinically important discrepancies was not significantly different; important discrepancies were as likely to be found in later reconciliations as in earlier ones. As subsequent medication reconciliation visits were performed, an increasing proportion consisted of post-hospital discharge visits, long-term anticoagulation managed by a clinical pharmacist, or both. Patients with a recent hospital discharge, on long-term anticoagulation management, or both, were more likely to have multiple sessions with a clinical pharmacist for medication reconciliation. These findings can help identify patients for whom medication reconciliation is warranted.

  11. The Impact of Repeated Health Checks for Adults with Intellectual Disabilities

    ERIC Educational Resources Information Center

    Felce, David; Baxter, Helen; Lowe, Kathy; Dunstan, Frank; Houston, Helen; Jones, Glyn; Felce, Janet; Kerr, Michael

    2008-01-01

    Background: An earlier study (Baxter "et al." 2006) found that a structured health check conducted in primary care identified clinically significant previously unrecognized morbidity among adults with intellectual disabilities. The aim here was to examine whether follow-up health checks would identify equally significant newly identified morbidity…

  12. Research misconduct identified by the US Food and Drug Administration: out of sight, out of mind, out of the peer-reviewed literature.

    PubMed

    Seife, Charles

    2015-04-01

    Every year, the US Food and Drug Administration (FDA) inspects several hundred clinical sites performing biomedical research on human participants and occasionally finds evidence of substantial departures from good clinical practice and research misconduct. However, the FDA has no systematic method of communicating these findings to the scientific community, leaving open the possibility that research misconduct detected by a government agency goes unremarked in the peer-reviewed literature. To identify published clinical trials in which an FDA inspection found significant evidence of objectionable conditions or practices, to describe violations, and to determine whether the violations are mentioned in the peer-reviewed literature. Cross-sectional analysis of publicly available documents, dated from January 1, 1998, to September 30, 2013, describing FDA inspections of clinical trial sites in which significant evidence of objectionable conditions or practices was found. For each inspection document that could be linked to a specific published clinical trial, the main measure was a yes/no determination of whether there was mention in the peer-reviewed literature of problems the FDA had identified. Fifty-seven published clinical trials were identified for which an FDA inspection of a trial site had found significant evidence of 1 or more of the following problems: falsification or submission of false information, 22 trials (39%); problems with adverse events reporting, 14 trials (25%); protocol violations, 42 trials (74%); inadequate or inaccurate recordkeeping, 35 trials (61%); failure to protect the safety of patients and/or issues with oversight or informed consent, 30 trials (53%); and violations not otherwise categorized, 20 trials (35%). Only 3 of the 78 publications (4%) that resulted from trials in which the FDA found significant violations mentioned the objectionable conditions or practices found during the inspection. No corrections, retractions, expressions of concern, or other comments acknowledging the key issues identified by the inspection were subsequently published. When the FDA finds significant departures from good clinical practice, those findings are seldom reflected in the peer-reviewed literature, even when there is evidence of data fabrication or other forms of research misconduct.

  13. Longitudinal Analysis of New Information Types in Clinical Notes

    PubMed Central

    Zhang, Rui; Pakhomov, Serguei; Melton, Genevieve B.

    2014-01-01

    It is increasingly recognized that redundant information in clinical notes within electronic health record (EHR) systems is ubiquitous, significant, and may negatively impact the secondary use of these notes for research and patient care. We investigated several automated methods to identify redundant versus relevant new information in clinical reports. These methods may provide a valuable approach to extract clinically pertinent information and further improve the accuracy of clinical information extraction systems. In this study, we used UMLS semantic types to extract several types of new information, including problems, medications, and laboratory information. Automatically identified new information highly correlated with manual reference standard annotations. Methods to identify different types of new information can potentially help to build up more robust information extraction systems for clinical researchers as well as aid clinicians and researchers in navigating clinical notes more effectively and quickly identify information pertaining to changes in health states. PMID:25717418

  14. Religion, assessment and the problem of 'normative uncertainty' for mental health student nurses: a critical incident-informed qualitative interview study.

    PubMed

    Bassett, A M; Baker, C; Cross, S

    2015-10-01

    There is limited research around how mental health (MH) student nurses interpret and differentiate between people's religious and cultural beliefs and the existence of psychopathological symptomatology and experiences. Here we focus on one cultural issue that arose from research exploring how MH student nurses approach and interpret religion and culture in their practice - that is, the difficulties in determining the clinical significance of the religious beliefs and experiences expressed by the people they care for. While problems with establishing the cultural boundaries of normality in clinical assessments are an important area of debate in cultural psychiatry, it remains a peripheral issue in MH nurse education. An anthropologically informed qualitative research design underpinned 'critical incident' (CI)-focused ethnographic interviews with 36 second and third-year MH nursing field students and seven undergraduate MH branch lecturers. Follow up focus groups were also carried out. Interview transcripts were subject to thematic analysis. Four subthemes were identified under the broad theme of the clinical significance of religious-type expression and experience: (1) identifying the difference between delusions and religious belief; (2) identifying whether an experience was hallucination or religious experience; (3) the clinical implications of such challenges; and (4) applying religion-specific knowledge. There are clinical implications that may result from the difficulties with assessing the clinical significance of religious beliefs and experiences, identified in both our research and within international cultural psychiatry literature and research. Misinterpretation and therefore wrongly assessing someone's experience as pathological is a significant concern. It is suggested that CI analysis could be adapted to help nurses, nursing students and nurse educators recognize the religious dimensions of mental distress, particularly those that then potentially impact upon the accuracy and person centeredness of clinical assessment. Further research is proposed to investigate the clinical assessment and training needs of nurses in the area of religion and mental distress. © 2015 John Wiley & Sons Ltd.

  15. Polygenic dissection of diagnosis and clinical dimensions of bipolar disorder and schizophrenia.

    PubMed

    Ruderfer, Douglas M; Fanous, Ayman H; Ripke, Stephan; McQuillin, Andrew; Amdur, Richard L; Gejman, Pablo V; O'Donovan, Michael C; Andreassen, Ole A; Djurovic, Srdjan; Hultman, Christina M; Kelsoe, John R; Jamain, Stephane; Landén, Mikael; Leboyer, Marion; Nimgaonkar, Vishwajit; Nurnberger, John; Smoller, Jordan W; Craddock, Nick; Corvin, Aiden; Sullivan, Patrick F; Holmans, Peter; Sklar, Pamela; Kendler, Kenneth S

    2014-09-01

    Bipolar disorder and schizophrenia are two often severe disorders with high heritabilities. Recent studies have demonstrated a large overlap of genetic risk loci between these disorders but diagnostic and molecular distinctions still remain. Here, we perform a combined genome-wide association study (GWAS) of 19 779 bipolar disorder (BP) and schizophrenia (SCZ) cases versus 19 423 controls, in addition to a direct comparison GWAS of 7129 SCZ cases versus 9252 BP cases. In our case-control analysis, we identify five previously identified regions reaching genome-wide significance (CACNA1C, IFI44L, MHC, TRANK1 and MAD1L1) and a novel locus near PIK3C2A. We create a polygenic risk score that is significantly different between BP and SCZ and show a significant correlation between a BP polygenic risk score and the clinical dimension of mania in SCZ patients. Our results indicate that first, combining diseases with similar genetic risk profiles improves power to detect shared risk loci and second, that future direct comparisons of BP and SCZ are likely to identify loci with significant differential effects. Identifying these loci should aid in the fundamental understanding of how these diseases differ biologically. These findings also indicate that combining clinical symptom dimensions and polygenic signatures could provide additional information that may someday be used clinically.

  16. [A study on participation in clinical decision making by home healthcare nurses].

    PubMed

    Kim, Se Young

    2010-12-01

    This study was done to identify participation by home healthcare nurses in clinical decision making and factors influencing clinical decision making. A descriptive survey was used to collect data from 68 home healthcare nurses in 22 hospital-based home healthcare services in Korea. To investigate participation, the researcher developed 3 scenarios through interviews with 5 home healthcare nurses. A self-report questionnaire composed of tools for characteristics, factors of clinical decision making, and participation was used. Participation was relatively high, but significantly lower in the design phase (F=3.51, p=.032). Competency in clinical decision making (r=.45, p<.001), perception of the decision maker role (r=.47, p<.001), and perception of the utility of clinical practice guidelines (r=.25, p=.043) were significantly correlated with participation. Competency in clinical decision making (Odds ratio [OR]=41.79, p=.007) and perception of the decision maker role (OR=15.09, p=.007) were significant factors predicting participation in clinical decision making by home healthcare nurses. In order to encourage participation in clinical decision making, education programs should be provided to home healthcare nurses. Official clinical practice guidelines should be used to support home healthcare nurses' participation in clinical decision making in cases where they can identify and solve the patient health problems.

  17. The effect of preparation strategies, qualification and professional background on clinical nurse educator confidence.

    PubMed

    Nguyen, Van N B; Forbes, Helen; Mohebbi, Mohammadreza; Duke, Maxine

    2018-06-12

    To describe how clinical nurse educators in Vietnam are prepared for their role; to identify which preparation strategies assist development of confidence in clinical teaching; and to measure the effect of educational qualifications and professional background on perceived confidence levels. The quality of clinical teaching can directly affect the quality of the student learning experience. The role of the clinical educator is complex and dynamic and requires a period of adjustment for successful role transition to occur. Planned orientation and specific preparation programs assist transition and reduce anxiety for new clinical nurse educators. There is, however, a lack of clear evidence to identify the form this preparation should take or which strategies are likely to facilitate the development of role confidence. Descriptive survey study. Cross-sectional surveys were used to collect data from 334 clinical nurse educators during January - March 2015. Eight preparation methods commonly used in Vietnam were identified. There was a small yet significant association between preparation and clinical nurse educators' perceived confidence. Formal preparation methods, as well as postgraduate qualifications and years of clinical teaching experience were linked to increased confidence in clinical teaching. Conversely, informal mentorship was found to hinder confidence development. This study identifies several preparation strategies that significantly enhance clinical educator confidence and readiness for their complex role. These preparation strategies drawn from the Vietnamese context, provide important examples for the wider nursing community to consider. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  18. Epidemiology of clinical feline herpesvirus infection in zoo-housed cheetahs (Acinonyx jubatus).

    PubMed

    Witte, Carmel L; Lamberski, Nadine; Rideout, Bruce A; Vaida, Florin; Citino, Scott B; Barrie, Michael T; Haefele, Holly J; Junge, Randall E; Murray, Suzan; Hungerford, Laura L

    2017-10-15

    OBJECTIVE To determine the incidence of and risk factors for clinical feline herpesvirus (FHV) infection in zoo-housed cheetahs and determine whether dam infection was associated with offspring infection. DESIGN Retrospective cohort study. ANIMALS 144 cheetah cubs born in 6 zoos from 1988 through 2007. PROCEDURES Data were extracted from the health records of cheetahs and their dams to identify incident cases of clinical FHV infection and estimate incidence from birth to 18 months of age. Univariate and multivariable Cox proportional hazards models, controlling for correlations among cheetahs with the same dam, were used to identify risk factors for incident FHV infection. RESULTS Cumulative incidence of FHV infection in cheetah cubs was 35% (50/144). No significant association between dam and offspring infection was identified in any model. Factors identified as significant through multivariable analysis varied by age group. For cheetahs up to 3 months of age, the most important predictor of FHV infection was having a dam that had received a preparturition FHV vaccine regimen that included a modified-live virus vaccine versus a dam that had received no preparturition vaccine. Other risk factors included being from a small litter, being born to a primiparous dam, and male sex. CONCLUSIONS AND CLINICAL RELEVANCE This study provided the first population-level characterization of the incidence of and risk factors for FHV infection in cheetahs, and findings confirmed the importance of this disease. Recognition that clinical FHV infection in the dam was not a significant predictor of disease in cubs and identification of other significant factors have implications for disease management.

  19. Prevalence and risk factors of maladaptive behaviour in young children with Autistic Disorder

    PubMed Central

    Hartley, S. L.; Sikora, D. M.; McCoy, R.

    2010-01-01

    Background Children with Autistic Disorder (AD) evidence more co-occurring maladaptive behaviours than their typically developing peers and peers with intellectual disability because of other aetiologies. The present study investigated the prevalence of Clinically Significant maladaptive behaviours during early childhood and identified at-risk subgroups of young children with AD. Method Parents rated their child’s maladaptive behaviours on the Child Behaviour Checklist (CBCL) in 169 children with AD aged 1.5 to 5.8 years. Results One-third of young children with AD had a CBCL Total Problems score in the Clinically Significant range. The highest percentage of Clinically Significant scores were in the Withdrawal, Attention, and Aggression CBCL syndrome scales. There was a high degree of co-morbidity of Clinically Significant maladaptive behaviours. Several subject characteristic risk factors for maladaptive behaviours were identified. Conclusions Findings highlight the need to include behavioural management strategies aimed at increasing social engagement, sustained attention and decreasing aggressive behaviour in comprehensive intervention programmes for young children with AD. PMID:18444989

  20. Emerging Bacterial Infection: Identification and Clinical Significance of Kocuria Species

    PubMed Central

    Palange, Padmavali; Vaish, Ritu; Bhatti, Adnan Bashir; Kale, Vinod; Kandi, Maheshwar Reddy; Bhoomagiri, Mohan Rao

    2016-01-01

    Recently there have been reports of gram-positive cocci which are morphologically similar to both Staphylococci and the Micrococci. These bacteria have been identified as Kocuria species with the help of automated identification system and other molecular methods including 16S rRNA (ribosomal ribonucleic acid) evaluation. Kocuria belongs to the family Micrococcaceae which also includes Staphylococcus species and Micrococcus species. Isolation and clinical significance of these bacteria from human specimens warrant great caution as it does not necessarily confirm infection due to their ubiquitous presence, and as a normal flora of skin and mucous membranes in human and animals. Most clinical microbiology laboratories ignore such bacteria as laboratory and specimen contaminants. With increasing reports of infections associated with these bacteria, it is now important for clinical microbiologists to identify and enumerate the virulence and antibiotic susceptibility patterns of such bacteria and assist clinicians in improving the patient care and management. We review the occurrence and clinical significance of Kocuria species. PMID:27630804

  1. 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 perform biopsy.

  2. 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.

  3. A Comprehensive Pan-Cancer Molecular Study of Gynecologic and Breast Cancers.

    PubMed

    Berger, Ashton C; Korkut, Anil; Kanchi, Rupa S; Hegde, Apurva M; Lenoir, Walter; Liu, Wenbin; Liu, Yuexin; Fan, Huihui; Shen, Hui; Ravikumar, Visweswaran; Rao, Arvind; Schultz, Andre; Li, Xubin; Sumazin, Pavel; Williams, Cecilia; Mestdagh, Pieter; Gunaratne, Preethi H; Yau, Christina; Bowlby, Reanne; Robertson, A Gordon; Tiezzi, Daniel G; Wang, Chen; Cherniack, Andrew D; Godwin, Andrew K; Kuderer, Nicole M; Rader, Janet S; Zuna, Rosemary E; Sood, Anil K; Lazar, Alexander J; Ojesina, Akinyemi I; Adebamowo, Clement; Adebamowo, Sally N; Baggerly, Keith A; Chen, Ting-Wen; Chiu, Hua-Sheng; Lefever, Steve; Liu, Liang; MacKenzie, Karen; Orsulic, Sandra; Roszik, Jason; Shelley, Carl Simon; Song, Qianqian; Vellano, Christopher P; Wentzensen, Nicolas; Weinstein, John N; Mills, Gordon B; Levine, Douglas A; Akbani, Rehan

    2018-04-09

    We analyzed molecular data on 2,579 tumors from The Cancer Genome Atlas (TCGA) of four gynecological types plus breast. Our aims were to identify shared and unique molecular features, clinically significant subtypes, and potential therapeutic targets. We found 61 somatic copy-number alterations (SCNAs) and 46 significantly mutated genes (SMGs). Eleven SCNAs and 11 SMGs had not been identified in previous TCGA studies of the individual tumor types. We found functionally significant estrogen receptor-regulated long non-coding RNAs (lncRNAs) and gene/lncRNA interaction networks. Pathway analysis identified subtypes with high leukocyte infiltration, raising potential implications for immunotherapy. Using 16 key molecular features, we identified five prognostic subtypes and developed a decision tree that classified patients into the subtypes based on just six features that are assessable in clinical laboratories. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Predicting academic performance and clinical competency for international dental students: seeking the most efficient and effective measures.

    PubMed

    Stacey, D Graham; Whittaker, John M

    2005-02-01

    Measures used in the selection of international dental students to a U.S. D.D.S. program were examined to identify the grouping that most effectively and efficiently predicted academic performance and clinical competency. Archival records from the International Dental Program (IDP) at Loma Linda University provided data on 171 students who had trained in countries outside the United States. The students sought admission to the D.D.S. degree program, successful completion of which qualified them to sit for U.S. licensure. As with most dental schools, competition is high for admission to the D.D.S. program. The study's goal was to identify what measures contributed to a fair and accurate selection process for dental school applicants from other nations. Multiple regression analyses identified National Board Part II and dexterity measures as significant predictors of academic performance and clinical competency. National Board Part I, TOEFL, and faculty interviews added no significant additional help in predicting eventual academic performance and clinical competency.

  5. Predictors of job satisfaction among Academic Faculty: Do instructional and clinical faculty differ?

    PubMed Central

    Chung, Kevin C.; Song, Jae W.; Kim, H. Myra; Woolliscroft, James O.; Quint, Elisabeth H.; Lukacs, Nicholas W.; Gyetko, Margaret R.

    2010-01-01

    Objectives To identify and compare predictors of job satisfaction between the instructional and clinical faculty tracks. Method A 61-item faculty job satisfaction survey was distributed to 1,898 academic faculty at the University of Michigan Medical School. The anonymous survey was web-based. Questions covered topics on departmental organization, research, clinical and teaching support, compensation, mentorship, and promotion. Levels of satisfaction were contrasted between the two tracks, and predictors of job satisfaction were identified using linear regression models. Results The response rates for the instructional and clinical tracks were 43.1% and 41.3%, respectively. Clinical faculty reported being less satisfied with how they are mentored, and fewer reported understanding the process for promotion. There was no significant difference in overall job satisfaction between faculty tracks. Surprisingly, clinical faculty with mentors were significantly less satisfied with how they were being mentored, with career advancement and overall job satisfaction, compared to instructional faculty mentees. Additionally, senior-level clinical faculty were significantly less satisfied with their opportunities to mentor junior faculty compared to senior-level instructional faculty. Significant predictors of job satisfaction for both tracks included areas of autonomy, meeting career expectations, work-life balance, and departmental leadership. Unique to the clinical track, compensation and career advancement variables also emerged as significant predictors. Conclusion Greater effort must be placed in the continued attention to faculty well-being both at the institutional level and at the level of departmental leadership. Success in enhancing job satisfaction is more likely if directed by locally designed assessments involving department chairs, specifically in fostering more effective mentoring relationships focused on making available career advancement activities such as research activities. Our findings show this strategy to significantly impact the job satisfaction and retention of clinical track faculty members. PMID:20880368

  6. Identifying cases of undiagnosed, clinically significant COPD in primary care: qualitative insight from patients in the target population

    PubMed Central

    Leidy, Nancy K; Kim, Katherine; Bacci, Elizabeth D; Yawn, Barbara P; Mannino, David M; Thomashow, Byron M; Barr, R Graham; Rennard, Stephen I; Houfek, Julia F; Han, Meilan K; Meldrum, Catherine A; Make, Barry J; Bowler, Russ P; Steenrod, Anna W; Murray, Lindsey T; Walsh, John W; Martinez, Fernando

    2015-01-01

    Background: Many cases of chronic obstructive pulmonary disease (COPD) are diagnosed only after significant loss of lung function or during exacerbations. Aims: This study is part of a multi-method approach to develop a new screening instrument for identifying undiagnosed, clinically significant COPD in primary care. Methods: Subjects with varied histories of COPD diagnosis, risk factors and history of exacerbations were recruited through five US clinics (four pulmonary, one primary care). Phase I: Eight focus groups and six telephone interviews were conducted to elicit descriptions of risk factors for COPD, recent or historical acute respiratory events, and symptoms to inform the development of candidate items for the new questionnaire. Phase II: A new cohort of subjects participated in cognitive interviews to assess and modify candidate items. Two peak expiratory flow (PEF) devices (electronic, manual) were assessed for use in screening. Results: Of 77 subjects, 50 participated in Phase I and 27 in Phase II. Six themes informed item development: exposure (smoking, second-hand smoke); health history (family history of lung problems, recurrent chest infections); recent history of respiratory events (clinic visits, hospitalisations); symptoms (respiratory, non-respiratory); impact (activity limitations); and attribution (age, obesity). PEF devices were rated easy to use; electronic values were significantly higher than manual (P<0.0001). Revisions were made to the draft items on the basis of cognitive interviews. Conclusions: Forty-eight candidate items are ready for quantitative testing to select the best, smallest set of questions that, together with PEF, can efficiently identify patients in need of diagnostic evaluation for clinically significant COPD. PMID:26028486

  7. Identification of metabolites, clinical chemistry markers and transcripts associated with hepatotoxicity.

    PubMed

    Buness, Andreas; Roth, Adrian; Herrmann, Annika; Schmitz, Oliver; Kamp, Hennicke; Busch, Kristina; Suter, Laura

    2014-01-01

    Early and accurate pre-clinical and clinical biomarkers of hepatotoxicity facilitate the drug development process and the safety monitoring in clinical studies. We selected eight known model compounds to be administered to male Wistar rats to identify biomarkers of drug induced liver injury (DILI) using transcriptomics, metabolite profiling (metabolomics) and conventional endpoints. We specifically explored early biomarkers in serum and liver tissue associated with histopathologically evident acute hepatotoxicity. A tailored data analysis strategy was implemented to better differentiate animals with no treatment-related findings in the liver from animals showing evident hepatotoxicity as assessed by histopathological analysis. From the large number of assessed parameters, our data analysis strategy allowed us to identify five metabolites in serum and five in liver tissue, 58 transcripts in liver tissue and seven clinical chemistry markers in serum that were significantly associated with acute hepatotoxicity. The identified markers comprised metabolites such as taurocholic acid and putrescine (measured as sum parameter together with agmatine), classical clinical chemistry markers like AST (aspartate aminotransferase), ALT (alanine aminotransferase), and bilirubin, as well as gene transcripts like Igfbp1 (insulin-like growth factor-binding protein 1) and Egr1 (early growth response protein 1). The response pattern of the identified biomarkers was concordant across all types of parameters and sample matrices. Our results suggest that a combination of several of these biomarkers could significantly improve the robustness and accuracy of an early diagnosis of hepatotoxicity.

  8. Identification of non-tuberculous mycobacteria isolated from clinical specimens at a tertiary care hospital: a cross-sectional study

    PubMed Central

    2013-01-01

    Background Non-tuberculous mycobacteria (NTM) are opportunistic pathogens in immuno-compromised patients. They are also increasingly recognized as pathogens in immuno-competent individuals. Globally, an increase in NTM isolation is being reported with a varied geographic prevalence of different species around the world. There is lack of data on species distribution of these organisms from Pakistan. Treatment options differ according to the species isolated and its susceptibility profile. Knowledge of local species variation would help targeted therapy. This study was performed to determine frequencies of different NTM species isolated from various clinical specimens submitted at a tertiary care hospital laboratory. Methods NTM isolated from 25955 clinical specimens over a period of two years (2010 to 2011) were included. All NTM were identified using conventional tests. Drug susceptibility testing (DST) was performed by broth microdilution and interpreted according to Clinical and Laboratory Standards Institute’s document M24-A2. Results A total of 104 NTM were included in the study. Of these, 76% (54/71) rapidly growing mycobacteria (RGM) and 57.6% (19/33) slow growing mycobacteria (SGM) could be further identified. Mycobacterium fortuitum (21/54) was the commonest NTM identified among RGM followed by M. mucogenicum (12/54) and M. smegmatis (11/54). Among SGM, M. avium complex (MAC) was the most frequent (14/19). Clinical significance could be assessed in a limited number (52/104) of NTM isolates and MAC appeared to be the commonest significant NTM. Three extra-pulmonary cases were found to be healthcare associated infections. DST results for RGM showed susceptibility to amikacin (100%), clarithromycin (100%, except M. fortuitum where it is not reportable), linezolid (90%) and moxifloxacin (75%). Whereas SGM were susceptible to clarithromycin (100%), linezolid (58.8%) and moxifloxacin (64.7%). Conclusion This is the first study reporting NTM species and their clinical significance isolated from clinical specimens from Pakistan. Isolation of NTM from clinical specimens should prompt to evaluate their clinical significance. PMID:24148198

  9. Identification of non-tuberculous mycobacteria isolated from clinical specimens at a tertiary care hospital: a cross-sectional study.

    PubMed

    Ahmed, Imran; Jabeen, Kauser; Hasan, Rumina

    2013-10-22

    Non-tuberculous mycobacteria (NTM) are opportunistic pathogens in immuno-compromised patients. They are also increasingly recognized as pathogens in immuno-competent individuals. Globally, an increase in NTM isolation is being reported with a varied geographic prevalence of different species around the world. There is lack of data on species distribution of these organisms from Pakistan. Treatment options differ according to the species isolated and its susceptibility profile. Knowledge of local species variation would help targeted therapy. This study was performed to determine frequencies of different NTM species isolated from various clinical specimens submitted at a tertiary care hospital laboratory. NTM isolated from 25955 clinical specimens over a period of two years (2010 to 2011) were included. All NTM were identified using conventional tests. Drug susceptibility testing (DST) was performed by broth microdilution and interpreted according to Clinical and Laboratory Standards Institute's document M24-A2. A total of 104 NTM were included in the study. Of these, 76% (54/71) rapidly growing mycobacteria (RGM) and 57.6% (19/33) slow growing mycobacteria (SGM) could be further identified. Mycobacterium fortuitum (21/54) was the commonest NTM identified among RGM followed by M. mucogenicum (12/54) and M. smegmatis (11/54). Among SGM, M. avium complex (MAC) was the most frequent (14/19). Clinical significance could be assessed in a limited number (52/104) of NTM isolates and MAC appeared to be the commonest significant NTM. Three extra-pulmonary cases were found to be healthcare associated infections. DST results for RGM showed susceptibility to amikacin (100%), clarithromycin (100%, except M. fortuitum where it is not reportable), linezolid (90%) and moxifloxacin (75%). Whereas SGM were susceptible to clarithromycin (100%), linezolid (58.8%) and moxifloxacin (64.7%). This is the first study reporting NTM species and their clinical significance isolated from clinical specimens from Pakistan. Isolation of NTM from clinical specimens should prompt to evaluate their clinical significance.

  10. Comparison of untreated adolescent idiopathic scoliosis with normal controls: a review and statistical analysis of the literature.

    PubMed

    Rushton, Paul R P; Grevitt, Michael P

    2013-04-20

    Review and statistical analysis of studies evaluating health-related quality of life (HRQOL) in adolescents with untreated adolescent idiopathic scoliosis (AIS) using Scoliosis Research Society (SRS) outcomes. To apply normative values and minimum clinical important differences for the SRS-22r to the literature. Identify whether the HRQOL of adolescents with untreated AIS differs from unaffected peers and whether any differences are clinically relevant. The effect of untreated AIS on adolescent HRQOL is uncertain. The lack of published normative values and minimum clinical important difference for the SRS-22r has so far hindered our interpretation of previous studies. The publication of this background data allows these studies to be re-examined. Using suitable inclusion criteria, a literature search identified studies examining HRQOL in untreated adolescents with AIS. Each cohort was analyzed individually. Statistically significant differences were identified by using 95% confidence intervals for the difference in SRS-22r domain mean scores between the cohorts with AIS and the published data for unaffected adolescents. If the lower bound of the confidence interval was greater than the minimum clinical important difference, the difference was considered clinically significant. Of the 21 included patient cohorts, 81% reported statistically worse pain than those unaffected. Yet in only 5% of cohorts was this difference clinically important. Of the 11 cohorts included examining patient self-image, 91% reported statistically worse scores than those unaffected. In 73% of cohorts this difference was clinically significant. Affected cohorts tended to score well in function/activity and mental health domains and differences from those unaffected rarely reached clinically significant values. Pain and self-image tend to be statistically lower among cohorts with AIS than those unaffected. The literature to date suggests that it is only self-image which consistently differs clinically. This should be considered when assessing the possible benefits of surgery.

  11. Targeted next-generation sequencing makes new molecular diagnoses and expands genotype-phenotype relationship in Ehlers-Danlos syndrome.

    PubMed

    Weerakkody, Ruwan A; Vandrovcova, Jana; Kanonidou, Christina; Mueller, Michael; Gampawar, Piyush; Ibrahim, Yousef; Norsworthy, Penny; Biggs, Jennifer; Abdullah, Abdulshakur; Ross, David; Black, Holly A; Ferguson, David; Cheshire, Nicholas J; Kazkaz, Hanadi; Grahame, Rodney; Ghali, Neeti; Vandersteen, Anthony; Pope, F Michael; Aitman, Timothy J

    2016-11-01

    Ehlers-Danlos syndrome (EDS) comprises a group of overlapping hereditary disorders of connective tissue with significant morbidity and mortality, including major vascular complications. We sought to identify the diagnostic utility of a next-generation sequencing (NGS) panel in a mixed EDS cohort. We developed and applied PCR-based NGS assays for targeted, unbiased sequencing of 12 collagen and aortopathy genes to a cohort of 177 unrelated EDS patients. Variants were scored blind to previous genetic testing and then compared with results of previous Sanger sequencing. Twenty-eight pathogenic variants in COL5A1/2, COL3A1, FBN1, and COL1A1 and four likely pathogenic variants in COL1A1, TGFBR1/2, and SMAD3 were identified by the NGS assays. These included all previously detected single-nucleotide and other short pathogenic variants in these genes, and seven newly detected pathogenic or likely pathogenic variants leading to clinically significant diagnostic revisions. Twenty-two variants of uncertain significance were identified, seven of which were in aortopathy genes and required clinical follow-up. Unbiased NGS-based sequencing made new molecular diagnoses outside the expected EDS genotype-phenotype relationship and identified previously undetected clinically actionable variants in aortopathy susceptibility genes. These data may be of value in guiding future clinical pathways for genetic diagnosis in EDS.Genet Med 18 11, 1119-1127.

  12. Use of diagnosis codes for detection of clinically significant opioid poisoning in the emergency department: A retrospective analysis of a surveillance case definition.

    PubMed

    Reardon, Joseph M; Harmon, Katherine J; Schult, Genevieve C; Staton, Catherine A; Waller, Anna E

    2016-02-08

    Although fatal opioid poisonings tripled from 1999 to 2008, data describing nonfatal poisonings are rare. Public health authorities are in need of tools to track opioid poisonings in near real time. We determined the utility of ICD-9-CM diagnosis codes for identifying clinically significant opioid poisonings in a state-wide emergency department (ED) surveillance system. We sampled visits from four hospitals from July 2009 to June 2012 with diagnosis codes of 965.00, 965.01, 965.02 and 965.09 (poisoning by opiates and related narcotics) and/or an external cause of injury code of E850.0-E850.2 (accidental poisoning by opiates and related narcotics), and developed a novel case definition to determine in which cases opioid poisoning prompted the ED visit. We calculated the percentage of visits coded for opioid poisoning that were clinically significant and compared it to the percentage of visits coded for poisoning by non-opioid agents in which there was actually poisoning by an opioid agent. We created a multivariate regression model to determine if other collected triage data can improve the positive predictive value of diagnosis codes alone for detecting clinically significant opioid poisoning. 70.1 % of visits (Standard Error 2.4 %) coded for opioid poisoning were primarily prompted by opioid poisoning. The remainder of visits represented opioid exposure in the setting of other primary diseases. Among non-opioid poisoning codes reviewed, up to 36 % were reclassified as an opioid poisoning. In multivariate analysis, only naloxone use improved the positive predictive value of ICD-9-CM codes for identifying clinically significant opioid poisoning, but was associated with a high false negative rate. This surveillance mechanism identifies many clinically significant opioid overdoses with a high positive predictive value. With further validation, it may help target control measures such as prescriber education and pharmacy monitoring.

  13. Clinical, Functional and Health-Related Quality of Life Correlates of Clinically Significant Symptoms of Anxiety and Depression in Patients with Systemic Sclerosis: A Cross-Sectional Survey

    PubMed Central

    Nguyen, Christelle; Ranque, Brigitte; Baubet, Thierry; Bérezné, Alice; Mestre-Stanislas, Caroline; Rannou, François; Papelard, Agathe; Morell-Dubois, Sandrine; Revel, Michel; Moro, Marie-Rose; Guillevin, Loïc; Poiraudeau, Serge; Mouthon, Luc

    2014-01-01

    Objectives To identify clinical, functional and health-related quality of life (HRQoL) correlates of clinically significant symptoms of anxiety and depression in patients with systemic sclerosis (SSc). Methods Three-hundred-and-eighty-one patients fulfilling the American College of Rheumatology and/or the Leroy and Medsger criteria for SSc were assessed for visceral involvement, disability and HRQoL (assessed by SF-36). Clinically significant symptoms of anxiety and depression were evaluated with the Hospital Anxiety Depression Scale (HAD) (defined cut-off≥8). Results 9.2% the patients had limited SSc, 50.5% limited cutaneous SSc (lcSSc), and 40.3% diffuse cutaneous SSc (dcSSc). Overall, 40.4% and 58.8% of the patients had clinically significant symptoms of depression and anxiety, respectively. Compared to patients without clinically significant symptoms of depression, patients with clinically significant symptoms of depression had poorer health status, HRQoL mental and physical component, and greater global disability, hand disability and aesthetic impairment. Compared to patients without clinically significant symptoms of anxiety, patients with clinically significant symptoms of anxiety had poorer SF-36 mental and physical component scores. On multivariable analysis, excluding mental component score of SF-36, variables independently associated with clinically significant symptoms of depression and anxiety were global disability and physical component of SF-36, plus female gender for clinically significant symptoms of anxiety only. Remarkably, patients with and without clinically significant psychiatric symptoms were comparable for all disease-related clinical features assessed. Conclusion High levels of clinically significant symptoms of anxiety and depression are observed among SSc patients. Clinically significant psychiatric symptoms are rather associated with increased disability and altered HRQoL, than with disease-specific organ manifestations. PMID:24587375

  14. 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

  15. Does specific psychopathology predict development of psychosis in ultra high-risk (UHR) patients?

    PubMed

    Thompson, Andrew; Nelson, Barnaby; Bruxner, Annie; O'Connor, Karen; Mossaheb, Nilufar; Simmons, Magenta B; Yung, Alison

    2013-04-01

    Studies have attempted to identify additional risk factors within the group identified as 'ultra high risk' (UHR) for developing psychotic disorders in order to characterise those at highest risk. However, these studies have often neglected clinical symptom types as additional risk factors. We aimed to investigate the relationship between baseline clinical psychotic or psychotic-like symptoms and the subsequent transition to a psychotic disorder in a UHR sample. A retrospective 'case-control' methodology was used. We identified all individuals from a UHR clinic who had subsequently developed a psychotic disorder (cases) and compared these to a random sample of individuals from the clinic who did not become psychotic within the sampling time frame (controls). The sample consisted of 120 patients (60 cases, 60 controls). An audit tool was used to identify clinical symptoms reported at entry to the clinic (baseline) using the clinical file. Diagnosis at transition was assessed using the Operational Criteria for Psychotic Illness (OPCRIT) computer program. The relationship between transition to a psychotic disorder and baseline symptoms was explored using survival analysis. Presence of thought disorder, any delusions and elevated mood significantly predicted transition to a psychotic disorder. When other symptoms were adjusted for, only the presence of elevated mood significantly predicted subsequent transition (hazard ratio 2.69, p = 0.002). Thought disorder was a predictor of transition to a schizophrenia-like psychotic disorder (hazard ratio 3.69, p = 0.008). Few individual clinical symptoms appear to be predictive of transition to a psychotic disorder in the UHR group. Clinicians should be cautious about the use of clinical profile alone in such individuals when determining who is at highest risk.

  16. Risk Stratification Among Men With Prostate Imaging Reporting and Data System Version 2 Category 3 Transition Zone Lesions: Is Biopsy Always Necessary?

    PubMed Central

    Felker, Ely R.; Raman, Steven S.; Margolis, Daniel J.; Lu, David S. K.; Shaheen, Nicholas; Natarajan, Shyam; Sharma, Devi; Huang, Jiaoti; Dorey, Fred; Marks, Leonard S.

    2017-01-01

    OBJECTIVE The objective of our study was to determine the clinical and MRI characteristics of clinically significant prostate cancer (PCA) (Gleason score ≥ 3 + 4) in men with Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) category 3 transition zone (TZ) lesions. MATERIALS AND METHODS From 2014 to 2016, 865 men underwent prostate MRI and MRI/ultrasound (US) fusion biopsy (FB). A subset of 90 FB-naïve men with 96 PI-RADSv2 category 3 TZ lesions was identified. Patients were imaged at 3 T using a body coil. Images were assigned a PI-RADSv2 category by an experienced radiologist. Using clinical data and imaging features, we performed univariate and multivariate analyses to identify predictors of clinically significant PCA. RESULTS The mean patient age was 66 years, and the mean prostate-specific antigen density (PSAD) was 0.13 ng/mL2. PCA was detected in 34 of 96 (35%) lesions, 14 of which (15%) harbored clinically significant PCA. In univariate analysis, DWI score, prostate volume, and PSAD were significant predictors (p < 0.05) of clinically significant PCA with a suggested significance for apparent diffusion coefficient (ADC) and prostate-specific antigen value (p < 0.10). On multivariate analysis, PSAD and lesion ADC were the most important covariates. The combination of both PSAD of 0.15 ng/mL2 or greater and an ADC value of less than 1000 mm2/s yielded an AUC of 0.91 for clinically significant PCA (p < 0.001). If FB had been restricted to these criteria, only 10 of 90 men would have undergone biopsy, resulting in diagnosis of clinically significant PCA in 60% with eight men (9%) misdiagnosed (false-negative). CONCLUSION The yield of FB in men with PI-RADSv2 category 3 TZ lesions for clinically significant PCA is 15% but significantly improves to 60% (AUC > 0.9) among men with PSAD of 0.15 ng/mL2 or greater and lesion ADC value of less than 1000 mm2/s. PMID:28858541

  17. Strategies to identify future shortages due to interruptions in the health care procurement supply chain and their impact on health services: a method from the English National Health Service.

    PubMed

    Grose, Jane; Richardson, Janet

    2014-01-01

    The uninterrupted supply of essential items for patient care is crucial for organizations that deliver health care. Many products central to health care are derived from natural resources such as oil and cotton, supplies of which are vulnerable to climate change and increasing global demand. The purpose of this study was to identify which items would have the greatest effect on service delivery and patient outcomes should they no longer be available. Using a consensus development approach, all items bought by one hospital, over one year, were subjected to a filtering process. Criteria were developed to identify at-risk products and assess them against specific risks and opportunities. Seventy-two items were identified for assessment against a range of potential impacts on service delivery and patient outcomes, from no impact to significant impact. Clinical and non-clinical participants rated the items. In the category of significant impact, consensus was achieved for 20 items out of 72. There were differences of opinion between clinical and non-clinical participants in terms of significant impact in relation to 18 items, suggesting that priority over purchasing decisions may create areas of conflict. Reducing reliance on critically scarce resources and reducing demand were seen as the most important criteria in developing sustainable procurement. The method was successful in identifying items vulnerable to supply chain interruption and should be repeated in other areas to test its ability to adapt to local priorities, and to assess how it functions in a variety of public and private settings.

  18. Parental functioning and pediatric sleep disturbance: an examination of factors associated with parenting stress in children clinically referred for evaluation of insomnia.

    PubMed

    Byars, Kelly C; Yeomans-Maldonado, Gloria; Noll, Jennie G

    2011-10-01

    Parenting stress is an aspect of parent functioning relevant in clinical settings. Within the context of behavioral sleep medicine, the role of parenting stress is not well understood. Prospective evaluation of patients 1.5-10 years old with insomnia. Subjects were 156 primary caregiver-child pairs who completed the Parenting Stress Index-Short Form (PSI-SF), Child Sleep Habits Questionnaire (CSHQ) and Child Behavior Checklist (CBCL). (1) determine prevalence of clinically significant parenting stress in primary caregivers of children clinically referred for insomnia; (2) identify childhood sleep problems that play a role in parenting stress; (3) identify relevant correlates of parenting stress within the context of a behavioral sleep medicine clinic; and (4) identify the most salient child sleep and behavioral variables associated with parenting stress. Forty-seven percent of primary caregivers had clinically significant parenting stress. When examining the relationship between child sleep problems and parenting stress, bedtime resistance (p=0.030) and daytime sleepiness (p=0.0003) stood alone as having the most salient associations with parenting stress. When considering a broader range of covariates (child age and child gender) and clinically relevant variables (parent history of sleep problems, parent history of psychiatric conditions, child behavior problems and child sleep problems) in a single regression equation, both child externalizing behavior problems (β=0.570, p<0.0001) and child daytime sleepiness (β=0.152, p=0.028) independently explained significant variability in parenting stress. Many primary caregivers of children clinically-referred for insomnia evaluation and treatment have significant parenting stress. Parenting stress is associated with daytime behavioral problems and sleepiness in children with insomnia. Clinicians working with pediatric insomnia patients should carefully evaluate parenting stress and child daytime behavior as these aspects of functioning may have an impact on service delivery and treatment outcomes. Copyright © 2011 Elsevier B.V. All rights reserved.

  19. Three cases of Moraxella osloensis meningitis: a difficult experience in species identification and determination of clinical significance.

    PubMed

    Roh, Kyoung Ho; Kim, Chang Ki; Koh, Eunmi; Kim, Myung Sook; Yong, Dongeun; Park, Soo Chul; Lee, Kyungwon; Chong, Yunsop

    2010-03-01

    We had three cases of Moraxella osloensis meningitis. The species identification was impossible by conventional and commercial phenotypic tests. However, we could identify the species using the 16S rRNA gene sequencing. Determination of clinical significance was difficult in one patient. All three patients recovered by appropriate antimicrobial therapy.

  20. Blood Group Antibodies in Obstetrics

    PubMed Central

    Neurath, Doris; Nimrod, Carl

    1991-01-01

    A retrospective survey of the frequency, nature, and effect of blood group antibodies on obstetrical outcome was conducted over 4 years in a large community hospital. A total of 189 antibodies were identified in 165 patients. Twenty clinically significant outcomes occurred, including three stillbirths. All clinically significant cases of hemolytic disease of the newborn were caused by Rh antibodies. PMID:21229104

  1. A guided interview process to improve student pharmacists' identification of drug therapy problems.

    PubMed

    Rovers, John; Miller, Michael J; Koenigsfeld, Carrie; Haack, Sally; Hegge, Karly; McCleeary, Erin

    2011-02-10

    To measure agreement between advanced pharmacy practice experience students using a guided interview process and experienced clinical pharmacists using standard practices to identify drug therapy problems. Student pharmacists enrolled in an advanced pharmacy practice experience (APPE) and clinical pharmacists conducted medication therapy management interviews to identify drug therapy problems in elderly patients recruited from the community. Student pharmacists used a guided interview tool, while clinical pharmacists' interviews were conducted using their usual and customary practices. Student pharmacists also were surveyed to determine their perceptions of the interview tool. Fair to moderate agreement was observed on student and clinical pharmacists' identification of 4 of 7 drug therapy problems. Of those, agreement was significantly higher than chance for 3 drug therapy problems (adverse drug reaction, dosage too high, and needs additional drug therapy) and not significant for 1 (unnecessary drug therapy). Students strongly agreed that the interview tool was useful but agreed less strongly on recommending its use in practice. The guided interview process served as a useful teaching aid to assist student pharmacists to identify drug therapy problems.

  2. A Guided Interview Process to Improve Student Pharmacists' Identification of Drug Therapy Problems

    PubMed Central

    Miller, Michael J.; Koenigsfeld, Carrie; Haack, Sally; Hegge, Karly; McCleeary, Erin

    2011-01-01

    Objective To measure agreement between advanced pharmacy practice experience students using a guided interview process and experienced clinical pharmacists using standard practices to identify drug therapy problems. Methods Student pharmacists enrolled in an advanced pharmacy practice experience (APPE) and clinical pharmacists conducted medication therapy management interviews to identify drug therapy problems in elderly patients recruited from the community. Student pharmacists used a guided interview tool, while clinical pharmacists' interviews were conducted using their usual and customary practices. Student pharmacists also were surveyed to determine their perceptions of the interview tool. Results Fair to moderate agreement was observed on student and clinical pharmacists' identification of 4 of 7 drug therapy problems. Of those, agreement was significantly higher than chance for 3 drug therapy problems (adverse drug reaction, dosage too high, and needs additional drug therapy) and not significant for 1 (unnecessary drug therapy). Students strongly agreed that the interview tool was useful but agreed less strongly on recommending its use in practice. Conclusions The guided interview process served as a useful teaching aid to assist student pharmacists to identify drug therapy problems. PMID:21451770

  3. Clinical implementation of a knowledge based planning tool for prostate VMAT.

    PubMed

    Powis, Richard; Bird, Andrew; Brennan, Matthew; Hinks, Susan; Newman, Hannah; Reed, Katie; Sage, John; Webster, Gareth

    2017-05-08

    A knowledge based planning tool has been developed and implemented for prostate VMAT radiotherapy plans providing a target average rectum dose value based on previously achievable values for similar rectum/PTV overlap. The purpose of this planning tool is to highlight sub-optimal clinical plans and to improve plan quality and consistency. A historical cohort of 97 VMAT prostate plans was interrogated using a RayStation script and used to develop a local model for predicting optimum average rectum dose based on individual anatomy. A preliminary validation study was performed whereby historical plans identified as "optimal" and "sub-optimal" by the local model were replanned in a blinded study by four experienced planners and compared to the original clinical plan to assess whether any improvement in rectum dose was observed. The predictive model was then incorporated into a RayStation script and used as part of the clinical planning process. Planners were asked to use the script during planning to provide a patient specific prediction for optimum average rectum dose and to optimise the plan accordingly. Plans identified as "sub-optimal" in the validation study observed a statistically significant improvement in average rectum dose compared to the clinical plan when replanned whereas plans that were identified as "optimal" observed no improvement when replanned. This provided confidence that the local model can identify plans that were suboptimal in terms of rectal sparing. Clinical implementation of the knowledge based planning tool reduced the population-averaged mean rectum dose by 5.6Gy. There was a small but statistically significant increase in total MU and femoral head dose and a reduction in conformity index. These did not affect the clinical acceptability of the plans and no significant changes to other plan quality metrics were observed. The knowledge-based planning tool has enabled substantial reductions in population-averaged mean rectum dose for prostate VMAT patients. This suggests plans are improved when planners receive quantitative feedback on plan quality against historical data.

  4. Clinical impact of reducing routine blood culture incubation time from 7 to 5 days.

    PubMed

    Marginson, Michael J; Daveson, Kathryn L; Kennedy, Karina J

    2014-12-01

    The aim of this study was to determine the clinical impact of reducing the blood culture incubation protocol from 7 to 5 days.A laboratory data extraction identified positive blood cultures occurring after 5 or more days of incubation at Canberra Hospital, Australia between 1 January 2001 and 31 August 2011. Isolates were identified as clinically significant using a pre-existing prospective bacteraemia database. Medical records review determined whether the positive result affected clinical management.Positive blood cultures after 5 or more days of incubation accounted for 2.65% (423/15979) of all positive blood cultures, although the majority were false positives or contaminants. Eighty-five were significant/indeterminate, representing an average of eight cases per year or 0.47% (85/15979) of all positive blood cultures sets. Forty-three were isolated for the first time, representing 1.1% of all significant/indeterminate blood culture episodes. Fungi and anaerobic bacteria compromised over 50% of isolates. In 26 cases (2.4 cases per year), the culture result led to a change in patient management.A 7 day incubation protocol is preferable due to late isolation of organisms; however, if space is required to accommodate increasing blood culture numbers, reducing to a 5 or 6 day protocol would miss only a small percentage of clinically significant isolates.

  5. Clinically significant cognitive impairment in older adults with type 1 diabetes.

    PubMed

    Chaytor, Naomi S; Barbosa-Leiker, Celestina; Ryan, Christopher M; Germine, Laura T; Hirsch, Irl B; Weinstock, Ruth S

    2018-04-14

    Little is known about cognition in older adults with type 1 diabetes. The aim of this study was to identify correlates of clinically significant cognitive impairment. Neuropsychological, diabetes-related and glycemic (HbA1c, Continuous Glucose Monitoring; CGM) data were collected from 201 older adults (≥60 years) with longstanding type 1 diabetes. Clinically significant cognitive impairment (≥2 cognitive tests ≥1.5 SD below normative data) occurred in 48% of the sample. After controlling for age, gender, education and diabetes duration, we found that hypoglycemia unawareness, recent severe hypoglycemic events, any microvascular complication, higher HbA1c and CGM average nocturnal glucose were all associated with increased odds of clinically significant cognitive impairment (ORs = 1.01-2.61), while CGM nocturnal % time below 60 mg/dL was associated with a decreased odds of cognitive impairment (OR = 0.94). Diabetes duration, diagnosis age, daytime CGM, and lifetime severe hypoglycemic events were not related to cognitive impairment status. Clinically significant cognitive impairment was common in older adults with type 1 diabetes. Diabetes-related correlates of cognitive impairment were identified, including hypoglycemia unawareness, recent severe hypoglycemic events, and CGM variables. Longitudinal research is needed to determine if these variables predict cognitive decline and if their modification alters outcomes. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. An exploration into study design for biomarker identification: issues and recommendations.

    PubMed

    Hall, Jacqueline A; Brown, Robert; Paul, Jim

    2007-01-01

    Genomic profiling produces large amounts of data and a challenge remains in identifying relevant biological processes associated with clinical outcome. Many candidate biomarkers have been identified but few have been successfully validated and make an impact clinically. This review focuses on some of the study design issues encountered in data mining for biomarker identification with illustrations of how study design may influence the final results. This includes issues of clinical endpoint use and selection, power, statistical, biological and clinical significance. We give particular attention to study design for the application of supervised clustering methods for identification of gene networks associated with clinical outcome and provide recommendations for future work to increase the success of identification of clinically relevant biomarkers.

  7. Expression of thymidylate synthase (TS) and its prognostic significance in patients with cutaneous angiosarcoma.

    PubMed

    Shimizu, A; Kaira, K; Okubo, Y; Utsumi, D; Bolag, A; Yasuda, M; Takahashi, K; Ishikawa, O

    2017-01-01

    Cutaneous angiosarcoma (CA) is extremely rare, and little is known about the biological significance of possible biomarkers for chemotherapeutic agents. Thymidylate synthase (TS) is an attractive target for cancer treatment in various human neoplasms. It remains unclear whether the expression of TS is associated with the clinicopathological features of CA patients. The aim of this study was to elucidate the relationship between TS expression and the clinicopathological significance in CA patients. Fifty-one patients with CA were included in this study. TS expression and Ki-67 labeling index were examined using immunohistochemical analysis. TS was positively expressed in 39% (20/51) of CA patients. No statistically significant prognostic factor was identified as a predictor of overall survival (OS) for all patients by univariate analysis, whereas a significant prognostic variable for progression free survival (PFS) was found to be the clinical stage. In addition, both univariate and multivariate analyses confirmed that positive expression of TS was a significant predictor of worse PFS in CA patients of clinical stage 1. Positive TS expression in CA was identified as a significant predictor of worse outcome in patients of clinical stage 1.

  8. Impact of an Onsite Clinic on Utilization of Preventive Services.

    PubMed

    Ostovari, Mina; Yu, Denny; Yih, Yuehwern; Steele-Morris, Charlotte Joy

    2017-07-01

    To assess impact of an onsite clinic on healthcare utilization of preventive services for employees of a public university and their dependents. Descriptive statistics, logistic regression and classification tree techniques were used to assess health claim data to identify changes in patterns of healthcare utilization and factors impacting usage of onsite clinic. Utilization of preventive services significantly increased for women and men employees by 9% and 14% one year after implementation of the onsite clinic. Hourly-paid employees, employees without diabetes, employees with spouse opt out or no coverage were more likely to go to the onsite clinic. Adapted framework for assessing performance of onsite clinics based on usage of health informatics would help to identify health utilization patterns and interaction between onsite clinic and offsite health providers.

  9. Exploring the screening capacity of the Fear of Cancer Recurrence Inventory-Short Form for clinical levels of fear of cancer recurrence.

    PubMed

    Fardell, Joanna E; Jones, Georden; Smith, Allan Ben; Lebel, Sophie; Thewes, Belinda; Costa, Daniel; Tiller, Kerry; Simard, Sébastien; Feldstain, Andrea; Beattie, Sara; McCallum, Megan; Butow, Phyllis

    2018-02-01

    Fear of cancer recurrence (FCR) is a common concern among cancer survivors. Identifying survivors with clinically significant FCR requires validated screening measures and clinical cut-offs. We evaluated the Fear of Cancer Recurrence Inventory-Short Form (FCRI-SF) clinical cut-off in 2 samples. Level of FCR in study 1 participants (from an Australian randomized controlled trial: ConquerFear) was compared with FCRI-SF scores. Based on a biopsychosocial interview, clinicians rated participants as having nonclinical, subclinical, or clinical FCR. Study 2 participants (from a Canadian FCRI-English validation study) were classified as having clinical or nonclinical FCR by using the semistructured clinical interview for FCR (SIFCR). Receiver operating characteristic analyses evaluated the screening ability of the FCRI-SF against clinician ratings (study 1) and the SIFCR (study 2). In study 1, 167 cancer survivors (mean age: 53 years, SD = 10.1) participated. Clinicians rated 43% as having clinical FCR. In study 2, 40 cancer survivors (mean age: 68 years, SD = 7.0) participated; 25% met criteria for clinical FCR according to the SIFCR. For both studies 1 and 2, receiver operating characteristic analyses suggested a cut-off ≥22 on the FCRI-SF identified cancer survivors with clinical levels of FCR with adequate sensitivity and specificity. Establishing clinical cut-offs on FCR screening measures is crucial to tailoring individual care and conducting rigorous research. Our results suggest using a higher cut-off on the FCRI-SF than previously reported to identify clinically significant FCR. Continued evaluation and validation of the FCRI-SF cut-off is required across diverse cancer populations. Copyright © 2017 John Wiley & Sons, Ltd.

  10. Three Cases of Moraxella osloensis Meningitis: A Difficult Experience in Species Identification and Determination of Clinical Significance

    PubMed Central

    Roh, Kyoung Ho; Kim, Chang Ki; Koh, Eunmi; Kim, Myung Sook; Yong, Dongeun; Park, Soo Chul; Chong, Yunsop

    2010-01-01

    We had three cases of Moraxella osloensis meningitis. The species identification was impossible by conventional and commercial phenotypic tests. However, we could identify the species using the 16S rRNA gene sequencing. Determination of clinical significance was difficult in one patient. All three patients recovered by appropriate antimicrobial therapy. PMID:20191057

  11. Detection of Significant Pneumococcal Meningitis Biomarkers by Ego Network.

    PubMed

    Wang, Qian; Lou, Zhifeng; Zhai, Liansuo; Zhao, Haibin

    2017-06-01

    To identify significant biomarkers for detection of pneumococcal meningitis based on ego network. Based on the gene expression data of pneumococcal meningitis and global protein-protein interactions (PPIs) data recruited from open access databases, the authors constructed a differential co-expression network (DCN) to identify pneumococcal meningitis biomarkers in a network view. Here EgoNet algorithm was employed to screen the significant ego networks that could accurately distinguish pneumococcal meningitis from healthy controls, by sequentially seeking ego genes, searching candidate ego networks, refinement of candidate ego networks and significance analysis to identify ego networks. Finally, the functional inference of the ego networks was performed to identify significant pathways for pneumococcal meningitis. By differential co-expression analysis, the authors constructed the DCN that covered 1809 genes and 3689 interactions. From the DCN, a total of 90 ego genes were identified. Starting from these ego genes, three significant ego networks (Module 19, Module 70 and Module 71) that could predict clinical outcomes for pneumococcal meningitis were identified by EgoNet algorithm, and the corresponding ego genes were GMNN, MAD2L1 and TPX2, respectively. Pathway analysis showed that these three ego networks were related to CDT1 association with the CDC6:ORC:origin complex, inactivation of APC/C via direct inhibition of the APC/C complex pathway, and DNA strand elongation, respectively. The authors successfully screened three significant ego modules which could accurately predict the clinical outcomes for pneumococcal meningitis and might play important roles in host response to pathogen infection in pneumococcal meningitis.

  12. Clinical Value of Prognosis Gene Expression Signatures in Colorectal Cancer: A Systematic Review

    PubMed Central

    Cordero, David; Riccadonna, Samantha; Solé, Xavier; Crous-Bou, Marta; Guinó, Elisabet; Sanjuan, Xavier; Biondo, Sebastiano; Soriano, Antonio; Jurman, Giuseppe; Capella, Gabriel; Furlanello, Cesare; Moreno, Victor

    2012-01-01

    Introduction The traditional staging system is inadequate to identify those patients with stage II colorectal cancer (CRC) at high risk of recurrence or with stage III CRC at low risk. A number of gene expression signatures to predict CRC prognosis have been proposed, but none is routinely used in the clinic. The aim of this work was to assess the prediction ability and potential clinical usefulness of these signatures in a series of independent datasets. Methods A literature review identified 31 gene expression signatures that used gene expression data to predict prognosis in CRC tissue. The search was based on the PubMed database and was restricted to papers published from January 2004 to December 2011. Eleven CRC gene expression datasets with outcome information were identified and downloaded from public repositories. Random Forest classifier was used to build predictors from the gene lists. Matthews correlation coefficient was chosen as a measure of classification accuracy and its associated p-value was used to assess association with prognosis. For clinical usefulness evaluation, positive and negative post-tests probabilities were computed in stage II and III samples. Results Five gene signatures showed significant association with prognosis and provided reasonable prediction accuracy in their own training datasets. Nevertheless, all signatures showed low reproducibility in independent data. Stratified analyses by stage or microsatellite instability status showed significant association but limited discrimination ability, especially in stage II tumors. From a clinical perspective, the most predictive signatures showed a minor but significant improvement over the classical staging system. Conclusions The published signatures show low prediction accuracy but moderate clinical usefulness. Although gene expression data may inform prognosis, better strategies for signature validation are needed to encourage their widespread use in the clinic. PMID:23145004

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

    PubMed

    Krishnan, K; Lin, C-Y; Keswani, R; Pandolfino, J E; Kahrilas, P J; Komanduri, S

    2014-08-01

    Esophageal motor disorders are a heterogeneous group of conditions identified by esophageal manometry that lead to esophageal dysfunction. The aim of this study was to assess the clinical utility of endoscopic ultrasound (EUS) in the further evaluation of patients with esophageal motor disorders categorized using the updated Chicago Classification. We performed a retrospective, single center study of 62 patients with esophageal motor disorders categorized according to the Chicago Classification. All patients underwent standard radial endosonography to assess for extra-esophageal findings or alternative explanations for esophageal outflow obstruction. Secondary outcomes included esophageal wall thickness among the different patient subsets within the Chicago Classification. EUS identified 9/62 (15%) clinically relevant findings that altered patient management and explained the etiology of esophageal outflow obstruction. We further identified substantial variability in esophageal wall thickness in a proportion of patients including some with a significantly thickened non-muscular layer. EUS findings are clinically relevant in a significant number of patients with motor disorders and can alter clinical management. Variability in esophageal wall thickness of the muscularis propria and non-muscular layers identified by EUS may also explain the observed variability in response to standard therapies for achalasia. © 2014 John Wiley & Sons Ltd.

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

    PubMed Central

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

    2015-01-01

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

  15. Improving client satisfaction and clinic revenues through systems simulation: the case of a university nutrition clinic.

    PubMed

    Thompson, R C; Scammon, D L

    1994-01-01

    A client-responsive strategy was developed based upon input from nutrition clinic personnel, administrators, and clients. Systems simulation identified the strategy most likely to lead to client satisfaction while also meeting the needs of clinic personnel and administration. The strategy was subsequently introduced into the clinic and patient satisfaction and operating revenues were monitored following implementation. Both measures of impact demonstrated significant improvement.

  16. Differences in the API 20E biochemical patterns of clinical and environmental Vibrio parahaemolyticus isolates.

    PubMed

    Martinez-Urtaza, Jaime; Lozano-Leon, Antonio; Viña-Feas, Alejandro; de Novoa, Jacobo; Garcia-Martin, Oscar

    2006-02-01

    Genetic differences in clinical and environmental strains of Vibrio parahaemolyticus have been widely used as criteria in identifying pathogenic isolates. However, few studies have been carried out to assess the differences in biochemical characteristics of V. parahaemolyticus isolates from human and environmental sources. We compared the biochemical profiles obtained by the characterization of V. parahaemolyticus isolates from human infections and the marine environment using the API 20E system. Environmental and clinical isolates showed significant differences in the gelatin and arabinose tests. Additionally, clinical isolates were correctly identified according to the API 20E profile using 0.85% NaCl diluent, but they presented nonspecific profiles with 2% NaCl diluent. In contrast, use of 2% NaCl diluent facilitated correct identification of the environmental isolates. Clinical isolates showed significant differences in up to five biochemical tests with respect to the API 20E database. The API 20E system is widely used in routine identification of bacteria in clinical laboratories, and this discrepancy in an important number of biochemical tests may lead to misidentification of V. parahaemolyticus infection.

  17. Needs assessment for collaborative network in pediatric clinical research and education.

    PubMed

    Ishiguro, Akira; Sasaki, Hatoko; Yahagi, Naohisa; Kato, Hitoshi; Kure, Shigeo; Mori, Rintaro

    2017-01-01

    A collaborative network for pediatric research has not been fully established in Japan. To identify the network infrastructure, we conducted a survey on the support and education for clinical research currently available in children's hospitals. In November 2014, a 27-question survey was distributed to 31 hospitals belonging to the Japanese Association of Children's Hospitals and Related Institutions (JACHRI) to assess clinical research support, research education, research achievements, and their expectations. All the hospitals responded to the survey. Overall, 74.2% of hospitals had clinical research support divisions. Although all hospitals had ethics committees, <30% of the hospitals had a data manager, intellectual property management unit, biostatistician, and English-language editor. Seven hospitals had education programs for clinical research. The number of seminars and workshops for clinical research had significant correlations with the number of physicians (r = 0.927), pediatricians (r = 0.922), and clinical trial management physicians (r = 0.962). There was a significant difference in the number of clinical trials initiated by physicians between hospitals with research education programs and those without (P < 0.01). The number of education programs was significantly correlated with the number of original articles and case reports in English (r = 0.788), and the number of publications in Japanese (r = 0.648). All hospitals recognized the need for a leader to establish a collaborative network for clinical research. Important factors for creating a collaborative system for pediatric research in Japan were identified. Human resources to support clinical research are a key factor to improve clinical research education and research achievements. © 2016 Japan Pediatric Society.

  18. Urogenital Chlamydia trachomatis infections among ethnic groups in Paramaribo, Suriname; determinants and ethnic sexual mixing patterns.

    PubMed

    van der Helm, Jannie J; Bom, Reinier J M; Grünberg, Antoon W; Bruisten, Sylvia M; Schim van der Loeff, Maarten F; Sabajo, Leslie O A; de Vries, Henry J C

    2013-01-01

    Little is known about the epidemiology of urogenital Chlamydia trachomatis infection (chlamydia) in Suriname. Suriname is a society composed of many ethnic groups, such as Creoles, Maroons, Hindustani, Javanese, Chinese, Caucasians, and indigenous Amerindians. We estimated determinants for chlamydia, including the role of ethnicity, and identified transmission patterns and ethnic sexual networks among clients of two clinics in Paramaribo, Suriname. Participants were recruited at two sites a sexually transmitted infections (STI) clinic and a family planning (FP) clinic in Paramaribo. Urine samples from men and nurse-collected vaginal swabs were obtained for nucleic acid amplification testing. Logistic regression analysis was used to identify determinants of chlamydia. Multilocus sequence typing (MLST) was performed to genotype C. trachomatis. To identify transmission patterns and sexual networks, a minimum spanning tree was created, using full MLST profiles. Clusters in the minimum spanning tree were compared for ethnic composition. Between March 2008 and July 2010, 415 men and 274 women were included at the STI clinic and 819 women at the FP clinic. Overall chlamydia prevalence was 15% (224/1508). Age, ethnicity, and recruitment site were significantly associated with chlamydia in multivariable analysis. Participants of Creole and Javanese ethnicity were more frequently infected with urogenital chlamydia. Although sexual mixing with other ethnic groups did differ significantly per ethnicity, this mixing was not independently significantly associated with chlamydia. We typed 170 C. trachomatis-positive samples (76%) and identified three large C. trachomatis clusters. Although the proportion from various ethnic groups differed significantly between the clusters (P = 0.003), all five major ethnic groups were represented in all three clusters. Chlamydia prevalence in Suriname is high and targeted prevention measures are required. Although ethnic sexual mixing differed between ethnic groups, differences in prevalence between ethnic groups could not be explained by sexual mixing.

  19. Urogenital Chlamydia trachomatis Infections among Ethnic Groups in Paramaribo, Suriname; Determinants and Ethnic Sexual Mixing Patterns

    PubMed Central

    van der Helm, Jannie J.; Bom, Reinier J. M.; Grünberg, Antoon W.; Bruisten, Sylvia M.; Schim van der Loeff, Maarten F.; Sabajo, Leslie O. A.; de Vries, Henry J. C.

    2013-01-01

    Background Little is known about the epidemiology of urogenital Chlamydia trachomatis infection (chlamydia) in Suriname. Suriname is a society composed of many ethnic groups, such as Creoles, Maroons, Hindustani, Javanese, Chinese, Caucasians, and indigenous Amerindians. We estimated determinants for chlamydia, including the role of ethnicity, and identified transmission patterns and ethnic sexual networks among clients of two clinics in Paramaribo, Suriname. Methods Participants were recruited at two sites a sexually transmitted infections (STI) clinic and a family planning (FP) clinic in Paramaribo. Urine samples from men and nurse-collected vaginal swabs were obtained for nucleic acid amplification testing. Logistic regression analysis was used to identify determinants of chlamydia. Multilocus sequence typing (MLST) was performed to genotype C. trachomatis. To identify transmission patterns and sexual networks, a minimum spanning tree was created, using full MLST profiles. Clusters in the minimum spanning tree were compared for ethnic composition. Results Between March 2008 and July 2010, 415 men and 274 women were included at the STI clinic and 819 women at the FP clinic. Overall chlamydia prevalence was 15% (224/1508). Age, ethnicity, and recruitment site were significantly associated with chlamydia in multivariable analysis. Participants of Creole and Javanese ethnicity were more frequently infected with urogenital chlamydia. Although sexual mixing with other ethnic groups did differ significantly per ethnicity, this mixing was not independently significantly associated with chlamydia. We typed 170 C. trachomatis-positive samples (76%) and identified three large C. trachomatis clusters. Although the proportion from various ethnic groups differed significantly between the clusters (P = 0.003), all five major ethnic groups were represented in all three clusters. Conclusion Chlamydia prevalence in Suriname is high and targeted prevention measures are required. Although ethnic sexual mixing differed between ethnic groups, differences in prevalence between ethnic groups could not be explained by sexual mixing. PMID:23874730

  20. Use of diagnostic imaging in the emergency department for cervical spine injuries in Kingston, Ontario.

    PubMed

    Pickett, William; Kukaswadia, Atif; Thompson, Wendy; Frechette, Mylene; McFaull, Steven; Dowdall, Hilary; Brison, Robert J

    2014-01-01

    This study assessed the use and clinical yield of diagnostic imaging (radiography, computed tomography, and medical resonance imaging) ordered to assist in the diagnosis of acute neck injuries presenting to emergency departments (EDs) in Kingston, Ontario, from 2002-2003 to 2009-2010. Acute neck injury cases were identified using records from the Kingston sites of the Canadian National Ambulatory Care Reporting System. Use of radiography was analyzed over time and related to proportions of cases diagnosed with clinically significant cervical spine injuries. A total of 4,712 neck injury cases were identified. Proportions of cases referred for diagnostic imaging to the neck varied significantly over time, from 30.4% in 2002-2003 to 37.6% in 2009-2010 (ptrend  =  0.02). The percentage of total cases that were positive for clinically significant cervical spine injury ("clinical yield") also varied from a low of 5.8% in 2005-2006 to 9.2% in 2008-2009 (ptrend  =  0.04), although the clinical yield of neck-imaged cases did not increase across the study years (ptrend  =  0.23). Increased clinical yield was not observed in association with higher neck imaging rates whether that yield was expressed as a percentage of total cases positive for clinically significant injury (p  =  0.29) or as a percentage of neck-imaged cases that were positive (p  =  0.77). We observed increases in the use of diagnostic images over time, reflecting a need to reinforce an existing clinical decision rule for cervical spine radiography. Temporal increases in the clinical yield for total cases may suggest a changing case mix or more judicious use of advanced types of diagnostic imaging.

  1. Can clinical supervision sustain our workforce in the current healthcare landscape? Findings from a Queensland study of allied health professionals.

    PubMed

    Saxby, Christine; Wilson, Jill; Newcombe, Peter

    2015-09-01

    Clinical supervision is widely recognised as a mechanism for providing professional support, professional development and clinical governance for healthcare workers. There have been limited studies about the effectiveness of clinical supervision for allied health and minimal studies conducted within the Australian health context. The aim of the present study was to identify whether clinical supervision was perceived to be effective by allied health professionals and to identify components that contributed to effectiveness. Participants completed an anonymous online questionnaire, administered through the health service's intranet. A cross-sectional study was conducted with community allied health workers (n = 82) 8 months after implementation of structured clinical supervision. Demographic data (age, gender), work-related history (profession employment level, years of experience), and supervision practice (number and length of supervision sessions) were collected through an online survey. The outcome measure, clinical supervision effectiveness, was operationalised using the Manchester Clinical Supervision Scale-26 (MCSS-26). Data were analysed with Pearson correlation (r) and independent sample t-tests (t) with significance set at 0.05 (ie the probability of significant difference set at P < 0.05). The length of the supervision sessions (r(s) ≥ 0.44), the number of sessions (r(s) ≥ 0.35) and the total period supervision had been received (r(s) ≥ 0.42) were all significantly positively correlated with the MCSS-26 domains of clinical supervision effectiveness. Three individual variables, namely 'receiving clinical supervision', 'having some choice in the allocation of clinical supervisor' and 'having a completed clinical supervision agreement', were also significantly associated with higher total MCSS-26 scores (P(s) < 0.014). The results of the study demonstrate that when clinical supervision uses best practice principles, it can provide professional support for allied health workers, even during times of rapid organisational change.

  2. Factors affecting delays in first trimester pregnancy termination services in New Zealand.

    PubMed

    Silva, Martha; McNeill, Rob; Ashton, Toni

    2011-04-01

    To identify the factors affecting the timeliness of services in first trimester abortion service in New Zealand. Primary data were collected from all patients attending nine abortion clinics between February and May 2009. The outcome measured was delay between the first visit with a referring doctor and the date of the abortion procedure. Patient records (n=2,950) were audited to determine the timeline between the first point of entry to the health system and the date of abortion. Women were also invited to fill out a questionnaire identifying personal factors affecting access to services (n=1,086, response rate = 36.8%). Women who went to private clinic had a significantly shorter delay compared to public clinics. Controlling for clinic type, women who went to clinics that offered medical abortions or clinics that offered single day services experienced less delay. Also, women who had more than one visit with their referring doctor experienced a greater delay than those who had a single visit. The earlier in pregnancy women sought services the longer the delay. Women's decision-making did not have a significant effect on delay. Several clinic level and systemic factors are significantly associated with delay in first trimester abortion services. In order to ensure the best physical and emotional outcomes, timeliness of services must improve. © 2011 The Authors. ANZJPH © 2011 Public Health Association of Australia.

  3. Prenatal Diagnosis of DNA Copy Number Variations by Genomic Single-Nucleotide Polymorphism Array in Fetuses with Congenital Heart Defects.

    PubMed

    Tang, Shaohua; Lv, Jiaojiao; Chen, Xiangnan; Bai, Lili; Li, Huanzheng; Chen, Chong; Wang, Ping; Xu, Xueqin; Lu, Jianxin

    2016-01-01

    To evaluate the usefulness of single-nucleotide polymorphism (SNP) array for prenatal genetic diagnosis of congenital heart defect (CHD), we used this approach to detect clinically significant copy number variants (CNVs) in fetuses with CHDs. A HumanCytoSNP-12 array was used to detect genomic samples obtained from 39 fetuses that exhibited cardiovascular abnormalities on ultrasound and had a normal karyotype. The relationship between CNVs and CHDs was identified by using genotype-phenotype comparisons and searching of chromosomal databases. All clinically significant CNVs were confirmed by real-time PCR. CNVs were detected in 38/39 (97.4%) fetuses: variants of unknown significance were detected in 2/39 (5.1%), and clinically significant CNVs were identified in 7/39 (17.9%). In 3 of the 7 fetuses with clinically significant CNVs, 3 rare and previously undescribed CNVs were detected, and these CNVs encompassed the CHD candidate genes FLNA (Xq28 dup), BCOR (Xp11.4 dup), and RBL2 (16q12.2 del). Compared with conventional cytogenetic genomics, SNP array analysis provides significantly improved detection of submicroscopic genomic aberrations in pregnancies with CHDs. Based on these results, we propose that genomic SNP array is an effective method which could be used in the prenatal diagnostic test to assist genetic counseling for pregnancies with CHDs. © 2015 S. Karger AG, Basel.

  4. Axillary Ultrasound Accurately Excludes Clinically Significant Lymph Node Disease in Patients with Early Stage Breast Cancer

    PubMed Central

    Tucker, Natalia S.; Cyr, Amy E.; Ademuyiwa, Foluso O.; Tabchy, Adel; George, Krystl; Sharma, Piyush; Jin, Linda X.; Sanati, Souzan; Aft, Rebecca; Gao, Feng; Margenthaler, Julie A.; Gillanders, William E.

    2016-01-01

    Objective Assess the performance characteristics of axillary ultrasound (AUS) for accurate exclusion of clinically significant axillary lymph node (ALN) disease. Background Sentinel lymph node biopsy (SLNB) is currently the standard of care for staging the axilla in patients with clinical T1–T2, N0 breast cancer. AUS is a noninvasive alternative to SLNB for staging the axilla. Methods Patients were identified using a prospectively maintained database. Sensitivity, specificity, and negative predictive value (NPV) were calculated by comparing AUS findings to pathology results. Multivariate analyses were performed to identify patient and/or tumor characteristics associated with false negative (FN) AUS. A blinded review of FN and matched true negative cases was performed by two independent medical oncologists to compare treatment recommendations and actual treatment received. Recurrence-free survival was described using Kaplan-Meier product limit methods. Results 647 patients with clinical T1–T2, N0 breast cancer underwent AUS between January, 2008 and March, 2013. AUS had a sensitivity of 70%, NPV of 84% and PPV of 56% for the detection of ALN disease. For detection of clinically significant disease (> 2.0 mm), AUS had a sensitivity of 76% and NPV of 89%. FN AUS did not significantly impact adjuvant medical decision making. Patients with FN AUS had recurrence-free survival equivalent to patients with pathologic N0 disease. Conclusions AUS accurately excludes clinically significant ALN disease in patients with clinical T1–T2, N0 breast cancer. AUS may be an alternative to SLNB in these patients where axillary surgery is no longer considered therapeutic, and predictors of tumor biology are increasingly used to make adjuvant therapy decisions. PMID:26779976

  5. Clinical insomnia and associated factors in failed back surgery syndrome: a retrospective cross-sectional study.

    PubMed

    Yun, Soon Young; Kim, Do Heon; Do, Hae Yoon; Kim, Shin Hyung

    2017-01-01

    Background Insomnia frequently occurs to patients with persistent back pain. By worsening pain, mood, and physical functioning, insomnia could lead to the negative clinical consequences of patients with failed back surgery syndrome (FBSS). This retrospective and cross-sectional study aims to identify the risk factors associated with clinical insomnia in FBSS patients. Methods A total of 194 patients with FBSS, who met the study inclusion criteria, were included in this analysis. The Insomnia Severity Index (ISI) was utilized to ascertain the presence of clinical insomnia (ISI score ≥ 15). Logistic regression analysis evaluates patient demographic factors, clinical factors including prior surgical factors, and psychological factors to identify the risk factors of clinical insomnia in FBSS patients. Results After the persistent pain following lumbar spine surgery worsened, 63.4% of patients reported a change from mild to severe insomnia. In addition, 26.2% of patients met the criteria for clinically significant insomnia. In a multivariate logistic regression analysis, high pain intensity (odds ratio (OR) =2.742, 95% confidence interval (CI): 1.022 - 7.353, P =0.045), high pain catastrophizing (OR=4.185, 95% CI: 1.697 - 10.324, P =0.002), greater level of depression (OR =3.330, 95% CI: 1.127 - 9.837, P =0.030) were significantly associated with clinical insomnia. However, patient demographic factors and clinical factors including prior surgical factors were not significantly associated with clinical insomnia. Conclusions Insomnia should be addressed as a critical part of pain management in FBSS patients with these risk factors, especially in patients with high pain catastrophizing.

  6. The Canadian Pharmacogenomics Network for Drug Safety: a model for safety pharmacology.

    PubMed

    Ross, Colin J D; Visscher, Henk; Sistonen, Johanna; Brunham, Liam R; Pussegoda, Kusala; Loo, Tenneille T; Rieder, Michael J; Koren, Gideon; Carleton, Bruce C; Hayden, Michael R

    2010-07-01

    Adverse drug reactions (ADRs) rank as one of the top 10 leading causes of death in the developed world, and the direct medical costs of ADRs exceed $100 billion annually in the United States alone. Pharmacogenomics research seeks to identify genetic factors that are responsible for individual differences in drug efficacy and susceptibility to ADRs. This has led to several genetic tests that are currently being used to provide clinical recommendations. The Canadian Pharmacogenomics Network for Drug Safety is a nation-wide effort established in Canada to identify novel predictive genomic markers of severe ADRs in children and adults. A surveillance network has been established in 17 of Canada's major hospitals to identify patients experiencing specific ADRs and to collect biological samples and relevant clinical history for genetic association studies. To identify ADR-associated genetic markers that could be incorporated into predictive tests that will reduce the occurrence of serious ADRs, high-throughput genomic analyses are conducted with samples from patients that have suffered serious ADRs and matched control patients. ADRs represent a significant unmet medical problem with significant morbidity and mortality, and Canadian Pharmacogenomics Network for Drug Safety is a nation-wide network in Canada that seeks to identify genetic factors responsible for interindividual differences in susceptibility to serious ADRs. Active ADR surveillance is necessary to identify and recruit patients who suffer from serious ADRs. National and international collaborations are required to recruit sufficient patients for these studies. Several pharmacogenomics tests are currently in clinical use to provide dosing recommendations, and the number of pharmacogenomics tests is expected to significantly increase in the future.

  7. Gender bias in clinical case reports: A cross-sectional study of the "big five" medical journals.

    PubMed

    Allotey, Pascale; Allotey-Reidpath, Caitlin; Reidpath, Daniel D

    2017-01-01

    Gender bias in medical journals can affect the science and the benefit to patients. It has never been investigated in clinical case reports. The oversight is important because of the role clinical case reports play in hypothesis generation and medical education. We investigated contemporary gender bias in case reports for the highest ranked journals in general and internal medicine. PubMed case reports data from 2011 to 2016 were extracted for the Annals of Internal Medicine, British Medical Journal, the Journal of the American Medical Association, The Lancet, and New England Journal of Medicine. The gender of the patients were identified and a text analysis of the Medical Subject Headings conducted. A total of 2,742 case reports were downloaded and 2,582 (95.6%) reports contributed to the final analysis. A pooled analysis showed a statistically significant gender bias against female case reports (0.45; 95%CI: 0.43-0.47). The Annals of Internal Medicine was the only journal with a point estimate (non significant) in the direction of a bias against male patients. The text analysis identified no substantive difference in the focus of the case reports and no obvious explanation for the bias. Gender bias, previously identified in clinical research and in clinical authorship, extends into the patients presented in clinical case reports. Whether it is driven by authors or editors is not clear, but it likely contributes to and supports an overall male bias of clinical medicine.

  8. 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

  9. 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.

  10. Predictors of job satisfaction among academic faculty members: do instructional and clinical staff differ?

    PubMed

    Chung, Kevin C; Song, Jae W; Kim, H Myra; Woolliscroft, James O; Quint, Elisabeth H; Lukacs, Nicholas W; Gyetko, Margaret R

    2010-10-01

    This study aimed to identify and compare predictors of job satisfaction between instructional and clinical faculty members. A 61-item faculty job satisfaction survey was distributed to 1898 academic faculty members at the University of Michigan Medical School. The anonymous survey was web-based. Questions covered topics on departmental organisation, research, clinical and teaching support, compensation, mentorship, and promotion. Levels of satisfaction were contrasted between faculty members on the two tracks, and predictors of job satisfaction were identified using linear regression models. Response rates for the instructional and clinical faculty groups were 43.1% and 46.7%, respectively. Clinical faculty members reported being less satisfied with how they were mentored and fewer reported understanding the process for promotion. There was no significant difference in overall job satisfaction between the two faculty groups. Surprisingly, clinical faculty members with mentors were significantly less satisfied with how they were mentored and with career advancement, and were significantly less likely to choose an academic career if they had to do it all over again compared with instructional faculty mentees. Additionally, senior-level clinical faculty members were significantly less satisfied with their opportunities to mentor junior faculty members compared with senior-level instructional faculty staff. Significant predictors of job satisfaction for both groups included areas of autonomy, meeting career expectations, work-life balance, and departmental leadership. In the clinical track only, compensation and career advancement variables also emerged as significant predictors of overall job satisfaction. Greater emphasis must be placed on faculty members' well-being at both the institutional level and the level of departmental leadership. Efforts to enhance job satisfaction and improve retention are more likely to succeed if they are directed by locally designed assessments involving department chairs and are specifically aimed at fostering more effective mentoring relationships and increasing the opportunities available for career advancement activities such as research work. Our findings show that these strategies can have significant impacts on job satisfaction and the retention of clinical track faculty members. © Blackwell Publishing Ltd 2010.

  11. Molecular subgroups of adult medulloblastoma: a long-term single-institution study.

    PubMed

    Zhao, Fu; Ohgaki, Hiroko; Xu, Lei; Giangaspero, Felice; Li, Chunde; Li, Peng; Yang, Zhijun; Wang, Bo; Wang, Xingchao; Wang, Zhenmin; Ai, Lin; Zhang, Jing; Luo, Lin; Liu, Pinan

    2016-07-01

    Recent transcriptomic approaches have demonstrated that there are at least 4 distinct subgroups in medulloblastoma (MB); however, survival studies of molecular subgroups in adult MB have been inconclusive because of small sample sizes. The aim of this study is to investigate the molecular subgroups in adult MB and identify their clinical and prognostic implications in a large, single-institution cohort. We determined gene expression profiles for 13 primary adult MBs. Bioinformatics tools were used to establish distinct molecular subgroups based on the most informative genes in the dataset. Immunohistochemistry with subgroup-specific antibodies was then used for validation within an independent cohort of 201 formalin-fixed MB tumors, in conjunction with a systematic analysis of clinical and histological characteristics. Three distinct molecular variants of adult MB were identified: the SHH, WNT, and group 4 subgroups. Validation of these subgroups in the 201-tumor cohort by immunohistochemistry identified significant differences in subgroup-specific demographics, histology, and metastatic status. The SHH subgroup accounted for the majority of the tumors (62%), followed by the group 4 subgroup (28%) and the WNT subgroup (10%). Group 4 tumors had significantly worse progression-free and overall survival compared with tumors of the other molecular subtypes. We have identified 3 subgroups of adult MB, characterized by distinct expression profiles, clinical features, pathological features, and prognosis. Clinical variables incorporated with molecular subgroup are more significantly informative for predicting adult patient outcome. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. Specialized inpatient treatment of adult anorexia nervosa: effectiveness and clinical significance of changes.

    PubMed

    Schlegl, Sandra; Quadflieg, Norbert; Löwe, Bernd; Cuntz, Ulrich; Voderholzer, Ulrich

    2014-09-06

    Previous studies have predominantly evaluated the effectiveness of inpatient treatment for anorexia nervosa at the group level. The aim of this study was to evaluate treatment outcomes at an individual level based on the clinical significance of improvement. Patients' treatment outcomes were classified into four groups: deteriorated, unchanged, reliably improved and clinically significantly improved. Furthermore, the study set out to explore predictors of clinically significant changes in eating disorder psychopathology. A total of 435 inpatients were assessed at admission and at discharge on the following measures: body-mass-index, eating disorder symptoms, general psychopathology, depression and motivation for change. 20.0-32.0% of patients showed reliable changes and 34.1-55.3% showed clinically significant changes in the various outcome measures. Between 23.0% and 34.5% remained unchanged and between 1.7% and 3.0% deteriorated. Motivation for change and depressive symptoms were identified as positive predictors of clinically significant changes in eating disorder psychopathology, whereas body dissatisfaction, impulse regulation, social insecurity and education were negative predictors. Despite high rates of reliable and clinically significant changes following intensive inpatient treatment, about one third of anorexia nervosa patients showed no significant response to treatment. Future studies should focus on the identification of non-responders as well as on the development of treatment strategies for these patients.

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

    PubMed Central

    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

    2016-01-01

    Objective 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. Methods 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. Results 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). Conclusions Our findings provide clues to better understand the pathogenesis of gout and will be useful for development of companion diagnostics. PMID:25646370

  14. Clinical characteristics of 150 consecutive fibromyalgia patients attending an Australian public hospital clinic.

    PubMed

    Guymer, Emma K; Maruff, Paul; Littlejohn, Geoffrey O

    2012-08-01

    To describe clinical characteristics of fibromyalgia in an Australian population. Data was collected from 150 consecutive patients with clinical features of fibromyalgia seen in an Australian public hospital clinic. Demographic information and clinical characteristics were recorded. Significant correlations between clinical characteristics were identified, then used in multiple regression analyses to identify factors influencing outcome in physical function, pain, fatigue and sleep disturbance. Clinical features in groups who were or were not using different treatment strategies were compared. Most patients were female and Caucasian. The majority reported a recognizable trigger factor and many had associated conditions, most commonly headache and irritable bowel syndrome. Physical function was significantly accounted for by pain levels (P = 0.001); pain score was significantly predicted by tenderness (P = 0.002) and physical function level (P = 0.001); fatigue levels were significantly influenced by age (P = 0.007) and sleep disturbance (P < 0.001), and sleep disturbance was significantly predicted by fatigue (P < 0.001). Just over one-third (34%) of patients were using fibromyalgia medications (low-dose tricyclic antidepressant, pregabalin or duloxetine); however, they had less anxiety (P = 0.006) and better reported physical function (P = 0.04) than those who were not. Less than half (43.6%) of the patients were regularly exercising; however, they had reduced overall illness impact scores (P = 0.004), better physical function (P = 0.01) and less fatigue (P = 0.03), anxiety (P = 0.02) and depressive features (P = 0.008) than non-exercisers. Baseline clinical characteristics in this group were comparable to other study populations. The use of management modalities with proven benefit in fibromyalgia was limited; however, those patients who were engaged in regular exercise or using medication had better self-reported outcome measures than those who were not. © 2012 The Authors International Journal of Rheumatic Diseases © 2012 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  15. Novel therapeutic strategies in myelodysplastic syndromes: do molecular genetics help?

    PubMed

    Chung, Stephen S

    2016-03-01

    Many studies over the past decade have together identified genes that are recurrently mutated in the myelodysplastic syndromes (MDS). We will summarize how this information has informed our understanding of disease pathogenesis and behavior, with an emphasis on how this information may inform therapeutic strategies. Genomic sequencing techniques have allowed for the identification of many recurrently mutated genes in MDS, with the most common mutations being found in epigenetic modifiers and components of the splicing machinery. Although many mutations are associated with clinical outcomes and disease phenotypes, at the current time they add relatively little to already robust clinical prognostic algorithms. However, as molecular genetic data are accumulated in larger numbers of patients, it is likely that the clinical significance of co-occurring mutations and less common mutations will come to light. Finally, mutated genes may identify biologically distinct subgroups of MDS that may benefit from novel therapies, and a subset of these genes may themselves serve as therapeutic targets. Advances in our knowledge of the molecular genetics of MDS have significantly improved our understanding of disease biology and promise to improve tools for clinical decision-making and identify new therapies for patients.

  16. Alarming Prevalence of Emergency Hypertension Levels in the General Public Identified by a Hypertension Awareness Campaign.

    PubMed

    Caligiuri, Stephanie P B; Austria, Jose Alejandro; Pierce, Grant N

    2017-03-01

    Hypertension is a major cause of mortality and morbidity today. The "silent" nature of hypertension makes it critical to determine its prevalence and its severity in the general public and to identify strategies to identify people unaware of its presence. A mobile hypertension awareness campaign was created to: (i) determine the prevalence and types of hypertension in an urban North American center, (ii) increase hypertension awareness, and (iii) identify reasons for lack of therapy adherence. Mobile clinics were provided at shopping malls, workplaces, hospitals, and community centres to measure blood pressure in the public. Blood pressure recordings were done on a voluntary basis. Of 1097 participants, 50% presented with high blood pressure which was higher than expected. Of particular clinical significance, an unexpectedly large number of participants (2%) exhibited a hypertensive urgency/emergency. Most of these people were not adherent to medications (if their hypertension was detected previously), were unaware of their hypertensive state, and/or unwilling to acknowledge or ignored the clinical significance of the extremely high blood pressure readings. Reasons for lack of adherence included: denial, being unaware of health consequences, and proper management of hypertension. A relatively large segment of an urban population lives unaware of severe emergency levels of hypertension. A public mobile hypertension clinic provides a valuable strategy for identifying hypertension in the general public and for knowledge translation of hypertension management. © American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  17. Influence of a Phototherapy Unit on Detection of Neonatal Jaundice and Hyperbilirubinemia

    PubMed Central

    Jolly, Donald T.

    1984-01-01

    The introduction of a phototherapy unit in a rural community hospital resulted in a significant increase in the detection of neonatal jaundice and hyperbilirubinemia in otherwise healthy term infants. Jaundiced newborns who were either missed or ignored in the past were now identified and monitored. Both the number of breast-fed infants and the number of primiparous women delivered increased significantly after the unit was obtained. However, these factors alone did not account for the marked increase in the detection rate of jaundice and hyperbilirubinemia. A sub-population of 94 infants was selected to evaluate the clinical assessment of jaundice in the term infant. The accuracy rate for clinical assessment was 70%; 13.8% of newborns with serum bilirubins above 10 mg/dl (170 umol/L) were not identified clinically. PMID:21279119

  18. Novel histopathologic feature identified through image analysis augments stage II colorectal cancer clinical reporting

    PubMed Central

    Caie, Peter D.; Zhou, Ying; Turnbull, Arran K.; Oniscu, Anca; Harrison, David J.

    2016-01-01

    A number of candidate histopathologic factors show promise in identifying stage II colorectal cancer (CRC) patients at a high risk of disease-specific death, however they can suffer from low reproducibility and none have replaced classical pathologic staging. We developed an image analysis algorithm which standardized the quantification of specific histopathologic features and exported a multi-parametric feature-set captured without bias. The image analysis algorithm was executed across a training set (n = 50) and the resultant big data was distilled through decision tree modelling to identify the most informative parameters to sub-categorize stage II CRC patients. The most significant, and novel, parameter identified was the ‘sum area of poorly differentiated clusters’ (AreaPDC). This feature was validated across a second cohort of stage II CRC patients (n = 134) (HR = 4; 95% CI, 1.5– 11). Finally, the AreaPDC was integrated with the significant features within the clinical pathology report, pT stage and differentiation, into a novel prognostic index (HR = 7.5; 95% CI, 3–18.5) which improved upon current clinical staging (HR = 4.26; 95% CI, 1.7– 10.3). The identification of poorly differentiated clusters as being highly significant in disease progression presents evidence to suggest that these features could be the source of novel targets to decrease the risk of disease specific death. PMID:27322148

  19. Uncovering precision phenotype-biomarker associations in traumatic brain injury using topological data analysis

    PubMed Central

    Nielson, Jessica L.; Cooper, Shelly R.; Sorani, Marco D.; Inoue, Tomoo; Yuh, Esther L.; Mukherjee, Pratik; Petrossian, Tanya C.; Lum, Pek Y.; Lingsma, Hester F.; Gordon, Wayne A.; Okonkwo, David O.; Manley, Geoffrey T.

    2017-01-01

    Background Traumatic brain injury (TBI) is a complex disorder that is traditionally stratified based on clinical signs and symptoms. Recent imaging and molecular biomarker innovations provide unprecedented opportunities for improved TBI precision medicine, incorporating patho-anatomical and molecular mechanisms. Complete integration of these diverse data for TBI diagnosis and patient stratification remains an unmet challenge. Methods and findings The Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Pilot multicenter study enrolled 586 acute TBI patients and collected diverse common data elements (TBI-CDEs) across the study population, including imaging, genetics, and clinical outcomes. We then applied topology-based data-driven discovery to identify natural subgroups of patients, based on the TBI-CDEs collected. Our hypothesis was two-fold: 1) A machine learning tool known as topological data analysis (TDA) would reveal data-driven patterns in patient outcomes to identify candidate biomarkers of recovery, and 2) TDA-identified biomarkers would significantly predict patient outcome recovery after TBI using more traditional methods of univariate statistical tests. TDA algorithms organized and mapped the data of TBI patients in multidimensional space, identifying a subset of mild TBI patients with a specific multivariate phenotype associated with unfavorable outcome at 3 and 6 months after injury. Further analyses revealed that this patient subset had high rates of post-traumatic stress disorder (PTSD), and enrichment in several distinct genetic polymorphisms associated with cellular responses to stress and DNA damage (PARP1), and in striatal dopamine processing (ANKK1, COMT, DRD2). Conclusions TDA identified a unique diagnostic subgroup of patients with unfavorable outcome after mild TBI that were significantly predicted by the presence of specific genetic polymorphisms. Machine learning methods such as TDA may provide a robust method for patient stratification and treatment planning targeting identified biomarkers in future clinical trials in TBI patients. Trial Registration ClinicalTrials.gov Identifier NCT01565551 PMID:28257413

  20. Comparison of reporting phase III randomized controlled trials of antibiotic treatment for common bacterial infections in ClinicalTrials.gov and matched publications.

    PubMed

    Shepshelovich, D; Yelin, D; Gafter-Gvili, A; Goldman, S; Avni, T; Yahav, D

    2018-02-15

    Discrepancies between ClinicalTrials.gov entries and matching publications were previously described in general medicine. We aimed to evaluate the consistency of reporting in trials addressing systemic antibiotic therapy. We searched ClinicalTrials.gov for completed phase III trials comparing antibiotic regimens until May 2017. Matched publications were identified in PubMed. Two independent reviewers extracted data and identified inconsistencies. Reporting was assessed among studies started before and after 1 July 2005, when the International Committee of Medical Journal Editors (ICMJE) required mandatory registration as a prerequisite for considering a trial for publication. Matching publications were identified for 75 (70%) of 107 ClinicalTrials.gov entries. Median time from study completion to publication was 26 months (interquartile range 19-42). Primary outcome definition was inconsistent between ClinicalTrials.gov and publications in seven trials (7/72, 10%) and reporting of the primary outcome timeframe was inconsistent in 14 (14/71, 20%). Secondary outcomes definitions were inconsistent in 36 trials (36/66, 55%). Reporting of inclusion criteria and study timeline were inconsistent in 17% (13/65) and 3% (2/65), respectively. Trials started after July 2005 were significantly less likely to have reporting inconsistencies and were published in higher impact factor journals. We found a lower inconsistency rate of outcome reporting compared with other medical disciplines. Reporting completeness and consistency were significantly better after July 2005. The ICMJE requirement for mandatory registration was associated with significant improvement in reporting quality in infectious diseases trials. Prolonged time lag to publication and missing data from unpublished trials should raise a discussion on current reporting and publishing procedures. Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  1. Staff nurses and students: the good, the bad, and the ugly.

    PubMed

    Koontz, Angela M; Mallory, Judy L; Burns, Jane A; Chapman, Shelia

    2010-01-01

    Elements identified by student nurses as impacting learning in the clinical learning environment were explored. A significant element identified by participants was the staff nurse. Strategies for improvement and increasing learning opportunities are included in the discussion.

  2. Reliability of clinical impact grading by healthcare professionals of common prescribing error and optimisation cases in critical care patients.

    PubMed

    Bourne, Richard S; Shulman, Rob; Tomlin, Mark; Borthwick, Mark; Berry, Will; Mills, Gary H

    2017-04-01

    To identify between and within profession-rater reliability of clinical impact grading for common critical care prescribing error and optimisation cases. To identify representative clinical impact grades for each individual case. Electronic questionnaire. 5 UK NHS Trusts. 30 Critical care healthcare professionals (doctors, pharmacists and nurses). Participants graded severity of clinical impact (5-point categorical scale) of 50 error and 55 optimisation cases. Case between and within profession-rater reliability and modal clinical impact grading. Between and within profession rater reliability analysis used linear mixed model and intraclass correlation, respectively. The majority of error and optimisation cases (both 76%) had a modal clinical severity grade of moderate or higher. Error cases: doctors graded clinical impact significantly lower than pharmacists (-0.25; P < 0.001) and nurses (-0.53; P < 0.001), with nurses significantly higher than pharmacists (0.28; P < 0.001). Optimisation cases: doctors graded clinical impact significantly lower than nurses and pharmacists (-0.39 and -0.5; P < 0.001, respectively). Within profession reliability grading was excellent for pharmacists (0.88 and 0.89; P < 0.001) and doctors (0.79 and 0.83; P < 0.001) but only fair to good for nurses (0.43 and 0.74; P < 0.001), for optimisation and error cases, respectively. Representative clinical impact grades for over 100 common prescribing error and optimisation cases are reported for potential clinical practice and research application. The between professional variability highlights the importance of multidisciplinary perspectives in assessment of medication error and optimisation cases in clinical practice and research. © The Author 2017. Published by Oxford University Press in association with the International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  3. Appending Limited Clinical Data to an Administrative Database for Acute Myocardial Infarction Patients: The Impact on the Assessment of Hospital Quality.

    PubMed

    Hannan, Edward L; Samadashvili, Zaza; Cozzens, Kimberly; Jacobs, Alice K; Venditti, Ferdinand J; Holmes, David R; Berger, Peter B; Stamato, Nicholas J; Hughes, Suzanne; Walford, Gary

    2016-05-01

    Hospitals' risk-standardized mortality rates and outlier status (significantly higher/lower rates) are reported by the Centers for Medicare and Medicaid Services (CMS) for acute myocardial infarction (AMI) patients using Medicare claims data. New York now has AMI claims data with blood pressure and heart rate added. The objective of this study was to see whether the appended database yields different hospital assessments than standard claims data. New York State clinically appended claims data for AMI were used to create 2 different risk models based on CMS methods: 1 with and 1 without the added clinical data. Model discrimination was compared, and differences between the models in hospital outlier status and tertile status were examined. Mean arterial pressure and heart rate were both significant predictors of mortality in the clinically appended model. The C statistic for the model with the clinical variables added was significantly higher (0.803 vs. 0.773, P<0.001). The model without clinical variables identified 10 low outliers and all of them were percutaneous coronary intervention hospitals. When clinical variables were included in the model, only 6 of those 10 hospitals were low outliers, but there were 2 new low outliers. The model without clinical variables had only 3 high outliers, and the model with clinical variables included identified 2 new high outliers. Appending even a small number of clinical data elements to administrative data resulted in a difference in the assessment of hospital mortality outliers for AMI. The strategy of adding limited but important clinical data elements to administrative datasets should be considered when evaluating hospital quality for procedures and other medical conditions.

  4. Centralized Research Recruitment—Evolving a Local Clinical Research Recruitment Web Application to Better Meet User Needs

    PubMed Central

    Dwyer‐White, Molly; Doshi, Aalap; Hill, Mary; Pienta, Kenneth J.

    2011-01-01

    Abstract  Recruiting volunteers into clinical research remains a significant challenge for many clinical research study teams, thus the Michigan Institute for Clinical and Health Research (MICHR) at the University of Michigan developed UMClinicalStudies (http://www.UMClinicalStudies.org)—a Web application that links the community to a single gateway for clinical research. UMClinicalStudies (formerly named “Engage”) is an integral piece of MICHR’s efforts to increase clinical research participation in order to advance medical discoveries. Despite the initial success of the application, barriers to research participation remain, including the applications accessibility for potential research volunteers and study team members. In response, new initiatives were instigated to identify user needs, in order to broaden the ability to simultaneously assist researchers in recruitment activities, while also aiding potential volunteers in the exploration of and participation in clinical research opportunities. To do this, improvements to the interface and functionality were identified and implemented for both the public and the research audiences through extensive system analysis, and through the application of human computer interactivity processes, resulting in significant improvements in usability and ultimately research volunteerism, indicating that utilizing such technology is pivotal in reaching broader audiences for clinical trial participation. Clin Trans Sci 2011; Volume 4: 363–368 PMID:22029810

  5. Data-Driven Identification of Risk Factors of Patient Satisfaction at a Large Urban Academic Medical Center.

    PubMed

    Li, Li; Lee, Nathan J; Glicksberg, Benjamin S; Radbill, Brian D; Dudley, Joel T

    2016-01-01

    The Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey is the first publicly reported nationwide survey to evaluate and compare hospitals. Increasing patient satisfaction is an important goal as it aims to achieve a more effective and efficient healthcare delivery system. In this study, we develop and apply an integrative, data-driven approach to identify clinical risk factors that associate with patient satisfaction outcomes. We included 1,771 unique adult patients who completed the HCAHPS survey and were discharged from the inpatient Medicine service from 2010 to 2012. We collected 266 clinical features including patient demographics, lab measurements, medications, disease categories, and procedures. We developed and applied a data-driven approach to identify risk factors that associate with patient satisfaction outcomes. We identify 102 significant risk factors associating with 18 surveyed questions. The most significantly recurrent clinical risk factors were: self-evaluation of health, education level, Asian, White, treatment in BMT oncology division, being prescribed a new medication. Patients who were prescribed pregabalin were less satisfied particularly in relation to communication with nurses and pain management. Explanation of medication usage was associated with communication with nurses (q = 0.001); however, explanation of medication side effects was associated with communication with doctors (q = 0.003). Overall hospital rating was associated with hospital environment, communication with doctors, and communication about medicines. However, patient likelihood to recommend hospital was associated with hospital environment, communication about medicines, pain management, and communication with nurse. Our study identified a number of putatively novel clinical risk factors for patient satisfaction that suggest new opportunities to better understand and manage patient satisfaction. Hospitals can use a data-driven approach to identify clinical risk factors for poor patient satisfaction to support development of specific interventions to improve patients' experience of care.

  6. Living and learning in a rural environment: a nursing student perspective.

    PubMed

    Pront, Leeanne; Kelton, Moira; Munt, Rebecca; Hutton, Alison

    2013-03-01

    This study investigates the influences on nursing student learning who live and learn in the same rural environment. A declining health workforce has been identified both globally and in Australia, the effects of which have become significantly apparent in the rural nursing sector. In support of rural educational programs the literature portrays rural clinical practice experiences as significant to student learning. However, there is little available research on what influences learning for the nursing student who studies in their own rural community. The aim of this study was to understand what influences student learning in the rural clinical environment. Through a multiple case study design five nursing students and two clinical preceptors from a rural clinical venue were interviewed. The interviews were transcribed and thematically analysed to identify factors that influenced student learning outcomes. The most significant influence on nursing student learning in the rural clinical environment was found to include the environment itself, the complex relationships unique to living and studying in a rural community along with the capacity to link theory to practice. The rural environment influences those in it, the demands placed on them, the relationships they form, the ability to promote learning and the time to teach and learn. Copyright © 2012. Published by Elsevier Ltd.

  7. 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.

  8. Prognostic role of CD133 expression in colorectal cancer: a meta-analysis.

    PubMed

    Wang, Ke; Xu, Jianjun; Zhang, Junshu; Huang, Jian

    2012-12-05

    CD133 has been identified as a putative cancer stem cell marker in colorectal cancer (CRC). However, the clinical and prognostic significance of CD133 in CRC remains controversial. Publications were identified which assessed the clinical or prognostic significance of CD133 in CRC up to October 2012. A meta-analysis was performed to clarify the association between CD133 expression and clinical outcomes. A total of 12 studies met the inclusion criteria, and comprised 3652 cases. Analysis of these data showed that CD133 was not significantly associated with the depth of CRC invasion (odds ratio [OR] = 1.44, 95% confidence interval [CI]: 0.77-2.68, Z = 1.15, P = 0.252) or tumor differentiation (OR = 0.63, 95% CI: 0.28-1.46, Z = -1.06, P = 0.286). Also, there was no statistically significant association of CD133 with lymph node metastasis (OR = 1.16, 95% CI: 0.87-1.54, Z = 1.05, P = 0.315) or lymphatic invasion (OR = 1.08, 95% CI: 0.81-1.43, Z = 0.53, P = 0.594). However, in identified studies, overexpression of CD133 was highly correlated with reduced overall survival (relative risk [RR] = 2.14, 95% CI: 1.45-3.17, Z = 3.81, P = 0.0001). CD133 may play an important role in the progression of CRC, and overexpression of CD133 is closely related with poorer patient survival. If these findings are confirmed by well-designed prospective studies, CD133 may be a useful maker for clinical applications.

  9. 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 identification of computer-based protocol care strategies that justify expensive and burdensome clinical trials. PMID:26228765

  10. Improving performance with clinical decision support.

    PubMed

    Brailer, D J; Goldfarb, S; Horgan, M; Katz, F; Paulus, R A; Zakrewski, K

    1996-07-01

    CADU/CIS (Clinical and Administrative Decision-support Utility and Clinical Information System) is a clinical decision-support workstation that allows large volumes of clinical information systems data to be analyzed in a timely and user-friendly fashion. CARE PROCESS MEASUREMENT: For any given disease, subgroups of patients are identified, and automated, customized "clinical pathways" are generated. For each subgroup, the best practice norms for use of test and therapies are identified. Practice style variations are then compared to outcomes to focus inquiry on decisions that significantly affect outcomes. INTESTINAL OBSTRUCTION: Graduate Health Systems, a multisite integrated provider in the Philadelphia area, has used CADU/CIS to improve quality problems, reduce treatment-intensity variations, and improve clinical participation in care process evaluation and decision making. A task force selected intestinal obstruction without hernia as its first study because of the related high-volume and high-morbidity complications. Use of a ten-step method for clinical performance improvement showed that the intravenous administration of unnecessary fluids to 104 patients with intestinal obstruction induced congestive heart failure (CHF) in 5 patients. Task force members and other practicing physicians are now developing guidelines and other interventions aimed at fluid use. Indeed, the task force used CADU/CIS to identify an additional 250 patients in one year whose conditions were complicated by CHF. A clinical decision support tool can be instrumental in detecting problems with important clinical and economic implications, identifying their important underlying causes, tracking the associated tests and therapies, and monitoring interventions.

  11. Pharmacists' interventions on clinical asthma outcomes: a systematic review.

    PubMed

    Garcia-Cardenas, Victoria; Armour, Carol; Benrimoj, Shalom I; Martinez-Martinez, Fernando; Rotta, Inajara; Fernandez-Llimos, Fernando

    2016-04-01

    The objective of this systematic review was to evaluate the impact of pharmacists' interventions on clinical asthma outcomes on adult patients and to identify the outcome indicators used.PubMed, Scopus, Web of Science and Scielo were searched. Studies addressing pharmacists' interventions on adult asthma patients reporting clinical asthma outcomes were incorporated.11 clinical outcomes were identified in 21 studies. 10 studies measured the impact of the intervention on asthma control. Randomised controlled trials (RCT) and non-RCTs found positive results in percentages of controlled patients and Asthma Control Questionnaire (ACQ) scores. Discordant results were found for Asthma Control Test results. Asthma severity was assessed in four studies. One RCT found a significant decrease in the percentage of severe patients; two non-RCTs found significant improvements in severity scores. 11 studies reported pulmonary function indicators, showing inconsistent results. Eight studies measured asthma symptoms; three RCTs and four non-RCTs showed significant improvements.RCTs and non-RCTs generated similar results for most outcomes. Based on the evidence generated by RCTs, pharmacists' have a positive impact on the percentage of controlled patients, ACQ scores, severity and symptoms. Future research should report using the core outcome set of indicators established for asthma (PROSPERO CRD42014007019). Copyright ©ERS 2016.

  12. Comparison of Four Views to Single-view Ultrasound Protocols to Identify Clinically Significant Pneumothorax.

    PubMed

    Helland, Gregg; Gaspari, Romolo; Licciardo, Samuel; Sanseverino, Alexandra; Torres, Ulises; Emhoff, Timothy; Blehar, David

    2016-10-01

    Ultrasound (US) has been shown to be effective at identifying a pneumothorax (PTX); however, the additional value of adding multiple views has not been studied. Single- and four-view protocols have both been described in the literature. The objective of this study was to compare the diagnostic accuracy of single-view versus four-view lung US to detect clinically significant PTX in trauma patients. This was a randomized, prospective trial on trauma patients. Adult patients with acute traumatic injury undergoing computed tomography (CT) scan of the chest were eligible for enrollment. Patients were randomized to a single view or four views of each hemithorax prior to any imaging. USs were performed and interpreted by credentialed physicians using a 7.5-Mhz linear array transducer on a portable US machine with digital clips recorded for later review. Attending radiologist interpretation of the chest CT was reviewed for presence or absence of PTX with descriptions of small foci of air or minimal PTX categorized as clinically insignificant. A total of 260 patients were enrolled over a 2-year period. A total of 139 patients received a single view of each chest wall and 121 patients received four views. There were a total of 49 patients that had a PTX (19%), and 29 of these were clinically significant (11%). In diagnosis of any PTX, both single-view and four-view techniques showed poor sensitivity (54.2 and 68%) but high specificity (99 and 98%). For clinically significant PTX, single-view US demonstrated a sensitivity of 93% (95% confidence interval [CI] = 64.1% to 99.6%) and a specificity of 99.2% (95% CI = 95.5% to 99.9%), with sensitivity of 93.3% (95% CI = 66% to 99.7%) and specificity of 98% (95% CI = 92.1% to 99.7%) for four views. Single-view and four-view chest wall USs demonstrate comparable sensitivity and specificity for PTX. The additional time to obtain four views should be weighed against the absence of additional diagnostic yield over a single view when using US to identify a clinically significant PTX. © 2016 by the Society for Academic Emergency Medicine.

  13. Cinnamon intake lowers fasting blood glucose: an updated meta-analysis

    USDA-ARS?s Scientific Manuscript database

    OBJECTIVE – To determine if meta-analysis of recent clinical studies of cinnamon intake by people with Type II diabetes and/or prediabetes resulted in significant changes in fasting blood glucose. RESEARCH DESIGN AND METHODS -- Published clinical studies were identified using a literature search (P...

  14. [Clinical observation of modified Da Chaihu decoction in treating essential hypertension with anxiety].

    PubMed

    Zhang, Xiang-Dong; Cheng, Wang-Qiang; Wang, Yong-Gang; Zhang, Zheng

    2017-06-01

    To observe the clinical efficacy of modified Da Chaihu decoction in treating essential hypertension with anxiety, the randomized, controlled, clinical trial was performed in this study. One hundred and twenty-six hypertensive patients with anxiety meeting the inclusive criteria were randomized into the treatment group and the control group. All of the included patients in the above 2 groups were treated by amlodipine besylate tablets. Patients in the treatment group were given Chinese herbal medicine modified Da Chaihu decoction every day. And patients in the control group were given flupentixol and melitracen tablets. The treatment course was 4 weeks. Blood pressure, the score of traditional Chinese medicine syndrome, blood lipids, C reactive protein, the Hamilton anxiety scale score and adverse effects were observed. It has been identified that, both systolic and diastolic blood pressure were significantly reduced (P<0.05). However, no significant difference between the treatment group and the control group was identified. For traditional Chinese medicine syndrome, it was significantly improved in the treatment group (P<0.05). For blood lipids, TC, TG, HDL-C, and LDL-C were significantly improved in the treatment group (P<0.05). After treatment, only TC was significantly reduced in the treatment group when compared to the control group (P<0.05). For C reactive protein, it was significantly reduced in the treatment group after treatment (P<0.05). For anxiety, no significant difference between the treatment group and the control group on the Hamilton anxiety scale score was identified. For adverse effect, no severe adverse effect was identified in this study. The modified Da Chaihu decoction maybe effective in the treatment of essential hypertension with anxiety. In addition to a certain role in lowering blood pressure, the modified Da Chaihu decoction was also effective in improving traditional Chinese medicine syndrome and blood lipids, reducing the level of C reactive protein, relieving anxiety with little adverse effect. Copyright© by the Chinese Pharmaceutical Association.

  15. Predicting functional mitral stenosis after restrictive annuloplasty for ischemic mitral regurgitation.

    PubMed

    Li, Baotong; Wu, Hengchao; Sun, Hansong; Xu, Jianping; Song, Yunhu; Wang, Wei; Wang, Shuiyun

    2018-03-07

    Although it has been realized that restrictive mitral valve annuloplasty (MVA) may result in clinically significant functional mitral stenosis (MS), it still cannot be predicted. The purpose of this study was to identify risk factors for clinically significant functional MS following restrictive MVA surgery for chronic ischemic mitral regurgitation (CIMR). 114 patients who underwent restrictive MVA with coronary artery bypass grafting (CABG) for treatment of CIMR were retrospectively reviewed. Clinically significant functional MS was defined as resting transmitral peak pressure gradient (PPG) ≥ 13 mmHg. During the follow-up period (range 6-12 months), 28 (24.56%) patients developed clinically significant functional MS. The PPG at follow-up was significantly higher than that measured in the early postoperative stage (3-5 days after surgery). Moreover, there was a linear correlation between the two measurements (r = 0.398, p < 0.001). Annuloplasty size ≤ 27 mm and early postoperative PPG ≥ 7.4 mmHg could predict clinically significant functional MS at 6-12 months postoperatively. Chronic ischemic mitral regurgitation patients treated with restrictive MVA and CABG have significant increases in PPG postoperatively. Annuloplasty size ≤ 27 mm and early postoperative PPG ≥ 7.4 mmHg can predict clinically significant functional MS at 6-12 months after surgery.

  16. Single and Multiple Clinical Syndromes in Incarcerated Offenders: Associations With Dissociative Experiences and Emotionality

    PubMed Central

    Garofalo, Carlo; Velotti, Patrizia; Crocamo, Cristina; Carrà, Giuseppe

    2017-01-01

    The present study examined the prevalence and correlates of clinical syndromes in a large group (N = 438) of incarcerated violent offenders, looking at differences between inmates with one and those with more than one clinical syndromes. More than a half of the sample (57%) reported clinically relevant symptoms for at least one clinical syndrome (n = 252), and the majority of them (38%) reported more syndromes in comorbidity (n = 169). Increased severity of clinical conditions (none, one, more than one syndrome) corresponded with significantly greater levels of personality disorder traits, psychological symptoms, dissociation, and negative emotionality, with large effect sizes. After controlling for co-occurrence of personality disorder traits and other symptoms, the presence of more than one comorbid syndrome significantly predicted unique variance in dissociation (positively) and positive emotionality (negatively). The presence of one clinical syndrome significantly and positively predicted negative emotionality. Findings support the possibility that the complexity, and not just the presence, of psychopathology could identify different groups of inmates. PMID:27913716

  17. Single and Multiple Clinical Syndromes in Incarcerated Offenders: Associations With Dissociative Experiences and Emotionality.

    PubMed

    Garofalo, Carlo; Velotti, Patrizia; Crocamo, Cristina; Carrà, Giuseppe

    2018-04-01

    The present study examined the prevalence and correlates of clinical syndromes in a large group ( N = 438) of incarcerated violent offenders, looking at differences between inmates with one and those with more than one clinical syndromes. More than a half of the sample (57%) reported clinically relevant symptoms for at least one clinical syndrome ( n = 252), and the majority of them (38%) reported more syndromes in comorbidity ( n = 169). Increased severity of clinical conditions (none, one, more than one syndrome) corresponded with significantly greater levels of personality disorder traits, psychological symptoms, dissociation, and negative emotionality, with large effect sizes. After controlling for co-occurrence of personality disorder traits and other symptoms, the presence of more than one comorbid syndrome significantly predicted unique variance in dissociation (positively) and positive emotionality (negatively). The presence of one clinical syndrome significantly and positively predicted negative emotionality. Findings support the possibility that the complexity, and not just the presence, of psychopathology could identify different groups of inmates.

  18. Molecular Targets in Advanced Therapeutics of Cancers: The Role of Pharmacogenetics.

    PubMed

    Abubakar, Murtala B; Gan, Siew Hua

    2016-01-01

    The advent of advanced molecular targeted therapy has resulted in improved prognoses for patients with advanced malignancies. However, despite the significant success and specificity of this advocated targeted therapy, significant on- and off-target adverse effects and inter-individual variability in treatment responses have been reported. The interpatient variability in drug response has been suggested to be partly due to variations in patient genomes. Therefore, the identification of genetic biomarkers by conducting pharmacogenetics studies can help predict patient responses to targeted therapy and may serve as a basis for individualized treatment. In this review, both clinically established and potential molecular targets are highlighted. Overall, current literature suggests that individualization of targeted therapy is promising; however, integrating the clinical benefits of identified biomarkers into clinical practice for personalized medicine remains a major challenge, and further studies to validate these markers and identify novel therapeutic approaches are needed. © 2016 S. Karger AG, Basel.

  19. Clinical and epidemiological characteristics of cutaneous leishmaniasis in Sri Lanka.

    PubMed

    Iddawela, Devika; Vithana, Sanura Malinda Pallegoda; Atapattu, Dhilma; Wijekoon, Lanka

    2018-03-06

    Leishmaniasis, a vector borne tropical/subtropical disease caused by the protozoan Leishmania is transmitted to humans by sandfly vectors Phlebotomus and Lutzomyia. The principal form found in Sri Lanka is cutaneous leishmaniasis (CL) and is caused by Leishmania donovani. A rising trend in disease prevalence has been observed recently in Sri Lanka and the island is in fact the newest endemic focus in South Asia. Determining the prevalence of smear positivity among clinically suspected CL patients, identifying risk factors and specific clinical presentations of CL in order to implement preventive and early treatment strategies were the objectives of this study. A sample of 509 clinically suspected cases of CL referred to the Department of Parasitology from all across Sri Lanka between 2005 and 2015 was selected consecutively. Diagnosis was confirmed by microscopic visualization of the Leishmania amastigote from the slit skin smear. A structured questionnaire was used to identify exposure related risk factors and a clinical examination was performed to identify lesion characteristics. Out of 509 clinical cases, 41.5% (n = 211) were smear positive. The study population ranged from ages 1 to 80 years (mean age = 34.76) and the most affected age group was 40-49. Of the smear positives, 58.85% were males. Majority (47.86%) were from the North Western region (Kurunegala) of the country and were exposed to scrub jungles. Sand fly exposure (p = 0.04) and positive contact history (p = 0.005) were significant risk factors for smear positivity. Erythema (p = 0.02), lack of pruritus (p = 0.02) and scaly appearance (p = 0.003) were significant lesion characteristics in smear positivity. Lesions were commonly found in the exposed areas and the commonest morphological type was papulo-nodular. An increasing trend in the spread of cutaneous leishmaniasis from endemic to non-endemic areas has become evident. Positive contact history and sandfly exposure were significant risk factors for smear positivity which may indicate the possibility of human reservoir hosts in infection transmission. Lack of pruritus, scaly appearance and erythema were highly significant lesion characteristics associated with Leishmania positive smears which can be used for the clinical diagnosis of CL.

  20. Remote preconditioning and major clinical complications following adult cardiovascular surgery: systematic review and meta-analysis.

    PubMed

    Healy, D A; Khan, W A; Wong, C S; Moloney, M Clarke; Grace, P A; Coffey, J C; Dunne, C; Walsh, S R; Sadat, U; Gaunt, M E; Chen, S; Tehrani, S; Hausenloy, D J; Yellon, D M; Kramer, R S; Zimmerman, R F; Lomivorotov, V V; Shmyrev, V A; Ponomarev, D N; Rahman, I A; Mascaro, J G; Bonser, R S; Jeon, Y; Hong, D M; Wagner, R; Thielmann, M; Heusch, G; Zacharowski, K; Meybohm, P; Bein, B; Tang, T Y

    2014-09-01

    A number of 'proof-of-concept' trials suggest that remote ischaemic preconditioning (RIPC) reduces surrogate markers of end-organ injury in patients undergoing major cardiovascular surgery. To date, few studies have involved hard clinical outcomes as primary end-points. Randomised clinical trials of RIPC in major adult cardiovascular surgery were identified by a systematic review of electronic abstract databases, conference proceedings and article reference lists. Clinical end-points were extracted from trial reports. In addition, trial principal investigators provided unpublished clinical outcome data. In total, 23 trials of RIPC in 2200 patients undergoing major adult cardiovascular surgery were identified. RIPC did not have a significant effect on clinical end-points (death, peri-operative myocardial infarction (MI), renal failure, stroke, mesenteric ischaemia, hospital or critical care length of stay). Pooled data from pilot trials cannot confirm that RIPC has any significant effect on clinically relevant end-points. Heterogeneity in study inclusion and exclusion criteria and in the type of preconditioning stimulus limits the potential for extrapolation at present. An effort must be made to clarify the optimal preconditioning stimulus. Following this, large-scale trials in a range of patient populations are required to ascertain the role of this simple, cost-effective intervention in routine practice. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  1. Provision and practice of specialist preterm labour clinics: a UK survey of practice.

    PubMed

    Sharp, A N; Alfirevic, Z

    2014-03-01

    To identify the current status of specialist preterm labour (PTL) clinic provision and management within the UK. Postal survey of clinical practice. All consultant-led obstetric units within the UK. A questionnaire was sent by post to all 210 NHS consultant-led obstetric units within the UK. Units that had a specialist PTL clinic were asked to complete a further 20 questions defining their protocol for risk stratification and management. Current practice in specialist preterm labour clinics. We have identified 23 specialist clinics; the most common indications for attendance were previous PTL (100%), preterm prelabour rupture of membranes (95%), two large loop excisions of the transformation zone (95%) or cone biopsy (95%). There was significant heterogeneity in the indications for and method of primary treatment for short cervix, with cervical cerclage used in 45% of units, progesterone in 18% of units and Arabin cervical pessary in 5%. A further 23% used multiple treatment modalities in combination. A significant heterogeneity in all topics surveyed suggests an urgent need for networking, more evidence-based guidelines and prospective comparative audits to ascertain the real impact of specialist PTL clinics on the reduction in preterm birth and its sequelae. © 2013 Royal College of Obstetricians and Gynaecologists.

  2. Emerging biomarkers in anaplastic oligodendroglioma: implications for clinical investigation and patient management.

    PubMed

    Sahebjam, Solmaz; McNamara, Mairéad G; Mason, Warren P

    2013-07-01

    Oligodendrogliomas are heterogeneous tumors with a variable response to treatment. This clinical variability underlines the urgent need for markers that can reliably aid diagnosis and guide clinical decision-making. Long-term follow-up data from the EORTC 26951 and RTOG 9402 clinical trials in newly diagnosed anaplastic oligodendroglioma have established chromosome 1p19q codeletion as a predictive marker of response to procarbazine, lomustine and vincristine chemotherapy in anaplastic oligodendrogliomas. In addition, MGMT promoter hypermethylation has been strongly associated with glioma CpG island hypermethylation phenotype (G-CIMP+) status, this has been suggested as an epiphenomenon of genome-wide methylation, conferring a more favorable prognosis. Molecular profiling of these tumors has identified several other markers with potential clinical significance: mutations of IDH, CIC, FUBP1 and CDKN2A require further validation before they can be implemented as clinical decision-making tools. Additionally, recent data on the clinical significance of intrinsic glioma subtyping appears promising. Indeed, existing evidence suggests that comprehensive analyses such as intrinsic glioma subtyping or G-CIMP status are superior to single molecular markers. Clearly, with evolving treatment strategies and in the era of individualized therapy, broader omics-based molecular evaluations are required to improve outcome prediction and to identify patients who will benefit from specific treatment strategies.

  3. Sentinel lymph node mapping in gynecological oncology

    PubMed Central

    Du, Jiang; Li, Yaling; Wang, Qing; Batchu, Nasra; Zou, Junkai; Sun, Chao; Lv, Shulan; Song, Qing; Li, Qiling

    2017-01-01

    The intraoperative mapping of sentinel lymph nodes (SLNs) is part of the treatment strategy for a number of types of tumor. To retrospectively compare results from the mapping of pelvic SLNs for gynecological oncology, using distinct dyes, the present review was conducted to determine the clinical significance of SLN mapping for gynecological oncology. In addition, the present study aimed at identifying an improved choice for SLN mapping tracers in clinical application. Each dye exhibits demerits when applied in the clinical environment. The combination of radioisotopes and blue dyes was identified to exhibit the most accurate detection rate of SLN drainage of gynecological oncology. However, contrast agents were unable to identify whether a SLN is positive or negative for metastasis prior to pathologic examination; additional studies are required. PMID:29344213

  4. Therapist effects and IAPT Psychological Wellbeing Practitioners (PWPs): a multilevel modelling and mixed methods analysis.

    PubMed

    Green, Helen; Barkham, Michael; Kellett, Stephen; Saxon, David

    2014-12-01

    The aim of this research was (a) to determine the extent of therapist effects in Psychological Wellbeing Practitioners (PWPs) delivering guided self-help in IAPT services and (b) to identify factors that defined effective PWP clinical practice. Using patient (N = 1122) anxiety and depression outcomes (PHQ-9 and GAD-7), the effectiveness of N = 21 PWPs across 6 service sites was examined using multi-level modelling. PWPs and their clinical supervisors were also interviewed and completed measures of ego strength, intuition and resilience. Therapist effects accounted for around 9 per cent of the variance in patient outcomes. One PWP had significantly better than average outcomes on both PHQ-9 and GAD-7 while 3 PWPs were significantly below average on the PHQ-9 and 2 were below average on the GAD-7. Computed PWP ranks identified quartile clusters of the most (N = 5) and least (N = 5) effective PWPs. More effective PWPs generated higher rates of reliable and clinically significant change and displayed greater resilience, organisational abilities, knowledge and confidence. Study weaknesses are identified and methodological considerations for future studies examining therapist effects in low intensity cognitive behaviour therapy are provided. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Factors influencing the perceived quality of clinical supervision of occupational therapists in a large Australian state.

    PubMed

    Martin, Priya; Kumar, Saravana; Lizarondo, Lucylynn; Tyack, Zephanie

    2016-10-01

    Clinical supervision is important for effective health service delivery, professional development and practice. Despite its importance there is a lack of evidence regarding the factors that improve its quality. This study aimed to investigate the factors that influence the quality of clinical supervision of occupational therapists employed in a large public sector health service covering mental health, paediatrics, adult physical and other practice areas. A mixed method, sequential explanatory study design was used consisting of two phases. This article reports the quantitative phase (Phase One) which involved administration of the Manchester Clinical Supervision Scale (MCSS-26) to 207 occupational therapists. Frequency of supervision sessions, choice of supervisor and the type of supervision were found to be the predictor variables with a positive and significant influence on the quality of clinical supervision. Factors such as age, length of supervision and the area of practice were found to be the predictor variables with a negative and significant influence on the quality of clinical supervision. Factors that influence the perceived quality of clinical supervision among occupational therapists have been identified. High quality clinical supervision is an important component of clinical governance and has been shown to be beneficial to practitioners, patients and the organisation. Information on factors that make clinical supervision effective identified in this study can be added to existing supervision training and practices to improve the quality of clinical supervision. © 2016 Occupational Therapy Australia.

  6. Effect of vitamin D supplementation on knee osteoarthritis: A systematic review and meta-analysis of randomized clinical trials.

    PubMed

    Diao, Naicheng; Yang, Bo; Yu, Fei

    2017-12-01

    To provide evidence regarding the effect of vitamin D supplementation on symptomatic knee osteoarthritis (OA). A systematic review and meta-analysis was performed to quantitatively pool the results from randomized clinical trials. Studies were identified from a search of the Embase, MEDLINE and Web of Science databases up to January 22, 2017, and also from conference abstracts, ClinicalTrials.gov and the reference lists of identified studies. A standardized mean difference (SMD) was used to assess effect sizes, as outcomes were reported on different scales. Depending on the degree of heterogeneity, random-effects or fixed-effects models were used to pool outcomes. Up to January 22, 2017, four clinical trials containing 570 subjects in the vitamin D supplementation group and 560 subjects in the placebo group were identified. All of the included studies were of high quality and had a low risk of bias for each domain. The results indicated that vitamin D supplementation had a statistically significant but small-to-moderate effect on pain control in patients with knee OA (SMD=-0.32, 95% CI: -0.63 to -0.02). However, no effects were observed for the change in tibial cartilage volume (SMD=0.12, 95% CI: -0.05 to 0.29) or joint space width (SMD=0.07, 95% CI: -0.08 to 0.23). The subgroup analysis indicated that vitamin D supplementation had no significant effect regardless of whether patients had sufficient or insufficient serum 25(OH)D levels at baseline. The results of this study indicate that vitamin D supplementation may not have a clinically significant effect on pain control or structure progression among patients with knee OA. Longer-term clinical trials with rigorous measurement of symptom and radiologic changes are required to further clarify the effect of vitamin D supplementation in patients with symptomatic knee OA and low serum 25(OH)D levels. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  7. Culture-independent Analysis of Pediatric Broncho-alveolar Lavage (BAL) Specimens.

    PubMed

    Zachariah, Philip; Ryan, Chanelle; Nadimpalli, Sruti; Coscia, Gina; Kolb, Michelle; Smith, Hannah; Foca, Marc; Saiman, Lisa; Planet, Paul J

    2018-06-07

    The clinical utility of culture-independent testing of pediatric bronchoalveolar lavage (BAL) specimens is unknown. Additionally, the variability of the pediatric pulmonary microbiome with patient characteristics is not well understood. Study subjects were ≤22 years old and underwent BAL from May 2013 - July 2015 as part of clinical care. DNA extracted from BAL specimens was used for 16S rRNA gene-based (16S-based) microbiome analysis, and results compared to routine cultures from the same samples. Indices of microbial diversity and relative taxon abundances were compared based on subject characteristics. From 81 participants (51% male, median age 9 years), 89 samples were collected and the 16S rRNA genes of 77 (86.5%) samples were successfully analyzed. Subjects included 23 cystic fibrosis (CF), 19 immunocompromised (IC), and 28 non-immunocompromised (nIC) patients. Of 68 organisms identified in culture, 16S-based analyses were concordant with culture results in 66 (97.1%), and also identified potentially clinically significant taxa missed by cultures (e.g. Staphylococcus, Legionella, Pseudomonas). Significant differences in abundance were noted mostly for non-cultured taxa with diagnosis and antibiotic use (Veillonella, Corynebacterium, Haemophilus). The microbiota of CF samples was less diverse and a "core" group of fifteen taxa shared across samples was identified. 16S-based culture independent analysis was concordant with routine cultures and showed potential to detect non-cultured pathogens. While 16S- based testing identified relative changes in organism abundance associated with clinical characteristics, distinct microbiome profiles associated with disease states were not identified.

  8. Defining the Developmental Parameters of Temper Loss in Early Childhood: Implications for Developmental Psychopathology

    ERIC Educational Resources Information Center

    Wakschlag, Lauren S.; Choi, Seung W.; Carter, Alice S.; Hullsiek, Heide; Burns, James; McCarthy, Kimberly; Leibenluft, Ellen; Briggs-Gowan, Margaret J.

    2012-01-01

    Background: Temper modulation problems are both a hallmark of early childhood and a common mental health concern. Thus, characterizing specific behavioral manifestations of temper loss along a dimension from normative misbehaviors to clinically significant problems is an important step toward identifying clinical thresholds. Methods:…

  9. Outbreak of Tsukamurella species bloodstream infection among patients at an oncology clinic, West Virginia, 2011-2012.

    PubMed

    See, Isaac; Nguyen, Duc B; Chatterjee, Somu; Shwe, Thein; Scott, Melissa; Ibrahim, Sherif; Moulton-Meissner, Heather; McNulty, Steven; Noble-Wang, Judith; Price, Cindy; Schramm, Kim; Bixler, Danae; Guh, Alice Y

    2014-03-01

    To determine the source and identify control measures of an outbreak of Tsukamurella species bloodstream infections at an outpatient oncology facility. Epidemiologic investigation of the outbreak with a case-control study. A case was an infection in which Tsukamurella species was isolated from a blood or catheter tip culture during the period January 2011 through June 2012 from a patient of the oncology clinic. Laboratory records of area hospitals and patient charts were reviewed. A case-control study was conducted among clinic patients to identify risk factors for Tsukamurella species bloodstream infection. Clinic staff were interviewed, and infection control practices were assessed. Fifteen cases of Tsukamurella (Tsukamurella pulmonis or Tsukamurella tyrosinosolvens) bloodstream infection were identified, all in patients with underlying malignancy and indwelling central lines. The median age of case patients was 68 years; 47% were male. The only significant risk factor for infection was receipt of saline flush from the clinic during the period September-October 2011 (P = .03), when the clinic had been preparing saline flush from a common-source bag of saline. Other infection control deficiencies that were identified at the clinic included suboptimal procedures for central line access and preparation of chemotherapy. Although multiple infection control lapses were identified, the outbreak was likely caused by improper preparation of saline flush syringes by the clinic. The outbreak demonstrates that bloodstream infections among oncology patients can result from improper infection control practices and highlights the critical need for increased attention to and oversight of infection control in outpatient oncology settings.

  10. Incidental Findings in Imaging Research: Evaluating Incidence, Benefit and Burden

    PubMed Central

    Orme, Nicholas M.; Fletcher, Joel G.; Siddiki, Hassan A.; Harmsen, W. Scott; O’Byrne, Megan M.; Port, John D.; Tremaine, William J.; Pitot, Henry C.; McFarland, Beth; Robinson, Marguerite E.; Koenig, Barabara A.; King, Bernard F.; Wolf, Susan M.

    2013-01-01

    Context Little information exists concerning the frequency of clinically significant incidental findings (IFs) identified in the course of imaging research across a broad spectrum of imaging modalities and body regions. Objective To estimate the frequency with which research imaging IFs generate further clinical action, and the medical benefit/burden of identifying these IFs. Design, Setting, and Participants Retrospective review of subjects undergoing a research imaging exam that was interpreted by a radiologist for IFs in the first quarter of 2004, with 3-year clinical follow-up. An expert panel reviewed IFs generating clinical action to determine medical benefit/burden based on predefined criteria. Main Outcome Measures Frequency of (1) IFs that generated further clinical action by modality, body part, age, gender, and (2) IFs resulting in clear medical benefit or burden. Results 1376 patients underwent 1426 research imaging studies. 40% (567/1426) of exams had at least one IF (1055 total). Risk of an IF increased significantly by age (OR=1.5; [1.4–1.7=95% C.I.] per decade increase). Abdominopelvic CT generated more IFs than other exams (OR=18.9 compared with ultrasound; 9.2% with subsequent clinical action), with CT Thorax and MR brain next (OR=11.9 and 5.9; 2.8% and 2.2% with action, respectively). Overall 6.2% of exams (35/567) with an IF generated clinical action, resulting in clear medical benefit in 1.1% (6/567) and clear medical burden in 0.5% (3/567). In most instances, medical benefit/burden was unclear (4.6%; 26/567). Conclusions The frequency of IFs in imaging research exams varies significantly by imaging modality, body region and age. Research imaging studies at high risk for generating IFs can be identified. Routine evaluation of research images by radiologists may result in identification of IFs in a substantial number of cases and subsequent clinical action to address them in much smaller number. Such clinical action can result in medical benefit to a small number of patients. PMID:20876402

  11. Cetuximab for treating non-small cell lung cancer.

    PubMed

    Mazzarella, Luca; Guida, Alessandro; Curigliano, Giuseppe

    2018-04-01

    Epidermal Growth Factor Receptor (EGFR)-dependent signaling plays a crucial role in epithelial cancer biology, and dictated the development of several targeting agents. The mouse-human chimeric antibody Cetuximab was among the first to be developed. After about two decades of clinical research it has gained a significant place in the management of advanced colorectal and head and neck cancers, whereas its development in non small cell lung cancer (NSCLC) has not led to a place in routine clinical practice, because of marginal clinical benefit despite statistically significant Phase III trials. Recent data from ongoing trials suggest that more careful selection based on molecular markers may identify good responders. Areas covered: In this article, the authors review the literature concerning basic science studies identifying EGFR as a therapeutic target, pharmacological development of Cetuximab, its pharmacodynamics and pharmacokinetics, and clinical trials on Cetuximab in NSCLC, focusing on recent findings on putative predictive biomarkers. Expert opinion: Cetuximab currently has no role in NSCLC treatment outside of research settings. We argue that failure to identify a predictive biomarker early on has hampered its chances to enter routine practice. Although recent research suggests benefit in highly selected patient subsets, its potential impact is severely dampened by lack of regulatory body approval and the emergence of competitors for the same niches.

  12. Epidemiology, clinical characteristics, and risk factors for mortality of early- and late-onset invasive candidiasis in intensive care units in China

    PubMed Central

    Yang, Yi; Guo, Fengmei; Kang, Yan; Zang, Bin; Cui, Wei; Qin, Bingyu; Qin, Yingzhi; Fang, Qiang; Qin, Tiehe; Jiang, Dongpo; Cai, Bojing; Li, Ruoyu; Qiu, Haibo

    2017-01-01

    Abstract To identify the epidemiology, treatments, outcomes, and risk factors for patients with early- or late-onset invasive candidiasis (EOIC or LOIC) in intensive care units in China. Patients were classified as EOIC (≤10 days) or LOIC (>10 days) according to the time from hospital admission to IC onset to identify distinct clinical characteristics. There were 105 EOIC cases and 201 LOIC cases in this study. EOIC was related to more severe clinical conditions at ICU admission or prior to IC. Significantly, more cases of Candida parapsilosis infection were found in patients with LOIC than in those with EOIC. The mortality of EOIC was significantly lower than that for LOIC. Sequential Organ Failure Assessment (SOFA) score at ICI diagnosis in the EOIC group and the interval from ICU admission to ICI occurrence in the LOIC group were identified as risk factors for mortality. Susceptibility to the first-line agent was associated with a lower risk of mortality in the LOIC group. The mortality rate was significantly lower in the EOIC group, and there were more cases of non-albicans infection in the LOIC group. Susceptibility to the first-line agent was an important predictor of mortality in the LOIC group. SOFA score at ICI diagnosis in the EOIC group and interval from ICU admission to ICI occurrence in the LOIC group were identified as risk factors for mortality. PMID:29049184

  13. Molecular characterization of the presence of Eubacterium spp and Streptococcus spp in endodontic infections.

    PubMed

    Fouad, A F; Kum, K-Y; Clawson, M L; Barry, J; Abenoja, C; Zhu, Q; Caimano, M; Radolf, J D

    2003-08-01

    Eubacterium spp. and Streptococcus spp. are virulent, commonly identified microorganisms in endodontic infections. The purpose of this study was to use molecular methods to identify these organisms in 22 infected root canals that include eight cases with preoperative clinical symptoms and five cases with a history of diabetes mellitus. The presence of Streptococcus spp. and Eubacterium spp. was examined using two sets of PCR primers specific with multiple species within the respective genera. Positive specimens had their PCR products sequenced and phylogenetically analyzed to identify the specific species. Sixteen specimens (73%) contained Eubacterium spp. and nine (41%) were positive for Streptococcus spp. Eubacterium infirmum was the most prevalent Eubacterium sp. This organism was significantly associated with a history of diabetes (OR = 9.6; P = 0.04). Streptococcus anginosus was the most common Streptococcus sp., but neither it nor any of the other streptococci were significantly associated with the clinical parameters evaluated.

  14. 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.

  15. Using EHR Data to Detect Prescribing Errors in Rapidly Discontinued Medication Orders.

    PubMed

    Burlison, Jonathan D; McDaniel, Robert B; Baker, Donald K; Hasan, Murad; Robertson, Jennifer J; Howard, Scott C; Hoffman, James M

    2018-01-01

    Previous research developed a new method for locating prescribing errors in rapidly discontinued electronic medication orders. Although effective, the prospective design of that research hinders its feasibility for regular use. Our objectives were to assess a method to retrospectively detect prescribing errors, to characterize the identified errors, and to identify potential improvement opportunities. Electronically submitted medication orders from 28 randomly selected days that were discontinued within 120 minutes of submission were reviewed and categorized as most likely errors, nonerrors, or not enough information to determine status. Identified errors were evaluated by amount of time elapsed from original submission to discontinuation, error type, staff position, and potential clinical significance. Pearson's chi-square test was used to compare rates of errors across prescriber types. In all, 147 errors were identified in 305 medication orders. The method was most effective for orders that were discontinued within 90 minutes. Duplicate orders were most common; physicians in training had the highest error rate ( p  < 0.001), and 24 errors were potentially clinically significant. None of the errors were voluntarily reported. It is possible to identify prescribing errors in rapidly discontinued medication orders by using retrospective methods that do not require interrupting prescribers to discuss order details. Future research could validate our methods in different clinical settings. Regular use of this measure could help determine the causes of prescribing errors, track performance, and identify and evaluate interventions to improve prescribing systems and processes. Schattauer GmbH Stuttgart.

  16. Potential Use of γ-Secretase Modulators in the Treatment of Alzheimer Disease

    PubMed Central

    Wagner, Steven L.; Tanzi, Rudolph E.; Mobley, William C.; Galasko, Douglas

    2013-01-01

    Although significant progress has occurred in the past 20 years regarding our understanding of Alzheimer disease pathogenesis, we have yet to identify disease-modifying therapeutics capable of substantially altering the clinical course of this prevalent neurodegenerative disease. In this short review, we discuss 2 approaches that are currently being tested clinically (γ-secretase inhibition and γ-secretase modulation) and emphasize the significant differences between these 2 therapeutic approaches. We also discuss certain genetic- and biomarker-based translational and clinical trial paradigms that may assist in developing a useful therapeutic agent. PMID:22801784

  17. 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

  18. Case Definitions for Conditions Identified by Newborn Screening Public Health Surveillance.

    PubMed

    Sontag, Marci K; Sarkar, Deboshree; Comeau, Anne M; Hassell, Kathryn; Botto, Lorenzo D; Parad, Richard; Rose, Susan R; Wintergerst, Kupper A; Smith-Whitley, Kim; Singh, Sikha; Yusuf, Careema; Ojodu, Jelili; Copeland, Sara; Hinton, Cynthia F

    2018-01-01

    Newborn screening (NBS) identifies infants with rare conditions to prevent death or the onset of irreversible morbidities. Conditions on the Health and Human Services Secretary's Recommended Uniform Screening Panel have been adopted by most state NBS programs, providing a consistent approach for identification of affected newborns across the United States. Screen-positive newborns are identified and referred for confirmatory diagnosis and follow-up. The designation of a clinically significant phenotype precursor to a clinical diagnosis may vary between clinical specialists, resulting in diagnostic variation. Determination of disease burden and birth prevalence of the screened conditions by public health tracking is made challenging by these variations. This report describes the development of a core group of new case definitions, along with implications, plans for their use, and links to the definitions that were developed by panels of clinical experts. These definitions have been developed through an iterative process and are piloted in NBS programs. Consensus public health surveillance case definitions for newborn screened disorders will allow for consistent categorization and tracking of short- and long-term follow-up of identified newborns at the local, regional, and national levels.

  19. Case Definitions for Conditions Identified by Newborn Screening Public Health Surveillance

    PubMed Central

    Sontag, Marci K.; Sarkar, Deboshree; Comeau, Anne M.; Hassell, Kathryn; Botto, Lorenzo D.; Parad, Richard; Rose, Susan R.; Wintergerst, Kupper A.; Smith-Whitley, Kim; Singh, Sikha; Yusuf, Careema; Ojodu, Jelili; Copeland, Sara; Hinton, Cynthia F.

    2018-01-01

    Newborn screening (NBS) identifies infants with rare conditions to prevent death or the onset of irreversible morbidities. Conditions on the Health and Human Services Secretary’s Recommended Uniform Screening Panel have been adopted by most state NBS programs, providing a consistent approach for identification of affected newborns across the United States. Screen-positive newborns are identified and referred for confirmatory diagnosis and follow-up. The designation of a clinically significant phenotype precursor to a clinical diagnosis may vary between clinical specialists, resulting in diagnostic variation. Determination of disease burden and birth prevalence of the screened conditions by public health tracking is made challenging by these variations. This report describes the development of a core group of new case definitions, along with implications, plans for their use, and links to the definitions that were developed by panels of clinical experts. These definitions have been developed through an iterative process and are piloted in NBS programs. Consensus public health surveillance case definitions for newborn screened disorders will allow for consistent categorization and tracking of short- and long-term follow-up of identified newborns at the local, regional, and national levels.

  20. Is magnetic resonance imaging in addition to a computed tomographic scan necessary to identify clinically significant cervical spine injuries in obtunded blunt trauma patients?

    PubMed

    Fisher, Brian M; Cowles, Steven; Matulich, Jennifer R; Evanson, Bradley G; Vega, Diana; Dissanaike, Sharmila

    2013-12-01

    Guidelines are in place directing the clearance of the cervical spine in patients who are awake, alert, and oriented, but a gold standard has not been recognized for patients who are obtunded. Our study is designed to determine if magnetic resonance imaging (MRI) detects clinically significant injuries not seen on computed tomographic (CT) scans. The trauma registry was used to identify and retrospectively review medical records of blunt trauma patients from January 1, 2005, to March 30, 2012. Only obtunded patients with a CT scan and MRI of the cervical spine were included. The study cohort consisted of 277 patients. In 13 (5%) patients, MRI detected clinically significant cervical spine injuries that were missed by CT scans, and in 7 (3%) these injuries required intervention. The number needed to screen with MRI to prevent 1 missed injury was 21. The findings suggest that the routine use of MRI in clearing the cervical spine in the obtunded blunt trauma patient. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Hamate-pisiform coalition: morphology, clinical significance, and a simplified classification scheme for carpal coalition.

    PubMed

    Burnett, Scott E

    2011-03-01

    Hamate-pisiform coalition is characterized by the abnormal union of the pisiform bone and hamulus of the hamate. Because most reported cases are isolated, and literature on the subject is sparse, relatively little is known about this condition and its clinical significance. The purpose of this report is to discuss the occurrence, morphology, and frequency of hamate-pisiform coalition identified in a skeletal sample of native South Africans, and to conduct a metaanalysis of all known cases in order to clarify the sex distribution, laterality, form, and clinical significance of this condition. Five new cases (three male, two female) of hamate-pisiform coalition were identified in 527 native South Africans. Results indicate that hamate-pisiform coalition is infrequent (0.76%) but may be more likely encountered in individuals of African ancestry. Morphologically, non-osseous examples ranged in appearance from minor expressions involving pitting of an expanded hamulus base, to a variably pitted articulation between an elongated pisiform and hamulus. Osseous union between the two bones tends to extend beyond the hamulus base to adjacent areas of the hamate. Cases involving osseous union appear predisposed to fracture while ulnar neuropathy is significantly more frequent in individuals exhibiting non-osseous coalition. As both non-osseous and osseous cases can have clinical significance, awareness of the variable manifestations of this condition is necessary for hand specialists. A simplified classification system is suggested to more consistently characterize carpal coalitions. Copyright © 2010 Wiley-Liss, Inc.

  2. Mobile physician reporting of clinically significant events-a novel way to improve handoff communication and supervision of resident on call activities.

    PubMed

    Nabors, Christopher; Peterson, Stephen J; Aronow, Wilbert S; Sule, Sachin; Mumtaz, Arif; Shah, Tushar; Eskridge, Etta; Wold, Eric; Stallings, Gary W; Burak, Kathleen Kelly; Goldberg, Randy; Guo, Gary; Sekhri, Arunabh; Mathew, George; Khera, Sahil; Montoya, Jessica; Sharma, Mala; Paudel, Rajiv; Frishman, William H

    2014-12-01

    Reporting of clinically significant events represents an important mechanism by which patient safety problems may be identified and corrected. However, time pressure and cumbersome report entry procedures have discouraged the full participation of physicians. To improve the process, our internal medicine training program developed an easy-to-use mobile platform that combines the reporting process with patient sign-out. Between August 25, 2011, and January 25, 2012, our trainees entered clinically significant events into i-touch/i-phone/i-pad based devices functioning in wireless-synchrony with our desktop application. Events were collected into daily reports that were sent from the handoff system to program leaders and attending physicians to plan for rounds and to correct safety problems. Using the mobile module, residents entered 31 reportable events per month versus the 12 events per month that were reported via desktop during a previous 6-month study period. Advances in information technology now permit clinically significant events that take place during "off hours" to be identified and reported (via handoff) to next providers and to supervisors via collated reports. This information permits hospital leaders to correct safety issues quickly and effectively, while attending physicians are able to use information gleaned from the reports to optimize rounding plans and to provide additional oversight of trainee on call patient management decisions.

  3. Clinical predictors of colectomy in patients with ulcerative colitis: systematic review and meta-analysis of cohort studies.

    PubMed

    Dias, Cláudia Camila; Rodrigues, Pedro Pereira; da Costa-Pereira, Altamiro; Magro, Fernando

    2015-02-01

    Colectomy is a major event that may significantly affect the outcome of ulcerative colitis (UC) in terms of both quality of life and mortality. This paper aims to identify clinical prognostic factors that may be significantly associated with this event. PubMed, ISI Web of Knowledge and Scopus were searched to identify studies investigating the association between clinical factors in adult patients with UC and studied events.The clinical factors evaluated in this meta-analysis were gender, smoking habits, disease extent,use of corticosteroids, and episodes of hospitalization. Of the 3753 initially selected papers, 20 were included. The analysis showed a significantly lower risk of colectomy for female patients (odds ratio [OR] 0.78 [95% CI 0.68, 0.90]) and for smoking patients (OR 0.55 [0.33, 0.91]), and a higher risk for patients with extensive disease (OR 3.68 [2.39,5.69]), for patients who took corticosteroids at least once (OR 2.10 [1.05, 4.22]), and for patients who were hospitalized (OR 4.13 [3.23, 5.27]). Gender, smoking habits, disease extent, need for corticosteroids, and hospitalization were all significantly associated with UC prognosis. These results may clarify the relative influences of these and other prognostic factors in the natural course of the disease and therefore help improve the management approach, thus improving the follow-up of patients.

  4. Physician satisfaction with a critical care clinical information system using a multimethod evaluation of usability.

    PubMed

    Hudson, Darren; Kushniruk, Andre; Borycki, Elizabeth; Zuege, Danny J

    2018-04-01

    Physician satisfaction with electronic medical records has often been poor. Usability has frequently been identified as a source for decreased satisfaction. While surveys can identify many issues, and are logistically easier to administer, they may miss issues identified using other methods This study sought to understand the level of physician satisfaction and usability issues associated with a critical care clinical information system (eCritical Alberta) implemented throughout the province of Alberta, Canada. All critical care attending physicians using the system were invited to participate in an online survey. Questions included components of the User Acceptance of Information Technology and Usability Questionnaire as well as free text feedback on system components. Physicians were also invited to participate in a think aloud test using simulated scenarios. The transcribed think aloud text and questionnaire were subjected to textual analysis. 82% of all eligible physicians completed the on-line survey (n = 61). Eight physicians were invited and seven completed the think aloud test. Overall satisfaction with the system was moderate. Usability was identified as a significant factor contributing to satisfaction. The major usability factors identified were system response time and layout. The think aloud component identified additional factors beyond those identified in the on-line survey. This study found a modestly high level of physician satisfaction with a province-wide clinical critical care information system. Usability continues to be a significant factor in physician satisfaction. Using multiple methods of evaluation can capture the benefits of a large sample size and deeper understanding of the issues. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Utility of routine psychological screening in the childhood cancer survivor clinic.

    PubMed

    Recklitis, Christopher; O'Leary, Tara; Diller, Lisa

    2003-03-01

    This study examined the utility of routine psychologic screening in a childhood cancer survivor clinic by evaluating patient acceptance, comparing subjects' symptoms to normative data, examining the utility of specific tests, and identifying risk factors associated with psychological distress. During their annual clinic visit, 101 adult survivors of childhood cancer (median age, 25 years) completed the Symptom Checklist 90 Revised (SCL-90), as well as the Short Form 36 (SF-36), Beck Depression Inventory (BDI), and one additional suicide question. Psychological distress was operationally defined according to the published SCL-90 clinical case rule, classifying subjects with a consistent pattern of symptom elevations as clinical cases. The majority of subjects (80%) completed the screening in less than 30 minutes and reported little (15%) or no (84%) distress. Sixty-four percent believed it would help "very much" or "moderately" in getting to know them, and 35% thought it would help "slightly." On the SCL-90, 32 subjects (31.7%) had a positive screen, indicating significant psychological distress. All subjects with clinically significant symptoms on the BDI and SF-36 Mental Health Scale were cases on the SCL-90 (case-positive). Suicidal symptoms were reported in 13.9% of the sample, all of whom were SCL-90 cases. In a logistic regression model, subjects' dissatisfaction with physical appearance, poor physical health, and treatment with cranial radiation were associated with psychological distress. Results demonstrate that routine psychological screening can be successfully integrated into the cancer survivor clinic and may be effective in identifying those survivors with significant distress who require further evaluation.

  6. 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/

  7. Single-cell genomic profiling of acute myeloid leukemia for clinical use: A pilot study

    PubMed Central

    Yan, Benedict; Hu, Yongli; Ban, Kenneth H.K.; Tiang, Zenia; Ng, Christopher; Lee, Joanne; Tan, Wilson; Chiu, Lily; Tan, Tin Wee; Seah, Elaine; Ng, Chin Hin; Chng, Wee-Joo; Foo, Roger

    2017-01-01

    Although bulk high-throughput genomic profiling studies have led to a significant increase in the understanding of cancer biology, there is increasing awareness that bulk profiling approaches do not completely elucidate tumor heterogeneity. Single-cell genomic profiling enables the distinction of tumor heterogeneity, and may improve clinical diagnosis through the identification and characterization of putative subclonal populations. In the present study, the challenges associated with a single-cell genomics profiling workflow for clinical diagnostics were investigated. Single-cell RNA-sequencing (RNA-seq) was performed on 20 cells from an acute myeloid leukemia bone marrow sample. Putative blasts were identified based on their gene expression profiles and principal component analysis was performed to identify outlier cells. Variant calling was performed on the single-cell RNA-seq data. The present pilot study demonstrates a proof of concept for clinical single-cell genomic profiling. The recognized limitations include significant stochastic RNA loss and the relatively low throughput of the current proposed platform. Although the results of the present study are promising, further technological advances and protocol optimization are necessary for single-cell genomic profiling to be clinically viable. PMID:28454300

  8. Phosphoproteomics reveals ALK promote cell progress via RAS/ JNK pathway in neuroblastoma.

    PubMed

    Chen, Kai; Lv, Fan; Xu, Guofeng; Zhang, Min; Wu, Yeming; Wu, Zhixiang

    2016-11-15

    Emerging evidence suggests receptor tyrosine kinase ALK as a promising therapeutic target in neuroblastoma. However, clinical trials reveal that a limited proportion of ALK-positive neuroblastoma patients experience clinical benefits from Crizotinib, a clinically approved specific inhibitor of ALK. The precise molecular mechanisms of aberrant ALK activity in neuroblastoma remain elusive, limiting the clinical application of ALK as a therapeutic target in neuroblastoma. Here, we describe a deep quantitative phosphoproteomic approach in which Crizotinib-treated neuroblastoma cell lines bearing aberrant ALK are used to investigate downstream regulated phosphoproteins. We identified more than 19,500-and quantitatively analyzed approximately 10,000-phosphorylation sites from each cell line, ultimately detecting 450-790 significantly-regulated phosphorylation sites. Multiple layers of bioinformatic analysis of the significantly-regulated phosphoproteins identified RAS/JNK as a downstream signaling pathway of ALK, independent of the ALK variant present. Further experiments demonstrated that ALK/JNK signaling could be inactivated by either ALK- or JNK-specific inhibitors, resulting in cell growth inhibition by induction of cell cycle arrest and cell apoptosis. Our study broadly defines the phosphoproteome in response to ALK inhibition and provides a resource for further clinical investigation of ALK as therapeutic target for the treatment of neuroblastoma.

  9. Cytogenetic prognostication within medulloblastoma subgroups.

    PubMed

    Shih, David J H; Northcott, Paul A; Remke, Marc; Korshunov, Andrey; Ramaswamy, Vijay; Kool, Marcel; Luu, Betty; Yao, Yuan; Wang, Xin; Dubuc, Adrian M; Garzia, Livia; Peacock, John; Mack, Stephen C; Wu, Xiaochong; Rolider, Adi; Morrissy, A Sorana; Cavalli, Florence M G; Jones, David T W; Zitterbart, Karel; Faria, Claudia C; Schüller, Ulrich; Kren, Leos; Kumabe, Toshihiro; Tominaga, Teiji; Shin Ra, Young; Garami, Miklós; Hauser, Peter; Chan, Jennifer A; Robinson, Shenandoah; Bognár, László; Klekner, Almos; Saad, Ali G; Liau, Linda M; Albrecht, Steffen; Fontebasso, Adam; Cinalli, Giuseppe; De Antonellis, Pasqualino; Zollo, Massimo; Cooper, Michael K; Thompson, Reid C; Bailey, Simon; Lindsey, Janet C; Di Rocco, Concezio; Massimi, Luca; Michiels, Erna M C; Scherer, Stephen W; Phillips, Joanna J; Gupta, Nalin; Fan, Xing; Muraszko, Karin M; Vibhakar, Rajeev; Eberhart, Charles G; Fouladi, Maryam; Lach, Boleslaw; Jung, Shin; Wechsler-Reya, Robert J; Fèvre-Montange, Michelle; Jouvet, Anne; Jabado, Nada; Pollack, Ian F; Weiss, William A; Lee, Ji-Yeoun; Cho, Byung-Kyu; Kim, Seung-Ki; Wang, Kyu-Chang; Leonard, Jeffrey R; Rubin, Joshua B; de Torres, Carmen; Lavarino, Cinzia; Mora, Jaume; Cho, Yoon-Jae; Tabori, Uri; Olson, James M; Gajjar, Amar; Packer, Roger J; Rutkowski, Stefan; Pomeroy, Scott L; French, Pim J; Kloosterhof, Nanne K; Kros, Johan M; Van Meir, Erwin G; Clifford, Steven C; Bourdeaut, Franck; Delattre, Olivier; Doz, François F; Hawkins, Cynthia E; Malkin, David; Grajkowska, Wieslawa A; Perek-Polnik, Marta; Bouffet, Eric; Rutka, James T; Pfister, Stefan M; Taylor, Michael D

    2014-03-20

    Medulloblastoma comprises four distinct molecular subgroups: WNT, SHH, Group 3, and Group 4. Current medulloblastoma protocols stratify patients based on clinical features: patient age, metastatic stage, extent of resection, and histologic variant. Stark prognostic and genetic differences among the four subgroups suggest that subgroup-specific molecular biomarkers could improve patient prognostication. Molecular biomarkers were identified from a discovery set of 673 medulloblastomas from 43 cities around the world. Combined risk stratification models were designed based on clinical and cytogenetic biomarkers identified by multivariable Cox proportional hazards analyses. Identified biomarkers were tested using fluorescent in situ hybridization (FISH) on a nonoverlapping medulloblastoma tissue microarray (n = 453), with subsequent validation of the risk stratification models. Subgroup information improves the predictive accuracy of a multivariable survival model compared with clinical biomarkers alone. Most previously published cytogenetic biomarkers are only prognostic within a single medulloblastoma subgroup. Profiling six FISH biomarkers (GLI2, MYC, chromosome 11 [chr11], chr14, 17p, and 17q) on formalin-fixed paraffin-embedded tissues, we can reliably and reproducibly identify very low-risk and very high-risk patients within SHH, Group 3, and Group 4 medulloblastomas. Combining subgroup and cytogenetic biomarkers with established clinical biomarkers substantially improves patient prognostication, even in the context of heterogeneous clinical therapies. The prognostic significance of most molecular biomarkers is restricted to a specific subgroup. We have identified a small panel of cytogenetic biomarkers that reliably identifies very high-risk and very low-risk groups of patients, making it an excellent tool for selecting patients for therapy intensification and therapy de-escalation in future clinical trials.

  10. Cytogenetic Prognostication Within Medulloblastoma Subgroups

    PubMed Central

    Shih, David J.H.; Northcott, Paul A.; Remke, Marc; Korshunov, Andrey; Ramaswamy, Vijay; Kool, Marcel; Luu, Betty; Yao, Yuan; Wang, Xin; Dubuc, Adrian M.; Garzia, Livia; Peacock, John; Mack, Stephen C.; Wu, Xiaochong; Rolider, Adi; Morrissy, A. Sorana; Cavalli, Florence M.G.; Jones, David T.W.; Zitterbart, Karel; Faria, Claudia C.; Schüller, Ulrich; Kren, Leos; Kumabe, Toshihiro; Tominaga, Teiji; Shin Ra, Young; Garami, Miklós; Hauser, Peter; Chan, Jennifer A.; Robinson, Shenandoah; Bognár, László; Klekner, Almos; Saad, Ali G.; Liau, Linda M.; Albrecht, Steffen; Fontebasso, Adam; Cinalli, Giuseppe; De Antonellis, Pasqualino; Zollo, Massimo; Cooper, Michael K.; Thompson, Reid C.; Bailey, Simon; Lindsey, Janet C.; Di Rocco, Concezio; Massimi, Luca; Michiels, Erna M.C.; Scherer, Stephen W.; Phillips, Joanna J.; Gupta, Nalin; Fan, Xing; Muraszko, Karin M.; Vibhakar, Rajeev; Eberhart, Charles G.; Fouladi, Maryam; Lach, Boleslaw; Jung, Shin; Wechsler-Reya, Robert J.; Fèvre-Montange, Michelle; Jouvet, Anne; Jabado, Nada; Pollack, Ian F.; Weiss, William A.; Lee, Ji-Yeoun; Cho, Byung-Kyu; Kim, Seung-Ki; Wang, Kyu-Chang; Leonard, Jeffrey R.; Rubin, Joshua B.; de Torres, Carmen; Lavarino, Cinzia; Mora, Jaume; Cho, Yoon-Jae; Tabori, Uri; Olson, James M.; Gajjar, Amar; Packer, Roger J.; Rutkowski, Stefan; Pomeroy, Scott L.; French, Pim J.; Kloosterhof, Nanne K.; Kros, Johan M.; Van Meir, Erwin G.; Clifford, Steven C.; Bourdeaut, Franck; Delattre, Olivier; Doz, François F.; Hawkins, Cynthia E.; Malkin, David; Grajkowska, Wieslawa A.; Perek-Polnik, Marta; Bouffet, Eric; Rutka, James T.; Pfister, Stefan M.; Taylor, Michael D.

    2014-01-01

    Purpose Medulloblastoma comprises four distinct molecular subgroups: WNT, SHH, Group 3, and Group 4. Current medulloblastoma protocols stratify patients based on clinical features: patient age, metastatic stage, extent of resection, and histologic variant. Stark prognostic and genetic differences among the four subgroups suggest that subgroup-specific molecular biomarkers could improve patient prognostication. Patients and Methods Molecular biomarkers were identified from a discovery set of 673 medulloblastomas from 43 cities around the world. Combined risk stratification models were designed based on clinical and cytogenetic biomarkers identified by multivariable Cox proportional hazards analyses. Identified biomarkers were tested using fluorescent in situ hybridization (FISH) on a nonoverlapping medulloblastoma tissue microarray (n = 453), with subsequent validation of the risk stratification models. Results Subgroup information improves the predictive accuracy of a multivariable survival model compared with clinical biomarkers alone. Most previously published cytogenetic biomarkers are only prognostic within a single medulloblastoma subgroup. Profiling six FISH biomarkers (GLI2, MYC, chromosome 11 [chr11], chr14, 17p, and 17q) on formalin-fixed paraffin-embedded tissues, we can reliably and reproducibly identify very low-risk and very high-risk patients within SHH, Group 3, and Group 4 medulloblastomas. Conclusion Combining subgroup and cytogenetic biomarkers with established clinical biomarkers substantially improves patient prognostication, even in the context of heterogeneous clinical therapies. The prognostic significance of most molecular biomarkers is restricted to a specific subgroup. We have identified a small panel of cytogenetic biomarkers that reliably identifies very high-risk and very low-risk groups of patients, making it an excellent tool for selecting patients for therapy intensification and therapy de-escalation in future clinical trials. PMID:24493713

  11. Identification of a novel locus on chromosome 2q13, which predisposes to clinical vertebral fractures independently of bone density.

    PubMed

    Alonso, Nerea; Estrada, Karol; Albagha, Omar M E; Herrera, Lizbeth; Reppe, Sjur; Olstad, Ole K; Gautvik, Kaare M; Ryan, Niamh M; Evans, Kathryn L; Nielson, Carrie M; Hsu, Yi-Hsiang; Kiel, Douglas P; Markozannes, George; Ntzani, Evangelia E; Evangelou, Evangelos; Feenstra, Bjarke; Liu, Xueping; Melbye, Mads; Masi, Laura; Brandi, Maria Luisa; Riches, Philip; Daroszewska, Anna; Olmos, José Manuel; Valero, Carmen; Castillo, Jesús; Riancho, José A; Husted, Lise B; Langdahl, Bente L; Brown, Matthew A; Duncan, Emma L; Kaptoge, Stephen; Khaw, Kay-Tee; Usategui-Martín, Ricardo; Del Pino-Montes, Javier; González-Sarmiento, Rogelio; Lewis, Joshua R; Prince, Richard L; D'Amelio, Patrizia; García-Giralt, Natalia; Nogués, Xavier; Mencej-Bedrac, Simona; Marc, Janja; Wolstein, Orit; Eisman, John A; Oei, Ling; Medina-Gómez, Carolina; Schraut, Katharina E; Navarro, Pau; Wilson, James F; Davies, Gail; Starr, John; Deary, Ian; Tanaka, Toshiko; Ferrucci, Luigi; Gianfrancesco, Fernando; Gennari, Luigi; Lucas, Gavin; Elosua, Roberto; Uitterlinden, André G; Rivadeneira, Fernando; Ralston, Stuart H

    2018-03-01

    To identify genetic determinants of susceptibility to clinical vertebral fractures, which is an important complication of osteoporosis. Here we conduct a genome-wide association study in 1553 postmenopausal women with clinical vertebral fractures and 4340 controls, with a two-stage replication involving 1028 cases and 3762 controls. Potentially causal variants were identified using expression quantitative trait loci (eQTL) data from transiliac bone biopsies and bioinformatic studies. A locus tagged by rs10190845 was identified on chromosome 2q13, which was significantly associated with clinical vertebral fracture (P=1.04×10 -9 ) with a large effect size (OR 1.74, 95% CI 1.06 to 2.6). Bioinformatic analysis of this locus identified several potentially functional SNPs that are associated with expression of the positional candidate genes TTL (tubulin tyrosine ligase) and SLC20A1 (solute carrier family 20 member 1). Three other suggestive loci were identified on chromosomes 1p31, 11q12 and 15q11. All these loci were novel and had not previously been associated with bone mineral density or clinical fractures. We have identified a novel genetic variant that is associated with clinical vertebral fractures by mechanisms that are independent of BMD. Further studies are now in progress to validate this association and evaluate the underlying mechanism. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  12. Anger and Sadness Perception in Clinically Referred Preschoolers: Emotion Processes and Externalizing Behavior Symptoms

    ERIC Educational Resources Information Center

    Martin, Sarah E.; Boekamp, John R.; McConville, David W.; Wheeler, Elizabeth E.

    2010-01-01

    This study examined emotion perception processes in preschool aged children presenting with clinically significant emotional and behavior problems, with emphasis on sadness perception accuracy (i.e., the ability to correctly identify sadness from expressive and situational cues) and anger perception bias (i.e., the tendency to perceive anger in…

  13. Practicing what we know: Multicultural counseling competence among clinical psychology trainees and experienced multicultural psychologists.

    PubMed

    Sehgal, Radhika; Saules, Karen; Young, Amy; Grey, Melissa J; Gillem, Angela R; Nabors, Nina A; Byrd, Michelle R; Jefferson, Stephen

    2011-01-01

    Multicultural (MC) competence is considered a necessary skill for clinical and counseling psychologists; however, there is little to no research on the assessment of demonstrated multicultural counseling competence (DMCCC) of clinical psychology graduate students. In this study, we developed a MC assessment instrument to assess DMCCC of clinical psychology graduate students compared with MC-experienced psychologists. In addition, we assessed for differences between the endorsement of MC-appropriate strategies and actual use of these strategies in clinical practice, both by MC-experienced psychologists and clinical psychology students. Results revealed significant differences between the DMCCC of clinical psychology graduate students and MC-experienced psychologists. Significant differences also emerged between endorsement of strategies as multiculturally appropriate and likelihood of actual use of these strategies. Findings suggest that future training and competence models should incorporate participants' ability to not only identify multiculturally appropriate strategies but also use these strategies in therapy.

  14. Factors influencing patients seeking oral health care in the oncology dental support clinic at an urban university dental school setting.

    PubMed

    Corrigan, Dale M; Walker, Mary P; Liu, Ying; Mitchell, Tanya Villalpando

    2014-01-01

    The purpose of this study was to identify predictors and/or factors associated with medically compromised patients seeking dental care in the oncology dental support clinic (ODSC) at the University of Missouri-Kansas City (UMKC) School of Dentistry. An 18-item survey was mailed to 2,541 patients who were new patients to the clinic from 2006 to 2011. The response rate was approximately 18% (n = 450). Analyses included descriptive statistics of percentages/frequencies as well as predictors based on correlations. Fifty percent of participants, 100 females and 119 males, identified their primary medical diagnosis as cancer. Total household income (p < .001) and the importance of receiving dental care (p < .001) were significant factors in relation to self-rated dental health. Perceived overall health (p < .001) also had a significant association with cancer status and the need for organ transplants. This study provided the ODSC at UMKC and other specialty clinics with vital information that can contribute to future planning efforts. © 2013 Special Care Dentistry Association and Wiley Periodicals, Inc.

  15. [Identifying gaps between guidelines and clinical practice in Clostridium difficile infection].

    PubMed

    Rodríguez-Martín, C; Serrano-Morte, A; Sánchez-Muñoz, L A; de Santos-Castro, P A; Bratos-Pérez, M A; Ortiz de Lejarazu-Leonardo, R

    2016-01-01

    The first aim was to determine whether patients are being treated in accordance with the Society for Healthcare Epidemiology of America and the Infectious Diseases Society of America (IDSA/SHEA) Clostridium difficile guidelines and whether adherence impacts patient outcomes. The second aim was to identify specific action items in the guidelines that are not being translated into clinical practice, for their subsequent implementation. A retrospective, descriptive study was conducted over a 36 month period, on patients with compatible clinical symptoms and positive test for C. difficile toxins A and/or B in stool samples, in an internal medicine department of a tertiary medical centre. Patient demographic and clinical data (outcomes, comorbidity, risk factors) and compliance with guidelines, were examined A total of 77 patients with C. difficile infection were identified (87 episodes). Stratified by disease severity criteria, 49.3% of patients were mild-moderate, 35.1% severe, and 15.6% severe-complicated. Full adherence with the guidelines was observed in only 40.2% of patients, and was significantly better for mild-moderate (71.0%), than in severe (7.4%) or severe-complicated patients (16.6%) (P<.003). Adherence was significantly associated with clinical cure (57% vs 42%), fewer recurrences (22.2% vs 77.7%), and mortality (25% vs 75%) (P<.01). The stratification of severity of the episode, and the adequacy of antibiotic to clinical severity, need improvement. Overall adherence with the guidelines for management of Clostridium difficile infection was poor, especially in severe and severe-complicated patients, being associated with worse clinical outcomes. Educational interventions aimed at improving guideline adherence are warranted. Copyright © 2015 SECA. Published by Elsevier Espana. All rights reserved.

  16. Patient-reported outcomes in randomised controlled trials of colorectal cancer: an analysis determining the availability of robust data to inform clinical decision-making

    PubMed Central

    Whale, Katie; Fish, Daniel; Fayers, Peter; Cafaro, Valentina; Pusic, Andrea; Blazeby, Jane M.; Efficace, Fabio

    2016-01-01

    Purpose Randomised controlled trials (RCTs) are the most robust study design measuring outcomes of colorectal cancer (CRC) treatments, but to influence clinical practice trial design and reporting of patient-reported outcomes (PROs) must be of high quality. Objectives of this study were as follows: to examine the quality of PRO reporting in RCTs of CRC treatment; to assess the availability of robust data to inform clinical decision-making; and to investigate whether quality of reporting improved over time. Methods A systematic review from January 2004–February 2012 identified RCTs of CRC treatment describing PROs. Relevant abstracts were screened and manuscripts obtained. Methodological quality was assessed using International Society for Quality of Life Research—patient-reported outcome reporting standards. Changes in reporting quality over time were established by comparison with previous data, and risk of bias was assessed with the Cochrane risk of bias tool. Results Sixty-six RCTs were identified, seven studies (10 %) reported survival benefit favouring the experimental treatment, 35 trials (53 %) identified differences in PROs between treatment groups, and the clinical significance of these differences was discussed in 19 studies (29 %). The most commonly reported treatment type was chemotherapy (n = 45; 68 %). Improvements over time in key methodological issues including the documentation of missing data and the discussion of the clinical significance of PROs were found. Thirteen trials (20 %) had high-quality reporting. Conclusions Whilst improvements in PRO quality reporting over time were found, several recent studies still fail to robustly inform clinical practice. Quality of PRO reporting must continue to improve to maximise the clinical impact of PRO findings. PMID:25910987

  17. An integrative somatic mutation analysis to identify pathways linked with survival outcomes across 19 cancer types

    PubMed Central

    Park, Sunho; Kim, Seung-Jun; Yu, Donghyeon; Peña-Llopis, Samuel; Gao, Jianjiong; Park, Jin Suk; Chen, Beibei; Norris, Jessie; Wang, Xinlei; Chen, Min; Kim, Minsoo; Yong, Jeongsik; Wardak, Zabi; Choe, Kevin; Story, Michael; Starr, Timothy; Cheong, Jae-Ho; Hwang, Tae Hyun

    2016-01-01

    Motivation: Identification of altered pathways that are clinically relevant across human cancers is a key challenge in cancer genomics. Precise identification and understanding of these altered pathways may provide novel insights into patient stratification, therapeutic strategies and the development of new drugs. However, a challenge remains in accurately identifying pathways altered by somatic mutations across human cancers, due to the diverse mutation spectrum. We developed an innovative approach to integrate somatic mutation data with gene networks and pathways, in order to identify pathways altered by somatic mutations across cancers. Results: We applied our approach to The Cancer Genome Atlas (TCGA) dataset of somatic mutations in 4790 cancer patients with 19 different types of tumors. Our analysis identified cancer-type-specific altered pathways enriched with known cancer-relevant genes and targets of currently available drugs. To investigate the clinical significance of these altered pathways, we performed consensus clustering for patient stratification using member genes in the altered pathways coupled with gene expression datasets from 4870 patients from TCGA, and multiple independent cohorts confirmed that the altered pathways could be used to stratify patients into subgroups with significantly different clinical outcomes. Of particular significance, certain patient subpopulations with poor prognosis were identified because they had specific altered pathways for which there are available targeted therapies. These findings could be used to tailor and intensify therapy in these patients, for whom current therapy is suboptimal. Availability and implementation: The code is available at: http://www.taehyunlab.org. Contact: jhcheong@yuhs.ac or taehyun.hwang@utsouthwestern.edu or taehyun.cs@gmail.com Supplementary information: Supplementary data are available at Bioinformatics online. PMID:26635139

  18. Development of a case definition for clinical feline herpesvirus infection in cheetahs (Acinonyx jubatus) housed in zoos.

    PubMed

    Witte, Carmel L; Lamberski, Nadine; Rideout, Bruce A; Fields, Victoria; Teare, Cyd Shields; Barrie, Michael; Haefele, Holly; Junge, Randall; Murray, Suzan; Hungerford, Laura L

    2013-09-01

    The identification of feline herpesvirus (FHV) infected cheetahs (Acinonyx jubatus) and characterization of shedding episodes is difficult due to nonspecific clinical signs and limitations of diagnostic tests. The goals of this study were to develop a case definition for clinical FHV and describe the distribution of signs. Medical records from six different zoologic institutions were reviewed to identify cheetahs with diagnostic test results confirming FHV. Published literature, expert opinion, and results of a multiple correspondence analysis (MCA) were used to develop a clinical case definition based on 69 episodes in FHV laboratory confirmed (LC) cheetahs. Four groups of signs were identified in the MCA: general ocular signs, serious ocular lesions, respiratory disease, and cutaneous lesions. Ocular disease occurred with respiratory signs alone, with skin lesions alone, and with both respiratory signs and skin lesions. Groups that did not occur together were respiratory signs and skin lesions. The resulting case definition included 1) LC cheetahs; and 2) clinically compatible (CC) cheetahs that exhibited a minimum of 7 day's duration of the clinical sign groupings identified in the MCA or the presence of corneal ulcers or keratitis that occurred alone or in concert with other ocular signs and skin lesions. Exclusion criteria were applied. Application of the case definition to the study population identified an additional 78 clinical episodes, which represented 58 CC cheetahs. In total, 28.8% (93/322) of the population was identified as LC or CC. The distribution of identified clinical signs was similar across LC and CC cheetahs. Corneal ulcers and/or keratitis, and skin lesions were more frequently reported in severe episodes; in mild episodes, there were significantly more cheetahs with ocular-only or respiratory-only disease. Our results provide a better understanding of the clinical presentation of FHV, while presenting a standardized case definition that can both contribute to earlier diagnoses and be used for population-level studies.

  19. A Comprehensive Pan-Cancer Molecular Study of Gynecologic and Breast Cancers. | Office of Cancer Genomics

    Cancer.gov

    We analyzed molecular data on 2,579 tumors from The Cancer Genome Atlas (TCGA) of four gynecological types plus breast. Our aims were to identify shared and unique molecular features, clinically significant subtypes, and potential therapeutic targets. We found 61 somatic copy-number alterations (SCNAs) and 46 significantly mutated genes (SMGs). Eleven SCNAs and 11 SMGs had not been identified in previous TCGA studies of the individual tumor types. We found functionally significant estrogen receptor-regulated long non-coding RNAs (lncRNAs) and gene/lncRNA interaction networks.

  20. T wave abnormalities, high body mass index, current smoking and high lipoprotein (a) levels predict the development of major abnormal Q/QS patterns 20 years later. A population-based study

    PubMed Central

    Moller, Christina Strom; Byberg, Liisa; Sundstrom, Johan; Lind, Lars

    2006-01-01

    Background Most studies on risk factors for development of coronary heart disease (CHD) have been based on the clinical outcome of CHD. Our aim was to identify factors that could predict the development of ECG markers of CHD, such as abnormal Q/QS patterns, ST segment depression and T wave abnormalities, in 70-year-old men, irrespective of clinical outcome. Methods Predictors for development of different ECG abnormalities were identified in a population-based study using stepwise logistic regression. Anthropometrical and metabolic factors, ECG abnormalities and vital signs from a health survey of men at age 50 were related to ECG abnormalities identified in the same cohort 20 years later. Results At the age of 70, 9% had developed a major abnormal Q/QS pattern, but 63% of these subjects had not been previously hospitalized due to MI, while 57% with symptomatic MI between age 50 and 70 had no major Q/QS pattern at age 70. T wave abnormalities (Odds ratio 3.11, 95% CI 1.18–8.17), high lipoprotein (a) levels, high body mass index (BMI) and smoking were identified as significant independent predictors for the development of abnormal major Q/QS patterns. T wave abnormalities and high fasting glucose levels were significant independent predictors for the development of ST segment depression without abnormal Q/QS pattern. Conclusion T wave abnormalities on resting ECG should be given special attention and correlated with clinical information. Risk factors for major Q/QS patterns need not be the same as traditional risk factors for clinically recognized CHD. High lipoprotein (a) levels may be a stronger risk factor for silent myocardial infarction (MI) compared to clinically recognized MI. PMID:16519804

  1. A Partial Least-Squares Analysis of Health-Related Quality-of-Life Outcomes After Aneurysmal Subarachnoid Hemorrhage.

    PubMed

    Young, Julia M; Morgan, Benjamin R; Mišić, Bratislav; Schweizer, Tom A; Ibrahim, George M; Macdonald, R Loch

    2015-12-01

    Individuals who have aneurysmal subarachnoid hemorrhages (SAHs) experience decreased health-related qualities of life (HRQoLs) that persist after the primary insult. To identify clinical variables that concurrently associate with HRQoL outcomes by using a partial least-squares approach, which has the distinct advantage of explaining multidimensional variance where predictor variables may be highly collinear. Data collected from the CONSCIOUS-1 trial was used to extract 29 clinical variables including SAH presentation, hospital procedures, and demographic information in addition to 5 HRQoL outcome variables for 256 individuals. A partial least-squares analysis was performed by calculating a heterogeneous correlation matrix and applying singular value decomposition to determine components that best represent the correlations between the 2 sets of variables. Bootstrapping was used to estimate statistical significance. The first 2 components accounting for 81.6% and 7.8% of the total variance revealed significant associations between clinical predictors and HRQoL outcomes. The first component identified associations between disability in self-care with longer durations of critical care stay, invasive intracranial monitoring, ventricular drain time, poorer clinical grade on presentation, greater amounts of cerebral spinal fluid drainage, and a history of hypertension. The second component identified associations between disability due to pain and discomfort as well as anxiety and depression with greater body mass index, abnormal heart rate, longer durations of deep sedation and critical care, and higher World Federation of Neurosurgical Societies and Hijdra scores. By applying a data-driven, multivariate approach, we identified robust associations between SAH clinical presentations and HRQoL outcomes. EQ-VAS, EuroQoL visual analog scaleHRQoL, health-related quality of lifeICU, intensive care unitIVH, intraventricular hemorrhagePLS, partial least squaresSAH, subarachnoid hemorrhageSVD, singular value decompositionWFNS, World Federation of Neurosurgical Societies.

  2. Clinical utility of transperineal template-guided mapping biopsy of the prostate after negative magnetic resonance imaging-guided transrectal biopsy.

    PubMed

    Sivaraman, Arjun; Sanchez-Salas, Rafael; Ahmed, Hashim U; Barret, Eric; Cathala, Nathalie; Mombet, Annick; Uriburu Pizarro, Facundo; Carneiro, Arie; Doizi, Steeve; Galiano, Marc; Rozet, Francois; Prapotnich, Dominique; Cathelineau, Xavier

    2015-07-01

    We evaluated the prostate cancer detection with transperineal template-guided mapping biopsy in patients with elevated prostate-specific antigen and negative magnetic resonance imaging (MRI)-guided biopsy. Totally 75 patients underwent transperineal template-guided mapping biopsy for prior negative MRI-guided (cognitive registration) biopsy during April 2013 to August 2014. Primary objective was to report clinically significant cancer detection in this cohort of patients. Significant cancer was defined using varying thresholds of MCL or Gleason grade 3+4 or greater or both. Cancers with more than 80% of positive core length anterior to the level of urethra were termed anterior zone cancer. Secondary objective was to evaluate the potential clinical and radiological predictors for significant cancer detection. The mean age was 61.6 ± 6.5 years and median prostate-specific antigen was 10.4 ng/dl (7.9-18) with a mean MRI target size of 7.2mm (4-11). Transperineal template-guided mapping biopsy identified cancer in 36% (27/75) patients and 66.6% (18/27) of them were anterior zone cancers. The rates of detection of clinically significant and insignificant cancer according to the several definitions used range from 22.7% to 30.7% and 5.3% to 13.3%, respectively. Multivariate analysis did not identify any predictors for finding clinically significant and anterior cancers in this group of patients. Transperineal template-guided mapping biopsy appears to be an excellent biopsy protocol for downstream management following negative MRI-guided biopsy. Most of the cancers detected were predominantly anterior tumors. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Empiric transcatheter arterial embolization for massive bleeding from duodenal ulcers: efficacy and complications.

    PubMed

    Ichiro, Ikushima; Shushi, Higashi; Akihiko, Ishii; Yasuhiko, Iryo; Yasuyuki, Yamashita

    2011-07-01

    To evaluate the efficacy and safety of empiric transcatheter arterial embolization (TAE) for patients with massive bleeding from duodenal ulcers. During January 2000 and December 2009, 59 patients with duodenal ulcer bleeding in whom TAE was attempted after endoscopic therapy failed were retrospectively analyzed. The patients were divided into empiric TAE (n = 36) and identifiable TAE (n = 23) groups according to angiographic findings with or without identification of the bleeding sites. The technical and clinical success rate, recurrent bleeding rate, procedure-related complications, and clinical outcomes were evaluated. The technical and clinical success rates of TAE were 100% and 83%. The recurrent bleeding rate, clinical success, duodenal stenosis, and 30-day mortality after TAE were not significantly different between the empiric and identifiable TAE groups. A high rate of technical and clinical success was obtained with empiric TAE comparable to identifiable TAE in patients with massive bleeding from duodenal ulcers. There were no severe complications. Empiric TAE is an effective and safe method when a bleeding site cannot determined by angiography. Copyright © 2011 SIR. Published by Elsevier Inc. All rights reserved.

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

    PubMed Central

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

    2016-01-01

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

  5. Insufficient sleep predicts clinical burnout.

    PubMed

    Söderström, Marie; Jeding, Kerstin; Ekstedt, Mirjam; Perski, Aleksander; Akerstedt, Torbjörn

    2012-04-01

    The present prospective study aimed to identify risk factors for subsequent clinical burnout. Three hundred eighty-eight working individuals completed a baseline questionnaire regarding work stress, sleep, mood, health, and so forth. During a 2-year period, 15 subjects (7 women and 8 men) of the total sample were identified as "burnout cases," as they were assessed and referred to treatment for clinical burnout. Questionnaire data from the baseline measurement were used as independent variables in a series of logistic regression analyses to predict clinical burnout. The results identified "too little sleep (< 6 h)" as the main risk factor for burnout development, with adjustment for "work demands," "thoughts of work during leisure time," and "sleep quality." The first two factors were significant predictors in earlier steps of the multivariate regression. The results indicate that insufficient sleep, preoccupation with thoughts of work during leisure time, and high work demands are risk factors for subsequent burnout. The results suggest a chain of causation. PsycINFO Database Record (c) 2012 APA, all rights reserved.

  6. Pre-clinical and clinical development of the first placental malaria vaccine.

    PubMed

    Pehrson, Caroline; Salanti, Ali; Theander, Thor G; Nielsen, Morten A

    2017-06-01

    Malaria during pregnancy is a massive health problem in endemic areas. Placental malaria infections caused by Plasmodium falciparum are responsible for up to one million babies being born with a low birth weight every year. Significant efforts have been invested into preventing the condition. Areas covered: Pub Med was searched using the broad terms 'malaria parasite placenta' to identify studies of interactions between parasite and host, 'prevention of placental malaria' to identify current strategies to prevent placental malaria, and 'placental malaria vaccine' to identify pre-clinical vaccine development. However, all papers from these searches were not systematically included. Expert commentary: The first phase I clinical trials of vaccines are well underway. Trials testing efficacy are more complicated to carry out as only women that are exposed to parasites during pregnancy will contribute to endpoint measurements, further it may require extensive follow-up to establish protection. Future second generation vaccines may overcome the inherent challenges in making an effective placental malaria vaccine.

  7. Poor reporting of scientific leadership information in clinical trial registers.

    PubMed

    Sekeres, Melanie; Gold, Jennifer L; Chan, An-Wen; Lexchin, Joel; Moher, David; Van Laethem, Marleen L P; Maskalyk, James; Ferris, Lorraine; Taback, Nathan; Rochon, Paula A

    2008-02-20

    In September 2004, the International Committee of Medical Journal Editors (ICMJE) issued a Statement requiring that all clinical trials be registered at inception in a public register in order to be considered for publication. The World Health Organization (WHO) and ICMJE have identified 20 items that should be provided before a trial is considered registered, including contact information. Identifying those scientifically responsible for trial conduct increases accountability. The objective is to examine the proportion of registered clinical trials providing valid scientific leadership information. We reviewed clinical trial entries listing Canadian investigators in the two largest international and public trial registers, the International Standard Randomized Controlled Trial Number (ISRCTN) register, and ClinicalTrials.gov. The main outcome measures were the proportion of clinical trials reporting valid contact information for the trials' Principal Investigator (PI)/Co-ordinating Investigator/Study Chair/Site PI, and trial e-mail contact address, stratified by funding source, recruiting status, and register. A total of 1388 entries (142 from ISRCTN and 1246 from ClinicalTrials.gov) comprised our sample. We found non-compliance with mandatory registration requirements regarding scientific leadership and trial contact information. Non-industry and partial industry funded trials were significantly more likely to identify the individual responsible for scientific leadership (OR = 259, 95% CI: 95-701) and to provide a contact e-mail address (OR = 9.6, 95% CI: 6.6-14) than were solely industry funded trials. Despite the requirements set by WHO and ICMJE, data on scientific leadership and contact e-mail addresses are frequently omitted from clinical trials registered in the two leading public clinical trial registers. To promote accountability and transparency in clinical trials research, public clinical trials registers should ensure adequate monitoring of trial registration to ensure completion of mandatory contact information fields identifying scientific leadership.

  8. CNV-RF Is a Random Forest-Based Copy Number Variation Detection Method Using Next-Generation Sequencing.

    PubMed

    Onsongo, Getiria; Baughn, Linda B; Bower, Matthew; Henzler, Christine; Schomaker, Matthew; Silverstein, Kevin A T; Thyagarajan, Bharat

    2016-11-01

    Simultaneous detection of small copy number variations (CNVs) (<0.5 kb) and single-nucleotide variants in clinically significant genes is of great interest for clinical laboratories. The analytical variability in next-generation sequencing (NGS) and artifacts in coverage data because of issues with mappability along with lack of robust bioinformatics tools for CNV detection have limited the utility of targeted NGS data to identify CNVs. We describe the development and implementation of a bioinformatics algorithm, copy number variation-random forest (CNV-RF), that incorporates a machine learning component to identify CNVs from targeted NGS data. Using CNV-RF, we identified 12 of 13 deletions in samples with known CNVs, two cases with duplications, and identified novel deletions in 22 additional cases. Furthermore, no CNVs were identified among 60 genes in 14 cases with normal copy number and no CNVs were identified in another 104 patients with clinical suspicion of CNVs. All positive deletions and duplications were confirmed using a quantitative PCR method. CNV-RF also detected heterozygous deletions and duplications with a specificity of 50% across 4813 genes. The ability of CNV-RF to detect clinically relevant CNVs with a high degree of sensitivity along with confirmation using a low-cost quantitative PCR method provides a framework for providing comprehensive NGS-based CNV/single-nucleotide variant detection in a clinical molecular diagnostics laboratory. Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

  9. Common data elements for secondary use of electronic health record data for clinical trial execution and serious adverse event reporting.

    PubMed

    Bruland, Philipp; McGilchrist, Mark; Zapletal, Eric; Acosta, Dionisio; Proeve, Johann; Askin, Scott; Ganslandt, Thomas; Doods, Justin; Dugas, Martin

    2016-11-22

    Data capture is one of the most expensive phases during the conduct of a clinical trial and the increasing use of electronic health records (EHR) offers significant savings to clinical research. To facilitate these secondary uses of routinely collected patient data, it is beneficial to know what data elements are captured in clinical trials. Therefore our aim here is to determine the most commonly used data elements in clinical trials and their availability in hospital EHR systems. Case report forms for 23 clinical trials in differing disease areas were analyzed. Through an iterative and consensus-based process of medical informatics professionals from academia and trial experts from the European pharmaceutical industry, data elements were compiled for all disease areas and with special focus on the reporting of adverse events. Afterwards, data elements were identified and statistics acquired from hospital sites providing data to the EHR4CR project. The analysis identified 133 unique data elements. Fifty elements were congruent with a published data inventory for patient recruitment and 83 new elements were identified for clinical trial execution, including adverse event reporting. Demographic and laboratory elements lead the list of available elements in hospitals EHR systems. For the reporting of serious adverse events only very few elements could be identified in the patient records. Common data elements in clinical trials have been identified and their availability in hospital systems elucidated. Several elements, often those related to reimbursement, are frequently available whereas more specialized elements are ranked at the bottom of the data inventory list. Hospitals that want to obtain the benefits of reusing data for research from their EHR are now able to prioritize their efforts based on this common data element list.

  10. 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.

  11. Collaborators and Communication Channels in Eight Patient-Centered Medical Homes.

    PubMed

    Chase, Dian A; Dorr, David A; Cohen, Deborah J; Ash, Joan S

    2017-01-01

    The patient-centered medical home (PCMH) concept requires collaboration among clinicians both within the medical home clinic, and outside the clinic. As we redesign health information technology (HIT) to support transformation to the PCMH, we need to better understand these collaboration patterns. This study provides quantitative data describing these collaborations in order to facilitate the design of systems to allow for more efficient collaboration. Eighty-four clinicians in eight clinics identified their two most recent significant collaborators - one each within the clinic and in the medical neighborhood. They also identified the communication channels used in these collaborations. We used k-means clustering to identify communication patterns. Within the clinic, half of the primary care providers (PCPs) identified a care manager as their most recent collaborator. Outside specialists were their most common external collaborators. Ninety-two percent of the non-PCP participants identified PCP's as their most recent internal collaborators. The best model for communication channel usage (p < .0001) had six clusters. In general, inside communications were more informal but outside collaborations were more often formal written communications (faxes, letters) or the exchange of electronic health record progress notes. But there were exceptions to these patterns and in many cases multiple channels were used for the same collaboration. Systems design (and redesign) needs to focus on reducing communications load and increasing communication effectiveness while maintaining flexibility.

  12. 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.

  13. Specialist health visitor-led weight management intervention in primary care: exploratory evaluation.

    PubMed

    Jackson, Cath; Coe, Anne; Cheater, Francine M; Wroe, Stephen

    2007-04-01

    This paper is a report of an exploratory study to evaluate the effectiveness and acceptability of a specialist health visitor-led weight management clinic in primary care. Tackling obesity is a global health priority. Whilst there is evidence to support a role for primary healthcare professionals in its management, provision in England varies widely. Using designated 'obesity specialists' is an approach warranting further investigation. In 2003-2004, patients with a body mass index of 30 or more received a specialist health visitor-led intervention based on the Jan Felgens 'I2E2' model. Clinical outcome data and self-reported dietary consumption data were collected at weeks 1, 13, 27 and 52. Quantitative and qualitative data on patient acceptability of the clinic were collected at week 26. Eighty-nine patients attended the clinic. Mean body weight and body mass index and systolic and diastolic blood pressure decreased over time by statistically significant amounts. There was a non-significant decrease in fasting blood sugar over time, but approximately one in 10 patients with undiagnosed diabetes were identified. No statistically significant change was evident for cholesterol levels. Mean self-reported weekly consumption of cakes, desserts and snacks decreased and that of fruit and vegetables increased, each by statistically significant amounts. Participants found the clinic highly acceptable and identified the specialist health visitor as fundamental to its success. A partnership approach to weight management through which patients are empowered to make sustainable lifestyle changes now needs to be tested in a multi-centre randomized controlled trial.

  14. Conflicts Between Parents and Health Professionals About a Child's Medical Treatment: Using Clinical Ethics Records to Find Gaps in the Bioethics Literature.

    PubMed

    McDougall, Rosalind; Notini, Lauren; Phillips, Jessica

    2015-09-01

    Clinical ethics records offer bioethics researchers a rich source of cases that clinicians have identified as ethically complex. In this paper, we suggest that clinical ethics records can be used to point to types of cases that lack attention in the current bioethics literature, identifying new areas in need of more detailed bioethical work. We conducted an analysis of the clinical ethics records of one paediatric hospital in Australia, focusing specifically on conflicts between parents and health professionals about a child's medical treatment. We identified, analysed, and compared cases of this type from the clinical ethics records with cases of this type discussed in bioethics journals. While the cases from journals tended to describe situations involving imminent risk to the child's life, a significant proportion of the clinical ethics records cases involved different stakes for the child involved. These included distress, poorer functional outcome, poorer psychosocial outcome, or increased risk of surgical complications. Our analysis suggests that one type of case that warrants more detailed ethics research is parental refusal of recommended treatment, where the refusal does not endanger the child's life but rather some other aspect of the child's well-being.

  15. Development and validation of a comprehensive genomic diagnostic tool for myeloid malignancies

    PubMed Central

    McKerrell, Thomas; Moreno, Thaidy; Ponstingl, Hannes; Bolli, Niccolo; Dias, João M. L.; Tischler, German; Colonna, Vincenza; Manasse, Bridget; Bench, Anthony; Bloxham, David; Herman, Bram; Fletcher, Danielle; Park, Naomi; Quail, Michael A.; Manes, Nicla; Hodkinson, Clare; Baxter, Joanna; Sierra, Jorge; Foukaneli, Theodora; Warren, Alan J.; Chi, Jianxiang; Costeas, Paul; Rad, Roland; Huntly, Brian; Grove, Carolyn; Ning, Zemin; Tyler-Smith, Chris; Varela, Ignacio; Scott, Mike; Nomdedeu, Josep; Mustonen, Ville

    2016-01-01

    The diagnosis of hematologic malignancies relies on multidisciplinary workflows involving morphology, flow cytometry, cytogenetic, and molecular genetic analyses. Advances in cancer genomics have identified numerous recurrent mutations with clear prognostic and/or therapeutic significance to different cancers. In myeloid malignancies, there is a clinical imperative to test for such mutations in mainstream diagnosis; however, progress toward this has been slow and piecemeal. Here we describe Karyogene, an integrated targeted resequencing/analytical platform that detects nucleotide substitutions, insertions/deletions, chromosomal translocations, copy number abnormalities, and zygosity changes in a single assay. We validate the approach against 62 acute myeloid leukemia, 50 myelodysplastic syndrome, and 40 blood DNA samples from individuals without evidence of clonal blood disorders. We demonstrate robust detection of sequence changes in 49 genes, including difficult-to-detect mutations such as FLT3 internal-tandem and mixed-lineage leukemia (MLL) partial-tandem duplications, and clinically significant chromosomal rearrangements including MLL translocations to known and unknown partners, identifying the novel fusion gene MLL-DIAPH2 in the process. Additionally, we identify most significant chromosomal gains and losses, and several copy neutral loss-of-heterozygosity mutations at a genome-wide level, including previously unreported changes such as homozygosity for DNMT3A R882 mutations. Karyogene represents a dependable genomic diagnosis platform for translational research and for the clinical management of myeloid malignancies, which can be readily adapted for use in other cancers. PMID:27121471

  16. Patient perspectives on medical photography in dermatology.

    PubMed

    Leger, Marie C; Wu, Timothy; Haimovic, Adele; Kaplan, Rachel; Sanchez, Miguel; Cohen, David; Leger, Elizabeth A; Stein, Jennifer A

    2014-09-01

    Clinical photography enhances medical care, research, and teaching. Empirical data are needed to guide best practices regarding dermatologic photography. To investigate patient opinion about clinical photography and identify demographic factors that influence these opinions. Four hundred patients representing a broad range of ages, self-identified ethnic/racial groups, and socioeconomic levels were recruited from 4 dermatology settings in New York City. Patients were administered a survey about perceptions of photography, willingness to allow photographs to be used in a variety of settings, preferences for photographer and photographic equipment, and methods of consent. Eighty-eight percent of patients agreed that photography enhanced their quality of care. Most patients would allow their photographs to be used for medical, teaching, and research purposes with significantly more acceptance when patients were not identifiable. Patients preferred photographs taken by a physician rather than a nurse or student, photographers of the same gender, clinic-owned cameras to personal cameras or cell phones, and written consent to verbal consent. There were significant racial/ethnicity and age-related variations in responses, with white and older patients being more permissive than other groups. We use the results of this study to recommend best practices for photography in dermatology.

  17. Content and Usability Evaluation of Patient Oriented Drug-Drug Interaction Websites.

    PubMed

    Adam, Terrence J; Vang, Joseph

    Drug-Drug Interactions (DDI) are an important source of preventable adverse drug events and a common reason for hospitalization among patients on multiple drug therapy regimens. DDI information systems are important patient safety tools with the capacity to identify and warn health professionals of clinically significant DDI risk. While substantial research has been completed on DDI information systems in professional settings such as community, hospital, and independent pharmacies; there has been limited research on DDI systems offered through online websites directly for use by ambulatory patients. The focus of this project is to test patient oriented website capacity to correctly identify drug interactions among well established and clinically significant medication combinations and convey clinical risk data to patients. The patient education capability was assessed by evaluating website Information Capacity, Patient Usability and Readability. The study results indicate that the majority of websites identified which met the inclusion and exclusion criteria operated similarly, but vary in risk severity assessment and are not optimally patient oriented to effectively deliver risk information. The limited quality of information and complex medical term content complicate DDI risk data conveyance and the sites may not provide optimal information delivery to allow medication consumers to understand and manage their medication regimens.

  18. Biomarkers of PTSD: military applications and considerations.

    PubMed

    Lehrner, Amy; Yehuda, Rachel

    2014-01-01

    Although there are no established biomarkers for posttraumatic stress disorder (PTSD) as yet, biological investigations of PTSD have made progress identifying the pathophysiology of PTSD. Given the biological and clinical complexity of PTSD, it is increasingly unlikely that a single biomarker of disease will be identified. Rather, investigations will more likely identify different biomarkers that indicate the presence of clinically significant PTSD symptoms, associate with risk for PTSD following trauma exposure, and predict or identify recovery. While there has been much interest in PTSD biomarkers, there has been less discussion of their potential clinical applications, and of the social, legal, and ethical implications of such biomarkers. This article will discuss possible applications of PTSD biomarkers, including the social, legal, and ethical implications of such biomarkers, with an emphasis on military applications. Literature on applications of PTSD biomarkers and on potential ethical and legal implications will be reviewed. Biologically informed research findings hold promise for prevention, assessment, treatment planning, and the development of prophylactic and treatment interventions. As with any biological indicator of disorder, there are potentially positive and negative clinical, social, legal, and ethical consequences of using such biomarkers. Potential clinical applications of PTSD biomarkers hold promise for clinicians, patients, and employers. The search for biomarkers of PTSD should occur in tandem with an interdisciplinary discussion regarding the potential implications of applying biological findings in clinical and employment settings.

  19. Process, cost, and clinical quality: the initial oral contraceptive visit.

    PubMed

    McMullen, Michael J; Woolford, Samuel W; Moore, Charles L; Berger, Barry M

    2013-01-01

    To demonstrate how the analysis of clinical process, cost, and outcomes can identify healthcare improvements that reduce cost without sacrificing quality, using the example of the initial visit associated with oral contraceptive pill use. Cross-sectional study using data collected by HealthMETRICS between 1996 and 2009. Using data collected from 106 sites in 24 states, the unintended pregnancy (UIP) rate, effectiveness of patient education, and unit visit cost were calculated. Staff type providing education and placement of education were recorded. Two-way analysis of variance models were created and tested for significance to identify differences between groups. Sites using nonclinical staff to provide education outside the exam were associated with lower cost, higher education scores, and a UIP rate no different from that of sites using clinical staff. Sites also providing patient education during the physical examination were associated with higher cost, lower education scores, and a UIP rate no lower than that of sites providing education outside of the exam. Through analyzing process, cost, and quality, lower-cost processes that did not reduce clinical quality were identified. This methodology is applicable to other clinical services for identifying low-cost processes that do not result in lower clinical quality. By using nonclinical staff educators to provide education outside of the physical examination, sites could save an average of 32% of the total cost of the visit.

  20. 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.

  1. An atypical anxious-impulsive pattern of social anxiety disorder in an adult clinical population.

    PubMed

    Mörtberg, Ewa; Tillfors, Maria; van Zalk, Nejra; Kerr, Margaret

    2014-08-01

    An atypical subgroup of Social Anxiety Disorder (SAD) with impulsive rather than inhibited traits has recently been reported. The current study examined whether such an atypical subgroup could be identified in a clinical population of 84 adults with SAD. The temperament dimensions harm avoidance and novelty seeking of the Temperament and Character Inventory, and the Liebowitz Social Anxiety Scale were used in cluster analyses. The identified clusters were compared on depressive symptoms, the character dimension self-directedness, and treatment outcome. Among the six identified clusters, 24% of the sample had atypical characteristics, demonstrating mainly generalized SAD in combination with coexisting traits of inhibition and impulsivity. As additional signs of severity, this group showed low self-directedness and high levels of depressive symptoms. We also identified a typically inhibited subgroup comprising generalized SAD with high levels of harm avoidance and low levels of novelty seeking, with a similar clinical severity as the atypical subgroup. Thus, higher levels of harm avoidance and social anxiety in combination with higher or lower levels of novelty seeking and low self-directedness seem to contribute to a more severe clinical picture. Post hoc examination of the treatment outcome in these subgroups showed that only 20 to 30% achieved clinically significant change. © 2014 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

  2. Review of nutritional screening and assessment tools and clinical outcomes in heart failure.

    PubMed

    Lin, Hong; Zhang, Haifeng; Lin, Zheng; Li, Xinli; Kong, Xiangqin; Sun, Gouzhen

    2016-09-01

    Recent studies have suggested that undernutrition as defined using multidimensional nutritional evaluation tools may affect clinical outcomes in heart failure (HF). The evidence supporting this correlation is unclear. Therefore, we conducted this systematic review to critically appraise the use of multidimensional evaluation tools in the prediction of clinical outcomes in HF. We performed descriptive analyses of all identified articles involving qualitative analyses. We used STATA to conduct meta-analyses when at least three studies that tested the same type of nutritional assessment or screening tools and used the same outcome were identified. Sensitivity analyses were conducted to validate our positive results. We identified 17 articles with qualitative analyses and 11 with quantitative analysis after comprehensive literature searching and screening. We determined that the prevalence of malnutrition is high in HF (range 16-90 %), particularly in advanced and acute decompensated HF (approximate range 75-90 %). Undernutrition as identified by multidimensional evaluation tools may be significantly associated with hospitalization, length of stay and complications and is particularly strongly associated with high mortality. The meta-analysis revealed that compared with other tools, Mini Nutritional Assessment (MNA) scores were the strongest predictors of mortality in HF [HR (4.32, 95 % CI 2.30-8.11)]. Our results remained reliable after conducting sensitivity analyses. The prevalence of malnutrition is high in HF, particularly in advanced and acute decompensated HF. Moreover, undernutrition as identified by multidimensional evaluation tools is significantly associated with unfavourable prognoses and high mortality in HF.

  3. 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 with good clinical supervision are preserved.

  4. A Deep Learning Method to Automatically Identify Reports of Scientifically Rigorous Clinical Research from the Biomedical Literature: Comparative Analytic Study.

    PubMed

    Del Fiol, Guilherme; Michelson, Matthew; Iorio, Alfonso; Cotoi, Chris; Haynes, R Brian

    2018-06-25

    A major barrier to the practice of evidence-based medicine is efficiently finding scientifically sound studies on a given clinical topic. To investigate a deep learning approach to retrieve scientifically sound treatment studies from the biomedical literature. We trained a Convolutional Neural Network using a noisy dataset of 403,216 PubMed citations with title and abstract as features. The deep learning model was compared with state-of-the-art search filters, such as PubMed's Clinical Query Broad treatment filter, McMaster's textword search strategy (no Medical Subject Heading, MeSH, terms), and Clinical Query Balanced treatment filter. A previously annotated dataset (Clinical Hedges) was used as the gold standard. The deep learning model obtained significantly lower recall than the Clinical Queries Broad treatment filter (96.9% vs 98.4%; P<.001); and equivalent recall to McMaster's textword search (96.9% vs 97.1%; P=.57) and Clinical Queries Balanced filter (96.9% vs 97.0%; P=.63). Deep learning obtained significantly higher precision than the Clinical Queries Broad filter (34.6% vs 22.4%; P<.001) and McMaster's textword search (34.6% vs 11.8%; P<.001), but was significantly lower than the Clinical Queries Balanced filter (34.6% vs 40.9%; P<.001). Deep learning performed well compared to state-of-the-art search filters, especially when citations were not indexed. Unlike previous machine learning approaches, the proposed deep learning model does not require feature engineering, or time-sensitive or proprietary features, such as MeSH terms and bibliometrics. Deep learning is a promising approach to identifying reports of scientifically rigorous clinical research. Further work is needed to optimize the deep learning model and to assess generalizability to other areas, such as diagnosis, etiology, and prognosis. ©Guilherme Del Fiol, Matthew Michelson, Alfonso Iorio, Chris Cotoi, R Brian Haynes. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 25.06.2018.

  5. Long-term behavioral outcomes after attendance at a secondary prevention clinic for cardiac patients.

    PubMed

    Worcester, Marian Una Christine; Stojcevski, Zlatko; Murphy, Barbara; Goble, Alan James

    2003-01-01

    Secondary prevention interventions, including hospital clinics, can help patients improve their risk factors and lifestyles after an acute cardiac event. This study aimed to investigate the long-term behavioral outcomes of attending and nonattending patients consecutively enrolled in a trial of a family-based clinic providing screening, advice, and support 3 months after hospital admission. The study also aimed to identify predictors of long-term smoking status, dietary habit, and physical activity. Semistructured interviews were conducted an average of 30 months after the acute cardiac event with 83 of the 103 nonattending patients and a random sample of 96 patients who had attended the clinic. Behavioral outcomes were investigated, and self-reported risk factors at the time of the acute illness were documented. The patients who had attended the clinic were significantly more likely than nonattenders to report positive dietary changes and, among former smokers, successful cessation of smoking. Furthermore, they reported being more physically active than nonattenders. Using logistic regression, clinic attendance was identified as a significant and independent predictor of all three outcomes. The results of this observational study suggest that attendance at a secondary prevention clinic facilitates maintenance of improved long-term health behaviors, although this finding is based on self-report. Factors possibly responsible for favorable outcomes include strong physician advice and support from a multidisciplinary team of health professionals. Furthermore, the timing of the intervention may have been appropriate for enrollment in a secondary prevention clinic.

  6. Microbiological investigation and clinical significance of Corynebacterium spp. in respiratory specimens.

    PubMed

    Nhan, Tu-Xuan; Parienti, Jean-Jacques; Badiou, Guillaume; Leclercq, Roland; Cattoir, Vincent

    2012-11-01

    The purpose of this retrospective study was to evaluate the pathogenic role of Corynebacterium species in lower respiratory tract infections as well as their routine laboratory investigation. From April 2007 to August 2009, 27 clinical isolates were significantly recovered from respiratory specimens of 27 different patients clinically suspected of having lower respiratory tract infections. The average age of patients was 65 years, while 22 (81%) patients presented at least 1 predisposing condition. Of the 27 patients, 15 (56%) were classified as infected according to Centers for Disease Control and Prevention/National Healthcare Safety Network criteria, with 93% of infections being hospital acquired. All isolates were accurately identified to the species level using molecular methods (i.e., 17 Corynebacterium pseudodiphtheriticum, 7 Corynebacterium striatum, and 3 Corynebacterium accolens), whereas phenotypic methods remained frequently unreliable for identifying C. striatum and C. accolens strains. All tested isolates were susceptible to amoxicillin, imipenem, vancomycin, linezolid, and tigecycline, whereas most of them were resistant to erythromycin. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Detecting Eating Psychopathology in Female Athletes by Asking About Exercise: Use of the Compulsive Exercise Test.

    PubMed

    Plateau, Carolyn R; Arcelus, Jon; Meyer, Caroline

    2017-11-01

    The present study assessed the suitability of the Compulsive Exercise Test (athlete version; CET-A) for identifying female athletes with clinically significant features related to or comparable with eating psychopathology. Three hundred and sixty-one female athletes (including 12 with a clinically diagnosed eating disorder) completed the Eating Disorders Examination Questionnaire and the CET-A. Receiver operating curve analysis was employed to identify a cut-off value on the CET-A, which could indicate clinically significant features related to or comparable with eating psychopathology among female athletes. The analysis demonstrated that a CET-A score of 10 successfully discriminated female athletes with a current eating disorder. The results suggest that the CET-A may be a suitable tool for detecting eating psychopathology in female athletes. Additional longitudinal research is needed to evaluate the predictive value of the CET-A. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

  8. Optical Magnetic Induction Tomography of the Heart

    NASA Astrophysics Data System (ADS)

    Marmugi, Luca; Renzoni, Ferruccio

    2016-04-01

    Atrial Fibrillation (AF) affects a significant fraction of the ageing population, causing a high level of morbidity and mortality. Despite its significance, the causes of AF are still not uniquely identified. This, combined with the lack of precise diagnostic and guiding tools, makes the clinical treatment of AF sub-optimal. We identify magnetic induction tomography as the most promising technique for the investigation of the causes of fibrillation and for its clinical practice. We therefore propose a novel optical instrument based on optical atomic magnetometers, fulfilling the requirements for diagnostic mapping of the heart’s conductivity. The feasibility of the device is here discussed in view of the final application. Thanks to the potential of atomic magnetometers for miniaturisation and extreme sensitivity at room temperature, a new generation of compact and non-invasive diagnostic instrumentation, with both bedside and intra-operative operation capability, is envisioned. Possible scenarios both in clinical practice and biomedical research are then discussed. The flexibility of the system makes it promising also for application in other fields, such as neurology and oncology.

  9. The Burn Wound Microenvironment

    PubMed Central

    Rose, Lloyd F.; Chan, Rodney K.

    2016-01-01

    Significance: While the survival rate of the severely burned patient has improved significantly, relatively little progress has been made in treatment or prevention of burn-induced long-term sequelae, such as contraction and fibrosis. Recent Advances: Our knowledge of the molecular pathways involved in burn wounds has increased dramatically, and technological advances now allow large-scale genomic studies, providing a global view of wound healing processes. Critical Issues: Translating findings from a large number of in vitro and preclinical animal studies into clinical practice represents a gap in our understanding, and the failures of a number of clinical trials suggest that targeting single pathways or cytokines may not be the best approach. Significant opportunities for improvement exist. Future Directions: Study of the underlying molecular influences of burn wound healing progression will undoubtedly continue as an active research focus. Increasing our knowledge of these processes will identify additional therapeutic targets, supporting informed clinical studies that translate into clinical relevance and practice. PMID:26989577

  10. Pharmacist consultations in general practice clinics: the Pharmacists in Practice Study (PIPS).

    PubMed

    Tan, Edwin C K; Stewart, Kay; Elliott, Rohan A; George, Johnson

    2014-01-01

    Medication-related problems (MRPs) are a concern in primary care settings. Pharmacists based in the community or community pharmacies are able to identify, resolve and prevent MRPs; however, the lack of a formal partnership with physicians and poor access to patients' medical records are limitations. In Australia, delivery of pharmacist services within general practice clinics is rare. To evaluate the effectiveness of consultations by pharmacists based within primary care medical practices. A prospective, before-after intervention study was conducted at two primary health care (general practice) clinics in Melbourne, Australia. Participants were clinic patients who had risk-factors for MRPs (e.g. polypharmacy). Patients received a consultation with the pharmacist in a private consulting room at the clinic or in their home. The pharmacist reviewed the patient's medication regimen and adherence, with full access to their medical record, provided patient education, and produced a report for the general practitioner. The primary outcome was the number of MRPs identified by the pharmacist, and the number that remained unresolved 6 months after the pharmacist consultation. Secondary outcomes included medication adherence, health service use, and patient satisfaction. Eighty-two patients were recruited and 62 (75.6%) completed the study. The median number of MRPs per patient identified by the practice pharmacist was 2 (interquartile range [IQR] 1, 4). Six months after review, this fell to 0 (IQR 0, 1), P < 0.001. The proportion of patients who were adherent to their medications improved significantly, according to both the Morisky (44.1% versus 62.7%, P = 0.023) and the Tool for Adherence Behaviour Screening (TABS) (35.6% versus 57.6%, P = 0.019) scales. There was no significant effect on health service use. Patients were highly satisfied with the pharmacist consultations. Consultations undertaken by pharmacists located within primary health care clinics were effective in identifying and resolving MRPs. The consultations were well received by patients and were associated with improvements in medication adherence. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. A Systematic Review and Appraisal of Clinical Practice Guidelines for Musculoskeletal Soft Tissue Injuries and Conditions.

    PubMed

    Pincus, Daniel; Kuhn, John E; Sheth, Ujash; Rizzone, Katie; Colbenson, Kristi; Dwyer, Tim; Karpinos, Ashley; Marks, Paul H; Wasserstein, David

    2017-05-01

    Clinical practice guidelines (CPGs) are published by several sports medicine institutions. A systematic evaluation can help identify the highest quality CPGs for clinical use and identify any deficiencies that remain. To identify and appraise CPGs relevant to clinical sports medicine professionals. Systematic review. Predetermined selection criteria were utilized by 2 reviewers who independently identified published CPGs before January 1, 2014. CPGs were excluded if they focused on injured workers, radiological criteria, medical pathology, or the axial skeleton (back/neck). The remaining guidelines were scored by 6 reviewers with different clinical backgrounds using the Appraisal of Guidelines for Research and Evaluation II (AGREE II). Scores lower than 50% indicated deficiency. Scores were also stratified by the publishing institution and anatomic location and compared using Kruskal-Wallis tests. The Spearman correlation coefficient was used to assess the range of interobserver agreement between the evaluators. Seventeen CPGs met the inclusion criteria. The majority of guidelines pertained to the knee, ankle, or shoulder. Interobserver agreement was strong ( r = 0.548-0.740), and mean total scores between nonsurgical (107.8) and surgical evaluators (109.3) were not statistically different. Overall guideline quality was variable but not deficient for 16 of 17 guidelines (>50%), except regarding clinical "applicability" and "editorial independence." No difference was found between CPGs of the knee, shoulder, foot/ankle, or chronic conditions. However, CPG publishing institutions had significantly different scores; the American Academy of Orthopaedic Surgeons (AAOS) guidelines scored significantly higher (141.4) than the total mean score (108.0). The overall quality of sports medicine CPGs was variable but generally not deficient, except regarding applicability and editorial independence. Bias through poor editorial independence is a concern. To improve future guideline quality, authors should pay particular attention to these areas and use existing highest quality guidelines, or the AGREE II instrument, as templates. CPGs dedicated to anatomic areas other than the knee, ankle, and shoulder are needed.

  12. Gene Expression Changes in Cervical Squamous Cell Carcinoma After Initiation of Chemoradiation and Correlation With Clinical Outcome

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

    Klopp, Ann H.; Jhingran, Anuja; Ramdas, Latha

    2008-05-01

    Purpose: The purpose of this study was to investigate early gene expression changes after chemoradiation in a human solid tumor, allowing identification of chemoradiation-induced gene expression changes in the tumor as well as the tumor microenvironment. In addition we aimed to identify a gene expression profile that was associated with clinical outcome. Methods and Materials: Microarray experiments were performed on cervical cancer specimens obtained before and 48 h after chemoradiation from 12 patients with Stage IB2 to IIIB squamous cell carcinoma of the cervix treated between April 2001 and August 2002. Results: A total of 262 genes were identified thatmore » were significantly changed after chemoradiation. Genes involved in DNA repair were identified including DDB2, ERCC4, GADD45A, and XPC. In addition, significantly regulated cell-to-cell signaling pathways included insulin-like growth factor-1 (IGF-1), interferon, and vascular endothelial growth factor signaling. At a median follow-up of 41 months, 5 of 12 patients had experienced either local or distant failure. Supervised clustering analysis identified a 58-gene set from the pretreatment samples that were differentially expressed between patients with and without recurrence. Genes involved in integrin signaling and apoptosis pathways were identified in this gene set. Immortalization-upregulated protein (IMUP), IGF-2, and ARHD had particularly marked differences in expression between patients with and without recurrence. Conclusions: Genetic profiling identified genes regulated by chemoradiation including DNA damage and cell-to-cell signaling pathways. Genes associated with recurrence were identified that will require validation in an independent patient data set to determine whether the 58-gene set associated with clinical outcome could be useful as a prognostic assay.« less

  13. A prospective observational study to assess the diagnostic accuracy of clinical decision rules for children presenting to emergency departments after head injuries (protocol): the Australasian Paediatric Head Injury Rules Study (APHIRST).

    PubMed

    Babl, Franz E; Lyttle, Mark D; Bressan, Silvia; Borland, Meredith; Phillips, Natalie; Kochar, Amit; Dalziel, Stuart R; Dalton, Sarah; Cheek, John A; Furyk, Jeremy; Gilhotra, Yuri; Neutze, Jocelyn; Ward, Brenton; Donath, Susan; Jachno, Kim; Crowe, Louise; Williams, Amanda; Oakley, Ed

    2014-06-13

    Head injuries in children are responsible for a large number of emergency department visits. Failure to identify a clinically significant intracranial injury in a timely fashion may result in long term neurodisability and death. Whilst cranial computed tomography (CT) provides rapid and definitive identification of intracranial injuries, it is resource intensive and associated with radiation induced cancer. Evidence based head injury clinical decision rules have been derived to aid physicians in identifying patients at risk of having a clinically significant intracranial injury. Three rules have been identified as being of high quality and accuracy: the Canadian Assessment of Tomography for Childhood Head Injury (CATCH) from Canada, the Children's Head Injury Algorithm for the Prediction of Important Clinical Events (CHALICE) from the UK, and the prediction rule for the identification of children at very low risk of clinically important traumatic brain injury developed by the Pediatric Emergency Care Applied Research Network (PECARN) from the USA. This study aims to prospectively validate and compare the performance accuracy of these three clinical decision rules when applied outside the derivation setting. This study is a prospective observational study of children aged 0 to less than 18 years presenting to 10 emergency departments within the Paediatric Research in Emergency Departments International Collaborative (PREDICT) research network in Australia and New Zealand after head injuries of any severity. Predictor variables identified in CATCH, CHALICE and PECARN clinical decision rules will be collected. Patients will be managed as per the treating clinicians at the participating hospitals. All patients not undergoing cranial CT will receive a follow up call 14 to 90 days after the injury. Outcome data collected will include results of cranial CTs (if performed) and details of admission, intubation, neurosurgery and death. The performance accuracy of each of the rules will be assessed using rule specific outcomes and inclusion and exclusion criteria. This study will allow the simultaneous comparative application and validation of three major paediatric head injury clinical decision rules outside their derivation setting. The study is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR)- ACTRN12614000463673 (registered 2 May 2014).

  14. Prevalence and clinical correlates of explosive outbursts in Tourette Syndrome

    PubMed Central

    Chen, Kevin; Budman, Cathy L.; Herrera, Luis Diego; Witkin, Joanna E.; Weiss, Nicholas T.; Lowe, Thomas L.; Freimer, Nelson B.; Reus, Victor I.; Mathews, Carol A.

    2012-01-01

    The aim of this study was to examine the prevalence and clinical correlates of explosive outbursts in two large samples of individuals with TS, including one collected primarily from non-clinical sources. Participants included 218 TS-affected individuals who were part of a genetic study (N=104 from Costa Rica (CR) and N=114 from the US). The relationship between explosive outbursts and comorbid attention deficit hyperactivity disorder (ADHD), obsessive compulsive disorder (OCD), tic severity, and prenatal and perinatal complications were examined using regression analyses. Twenty percent of participants had explosive outbursts, with no significant differences in prevalence between the CR (non-clinical) and the US (primarily clinical) samples. In the overall sample, ADHD, greater tic severity, and lower age of tic onset were strongly associated with explosive outbursts. ADHD, prenatal exposure to tobacco, and male gender were significantly associated with explosive outbursts in the US sample. Lower age of onset and greater severity of tics were significantly associated with explosive outbursts in the CR sample. This study confirms previous studies that suggest that clinically significant explosive outbursts are common in TS and associated with ADHD and tic severity. An additional potential risk factor, prenatal exposure to tobacco, was also identified. PMID:23040794

  15. Clinical Features and Risk Factors of Skeletal-Related Events in Genitourinary Cancer Patients with Bone Metastasis: A Retrospective Analysis of Prostate Cancer, Renal Cell Carcinoma, and Urothelial Carcinoma.

    PubMed

    Owari, Takuya; Miyake, Makito; Nakai, Yasushi; Morizawa, Yosuke; Itami, Yoshitaka; Hori, Shunta; Anai, Satoshi; Tanaka, Nobumichi; Fujimoto, Kiyohide

    2018-06-06

    The objective of the present study was to report the incidence of skeletal-related events (SREs) and identify risk factors for SREs in patients with genitourinary cancer with newly diagnosed bone metastasis. This retrospective study included 180 patients with bone metastasis from prostate cancer (PCa; n = 111), renal cell carcinoma (RCC; n = 43), and urothelial carcinoma (UC; n = 26). Clinical factors at the time of diagnosis of bone metastasis were evaluated with Cox proportional hazards regression analysis to identify independent risk factors for SREs. During follow-up, 29 (26%) patients with PCa, 30 (70%) with RCC, and 15 (58%) with UC developed SREs. Treatment with bone-modifying agents (BMAs) before the development of SREs and within 6 months from the diagnosis of bone metastasis significantly delayed the time to first SRE as compared to nonuse of BMAs. Multivariate analysis identified type of primary cancer (PCa vs. RCC, PCa vs. UC), performance status, and bone pain as significant independent predictive risk factors for SREs. Treatment with BMAs significantly delayed the development of first SREs. The identified predictors of SREs might be useful to select patients who would benefit most from early treatment with BMAs. © 2018 S. Karger AG, Basel.

  16. The effect of electronic monitoring feedback on medication adherence and clinical outcomes: A systematic review

    PubMed Central

    van den Ende, Cornelia H. M.; Houterman, Anne E. J.; Heemskerk, Charlotte P. M.; van Dulmen, Sandra; van den Bemt, Bart J. F.

    2017-01-01

    Objective This study aims to assess the efficacy of Electronic Monitoring Feedback (EMF) as an intervention to improve medication adherence (i.e. dose- or full adherence) and clinical outcomes in adult patients. Methods A systematic search was performed in Medline, EMBASE, PsycINFO and Web of Science and reported according to the PRISMA guidelines. Randomised controlled trials (RCTs) comparing EMF with usual care were identified to systematically summarise the evidence for use of EMF in improving medication adherence and clinical outcomes. The GRADE approach was used to assess the quality of the body of evidence. Results Of 9,993 initially-identified studies, ten studies (four of high-quality and six of low-quality) were included. The sample size of the studies included varied from 18 to 205 patients. Four of the six studies (66.7%) reported a significant positive effect of EMF on mean dose adherence levels, whereas a significant positive effect of EMF on mean full adherence levels was found in all of the included studies (100%, five out of five of the studies included). A significant positive effect of EMF on clinical outcomes was reported in one of the seven studies included. The overall effect of EMF on mean dose- and full adherence was positive and the overall effect of EMF on clinical outcomes was inconclusive. Conclusion Considering the positive effect of EMF on medication adherence, EMF might be a promising intervention to enhance medication adherence. However, the effect of EMF on clinical outcomes was inconclusive. Prior to implementing EMF in clinical practice, future research with high-quality studies (e.g. adequate sample sizes, follow-up periods and no interfering co-interventions) is required to examine the (long-term) efficacy of EMF. PMID:28991903

  17. The effect of electronic monitoring feedback on medication adherence and clinical outcomes: A systematic review.

    PubMed

    van Heuckelum, Milou; van den Ende, Cornelia H M; Houterman, Anne E J; Heemskerk, Charlotte P M; van Dulmen, Sandra; van den Bemt, Bart J F

    2017-01-01

    This study aims to assess the efficacy of Electronic Monitoring Feedback (EMF) as an intervention to improve medication adherence (i.e. dose- or full adherence) and clinical outcomes in adult patients. A systematic search was performed in Medline, EMBASE, PsycINFO and Web of Science and reported according to the PRISMA guidelines. Randomised controlled trials (RCTs) comparing EMF with usual care were identified to systematically summarise the evidence for use of EMF in improving medication adherence and clinical outcomes. The GRADE approach was used to assess the quality of the body of evidence. Of 9,993 initially-identified studies, ten studies (four of high-quality and six of low-quality) were included. The sample size of the studies included varied from 18 to 205 patients. Four of the six studies (66.7%) reported a significant positive effect of EMF on mean dose adherence levels, whereas a significant positive effect of EMF on mean full adherence levels was found in all of the included studies (100%, five out of five of the studies included). A significant positive effect of EMF on clinical outcomes was reported in one of the seven studies included. The overall effect of EMF on mean dose- and full adherence was positive and the overall effect of EMF on clinical outcomes was inconclusive. Considering the positive effect of EMF on medication adherence, EMF might be a promising intervention to enhance medication adherence. However, the effect of EMF on clinical outcomes was inconclusive. Prior to implementing EMF in clinical practice, future research with high-quality studies (e.g. adequate sample sizes, follow-up periods and no interfering co-interventions) is required to examine the (long-term) efficacy of EMF.

  18. Does Quality of Radiotherapy Predict Outcomes of Multicentre Cooperative Group Trials? A Literature Review

    PubMed Central

    Fairchild, Alysa; Straube, William; Laurie, Fran; Followill, David

    2013-01-01

    Central review of radiotherapy (RT) delivery within multicentre clinical trials was initiated in the early 1970’s in the USA. Early quality assurance (QA) publications often focused on metrics related to process, logistics and timing. Our objective was to review the available evidence supporting correlation of RT quality with clinical outcomes within cooperative group trials. Medline search was performed to identify multicentre studies which described central subjective assessment of RT protocol compliance (quality). Data abstracted included method of central review, definition of deviations, and clinical outcomes. Seventeen multicentre studies (1980–2012) were identified, plus one Patterns of Care Study. Disease sites were hematologic, head and neck, lung, breast and pancreas. Between 0% and 97% of treatment plans received an overall grade of acceptable. In seven trials, failure rates were significantly higher after inadequate versus adequate RT. 5/9 and 2/5 trials reported significantly worse overall and progression-free survival after poor quality RT, respectively. One reported a significant correlation and two reported non-significant trends towards increased toxicity with non-compliant RT. Although more data are required, protocol-compliant RT may decrease failure rates and increase overall survival and likely contributes to the ability of collected data to answer the central trial question. PMID:23683829

  19. An integrated, ethically driven environmental model of clinical decision making in emergency settings.

    PubMed

    Wolf, Lisa

    2013-02-01

    To explore the relationship between multiple variables within a model of critical thinking and moral reasoning. A quantitative descriptive correlational design using a purposive sample of 200 emergency nurses. Measured variables were accuracy in clinical decision-making, moral reasoning, perceived care environment, and demographics. Analysis was by bivariate correlation using Pearson's product-moment correlation coefficients, chi square and multiple linear regression analysis. The elements as identified in the integrated ethically-driven environmental model of clinical decision-making (IEDEM-CD) corrected depict moral reasoning and environment of care as factors significantly affecting accuracy in decision-making. The integrated, ethically driven environmental model of clinical decision making is a framework useful for predicting clinical decision making accuracy for emergency nurses in practice, with further implications in education, research and policy. A diagnostic and therapeutic framework for identifying and remediating individual and environmental challenges to accurate clinical decision making. © 2012, The Author. International Journal of Nursing Knowledge © 2012, NANDA International.

  20. Robotic Enucleation for Benign or Borderline Tumours of the Pancreas: A Retrospective Analysis and Comparison from a High-Volume Centre in Asia.

    PubMed

    Jin, Jia-Bin; Qin, Kai; Li, Hua; Wu, Zhi-Chong; Zhan, Qian; Deng, Xia-Xing; Chen, Hao; Shen, Bai-Yong; Peng, Cheng-Hong; Li, Hong-Wei

    2016-12-01

    Enucleation is increasingly performed for benign or borderline tumours of the pancreas because it is a parenchyma-sparing and less invasive procedure compared to conventional pancreatectomy, which reduces the risk of exocrine and endocrine insufficiency. This study retrospectively evaluated and compared the pre-, intra-, and post-operative clinical characteristics after open and robotic approaches for pancreatic enucleation. Fifty-six cases of enucleation for benign or borderline tumours of the pancreas treated from March 2010 to July 2015 were identified by a retrospective search. These included 25 patients who underwent an open approach and 31 patients who underwent a robotic approach. The clinical characteristics were extracted and compared. The two groups had a similar location and pathology of the tumour. The robotic group had a significantly shorter operation time and significantly less blood loss than the open group. The rates of clinical pancreatic fistula (PF) formation and major complications were similar. The robotic approach could be applied for a tumour on the right side of the pancreas without increasing the incidence of clinical PF or other major complications. The patients with clinical PF had a significantly shorter distance between the lesion and the main pancreatic duct (MPD). Robotic enucleation appears to be a feasible and safe approach for benign or borderline tumours of the pancreas and was associated with similarly favourable surgical outcomes as the open approach. Identifying and avoiding the MPD is an important step during enucleation.

  1. 'BeAWARE': supporting non-clinical staff within general practice to promptly identify patients presenting with warning signs of heart attack or stroke.

    PubMed

    Poulter, Christopher; Stewart, Michelle; Fitzpatrick, Cliona; Keech, Wendy; Stavreski, Bill; Grenfell, Robert

    2014-06-01

    General practice requires systems to deal with patients presenting with urgent needs. BeAWARE was developed to support non-clinical staff to promptly identify patients with symptoms of heart attack or stroke. Data were collected from May 2012 to December 2012 on participants completing the BeAWARE learning module, including pre- and post-assessments on knowledge, confidence and intended action. From May 2012 to December 2012, 1865 participants completed the module. There were significant increases in recall of heart attack and stroke symptoms among non-clinical participants, including chest tightness (23.4-48.7%, P DISCUSSION: BeAWARE fulfils a practice gap in patient safety by improving non-clinical staff's knowledge, confidence and intended action in response to patients presenting with heart attack or stroke warning signs.

  2. Clinical significance of coryneform Gram-positive rods from blood identified by MALDI-TOF mass spectrometry and their susceptibility profiles - a retrospective chart review.

    PubMed

    Mushtaq, Ammara; Chen, Derrick J; Strand, Gregory J; Dylla, Brenda L; Cole, Nicolynn C; Mandrekar, Jayawant; Patel, Robin

    2016-07-01

    With the advent of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), most Gram-positive rods (GPRs) are readily identified; however, their clinical relevance in blood cultures remains unclear. Herein, we assessed the clinical significance of GPRs isolated from blood and identified in the era of MALDI-TOF MS. A retrospective chart review of patients presenting to the Mayo Clinic, Rochester, MN, from January 1, 2013, to October 13, 2015, was performed. Any episode of a positive blood culture for a GPR was included. We assessed the number of bottles positive for a given isolate, time to positivity of blood cultures, patient age, medical history, interpretation of culture results by the healthcare team and whether infectious diseases consultation was obtained. We also evaluated the susceptibility profiles of a larger collection of GPRs tested in the clinical microbiology laboratory of the Mayo Clinic, Rochester, MN from January 1, 2013, to October 31, 2015. There were a total of 246 GPRs isolated from the blood of 181 patients during the study period. 56% (n = 101) were deemed contaminants by the healthcare team and were not treated; 33% (n = 59) were clinically determined to represent true bacteremia and were treated; and 8% (n = 14) were considered of uncertain significance, with patients prescribed treatment regardless. Patient characteristics associated with an isolate being treated on univariate analysis included younger age (P = 0.02), identification to the species level (P = 0.02), higher number of positive blood culture sets (P < 0.0001), lower time to positivity (P < 0.0001), immunosuppression (P = 0.03), and recommendation made by an infectious disease consultant (P = 0.0005). On multivariable analysis, infectious diseases consultation (P = 0.03), higher number of positive blood culture sets (P = 0.0005) and lower time to positivity (P = 0.03) were associated with an isolate being treated. 100, 83, 48 and 34% of GPRs were susceptible to vancomycin, meropenem, penicillin and ceftriaxone, respectively. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Reliability and Validity of the Rational Behavior Inventory with a Clinical Population.

    ERIC Educational Resources Information Center

    Shorkey, Clayton T.; Sutton-Simon, Karen

    1983-01-01

    The Rational Behavior Inventory and other scales of psychological adjustment were administered to mental health outpatients (N=75) who were receiving psychotherapy. Significant correlations were found between all measures in expected directions, and significant pre- to postscale differences identified consistently with expected effects of…

  4. Comparative Profiling of Primary Colorectal Carcinomas and Liver Metastases Identifies LEF1 as a Prognostic Biomarker

    PubMed Central

    Lin, Albert Y.; Chua, Mei-Sze; Choi, Yoon-La; Yeh, William; Kim, Young H.; Azzi, Raymond; Adams, Gregg A.; Sainani, Kristin; van de Rijn, Matt; So, Samuel K.; Pollack, Jonathan R.

    2011-01-01

    Purpose We sought to identify genes of clinical significance to predict survival and the risk for colorectal liver metastasis (CLM), the most common site of metastasis from colorectal cancer (CRC). Patients and Methods We profiled gene expression in 31 specimens from primary CRC and 32 unmatched specimens of CLM, and performed Significance Analysis of Microarrays (SAM) to identify genes differentially expressed between these two groups. To characterize the clinical relevance of two highly-ranked differentially-expressed genes, we analyzed the expression of secreted phosphoprotein 1 (SPP1 or osteopontin) and lymphoid enhancer factor-1 (LEF1) by immunohistochemistry using a tissue microarray (TMA) representing an independent set of 154 patients with primary CRC. Results Supervised analysis using SAM identified 963 genes with significantly higher expression in CLM compared to primary CRC, with a false discovery rate of <0.5%. TMA analysis showed SPP1 and LEF1 protein overexpression in 60% and 44% of CRC cases, respectively. Subsequent occurrence of CLM was significantly correlated with the overexpression of LEF1 (chi-square p = 0.042), but not SPP1 (p = 0.14). Kaplan Meier analysis revealed significantly worse survival in patients with overexpression of LEF1 (p<0.01), but not SPP1 (p = 0.11). Both univariate and multivariate analyses identified stage (p<0.0001) and LEF1 overexpression (p<0.05) as important prognostic markers, but not tumor grade or SPP1. Conclusion Among genes differentially expressed between CLM and primary CRC, we demonstrate overexpression of LEF1 in primary CRC to be a prognostic factor for poor survival and increased risk for liver metastasis. PMID:21383983

  5. An Overview of the Evidence and Mechanisms of Herb–Drug Interactions

    PubMed Central

    Fasinu, Pius S.; Bouic, Patrick J.; Rosenkranz, Bernd

    2012-01-01

    Despite the lack of sufficient information on the safety of herbal products, their use as alternative and/or complementary medicine is globally popular. There is also an increasing interest in medicinal herbs as precursor for pharmacological actives. Of serious concern is the concurrent consumption of herbal products and conventional drugs. Herb–drug interaction (HDI) is the single most important clinical consequence of this practice. Using a structured assessment procedure, the evidence of HDI presents with varying degree of clinical significance. While the potential for HDI for a number of herbal products is inferred from non-human studies, certain HDIs are well established through human studies and documented case reports. Various mechanisms of pharmacokinetic HDI have been identified and include the alteration in the gastrointestinal functions with consequent effects on drug absorption; induction and inhibition of metabolic enzymes and transport proteins; and alteration of renal excretion of drugs and their metabolites. Due to the intrinsic pharmacologic properties of phytochemicals, pharmacodynamic HDIs are also known to occur. The effects could be synergistic, additive, and/or antagonistic. Poor reporting on the part of patients and the inability to promptly identify HDI by health providers are identified as major factors limiting the extensive compilation of clinically relevant HDIs. A general overview and the significance of pharmacokinetic and pharmacodynamic HDI are provided, detailing basic mechanism, and nature of evidence available. An increased level of awareness of HDI is necessary among health professionals and drug discovery scientists. With the increasing number of plant-sourced pharmacological actives, the potential for HDI should always be assessed in the non-clinical safety assessment phase of drug development process. More clinically relevant research is also required in this area as current information on HDI is insufficient for clinical applications. PMID:22557968

  6. Impact of postgraduate training on communication skills teaching: a controlled study.

    PubMed

    Junod Perron, Noelle; Nendaz, Mathieu; Louis-Simonet, Martine; Sommer, Johanna; Gut, Anne; Cerutti, Bernard; van der Vleuten, Cees P; Dolmans, Diana

    2014-04-14

    Observation of performance followed by feedback is the key to good teaching of communication skills in clinical practice. The fact that it occurs rarely is probably due to clinical supervisors' perceived lack of competence to identify communication skills and give effective feedback. We evaluated the impact of a faculty development programme on communication skills teaching on clinical supervisors' ability to identify residents' good and poor communication skills and to discuss them interactively during feedback. We conducted a pre-post controlled study in which clinical supervisors took part to a faculty development program on teaching communication skills in clinical practice. Outcome measures were the number and type of residents' communication skills identified by supervisors in three videotaped simulated resident-patient encounters and the number and type of communication skills discussed interactively with residents during three feedback sessions. 48 clinical supervisors (28 intervention group; 20 control group) participated. After the intervention, the number and type of communication skills identified did not differ between both groups. There was substantial heterogeneity in the number and type of communication skills identified. However, trained participants engaged in interactive discussions with residents on a significantly higher number of communication items (effect sizes 0.53 to 1.77); communication skills items discussed interactively included both structural and patient-centered elements that were considered important to be observed by expert teachers. The faculty development programme did not increase the number of communication skills recognised by supervisors but was effective in increasing the number of communication issues discussed interactively in feedback sessions. Further research should explore the respective impact of accurate identification of communication skills and effective teaching skills on achieving more effective communication skills teaching in clinical practice.

  7. Impact of postgraduate training on communication skills teaching: a controlled study

    PubMed Central

    2014-01-01

    Background Observation of performance followed by feedback is the key to good teaching of communication skills in clinical practice. The fact that it occurs rarely is probably due to clinical supervisors’ perceived lack of competence to identify communication skills and give effective feedback. We evaluated the impact of a faculty development programme on communication skills teaching on clinical supervisors’ ability to identify residents’ good and poor communication skills and to discuss them interactively during feedback. Methods We conducted a pre-post controlled study in which clinical supervisors took part to a faculty development program on teaching communication skills in clinical practice. Outcome measures were the number and type of residents’ communication skills identified by supervisors in three videotaped simulated resident-patient encounters and the number and type of communication skills discussed interactively with residents during three feedback sessions. Results 48 clinical supervisors (28 intervention group; 20 control group) participated. After the intervention, the number and type of communication skills identified did not differ between both groups. There was substantial heterogeneity in the number and type of communication skills identified. However, trained participants engaged in interactive discussions with residents on a significantly higher number of communication items (effect sizes 0.53 to 1.77); communication skills items discussed interactively included both structural and patient-centered elements that were considered important to be observed by expert teachers. Conclusions The faculty development programme did not increase the number of communication skills recognised by supervisors but was effective in increasing the number of communication issues discussed interactively in feedback sessions. Further research should explore the respective impact of accurate identification of communication skills and effective teaching skills on achieving more effective communication skills teaching in clinical practice. PMID:24731477

  8. Dynamic transcriptional signatures and network responses for clinical symptoms in influenza-infected human subjects using systems biology approaches.

    PubMed

    Linel, Patrice; Wu, Shuang; Deng, Nan; Wu, Hulin

    2014-10-01

    Recent studies demonstrate that human blood transcriptional signatures may be used to support diagnosis and clinical decisions for acute respiratory viral infections such as influenza. In this article, we propose to use a newly developed systems biology approach for time course gene expression data to identify significant dynamically response genes and dynamic gene network responses to viral infection. We illustrate the methodological pipeline by reanalyzing the time course gene expression data from a study with healthy human subjects challenged by live influenza virus. We observed clear differences in the number of significant dynamic response genes (DRGs) between the symptomatic and asymptomatic subjects and also identified DRG signatures for symptomatic subjects with influenza infection. The 505 common DRGs shared by the symptomatic subjects have high consistency with the signature genes for predicting viral infection identified in previous works. The temporal response patterns and network response features were carefully analyzed and investigated.

  9. Prevalence of lymphoplasmacytic synovitis in dogs with naturally occurring cranial cruciate ligament rupture.

    PubMed

    Erne, Jay B; Goring, Robert L; Kennedy, Fidelma A; Schoenborn, William C

    2009-08-15

    To determine the prevalence of lymphoplasmacytic synovitis (LPS) in dogs with naturally occurring cranial cruciate ligament (CCL) rupture and compare clinical, radiographic, cytologic, and histologic findings in dogs with and without LPS. Cross-sectional study. 110 dogs with naturally occurring CCL rupture. Histologic examination of synovial biopsy specimens obtained at the time of surgical treatment was used to identify dogs with LPS. Clinical, radiographic, cytologic, and histologic findings were compared between dogs with and without LPS. 56 (51%) dogs had histologic evidence of LPS. There were no significant differences in age, body weight, duration of lameness, severity of lameness, severity of radiographic signs of degenerative joint disease, extent of CCL rupture (partial vs complete), or gross appearance of the medial meniscus between dogs with and without LPS. Mean tibial plateau angle was significantly lower in dogs with LPS than in dogs without LPS, and dogs with LPS were significantly more likely to have neutrophils in their synovial fluid. Lymphocytes were seen in synovial fluid from a single dog with LPS. Results suggested that LPS was common in dogs with naturally occurring CCL rupture. However, only minor clinical, radiographic, cytologic, and histologic differences were identified between dogs with and without LPS.

  10. Boric acid for recurrent vulvovaginal candidiasis: the clinical evidence.

    PubMed

    Iavazzo, Christos; Gkegkes, Ioannis D; Zarkada, Ioanna M; Falagas, Matthew E

    2011-08-01

    Recurrent vulvovaginal candidiasis (VVC) remains a challenge to manage in clinical practice. Recent epidemiologic studies indicate that non-albicans Candida spp. are more resistant to conventional antifungal treatment with azoles and are considered as causative pathogens of vulvovaginal candidiasis. We searched PubMed and Scopus for studies that reported clinical evidence on the intravaginal use of boric acid for vulvovaginal candidiasis. We identified 14 studies (2 randomized clinical trials [RCTs], 9 case series, and 4 case reports) as eligible for inclusion in this review. Boric acid was compared with nystatin, terconazole, flucytosine, itraconazole, clotrimazole, ketoconazole, fluconazole, buconazole, and miconazole; as monotherapy, boric acid was studied in 7 studies. The mycologic cure rates varied from 40% to 100% in patients treated with boric acid; 4 of the 9 included case series reported statistically significant outcomes regarding cure (both mycologic and clinical) rates. None of the included studies reported statistically significant differences in recurrence rates. Regarding the adverse effects caused by boric acid use, vaginal burning sensation (<10% of cases), water discharge during treatment, and vaginal erythema were identified in 7 studies. Our findings suggest that boric acid is a safe, alternative, economic option for women with recurrent and chronic symptoms of vaginitis when conventional treatment fails because of the involvement of non-albicans Candida spp. or azole-resistant strains.

  11. Subcortical volumetric differences between clinical stages of young people with affective and psychotic disorders.

    PubMed

    Eggins, Peta S; Hatton, Sean N; Hermens, Daniel F; Hickie, Ian B; Lagopoulos, Jim

    2018-01-30

    The aim of this study was to investigate differences in subcortical and hippocampal volumes between healthy controls, young people at an early stage of affective and psychotic disorders and those in more advanced stages, to identify markers associated with functional outcomes and illness severity. Young people presenting to youth mental health services with admixtures of depressive, manic and psychotic symptoms (n = 141), and healthy counterparts (n = 49), aged 18-25 were recruited. Participants underwent magnetic resonance imaging, clinical assessments and were rated as to their current clinical stage. Eighty-four patients were classified at the attenuated syndrome stage (Stage 1b) and 57 were classified as having discrete and persistent disorders (Stage 2+). Automated segmentation was performed using NeuroQuant® to determine volumes of subcortical and hippocampus structures which were compared between groups and correlated with clinical and functional outcomes. Compared to healthy controls, Stage 2+ patients showed significantly reduced right amygdala volumes. Whereas Stage 1b patients showed significantly reduced left caudate volumes compared to healthy controls. Smaller left caudate volume correlated with greater psychological distress and impaired functioning. This study shows a clinical application for an automated program to identify and track subcortical changes evident in young people with emerging psychopathology. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  12. A proteomic approach to identifying new drug targets (potentiating topoisomerase II poisons).

    PubMed

    Jenkins, J R

    2008-10-01

    Topoisomerase II poisons are an established part of best clinical practice for the treatment of a number of solid tumours and haematological malignancies. However, toxicity and resistance to chemotherapeutic drugs often complicate the treatment. Furthermore, topoisomerase II poisons can also induce sister chromatid exchange, chromosomal recombination and chromosome aberrations and are associated with a significant risk of secondary leukaemia. It would therefore be of great clinical benefit if the efficacy of topoisomerase II inhibitors could be enhanced without the increased toxic side effects. It is proposed that clinical agents targeting topoisomerase II can be enhanced by inhibiting proteins that modulate topoisomerase II. The aim is to identify proteins, that by the nature of their interaction with topoisomerase II, represent putative drug targets.

  13. Genetics and the Placebo Effect: the Placebome

    PubMed Central

    Hall, Kathryn T.; Loscalzo, Joseph; Kaptchuk, Ted J.

    2015-01-01

    Placebos are indispensable controls in randomized clinical trials (RCTs), and placebo responses significantly contribute to routine clinical outcomes. Recent neurophysiological studies reveal neurotransmitter pathways that mediate placebo effects. Evidence that genetic variations in these pathways can modify placebo effects raises the possibility of using genetic screening to identify placebo responders and thereby increase RCT efficacy and improve therapeutic care. Furthermore, the possibility of interaction between placebo and drug molecular pathways warrants consideration in RCT design. The study of genomic effects on placebo response, “the placebome”, is in its infancy. Here, we review evidence from placebo studies and RCTs to identify putative genes in the placebome, examine evidence for placebo-drug interactions, and discuss implications for RCTs and clinical care. PMID:25883069

  14. Escherichia fergusonii bacteremia in a diabetic patient with pancreatic cancer.

    PubMed

    Lai, Chih-Cheng; Cheng, Aristine; Huang, Yu-Tsung; Chung, Kuei-Pin; Lee, Meng-Rui; Liao, Chun-Hsing; Hsueh, Po-Ren

    2011-11-01

    Although Escherichia fergusonii has been identified for decades, it has rarely been recovered from clinical specimens and its clinical significance remains unclear. We describe a case of E. fergusonii bacteremia in a diabetic patient with pancreatic cancer. The isolate was confirmed by three commercial identification systems and 16S rRNA gene sequence analysis. The patient's clinical condition gradually improved, and repeated blood cultures were negative after antibiotic treatment with an in vitro active agent (ceftriaxone).

  15. 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 was 4.5 and during the surgery, a mean of four perforators was identified (4.5 vs. 4; mean difference 0.377; P <0.001). The color Doppler combined with the clinical examination lead to only four unnecessary explorations per 10 patients. Conclusion A combination of both the clinical tests and the color Doppler ultrasound has a higher accuracy in detecting perforator incompetence and can reduce the number of negative explorations by the rate of 16 unnecessary explorations per 10 patients.

  16. Clinical guidance of community physiotherapists regarding people with MS: professional development and continuity of care.

    PubMed

    Normann, Britt; Sørgaard, Knut W; Salvesen, Rolf; Moe, Siri

    2014-03-01

    Clinical guidance to community physiotherapists (cPTs) is an integral part of physiotherapy service offered in hospital outpatient (OP) clinics for people with multiple sclerosis (PwMS). There is currently a lack of knowledge on the significance of such guidance. The aims of this study were 1) to identify the features that cPTs perceive to be significant in clinical guidance and 2) how this guidance may affect the cPTs' subsequent treatment of PwMS. A phenomenological-hermeneutical framework was selected, and qualitative research interviews were performed and complemented with non-participating observations of a strategic sample of nine cPTs who received clinical guidance for their patients. The interviews were recorded and transcribed, and content analysis was conducted by using systematic text condensation, using theories of practice knowledge as analytic perspectives. The results indicate that cPTs identify participation in authentic movement analysis of a familiar patient as significant for professional development. Vital features are evaluation of the interplay between body parts, exploration of improvement of movement embedded in the OP clinic physiotherapist's explanations, followed by discussion. These elements provide access to dynamic elements in practice knowledge that are available only through first-hand experience and promote clinical reasoning through enhanced reflection during action as well as following action. Such guidance suggests direction for subsequent treatment and may enhance the continuity of care, particularly if the cPTs are experienced. Mutual information flow implementing the cPTs' perspective is requested, as are the use of plain language and supervision of the cPTs handling skills. Professional guidance for cPTs in OP clinics for PwMS should be considered when programmes aiming to develop competency in neurological physiotherapy are designed and when continuity of care for PwMS is discussed. More research regarding potential long-term impact of professional guidance in these clinics is requested. Copyright © 2013 John Wiley & Sons, Ltd.

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

    PubMed

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

    2017-01-01

    The purpose of the current study was to assess the penetrance of NRXN1 deletions. We compared the prevalence and genomic extent of NRXN1 deletions identified among 19,263 clinically referred cases to that of 15,264 controls. The burden of additional clinically relevant copy-number variations (CNVs) was used as a proxy to estimate the relative penetrance of NRXN1 deletions. We identified 41 (0.21%) previously unreported exonic NRXN1 deletions ascertained for developmental delay/intellectual disability that were significantly greater than in controls (odds ratio (OR) = 8.14; 95% confidence interval (CI): 2.91-22.72; P < 0.0001). Ten (22.7%) of these had a second clinically relevant CNV. Subjects with a deletion near the 3' end of NRXN1 were significantly more likely to have a second rare CNV than subjects with a 5' NRXN1 deletion (OR = 7.47; 95% CI: 2.36-23.61; P = 0.0006). The prevalence of intronic NRXN1 deletions was not statistically different between cases and controls (P = 0.618). The majority (63.2%) of intronic NRXN1 deletion cases had a second rare CNV at a prevalence twice as high as that for exonic NRXN1 deletion cases (P = 0.0035). The results support the importance of exons near the 5' end of NRXN1 in the expression of neurodevelopmental disorders. Intronic NRXN1 deletions do not appear to substantially increase the risk for clinical phenotypes.Genet Med 19 1, 53-61.

  18. Novel subgroups of attention-deficit/hyperactivity disorder identified by topological data analysis and their functional network modular organizations

    PubMed Central

    Kyeong, Sunghyon; Kim, Jae-Jin; Kim, Eunjoo

    2017-01-01

    Attention-deficit/hyperactivity disorder (ADHD) is a clinically heterogeneous condition and identification of clinically meaningful subgroups would open up a new window for personalized medicine. Thus, we aimed to identify new clinical phenotypes in children and adolescents with ADHD and to investigate whether neuroimaging findings validate the identified phenotypes. Neuroimaging and clinical data from 67 children with ADHD and 62 typically developing controls (TDCs) from the ADHD-200 database were selected. Clinical measures of ADHD symptoms and intelligence quotient (IQ) were used as input features into a topological data analysis (TDA) to identify ADHD subgroups within our sample. As external validators, graph theoretical measures obtained from the functional connectome were compared to address the biological meaningfulness of the identified subtypes. The TDA identified two unique subgroups of ADHD, labelled as mild symptom ADHD (mADHD) and severe symptom ADHD (sADHD). The output topology shape was repeatedly observed in the independent validation dataset. The graph theoretical analysis showed a decrease in the degree centrality and PageRank in the bilateral posterior cingulate cortex in the sADHD group compared with the TDC group. The mADHD group showed similar patterns of intra- and inter-module connectivity to the sADHD group. Relative to the TDC group, the inter-module connectivity between the default mode network and executive control network were significantly increased in the sADHD group but not in the mADHD group. Taken together, our results show that the data-driven TDA is potentially useful in identifying objective and biologically relevant disease phenotypes in children and adolescents with ADHD. PMID:28829775

  19. Identifying Victims of Abuse Using the Personality Inventory for Children: I. Applications for Adolescent Runaways.

    ERIC Educational Resources Information Center

    Rohr, Michael E.; And Others

    The physical and sexual abuse of children and adolescents has been gaining attention as a national problem of social and clinical significance. In this study a model was developed in order to identify abuse (victimization) in an adolescent population (n=52). Four scales (Adjustment, Delinquency, Family Relations, and Anxiety) of the Personality…

  20. Interpreting SF-12 mental component score: an investigation of its convergent validity with CESD-10.

    PubMed

    Yu, Doris S F; Yan, Elsie C W; Chow, Choi Kai

    2015-09-01

    To examine the convergent validity of Mental Component Scale of the Short-Form 12 (SF-12 MCS) with the Center for Epidemiologic Studies Depression Scale (CESD-10). The CESD-10 is a screening tool for probably clinically significant depression in the Chinese population. Data were obtained from a household survey carried out in Hong Kong. A two-stage stratified sampling method successfully interviewed 1795 adult subjects from 1239 households. Data on SF-12 MCS and the CESD-10 were extracted. Receiver operating characteristics (ROC) analyses were performed to examine the convergent validity of SF-12 MCS against the CESD-10 threshold for probably clinically significant depression for the younger to middle-aged, late middle-aged and older population cohorts. ROC analysis indicated the excellent convergent validity of SF-12 MCS with the CESD-10 threshold for identifying probably clinically significant depression, with the area under curve ranged from 0.81 to 0.85. The optimal cutoff scores for depression among the younger to middle age group, late middle age group and older age group were 48.1, 50.2 and 50.2, respectively, with sensitivities ranged from 77 to 83 % and specificities ranged from 73 to 78 %. Bootstrapping estimates of the mean difference indicated no significant difference in the optimal cutoff scores between these age cohorts. SF-12 is a widely adopted measure to capture the health profile of Chinese population. The study findings indicated the satisfactory performance of the SF-12 MCS in identifying probably clinical depression. Future study is warrant to examine the diagnostic validity of the SF-12 MCS by using gold standard to assess clinical depression.

  1. Altered metabolites in the plasma of autism spectrum disorder: a capillary electrophoresis time-of-flight mass spectroscopy study.

    PubMed

    Kuwabara, Hitoshi; Yamasue, Hidenori; Koike, Shinsuke; Inoue, Hideyuki; Kawakubo, Yuki; Kuroda, Miho; Takano, Yosuke; Iwashiro, Norichika; Natsubori, Tatsunobu; Aoki, Yuta; Kano, Yukiko; Kasai, Kiyoto

    2013-01-01

    Clinical diagnosis and severity of autism spectrum disorders (ASD) are determined by trained clinicians based on clinical evaluations of observed behaviors. As such, this approach is inevitably dependent on the expertise and subjective assessment of those administering the clinical evaluations. There is a need to identify objective biological markers associated with diagnosis or clinical severity of the disorder. To identify novel candidate metabolites as potential biomarkers for ASD, the current study applied capillary electrophoresis time-of-flight mass spectroscopy (CE-TOFMS) for high-throughput profiling of metabolite levels in the plasma of 25 psychotropic-naïve adult males with high-functioning ASD and 28 age-matched typically-developed control subjects. Ten ASD participants and ten age-matched controls were assigned in the first exploration set, while 15 ASD participants and 18 controls were included in the second replication set. By CE-TOFMS analysis, a total of 143 metabolites were detected in the plasma of the first set. Of these, 17 metabolites showed significantly different relative areas between the ASD participants and the controls (p<0.05). Of the 17 metabolites, we consistently found that the ASD participants had significantly high plasma levels of arginine (p = 0.024) and taurine (p = 0.018), and significantly low levels of 5-oxoproline (p<0.001) and lactic acid (p = 0.031) compared with the controls in the second sample set. Further confirmatory analysis using quantification of absolute metabolite concentrations supported the robustness of high arginine (p = 0.001) and low lactic acid (p = 0.003) in the combined sample (n = 53). The present study identified deviated plasma metabolite levels associated with oxidative stress and mitochondrial dysfunction in individuals with ASD.

  2. Prediction of transition from ultra-high risk to first-episode psychosis using a probabilistic model combining history, clinical assessment and fatty-acid biomarkers.

    PubMed

    Clark, S R; Baune, B T; Schubert, K O; Lavoie, S; Smesny, S; Rice, S M; Schäfer, M R; Benninger, F; Feucht, M; Klier, C M; McGorry, P D; Amminger, G P

    2016-09-20

    Current criteria identifying patients with ultra-high risk of psychosis (UHR) have low specificity, and less than one-third of UHR cases experience transition to psychosis within 3 years of initial assessment. We explored whether a Bayesian probabilistic multimodal model, combining baseline historical and clinical risk factors with biomarkers (oxidative stress, cell membrane fatty acids, resting quantitative electroencephalography (qEEG)), could improve this specificity. We analyzed data of a UHR cohort (n=40) with a 1-year transition rate of 28%. Positive and negative likelihood ratios were calculated for predictor variables with statistically significant receiver operating characteristic curves (ROCs), which excluded oxidative stress markers and qEEG parameters as significant predictors of transition. We clustered significant variables into historical (history of drug use), clinical (Positive and Negative Symptoms Scale positive, negative and general scores and Global Assessment of Function) and biomarker (total omega-3, nervonic acid) groups, and calculated the post-test probability of transition for each group and for group combinations using the odds ratio form of Bayes' rule. Combination of the three variable groups vastly improved the specificity of prediction (area under ROC=0.919, sensitivity=72.73%, specificity=96.43%). In this sample, our model identified over 70% of UHR patients who transitioned within 1 year, compared with 28% identified by standard UHR criteria. The model classified 77% of cases as very high or low risk (P>0.9, <0.1) based on history and clinical assessment, suggesting that a staged approach could be most efficient, reserving fatty-acid markers for 23% of cases remaining at intermediate probability following bedside interview.

  3. Altered Metabolites in the Plasma of Autism Spectrum Disorder: A Capillary Electrophoresis Time-of-Flight Mass Spectroscopy Study

    PubMed Central

    Kuwabara, Hitoshi; Yamasue, Hidenori; Koike, Shinsuke; Inoue, Hideyuki; Kawakubo, Yuki; Kuroda, Miho; Takano, Yosuke; Iwashiro, Norichika; Natsubori, Tatsunobu; Aoki, Yuta; Kano, Yukiko; Kasai, Kiyoto

    2013-01-01

    Clinical diagnosis and severity of autism spectrum disorders (ASD) are determined by trained clinicians based on clinical evaluations of observed behaviors. As such, this approach is inevitably dependent on the expertise and subjective assessment of those administering the clinical evaluations. There is a need to identify objective biological markers associated with diagnosis or clinical severity of the disorder. To identify novel candidate metabolites as potential biomarkers for ASD, the current study applied capillary electrophoresis time-of-flight mass spectroscopy (CE-TOFMS) for high-throughput profiling of metabolite levels in the plasma of 25 psychotropic-naïve adult males with high-functioning ASD and 28 age-matched typically-developed control subjects. Ten ASD participants and ten age-matched controls were assigned in the first exploration set, while 15 ASD participants and 18 controls were included in the second replication set. By CE-TOFMS analysis, a total of 143 metabolites were detected in the plasma of the first set. Of these, 17 metabolites showed significantly different relative areas between the ASD participants and the controls (p<0.05). Of the 17 metabolites, we consistently found that the ASD participants had significantly high plasma levels of arginine (p = 0.024) and taurine (p = 0.018), and significantly low levels of 5-oxoproline (p<0.001) and lactic acid (p = 0.031) compared with the controls in the second sample set. Further confirmatory analysis using quantification of absolute metabolite concentrations supported the robustness of high arginine (p = 0.001) and low lactic acid (p = 0.003) in the combined sample (n = 53). The present study identified deviated plasma metabolite levels associated with oxidative stress and mitochondrial dysfunction in individuals with ASD. PMID:24058493

  4. Can the Cancer-related Fatigue Case-definition Criteria Be Applied to Chronic Medical Illness? A Comparison between Breast Cancer and Systemic Sclerosis.

    PubMed

    Kwakkenbos, Linda; Minton, Ollie; Stone, Patrick C; Alexander, Susanna; Baron, Murray; Hudson, Marie; Thombs, Brett D

    2015-07-01

    Fatigue is a crucial determinant of quality of life across rheumatic diseases, but the lack of agreed-upon standards for identifying clinically significant fatigue hinders research and clinical management. Case definition criteria for cancer-related fatigue were proposed for inclusion in the International Classification of Diseases. The objective was to evaluate whether the cancer-related fatigue case definition performed equivalently in women with breast cancer and systemic sclerosis (SSc) and could be used to identify patients with chronic illness-related fatigue. The cancer-related fatigue interview (case definition criteria met if ≥ 5 of 9 fatigue-related symptoms present with functional impairment) was completed by 291 women with SSc and 278 women successfully treated for breast cancer. Differential item functioning was assessed with the multiple indicator multiple cause model. Items 3 (concentration) and 10 (short-term memory) were endorsed significantly less often by women with SSc compared with cancer, controlling for responses on other items. Omitting these 2 items from the case definition and requiring 4 out of the 7 remaining symptoms resulted in a similar overall prevalence of cancer-related fatigue in the cancer sample compared with the original criteria (37.4% vs 37.8%, respectively), with 97.5% of patients diagnosed identically with both definitions. Prevalence of chronic illness-related fatigue was 36.1% in SSc using 4 of 7 symptoms. The cancer-related fatigue criteria can be used equivalently to identify patients with chronic illness-related fatigue when 2 cognitive fatigue symptoms are omitted. Harmonized definitions and measurement of clinically significant fatigue will advance research and clinical management of fatigue in rheumatic diseases and other conditions.

  5. The incidence of avascular necrosis and the radiographic outcome following medial open reduction in children with developmental dysplasia of the hip: a systematic review.

    PubMed

    Gardner, R O E; Bradley, C S; Howard, A; Narayanan, U G; Wedge, J H; Kelley, S P

    2014-02-01

    The incidence of clinically significant avascular necrosis (AVN) following medial open reduction of the dislocated hip in children with developmental dysplasia of the hip (DDH) remains unknown. We performed a systematic review of the literature to identify all clinical studies reporting the results of medial open reduction surgery. A total of 14 papers reporting 734 hips met the inclusion criteria. The mean follow-up was 10.9 years (2 to 28). The rate of clinically significant AVN (types 2 to 4) was 20% (149/734). From these papers 221 hips in 174 children had sufficient information to permit more detailed analysis. The rate of AVN increased with the length of follow-up to 24% at skeletal maturity, with type 2 AVN predominating in hips after five years' follow-up. The presence of AVN resulted in a higher incidence of an unsatisfactory outcome at skeletal maturity (55% vs 20% in hips with no AVN; p < 0.001). A higher rate of AVN was identified when surgery was performed in children aged < 12 months, and when hips were immobilised in ≥ 60° of abduction post-operatively. Multivariate analysis showed that younger age at operation, need for further surgery and post-operative hip abduction of ≥ 60° increased the risk of the development of clinically significant AVN.

  6. A comparison of the clinical characteristics of women with recurrent major depression with and without suicidal symptomatology.

    PubMed

    Bi, B; Xiao, X; Zhang, H; Gao, J; Tao, M; Niu, H; Wang, Y; Wang, Q; Chen, C; Sun, N; Li, K; Fu, J; Gan, Z; Sang, W; Zhang, G; Yang, L; Tian, T; Li, Q; Yang, Q; Sun, L; Li, Ying; Rong, H; Guan, C; Zhao, X; Ye, D; Zhang, Y; Ma, Z; Li, H; He, K; Chen, J; Cai, Y; Zhou, C; Luo, Y; Wang, S; Gao, S; Liu, J; Guo, L; Guan, J; Kang, Z; Di, D; Li, Yajuan; Shi, S; Li, Yihan; Chen, Y; Flint, J; Kendler, K; Liu, Y

    2012-12-01

    The relationship between recurrent major depression (MD) in women and suicidality is complex. We investigated the extent to which patients who suffered with various forms of suicidal symptomatology can be distinguished from those subjects without such symptoms. We examined the clinical features of the worst episode in 1970 Han Chinese women with recurrent DSM-IV MD between the ages of 30 and 60 years from across China. Student's t tests, and logistic and multiple logistic regression models were used to determine the association between suicidality and other clinical features of MD. Suicidal symptomatology is significantly associated with a more severe form of MD, as indexed by both the number of episodes and number of MD symptoms. Patients reporting suicidal thoughts, plans or attempts experienced a significantly greater number of stressful life events. The depressive symptom most strongly associated with lifetime suicide attempt was feelings of worthlessness (odds ratio 4.25, 95% confidence interval 2.9-6.3). Excessive guilt, diminished concentration and impaired decision-making were also significantly associated with a suicide attempt. This study contributes to the existing literature on risk factors for suicidal symptomatology in depressed women. Identifying specific depressive symptoms and co-morbid psychiatric disorders may help improve the clinical assessment of suicide risk in depressed patients. These findings could be helpful in identifying those who need more intense treatment strategies in order to prevent suicide.

  7. Identifying and Assessing Interesting Subgroups in a Heterogeneous Population.

    PubMed

    Lee, Woojoo; Alexeyenko, Andrey; Pernemalm, Maria; Guegan, Justine; Dessen, Philippe; Lazar, Vladimir; Lehtiö, Janne; Pawitan, Yudi

    2015-01-01

    Biological heterogeneity is common in many diseases and it is often the reason for therapeutic failures. Thus, there is great interest in classifying a disease into subtypes that have clinical significance in terms of prognosis or therapy response. One of the most popular methods to uncover unrecognized subtypes is cluster analysis. However, classical clustering methods such as k-means clustering or hierarchical clustering are not guaranteed to produce clinically interesting subtypes. This could be because the main statistical variability--the basis of cluster generation--is dominated by genes not associated with the clinical phenotype of interest. Furthermore, a strong prognostic factor might be relevant for a certain subgroup but not for the whole population; thus an analysis of the whole sample may not reveal this prognostic factor. To address these problems we investigate methods to identify and assess clinically interesting subgroups in a heterogeneous population. The identification step uses a clustering algorithm and to assess significance we use a false discovery rate- (FDR-) based measure. Under the heterogeneity condition the standard FDR estimate is shown to overestimate the true FDR value, but this is remedied by an improved FDR estimation procedure. As illustrations, two real data examples from gene expression studies of lung cancer are provided.

  8. A concept mapping study evaluating the UK's first NHS generic fatigue clinic.

    PubMed

    Hackett, Katie L; Lambson, Rebecca L; Strassheim, Victoria; Gotts, Zoe; Deary, Vincent; Newton, Julia L

    2016-10-01

    Fatigue is a significant and debilitating symptom affecting 25% of the population. It occurs in those with a range of chronic diseases, can be idiopathic and in 0.2-0.4% of the UK population occurs in combination with other symptoms that together constitute chronic fatigue syndrome (CFS). Until recently, NHS clinical services only focussed upon CFS and excluded the majority of fatigued patients who did not meet the CFS diagnostic criteria. The CRESTA Fatigue interdisciplinary clinic was established in 2013 in response to this unmet need. To identify the service needs of the heterogeneous group of patients accessing the CRESTA Fatigue Clinic, to prioritize these needs, to determine whether each is being met and to plan targeted service enhancements. Using a group concept mapping approach, we objectively identified the shared understanding of service users accessing this novel clinic. NHS Clinics for Research & Service in Themed Assessment (CRESTA) Fatigue Clinic, Newcastle Upon Tyne, UK. Patients (n = 30) and referrers (n = 10) to the CRESTA Fatigue Clinic contributed towards a statement generation exercise to identify ways the clinic could support service users to improve their quality of life. Patients (n = 46) participated in the sorting and rating task where resulting statements were sorted into groups similar in meaning and rated for 'importance' and 'current success'. We mapped the needs of patients attending the CRESTA Fatigue Clinic and identified which high-priority needs were being successfully met and which were not. Multidimensional scaling and hierarchical cluster analysis depicted the following eight themed clusters from the data which related to various service-user requirements: 'clinic ethos', 'communication', 'support to self-manage', 'peer support', 'allied health services', 'telemedicine', 'written information' and 'service operation'. Service improvement targets were identified within value bivariate plots of the statements. Service development concepts were grouped into thematic clusters and prioritized for both importance and current success. The resulting concept maps depict where the CRESTA Fatigue Clinic successfully addresses issues which matter to patients and highlights areas for service enhancement. Unmet needs of patients have been identified in a rigorous service evaluation, and these are currently being addressed in collaboration with a service-user group. © 2015 The Authors. Health Expectations. Published by John Wiley & Sons Ltd.

  9. Frontotemporal dementia with the C9ORF72 hexanucleotide repeat expansion: clinical, neuroanatomical and neuropathological features

    PubMed Central

    Mahoney, Colin J.; Beck, Jon; Rohrer, Jonathan D.; Lashley, Tammaryn; Mok, Kin; Shakespeare, Tim; Yeatman, Tom; Warrington, Elizabeth K.; Schott, Jonathan M.; Fox, Nick C.; Rossor, Martin N.; Hardy, John; Collinge, John; Revesz, Tamas; Mead, Simon

    2012-01-01

    An expanded hexanucleotide repeat in the C9ORF72 gene has recently been identified as a major cause of familial frontotemporal lobar degeneration and motor neuron disease, including cases previously identified as linked to chromosome 9. Here we present a detailed retrospective clinical, neuroimaging and histopathological analysis of a C9ORF72 mutation case series in relation to other forms of genetically determined frontotemporal lobar degeneration ascertained at a specialist centre. Eighteen probands (19 cases in total) were identified, representing 35% of frontotemporal lobar degeneration cases with identified mutations, 36% of cases with clinical evidence of motor neuron disease and 7% of the entire cohort. Thirty-three per cent of these C9ORF72 cases had no identified relevant family history. Families showed wide variation in clinical onset (43–68 years) and duration (1.7–22 years). The most common presenting syndrome (comprising a half of cases) was behavioural variant frontotemporal dementia, however, there was substantial clinical heterogeneity across the C9ORF72 mutation cohort. Sixty per cent of cases developed clinical features consistent with motor neuron disease during the period of follow-up. Anxiety and agitation and memory impairment were prominent features (between a half to two-thirds of cases), and dominant parietal dysfunction was also frequent. Affected individuals showed variable magnetic resonance imaging findings; however, relative to healthy controls, the group as a whole showed extensive thinning of frontal, temporal and parietal cortices, subcortical grey matter atrophy including thalamus and cerebellum and involvement of long intrahemispheric, commissural and corticospinal tracts. The neuroimaging profile of the C9ORF72 expansion was significantly more symmetrical than progranulin mutations with significantly less temporal lobe involvement than microtubule-associated protein tau mutations. Neuropathological examination in six cases with C9ORF72 mutation from the frontotemporal lobar degeneration series identified histomorphological features consistent with either type A or B TAR DNA-binding protein-43 deposition; however, p62-positive (in excess of TAR DNA-binding protein-43 positive) neuronal cytoplasmic inclusions in hippocampus and cerebellum were a consistent feature of these cases, in contrast to the similar frequency of p62 and TAR DNA-binding protein-43 deposition in 53 control cases with frontotemporal lobar degeneration–TAR DNA-binding protein. These findings corroborate the clinical importance of the C9ORF72 mutation in frontotemporal lobar degeneration, delineate phenotypic and neuropathological features that could help to guide genetic testing, and suggest hypotheses for elucidating the neurobiology of a culprit subcortical network. PMID:22366791

  10. Identifying high risk medications causing potential drug-drug interactions in outpatients: A prescription database study based on an online surveillance system.

    PubMed

    Toivo, T M; Mikkola, J A V; Laine, K; Airaksinen, M

    2016-01-01

    Drug-drug interactions (DDIs) are a significant cause for adverse drug events (ADEs). DDIs are often predictable and preventable, but their prevention and management require systematic service development. Most DDI studies focus on interaction rates in hospitalized patients. Less is known of DDIs in outpatients, particularly how community pharmacists could contribute to DDI management by applying their surveillance systems for identifying high-risk medications. The study was related to the implementation of the first online DDI surveillance system in Finnish community pharmacies. The goal was to demonstrate how community pharmacies can utilize their prospective surveillance system 1) for identifying high risk medications causing potential DDIs in outpatients, 2) for collaborative service development with local physicians, and 3) for academic risk management research purposes. All DDI alerts given by the online surveillance system were collected during a one-month period in 16 out of 17 University Pharmacy outlets in Finland, covering approximately 10% of the national outpatient prescription volume. The surveillance system was based on the FASS database, which categorizes DDIs into four classes (A-D) according to their clinical significance. Potential drug-drug DDIs were analyzed for 276,891 dispensed community pharmacy prescriptions. Potential DDIs were associated with 10.8%, or 31,110 of these prescriptions. Clinically significant interaction alerts categorized as FASS classes D (most severe, should be avoided) and C (clinically significant but controllable) were associated with 0.5% and 7.0% of the prescriptions, respectively. Methotrexate and warfarin had the highest risk of causing potentially serious (class D) interactions. These interaction alerts were most frequently between methotrexate and NSAIDs and warfarin and NSAIDs. In general, NSAIDs were the most commonly interacting drugs in this study. This study demonstrates that community pharmacies can actively contribute to DDI risk management and systematically use their surveillance systems for identifying patients having clinically significant DDIs. The findings also indicate that the majority of potentially serious interactions in outpatients involve a limited number of drugs, particularly NSAIDs, warfarin and methotrexate. Further research should focus on community pharmacists' involvement in DDI risk management in collaboration with local health care providers. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. 76 FR 47148 - Application(s) for Duty-Free Entry of Scientific Instruments

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-04

    ... work in microbiology and pathology, to study biological materials in order to identify bacterial or viral pathogens with clinical significance in veterinary medicine. Justification for Duty-Free Entry: No...

  12. Depression, anxiety, and prevalent diabetes in the Chinese population: Findings from the China Kadoorie Biobank of 0.5 million people

    PubMed Central

    Mezuk, Briana; Chen, Yiping; Yu, Canqing; Guo, Yu; Bian, Zheng; Collins, Rory; Chen, Junshi; Pang, Zengchang; Wang, Huijun; Peto, Richard; Que, Xiangsan; Zhang, Hui; Tan, Zhongwen; Kendler, Kenneth S.; Li, Liming; Chen, Zhengming

    2013-01-01

    Objective Despite previous investigation, uncertainty remains about the nature of the associations of major depression (MD) with type 2 diabetes mellitus (T2DM), particularly in adult Chinese, and the relevance of generalized anxiety disorder (GAD) for T2DM. Methods Cross-sectional data from the China Kadoorie Biobank Study, a sample of approximately 500,000 adults from 10 geographically defined regions of China, were analyzed. Past year MD and GAD were assessed using the Composite International Diagnostic Inventory. T2DM was defined as either having self-reported physician diagnosis of diabetes at age 30 or later (“clinically-identified” cases) or having a non-fasting blood glucose ≥11.1 mmol/L or fasting blood glucose ≥7.0 mmol/L but no prior diagnosis of diabetes (“screen-detected” cases). Logistic regression was used to assess the relationship between MD and GAD with clinically-identified and screen-detected T2DM, adjusting for demographic characteristics and health behaviors. Results The prevalence of T2DM was 5.3% (3.2% clinically-identified and 2.1% screen-detected). MD was significantly associated with clinically-identified T2DM (Odds ratio [OR]: 1.75, 95% Confidence Interval (CI): 1.47 – 2.08), but not with screen-detected T2DM (OR: 1.18, 95% CI: 0.92 – 1.51). GAD was associated with both clinically-identified (OR: 2.14, 95% CI: 1.60 – 2.88) and screen-detected (OR: 1.44, 95% CI: 0.99 – 2.08) T2DM. The relationship between MD and GAD with T2DM was moderated by obesity. Conclusion MD is associated with clinically-identified, but not screen-detected T2DM. GAD is associated with both clinically-identified and screen-detected T2DM. The relationship between MD and T2DM is strongest among those who are not obese. PMID:24290039

  13. Measuring Severity of Anxiety and Depression in Patients with Inflammatory Bowel Disease: Low Concordance Between Patients and Male Gastroenterologists.

    PubMed

    Janmohamed, Neha; Steinhart, A Hillary

    2017-07-01

    Studies have indicated that anxiety and depression are significant contributors to reporting of increased disease activity in patients with inflammatory bowel disease (IBD). Thus, for the appropriate clinical management of these patients, it is important that gastroenterologists are able to recognize these conditions. This study aimed to examine the level of agreement between gastroenterologists and patients with IBD for the presence of clinically significant anxiety and depression. Before consultation, patients completed the Hospital Anxiety and Depression Survey. After the consultation, the gastroenterologist recorded whether they believed the patient was anxious and depressed and if so, whether any further action had been taken. Seventy-five patients participated in this study, with a response rate of 88%. Self-reported questionnaires indicated that 31% and 11% of patients were identified as probable for having anxiety and depression, respectively. The level of agreement between the patient and gastroenterologist as to the presence of anxiety or depression was fair to moderate (kappa statistic 0.32 and 0.41, respectively). In only 50% of cases was further action taken by gastroenterologists during consultation for distressed patients, mostly in the form of a patient discussion. Agreement between gastroenterologists and IBD patients regarding the presence of clinically significant anxiety or depression was low, with no further action taken after consultation for 50% of patients who were identified by gastroenterologists as being anxious or depressed. This study highlights the need for educating gastroenterologists to improve their ability to identify IBD patient distress.

  14. Clinical characteristics in patients with asymmetric idiopathic pulmonary fibrosis.

    PubMed

    Callahan, Sean J; Xia, Meng; Murray, Susan; Flaherty, Kevin R

    2016-10-01

    A group of patients with idiopathic pulmonary fibrosis (IPF) presents with disease affecting one lung markedly more than the other. At this time, it is unclear how this population differs from those who present with more symmetric disease. We sought to explain the characteristics of the asymmetric group and how their disease progresses. In this retrospective case-control study we accessed an interstitial lung disease (ILD) database and identified 14 asymmetric IPF cases via high-resolution computed tomography (HRCT) scoring of each lung lobe's disease severity. We identified 28 symmetric IPF controls from the same database using the same methods, and compared the clinical features of each group. Patients with asymmetric disease exhibited similar demographics as those in the general IPF population; they were predominantly male (64%), elderly (69 years old), and used tobacco (57%). We found a trend toward significantly increased all-cause mortality in the case population two years following diagnosis (p = 0.089). Pulmonary function tests were significantly lower in the case group at the time of diagnosis, then both groups experienced gradual decline. We found no statistically significant differences in number of IPF exacerbations (cases 43%, controls 39%, p = 0.824) and gastro-esophageal reflux (both groups 50%). Patients with asymmetric IPF resemble patients in the general IPF population but may have a lower overall survival rate. Further systemic factors may be studied to identify reasons for disease asymmetry and clinical decline in this population. Published by Elsevier Ltd.

  15. Transcriptome profiling identified differentially expressed genes and pathways associated with tamoxifen resistance in human breast cancer

    PubMed Central

    Men, Xin; Ma, Jun; Wu, Tong; Pu, Junyi; Wen, Shaojia; Shen, Jianfeng; Wang, Xun; Wang, Yamin; Chen, Chao; Dai, Penggao

    2018-01-01

    Tamoxifen (TAM) resistance is an important clinical problem in the treatment of breast cancer. In order to identify the mechanism of TAM resistance for estrogen receptor (ER)-positive breast cancer, we screened the transcriptome using RNA-seq and compared the gene expression profiles between the MCF-7 mamma carcinoma cell line and the TAM-resistant cell line TAMR/MCF-7, 52 significant differential expression genes (DEGs) were identified including SLIT2, ROBO, LHX, KLF, VEGFC, BAMBI, LAMA1, FLT4, PNMT, DHRS2, MAOA and ALDH. The DEGs were annotated in the GO, COG and KEGG databases. Annotation of the function of the DEGs in the KEGG database revealed the top three pathways enriched with the most DEGs, including pathways in cancer, the PI3K-AKT pathway, and focal adhesion. Then we compared the gene expression profiles between the Clinical progressive disease (PD) and the complete response (CR) from the cancer genome altas (TCGA). 10 common DEGs were identified through combining the clinical and cellular analysis results. Protein-protein interaction network was applied to analyze the association of ER signal pathway with the 10 DEGs. 3 significant genes (GFRA3, NPY1R and PTPRN2) were closely related to ER related pathway. These significant DEGs regulated many biological activities such as cell proliferation and survival, motility and migration, and tumor cell invasion. The interactions between these DEGs and drug resistance phenomenon need to be further elucidated at a functional level in further studies. Based on our findings, we believed that these DEGs could be therapeutic targets, which can be explored to develop new treatment options. PMID:29423105

  16. Clinical genomics information management software linking cancer genome sequence and clinical decisions.

    PubMed

    Watt, Stuart; Jiao, Wei; Brown, Andrew M K; Petrocelli, Teresa; Tran, Ben; Zhang, Tong; McPherson, John D; Kamel-Reid, Suzanne; Bedard, Philippe L; Onetto, Nicole; Hudson, Thomas J; Dancey, Janet; Siu, Lillian L; Stein, Lincoln; Ferretti, Vincent

    2013-09-01

    Using sequencing information to guide clinical decision-making requires coordination of a diverse set of people and activities. In clinical genomics, the process typically includes sample acquisition, template preparation, genome data generation, analysis to identify and confirm variant alleles, interpretation of clinical significance, and reporting to clinicians. We describe a software application developed within a clinical genomics study, to support this entire process. The software application tracks patients, samples, genomic results, decisions and reports across the cohort, monitors progress and sends reminders, and works alongside an electronic data capture system for the trial's clinical and genomic data. It incorporates systems to read, store, analyze and consolidate sequencing results from multiple technologies, and provides a curated knowledge base of tumor mutation frequency (from the COSMIC database) annotated with clinical significance and drug sensitivity to generate reports for clinicians. By supporting the entire process, the application provides deep support for clinical decision making, enabling the generation of relevant guidance in reports for verification by an expert panel prior to forwarding to the treating physician. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Screening for important unwarranted variation in clinical practice: a triple-test of processes of care, costs and patient outcomes.

    PubMed

    Partington, Andrew; Chew, Derek P; Ben-Tovim, David; Horsfall, Matthew; Hakendorf, Paul; Karnon, Jonathan

    2017-03-01

    Objective Unwarranted variation in clinical practice is a target for quality improvement in health care, but there is no consensus on how to identify such variation or to assess the potential value of initiatives to improve quality in these areas. This study illustrates the use of a triple test, namely the comparative analysis of processes of care, costs and outcomes, to identify and assess the burden of unwarranted variation in clinical practice. Methods Routinely collected hospital and mortality data were linked for patients presenting with symptoms suggestive of acute coronary syndromes at the emergency departments of four public hospitals in South Australia. Multiple regression models analysed variation in re-admissions and mortality at 30 days and 12 months, patient costs and multiple process indicators. Results After casemix adjustment, an outlier hospital with statistically significantly poorer outcomes and higher costs was identified. Key process indicators included admission patterns, use of invasive diagnostic procedures and length of stay. Performance varied according to patients' presenting characteristics and time of presentation. Conclusions The joint analysis of processes, outcomes and costs as alternative measures of performance inform the importance of reducing variation in clinical practice, as well as identifying specific targets for quality improvement along clinical pathways. Such analyses could be undertaken across a wide range of clinical areas to inform the potential value and prioritisation of quality improvement initiatives. What is known about the topic? Variation in clinical practice is a long-standing issue that has been analysed from many different perspectives. It is neither possible nor desirable to address all forms of variation in clinical practice: the focus should be on identifying important unwarranted variation to inform actions to reduce variation and improve quality. What does this paper add? This paper proposes the comparative analysis of processes of care, costs and outcomes for patients with similar diagnoses presenting at alternative hospitals, using linked, routinely collected data. This triple test of performance indicators extracts maximum value from routine data to identify priority areas for quality improvement to reduce important and unwarranted variations in clinical practice. What are the implications for practitioners? The proposed analyses need to be applied to other clinical areas to demonstrate the general application of the methods. The outputs can then be validated through the application of quality improvement initiatives in clinical areas with identified important and unwarranted variation. Validated frameworks for the comparative analysis of clinical practice provide an efficient approach to valuing and prioritising actions to improve health service quality.

  18. Identification of urine protein biomarkers with the potential for early detection of lung cancer.

    PubMed

    Zhang, Hongjuan; Cao, Jing; Li, Lin; Liu, Yanbin; Zhao, Hong; Li, Nan; Li, Bo; Zhang, Aiqun; Huang, Huanwei; Chen, She; Dong, Mengqiu; Yu, Lei; Zhang, Jian; Chen, Liang

    2015-07-02

    Lung cancer is the leading cause of cancer-related deaths and has an overall 5-year survival rate lower than 15%. Large-scale clinical trials have demonstrated a significant relative reduction in mortality in high-risk individuals with low-dose computed tomography screening. However, biomarkers capable of identifying the most at-risk population and detecting lung cancer before it becomes clinically apparent are urgently needed in the clinic. Here, we report the identification of urine biomarkers capable of detecting lung cancer. Using the well-characterized inducible Kras (G12D) mouse model of lung cancer, we identified alterations in the urine proteome in tumor-bearing mice compared with sibling controls. Marked differences at the proteomic level were also detected between the urine of patients and that of healthy population controls. Importantly, we identified 7 proteins commonly found to be significantly up-regulated in both tumor-bearing mice and patients. In an independent cohort, we showed that 2 of the 7 proteins were up-regulated in urine samples from lung cancer patients but not in those from controls. The kinetics of these proteins correlated with the disease state in the mouse model. These tumor biomarkers could potentially aid in the early detection of lung cancer.

  19. A usability evaluation of four commercial dental computer-based patient record systems

    PubMed Central

    Thyvalikakath, Thankam P.; Monaco, Valerie; Thambuganipalle, Hima Bindu; Schleyer, Titus

    2008-01-01

    Background The usability of dental computer-based patient record (CPR) systems has not been studied, despite early evidence that poor usability is a problem for dental CPR system users at multiple levels. Methods The authors conducted formal usability tests of four dental CPR systems by using a purposive sample of four groups of five novice users. The authors measured task outcomes (correctly completed, incorrectly completed and incomplete) in each CPR system while the participants performed nine clinical documentation tasks, as well as the number of usability problems identified in each CPR system and their potential relationship to task outcomes. The authors reviewed the software application design aspects responsible for these usability problems. Results The range for correctly completed tasks was 16 to 64 percent, for incorrectly completed tasks 18 to 38 percent and for incomplete tasks 9 to 47 percent. The authors identified 286 usability problems. The main types were three unsuccessful attempts, negative affect and task incorrectly completed. They also identified six problematic interface and interaction designs that led to usability problems. Conclusion The four dental CPR systems studied have significant usability problems for novice users, resulting in a steep learning curve and potentially reduced system adoption. Clinical Implications The significant number of data entry errors raises concerns about the quality of documentation in clinical practice. PMID:19047669

  20. Albumin Homodimers in Patients with Cirrhosis: Clinical and Prognostic Relevance of a Novel Identified Structural Alteration of the Molecule

    PubMed Central

    Baldassarre, Maurizio; Domenicali, Marco; Naldi, Marina; Laggetta, Maristella; Giannone, Ferdinando A.; Biselli, Maurizio; Patrono, Daniela; Bertucci, Carlo; Bernardi, Mauro; Caraceni, Paolo

    2016-01-01

    Decompensated cirrhosis is associated to extensive post-transcriptional changes of human albumin (HA). This study aims to characterize the occurrence of HA homodimerization in a large cohort of patients with decompensated cirrhosis and to evaluate its association with clinical features and prognosis. HA monomeric and dimeric isoforms were identified in peripheral blood by using a HPLC-ESI-MS technique in 123 cirrhotic patients hospitalized for acute decompensation and 50 age- and sex-comparable healthy controls. Clinical and biochemical parameters were recorded and patients followed up to one year. Among the monomeric isoforms identified, the N- and C-terminal truncated and the native HA underwent homodimerization. All three homodimers were significantly more abundant in patients with cirrhosis, acute-on-chronic liver failure and correlate with the prognostic scores. The homodimeric N-terminal truncated isoform was independently associated to disease complications and was able to stratify 1-year survival. As a result of all these changes, the monomeric native HA was significantly decreased in patients with cirrhosis, being also associated with a poorer prognosis. In conclusion homodimerization is a novel described structural alteration of the HA molecule in decompensated cirrhosis and contributes to the progressive reduction of the monomeric native HA, the only isoform provided of structural and functional integrity. PMID:27782157

  1. Albumin Homodimers in Patients with Cirrhosis: Clinical and Prognostic Relevance of a Novel Identified Structural Alteration of the Molecule.

    PubMed

    Baldassarre, Maurizio; Domenicali, Marco; Naldi, Marina; Laggetta, Maristella; Giannone, Ferdinando A; Biselli, Maurizio; Patrono, Daniela; Bertucci, Carlo; Bernardi, Mauro; Caraceni, Paolo

    2016-10-26

    Decompensated cirrhosis is associated to extensive post-transcriptional changes of human albumin (HA). This study aims to characterize the occurrence of HA homodimerization in a large cohort of patients with decompensated cirrhosis and to evaluate its association with clinical features and prognosis. HA monomeric and dimeric isoforms were identified in peripheral blood by using a HPLC-ESI-MS technique in 123 cirrhotic patients hospitalized for acute decompensation and 50 age- and sex-comparable healthy controls. Clinical and biochemical parameters were recorded and patients followed up to one year. Among the monomeric isoforms identified, the N- and C-terminal truncated and the native HA underwent homodimerization. All three homodimers were significantly more abundant in patients with cirrhosis, acute-on-chronic liver failure and correlate with the prognostic scores. The homodimeric N-terminal truncated isoform was independently associated to disease complications and was able to stratify 1-year survival. As a result of all these changes, the monomeric native HA was significantly decreased in patients with cirrhosis, being also associated with a poorer prognosis. In conclusion homodimerization is a novel described structural alteration of the HA molecule in decompensated cirrhosis and contributes to the progressive reduction of the monomeric native HA, the only isoform provided of structural and functional integrity.

  2. Resveratrol and cancer: Challenges for clinical translation

    PubMed Central

    Singh, Chandra K.; Ndiaye, Mary A.; Ahmad, Nihal

    2014-01-01

    Significant work has been done towards identifying the health-beneficial effects of the grape antioxidant resveratrol in a variety of bioassay- and disease- models, with much research being focused on its possible application to cancer management. Despite the large number of preclinical studies dealing with different aspects of the biological effects of resveratrol, it’s translation to clinics is far from reality due to a variety of challenges. In this review, we discuss the issues and questions associated with resveratrol becoming an effective in vivo anticancer drug, from basic metabolic issues to the problems faced by incomplete understanding of the mechanism(s) of action in the body. We also explore efforts taken by researchers, both public and private, to contend with some of these issues. By examining the published data and previous clinical trials, we have attempted to identify the problems and issues that hinder the clinical translation of resveratrol for cancer management. PMID:25446990

  3. Review of ongoing clinical trials in non-small-cell lung cancer: a status report for 2012 from the ClinicalTrials.gov Web site.

    PubMed

    Subramanian, Janakiraman; Regenbogen, Thomas; Nagaraj, Gayathri; Lane, Alex; Devarakonda, Siddhartha; Zhou, Gongfu; Govindan, Ramaswamy

    2013-07-01

    Clinical research in non-small-cell lung cancer (NSCLC) is a rapidly evolving field. In an effort to identify the current trends in lung cancer clinical research, we reviewed ongoing clinical trials in NSCLC listed in the ClinicalTrials.gov registry in 2012, and we also compared this data to a similar survey conducted by us in 2009. The Web site's advanced search function was used to search for the term "non-small cell lung cancer." The search was further refined by using the following options from the search page drop-down menu, "open studies" and "interventional." Studies with non-NSCLC tumor histologies and pediatric studies were excluded. Of the 477 trials included in the analysis, 105 (22.0%) were phase I, 223 phase II (46.8%), and 63 phase III trials (13.2%). When compared with data from 2009, university-sponsored trials decreased in number (45.4%-34.2%; p < 0.001) whereas industry-sponsored trials remained almost the same. There was a significant increase in trials conducted exclusively outside of the United States (35.9%-48.8%; p = 0.001). The number of studies with locations in China (61, 12.8%) was second only to that in the United States (244, 51.2%). Studies reporting biomarker analysis increased significantly from 37.5% to 49.1% in 2012 (p < 0.001). Biomarker-based patient selection also increased significantly from 7.9% to 25.8% (p < 0.001). Targeted therapies were evaluated in 70.6% of phase I/II and II trials, and the most common class of targeted agent studied was epidermal growth factor receptor tyrosine kinase inhibitors (38.0%). Prespecified accrual times were observed to increase when compared with data reported in 2009, especially among industry-sponsored studies. Our survey identified major changes in lung cancer clinical research since 2009. Almost half of all studies registered at the ClinicalTrials.gov Web site are being conducted outside the United States, and several novel molecularly targeted agents are being evaluated in the treatment of patients with NSCLC. More importantly, we identified a threefold increase in the number of studies that perform biomarker testing to determine patient selection over the last 3 years.

  4. Detection of Metastatic Potential in Breast Cancer by RhoC-GTPase and WISP3 Proteins

    DTIC Science & Technology

    2005-05-01

    clinical utility of RhoC- GTPase and WISP3 proteins in breast cancer patients. These two genes were identified as key genetic determinants of...information, linked to a clinical database, and to better understand the functional significance of the WISP3 gene in Inflammatory Breast Cancer (IBC), to...pathological and clinical information. The idea behind this decision was to be able to link the results of the TMA scoring with the patient pathological

  5. Spontaneous Swallowing Frequency [Has Potential to] Identify Dysphagia in Acute Stroke

    PubMed Central

    Carnaby, Giselle D; Sia, Isaac; Khanna, Anna; Waters, Michael

    2014-01-01

    Background and Purpose Spontaneous swallowing frequency has been described as an index of dysphagia in various health conditions. This study evaluated the potential of spontaneous swallow frequency analysis as a screening protocol for dysphagia in acute stroke. Methods In a cohort of 63 acute stroke cases swallow frequency rates (swallows per minute: SPM) were compared to stroke and swallow severity indices, age, time from stroke to assessment, and consciousness level. Mean differences in SPM were compared between patients with vs. without clinically significant dysphagia. ROC analysis was used to identify the optimal threshold in SPM which was compared to a validated clinical dysphagia examination for identification of dysphagia cases. Time series analysis was employed to identify the minimally adequate time period to complete spontaneous swallow frequency analysis. Results SPM correlated significantly with stroke and swallow severity indices but not with age, time from stroke onset, or consciousness level. Patients with dysphagia demonstrated significantly lower SPM rates. SPM differed by dysphagia severity. ROC analysis yielded a threshold of SPM ≤ 0.40 which identified dysphagia (per the criterion referent) with 0.96 sensitivity, 0.68 specificity, and 0.96 negative predictive value. Time series analysis indicated that a 5 to 10 minute sampling window was sufficient to calculate spontaneous swallow frequency to identify dysphagia cases in acute stroke. Conclusions Spontaneous swallowing frequency presents high potential to screen for dysphagia in acute stroke without the need for trained, available personnel. PMID:24149008

  6. Spontaneous swallowing frequency has potential to identify dysphagia in acute stroke.

    PubMed

    Crary, Michael A; Carnaby, Giselle D; Sia, Isaac; Khanna, Anna; Waters, Michael F

    2013-12-01

    Spontaneous swallowing frequency has been described as an index of dysphagia in various health conditions. This study evaluated the potential of spontaneous swallow frequency analysis as a screening protocol for dysphagia in acute stroke. In a cohort of 63 acute stroke cases, swallow frequency rates (swallows per minute [SPM]) were compared with stroke and swallow severity indices, age, time from stroke to assessment, and consciousness level. Mean differences in SPM were compared between patients with versus without clinically significant dysphagia. Receiver operating characteristic curve analysis was used to identify the optimal threshold in SPM, which was compared with a validated clinical dysphagia examination for identification of dysphagia cases. Time series analysis was used to identify the minimally adequate time period to complete spontaneous swallow frequency analysis. SPM correlated significantly with stroke and swallow severity indices but not with age, time from stroke onset, or consciousness level. Patients with dysphagia demonstrated significantly lower SPM rates. SPM differed by dysphagia severity. Receiver operating characteristic curve analysis yielded a threshold of SPM≤0.40 that identified dysphagia (per the criterion referent) with 0.96 sensitivity, 0.68 specificity, and 0.96 negative predictive value. Time series analysis indicated that a 5- to 10-minute sampling window was sufficient to calculate spontaneous swallow frequency to identify dysphagia cases in acute stroke. Spontaneous swallowing frequency presents high potential to screen for dysphagia in acute stroke without the need for trained, available personnel.

  7. Validation of the Intensive Care Unit Early Warning Dashboard: Quality Improvement Utilizing a Retrospective Case-Control Evaluation.

    PubMed

    Kavanaugh, Michael J; So, Joanne D; Park, Peter J; Davis, Konrad L

    2017-02-01

    Risk stratification with the Modified Early Warning System (MEWS) or electronic cardiac arrest trigger (eCART) has been utilized with ward patients to preemptively identify high-risk patients who might benefit from enhanced monitoring, including early intensive care unit (ICU) transfer. In-hospital mortality from cardiac arrest is ∼80%, making preventative interventions an important focus area. ICUs have lower patient to nurse ratios than wards, resulting in less emphasis on the development of ICU early warning systems. Our institution developed an early warning dashboard (EWD) identifying patients who may benefit from earlier interventions. Using the adverse outcomes of cardiac arrest, ICU mortality, and ICU readmissions, a retrospective case-control study was performed using three demographic items (age, diabetes, and morbid obesity) and 24 EWD measured items, including vital signs, laboratory values, ventilator information, and other clinical information, to validate the EWD. Ten statistically significant areas were identified for cardiac arrest and 13 for ICU death. Identified items included heart rate, dialysis, leukocytosis, and lactate. The ICU readmission outcome was compared to controls from both ICU patients and ward patients, and statistical significance was identified for respiratory rate >30. With several statistically significant data elements, the EWD parameters have been incorporated into advanced clinical decision algorithms to identify at-risk ICU patients. Earlier identification and treatment of organ failure in the ICU improve outcomes and the EWD can serve as a safety measure for both at-risk in-house patients and also extend critical care expertise through telemedicine to smaller hospitals.

  8. Study to determine the clinical significance of HEmolysis During Orbital AtheRectomy (CLEAR study).

    PubMed

    Staniloae, Cezar S; Korabathina, Ravikiran; Lane, Thomas A; Dattilo, Raymond; Church, Kevin J; Mody, Kanika P; Mayeda, Guy S

    2011-02-01

    To evaluate the incidence of clinically evident hemolysis associated with orbital atherectomy used to treat severe peripheral artery disease. The observational CLEAR study enrolled 31 subjects (16 men; mean age 71 ± 10 years, range 44-92) with claudication (58.1%) or critical limb ischemia (38.7%) who underwent orbital atherectomy with the Diamondback 360 system at 4 US centers. The 42 lesions in 31 limbs were located in the superficial femoral (n = 19, 45.2%), popliteal (n = 8, 19.0%), and tibial arteries (n = 15, 35.8%). The majority of lesions (34, 81.0%) were de novo; moderate or severe calcification was identified in 90.5% of cases. Lesion and procedural parameters were analyzed at a core laboratory. Blood samples were collected during and post procedure and analyzed for markers of hemolysis. The primary endpoint was the occurrence of clinically significant hemolysis. The secondary endpoints included the occurrence of any clinical symptoms/signs potentially related to hemolysis. Statistical analysis was performed to identify predictors for hemolysis. Laboratory evidence of hemolysis was seen in 11 (35.5%) subjects. No one met the clinical event criteria, and so the primary endpoint of the study was not reached. The secondary endpoints were hypertensive crisis (1, 3.2%) and transient hemoglobinuria (3, 9.7%). Lower glomerular filtration rates, calcified plaque, long atherectomy runs, and solid crown selection were independent predictors of hemolysis. There was no clinically significant hemolysis after orbital atherectomy. The results of this study will enable users to predict conditions that predispose to high levels of red cell hemolysis following orbital atherectomy and to take appropriate measures to limit its occurrence.

  9. Baseline Factors Predicting Placebo Response to Treatment in Children and Adolescents With Autism Spectrum Disorders

    PubMed Central

    King, Bryan H.; Dukes, Kimberly; Donnelly, Craig L.; Sikich, Linmarie; McCracken, James T.; Scahill, Lawrence; Hollander, Eric; Bregman, Joel D.; Anagnostou, Evdokia; Robinson, Fay; Sullivan, Lisa; Hirtz, Deborah

    2016-01-01

    IMPORTANCE The finding of factors that differentially predict the likelihood of response to placebo over that of an active drug could have a significant impact on study design in this population. OBJECTIVE To identify possible nonspecific, baseline predictors of response to intervention in a large randomized clinical trial of children and adolescents with autism spectrum disorders. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial of citalopram hydrobromide for children and adolescents with autism spectrum disorders and prominent repetitive behavior. Baseline data at study entry were examined with respect to final outcome to determine if response predictors could be identified. A total of 149 children and adolescents 5 to 17 years of age (mean [SD] age, 9.4 [3.1] years) from 6 academic centers were randomly assigned to citalopram (n = 73) or placebo (n = 76). Participants had autistic disorder, Asperger syndrome, or pervasive developmental disorder, not otherwise specified; had illness severity ratings that were moderate or more than moderate on the Clinical Global Impression–Severity scale; and scored moderate or more than moderate on compulsive behaviors measured with the modified Children’s Yale-Brown Obsessive-Compulsive Scale. INTERVENTIONS Twelve weeks of treatment with citalopram (10 mg/5 mL) or placebo. The mean (SD) maximum dose of citalopram was 16.5 (6.5) mg by mouth daily (maximum dose, 20 mg/d). MAIN OUTCOMES AND MEASURES A positive response was defined as having a score of at least much improved on the Clinical Global Impression–Improvement scale at week 12. Baseline measures included demographic (sex, age, weight, and pubertal status), clinical, and family measures. Clinical variables included baseline illness severity ratings (the Aberrant Behavior Checklist, the Child and Adolescent Symptom Inventory, the Vineland Adaptive Behavior Scales, the Repetitive Behavior Scale–Revised, and the Children’s Yale-Brown Obsessive-Compulsive Scale). Family measures included the Caregiver Strain Questionnaire. RESULTS Several baseline predictors of response were identified, and a principal component analysis yielded 3 composite measures (disruptive behavior, autism/mood, and caregiver strain) that significantly predicted response at week 12. Specifically, participants in the placebo group were significantly less likely than participants in the citalopram group to respond at week 12 if they entered the study more symptomatic on each of the 3 composite measures, and they were at least 2 times less likely to be responders. CONCLUSIONS AND RELEVANCE This analysis suggests strategies that may be useful in anticipating and potentially mitigating the nonspecific response in randomized clinical trials of children and adolescents with autism spectrum disorders. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00086645 PMID:24061784

  10. Factors influencing nurses' decisions to activate medical emergency teams.

    PubMed

    Pantazopoulos, Ioannis; Tsoni, Aikaterini; Kouskouni, Evangelia; Papadimitriou, Lila; Johnson, Elizabeth O; Xanthos, Theodoros

    2012-09-01

    To evaluate the relationship between nurse demographics and correct identification of clinical situations warranting specific nursing actions, including activation of the medical emergency team. If abnormal physiology is left untreated, the patient may develop cardiac arrest. Nurses in general wards are those who perceive any clinical deterioration in patients. A descriptive, quantitative design was selected. An anonymous survey with 13 multiple choice questions was distributed to 150 randomly selected nurses working in general medical and surgical wards of a large tertiary hospital in Athens, Greece. After explanation of the purposes of the study, 94 nurses (response ratio: 62%) agreed to respond to the questionnaire. Categories with the greatest nursing concern were patients with heart rate<40/minute, an atypical thoracic pain, foreign body airway obstruction and bronchial secretions, respiratory rate<5/minute and heart rate=100/minute. However, almost 50% of nurses were able to accurately identify the critical nursing action for patients with respiratory rate<4/minute, 72% for patients with airway obstruction and 73% for patients with chest pain. Nurses who had graduated from a four-year educational programme identified clinical situations that necessitated medical emergency team activation in a significantly higher rate and also scored significantly higher in questions concerning clinical evaluation than nurses who had graduated from a two-year educational programme. Activation of the medical emergency team is influenced by factors such as level of education and cardiopulmonary resuscitation courses attendance. Graduating from a four-year educational programme helps nurses identify emergencies. However, irrespective of the educational programme they have followed, undertaking a basic life support or advanced life support provider course is critical as it helps them identify cardiac or respiratory emergencies. © 2012 Blackwell Publishing Ltd.

  11. Using a pedagogical approach to integrate evidence-based teaching in an undergraduate women's health course.

    PubMed

    Dawley, Katy; Bloch, Joan Rosen; Suplee, Patricia Dunphy; McKeever, Amy; Scherzer, Gerri

    2011-06-01

    Evidence-based practice (EBP) is promoted as a foundation for nursing practice. However, the 2005 U.S. survey of nurses revealed that they do not have requisite skills for EBP. PURPOSE AND GOALS: To evaluate a pedagogical approach aimed at (1) fostering undergraduate nursing students EBP competencies, and (2) identifying gaps in the literature to direct future women's health research. A secondary analysis of data abstracted from required EBP clinical journals for an undergraduate women's health course in which students (n = 198) were asked to find evidence to answer their clinical questions. Content analysis was used to identify main themes of the topics of inquiry. Students identified 1,808 clinical questions and 30.3% (n = 547) of these could not be answered or supported by evidence in the literature. This assignment was an important teaching and assessment tool for EBP. Questions reflected critical thinking and quest for in-depth knowledge to support nursing practice. Some students lacked skills in searching databases and a significant number of knowledge gaps were identified that can direct women's health research. Copyright ©2010 Sigma Theta Tau International.

  12. Clinical characteristics and outcomes of the meningitides in systemic lupus erythematosus.

    PubMed

    Baizabal-Carvallo, José Fidel; Delgadillo-Márquez, German; Estañol, Bruno; García-Ramos, Guillermo

    2009-01-01

    The meningitides are rare but well-identified complications in patients with systemic lupus erythematosus (SLE). To determine the clinical characteristics, risk factors, prevalence and outcomes of the meningitides (septic and aseptic) in patients with SLE. From January 1988 to December 2006, we identified patients with SLE and septic or aseptic meningitis. We identified 25 episodes of meningitis in 23 patients with SLE, from a total of 1,411 SLE patients (1.63%); in 15 out of 25 episodes, a microorganism was identified. Mycobacterium tuberculosis, Listeria monocytogenes and Criptococcus neoformans represented the main microorganisms. In 10 episodes, aseptic meningitis was diagnosed. Lymphopenia, steroid use, chronic damage and systemic activity of SLE were frequent in both kinds of meningitis. Although the clinical presentation did not differ significantly, patients with septic meningitis had more residual neurological deficits (p = 0.04). Meningitis was observed in about 1.6% of the patients with SLE; in 40% of the cases, no microorganism could be isolated. A residual neurological deficit was more common in patients with septic meningitis. Copyright (c) 2008 S. Karger AG, Basel.

  13. Private prayer associations with depression, anxiety and other health conditions: an analytical review of clinical studies.

    PubMed

    Anderson, James W; Nunnelley, Paige A

    2016-09-01

    To critically analyze appropriate clinical studies to assess the relationship between health conditions and the frequency of private prayer. Private prayer is defined as individuals praying for themselves. Using PubMed and other search engines, we identified over 300 articles reporting relationships between prayer and health conditions. We identified 41 observational clinical studies that evaluated the relationship between private prayer and health conditions. Prayer scores of 5 to 1 were assigned to studies, with 5 being private prayer for health and 1 being prayer in combination with meditation or Bible study. Frequency scores ranged from 3 to 1 with 3 being twice daily or more and 0 when frequency was not assessed. Studies were ranked from 8 to 1 based on the sum of Prayer and Frequency Scores. Twenty-one studies had Prayer-Frequency scores of 5 to 8, indicating that they evaluated private prayer (praying for one's own health) of suitable frequency in association with health conditions. Nine of 11 studies indicated that private prayer was associated with a significantly lower prevalence of depression (P value, <0.01). Optimism as well as coping were significantly improved by prayer in four studies (P value, P < 0.01). In 10 studies of mental health conditions-including anxiety and confusion-there was a significant benefit associated with prayer (P < 0.01), In the reviewed studies, prayer did not have a significant effect on physical health or blood pressure. The reported observational studies suggest that frequent private prayer is associated with a significant benefit for depression, optimism, coping, and other mental health conditions such as anxiety. Controlled clinical trials are required to critically assess the associations of private prayer and health conditions.

  14. 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.

  15. Early detection and treatment of sexually transmitted disease in pregnant adolescents of low socioeconomic status.

    PubMed

    Matson, S C; Pomeranz, A J; Kamps, K A

    1993-10-01

    This study evaluated the prevalence of sexually transmitted disease (STD) in adolescents presenting to a primary pediatric care clinic (PPCC) for the diagnosis of pregnancy and our ability to eradicate identified infections. We followed 168 pregnant adolescents of low socioeconomic status from their original pregnancy diagnosis until their first prenatal clinic visit. We collected screening cervical cultures for Neisseria gonorrhoeae and Chlamydia trachomatis by completing a pelvic examination on 91 patients at our PPCC. At the PPCC visit, 29% were positive for gonorrhea, chlamydia, or both. Screening tests for these infections were collected on all patients at the initial prenatal clinic visit. The risk for presenting to the prenatal clinic with a STD was significantly greater in patients not screened and treated for STD at the PPCC. Average delay from diagnosis to first prenatal clinic visit was 35.7 days. Thus, in this adolescent population, primary care providers are missing an important therapeutic opportunity by failing to identify and treat STD at initial diagnosis of pregnancy.

  16. Comparison of atypical Brachyspira spp. clinical isolates and classic strains in a mouse model of swine dysentery.

    PubMed

    Burrough, Eric; Strait, Erin; Kinyon, Joann; Bower, Leslie; Madson, Darin; Schwartz, Kent; Frana, Timothy; Songer, J Glenn

    2012-12-07

    Multiple Brachyspira spp. can colonize the porcine colon, and the presence of the strongly beta-hemolytic Brachyspira hyodysenteriae is typically associated with clinical swine dysentery. Recently, several Brachyspira spp. have been isolated from the feces of pigs with clinical disease suggestive of swine dysentery, yet these isolates were not identified as B. hyodysenteriae by genotypic or phenotypic methods. This study used a mouse model of swine dysentery to compare the pathogenic potential of seventeen different Brachyspira isolates including eight atypical clinical isolates, six typical clinical isolates, the standard strain of B. hyodysenteriae (B204), and reference strains of Brachyspira intermedia and Brachyspira innocens. Results revealed that strongly beta-hemolytic isolates induced significantly greater cecal inflammation than weakly beta-hemolytic isolates regardless of the genetic identification of the isolate, and that strongly beta-hemolytic isolates identified as 'Brachyspira sp. SASK30446' and B. intermedia by PCR produced lesions indistinguishable from those caused by B. hyodysenteriae in this model. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Diagnostic discrepancies in retinopathy of prematurity classification

    PubMed Central

    Campbell, J. Peter; Ryan, Michael C.; Lore, Emily; Tian, Peng; Ostmo, Susan; Jonas, Karyn; Chan, R.V. Paul; Chiang, Michael F.

    2016-01-01

    Objective To identify the most common areas for discrepancy in retinopathy of prematurity (ROP) classification between experts. Design Prospective cohort study. Subjects, Participants, and/or Controls 281 infants were identified as part of a multi-center, prospective, ROP cohort study from 7 participating centers. Each site had participating ophthalmologists who provided the clinical classification after routine examination using binocular indirect ophthalmoscopy (BIO), and obtained wide-angle retinal images, which were independently classified by two study experts. Methods Wide-angle retinal images (RetCam; Clarity Medical Systems, Pleasanton, CA) were obtained from study subjects, and two experts evaluated each image using a secure web-based module. Image-based classifications for zone, stage, plus disease, overall disease category (no ROP, mild ROP, Type II or pre-plus, and Type I) were compared between the two experts, and to the clinical classification obtained by BIO. Main Outcome Measures Inter-expert image-based agreement and image-based vs. ophthalmoscopic diagnostic agreement using absolute agreement and weighted kappa statistic. Results 1553 study eye examinations from 281 infants were included in the study. Experts disagreed on the stage classification in 620/1553 (40%) of comparisons, plus disease classification (including pre-plus) in 287/1553 (18%), zone in 117/1553 (8%), and overall ROP category in 618/1553 (40%). However, agreement for presence vs. absence of type 1 disease was >95%. There were no differences between image-based and clinical classification except for zone III disease. Conclusions The most common area of discrepancy in ROP classification is stage, although inter-expert agreement for clinically-significant disease such as presence vs. absence of type 1 and type 2 disease is high. There were no differences between image-based grading and the clinical exam in the ability to detect clinically-significant disease. This study provides additional evidence that image-based classification of ROP reliably detects clinically significant levels of ROP with high accuracy compared to the clinical exam. PMID:27238376

  18. A network-based, integrative study to identify core biological pathways that drive breast cancer clinical subtypes

    PubMed Central

    Dutta, B; Pusztai, L; Qi, Y; André, F; Lazar, V; Bianchini, G; Ueno, N; Agarwal, R; Wang, B; Shiang, C Y; Hortobagyi, G N; Mills, G B; Symmans, W F; Balázsi, G

    2012-01-01

    Background: The rapid collection of diverse genome-scale data raises the urgent need to integrate and utilise these resources for biological discovery or biomedical applications. For example, diverse transcriptomic and gene copy number variation data are currently collected for various cancers, but relatively few current methods are capable to utilise the emerging information. Methods: We developed and tested a data-integration method to identify gene networks that drive the biology of breast cancer clinical subtypes. The method simultaneously overlays gene expression and gene copy number data on protein–protein interaction, transcriptional-regulatory and signalling networks by identifying coincident genomic and transcriptional disturbances in local network neighborhoods. Results: We identified distinct driver-networks for each of the three common clinical breast cancer subtypes: oestrogen receptor (ER)+, human epidermal growth factor receptor 2 (HER2)+, and triple receptor-negative breast cancers (TNBC) from patient and cell line data sets. Driver-networks inferred from independent datasets were significantly reproducible. We also confirmed the functional relevance of a subset of randomly selected driver-network members for TNBC in gene knockdown experiments in vitro. We found that TNBC driver-network members genes have increased functional specificity to TNBC cell lines and higher functional sensitivity compared with genes selected by differential expression alone. Conclusion: Clinical subtype-specific driver-networks identified through data integration are reproducible and functionally important. PMID:22343619

  19. Comparisons of Patient Demographics in Prospective Sports, Shoulder, and National Database Initiatives.

    PubMed

    Saltzman, Bryan M; Cvetanovich, Gregory L; Bohl, Daniel D; Cole, Brian J; Bach, Bernard R; Romeo, Anthony A

    2016-09-01

    There has been increased emphasis in orthopaedics on high-quality prospective research to provide evidence-based treatment guidelines, particularly in sports medicine/shoulder surgery. The external validity of these studies has not been established, and the generalizability of the results to clinical practice in the United States is unknown. Comparison of patient demographics in major prospective studies of arthroscopic sports and shoulder surgeries to patients undergoing the same procedures in the National Surgical Quality Improvement Program (NSQIP) database will show substantial differences to question the generalizability and external validity of those studies. Cross-sectional study; Level of evidence, 3. This study utilized patients undergoing arthroscopic anterior cruciate ligament reconstruction (ACLR), meniscectomy (MX), rotator cuff repair (RCR), and shoulder stabilization (SS) from the NSQIP database (2005-2013). Two prospective studies (either randomized controlled trials or, in 1 case, a major cohort study) were identified for each of the 4 procedures for comparison. Demographic variables available for comparison in both the identified prospective studies and the NSQIP included age, sex, and body mass index (BMI). From the NSQIP database, 5576 ACLR patients, 18,882 MX patients, 7282 RCR patients, and 993 SS patients were identified. The comparison clinical studies included cohort sizes as follows: ACLR, n = 121 and 2683; MX, n = 146 and 330; RCR, n = 90 and 103; SS, n = 88 and 196. Age differed significantly between the NSQIP and the patients in 6 of the 8 prospective clinical studies. Sex differed significantly between the NSQIP and the patients in 7 of the 8 prospective clinical studies. BMI differed significantly between the NSQIP and the patients of all 4 of the prospective clinical studies that reported this demographic variable. Significant differences exist for patient age, sex, and BMI between patients included in major sports medicine/shoulder prospective studies and corresponding patients undergoing the same procedures in a nationwide database of academic and community centers in the United States. Future work is needed to understand whether major prospective clinical studies-frequently performed in high-volume, specialized practices-are truly indicative of the types of patients treated and expected results in the general orthopaedic practice. This study additionally argues for the importance of initiating a national registry dedicated to patients undergoing orthopaedic procedures in the United States.

  20. Improving medication safety and diabetes management in Hong Kong: a multidisciplinary approach.

    PubMed

    Chung, A Ys; Anand, S; Wong, I Ck; Tan, K Cb; Wong, C Ff; Chui, W Cm; Chan, E W

    2017-04-01

    Patients with diabetes often require complex medication regimens. The positive impact of pharmacists on improving diabetes management or its co-morbidities has been recognised worldwide. This study aimed to characterise drug-related problems among diabetic patients in Hong Kong and their clinical significance, and to explore the role of pharmacists in the multidisciplinary diabetes management team by evaluating the outcome of their clinical interventions. An observational study was conducted at the Diabetes Clinic of a public hospital in Hong Kong from October 2012 to March 2014. Following weekly screening, and prior to the doctor's consultation, selected high-risk patients were interviewed by a pharmacist for medication reconciliation and review. Drug-related problems were identified and documented by the pharmacist who presented clinical recommendations to doctors to optimise a patient's drug regimen and resolve or prevent potential drug-related problems. A total of 522 patients were analysed and 417 drug-related problems were identified. The incidence of patients with drug-related problems was 62.8% with a mean of 0.9 (standard deviation, 0.6) drug-related problems per patient. The most common categories of drug-related problems were associated with dosing (43.9%), drug choice (17.3%), and non-allergic adverse reactions (15.6%). Drugs most frequently involved targeted the endocrine or cardiovascular system. The majority (71.9%) of drug-related problems were of moderate clinical significance and 28.1% were considered minor problems. Drug-related problems were totally solved (50.1%) and partially solved (11.0%) by doctors' acceptance of pharmacist recommendations, or received acknowledgement from doctors (5.5%). Pharmacists, in collaboration with the multidisciplinary team, demonstrated a positive impact by identifying, resolving, and preventing drug-related problems in patients with diabetes. Further plans for sustaining pharmacy service in the Diabetes Clinic would enable further studies to explore the long-term impact of pharmacists in improving patients' clinical outcomes in diabetes management.

  1. Online video in clinical skills education of oral medication administration for undergraduate student nurses: a mixed methods, prospective cohort study.

    PubMed

    Holland, Agi; Smith, Fiona; McCrossan, Gill; Adamson, Elizabeth; Watt, Susan; Penny, Kay

    2013-06-01

    Improvements in the safety of the prescribing, dispensing and administration of medicines are identified as a priority across international healthcare systems. It is therefore essential that higher education institutions play their part in helping to meet this patient safety objective. New developments in clinical skills education which are aligned to emerging educational theory are available, but evaluations and supportive evidence are limited. To evaluate the use of an online best practice exemplar as an adjunct to the clinical skills teaching of oral medication administration to undergraduate student nurses. Mixed-methods prospective cohort design. Two intakes of undergraduate nursing students (n=168, n=154) undertaking a first year clinical skills based module at a British university. The Control group received standard teaching using lectures and skills classes facilitated by experienced clinical skills lecturers. The Intervention group received the standard teaching and unlimited access to an online video clip of medication administration. Performance and satisfaction were measured using module assessment results and a satisfaction questionnaire. Qualitative data were gathered using focus groups (n=16, n=20). The Intervention group was significantly (p=0.021) more likely to pass the assessment and rate their satisfaction with the teaching significantly higher (p<0.05) on more than half of the items from the Student Satisfaction Survey. Two Categories were identified from focus group data; Classroom Learning and Transfer to Practice. Classroom Learning included four themes of Peers, Self, Teaching and Time and when Classroom Learning was positive, the Transfer to Practice of the clinical skill was enhanced. An online video of a best practice exemplar as an adjunct to taught clinical skills sessions improves student assessment results and satisfaction ratings. The video was also reported to positively influence all themes identified in Classroom Learning and was perceived to promote the Transfer to Practice of teaching input. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Impact of margin status and lymphadenectomy on clinical outcomes in resected pancreatic adenocarcinoma: implications for adjuvant radiotherapy.

    PubMed

    Osipov, Arsen; Naziri, Jason; Hendifar, Andrew; Dhall, Deepti; Rutgers, Joanne K; Chopra, Shefali; Li, Quanlin; Tighiouart, Mourad; Annamalai, Alagappan; Nissen, Nicholas N; Tuli, Richard

    2016-04-01

    Adjuvant chemoradiotherapy (CRT) in the treatment of pancreatic ductal adenocarcinoma (PDA) is controversial. Minimal data exists regarding the clinical significance of margin clearance distance and lymph node (LN) parameters, such as extent of dissection and LN ratio. We assessed the impact of these variables on clinical outcomes to more clearly define the subset of patients who may benefit from adjuvant radiotherapy (RT). We identified 106 patients with resected stage 1-3 PDA from 2007-2013. Resection margins were categorized as positive (tumor at ink), ≤1, or >1 mm. LN evaluation included total number examined (NE), number of positive nodes (NP), ratio of NP to NE (NR), extent of dissection, and positive periportal LNs. The impact of these variables was assessed on disease-free survival (DFS) and overall survival (OS) using multivariate cox proportional hazards modeling. In patients receiving adjuvant chemotherapy (CT) alone, greater margin clearance led to improved DFS (P=0.0412, HR =0.51). Range of NE was 4-37, with a mean of 19. NE was not associated with DFS or OS, yet absolute NP of 5 or more was associated with a significantly worse DFS (P=0.005). Whereas periportal lymphadenectomy did not result in improved DFS or OS, patients with positive periportal LN had worse clinical outcomes (DFS, P=0.0052; OS, P=0.023). The use of adjuvant CRT was associated with improved OS (P=0.049; HR=0.29). In patients receiving adjuvant CT alone, there was a clinically significant benefit to clearing the surgical margin beyond tumor at ink. Having ≥5 NP and positive periportal LN led to significantly worse clinical outcomes. The addition of adjuvant RT to CT in resected PDA improved OS. A comprehensive evaluation of resection margin distance and LN parameters may identify more patients at risk for locoregional failure who may benefit from adjuvant CRT.

  3. Impact of margin status and lymphadenectomy on clinical outcomes in resected pancreatic adenocarcinoma: implications for adjuvant radiotherapy

    PubMed Central

    Osipov, Arsen; Naziri, Jason; Hendifar, Andrew; Dhall, Deepti; Rutgers, Joanne K.; Chopra, Shefali; Li, Quanlin; Tighiouart, Mourad; Annamalai, Alagappan; Nissen, Nicholas N.

    2016-01-01

    Background Adjuvant chemoradiotherapy (CRT) in the treatment of pancreatic ductal adenocarcinoma (PDA) is controversial. Minimal data exists regarding the clinical significance of margin clearance distance and lymph node (LN) parameters, such as extent of dissection and LN ratio. We assessed the impact of these variables on clinical outcomes to more clearly define the subset of patients who may benefit from adjuvant radiotherapy (RT). Methods We identified 106 patients with resected stage 1-3 PDA from 2007-2013. Resection margins were categorized as positive (tumor at ink), ≤1, or >1 mm. LN evaluation included total number examined (NE), number of positive nodes (NP), ratio of NP to NE (NR), extent of dissection, and positive periportal LNs. The impact of these variables was assessed on disease-free survival (DFS) and overall survival (OS) using multivariate cox proportional hazards modeling. Results In patients receiving adjuvant chemotherapy (CT) alone, greater margin clearance led to improved DFS (P=0.0412, HR =0.51). Range of NE was 4-37, with a mean of 19. NE was not associated with DFS or OS, yet absolute NP of 5 or more was associated with a significantly worse DFS (P=0.005). Whereas periportal lymphadenectomy did not result in improved DFS or OS, patients with positive periportal LN had worse clinical outcomes (DFS, P=0.0052; OS, P=0.023). The use of adjuvant CRT was associated with improved OS (P=0.049; HR=0.29). Conclusions In patients receiving adjuvant CT alone, there was a clinically significant benefit to clearing the surgical margin beyond tumor at ink. Having ≥5 NP and positive periportal LN led to significantly worse clinical outcomes. The addition of adjuvant RT to CT in resected PDA improved OS. A comprehensive evaluation of resection margin distance and LN parameters may identify more patients at risk for locoregional failure who may benefit from adjuvant CRT. PMID:27034792

  4. Information and Communication Technologies for the Dissemination of Clinical Practice Guidelines to Health Professionals: A Systematic Review.

    PubMed

    De Angelis, Gino; Davies, Barbara; King, Judy; McEwan, Jessica; Cavallo, Sabrina; Loew, Laurianne; Wells, George A; Brosseau, Lucie

    2016-11-30

    The transfer of research knowledge into clinical practice can be a continuous challenge for researchers. Information and communication technologies, such as websites and email, have emerged as popular tools for the dissemination of evidence to health professionals. The objective of this systematic review was to identify research on health professionals' perceived usability and practice behavior change of information and communication technologies for the dissemination of clinical practice guidelines. We used a systematic approach to retrieve and extract data about relevant studies. We identified 2248 citations, of which 21 studies met criteria for inclusion; 20 studies were randomized controlled trials, and 1 was a controlled clinical trial. The following information and communication technologies were evaluated: websites (5 studies), computer software (3 studies), Web-based workshops (2 studies), computerized decision support systems (2 studies), electronic educational game (1 study), email (2 studies), and multifaceted interventions that consisted of at least one information and communication technology component (6 studies). Website studies demonstrated significant improvements in perceived usefulness and perceived ease of use, but not for knowledge, reducing barriers, and intention to use clinical practice guidelines. Computer software studies demonstrated significant improvements in perceived usefulness, but not for knowledge and skills. Web-based workshop and email studies demonstrated significant improvements in knowledge, perceived usefulness, and skills. An electronic educational game intervention demonstrated a significant improvement from baseline in knowledge after 12 and 24 weeks. Computerized decision support system studies demonstrated variable findings for improvement in skills. Multifaceted interventions demonstrated significant improvements in beliefs about capabilities, perceived usefulness, and intention to use clinical practice guidelines, but variable findings for improvements in skills. Most multifaceted studies demonstrated significant improvements in knowledge. The findings suggest that health professionals' perceived usability and practice behavior change vary by type of information and communication technology. Heterogeneity and the paucity of properly conducted studies did not allow for a clear comparison between studies and a conclusion on the effectiveness of information and communication technologies as a knowledge translation strategy for the dissemination of clinical practice guidelines. ©Gino De Angelis, Barbara Davies, Judy King, Jessica McEwan, Sabrina Cavallo, Laurianne Loew, George A Wells, Lucie Brosseau. Originally published in JMIR Medical Education (http://mededu.jmir.org), 30.11.2016.

  5. eFAST for Pneumothorax: Real-Life Application in an Urban Level 1 Center by Trauma Team Members.

    PubMed

    Maximus, Steven; Figueroa, Cesar; Whealon, Matthew; Pham, Jacqueline; Kuncir, Eric; Barrios, Cristobal

    2018-02-01

    The focused assessment with sonography for trauma (FAST) examination has become the standard of care for rapid evaluation of trauma patients. Extended FAST (eFAST) is the use of ultrasonography for the detection of pneumothorax (PTX). The exact sensitivity and specificity of eFAST detecting traumatic PTX during practical "real-life" application is yet to be investigated. This is a retrospective review of all trauma patients with a diagnosis of PTX, who were treated at a large level 1 urban trauma center from March 2013 through July 2014. Charts were reviewed for results of imaging, which included eFAST, chest X-ray, and CT scan. The requirement of tube thoracostomy and mechanism of injury were also analyzed. A total of 369 patients with a diagnosis of PTX were identified. A total of 69 patients were excluded, as eFAST was either not performed or not documented, leaving 300 patients identified with PTX. A total of 113 patients had clinically significant PTX (37.6%), requiring immediate tube thoracostomy placement. eFAST yielded a positive diagnosis of PTX in 19 patients (16.8%), and all were clinically significant, requiring tube thoracostomy. Chest X-ray detected clinically significant PTX in 105 patients (92.9%). The literature on the utility of eFAST for PTX in trauma is variable. Our data show that although specific for clinically significant traumatic PTX, it has poor sensitivity when performed by clinicians with variable levels of ultrasound training. We conclude that CT is still the gold standard in detecting PTX, and clinicians performing eFAST should have adequate training.

  6. Acute posttraumatic stress symptoms and depression after exposure to the 2005 Saskatchewan Centennial Air Show disaster: prevalence and predictors.

    PubMed

    Taylor, Steven; Asmundson, Gordon J G; Carleton, R Nicholas; Brundin, Peter

    2007-01-01

    The purpose of this study was to determine the prevalence of acute distress-that is, clinically significant posttraumatic stress symptoms (PTSS) and depression-and to identify predictors of each in a sample of people who witnessed a fatal aircraft collision at the 2005 Saskatchewan Centennial Air Show. Air Show attendees (N = 157) were recruited by advertisements in the local media and completed an Internet-administered battery of questionnaires. Based on previously established cut-offs, 22 percent respondents had clinically significant PTSS and 24 percent had clinically significant depressive symptoms. Clinically significant symptoms were associated with posttrauma impairment in social and occupational functioning. Acute distress was associated with several variables, including aspects of Air Show trauma exposure, severity of prior trauma exposure, low posttrauma social support (ie, negative responses by others), indices of poor coping (eg, intolerance of uncertainty, rumination about the trauma), and elevated scores on anxiety sensitivity, the personality trait of absorption, and dissociative tendencies. Results suggest that clinically significant acute distress is common in the aftermath of witnessed trauma. The statistical predictors (correlates) of acute distress were generally consistent with the results of studies of other forms of trauma. People with elevated scores on theoretical vulnerability factors (eg, elevated anxiety sensitivity) were particularly likely to develop acute distress.

  7. Genes with mutation significance were highly associated with the clinical pattern of patients with breast cancer.

    PubMed

    Ding, Wan-Jun; Zeng, Tao; Wang, Li-Jun; Lei, Hong-Bo; Ge, Wei; Wang, Zhi

    2017-11-17

    In the United States, breast cancer is the second leading cause of cancer death in women. Over the past 20 years, breast cancer incidence and mortality rates increased rapidly in developing regions. We aimed to identify the gene mutation patterns that associated with the clinical patterns, including survival status, histo-pathological classes and so forth, of breast cancer. We retrieved 1098 cases of the clinical information, and level-3 legacy data of mRNA expression level, protein expression data and mutation files from GDC data portal. The genes with mutation significance were obtained. We studied the impacts of mutation types on the expression levels of mRNA and protein. Different statistics methods were used to calculate the correlation between the mutation types and the expression data or histo-clinical measures. There were 24 genes with mutation significance identified. The most mutated genes were selected to study the role of specific mutations played on the patients with breast cancer. One interesting finding was the missense mutations on TP53 were related with high expression levels of mRNA and protein. The missense mutations on TP53 were highly related with the morphology, race, ER status, PR status and HER2 Status, while the truncated mutations were only related with the morphology, ER status and PR status. The missense mutation on PIK3CA was highly associated with the morphology, race, ER status and PR status. The mutants with different mutants and the wild type of the most mutated genes had different impacts on the histo-clinical measures that might help personalized therapy.

  8. Identifying Sources of Clinical Conflict: A Tool for Practice and Training in Bioethics Mediation.

    PubMed

    Bergman, Edward J

    2015-01-01

    Bioethics mediators manage a wide range of clinical conflict emanating from diverse sources. Parties to clinical conflict are often not fully aware of, nor willing to express, the true nature and scope of their conflict. As such, a significant task of the bioethics mediator is to help define that conflict. The ability to assess and apply the tools necessary for an effective mediation process can be facilitated by each mediator's creation of a personal compendium of sources that generate clinical conflict, to provide an orientation for the successful management of complex dilemmatic cases. Copyright 2015 The Journal of Clinical Ethics. All rights reserved.

  9. Using simulation modeling to improve patient flow at an outpatient orthopedic clinic.

    PubMed

    Rohleder, Thomas R; Lewkonia, Peter; Bischak, Diane P; Duffy, Paul; Hendijani, Rosa

    2011-06-01

    We report on the use of discrete event simulation modeling to support process improvements at an orthopedic outpatient clinic. The clinic was effective in treating patients, but waiting time and congestion in the clinic created patient dissatisfaction and staff morale issues. The modeling helped to identify improvement alternatives including optimized staffing levels, better patient scheduling, and an emphasis on staff arriving promptly. Quantitative results from the modeling provided motivation to implement the improvements. Statistical analysis of data taken before and after the implementation indicate that waiting time measures were significantly improved and overall patient time in the clinic was reduced.

  10. Critical appraisal of the top-down approach for vesicoureteral reflux.

    PubMed

    Abdelhalim, Ahmed; Khoury, Antoine E

    2017-06-01

    Vesicoureteral reflux (VUR) has been linked to recurrent urinary tract infections (UTIs), renal scarring, hypertension, renal insufficiency and end-stage kidney disease. Different imaging strategies have been proposed to approach children presenting with UTI to sort out patients with significant VUR while minimizing patient morbidity, radiation exposure and financial burden. None of these imaging strategies is universally accepted. The"top-down approach" (TDA) aims at restricting the number of voiding cystourethrograms (VCUGs) and its associated morbidity while identifying patients with clinically-significant reflux. In this approach, children presenting with febrile UTIs are acutely investigated with dimercapto-succinic acid (DMSA) renal scans to identify patients with renal parenchymal inflammation. Those with evidence of renal affection are offered VCUG and late DMSA scan to identify VUR and permanent renal scarring, respectively. Although TDA could identify clinically-significant VUR with high sensitivity, it is not without limitations. The approach segregates patients based on the presence of DMSA cortical lesions omitting the morbidity and the economic burden of UTI. Additionally, some of DMSA lesions are attributed to congenital dysplasia and unrelated to UTI. Ionizing radiation exposure, financial costs, limited availability of DMSA scans in the acute setting, variability in interpreting the results and low yield of actionable findings on DMSA scans are some other limitations. In this review, we tried to address the drawbacks of the TDA and reinforce the value of patient-centered approach for VUR.

  11. Critical appraisal of the top-down approach for vesicoureteral reflux

    PubMed Central

    Abdelhalim, Ahmed

    2017-01-01

    Vesicoureteral reflux (VUR) has been linked to recurrent urinary tract infections (UTIs), renal scarring, hypertension, renal insufficiency and end-stage kidney disease. Different imaging strategies have been proposed to approach children presenting with UTI to sort out patients with significant VUR while minimizing patient morbidity, radiation exposure and financial burden. None of these imaging strategies is universally accepted. The“top-down approach” (TDA) aims at restricting the number of voiding cystourethrograms (VCUGs) and its associated morbidity while identifying patients with clinically-significant reflux. In this approach, children presenting with febrile UTIs are acutely investigated with dimercapto-succinic acid (DMSA) renal scans to identify patients with renal parenchymal inflammation. Those with evidence of renal affection are offered VCUG and late DMSA scan to identify VUR and permanent renal scarring, respectively. Although TDA could identify clinically-significant VUR with high sensitivity, it is not without limitations. The approach segregates patients based on the presence of DMSA cortical lesions omitting the morbidity and the economic burden of UTI. Additionally, some of DMSA lesions are attributed to congenital dysplasia and unrelated to UTI. Ionizing radiation exposure, financial costs, limited availability of DMSA scans in the acute setting, variability in interpreting the results and low yield of actionable findings on DMSA scans are some other limitations. In this review, we tried to address the drawbacks of the TDA and reinforce the value of patient-centered approach for VUR. PMID:28612056

  12. Clinical Practice Guideline Selection, Development, Implementation, and Evaluation

    DTIC Science & Technology

    2000-02-01

    interventions for a particular diagnosis” (Henning, 1997) developed by members of the hospital staff. They can be Clinical Practice Guidelines6 conceptualized...health care environment , it is more important than ever for health care organizations to select the most cost-effective procedures, and to continuously...of the studies regarding the targeted illness/injury will enable this team to identify those interventions strongly supported by significant

  13. Staff and students' perceptions and experiences of teaching and assessment in Clinical Skills Laboratories: interview findings from a multiple case study.

    PubMed

    Houghton, Catherine E; Casey, Dympna; Shaw, David; Murphy, Kathy

    2012-08-01

    The Clinical Skills Laboratory has become an essential structure in nurse education and several benefits of its use have been identified. However, the literature identifies the need to examine the transferability of skills learned there into the reality of practice. This research explored the role of the Clinical Skills Laboratory in preparing nursing students for the real world of practice. This paper focuses specifically on the perceptions of the teaching and assessment strategies employed there. Qualitative multiple case study design. Five case study sites. Interviewees (n=58) included academic staff, clinical staff and nursing students. Semi-structured interviews. The Clinical Skills Laboratory can provide a pathway to practice and its authenticity is significant. Teaching strategies need to incorporate communication as well as psychomotor skills. Including audio-visual recording into assessment strategies is beneficial. Effective relationships between education institutions and clinical settings are needed to enhance the transferability of the skills learned. The Clinical Skills Laboratory should provide an authentic learning environment, with the appropriate use of teaching strategies. It is crucial that effective links between educators and clinical staff are established and maintained. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Whole Blood Gene Expression Profiling Predicts Severe Morbidity and Mortality in Cystic Fibrosis: A 5-Year Follow-Up Study.

    PubMed

    Saavedra, Milene T; Quon, Bradley S; Faino, Anna; Caceres, Silvia M; Poch, Katie R; Sanders, Linda A; Malcolm, Kenneth C; Nichols, David P; Sagel, Scott D; Taylor-Cousar, Jennifer L; Leach, Sonia M; Strand, Matthew; Nick, Jerry A

    2018-05-01

    Cystic fibrosis pulmonary exacerbations accelerate pulmonary decline and increase mortality. Previously, we identified a 10-gene leukocyte panel measured directly from whole blood, which indicates response to exacerbation treatment. We hypothesized that molecular characteristics of exacerbations could also predict future disease severity. We tested whether a 10-gene panel measured from whole blood could identify patient cohorts at increased risk for severe morbidity and mortality, beyond standard clinical measures. Transcript abundance for the 10-gene panel was measured from whole blood at the beginning of exacerbation treatment (n = 57). A hierarchical cluster analysis of subjects based on their gene expression was performed, yielding four molecular clusters. An analysis of cluster membership and outcomes incorporating an independent cohort (n = 21) was completed to evaluate robustness of cluster partitioning of genes to predict severe morbidity and mortality. The four molecular clusters were analyzed for differences in forced expiratory volume in 1 second, C-reactive protein, return to baseline forced expiratory volume in 1 second after treatment, time to next exacerbation, and time to morbidity or mortality events (defined as lung transplant referral, lung transplant, intensive care unit admission for respiratory insufficiency, or death). Clustering based on gene expression discriminated between patient groups with significant differences in forced expiratory volume in 1 second, admission frequency, and overall morbidity and mortality. At 5 years, all subjects in cluster 1 (very low risk) were alive and well, whereas 90% of subjects in cluster 4 (high risk) had suffered a major event (P = 0.0001). In multivariable analysis, the ability of gene expression to predict clinical outcomes remained significant, despite adjustment for forced expiratory volume in 1 second, sex, and admission frequency. The robustness of gene clustering to categorize patients appropriately in terms of clinical characteristics, and short- and long-term clinical outcomes, remained consistent, even when adding in a secondary population with significantly different clinical outcomes. Whole blood gene expression profiling allows molecular classification of acute pulmonary exacerbations, beyond standard clinical measures, providing a predictive tool for identifying subjects at increased risk for mortality and disease progression.

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

    PubMed

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

    2013-01-01

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

  16. Risk factors of significant pain syndrome 90 days after minor thoracic injury: trajectory analysis.

    PubMed

    Daoust, Raoul; Emond, Marcel; Bergeron, Eric; LeSage, Natalie; Camden, Stéphanie; Guimont, Chantal; Vanier, Laurent; Chauny, Jean-Marc

    2013-11-01

    The objective was to identify the risk factors of clinically significant pain at 90 days in patients with minor thoracic injury (MTI) discharged from the emergency department (ED). A prospective, multicenter, cohort study was conducted in four Canadian EDs from November 2006 to November 2010. All consecutive patients aged 16 years or older with MTI were eligible at discharge from EDs. They underwent standardized clinical and radiologic evaluations at 1 and 2 weeks, followed by standardized telephone interviews at 30 and 90 days. A pain trajectory model characterized groups of patients with different pain evolutions and ascertained specific risk factors in each group through multivariate analysis. In this cohort of 1,132 patients, 734 were eligible for study inclusion. The authors identified a pain trajectory that characterized 18.2% of the study population experiencing clinically significant pain (>3 of 10) at 90 days after a MTI. Multivariate modeling found two or more rib fractures, smoking, and initial oxygen saturation below 95% to be predictors of this group of patients. To the authors' knowledge, this is the first prospective study of trajectory modeling to detect risk factors associated with significant pain at 90 days after MTI. These factors may help in planning specific treatment strategies and should be validated in another prospective cohort. © 2013 by the Society for Academic Emergency Medicine.

  17. PREOPERATIVE MRI IMPROVES PREDICTION OF EXTENSIVE OCCULT AXILLARY LYMPH NODE METASTASES IN BREAST CANCER PATIENTS WITH A POSITIVE SENTINEL LYMPH NODE BIOPSY

    PubMed Central

    Loiselle, Christopher; Eby, Peter R.; Kim, Janice N.; Calhoun, Kristine E.; Allison, Kimberly H.; Gadi, Vijayakrishna K.; Peacock, Sue; Storer, Barry; Mankoff, David A.; Partridge, Savannah C.; Lehman, Constance D.

    2014-01-01

    Rationale and Objectives To test the ability of quantitative measures from preoperative Dynamic Contrast Enhanced MRI (DCE-MRI) to predict, independently and/or with the Katz pathologic nomogram, which breast cancer patients with a positive sentinel lymph node biopsy will have ≥ 4 positive axillary lymph nodes upon completion axillary dissection. Methods and Materials A retrospective review was conducted to identify clinically node-negative invasive breast cancer patients who underwent preoperative DCE-MRI, followed by sentinel node biopsy with positive findings and complete axillary dissection (6/2005 – 1/2010). Clinical/pathologic factors, primary lesion size and quantitative DCE-MRI kinetics were collected from clinical records and prospective databases. DCE-MRI parameters with univariate significance (p < 0.05) to predict ≥ 4 positive axillary nodes were modeled with stepwise regression and compared to the Katz nomogram alone and to a combined MRI-Katz nomogram model. Results Ninety-eight patients with 99 positive sentinel biopsies met study criteria. Stepwise regression identified DCE-MRI total persistent enhancement and volume adjusted peak enhancement as significant predictors of ≥4 metastatic nodes. Receiver operating characteristic (ROC) curves demonstrated an area under the curve (AUC) of 0.78 for the Katz nomogram, 0.79 for the DCE-MRI multivariate model, and 0.87 for the combined MRI-Katz model. The combined model was significantly more predictive than the Katz nomogram alone (p = 0.003). Conclusion Integration of DCE-MRI primary lesion kinetics significantly improved the Katz pathologic nomogram accuracy to predict presence of metastases in ≥ 4 nodes. DCE-MRI may help identify sentinel node positive patients requiring further localregional therapy. PMID:24331270

  18. Enhanced patient reported outcome measurement suitable for head and neck cancer follow-up clinics

    PubMed Central

    2012-01-01

    Background The ‘Worse-Stable-Better’ (W-S-B) question was introduced to capture patient-perceived change in University of Washington Quality of Life (UW-QOL) domains. Methods 202 head and neck cancer patients in remission prospectively completed UW-QOL and Patients Concerns Inventory (PCI). For each UW-QOL domain, patients indicated whether over the last month things had worsened (W), remained stable (S) or were better (B). Results 202 patients at 448 attendances selected 1752 PCI items they wanted to discuss in consultation, and 58% (1024/1752) of these were not covered by the UW-QOL. UW-QOL algorithms highlighted another 440 significant problems that the patient did not want to discuss (i.e. the corresponding items on the PCI were not selected). After making allowance for UW-QOL algorithms to identify 'significant problems' and PCI selection of corresponding issues for discussion there remained clear residual and notable variation in W-S-B responses, in particular to identify patients with significant problems that were getting worse, and patients without significant problems that wanted to discuss issues that were getting worse. Changes in mean UW-QOL scores were notably lower for those getting worse on the W-S-B question, typically by 10 or more units a magnitude that suggests clinically important changes in score. Conclusions The W-S-B question adds little questionnaire burden and could help to better identify patients who might benefit from intervention. The results of this study suggest that the UW-QOL with the W-S-B modification should be used together with the PCI to allow optimal identification of issues for patient-clinician discussion during routine outpatient clinics. PMID:22695251

  19. Clinical relevance of findings in trials of CBT for depression.

    PubMed

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

    2017-09-01

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

  20. Inactivation of Hippo Pathway Is Significantly Associated with Poor Prognosis in Hepatocellular Carcinoma.

    PubMed

    Sohn, Bo Hwa; Shim, Jae-Jun; Kim, Sang-Bae; Jang, Kyu Yun; Kim, Soo Mi; Kim, Ji Hoon; Hwang, Jun Eul; Jang, Hee-Jin; Lee, Hyun-Sung; Kim, Sang-Cheol; Jeong, Woojin; Kim, Sung Soo; Park, Eun Sung; Heo, Jeonghoon; Kim, Yoon Jun; Kim, Dae-Ghon; Leem, Sun-Hee; Kaseb, Ahmed; Hassan, Manal M; Cha, Minse; Chu, In-Sun; Johnson, Randy L; Park, Yun-Yong; Lee, Ju-Seog

    2016-03-01

    The Hippo pathway is a tumor suppressor in the liver. However, the clinical significance of Hippo pathway inactivation in HCC is not clearly defined. We analyzed genomic data from human and mouse tissues to determine clinical relevance of Hippo pathway inactivation in HCC. We analyzed gene expression data from Mst1/2(-/-) and Sav1(-/-) mice and identified a 610-gene expression signature reflecting Hippo pathway inactivation in the liver [silence of Hippo (SOH) signature]. By integrating gene expression data from mouse models with those from human HCC tissues, we developed a prediction model that could identify HCC patients with an inactivated Hippo pathway and used it to test its significance in HCC patients, via univariate and multivariate Cox analyses. HCC patients (National Cancer Institute cohort, n = 113) with the SOH signature had a significantly poorer prognosis than those without the SOH signature [P < 0.001 for overall survival (OS)]. The significant association of the signature with poor prognosis was further validated in the Korean (n = 100, P = 0.006 for OS) and Fudan University cohorts (n = 242, P = 0.001 for OS). On multivariate analysis, the signature was an independent predictor of recurrence-free survival (HR, 1.6; 95% confidence interval, 1.12-2.28: P = 0.008). We also demonstrated significant concordance between the SOH HCC subtype and the hepatic stem cell HCC subtype that had been identified in a previous study (P < 0.001). Inactivation of the Hippo pathway in HCC is significantly associated with poor prognosis. ©2015 American Association for Cancer Research.

  1. How large must a treatment effect be before it matters to practitioners? An estimation method and demonstration.

    PubMed

    Miller, William R; Manuel, Jennifer Knapp

    2008-09-01

    Treatment research is sometimes criticised as lacking in clinical relevance, and one potential source of this friction is a disconnection between statistical significance and what clinicians regard to be a meaningful difference in outcomes. This report demonstrates a novel methodology for estimating what substance abuse practitioners regard to be clinically important differences. To illustrate the estimation method, we surveyed 50 substance abuse treatment providers participating in the National Institute on Drug Abuse (NIDA) Clinical Trials Network. Practitioners identified thresholds for clinically meaningful differences on nine common outcome variables, indicated the size of effect that would justify their learning a new treatment method and estimated current outcomes from their services. Clinicians judged a difference between two treatments to be meaningful if outcomes were improved by about 10 - 12 points on the percentage of patients totally abstaining, arrested for driving while intoxicated, employed or having abnormal liver enzymes. A 5 percentage-point reduction in patient mortality was regarded as clinically significant. On continuous outcome measures (such as percentage of days abstinent or drinks per drinking day), practitioners judged an outcome to be significant when it doubled or halved the base rate. When a new treatment meets such criteria, practitioners were interested in learning it. Effects that are statistically significant in clinical trials may be unimpressive to practitioners. Clinicians' judgements of meaningful differences can inform the powering of clinical trials.

  2. SU-F-R-53: CT-Based Radiomics Analysis of Non-Small Cell Lung Cancer Patients Treated with Stereotactic Body Radiation Therapy

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

    Huynh, E; Coroller, T; Narayan, V

    Purpose: Stereotactic body radiation therapy (SBRT) is the standard of care for medically inoperable non-small cell lung cancer (NSCLC) patients and has demonstrated excellent local control and survival. However, some patients still develop distant metastases and local recurrence, and therefore, there is a clinical need to identify patients at high-risk of disease recurrence. The aim of the current study is to use a radiomics approach to identify imaging biomarkers, based on tumor phenotype, for clinical outcomes in SBRT patients. Methods: Radiomic features were extracted from free breathing computed tomography (CT) images of 113 Stage I-II NSCLC patients treated with SBRT.more » Their association to and prognostic performance for distant metastasis (DM), locoregional recurrence (LRR) and survival was assessed and compared with conventional features (tumor volume and diameter) and clinical parameters (e.g. performance status, overall stage). The prognostic performance was evaluated using the concordance index (CI). Multivariate model performance was evaluated using cross validation. All p-values were corrected for multiple testing using the false discovery rate. Results: Radiomic features were associated with DM (one feature), LRR (one feature) and survival (four features). Conventional features were only associated with survival and one clinical parameter was associated with LRR and survival. One radiomic feature was significantly prognostic for DM (CI=0.670, p<0.1 from random), while none of the conventional and clinical parameters were significant for DM. The multivariate radiomic model had a higher median CI (0.671) for DM than the conventional (0.618) and clinical models (0.617). Conclusion: Radiomic features have potential to be imaging biomarkers for clinical outcomes that conventional imaging metrics and clinical parameters cannot predict in SBRT patients, such as distant metastasis. Development of a radiomics biomarker that can identify patients at high-risk of recurrence could facilitate personalization of their treatment regimen for an optimized clinical outcome. R.M. had consulting interest with Amgen (ended in 2015).« less

  3. Optical Magnetic Induction Tomography of the Heart

    PubMed Central

    Marmugi, Luca; Renzoni, Ferruccio

    2016-01-01

    Atrial Fibrillation (AF) affects a significant fraction of the ageing population, causing a high level of morbidity and mortality. Despite its significance, the causes of AF are still not uniquely identified. This, combined with the lack of precise diagnostic and guiding tools, makes the clinical treatment of AF sub-optimal. We identify magnetic induction tomography as the most promising technique for the investigation of the causes of fibrillation and for its clinical practice. We therefore propose a novel optical instrument based on optical atomic magnetometers, fulfilling the requirements for diagnostic mapping of the heart’s conductivity. The feasibility of the device is here discussed in view of the final application. Thanks to the potential of atomic magnetometers for miniaturisation and extreme sensitivity at room temperature, a new generation of compact and non-invasive diagnostic instrumentation, with both bedside and intra-operative operation capability, is envisioned. Possible scenarios both in clinical practice and biomedical research are then discussed. The flexibility of the system makes it promising also for application in other fields, such as neurology and oncology. PMID:27040727

  4. Clinical features, proximate causes, and consequences of active convulsive epilepsy in Africa

    PubMed Central

    Kariuki, Symon M; Matuja, William; Akpalu, Albert; Kakooza-Mwesige, Angelina; Chabi, Martin; Wagner, Ryan G; Connor, Myles; Chengo, Eddie; Ngugi, Anthony K; Odhiambo, Rachael; Bottomley, Christian; White, Steven; Sander, Josemir W; Neville, Brian G R; Newton, Charles R J C

    2014-01-01

    Purpose Epilepsy is common in sub-Saharan Africa (SSA), but the clinical features and consequences are poorly characterized. Most studies are hospital-based, and few studies have compared different ecological sites in SSA. We described active convulsive epilepsy (ACE) identified in cross-sectional community-based surveys in SSA, to understand the proximate causes, features, and consequences. Methods We performed a detailed clinical and neurophysiologic description of ACE cases identified from a community survey of 584,586 people using medical history, neurologic examination, and electroencephalography (EEG) data from five sites in Africa: South Africa; Tanzania; Uganda; Kenya; and Ghana. The cases were examined by clinicians to discover risk factors, clinical features, and consequences of epilepsy. We used logistic regression to determine the epilepsy factors associated with medical comorbidities. Key Findings Half (51%) of the 2,170 people with ACE were children and 69% of seizures began in childhood. Focal features (EEG, seizure types, and neurologic deficits) were present in 58% of ACE cases, and these varied significantly with site. Status epilepticus occurred in 25% of people with ACE. Only 36% received antiepileptic drugs (phenobarbital was the most common drug [95%]), and the proportion varied significantly with the site. Proximate causes of ACE were adverse perinatal events (11%) for onset of seizures before 18 years; and acute encephalopathy (10%) and head injury prior to seizure onset (3%). Important comorbidities were malnutrition (15%), cognitive impairment (23%), and neurologic deficits (15%). The consequences of ACE were burns (16%), head injuries (postseizure) (1%), lack of education (43%), and being unmarried (67%) or unemployed (57%) in adults, all significantly more common than in those without epilepsy. Significance There were significant differences in the comorbidities across sites. Focal features are common in ACE, suggesting identifiable and preventable causes. Malnutrition and cognitive and neurologic deficits are common in people with ACE and should be integrated into the management of epilepsy in this region. Consequences of epilepsy such as burns, lack of education, poor marriage prospects, and unemployment need to be addressed. PMID:24116877

  5. Using the patients concerns inventory for distress screening in post-treatment head and neck cancer survivors.

    PubMed

    Ghazali, Naseem; Roe, Brenda; Lowe, Derek; Tandon, Sank; Jones, Terry; Shaw, Richard; Risk, Janet; Rogers, Simon N

    2017-10-01

    Cancer patients can experience significant distress during their cancer trajectory, which impacts upon clinical outcomes and quality of life. Screening for distress using holistic assessments can help identify and address unmet concerns/needs. The purpose of this study was to evaluate the relationship between concerns and distress, and the impact of distress on clinic outcomes in post-treatment head and neck cancer patients. 170 patients attending routine follow-up clinics were prospectively recruited. All patients completed the Patient Concerns Inventory (PCI) and the Distress thermometer (DT) at preconsultation. The rate of significant distress (i.e. DT cut-off score ≥4) was 36% (62/170). Significantly distressed patients selected more items overall than patients without distress (mean, median (QR) of 5.40, 5 (2-8) vs 2.61, 2 (0-4), p < 0.001). Significant distress was most strongly associated with Physical and Functional well-being (p < 0.001) and Psychological and Emotional well-being domains (p = 0.001). On balance, very little difference was noted between cut-off points of either ≥4 or ≥5 PCI items of concern selected. Both cut-off points demonstrated an acceptable level of sensitivity, specificity and predictive values for significant distress. Consultations were longer with increasing numbers of concerns. Just over one-third of patients are significantly distressed. They were more likely to express a higher number of concerns. A cutoff score ≥4 or ≥5 PCI items selected can identify those at risk of significant distress. Concerns causing significant distress were related to emotional/psychological issues and physical function. Copyright © 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  6. Antimicrobial resistance and beta-lactamase production of clinical isolates of prevotella and porphyromonas species.

    PubMed

    Bahar, Hrisi; Torun, Muzeyyen Mamal; Demirci, Mehmet; Kocazeybek, Bekir

    2005-03-01

    This study determined the beta-lactamase production and the antimicrobial resistance of 72 Prevotella species and 48 Porphyromonas species isolated from different clinical specimens. All strains were identified using API 32 ID. The beta-lactamase production was determined by nitrocefin disks. E test strips of benzylpenicillin, ampicillin + sulbactam, cefoxitin, clindamycin, metronidazole and imipenem were tested for each strain. Nineteen Prevotella melaninogenica, 18 Prevotella intermedia, 16 Prevotella denticola, 11 Prevotella loescheii and 8 Prevotella bivia strains were identified. Four were clindamycin resistant. The highest beta-lactamase production was found at a rate of 68.4% in P. melaninogenica species. Additionally, 33 Porphyromonas asaccharolytica and 15 Porphyromonas gingivalis strains were identified. None of them produced beta-lactamase. In view of the emerging antibiotic resistance among anaerobes, the current local susceptibility profile of our Prevotella and Porphyromonas species will establish the basis for additional surveys tracing significant changes in the antimicrobial resistance of our clinical isolates. Copyright 2005 S. Karger AG, Basel.

  7. Factors leading to overutilisation of hospital pathology testing: the junior doctor.

    PubMed

    Ericksson, William; Bothe, Janine; Cheung, Heidi; Zhang, Kate; Kelly, Simone

    2017-05-25

    Objective Pathology overutilisation is a significant issue affecting the quality and cost of health care. Because junior medical officers (JMOs) order most pathology tests in the hospital setting, the aim of the present study was to identify the main reasons for hospital pathology overutilisation from the perspective of the JMO. Methods A qualitative method, using focus group methodology, was undertaken. Sixteen JMOs from two hospitals participated in three focus groups. Data were analysed using thematic analysis. Results Three major themes contributed to overutilisation: the real and perceived expectations of senior colleagues, the level of JMO clinical experience and strategies to manage JMO workload around clinical systems. Within these themes, 12 subthemes were identified. Conclusions Overutilisation of hospital pathology testing occurs when there are high social costs to JMOs for underordering, with little cost for overordering. Interventions should restore this balance through reframing overutilisation as both a costly and potentially harmful activity, promoting a supportive culture with regular senior guidance, and addressing clinical systems in which missed tests create an excessive workload. What is known about the topic? Mean overutilisation rates of pathology testing are reported to be as high as 44%. Although numerous studies have reported successful efforts to decrease hospital pathology overutilisation, no primary research was identified that examined the JMO perspective on this subject. What does this paper add? Clinical need is not the primary factor guiding the pathology-ordering decisions of junior practitioners; rather, medical team culture, limited JMO experience and systems factors have a significant role. What are the implications for practitioners? The social and behavioural determinants of pathology ordering must be considered to achieve appropriate pathology test utilisation. These include senior medical officer engagement, the guidance of JMOs and clinical workflows.

  8. Admixture Mapping of Subclinical Atherosclerosis and Subsequent Clinical Events Among African Americans in Two Large Cohort Studies

    PubMed Central

    Shendre, Aditi; Wiener, Howard; Irvin, Marguerite R.; Zhi, Degui; Limdi, Nita A.; Overton, Edgar T.; Wassel, Christina L.; Divers, Jasmin; Rotter, Jerome I.; Post, Wendy S.; Shrestha, Sadeep

    2017-01-01

    Background Local ancestry may contribute to the disproportionate burden of subclinical and clinical cardiovascular disease (CVD) among admixed African Americans (AAs) compared to other populations, suggesting a rationale for admixture mapping. Methods and Results We estimated local European ancestry (LEA) using Local Ancestry Inference in adMixed Populations using Linkage Disequilibrium (LAMP-LD) and evaluated the association with common carotid artery intima-media thickness (cCIMT) using multivariable linear regression analysis among 1,554 AAs from the Multi-Ethnic Study of Atherosclerosis (MESA). We conducted secondary analysis to examine the significant cCIMT-LEA associations with clinical CVD events. We observed genome-wide significance in relation to cCIMT association with the secretion regulating guanine nucleotide exchange factor (SERGEF) gene (β=0.0137, P=2.98×10−4), also associated with higher odds of stroke (odds ratio (OR)=1.71, P=0.02). Several regions, in particular Ca2+-dependent secretion activator 1 (CADPS) gene region identified in MESA were also replicated in the Atherosclerosis Risk in Communities (ARIC) cohort. We observed other cCIMT-LEA regions associated with other clinical events, most notably the regions harboring creatine kinase, mitochondrial 2 (CKMT2) and Ras protein specific guanine nucleotide releasing factor 2 (RASGRF2) genes with all clinical events except stroke, the leucine rich repeat containing 3B (LRRC3B) gene with myocardial infarction, the protein arginine methyltransferase 3 (PRMT3) gene with stroke, and the lipoma high mobility group protein I-C (HMGIC) fusion partner-like 2 (LHFPL2) gene with hard and all coronary heart disease. Conclusions We identified several novel LEA regions, in addition to previously identified genomic regions, associated with cCIMT and CVD events among African Americans. PMID:28408707

  9. Prioritization in comparative effectiveness research: the CANCERGEN Experience.

    PubMed

    Thariani, Rahber; Wong, William; Carlson, Josh J; Garrison, Louis; Ramsey, Scott; Deverka, Patricia A; Esmail, Laura; Rangarao, Sneha; Hoban, Carolyn J; Baker, Laurence H; Veenstra, David L

    2012-05-01

    Systematic approaches to stakeholder-informed research prioritization are a central focus of comparative effectiveness research. Genomic testing in cancer is an ideal area to refine such approaches given rapid innovation and potentially significant impacts on patient outcomes. To develop and pilot test a stakeholder-informed approach to prioritizing genomic tests for future study in collaboration with the cancer clinical trials consortium SWOG. We conducted a landscape analysis to identify genomic tests in oncology using a systematic search of published and unpublished studies, and expert consultation. Clinically valid tests suitable for evaluation in a comparative study were presented to an external stakeholder group. Domains to guide the prioritization process were identified with stakeholder input, and stakeholders ranked tests using multiple voting rounds. A stakeholder group was created including representatives from patient-advocacy groups, payers, test developers, regulators, policy makers, and community-based oncologists. We identified 9 domains for research prioritization with stakeholder feedback: population impact; current standard of care, strength of association; potential clinical benefits, potential clinical harms, economic impacts, evidence of need, trial feasibility, and market factors. The landscape analysis identified 635 studies; of 9 tests deemed to have sufficient clinical validity, 6 were presented to stakeholders. Two tests in lung cancer (ERCC1 and EGFR) and 1 test in breast cancer (CEA/CA15-3/CA27.29) were identified as top research priorities. Use of a diverse stakeholder group to inform research prioritization is feasible in a pragmatic and timely manner. Additional research is needed to optimize search strategies, stakeholder group composition, and integration with existing prioritization mechanisms.

  10. Prioritization in Comparative Effectiveness Research: The CANCERGEN Experience in Cancer Genomics

    PubMed Central

    Thariani, Rahber; Wong, William; Carlson, Josh J; Garrison, Louis; Ramsey, Scott; Deverka, Patricia A; Esmail, Laura; Rangarao, Sneha; Hoban, Carolyn J; Baker, Laurence H; Veenstra, David L

    2012-01-01

    Background Systematic approaches to stakeholder-informed research prioritization are a central focus of comparative effectiveness research. Genomic testing in cancer is an ideal area to refine such approaches given rapid innovation and potentially significant impacts on patient outcomes. Objective To develop and pilot-test a stakeholder-informed approach to prioritizing genomic tests for future study in collaboration with the cancer clinical trials consortium SWOG. Methods We conducted a landscape-analysis to identify genomic tests in oncology using a systematic search of published and unpublished studies, and expert consultation. Clinically valid tests suitable for evaluation in a comparative study were presented to an external stakeholder group. Domains to guide the prioritization process were identified with stakeholder input, and stakeholders ranked tests using multiple voting rounds. Results A stakeholder group was created including representatives from patient-advocacy groups, payers, test developers, regulators, policy-makers, and community-based oncologists. We identified nine domains for research prioritization with stakeholder feedback: population impact; current standard of care, strength of association; potential clinical benefits, potential clinical harms, economic impacts, evidence of need, trial feasibility, and market factors. The landscape-analysis identified 635 studies; of 9 tests deemed to have sufficient clinical validity, 6 were presented to stakeholders. Two tests in lung cancer (ERCC1 and EGFR) and one test in breast cancer (CEA/CA15-3/CA27.29) were identified as top research priorities. Conclusions Use of a diverse stakeholder group to inform research prioritization is feasible in a pragmatic and timely manner. Additional research is needed to optimize search strategies, stakeholder group composition and integration with existing prioritization mechanisms. PMID:22274803

  11. Molecular Analysis and Clinical Significance of Lactobacillus spp. Recovered from Clinical Specimens Presumptively Associated with Disease

    PubMed Central

    Martinez, Raquel M.; Hulten, Kristina G.; Bui, Uyen

    2014-01-01

    Lactobacillus spp. are part of the normal human flora and are generally assumed to be nonpathogenic. We determined the genotypic identification of >100 Lactobacillus isolates from clinical specimens in the context of presumed pathogenic potential (e.g., recovered as the single/predominant isolate from a sterile site or at ≥105 CFU/ml from urine). This study assessed the clinical significance and the frequency of occurrence of each Lactobacillus sp. We identified 16 species of Lactobacillus by 16S rRNA gene sequence analysis, 10 of which could not be associated with disease. While Lactobacillus rhamnosus, Lactobacillus gasseri, and Lactobacillus paracasei were associated with infections, L. gasseri was also a common colonizing/contaminating species. Lactobacillus casei, Lactobacillus johnsonii, and Lactobacillus delbrueckii were associated with at least one infection. Species commonly used in probiotic products (e.g., L. rhamnosus and L. casei) were identical, by 16S rRNA gene sequencing, to our isolates associated with disease. Human isolates of Lactobacillus spp. have differing site associations and levels of clinical significance. Knowing the niche and pathogenic potential of each Lactobacillus sp. can be of importance to both clinical microbiology and the food and probiotic supplement industry. PMID:24131686

  12. Factors relating to transmission of viral hepatitis in a United States military population stationed in Thailand.

    PubMed

    Scott, R M; Schneider, R J; Snitbhan, R; Karwacki, J J

    1981-05-01

    To determine the incidence of clinical and inapparent hepatitis in a US military population stationed in Thailand, the authors prospectively studied a cohort of 326 men during one year. Clinical hepatitis A occurred in one man (clinical attack rate = 3.1/1000 men/year), and clinical hepatitis B was found in four men (clinical attack rate = 12.3/1000 men/year). No non-A, non-B hepatitis was identified. There was no serologically identified inapparent hepatitis A but inapparent hepatitis B occurred in 17 men. The apparent/inapparent ratio for hepatitis B was 1:4.25. Serotype analysis suggested that hepatitis B virus largely originated from Thai contacts, although 23% of cases were derived from western sources. To determine the relative contribution of 16 statistically significant (out of 67 studied) behavioral variables to the transmission of HBV, a factor analysis and a multivariate correlation analysis were employed. Factor analysis indicated that social and sexual contact with the indigenous population, including prostitutes, residence within the Thai community and marijuana use were behavioral areas that were associated with the acquisition of hepatitis B. Residence in the Thai community during the first four-month period in Thailand, sexual contact with a prostitute during the third four-month period, and ever having maintained a Thai mistress were found to be significant and independent risk factors by multiple regression analysis.

  13. The Portsmouth-based glaucoma refinement scheme: a role for virtual clinics in the future?

    PubMed

    Trikha, S; Macgregor, C; Jeffery, M; Kirwan, J

    2012-10-01

    Glaucoma referrals continue to impart a significant burden on Hospital Eye Services (HES), with a large proportion of these false positives. To evaluate the Portsmouth glaucoma scheme, utilising virtual clinics, digital technology, and community optometrists to streamline glaucoma referrals. The stages of the patient trail were mapped and, at each step of the process, 100 consecutive patient decisions were identified. The diagnostic outcomes of 50 consecutive patients referred from the refinement scheme to the HES were identified. A total of 76% of 'glaucoma' referrals were suitable for the refinement scheme. Overall, 94% of disc images were gradeable in the virtual clinic. In all, 11% of patients 'attending' the virtual clinic were accepted into HES, with 89% being discharged for community follow-up. Of referrals accepted into HES, the positive predictive value (glaucoma/ocular hypertension/suspect) was 0.78 vs 0.37 in the predating 'unrefined' scheme (95% CI 0.65-0.87). The scheme has released 1400 clinic slots/year for HES, and has produced a £244 200/year cost saving for Portsmouth Hospitals' Trust. The refinement scheme is streamlining referrals and increasing the positive predictive rate in the diagnosis of glaucoma, glaucoma suspect or ocular hypertension. This consultant-led practice-based commissioning scheme, if adopted widely, is likely to incur a significant cost saving while maintaining high quality of care within the NHS.

  14. Results of the National CT Colonography Trial: Questions and Answers

    Cancer.gov

    Learn the results of the National Computerized Tomographic Colonography (CTC) clinical trial, which evaluated how well CTC identifies participants with at least one significantly large polyp using colonoscopy as the gold (or reference) standard.

  15. Does Quality of Radiation Therapy Predict Outcomes of Multicenter Cooperative Group Trials? A Literature Review

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

    Fairchild, Alysa, E-mail: alysa.fairchild@albertahealthservices.ca; Straube, William; Laurie, Fran

    2013-10-01

    Central review of radiation therapy (RT) delivery within multicenter clinical trials was initiated in the early 1970s in the United States. Early quality assurance publications often focused on metrics related to process, logistics, and timing. Our objective was to review the available evidence supporting correlation of RT quality with clinical outcomes within cooperative group trials. A MEDLINE search was performed to identify multicenter studies that described central subjective assessment of RT protocol compliance (quality). Data abstracted included method of central review, definition of deviations, and clinical outcomes. Seventeen multicenter studies (1980-2012) were identified, plus one Patterns of Care Study. Diseasemore » sites were hematologic, head and neck, lung, breast, and pancreas. Between 0 and 97% of treatment plans received an overall grade of acceptable. In 7 trials, failure rates were significantly higher after inadequate versus adequate RT. Five of 9 and 2 of 5 trials reported significantly worse overall and progression-free survival after poor-quality RT, respectively. One reported a significant correlation, and 2 reported nonsignificant trends toward increased toxicity with noncompliant RT. Although more data are required, protocol-compliant RT may decrease failure rates and increase overall survival and likely contributes to the ability of collected data to answer the central trial question.« less

  16. Clinical significance of In vivo Cytarabine Induced Gene Expression Signature in AML

    PubMed Central

    Lamba, Jatinder K.; Pounds, Stanley; Cao, Xueyuan; Crews, Kristine R.; Cogle, Christopher R.; Bhise, Neha; Raimondi, Susana C.; Downing, James R.; Baker, Sharyn D.; Ribeiro, Raul C.; Rubnitz, Jeffrey E.

    2016-01-01

    Despite initial remission, approximately 60-70% of adult and 30% of pediatric patients experience relapse or refractory AML. Studies so far have identified base line gene expression profiles of pathogenic and prognostic significance in AML, however extent of change in gene expression post-initiation of treatment has not been investigated. Exposure of leukemic cells to chemotherapeutic agents such as cytarabine, a mainstay of AML chemotherapy can trigger adaptive response by influencing leukemic cell transcriptome and hence development of resistance or refractory disease. It is however challenging to perform such a study due to lack of availability of specimens post-drug treatment. In this study our primary objective was to identify in vivo cytarabine induced changes in leukemia cell transcriptome and to evaluate their impact on clinical outcome. Our results highlight genes relevant to cytarabine resistance and support the concept of targeting cytarabine-induced genes as a means of improving response. PMID:26366682

  17. Clinical significance of in vivo cytarabine-induced gene expression signature in AML.

    PubMed

    Lamba, Jatinder K; Pounds, Stanley; Cao, Xueyuan; Crews, Kristine R; Cogle, Christopher R; Bhise, Neha; Raimondi, Susana C; Downing, James R; Baker, Sharyn D; Ribeiro, Raul C; Rubnitz, Jeffrey E

    2016-01-01

    Despite initial remission, ∼60-70% of adult and 30% of pediatric patients experience relapse or refractory AML. Studies so far have identified base line gene expression profiles of pathogenic and prognostic significance in AML; however, the extent of change in gene expression post-initiation of treatment has not been investigated. Exposure of leukemic cells to chemotherapeutic agents such as cytarabine, a mainstay of AML chemotherapy, can trigger adaptive response by influencing leukemic cell transcriptome and, hence, development of resistance or refractory disease. It is, however, challenging to perform such a study due to lack of availability of specimens post-drug treatment. The primary objective of this study was to identify in vivo cytarabine-induced changes in leukemia cell transcriptome and to evaluate their impact on clinical outcome. The results highlight genes relevant to cytarabine resistance and support the concept of targeting cytarabine-induced genes as a means of improving response.

  18. 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 Doppler combined with the clinical tests was 4.5 and during the surgery, a mean of four perforators was identified (4.5 vs. 4; mean difference 0.377; P <0.001). The color Doppler combined with the clinical examination lead to only four unnecessary explorations per 10 patients. Conclusion A combination of both the clinical tests and the color Doppler ultrasound has a higher accuracy in detecting perforator incompetence and can reduce the number of negative explorations by the rate of 16 unnecessary explorations per 10 patients. PMID:29531879

  19. Accounting for disease modifying therapy in models of clinical progression in multiple sclerosis.

    PubMed

    Healy, Brian C; Engler, David; Gholipour, Taha; Weiner, Howard; Bakshi, Rohit; Chitnis, Tanuja

    2011-04-15

    Identifying predictors of clinical progression in patients with relapsing-remitting multiple sclerosis (RRMS) is complicated in the era of disease modifying therapy (DMT) because patients follow many different DMT regimens. To investigate predictors of progression in a treated RRMS sample, a cohort of RRMS patients was prospectively followed in the Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women's Hospital (CLIMB). Enrollment criteria were exposure to either interferon-β (IFN-β, n=164) or glatiramer acetate (GA, n=114) for at least 6 months prior to study entry. Baseline demographic and clinical features were used as candidate predictors of longitudinal clinical change on the Expanded Disability Status Scale (EDSS). We compared three approaches to account for DMT effects in statistical modeling. In all approaches, we analyzed all patients together and stratified based on baseline DMT. Model 1 used all available longitudinal EDSS scores, even those after on-study DMT changes. Model 2 used only clinical observations prior to changing DMT. Model 3 used causal statistical models to identify predictors of clinical change. When all patients were considered using Model 1, patients with a motor symptom as the first relapse had significantly larger change in EDSS scores during follow-up (p=0.04); none of the other clinical or demographic variables significantly predicted change. In Models 2 and 3, results were generally unchanged. DMT modeling choice had a modest impact on the variables classified as predictors of EDSS score change. Importantly, however, interpretation of these predictors is dependent upon modeling choice. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Text de-identification for privacy protection: a study of its impact on clinical text information content.

    PubMed

    Meystre, Stéphane M; Ferrández, Óscar; Friedlin, F Jeffrey; South, Brett R; Shen, Shuying; Samore, Matthew H

    2014-08-01

    As more and more electronic clinical information is becoming easier to access for secondary uses such as clinical research, approaches that enable faster and more collaborative research while protecting patient privacy and confidentiality are becoming more important. Clinical text de-identification offers such advantages but is typically a tedious manual process. Automated Natural Language Processing (NLP) methods can alleviate this process, but their impact on subsequent uses of the automatically de-identified clinical narratives has only barely been investigated. In the context of a larger project to develop and investigate automated text de-identification for Veterans Health Administration (VHA) clinical notes, we studied the impact of automated text de-identification on clinical information in a stepwise manner. Our approach started with a high-level assessment of clinical notes informativeness and formatting, and ended with a detailed study of the overlap of select clinical information types and Protected Health Information (PHI). To investigate the informativeness (i.e., document type information, select clinical data types, and interpretation or conclusion) of VHA clinical notes, we used five different existing text de-identification systems. The informativeness was only minimally altered by these systems while formatting was only modified by one system. To examine the impact of de-identification on clinical information extraction, we compared counts of SNOMED-CT concepts found by an open source information extraction application in the original (i.e., not de-identified) version of a corpus of VHA clinical notes, and in the same corpus after de-identification. Only about 1.2-3% less SNOMED-CT concepts were found in de-identified versions of our corpus, and many of these concepts were PHI that was erroneously identified as clinical information. To study this impact in more details and assess how generalizable our findings were, we examined the overlap between select clinical information annotated in the 2010 i2b2 NLP challenge corpus and automatic PHI annotations from our best-of-breed VHA clinical text de-identification system (nicknamed 'BoB'). Overall, only 0.81% of the clinical information exactly overlapped with PHI, and 1.78% partly overlapped. We conclude that automated text de-identification's impact on clinical information is small, but not negligible, and that improved clinical acronyms and eponyms disambiguation could significantly reduce this impact. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Are Mammographically Occult Additional Tumors Identified More Than 2 Cm Away From the Primary Breast Cancer on MRI Clinically Significant?

    PubMed

    Goodman, Sarah; Mango, Victoria; Friedlander, Lauren; Desperito, Elise; Wynn, Ralph; Ha, Richard

    2018-06-08

    To evaluate the clinical significance of mammographically occult additional tumors identified more than 2cm away from the primary breast cancer on preoperative magnetic resonance imaging (MRI). An Institutional Review Board approved review of consecutive preoperative breast MRIs performed from 1/1/08 to 12/31/14, yielded 667 patients with breast cancer. These patients underwent further assessment to identify biopsy proven mammographically occult breast tumors located more than 2cm away from the edge of the primary tumor. Additional MRI characteristics of the primary and secondary tumors and pathology were reviewed. Statistical analysis was performed using SPSS (v. 24). Of 667 patients with breast cancer, 129 patients had 150 additional ipsilateral mammographically occult tumors that were more than 2cm away from the edge of the primary tumor. One hundred twelve of 129 (86.8%) patients had one additional tumor and 17/129 (13.2%) had two or more additional tumors. In 71/129 (55.0%), additional tumors were located in a different quadrant and in 58/129 (45.0%) additional tumors were in the same quadrant but ≥2cm away. Overall, primary tumor size was significantly larger (mean 1.87± 1.25 cm) than the additional tumors (mean 0.79 ± 0.61cm, p < 0.001). However, in 20/129 (15.5%) the additional tumor was larger and in 26/129 (20.2%) the additional tumor was ≥1cm. The primary tumor was significantly more likely to be invasive (81.4%, 105/129) compared to additional tumors (70%, 105/150, p = 0.03). In 9/129 (7.0%) patients, additional tumors yielded unsuspected invasive cancer orhigher tumor grade. The additional tumor was more likely to be nonmass lesion type (37.3% vs 24% p = 0.02) and focus lesion type (10% vs 0.08%, p < 0.001) compared to primary tumor. Mammographically occult additional tumors identified more than 2cm away from the primary breast tumor on MRI are unlikely to be surgically treated if undiagnosed and may be clinically significant. Copyright © 2018 Academic Radiology. Published by Elsevier Inc. All rights reserved.

  2. Biomarkers and biometric measures of adherence to use of ARV-based vaginal rings.

    PubMed

    Stalter, Randy M; Moench, Thomas R; MacQueen, Kathleen M; Tolley, Elizabeth E; Owen, Derek H

    2016-01-01

    Poor adherence to product use has been observed in recent trials of antiretroviral (ARV)-based oral and vaginal gel HIV prevention products, resulting in an inability to determine product efficacy. The delivery of microbicides through vaginal rings is widely perceived as a way to achieve better adherence but vaginal rings do not eliminate the adherence challenges exhibited in clinical trials. Improved objective measures of adherence are needed as new ARV-based vaginal ring products enter the clinical trial stage. To identify technologies that have potential future application for vaginal ring adherence measurement, a comprehensive literature search was conducted that covered a number of biomedical and public health databases, including PubMed, Embase, POPLINE and the Web of Science. Published patents and patent applications were also searched. Technical experts were also consulted to gather more information and help evaluate identified technologies. Approaches were evaluated as to feasibility of development and clinical trial implementation, cost and technical strength. Numerous approaches were identified through our landscape analysis and classified as either point measures or cumulative measures of vaginal ring adherence. Point measurements are those that give a measure of adherence at a particular point in time. Cumulative measures attempt to measure ring adherence over a period of time. Approaches that require modifications to an existing ring product are at a significant disadvantage, as this will likely introduce additional regulatory barriers to the development process and increase manufacturing costs. From the point of view of clinical trial implementation, desirable attributes would be high acceptance by trial participants, and little or no additional time or training requirements on the part of participants or clinic staff. We have identified four promising approaches as being high priority for further development based on the following measurements: intracellular drug levels, drug levels in hair, the accumulation of a vaginal analyte that diffuses into the ring, and the depletion of an intrinsic ring constituent. While some approaches show significant promise over others, it is recommended that a strategy of using complementary biometric and behavioural approaches be adopted to best understand participants' adherence to ARV-based ring products in clinical trials.

  3. The internal audit of clinical areas: a pilot of the internal audit methodology in a health service emergency department.

    PubMed

    Brown, Alison; Santilli, Mario; Scott, Belinda

    2015-12-01

    Governing bodies of health services need assurance that major risks to achieving the health service objectives are being controlled. Currently, the main assurance mechanisms generated within the organization are through the review of implementation of policies and procedures and review of clinical audits and quality data. The governing bodies of health services need more robust, objective data to inform their understanding of the control of clinical risks. Internal audit provides a methodological framework that provides independent and objective assurance to the governing body on the control of significant risks. The article describes the pilot of the internal audit methodology in an emergency unit in a health service. An internal auditor was partnered with a clinical expert to assess the application of clinical criteria based on best practice guidelines. The pilot of the internal audit of a clinical area was successful in identifying significant clinical risks that required further management. The application of an internal audit methodology to a clinical area is a promising mechanism to gain robust assurance at the governance level regarding the management of significant clinical risks. This approach needs further exploration and trial in a range of health care settings. © The Author 2015. Published by Oxford University Press in association with the International Society for Quality in Health Care; all rights reserved.

  4. PCA3 Reference Set Application: T2-Erg-Martin Sanda-Emory (2014) — EDRN Public Portal

    Cancer.gov

    We hypothesize that combining T2:erg (T2:erg) fusion and PCA3 detection in urine collected after digital rectal exam can improve the specificity of identifying clinically significant prostate cancer presence over the standard PSA and DRE. To address this hypothesis we propose to validate the performance of the urinary T2:erg in a multiplex model predicting the diagnosis of clinically significant prostate cancer on subsequent prostate biopsy using post-DRE pre biopsy urine specimens from a cohort of 900 men on the EDRN’s PCA3 trial.

  5. Novel biomarkers in critical care: utility or futility?

    PubMed Central

    Ackland, Gareth L; Mythen, Michael G

    2007-01-01

    One of the holy grails of modern medicine, across a range of clinical sub-specialties, is establishing highly sensitive and specific biomarkers for various diseases. Significant success has been achieved in some of these clinical areas, most notably identifying high-sensitivity C-reactive peptide, troponin I/T and brain natriuretic peptide as significant prognosticators for both the acute outcome and the development of cardiovascular pathology. However, it is highly debatable whether this translates to complex, multi-system pathophysiological insults. Is critical care immune from the application of these novel biomarkers, given the numerous confounding factors interfering with their interpretation? PMID:18001503

  6. Boxing-related head injuries.

    PubMed

    Jayarao, Mayur; Chin, Lawrence S; Cantu, Robert C

    2010-10-01

    Fatalities in boxing are most often due to traumatic brain injury that occurs in the ring. In the past 30 years, significant improvements in ringside and medical equipment, safety, and regulations have resulted in a dramatic reduction in the fatality rate. Nonetheless, the rate of boxing-related head injuries, particularly concussions, remains unknown, due in large part to its variability in clinical presentation. Furthermore, the significance of repeat concussions sustained when boxing is just now being understood. In this article, we identify the clinical manifestations, pathophysiology, and management of boxing-related head injuries, and discuss preventive strategies to reduce head injuries sustained by boxers.

  7. Vorapaxar in atherosclerotic disease management.

    PubMed

    Cheng, Judy W M; Colucci, Vincent; Howard, Patricia A; Nappi, Jean M; Spinler, Sarah A

    2015-05-01

    To review the pharmacology, efficacy, and safety of vorapaxar, a protease activator receptor-1 (PAR-1) antagonist, in the management of atherosclerotic diseases. Peer-reviewed clinical trials and review articles were identified from MEDLINE and Current Content database (both 1966 to December 31, 2014) using the search terms vorapaxar and protease activator receptor antagonist. A total of 30 clinical studies were identified (16 clinical trials, including subanalyses, 14 related to pharmacology, pharmacokinetics, and pharmacodynamics and drug interactions). Two phase III clinical trials with vorapaxar have been published. In patients with non-ST segment elevation myocardial infarction (MI), vorapaxar failed to significantly reduce the primary efficacy end point (composite of cardiovascular death, MI, stroke, recurrent ischemia with hospitalization, and urgent coronary revascularization). Conversely, in a study of secondary prevention for patients with cardiovascular disease, the composite end point of cardiovascular death, MI, or stroke was significantly reduced. In both trials, the safety end points of major/minor bleeding were increased compared with placebo. In the secondary prevention trial, an increased incidence of intracranial hemorrhage led to the exclusion of patients with a prior history of stroke. Vorapaxar is approved for use with aspirin and/or clopidogrel in the secondary prevention of cardiovascular events in stable patients with peripheral arterial disease or a history of MI. However, the addition of vorapaxar to other antiplatelets can significantly increase the risk of bleeding. It is, therefore, essential to balance the need for further reduction of risk of thrombotic event with patient's individual bleeding risk. © The Author(s) 2015.

  8. Shared clinical decision making

    PubMed Central

    AlHaqwi, Ali I.; AlDrees, Turki M.; AlRumayyan, Ahmad; AlFarhan, Ali I.; Alotaibi, Sultan S.; AlKhashan, Hesham I.; Badri, Motasim

    2015-01-01

    Objectives: To determine preferences of patients regarding their involvement in the clinical decision making process and the related factors in Saudi Arabia. Methods: This cross-sectional study was conducted in a major family practice center in King Abdulaziz Medical City, Riyadh, Saudi Arabia, between March and May 2012. Multivariate multinomial regression models were fitted to identify factors associated with patients preferences. Results: The study included 236 participants. The most preferred decision-making style was shared decision-making (57%), followed by paternalistic (28%), and informed consumerism (14%). The preference for shared clinical decision making was significantly higher among male patients and those with higher level of education, whereas paternalism was significantly higher among older patients and those with chronic health conditions, and consumerism was significantly higher in younger age groups. In multivariate multinomial regression analysis, compared with the shared group, the consumerism group were more likely to be female [adjusted odds ratio (AOR) =2.87, 95% confidence interval [CI] 1.31-6.27, p=0.008] and non-dyslipidemic (AOR=2.90, 95% CI: 1.03-8.09, p=0.04), and the paternalism group were more likely to be older (AOR=1.03, 95% CI: 1.01-1.05, p=0.04), and female (AOR=2.47, 95% CI: 1.32-4.06, p=0.008). Conclusion: Preferences of patients for involvement in the clinical decision-making varied considerably. In our setting, underlying factors that influence these preferences identified in this study should be considered and tailored individually to achieve optimal treatment outcomes. PMID:26620990

  9. Does clinical presentation predict response to a nonsurgical chronic disease management program for endstage hip and knee osteoarthritis?

    PubMed

    Eyles, Jillian P; Lucas, Barbara R; Patterson, Jillian A; Williams, Matthew J; Weeks, Kate; Fransen, Marlene; Hunter, David J

    2014-11-01

    To identify baseline characteristics of participants who will respond favorably following 6 months of participation in a chronic disease management program for hip and knee osteoarthritis (OA). This prospective cohort study assessed 559 participants at baseline and following 6 months of participation in the Osteoarthritis Chronic Care Program. Response was defined as the minimal clinically important difference of an 18% and 9-point absolute improvement in the Western Ontario and McMaster Universities Arthritis Index global score. Multivariate logistic regression modeling was used to identify predictors of response. Complete data were available for 308 participants. Those who withdrew within the study period were imputed as nonresponders. Three variables were independently associated with response: signal joint (knee vs hip), sex, and high level of comorbidity. Index joint and sex were significant in the multivariate model, but the model was not a sensitive predictor of response. Strong predictors of response to a chronic disease management program for hip and knee OA were not identified. The significant predictors that were found should be considered in future studies.

  10. 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

  11. An evidence-based review of pregabalin for the treatment of fibromyalgia.

    PubMed

    Arnold, Lesley M; Choy, Ernest; Clauw, Daniel J; Oka, Hiroshi; Whalen, Ed; Semel, David; Pauer, Lynne; Knapp, Lloyd

    2018-04-16

    Pregabalin, an α2-δ agonist, is approved for the treatment of fibromyalgia (FM) in the United States, Japan, and 37 other countries. The purpose of this article was to provide an in-depth, evidence-based summary of pregabalin for FM as demonstrated in randomized, placebo-controlled clinical studies, including open-label extensions, meta-analyses, combination studies and post-hoc analyses of clinical study data. PubMed was searched using the term "pregabalin AND fibromyalgia" and the Cochrane Library with the term "pregabalin". Both searches were conducted on 2 March 2017 with no other date limits set. Eleven randomized, double-blind, placebo-controlled clinical studies were identified including parallel group, two-way crossover and randomized withdrawal designs. One was a neuroimaging study. Five open-label extensions were also identified. Evidence of efficacy was demonstrated across the studies identified with significant and clinically relevant improvements in pain, sleep quality and patient status. The safety and tolerability profile of pregabalin is consistent across all the studies identified, including in adolescents, with dizziness and somnolence the most common adverse events reported. These efficacy and safety data are supported by meta-analyses (13 studies). Pregabalin in combination with other pharmacotherapies (7 studies) is also efficacious. Post-hoc analyses have demonstrated the onset of pregabalin efficacy as early as 1-2 days after starting treatment, examined the effect of pregabalin on other aspects of sleep beyond quality, and shown it is effective irrespective of the presence of a wide variety of patient demographic and clinical characteristics. Pregabalin is a treatment option for FM; its clinical utility has been comprehensively demonstrated.

  12. Outcomes assessment of a pharmacist-directed seamless care program in an ambulatory oncology clinic.

    PubMed

    Edwards, Scott J; Abbott, Rick; Edwards, Jonathan; LeBlanc, Michael; Dranitsaris, George; Donnan, Jennifer; Laing, Kara; Whelan, Maria A; MacKinnon, Neil J

    2014-02-01

    The primary goal of seamless care is improved patient outcomes and improved standards of care for patients with cancer. The pharmacy service of the Newfoundland Cancer Treatment and Research Foundation conducted a randomized control study that measured clinical and humanistic outcomes of a pharmacist-directed seamless care program in an ambulatory oncology clinic. This article focuses on the intervention group, particularly the identification of drug-related problems (DRPs) and utilization of health care services as well the satisfaction of 3 types of health professionals with the services provided by the pharmacist-directed seamless care program. Overall, the seamless care pharmacist (SCP) identified an average of 3.7 DRPs per intervention patient; the most common DRP reported was a patient not receiving or taking a drug therapy for which there is an indication. The SCP identified more DRPs in patients receiving adjuvant treatment compared to those receiving palliative treatment. On average, family physicians, oncology nurses, and hospital pharmacists were satisfied with the SCP intervention indicating that they agreed the information collected and distributed by the SCP was useful to them. Pharmacist-directed seamless care services in an ambulatory oncology clinic have a significant impact on clinical outcomes and processes of patient care. The presence of a SCP can help identify and resolve DRPs experienced by patients in an outpatient oncology clinic, ensuring that patients are receiving the highest standard of care.

  13. Screening young adult cancer survivors for distress with the Distress Thermometer: Comparisons with a structured clinical diagnostic interview.

    PubMed

    Recklitis, Christopher J; Blackmon, Jaime E; Chang, Grace

    2016-01-15

    The validity of the Distress Thermometer (DT) as a screen for psychological distress in young adult cancer survivors was assessed by comparing it with the results of a psychiatric diagnostic interview, the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) (SCID), to evaluate the accuracy of the DT and identify optimal cutoff scores for this population. A total of 247 survivors aged 18 to 40 years completed the DT and SCID. Based on the SCID, participants were classified as having: 1) ≥ 1 SCID diagnoses; 2) significant symptoms, but no SCID diagnosis; or 3) no significant SCID symptoms. Receiver operating characteristic analyses determined the sensitivity and specificity of all possible DT cutoff scores for detecting survivors with a SCID diagnosis, and subsequently for survivors with significant SCID symptoms or a SCID diagnosis. The recommended DT cutoff score of ≥5 failed to identify 31.81% of survivors with a SCID diagnosis (sensitivity of 68.18% and specificity of 78.33%), and 32.81% of survivors with either significant SCID symptoms or a SCID diagnosis. No alternative DT cutoff score met the criteria for acceptable sensitivity (≥85%) and specificity (≥75%). The DT does not reliably identify young adult cancer survivors with psychiatric problems identified by a "gold standard" structured psychiatric interview. Therefore, the DT should not be used as a stand-alone psychological screen in this population. Cancer 2016;122:296-303. © 2015 American Cancer Society. © 2015 American Cancer Society.

  14. Identifying pain-related concerns in routine follow-up clinics following oral and oropharyngeal cancer.

    PubMed

    Rogers, Simon N; Cleator, Alexander J; Lowe, Derek; Ghazali, Naseem

    2012-08-10

    To describe clinical characteristics of head and neck cancer (HNC) patients with pain and those wishing to discuss pain concerns during consultation. Cross-sectional, questionnaire study using University of Washington Quality of Life, version 4 (UW-QOL) and the Patients Concerns Inventory (PCI) in disease-free, post-treatment HNC cohort. Significant pain on UW-QOL and indicating "Pain in head and neck" and "Pain elsewhere" on PCI. One hundred and seventy-seven patients completed UW-QOL and PCI. The prevalence of self-reported pain issues was 38% (67/177) comprising 25% (44/177) with significant problems despite medications and 13% (23/177) with lesser or no problems but wishing to discuss pain. Patients aged under 65 years and patients having treatment involving radiotherapy were more likely to have pain issues. Just over half, 55% (24/44) of patients with significant pain did not express a need to discuss this. Those with significant pain or others wanting to discuss pain in clinic had greater problems in physical and social-emotional functioning, reported suboptimal QOL, and also had more additional PCI items to discuss in clinic compared to those without significant pain and not wishing to discuss pain. Significant HNC-related pain is prevalent in the disease-free, posttreatment cohort. Onward referral to a specialist pain team may be beneficial. The UW-QOL and PCI package is a valuable tool that may routinely screen for significant pain in outpatient clinics.

  15. A study to derive a clinical decision rule for triage of emergency department patients with chest pain: design and methodology

    PubMed Central

    Hess, Erik P; Wells, George A; Jaffe, Allan; Stiell, Ian G

    2008-01-01

    Background Chest pain is the second most common chief complaint in North American emergency departments. Data from the U.S. suggest that 2.1% of patients with acute myocardial infarction and 2.3% of patients with unstable angina are misdiagnosed, with slightly higher rates reported in a recent Canadian study (4.6% and 6.4%, respectively). Information obtained from the history, 12-lead ECG, and a single set of cardiac enzymes is unable to identify patients who are safe for early discharge with sufficient sensitivity. The 2007 ACC/AHA guidelines for UA/NSTEMI do not identify patients at low risk for adverse cardiac events who can be safely discharged without provocative testing. As a result large numbers of low risk patients are triaged to chest pain observation units and undergo provocative testing, at significant cost to the healthcare system. Clinical decision rules use clinical findings (history, physical exam, test results) to suggest a diagnostic or therapeutic course of action. Currently no methodologically robust clinical decision rule identifies patients safe for early discharge. Methods/design The goal of this study is to derive a clinical decision rule which will allow emergency physicians to accurately identify patients with chest pain who are safe for early discharge. The study will utilize a prospective cohort design. Standardized clinical variables will be collected on all patients at least 25 years of age complaining of chest pain prior to provocative testing. Variables strongly associated with the composite outcome acute myocardial infarction, revascularization, or death will be further analyzed with multivariable analysis to derive the clinical rule. Specific aims are to: i) apply standardized clinical assessments to patients with chest pain, incorporating results of early cardiac testing; ii) determine the inter-observer reliability of the clinical information; iii) determine the statistical association between the clinical findings and the composite outcome; and iv) use multivariable analysis to derive a highly sensitive clinical decision rule to guide triage decisions. Discussion The study will derive a highly sensitive clinical decision rule to identify low risk patients safe for early discharge. This will improve patient care, lower healthcare costs, and enhance flow in our busy and overcrowded emergency departments. PMID:18254973

  16. Making genomic medicine evidence-based and patient-centered: a structured review and landscape analysis of comparative effectiveness research.

    PubMed

    Phillips, Kathryn A; Deverka, Patricia A; Sox, Harold C; Khoury, Muin J; Sandy, Lewis G; Ginsburg, Geoffrey S; Tunis, Sean R; Orlando, Lori A; Douglas, Michael P

    2017-10-01

    Comparative effectiveness research (CER) in genomic medicine (GM) measures the clinical utility of using genomic information to guide clinical care in comparison to appropriate alternatives. We summarized findings of high-quality systematic reviews that compared the analytic and clinical validity and clinical utility of GM tests. We focused on clinical utility findings to summarize CER-derived evidence about GM and identify evidence gaps and future research needs. We abstracted key elements of study design, GM interventions, results, and study quality ratings from 21 systematic reviews published in 2010 through 2015. More than half (N = 13) of the reviews were of cancer-related tests. All reviews identified potentially important clinical applications of the GM interventions, but most had significant methodological weaknesses that largely precluded any conclusions about clinical utility. Twelve reviews discussed the importance of patient-centered outcomes, although few described evidence about the impact of genomic medicine on these outcomes. In summary, we found a very limited body of evidence about the effect of using genomic tests on health outcomes and many evidence gaps for CER to address.Genet Med advance online publication 13 April 2017.

  17. Making genomic medicine evidence-based and patient-centered: a structured review and landscape analysis of comparative effectiveness research

    PubMed Central

    Phillips, Kathryn A.; Deverka, Patricia A.; Sox, Harold C.; Khoury, Muin J.; Sandy, Lewis G.; Ginsburg, Geoffrey S.; Tunis, Sean R.; Orlando, Lori A.; Douglas, Michael P.

    2017-01-01

    Comparative effectiveness research (CER) in genomic medicine (GM) measures the clinical utility of using genomic information to guide clinical care in comparison to appropriate alternatives. We summarized findings of high-quality systematic reviews that compared the analytic and clinical validity and clinical utility of GM tests. We focused on clinical utility findings to summarize CER-derived evidence about GM and identify evidence gaps and future research needs. We abstracted key elements of study design, GM interventions, results, and study quality ratings from 21 systematic reviews published in 2010 through 2015. More than half (N = 13) of the reviews were of cancer-related tests. All reviews identified potentially important clinical applications of the GM interventions, but most had significant methodological weaknesses that largely precluded any conclusions about clinical utility. Twelve reviews discussed the importance of patient-centered outcomes, although few described evidence about the impact of genomic medicine on these outcomes. In summary, we found a very limited body of evidence about the effect of using genomic tests on health outcomes and many evidence gaps for CER to address. Genet Med advance online publication 13 April 2017 PMID:28406488

  18. Identifying and Assessing Interesting Subgroups in a Heterogeneous Population

    PubMed Central

    Lee, Woojoo; Alexeyenko, Andrey; Pernemalm, Maria; Guegan, Justine; Dessen, Philippe; Lazar, Vladimir; Lehtiö, Janne; Pawitan, Yudi

    2015-01-01

    Biological heterogeneity is common in many diseases and it is often the reason for therapeutic failures. Thus, there is great interest in classifying a disease into subtypes that have clinical significance in terms of prognosis or therapy response. One of the most popular methods to uncover unrecognized subtypes is cluster analysis. However, classical clustering methods such as k-means clustering or hierarchical clustering are not guaranteed to produce clinically interesting subtypes. This could be because the main statistical variability—the basis of cluster generation—is dominated by genes not associated with the clinical phenotype of interest. Furthermore, a strong prognostic factor might be relevant for a certain subgroup but not for the whole population; thus an analysis of the whole sample may not reveal this prognostic factor. To address these problems we investigate methods to identify and assess clinically interesting subgroups in a heterogeneous population. The identification step uses a clustering algorithm and to assess significance we use a false discovery rate- (FDR-) based measure. Under the heterogeneity condition the standard FDR estimate is shown to overestimate the true FDR value, but this is remedied by an improved FDR estimation procedure. As illustrations, two real data examples from gene expression studies of lung cancer are provided. PMID:26339613

  19. Human Papilloma Virus Vaccination Among Adolescents in a Community Clinic Before and After Intervention.

    PubMed

    Varman, M; Sharlin, C; Fernandez, C; Vasudevan, J; Wichman, C

    2018-06-01

    Human Papilloma Virus (HPV) is the most common sexually transmitted disease with over 14 million infections in 2008. Certain HPV types have been identified in up to 70% of cases of cervical and anal cancers. Despite being safe and effective, HPV vaccination rates remain low. Vaccination and demographic data was collected pre-and post-intervention. Among 13 thru 17-year-old cohort females were significantly more likely to be fully vaccinated. Assessment also found that patients insured by Medicaid were significantly more likely to be fully vaccinated than patients insured privately. Post-intervention vaccination rate is similar to baseline rates. There was non-significant improvement in HPV vaccination coverage after intervention. Male and privately insured patients of Creighton's Pediatric Clinic have lower HPV vaccination coverage than their counterparts. More direct efforts are needed in vaccination process and policy in the clinic to improve immunization against HPV among children and adolescents.

  20. Importance of a specialty clinic for individuals with fragile X syndrome.

    PubMed

    Visootsak, Jeannie; Kidd, Sharon A; Anderson, Tovi; Bassell, Julia L; Sherman, Stephanie L; Berry-Kravis, Elizabeth M

    2016-12-01

    Advances in human genetics have identified a significant number of genetic disorders associated with intellectual disability. As a result, appropriate clinical management of these affected individuals and their family members have become critical in addressing medical needs to improve quality of life. We examine the importance of a Fragile X Clinic for individuals with fragile X syndrome (FXS) and their family members by conducting a retrospective chart review of 123 new patients with FXS evaluated at the Fragile X Clinic at Emory University. After the initial diagnosis of a proband with FXS with cascade testing, there were 345 family members identified with a mutation (70% with premutations; 30% with full mutations). In terms of the impact of the clinic visit, males had a substantial number of new diagnoses in all behavioral disorders (P < 0.001), with anxiety (62%) being the most common. For female probands, the most frequent diagnosis was also anxiety (87%). Prior to the clinic visit, very few patients were prescribed psychotropic medications. After the clinic visit, the most frequently prescribed psychotropic medications for males were stimulants (41%; P < 0.001) and SSRIs (40%; P < 0.001). For females, only stimulants (33%; P = 0.03) and SSRIs (44%; P = 0.008) were statistically significantly prescribed. Our results revealed that there is a gap in care to address the co-morbid behavioral issues, psychopharmacologic medication management, and genetic counseling needs regarding FXS. A multidisciplinary setting and approach, such as that offered by a Fragile X Clinic, is one method of treating the complex needs of patients with FXS. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  1. A psychometric study of the Fear of Sleep Inventory-Short Form (FoSI-SF).

    PubMed

    Pruiksma, Kristi E; Taylor, Daniel J; Ruggero, Camilo; Boals, Adriel; Davis, Joanne L; Cranston, Christopher; DeViva, Jason C; Zayfert, Claudia

    2014-05-15

    Fear of sleep may play a significant role in sleep disturbances in individuals with posttraumatic stress disorder (PTSD). This report describes a psychometric study of the Fear of Sleep Inventory (FoSI), which was developed to measure this construct. The psychometric properties of the FoSI were examined in a non-clinical sample of 292 college students (Study I) and in a clinical sample of 67 trauma-exposed adults experiencing chronic nightmares (Study II). Data on the 23 items of the FoSI were subjected to exploratory factor analyses (EFA) to identify items uniquely assessing fear of sleep. Next, reliability and validity of a 13-item version of the FoSI was examined in both samples. A 13-item Short-Form version (FoSI-SF) was identified as having a clear 2-factor structure with high internal consistency in both the non-clinical (α = 0.76-0.94) and clinical (α = 0.88-0.91) samples. Both studies demonstrated good convergent validity with measures of PTSD (0.48-0.61) and insomnia (0.39-0.48) and discriminant validity with a measure of sleep hygiene (0.19-0.27). The total score on the FoSI-SF was significantly higher in the clinical sample (mean = 17.90, SD = 12.56) than in the non-clinical sample (mean = 4.80, SD = 7.72); t(357) = 8.85 p < 0.001. Although all items are recommended for clinical purposes, the data support the use of the 13-item FoSI-SF for research purposes. Replication of the factor structure in clinical samples is needed. Results are discussed in terms of limitations of this study and directions for further research.

  2. Prevalence of HIV, STIs, and risk behaviors in a cross-sectional community- and clinic-based sample of men who have sex with men (MSM) in Lima, Peru.

    PubMed

    Perez-Brumer, Amaya G; Konda, Kelika A; Salvatierra, H Javier; Segura, Eddy R; Hall, Eric R; Montano, Silvia M; Coates, Thomas J; Klausner, Jeff D; Caceres, Carlos F; Clark, Jesse L

    2013-01-01

    Further research is necessary to understand the factors contributing to the high prevalence of HIV/STIs among men who have sex with men (MSM) in Peru. We compared HIV/STI prevalence and risk factors between two non-probability samples of MSM, one passively enrolled from an STI clinic and the other actively enrolled from community venues surrounding the clinic in Lima, Peru. A total of 560 self-identified MSM were enrolled between May-December, 2007. 438 subjects enrolled from a municipal STI clinic and 122 subjects enrolled during community outreach visits. All participants underwent screening for HIV, syphilis, HSV-2, gonorrhoea, and chlamydia and completed a survey assessing their history of HIV/STIs, prior HIV testing, and sexual behavior. HIV prevalence was significantly higher among MSM enrolled from the clinic, with previously undiagnosed HIV identified in 9.1% compared with 2.6% of community participants. 15.4 % of all MSM screened were infected with ≥ 1 curable STI, 7.4% with early syphilis (RPR ≥ 1:16) and 5.5% with urethral gonorrhoea and/or chlamydia. No significant differences between populations were reported in prevalence of STIs, number of male sex partners, history of unprotected anal intercourse, or alcohol and/or drug use prior to sex. Exchange of sex for money or goods was reported by 33.5% of MSM enrolled from the clinic and 21.2% of MSM from the community (p = 0.01). Our data demonstrate that the prevalence of HIV and STIs, including syphilis, gonorrhoea, and chlamydia are extremely high among MSM enrolled from both clinic and community venues in urban Peru. New strategies are needed to address differences in HIV/STI epidemiology between clinic- and community-enrolled samples of MSM.

  3. Inflammation factors in hepatoblastoma and their clinical significance as diagnostic and prognostic biomarkers.

    PubMed

    Guo, Fei; Ru, Qin; Zhang, Junjie; He, Shen; Yu, Jiekai; Zheng, Shu; Wang, Jiaxiang

    2017-09-01

    The aims of this study were to identify inflammation factors in hepatoblastoma tissue that correlated with different clinical characteristics, and to explore the probability as predictive biomarkers for diagnosis and prognosis. SELDI-TOF-MS was performed to screen protein peaks that were significantly highly expressed in tumor tissue compared with adjacent liver tissue. After removing proteins larger than 30kDa, the targeted peaks were separated by solid phase extraction and tricine-SDS-PAGE. Protein fragments produced by in-gel digestion were identified by LC-MS/MS. Immunohistochemical assays further confirmed these results. Overall survival curves were graphed by Kaplan-Meier method and multivariate analysis was performed by Cox proportional hazards regression model. Three protein peaks (m/z 12,138, m/z 13,462, and m/z 15,120) that were significantly upregulated in the tumor tissue were identified as macrophage migration inhibitory factor (MIF), chemokine (C-X-C motif) ligand 7 (CXCL7), and interleukin 25 (IL-25). These factors were closely related to clinical stage, lymph node metastasis, vascular invasion and serum AFP level. High expression of each inflammatory marker indicated poor prognosis. Multivariate analysis suggested that MIF, CXCL7, and IL-25 were prognostic factors independent of patient sex, age and tumor histological type. MIF, CXCL7, and IL-25 might be considered as effective inflammation factors for diagnosis and prognosis of hepatoblastoma and as potential novel treatment targets through inhibition of inflammatory function. Prognosis study LEVEL OF EVIDENCE: Level I. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Predictors of skilled attendance at delivery among antenatal clinic attendants in Ghana: a cross-sectional study of population data

    PubMed Central

    Amoakoh-Coleman, Mary; Ansah, Evelyn K; Agyepong, Irene Akua; Grobbee, Diederick E; Kayode, Gbenga A; Klipstein-Grobusch, Kerstin

    2015-01-01

    Objective To identify demographic, maternal and community predictors of skilled attendance at delivery among women who attend antenatal clinic at least once during their pregnancy in Ghana. Design A cross-sectional study using the 2008 Ghana Demographic and Health Survey (DHS) data. We used frequencies for descriptive analysis, χ2 test for associations and logistic regression to identify significant predictors. Predictive models were built with estimation of area under the receiver operating characteristic curves (AUC). Setting Ghana. Participants A total of 2041 women who had a live birth in the 5 years preceding the survey, and attended an antenatal clinic having a skilled provider, at least once, during the pregnancy. Outcome Skilled attendance at delivery. Results Overall, 60.5% (1235/2041) of women in our study sample reported skilled attendance at delivery. Significant positive associations existed between skilled attendance at delivery and the variables such as maternal educational level, wealth status class, ever use of contraception, previous pregnancy complications and health insurance coverage (p<0.001). Significant predictors of skilled attendance were wealth status class, residency, previous delivery complication, health insurance coverage and religion in a model with AUC (95% CI) of 0.85 (0.83 to 0.88). Conclusions Women less likely to have skilled attendance at delivery can be identified during antenatal care by using data on wealth status class, health insurance coverage, residence, history of previous birth complications and religion, and targeted with interventions to improve skilled attendance at delivery. PMID:25991459

  5. Relationship between Trypanosoma brucei rhodesiense genetic diversity and clinical spectrum among sleeping sickness patients in Uganda.

    PubMed

    Kato, Charles D; Mugasa, Claire M; Nanteza, Ann; Matovu, Enock; Alibu, Vincent P

    2017-10-27

    Human African trypanosomiasis (HAT) due to Trypanosoma brucei rhodesiense in East and southern Africa is reported to be clinically diverse. We tested the hypothesis that this clinical diversity is associated with a variation in trypanosome genotypes. Trypanosome DNA isolated from HAT patients was genotyped using 7 microsatellite markers directly from blood spotted FTA cards following a whole genome amplification. All markers were polymorphic and identified 17 multi-locus genotypes with 56% of the isolates having replicate genotypes. We did not observe any significant clustering between isolates and bootstrap values across major tree nodes were insignificant. When genotypes were compared among patients with varying clinical presentation or outcome, replicate genotypes were observed at both extremes showing no significant association between genetic diversity and clinical outcome. Our study shows that T. b. rhodesiense isolates are homogeneous within a focus and that observed clinical diversity may not be associated with parasite genetic diversity. Other factors like host genetics and environmental factors might be involved in determining clinical diversity. Our study may be important in designing appropriate control measures that target the parasite.

  6. Applying Advanced Analytical Approaches to Characterize the Impact of Specific Clinical Gaps and Profiles on the Management of Rheumatoid Arthritis.

    PubMed

    Ruiz-Cordell, Karyn D; Joubin, Kathy; Haimowitz, Steven

    2016-01-01

    The goal of this study was to add a predictive modeling approach to the meta-analysis of continuing medical education curricula to determine whether this technique can be used to better understand clinical decision making. Using the education of rheumatologists on rheumatoid arthritis management as a model, this study demonstrates how the combined methodology has the ability to not only characterize learning gaps but also identify those proficiency areas that have the greatest impact on clinical behavior. The meta-analysis included seven curricula with 25 activities. Learners who identified as rheumatologists were evaluated across multiple learning domains, using a uniform methodology to characterize learning gains and gaps. A performance composite variable (called the treatment individualization and optimization score) was then established as a target upon which predictive analytics were conducted. Significant predictors of the target included items related to the knowledge of rheumatologists and confidence concerning 1) treatment guidelines and 2) tests that measure disease activity. In addition, a striking demographic predictor related to geographic practice setting was also identified. The results demonstrate the power of advanced analytics to identify key predictors that influence clinical behaviors. Furthermore, the ability to provide an expected magnitude of change if these predictors are addressed has the potential to substantially refine educational priorities to those drivers that, if targeted, will most effectively overcome clinical barriers and lead to the greatest success in achieving treatment goals.

  7. Elevation of Autoantibody in Patients with Ischemic Stroke.

    PubMed

    Yoshida, Yoichi; Hiwasa, Takaki; Machida, Toshio; Kobayashi, Eiichi; Mine, Seiichiro; Matsushima, Jun; Takiguchi, Masaki; Iwadate, Yasuo

    2018-05-31

    Recent clinical research has revealed a significant correlation between atherosclerosis, one of the primary etiologies of ischemic stroke, and the immune system. Assuming that "disease-specific autoantibodies are produced in the sera of patients with ischemic stroke," we investigated multiple arteriosclerosis-related antibodies using the serological identification of antigens by recombinant cDNA expression cloning (SEREX), an established method for identifying antigenic proteins. We either screened a human aortic endothelial cell cDNA library or conducted protein array screening using the sera from patients with ischemic stroke, such as carotid artery stenosis or transient ischemic attack (TIA). Next, we measured serum antibody levels using amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) in patient/healthy donor (HD) cohorts and identified several antigens, the antibody levels of which were significantly higher in patients with ischemic stroke than in HDs. This review introduced the method of identifying antigens by the SEREX and protein microarray and summarized antigenic proteins. In particular, it focused on anti-replication protein A2 antibody and anti-programmed cell death 11 antibody, which are significantly related to atherosclerotic plaque and ischemic brain tissue, respectively, and proposed the mechanism of elevated autoantibody levels against them. Furthermore, this review suggests a possibility of clinical application as an atherosclerotic disease diagnostic marker for TIA or cerebral infarction.

  8. Identification and Characterization of Unique Subgroups of Chronic Pain Individuals with Dispositional Personality Traits.

    PubMed

    Mehta, S; Rice, D; McIntyre, A; Getty, H; Speechley, M; Sequeira, K; Shapiro, A P; Morley-Forster, P; Teasell, R W

    2016-01-01

    Objective. The current study attempted to identify and characterize distinct CP subgroups based on their level of dispositional personality traits. The secondary objective was to compare the difference among the subgroups in mood, coping, and disability. Methods. Individuals with chronic pain were assessed for demographic, psychosocial, and personality measures. A two-step cluster analysis was conducted in order to identify distinct subgroups of patients based on their level of personality traits. Differences in clinical outcomes were compared using the multivariate analysis of variance based on cluster membership. Results. In 229 participants, three clusters were formed. No significant difference was seen among the clusters on patient demographic factors including age, sex, relationship status, duration of pain, and pain intensity. Those with high levels of dispositional personality traits had greater levels of mood impairment compared to the other two groups (p < 0.05). Significant difference in disability was seen between the subgroups. Conclusions. The study identified a high risk group of CP individuals whose level of personality traits significantly correlated with impaired mood and coping. Use of pharmacological treatment alone may not be successful in improving clinical outcomes among these individuals. Instead, a more comprehensive treatment involving psychological treatments may be important in managing the personality traits that interfere with recovery.

  9. Enabling professional development in mental health nursing: the role of clinical leadership.

    PubMed

    Ennis, G; Happell, B; Reid-Searl, K

    2015-10-01

    Clinical leadership is acknowledged as important to the nursing profession. While studies continue to identify its significance in contributing to positive outcomes for consumers, the role that clinical leadership has in enabling and supporting professional development in mental health nursing is poorly understood. This study utilized a grounded theory methodology to explore the characteristics clinicians consider important for clinical leadership and its significance for mental health nursing in day-to-day clinical practice. Individual face-to-face, semi-structured interviews were conducted with nurses working in mental health settings. Participants described the important role that clinical leaders play in enabling professional development of others through role modelling and clinical teaching. They describe how nurses, whom they perceive as clinical leaders, use role modelling and clinical teaching to influence the professional development of nursing staff and undergraduate nursing students. Attributes such as professionalism and honesty were seen, by participants, as enablers for clinical leaders in effectively and positively supporting the professional development of junior staff and undergraduate nurses in mental health nursing. This paper examines clinical leadership from the perspective of mental health nurses delivering care, and highlights the important role of clinical leaders in supporting professional development in mental health nursing. © 2015 John Wiley & Sons Ltd.

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

    PubMed

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

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

  11. 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

  12. The Ottawa knee rules - a useful clinical decision tool.

    PubMed

    Yao, Kaihan; Haque, Tasneem

    2012-04-01

    Acute knee injuries are a common presentation in the primary care setting. The Ottawa knee rules provide guidance on how to identify which cases of knee injury require radiographic investigation. This article describes the Ottawa knee rules and outlines their sensitivity, reproducibility and application in the clinical setting. The Ottawa knee rules are a valuable tool for clinicians in the routine management of acute knee injuries. Studies show that they are highly sensitive at identifying patients with fractures of the knee and have a high degree of interobserver agreement and reproducible results. Application of the Ottawa knee rules in appropriate clinical scenarios may reduce the number of unnecessary radiographs ordered, streamlining patient throughput and allowing for significant cost savings. Although designed for use in adults, some studies have suggested that the Ottawa knee rules may also be applicable to the paediatric population.

  13. The Cognitive Effects of Antidepressants in Major Depressive Disorder: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

    PubMed Central

    Rosenblat, Joshua D; Kakar, Ron

    2016-01-01

    Background: Cognitive dysfunction is often present in major depressive disorder (MDD). Several clinical trials have noted a pro-cognitive effect of antidepressants in MDD. The objective of the current systematic review and meta-analysis was to assess the pooled efficacy of antidepressants on various domains of cognition in MDD. Methods: Trials published prior to April 15, 2015, were identified through searching the Cochrane Central Register of Controlled Trials, PubMed, Embase, PsychINFO, Clinicaltrials.gov, and relevant review articles. Data from randomized clinical trials assessing the cognitive effects of antidepressants were pooled to determine standard mean differences (SMD) using a random-effects model. Results: Nine placebo-controlled randomized trials (2 550 participants) evaluating the cognitive effects of vortioxetine (n = 728), duloxetine (n = 714), paroxetine (n = 23), citalopram (n = 84), phenelzine (n = 28), nortryptiline (n = 32), and sertraline (n = 49) were identified. Antidepressants had a positive effect on psychomotor speed (SMD 0.16; 95% confidence interval [CI] 0.05–0.27; I2 = 46%) and delayed recall (SMD 0.24; 95% CI 0.15–0.34; I2 = 0%). The effect on cognitive control and executive function did not reach statistical significance. Of note, after removal of vortioxetine from the analysis, statistical significance was lost for psychomotor speed. Eight head-to-head randomized trials comparing the effects of selective serotonin reuptake inhibitors (SSRIs; n = 371), selective serotonin and norepinephrine reuptake inhibitors (SNRIs; n = 25), tricyclic antidepressants (TCAs; n = 138), and norepinephrine and dopamine reuptake inhibitors (NDRIs; n = 46) were identified. No statistically significant difference in cognitive effects was found when pooling results from head-to-head trials of SSRIs, SNRIs, TCAs, and NDRIs. Significant limitations were the heterogeneity of results, limited number of studies, and small sample sizes. Conclusions: Available evidence suggests that antidepressants have a significant positive effect on psychomotor speed and delayed recall. PMID:26209859

  14. Improving clinical outcomes for naltrexone as a management of problem alcohol use

    PubMed Central

    Hulse, Gary K

    2013-01-01

    Despite being a relatively effective and safe treatment, the clinical management of alcohol abuse/dependence by oral naltrexone can be compromised due to the patient's non-compliance with daily use of this medication. Over the past decade an increasing body of research has suggested that the use of sustained release depot naltrexone preparations can overcome this issue and deliver improved clinical outcomes. However, at the same time, research findings from diverse areas of pharmacogenetics, neurobiology and behavioural psychology have also been converging to identify variables including genetic markers, patient psychosocial characteristics and drug use history differences, or clusters of these variables that play a major role in mediating the response of alcohol abuse/dependent persons to treatment by naltrexone. While this article does not attempt to review all available data pertaining to an individual alcohol dependent patient's response to treatment by naltrexone, it does identify relevant research areas and highlights the importance of data arising from them. The characterization of clinical markers, to identify those patients who are most likely to benefit from naltrexone and to tailor a more individual naltrexone treatment, will ultimately provide significant benefit to both patients and clinicians by optimizing treatment outcome. PMID:22946873

  15. Danish research-active clinical nurses overcome barriers in research utilization.

    PubMed

    Adamsen, Lis; Larsen, Kristian; Bjerregaard, Lene; Madsen, Jan K

    2003-03-01

    The aim of this study was to examine whether there was a difference between clinical nurses who were research-active, and clinical nurses who were nonresearch-active in utilization of research. A further aim was to identify the most significant barriers faced by a group of Danish clinical nurses in their use of research. Discrepancy between the improved quality of research results and the lack of implementing them was the starting point for a series of studies which showed the types of barriers clinical nurses found especially cumbersome when applying the research results of other researchers. This study investigates whether the clinical nurses' own engagement in research had any impact on their perception of research utilization. The study had an exploratory and descriptive design. Seventy-nine Danish clinical nurses participated and semi-structured interviewing was used as the research method. There was a statistically significant difference between the research-active and nonresearch-active nurses on various variables. The study showed that, to a larger extent, research-active nurses used evidence-based knowledge and were generally more internationally orientated. Furthermore, two important barriers for research utilization were identified by all 79 clinical nurses included in the study, i.e. 90% of the nurses explained that the quantity of research results was overwhelming, and 75% of them found that they were unable to evaluate the quality of the research. Clinical nurses, who were research-active themselves, experienced more success in overcoming some of the barriers, which existed in applying research to practice. The research potential found amongst clinical nurses in Denmark needed to be further supported through training and guidance in research methodology, establishing introductory stipends and part-time research positions. By doing so, some of the barriers affecting research utilization and the so-called theory-practice gap might be reduced. Further empirical studies, based on Giddens theory of sociological reflectivity, might see clinical nurses in a more serious light and simultaneously perceive them as producers of knowledge.

  16. Diagnostic and Therapeutic Yield of Endoscopy in Patients with Elevated INR and Gastrointestinal Bleeding.

    PubMed

    Peloquin, Joanna M; Seraj, Siamak M; King, Lindsay Y; Campbell, Emily J; Ananthakrishnan, Ashwin N; Richter, James M

    2016-06-01

    Gastrointestinal bleeding is a well-known risk of systemic anticoagulation. However, bleeding in the setting of supratherapeutic anticoagulation may have a milder natural history than unprovoked bleeding. It is a common clinical gestalt that endoscopy is common, but bleeding source identification or intervention is uncommon, yet few data exist to inform this clinical impression. Consequently, we sought to examine our institutional experience with gastrointestinal bleeding in the setting of supratherapeutic international normalized ratio (INR) with the aim of identifying predictors of endoscopically identifiable lesions, interventions, and outcomes. A retrospective review was conducted at a tertiary referral academic medical center to identify patients presenting with gastrointestinal bleeding in the setting of warfarin and a supratherapeutic INR (>3.5) who underwent an endoscopic procedure. Relevant clinical covariates, endoscopic findings, need for intervention, and outcomes were collected by review of the medical record. Logistic regression adjusting for potential confounders identified predictors of endoscopically significant lesions as well as intervention and outcomes. A total of 134 patients with INR 3.5 or greater (mean 5.5, range 3.5-17.1) presented with symptoms of gastrointestinal bleeding, most commonly as melena or symptomatic anemia. Antiplatelet agents were used by 54% of patients, and 60% of patients were on concomitant acid suppression on admission. Procedures included esophagogastroduodenoscopy (upper endoscopy; EGD) (n = 128), colonoscopy (n = 73), and video capsule endoscopy (n = 32). Active bleeding at first EGD or colonoscopy was found in only 19 patients (18%), with endoscopic intervention in only 26 patients (25%). At a critical threshold of INR 7.5 at presentation, the likelihood of finding an endoscopically significant lesion fell to <20%. On multivariate logistic regression, concomitant antiplatelet therapy (odds ratio [OR] 2.59; 95% confidence interval [CI], 1.13-5.94), timing of EGD within 12 hours of presentation (OR 3.71; 95% CI, 1.05-13.08), and INR level (OR 0.79; 95% CI, 0.64-0.98) were the only significant independent predictors of identifying a source of bleeding. A risk score incorporating these covariates performed modestly in identifying risk of significant finding on EGD (area under the curve 0.68). We found no association between identification of a significant lesion at EGD and future readmission for gastrointestinal bleeding. This study demonstrates that the relationship between INR elevation and identification of a bleeding source or endoscopic intervention at EGD are indeed antiparallel. Concomitant antiplatelet therapy increases the likelihood of bleeding source identification and intervention, as does EGD within 12 hours of presentation. However, regardless of source identification or endoscopic intervention, important clinical outcomes were unchanged, suggesting that decisions about endoscopy should be made on a case-by-case basis, particularly in patients with INR > 7.5. Future prospective studies on appropriate indications and timing of endoscopy in such patients are warranted. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Utilization of information and communication technology (ICT) among sexually transmitted disease clinics attendees with coexisting drinking problems

    PubMed Central

    2014-01-01

    Background Alcohol misuse remains a major risk factor for contracting sexually transmitted diseases (STDs) not typically addressed in STD clinic settings. Information and communication technology (ICT) can offer new avenues to deliver evidence-based screening and treatment for problematic drinking, however, few data exists regarding the utilization of ICT among STD clinic attendees with coexisting drinking problems. The objectives of this study are to identify STD clinics attendees with hazardous drinking, to examine socio-demographic factors associated with ICT use, and to explore individuals’ interests in engaging in ICT-based health interventions. Methods Cross-sectional questionnaires examining alcohol consumption and ICT use were administered to 396 persons attending two non-urban STD clinics. Descriptive statistics for ICT use were calculated for both hazardous drinkers and the entire sample. Multivariable logistic regression models among hazardous drinkers identified factors significantly associated with use of each kind of ICT. Results The mean age of the 396 participants was 25 years, 66% were females and 60% were African-Americans. One third of the sample met the criteria of hazardous drinking. ICT use in hazardous drinkers included 94% reporting having internet access at least monthly, 82% reporting having an email account, 85% reporting currently owning a cell phone, and 91% reporting use of any cell phone application. More than two thirds (73%) of hazardous drinkers were willing to play health-related video games during clinic waiting time, slightly higher than the entire sample (69%). Multivariable analyses indicated that younger age were significantly related to monthly internet use, and multifunction cell phone use, while being males and younger age were significantly associated with monthly video game playing. Conclusions Our study demonstrates commonality of ICT use among STD clinic attendees with hazardous drinking, indicating the viability of using ICT to assist screening and behavioural intervention for alcohol misuse in STD clinic settings. Future research is needed to demonstrate the effectiveness of ICT-based health behavioural interventions in the STD clinic settings or other venues that serve populations at high risk for substance abuse, HIV or other STDs. PMID:24670037

  18. Utilization of information and communication technology (ICT) among sexually transmitted disease clinics attendees with coexisting drinking problems.

    PubMed

    Hu, Xingdi; Dodd, Virginia J; Oliverio, James C; Cook, Robert L

    2014-03-26

    Alcohol misuse remains a major risk factor for contracting sexually transmitted diseases (STDs) not typically addressed in STD clinic settings. Information and communication technology (ICT) can offer new avenues to deliver evidence-based screening and treatment for problematic drinking, however, few data exists regarding the utilization of ICT among STD clinic attendees with coexisting drinking problems. The objectives of this study are to identify STD clinics attendees with hazardous drinking, to examine socio-demographic factors associated with ICT use, and to explore individuals' interests in engaging in ICT-based health interventions. Cross-sectional questionnaires examining alcohol consumption and ICT use were administered to 396 persons attending two non-urban STD clinics. Descriptive statistics for ICT use were calculated for both hazardous drinkers and the entire sample. Multivariable logistic regression models among hazardous drinkers identified factors significantly associated with use of each kind of ICT. The mean age of the 396 participants was 25 years, 66% were females and 60% were African-Americans. One third of the sample met the criteria of hazardous drinking. ICT use in hazardous drinkers included 94% reporting having internet access at least monthly, 82% reporting having an email account, 85% reporting currently owning a cell phone, and 91% reporting use of any cell phone application. More than two thirds (73%) of hazardous drinkers were willing to play health-related video games during clinic waiting time, slightly higher than the entire sample (69%). Multivariable analyses indicated that younger age were significantly related to monthly internet use, and multifunction cell phone use, while being males and younger age were significantly associated with monthly video game playing. Our study demonstrates commonality of ICT use among STD clinic attendees with hazardous drinking, indicating the viability of using ICT to assist screening and behavioural intervention for alcohol misuse in STD clinic settings. Future research is needed to demonstrate the effectiveness of ICT-based health behavioural interventions in the STD clinic settings or other venues that serve populations at high risk for substance abuse, HIV or other STDs.

  19. Somatic POLE mutations cause an ultramutated giant cell high-grade glioma subtype with better prognosis

    PubMed Central

    Erson-Omay, E. Zeynep; Çağlayan, Ahmet Okay; Schultz, Nikolaus; Weinhold, Nils; Omay, S. Bülent; Özduman, Koray; Köksal, Yavuz; Li, Jie; Serin Harmancı, Akdes; Clark, Victoria; Carrión-Grant, Geneive; Baranoski, Jacob; Çağlar, Caner; Barak, Tanyeri; Coşkun, Süleyman; Baran, Burçin; Köse, Doğan; Sun, Jia; Bakırcıoğlu, Mehmet; Moliterno Günel, Jennifer; Pamir, M. Necmettin; Mishra-Gorur, Ketu; Bilguvar, Kaya; Yasuno, Katsuhito; Vortmeyer, Alexander; Huttner, Anita J.; Sander, Chris; Günel, Murat

    2015-01-01

    Background Malignant high-grade gliomas (HGGs), including the most aggressive form, glioblastoma multiforme, show significant clinical and genomic heterogeneity. Despite recent advances, the overall survival of HGGs and their response to treatment remain poor. In order to gain further insight into disease pathophysiology by correlating genomic landscape with clinical behavior, thereby identifying distinct HGG molecular subgroups associated with improved prognosis, we performed a comprehensive genomic analysis. Methods We analyzed and compared 720 exome-sequenced gliomas (136 from Yale, 584 from The Cancer Genome Atlas) based on their genomic, histological, and clinical features. Results We identified a subgroup of HGGs (6 total, 4 adults and 2 children) that harbored a statistically significantly increased number of somatic mutations (mean = 9257.3 vs 76.2, P = .002). All of these “ultramutated” tumors harbored somatic mutations in the exonuclease domain of the polymerase epsilon gene (POLE), displaying a distinctive genetic profile, characterized by genomic stability and increased C-to-A transversions. Histologically, they all harbored multinucleated giant or bizarre cells, some with predominant infiltrating immune cells. One adult and both pediatric patients carried homozygous germline mutations in the mutS homolog 6 (MSH6) gene. In adults, POLE mutations were observed in patients younger than 40 years and were associated with a longer progression-free survival. Conclusions We identified a genomically, histologically, and clinically distinct subgroup of HGGs that harbored somatic POLE mutations and carried an improved prognosis. Identification of distinctive molecular and pathological HGG phenotypes has implications not only for improved classification but also for potential targeted treatments. PMID:25740784

  20. Defining the critical hurdles in cancer immunotherapy.

    PubMed

    Fox, Bernard A; Schendel, Dolores J; Butterfield, Lisa H; Aamdal, Steinar; Allison, James P; Ascierto, Paolo Antonio; Atkins, Michael B; Bartunkova, Jirina; Bergmann, Lothar; Berinstein, Neil; Bonorino, Cristina C; Borden, Ernest; Bramson, Jonathan L; Britten, Cedrik M; Cao, Xuetao; Carson, William E; Chang, Alfred E; Characiejus, Dainius; Choudhury, A Raja; Coukos, George; de Gruijl, Tanja; Dillman, Robert O; Dolstra, Harry; Dranoff, Glenn; Durrant, Lindy G; Finke, James H; Galon, Jerome; Gollob, Jared A; Gouttefangeas, Cécile; Grizzi, Fabio; Guida, Michele; Håkansson, Leif; Hege, Kristen; Herberman, Ronald B; Hodi, F Stephen; Hoos, Axel; Huber, Christoph; Hwu, Patrick; Imai, Kohzoh; Jaffee, Elizabeth M; Janetzki, Sylvia; June, Carl H; Kalinski, Pawel; Kaufman, Howard L; Kawakami, Koji; Kawakami, Yutaka; Keilholtz, Ulrich; Khleif, Samir N; Kiessling, Rolf; Kotlan, Beatrix; Kroemer, Guido; Lapointe, Rejean; Levitsky, Hyam I; Lotze, Michael T; Maccalli, Cristina; Maio, Michele; Marschner, Jens-Peter; Mastrangelo, Michael J; Masucci, Giuseppe; Melero, Ignacio; Melief, Cornelius; Murphy, William J; Nelson, Brad; Nicolini, Andrea; Nishimura, Michael I; Odunsi, Kunle; Ohashi, Pamela S; O'Donnell-Tormey, Jill; Old, Lloyd J; Ottensmeier, Christian; Papamichail, Michael; Parmiani, Giorgio; Pawelec, Graham; Proietti, Enrico; Qin, Shukui; Rees, Robert; Ribas, Antoni; Ridolfi, Ruggero; Ritter, Gerd; Rivoltini, Licia; Romero, Pedro J; Salem, Mohamed L; Scheper, Rik J; Seliger, Barbara; Sharma, Padmanee; Shiku, Hiroshi; Singh-Jasuja, Harpreet; Song, Wenru; Straten, Per Thor; Tahara, Hideaki; Tian, Zhigang; van Der Burg, Sjoerd H; von Hoegen, Paul; Wang, Ena; Welters, Marij Jp; Winter, Hauke; Withington, Tara; Wolchok, Jedd D; Xiao, Weihua; Zitvogel, Laurence; Zwierzina, Heinz; Marincola, Francesco M; Gajewski, Thomas F; Wigginton, Jon M; Disis, Mary L

    2011-12-14

    Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators; others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet if overcome, have the potential to improve outcomes of patients with cancer.

  1. Defining the critical hurdles in cancer immunotherapy

    PubMed Central

    2011-01-01

    Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators; others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet if overcome, have the potential to improve outcomes of patients with cancer. PMID:22168571

  2. Comparing data accuracy between structured abstracts and full-text journal articles: implications in their use for informing clinical decisions.

    PubMed

    Fontelo, Paul; Gavino, Alex; Sarmiento, Raymond Francis

    2013-12-01

    The abstract is the most frequently read section of a research article. The use of 'Consensus Abstracts', a clinician-oriented web application formatted for mobile devices to search MEDLINE/PubMed, for informing clinical decisions was proposed recently; however, inaccuracies between abstracts and the full-text article have been shown. Efforts have been made to improve quality. We compared data in 60 recent-structured abstracts and full-text articles from six highly read medical journals. Data inaccuracies were identified and then classified as either clinically significant or not significant. Data inaccuracies were observed in 53.33% of articles ranging from 3.33% to 45% based on the IMRAD format sections. The Results section showed the highest discrepancies (45%) although these were deemed to be mostly not significant clinically except in one. The two most common discrepancies were mismatched numbers or percentages (11.67%) and numerical data or calculations found in structured abstracts but not mentioned in the full text (40%). There was no significant relationship between journals and the presence of discrepancies (Fisher's exact p value =0.3405). Although we found a high percentage of inaccuracy between structured abstracts and full-text articles, these were not significant clinically. The inaccuracies do not seem to affect the conclusion and interpretation overall. Structured abstracts appear to be informative and may be useful to practitioners as a resource for guiding clinical decisions.

  3. Risk factors for invasive fungal disease in critically ill adult patients: a systematic review.

    PubMed

    Muskett, Hannah; Shahin, Jason; Eyres, Gavin; Harvey, Sheila; Rowan, Kathy; Harrison, David

    2011-01-01

    Over 5,000 cases of invasive Candida species infections occur in the United Kingdom each year, and around 40% of these cases occur in critical care units. Invasive fungal disease (IFD) in critically ill patients is associated with increased morbidity and mortality at a cost to both the individual and the National Health Service. In this paper, we report the results of a systematic review performed to identify and summarise the important risk factors derived from published multivariable analyses, risk prediction models and clinical decision rules for IFD in critically ill adult patients to inform the primary data collection for the Fungal Infection Risk Evaluation Study. An internet search was performed to identify articles which investigated risk factors, risk prediction models or clinical decisions rules for IFD in critically ill adult patients. Eligible articles were identified in a staged process and were assessed by two investigators independently. The methodological quality of the reporting of the eligible articles was assessed using a set of questions addressing both general and statistical methodologies. Thirteen articles met the inclusion criteria, of which eight articles examined risk factors, four developed a risk prediction model or clinical decision rule and one evaluated a clinical decision rule. Studies varied in terms of objectives, risk factors, definitions and outcomes. The following risk factors were found in multiple studies to be significantly associated with IFD: surgery, total parenteral nutrition, fungal colonisation, renal replacement therapy, infection and/or sepsis, mechanical ventilation, diabetes, and Acute Physiology and Chronic Health Evaluation II (APACHE II) or APACHE III score. Several other risk factors were also found to be statistically significant in single studies only. Risk factor selection process and modelling strategy also varied across studies, and sample sizes were inadequate for obtaining reliable estimates. This review shows a number of risk factors to be significantly associated with the development of IFD in critically ill adults. Methodological limitations were identified in the design and conduct of studies in this area, and caution should be used in their interpretation.

  4. Risk factors for invasive fungal disease in critically ill adult patients: a systematic review

    PubMed Central

    2011-01-01

    Introduction Over 5,000 cases of invasive Candida species infections occur in the United Kingdom each year, and around 40% of these cases occur in critical care units. Invasive fungal disease (IFD) in critically ill patients is associated with increased morbidity and mortality at a cost to both the individual and the National Health Service. In this paper, we report the results of a systematic review performed to identify and summarise the important risk factors derived from published multivariable analyses, risk prediction models and clinical decision rules for IFD in critically ill adult patients to inform the primary data collection for the Fungal Infection Risk Evaluation Study. Methods An internet search was performed to identify articles which investigated risk factors, risk prediction models or clinical decisions rules for IFD in critically ill adult patients. Eligible articles were identified in a staged process and were assessed by two investigators independently. The methodological quality of the reporting of the eligible articles was assessed using a set of questions addressing both general and statistical methodologies. Results Thirteen articles met the inclusion criteria, of which eight articles examined risk factors, four developed a risk prediction model or clinical decision rule and one evaluated a clinical decision rule. Studies varied in terms of objectives, risk factors, definitions and outcomes. The following risk factors were found in multiple studies to be significantly associated with IFD: surgery, total parenteral nutrition, fungal colonisation, renal replacement therapy, infection and/or sepsis, mechanical ventilation, diabetes, and Acute Physiology and Chronic Health Evaluation II (APACHE II) or APACHE III score. Several other risk factors were also found to be statistically significant in single studies only. Risk factor selection process and modelling strategy also varied across studies, and sample sizes were inadequate for obtaining reliable estimates. Conclusions This review shows a number of risk factors to be significantly associated with the development of IFD in critically ill adults. Methodological limitations were identified in the design and conduct of studies in this area, and caution should be used in their interpretation. PMID:22126425

  5. Comparative evaluation of the identification of rapidly growing non-tuberculous mycobacteria by mass spectrometry (MALDI-TOF MS), GenoType Mycobacterium CM/AS assay and partial sequencing of the rpoβ gene with phylogenetic analysis as a reference method.

    PubMed

    Costa-Alcalde, José Javier; Barbeito-Castiñeiras, Gema; González-Alba, José María; Aguilera, Antonio; Galán, Juan Carlos; Pérez-Del-Molino, María Luisa

    2018-06-02

    The American Thoracic Society and the Infectious Diseases Society of America recommend that clinically significant non-tuberculous mycobacteria (NTM) should be identified to the species level in order to determine their clinical significance. The aim of this study was to evaluate identification of rapidly growing NTM (RGM) isolated from clinical samples by using MALDI-TOF MS and a commercial molecular system. The results were compared with identification using a reference method. We included 46 clinical isolates of RGM and identified them using the commercial molecular system GenoType ® CM/AS (Hain, Lifescience, Germany), MALDI-TOF MS (Bruker) and, as reference method, partial rpoβ gene sequencing followed by BLAST and phylogenetic analysis with the 1093 sequences available in the GeneBank. The degree of agreement between GenoType ® and MALDI-TOF MS and the reference method, partial rpoβ sequencing, was 27/43 (62.8%) and 38/43 cases (88.3%) respectively. For all the samples correctly classified by GenoType ® , we obtained the same result with MALDI-TOF MS (27/27). However, MALDI-TOF MS also correctly identified 68.75% (11/16) of the samples that GenoType ® had misclassified (p=0.005). MALDI-TOF MS classified significantly better than GenoType ® . When a MALDI-TOF MS score >1.85 was achieved, MALDI-TOF MS and partial rpoβ gene sequencing were equivalent. GenoType ® was not able to distinguish between species belonging to the M. fortuitum complex. MALDI-TOF MS methodology is simple, rapid and associated with lower consumable costs than GenoType ® . The partial rpoβ sequencing methods with BLAST and phylogenetic analysis were not able to identify some RGM unequivocally. Therefore, sequencing of additional regions would be indicated in these cases. Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  6. Multicenter Evaluation of the Bruker MALDI Biotyper CA System for the Identification of Clinically Important Bacteria and Yeasts.

    PubMed

    Wilson, Deborah A; Young, Stephen; Timm, Karen; Novak-Weekley, Susan; Marlowe, Elizabeth M; Madisen, Neil; Lillie, Jennifer L; Ledeboer, Nathan A; Smith, Rebecca; Hyke, Josh; Griego-Fullbright, Christen; Jim, Patricia; Granato, Paul A; Faron, Matthew L; Cumpio, Joven; Buchan, Blake W; Procop, Gary W

    2017-06-01

    A report on the multicenter evaluation of the Bruker MALDI Biotyper CA System (MBT-CA; Bruker Daltonics, Billerica, MA) for the identification of clinically important bacteria and yeasts. In total, 4,399 isolates of medically important bacteria and yeasts were assessed in the MBT-CA. These included 2,262 aerobic gram-positive (AGP) bacteria, 792 aerobic gram-negative (AGN) bacteria 530 anaerobic (AnA) bacteria, and 815 yeasts (YSTs). Three processing methods were assesed. Overall, 98.4% (4,329/4,399) of all bacterial and yeast isolates were correctly identified to the genus and species/species complex level, and 95.7% of isolates were identified with a high degree of confidence. The percentage correctly identified and the percentage identified correctly with a high level of confidence, respectively, were as follows: AGP bacteria (98.6%/96.5%), AGN bacteria (98.5%/96.8%), AnA bacteria (98.5%/97.4%), and YSTs (97.8%/87.6%). The extended direct transfer method was only minimally superior to the direct transfer method for bacteria (89.9% vs 86.8%, respectively) but significantly superior for yeast isolates (74.0% vs 48.9%, respectively). The Bruker MALDI Biotyper CA System accurately identifies most clinically important bacteria and yeasts and has optional processing methods to improve isolate characterization. © American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  7. Pancreatic Autoantibodies Against CUZD1 and GP2 Are Associated with Distinct Clinical Phenotypes of Crohn's Disease.

    PubMed

    Michaels, Maike Anna; Jendrek, Sebastian Torben; Korf, Tobias; Nitzsche, Thomas; Teegen, Bianca; Komorowski, Lars; Derer, Stefanie; Schröder, Torsten; Baer, Florian; Lehnert, Henrik; Büning, Jürgen; Fellerman, Klaus; Sina, Christian

    2015-12-01

    Inflammatory bowel disease (IBD) is characterized by a broad spectrum of clinical phenotypes with different outcomes. In the last decades, several IBD-associated autoantibodies have been identified and investigated for their diagnostic relevance. Autoantibodies against the pancreatic glycoproteins (PAB) CUB and zona pellucida-like domains-containing protein 1 (CUZD1), and glycoprotein 2 (GP2) have been demonstrated to possess high specificity for the diagnosis of IBD. Although several studies have shown significant interrelations of anti-GP2 positivity with disease phenotype, associations of clinical phenotypes with anti-CUZD1 are still unknown. The aim was to identify the association of clinical phenotypes with anti-CUZD1 and anti-GP2 in a well-defined German IBD cohort. Patients with IBD (224 patients with Crohn's disease and 136 patients with ulcerative colitis), who were tested for anti-GP2 and anti-CUZD1 immunoglobulin G and immunoglobulin A by indirect immunofluorescence on transfected cells between 2005 and 2013, were included. Serotype and specified phenotypic data were collected in retrospect and statistically analyzed. Both anti-GP2 (P < 0.001) and anti-CUZD1 (P < 0.001) were significantly more prevalent in patients with Crohn's disease than in ulcerative colitis. PAB positivity was associated with ileocolonic disease (P = 0.002), perianal disease (P = 0.011), immunosuppressive treatment (P = 0.036), and ASCA positivity (P = 0.036). Anti-CUZD1 positivity was associated with ileocolonic (P = 0.016) and perianal disease (P = 0.002), whereas anti-GP2 positivity was positively associated with stricturing behavior (P = 0.016). We found distinct clinical phenotypes to be associated with PAB positivity. Therefore, determination of PABs and their subgroup analysis might identify patients with complicated disease behavior. However, the clinical relevance of our findings should be further evaluated in prospective cohorts.

  8. Stress and stressors in the clinical environment: a comparative study of fourth-year student nurses and newly qualified general nurses in Ireland.

    PubMed

    Suresh, Patricia; Matthews, Anne; Coyne, Imelda

    2013-03-01

    To measure and compare the perceived levels of job-related stress and stressors of newly qualified nurses and fourth-year student nurses in the clinical environment and to explore the participants' views on stress and stressors. Stress in the nursing workplace has significant consequences for the person, the patient and the organisation, such as psychological and physical health deterioration and impaired professional practice. To address this problem, stress and stressors need to be measured and identified. This study used a cross-sectional survey design and self-reporting questionnaires to measure and compare levels of stress in both groups. Convenience sampling involved all newly qualified nurses (n = 120) and fourth-year student nurses (n = 128) in Dublin North-East region in Ireland. The instrument used was 'The Nursing Stress Scale' (Gray-Toft & Anderson 1981, Journal of Behavioral Assessment 3, 11-23). Descriptive, qualitative analysis was conducted on an open-ended question. Data were obtained from newly qualified nurses (n = 31) and fourth-year student nurses (n = 40) in six acute hospital sites. Levels of perceived stress and stressors were high in both groups. Themes identified from the responses to the open question by both groups included excessive workload, difficult working relationships and unmet clinical learning needs. Student nurses also reported the combination of academic demands with clinical placement as a major stressor. There was no significant difference between each group. Stress continues to be a problem for nurses in the clinical setting. Excessive workload requires urgent attention by hospital managers in view of widespread retention difficulties. Themes identified could provide a framework for possible interventions for improving the clinical environment for nurses. These results can help stakeholders in nurse education and practice to develop interventions to reduce stress for both groups and to ease the transition from student to graduate nurse. © 2012 Blackwell Publishing Ltd.

  9. Validation of SURE, a four-item clinical checklist for detecting decisional conflict in patients.

    PubMed

    Ferron Parayre, Audrey; Labrecque, Michel; Rousseau, Michel; Turcotte, Stéphane; Légaré, France

    2014-01-01

    We sought to determine the psychometric properties of SURE, a 4-item checklist designed to screen for clinically significant decisional conflict in clinical practice. This study was a secondary analysis of a clustered randomized trial assessing the effect of DECISION+2, a 2-hour online tutorial followed by a 2-hour interactive workshop on shared decision making, on decisions to use antibiotics for acute respiratory infections. Patients completed SURE and also the Decisional Conflict Scale (DCS), as the gold standard, after consultation. We evaluated internal consistency of SURE using the Kuder-Richardson 20 coefficient (KR-20). We compared DCS and SURE scores using the Spearman correlation coefficient. We assessed sensitivity and specificity of SURE scores (cut-off score ≤3 out of 4) by identifying patients with and without clinically significant decisional conflict (DCS score >37.5 on a scale of 0-100). Of the 712 patients recruited during the trial, 654 completed both tools. SURE scores showed adequate internal consistency (KR-20 coefficient of 0.7). There was a significant correlation between DCS and SURE scores (Spearman's ρ = -0.45, P < 0.0001). The prevalence of clinically significant decisional conflict as estimated by the DCS was 5.2% (95% CI 3.7-7.3). Sensitivity and specificity of SURE ≤3 were 94.1% (95% CI 78.9-99.0) and 89.8% (95% CI 87.1-92.0), respectively. SURE shows adequate psychometric properties in a primary care population with a low prevalence of clinically significant decisional conflict. SURE has the potential to be a useful screening tool for practitioners, responding to the growing need for detecting clinically significant decisional conflict in patients.

  10. Can experiential-didactic training improve clinical STD practices?

    PubMed

    Dreisbach, Susan; Devine, Sharon; Fitch, John; Anderson, Teri; Lee, Terry; Rietmeijer, Cornelis; Corbett, Kitty K

    2011-06-01

    High rates of sexually transmitted diseases (STDs) present an ongoing costly public health challenge. One approach to reduce STD transmission is to increase the number of clinicians adopting the Centers for Disease Control and Prevention's STD Treatment Guidelines. This evaluation assesses the effectiveness of a 3-day experiential and didactic training to translate recommendations into practice by increasing clinician knowledge and skills and helping participants anticipate and overcome barriers to implementation. Between 2001 and 2004, 110 direct care clinicians from 10 states participated in one of 27 standardized 3-day interactive trainings offered by the Denver STD/human immunodeficiency virus (HIV) Prevention Training Center. STD/HIV knowledge and clinical skills were measured before, immediately after, and 6 months after training. Practice patterns were assessed before training and after 6 months. Structural barriers to implementation were identified 6 months post-training. Trainees demonstrated significant post-training gains in mean knowledge scores immediately post-training (P < 0.001) and 6 months post-training (P = 0.002). After 6 months, self-reported mean skill levels remained significantly improved compared to precourse (P < 0.05) for each of 27 skills including STD risk assessment, clinical examination, diagnosis, and treatment. Self-reported improvement in practice patterns was significant for 23 of 35 practices (P < 0.05) 6 months post-training. Participants indicated that inadequate time (52.9%), facilities/equipment (51.5%), and staffing (47.1%) interfered with implementation of recommended practices. Experiential-didactic STD/HIV training can modestly improve knowledge, clinical skills, and implementation of STD recommended practices 6 months after training. Further research is needed to identify the impact of improved clinical practices on STD/HIV transmission.

  11. Imaging tests in staging and surveillance of non-metastatic breast cancer: changes in routine clinical practice and cost implications.

    PubMed

    De Placido, S; De Angelis, C; Giuliano, M; Pizzi, C; Ruocco, R; Perrone, V; Bruzzese, D; Tommasielli, G; De Laurentiis, M; Cammarota, S; Arpino, G; Arpino, G

    2017-03-14

    Although guidelines do not recommend computerised tomography (CT), positron emission tomography (PET) or magnetic resonance imaging (MRI) for the staging or follow-up of asymptomatic patients with non-metastatic breast cancer, they are often requested in routine clinical practice. The aim of this study was to determine the staging and follow-up patterns, and relative costs in a large population of breast cancer patients living and treated in a Southern Italian region. We analysed the clinical computerised information recorded by 567 primary-care physicians assisting about 650 000 inhabitants in the Campania region. Patients with non-metastatic breast cancer were identified and divided into calendar years from 2001 to 2010. The number of diagnostic tests prescribed per 100 patients (N/Pts) and the mean cost per patient was determined 3 months before diagnosis and up to 1 year after diagnosis. Costs are expressed in constant 2011 euros. We identified 4680 newly diagnosed cases of asymptomatic non-metastatic breast cancer. N/Pts increased significantly (P<0.0001) from 2001 to 2010. The mean number of prescribed mammograms, bone scans, abdominal ultrasound and chest X-rays ('routine tests'), and costs was unchanged. However, the number of CT, PET scans and MRI ('new tests')prescriptions almost quadrupled and the mean cost per patient related to these procedures significantly increased from [euro ]357 in 2001 to [euro ]830 in 2010 (P<0.0001). New test prescriptions and relative costs significantly and steadily increased throughout the study period. At present there is no evidence that the delivery of new tests to asymptomatic patients improves breast cancer outcome. Well-designed clinical trials are urgently needed to shed light on the impact of these tests on clinical outcome and overall survival.

  12. Real-life assessment of the validity of patient global impression of change in fibromyalgia.

    PubMed

    Rampakakis, Emmanouil; Ste-Marie, Peter A; Sampalis, John S; Karellis, Angeliki; Shir, Yoram; Fitzcharles, Mary-Ann

    2015-01-01

    Patient Global Rating of Change (GRC) scales are commonly used in routine clinical care given their ease of use, availability and short completion time. This analysis aimed at assessing the validity of Patient Global Impression of Change (PGIC), a GRC scale commonly used in fibromyalgia, in a Canadian real-life setting. 167 fibromyalgia patients with available PGIC data were recruited in 2005-2013 from a Canadian tertiary-care multidisciplinary clinic. In addition to PGIC, disease severity was assessed with: pain visual analogue scale (VAS); Patient Global Assessment (PGA); Fibromyalgia Impact Questionnaire (FIQ); Health Assessment Questionnaire (HAQ); McGill Pain Questionnaire; body map. Multivariate linear regression assessed the PGIC relationship with disease parameter improvement while adjusting for follow-up duration and baseline parameter levels. The Spearman's rank coefficient assessed parameter correlation. Higher PGIC scores were significantly (p<0.001) associated with greater improvement in pain, PGA, FIQ, HAQ and the body map. A statistically significant moderate positive correlation was observed between PGIC and FIQ improvement (r=0.423; p<0.001); correlation with all remaining disease severity measures was weak. Regression analysis confirmed a significant (p<0.001) positive association between improvement in all disease severity measures and PGIC. Baseline disease severity and follow-up duration were identified as significant independent predictors of PGIC rating. Despite that only a weak correlation was identified between PGIC and standard fibromyalgia outcomes improvement, in the absence of objective outcomes, PGIC remains a clinically relevant tool to assess perceived impact of disease management. However, our analysis suggests that outcome measures data should not be considered in isolation but, within the global clinical context.

  13. Multireceptor fingerprints in progressive supranuclear palsy.

    PubMed

    Chiu, Wang Zheng; Donker Kaat, Laura; Boon, Agnita J W; Kamphorst, Wouter; Schleicher, Axel; Zilles, Karl; van Swieten, John C; Palomero-Gallagher, Nicola

    2017-04-17

    Progressive supranuclear palsy (PSP) with a frontal presentation, characterized by cognitive deficits and behavioral changes, has been recognized as an early clinical picture, distinct from the classical so-called Richardson and parkinsonism presentations. The midcingulate cortex is associated with executive and attention tasks and has consistently been found to be impaired in imaging studies of patients with PSP. The aim of the present study was to determine alterations in neurotransmission underlying the pathophysiology of PSP, as well as their significance for clinically identifiable PSP subgroups. In vitro receptor autoradiography was used to quantify densities of 20 different receptors in the caudate nucleus and midcingulate area 24' of patients with PSP (n = 16) and age- and sex-matched control subjects (n = 14). Densities of γ-aminobutyric acid type B, peripheral benzodiazepine, serotonin receptor type 2, and N-methyl-D-aspartate receptors were significantly higher in area 24' of patients with PSP, where tau impairment was stronger than in the caudate nucleus. Kainate and nicotinic cholinergic receptor densities were significantly lower, and adenosine receptor type 1 (A 1 ) receptors significantly higher, in the caudate nucleus of patients with PSP. Receptor fingerprints also segregated PSP subgroups when clinical parameters such as occurrence of frontal presentation and tau pathology severity were taken into consideration. We demonstrate, for the first time to our knowledge, that kainate and A 1 receptors are altered in PSP and that clinically identifiable PSP subgroups differ at the neurochemical level. Numerous receptors were altered in the midcingulate cortex, further suggesting that it may prove to be a key region in PSP. Finally, we add to the evidence that nondopaminergic systems play a role in the pathophysiology of PSP, thus highlighting potential novel treatment strategies.

  14. How to tell a patient's story? Influence of the case narrative design on the clinical reasoning process in virtual patients.

    PubMed

    Hege, Inga; Dietl, Anita; Kiesewetter, Jan; Schelling, Jörg; Kiesewetter, Isabel

    2018-02-28

    Virtual patients (VPs) are narrative-based educational activities to train clinical reasoning in a safe environment. Our aim was to explore the influence of the design of the narrative and level of difficulty on the clinical reasoning process, diagnostic accuracy and time-on-task. In a randomized controlled trial, we analyzed the clinical reasoning process of 46 medical students with six VPs in three different variations: (1) patients showing a friendly behavior, (2) patients showing a disruptive behavior and (3) a version without a patient story. For easy VPs, we did not see a significant difference in diagnostic accuracy. For difficult VPs, the diagnostic accuracy was significantly higher for participants who worked on the friendly VPs compared to the other two groups. Independent from VP difficulty, participants identified significantly more problems and tests for disruptive than for friendly VPs; time on task was comparable for these two groups. The extrinsic motivation of participants working on the VPs without a patient story was significantly lower than for the students working on the friendly VPs. Our results indicate that the measured VP difficulty has a higher influence on the clinical reasoning process and diagnostic accuracy than the variations in the narratives.

  15. The Ottawa panel clinical practice guidelines for the management of knee osteoarthritis. Part one: introduction, and mind-body exercise programs.

    PubMed

    Brosseau, Lucie; Taki, Jade; Desjardins, Brigit; Thevenot, Odette; Fransen, Marlene; Wells, George A; Imoto, Aline Mizusaki; Toupin-April, Karine; Westby, Marie; Gallardo, Inmaculada C Álvarez; Gifford, Wendy; Laferrière, Lucie; Rahman, Prinon; Loew, Laurianne; Angelis, Gino De; Cavallo, Sabrina; Shallwani, Shirin Mehdi; Aburub, Ala'; Bennell, Kim L; Van der Esch, Martin; Simic, Milena; McConnell, Sara; Harmer, Alison; Kenny, Glen P; Paterson, Gail; Regnaux, Jean-Philippe; Lefevre-Colau, Marie-Martine; McLean, Linda

    2017-05-01

    To identify effective mind-body exercise programs and provide clinicians and patients with updated, high-quality recommendations concerning non-traditional land-based exercises for knee osteoarthritis. A systematic search and adapted selection criteria included comparative controlled trials with mind-body exercise programs for patients with knee osteoarthritis. A panel of experts reached consensus on the recommendations using a Delphi survey. A hierarchical alphabetical grading system (A, B, C+, C, D, D+, D-) was used, based on statistical significance ( P < 0.5) and clinical importance (⩾15% improvement). The four high-quality studies identified demonstrated that various mind-body exercise programs are promising for improving the management of knee osteoarthritis. Hatha Yoga demonstrated significant improvement for pain relief (Grade B) and physical function (Grade C+). Tai Chi Qigong demonstrated significant improvement for quality of life (Grade B), pain relief (Grade C+) and physical function (Grade C+). Sun style Tai Chi gave significant improvement for pain relief (Grade B) and physical function (Grade B). Mind-body exercises are promising approaches to reduce pain, as well as to improve physical function and quality of life for individuals with knee osteoarthritis.

  16. Using natural language processing for identification of herpes zoster ophthalmicus cases to support population-based study.

    PubMed

    Zheng, Chengyi; Luo, Yi; Mercado, Cheryl; Sy, Lina; Jacobsen, Steven J; Ackerson, Brad; Lewin, Bruno; Tseng, Hung Fu

    2018-06-19

    Diagnosis codes are inadequate for accurately identifying herpes zoster ophthalmicus (HZO). There is significant lack of population-based studies on HZO due to the high expense of manual review of medical records. To assess whether HZO can be identified from the clinical notes using natural language processing (NLP). To investigate the epidemiology of HZO among HZ population based on the developed approach. A retrospective cohort analysis. A total of 49,914 southern California residents aged over 18 years, who had a new diagnosis of HZ. An NLP-based algorithm was developed and validated with the manually curated validation dataset (n=461). The algorithm was applied on over 1 million clinical notes associated with the study population. HZO versus non-HZO cases were compared by age, sex, race, and comorbidities. We measured the accuracy of NLP algorithm. NLP algorithm achieved 95.6% sensitivity and 99.3% specificity. Compared to the diagnosis codes, NLP identified significant more HZO cases among HZ population (13.9% versus 1.7%). Compared to the non-HZO group, the HZO group was older, had more males, had more Whites, and had more outpatient visits. We developed and validated an automatic method to identify HZO cases with high accuracy. As one of the largest studies on HZO, our finding emphasizes the importance of preventing HZ in the elderly population. This method can be a valuable tool to support population-based studies and clinical care of HZO in the era of big data. This article is protected by copyright. All rights reserved.

  17. Comprehensive methylome analysis of ovarian tumors reveals hedgehog signaling pathway regulators as prognostic DNA methylation biomarkers.

    PubMed

    Huang, Rui-Lan; Gu, Fei; Kirma, Nameer B; Ruan, Jianhua; Chen, Chun-Liang; Wang, Hui-Chen; Liao, Yu-Ping; Chang, Cheng-Chang; Yu, Mu-Hsien; Pilrose, Jay M; Thompson, Ian M; Huang, Hsuan-Cheng; Huang, Tim Hui-Ming; Lai, Hung-Cheng; Nephew, Kenneth P

    2013-06-01

    Women with advanced stage ovarian cancer (OC) have a five-year survival rate of less than 25%. OC progression is associated with accumulation of epigenetic alterations and aberrant DNA methylation in gene promoters acts as an inactivating "hit" during OC initiation and progression. Abnormal DNA methylation in OC has been used to predict disease outcome and therapy response. To globally examine DNA methylation in OC, we used next-generation sequencing technology, MethylCap-sequencing, to screen 75 malignant and 26 normal or benign ovarian tissues. Differential DNA methylation regions (DMRs) were identified, and the Kaplan-Meier method and Cox proportional hazard model were used to correlate methylation with clinical endpoints. Functional role of specific genes identified by MethylCap-sequencing was examined in in vitro assays. We identified 577 DMRs that distinguished (p < 0.001) malignant from non-malignant ovarian tissues; of these, 63 DMRs correlated (p < 0.001) with poor progression free survival (PFS). Concordant hypermethylation and corresponding gene silencing of sonic hedgehog pathway members ZIC1 and ZIC4 in OC tumors was confirmed in a panel of OC cell lines, and ZIC1 and ZIC4 repression correlated with increased proliferation, migration and invasion. ZIC1 promoter hypermethylation correlated (p < 0.01) with poor PFS. In summary, we identified functional DNA methylation biomarkers significantly associated with clinical outcome in OC and suggest our comprehensive methylome analysis has significant translational potential for guiding the design of future clinical investigations targeting the OC epigenome. Methylation of ZIC1, a putative tumor suppressor, may be a novel determinant of OC outcome.

  18. Malformations detected by abdominal ultrasound in children with congenital heart disease.

    PubMed

    Rosa, Rosana Cardoso Manique; Rosa, Rafael Fabiano Machado; Flores, José Antônio Monteiro; Golendziner, Eliete; Oliveira, Ceres Andréia Vieira de; Varella-Garcia, Marileila; Paskulin, Giorgio Adriano; Zen, Paulo Ricardo Gazzola

    2012-12-01

    Extracardiac malformations may be present in patients with congenital heart disease (CHD), bringing greater risk of comorbidity and mortality. Verify frequency and types of abdominal abnormalities detected in children with and without CHD through abdominal ultrasound (AUS), compare the patients in relation to their dysmorphic/cytogenetic findings and perform an estimative of the cost-effectiveness of the screening through AUS. We conducted a cross-sectional study with a control cohort. The cases consisted of patients with CHD admitted for the first time in a pediatric intensive care unit; the controls consisted of children without CHD who underwent AUS at the hospital shortly thereafter a case. All patients with CHD underwent AUS, high-resolution karyotype and fluorescence in situ hybridization (FISH) for microdeletion 22q11.2. AUS identified clinically significant abnormalities in 12.2% of the cases and 5.2% of controls (p= 0.009), with a power of significance of 76.6%. Most malformations with clinical significance were renal anomalies (10.4% in cases and 4.9% in controls; p= 0.034). In Brazil, the cost of an AUS examination for the Unified Health System is US$ 21. Since clinically significant abnormalities were observed in one in every 8.2 CHD patients, the cost to identify an affected child was calculated as approximately US$ 176. Patients with CHD present a significant frequency of abdominal abnormalities detected by AUS, an inexpensive and noninvasive diagnostic method with good sensitivity. The cost of screening for these defects is considerably lower than the cost to treat the complications of late diagnoses of abdominal malformations such as renal disease.

  19. Contrast-enhanced CT features of hepatoblastoma: Can we predict histopathology?

    PubMed

    Baheti, Akshay D; Luana Stanescu, A; Li, Ning; Chapman, Teresa

    Hepatoblastoma is the most common hepatic malignancy occurring in the pediatric population. Intratumoral cellular behavior varies, and the small-cell undifferentiated histopathology carries a poorer prognosis than other tissue subtypes. Neoadjuvant chemotherapy is recommended for this tumor subtype prior to surgical resection in most cases. Early identification of tumors with poor prognosis could have a significant clinical impact. Objective The aim of this work was to identify imaging features of small-cell undifferentiated subtype hepatoblastoma that can help distinguish this subtype from more favorable tumors and potentially guide the clinical management. We also sought to characterize contrast-enhanced CT (CECT) features of hepatoblastoma that correlate with metastatic disease and patient outcome. Our study included 34 patients (24 males, 10 females) with a mean age of 16months (range: 0-46months) with surgically confirmed hepatoblastoma and available baseline abdominal imaging by CECT. Clinical data and CT abdominal images were retrospectively analyzed. Five tumors with small-cell undifferentiated components were identified. All of these tumors demonstrated irregular margins on CT imaging. Advanced PRETEXT stage, vascular invasion and irregular margins were associated with metastatic disease and decreased survival. Capsular retraction was also significantly associated with decreased survival. Irregular tumor margins demonstrated statistically significant association with the presence of small-cell undifferentiated components. No other imaging feature showed statistically significant association. Tumor margin irregularity, vascular invasion, capsular retraction, and PRETEXT stage correlate with worse patient outcomes. Irregular tumor margin was the only imaging feature significantly associated with more aggressive tumor subtype. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. An 'inflammatory' variant of solar purpura: a simulant of leukocytoclastic vasculitis and neutrophilic dermatoses.

    PubMed

    Wood, Benjamin A; LeBoit, Philip E

    2013-08-01

    To study the clinical and pathological features of cases of apparent solar purpura, with attention to the recently described phenomenon of inflammatory changes within otherwise typical lesions. We studied 95 cases diagnosed as solar purpura and identified 10 cases (10.5%) in which significant neutrophilic inflammation was present, potentially simulating a leukocytoclastic vasculitis or neutrophilic dermatosis. An additional three cases were identified in subsequent routine practice. The clinical features, including follow-up for subsequent development of vasculitis and histological features were studied. In all cases the histological features were typical of solar purpura, with the exception of inflammatory changes, typically associated with clefting of elastotic stroma. Clinical follow-up information was available for all patients and none developed subsequent evidence of a cutaneous or systemic vasculitis or neutrophilic dermatosis. Inflammatory changes appear to be more frequent in solar purpura than is generally recognised. Awareness of this histological variation and correlation with the clinical findings and evolution is important in avoiding misdiagnosis.

  1. Assessing Bleeding Risk in Patients Taking Anticoagulants

    PubMed Central

    Shoeb, Marwa; Fang, Margaret C.

    2013-01-01

    Anticoagulant medications are commonly used for the prevention and treatment of thromboembolism. Although highly effective, they are also associated with significant bleeding risks. Numerous individual clinical factors have been linked to an increased risk of hemorrhage, including older age, anemia, and renal disease. To help quantify hemorrhage risk for individual patients, a number of clinical risk prediction tools have been developed. These risk prediction tools differ in how they were derived and how they identify and weight individual risk factors. At present, their ability to effective predict anticoagulant-associated hemorrhage remains modest. Use of risk prediction tools to estimate bleeding in clinical practice is most influential when applied to patients at the lower spectrum of thromboembolic risk, when the risk of hemorrhage will more strongly affect clinical decisions about anticoagulation. Using risk tools may also help counsel and inform patients about their potential risk for hemorrhage while on anticoagulants, and can identify patients who might benefit from more careful management of anticoagulation. PMID:23479259

  2. Hypnosis for procedure-related pain and distress in pediatric cancer patients: a systematic review of effectiveness and methodology related to hypnosis interventions.

    PubMed

    Richardson, Janet; Smith, Joanna E; McCall, Gillian; Pilkington, Karen

    2006-01-01

    The aim of this study was to systematically review and critically appraise the evidence on the effectiveness of hypnosis for procedure-related pain and distress in pediatric cancer patients. A comprehensive search of major biomedical and specialist complementary and alternative medicine databases was conducted. Citations were included from the databases' inception to March 2005. Efforts were made to identify unpublished and ongoing research. Controlled trials were appraised using predefined criteria. Clinical commentaries were obtained for each study. Seven randomized controlled clinical trials and one controlled clinical trial were found. Studies report positive results, including statistically significant reductions in pain and anxiety/distress, but a number of methodological limitations were identified. Systematic searching and appraisal has demonstrated that hypnosis has potential as a clinically valuable intervention for procedure-related pain and distress in pediatric cancer patients. Further research into the effectiveness and acceptability of hypnosis for pediatric cancer patients is recommended.

  3. Pathogenetic Significance of Biological Markers of Ventilator-Associated Lung Injury in Experimental and Clinical Studies*

    PubMed Central

    Frank, James A.; Parsons, Polly E.; Matthay, Michael A.

    2009-01-01

    For patients with acute lung injury, positive pressure mechanical ventilation is life saving. However, considerable experimental and clinical data have demonstrated that how clinicians set the tidal volume, positive end-expiratory pressure, and plateau airway pressure influences lung injury severity and patient outcomes including mortality. In order to better identify ventilator-associated lung injury (VALI), clinical investigators have sought to measure blood-borne and airspace biological markers of VALI. At the same time, several laboratory-based studies have focused on biological markers of inflammation and organ injury in experimental models in order to clarify the mechanisms of ventilator-induced lung injury (VILI) and VALI. This review summarizes data on biological markers of VALI and VILI from both clinical and experimental studies with an emphasis on markers identified in patients and in the experimental setting. This analysis suggests that measurement of some of these biological markers may be of value in diagnosing VALI and in understanding its pathogenesis. PMID:17167015

  4. Maintenance of pain in children with functional abdominal pain

    USDA-ARS?s Scientific Manuscript database

    A significant proportion of children with functional abdominal pain develop chronic pain. Identifying clinical characteristics predicting pain persistence is important in targeting interventions. We examined whether child anxiety and/or pain-stooling relations were related to maintenance of abdomina...

  5. Psychophysiological Outcome of Behavioral and Pharmacological Treatments of Agoraphobia.

    ERIC Educational Resources Information Center

    Michelson, Larry; Mavissakalian, Matig

    1985-01-01

    Examined relative and combined effectiveness of behavior therapy and pharmacotherapy in 62 severe, chronic agoraphobics. Identified differential temporal response and treatment patterns across psychophysiological domains. Synchrony/desynchrony phenomena yielded significant findings with regard to process and clinical outcome status. Exploratory…

  6. 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

  7. Frequency and clinical predictors of coronary artery disease in chronic renal failure renal transplant candidates.

    PubMed

    de Albuquerque Seixas, Emerson; Carmello, Beatriz Leone; Kojima, Christiane Akemi; Contti, Mariana Moraes; Modeli de Andrade, Luiz Gustavo; Maiello, José Roberto; Almeida, Fernando Antonio; Martin, Luis Cuadrado

    2015-05-01

    Cardiovascular diseases are major causes of mortality in chronic renal failure patients before and after renal transplantation. Among them, coronary disease presents a particular risk; however, risk predictors have been used to diagnose coronary heart disease. This study evaluated the frequency and importance of clinical predictors of coronary artery disease in chronic renal failure patients undergoing dialysis who were renal transplant candidates, and assessed a previously developed scoring system. Coronary angiographies conducted between March 2008 and April 2013 from 99 candidates for renal transplantation from two transplant centers in São Paulo state were analyzed for associations between significant coronary artery diseases (≥70% stenosis in one or more epicardial coronary arteries or ≥50% in the left main coronary artery) and clinical parameters. Univariate logistic regression analysis identified diabetes, angina, and/or previous infarction, clinical peripheral arterial disease and dyslipidemia as predictors of coronary artery disease. Multiple logistic regression analysis identified only diabetes and angina and/or previous infarction as independent predictors. The results corroborate previous studies demonstrating the importance of these factors when selecting patients for coronary angiography in clinical pretransplant evaluation.

  8. Supervisory needs of research doctoral students in a university teaching hospital setting.

    PubMed

    Caldwell, Patrina Hy; Oldmeadow, Wendy; Jones, Cheryl A

    2012-10-01

    Teaching hospitals affiliated with universities are now common sites for research higher degree supervision. We hypothesised that the hospital environment poses unique challenges to supervision compared with the traditional university research institute setting. This study aimed to identify and rank important supervision issues in a clinical setting from the students' perspective. Using the Delphi method to explore issues and facilitate consensus, small group discussions were conducted with 10 research doctoral students from a tertiary teaching hospital. We identified supervision issues that are unique to the hospital-based context. These include the demands placed on supervisors combining clinical and supervisory roles, the challenges of academic medical/scientific writing and career issues for students who are already established in their professions. Other issues identified, common to all doctoral students, include differing expectations between students and supervisors (with students wanting support for their career plans, training in research skills and increasing autonomy and responsibility), supervisor access, quality and frequency of meetings, lack of training in writing and dealing with conflicts. Our research identified that postgraduate students of supervisors who combine clinical and supervisory roles report significant issues with supervision, some of which are unique to the clinical setting. Clinician researchers who supervise postgraduate students need to balance clinical and supervisory responsibilities, identify and negotiate student expectations early in candidature and provide career counselling to students who are already highly experienced. Furthermore, clinician supervisors should undertake postgraduate supervisor training programme tailored to the hospital setting to better support their students. © 2012 The Authors. Journal of Paediatrics and Child Health © 2012 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

  9. Implementing Cough Reflex Testing in a Clinical Pathway for Acute Stroke: A Pragmatic Randomised Controlled Trial.

    PubMed

    Field, Makaela; Wenke, Rachel; Sabet, Arman; Lawrie, Melissa; Cardell, Elizabeth

    2018-05-15

    Silent aspiration is common after stroke and can lead to subsequent pneumonia. While standard bedside dysphagia assessments are ineffective at predicting silent aspiration, cough reflex testing (CRT) has shown promise for identifying patients at risk of silent aspiration. We investigated the impact of CRT on patient and service outcomes when embedded into a clinical pathway. 488 acute stoke patients were randomly allocated to receive either CRT or standard care (i.e. bedside assessment). Primary outcomes included confirmed pneumonia within 3 months post stroke and length of acute inpatient stay. Secondary outcomes related to the feasibility of implementing a CRT pathway and clinician and patient satisfaction. There was a non-significant reduction in pneumonia rates by 2.2% points in the CRT group (OR 0.32, 95% CI 0.06-1.62). There was a non-significant difference of 0.7 days (95% CI - 0.29 to 1.71 days) in length of stay between the standard care group and the CRT group. The CRT took on average 3 min longer to complete (p < 0.01) and resulted in a significant 6.7% increase in videofluoroscopic referrals (p = 0.02); however, these results are clinically insignificant. High patient and clinician satisfaction with CRT was found, with clinicians reporting additional knowledge and confidence in decision making for dysphagia management. Post hoc subgroup analyses according to stroke types were conducted and revealed no significant differences in pneumonia rates after adjustment for multiple comparisons. In conclusion, it was possible to implement a CRT pathway with minimal increases in clinician resources. While clinicians perceived CRT as beneficial in clinical decision making, the efficacy of CRT for reducing pneumonia rates in acute stroke remains to be established.Clinical Trial Registration-URL: http://www.anzctr.org.au . Unique identifier: ACTRN12616000724471.

  10. Single nucleotide polymorphisms in multiple sclerosis: disease susceptibility and treatment response biomarkers.

    PubMed

    Pravica, Vera; Popadic, Dusan; Savic, Emina; Markovic, Milos; Drulovic, Jelena; Mostarica-Stojkovic, Marija

    2012-04-01

    Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system characterized by unpredictable and variable clinical course. Etiology of MS involves both genetic and environmental factors. New technologies identified genetic polymorphisms associated with MS susceptibility among which immunologically relevant genes are significantly overrepresented. Although individual genes contribute only a small part to MS susceptibility, they might be used as biomarkers, thus helping to identify accurate diagnosis, predict clinical disease course and response to therapy. This review focuses on recent progress in research on MS genetics with special emphasis on the possibility to use single nucleotide polymorphism of candidate genes as biomarkers of susceptibility to disease and response to therapy.

  11. High doses of corticosteroid suppress resistance to Ichthyophonus in starry flounder

    USGS Publications Warehouse

    Perry, J.A.; Kocan, R.M.; Winton, J.R.; Hershberger, P.K.

    2004-01-01

    Application of pharmacological doses of the corticosteroid dexamethasone phosphate to starry flounder Platichthys stellatus resulted in a predisposition to clinical ichthyophoniasis and a progression from latent Ichthyophonus infections to patent, histologically identifiable infections. Among Ichthyophonus-challenged starry flounder, the prevalences of clinical infections and histologically identifiable infections were significantly greater in two groups that received dexamethasone (100% and 31%, respectively) than in the respective control groups (8% and 0%). Proliferation of Ichthyophonus infections in corticosteroid-treated groups may have resulted from suppression of the cellular immune response that typically follows corticosteroid application; however, further studies are needed to determine whether these effects occur at lower, physiological concentrations of corticosteroids.

  12. Guidelines for Initiating a Research Agenda: Topic Selection and Evidence of Impact.

    PubMed

    Delost, Maria E; Nadder, Teresa S

    2014-01-01

    The focus on scholarly productivity as an outcome measure for performance evaluations of personnel and/or units and benchmarking purposes is increasing in both the academic and clinical settings. This article presents avenues for identifying achievable research projects in both the academic and clinical settings. Factors for consideration when selecting a project include its significance or impact on the profession, feasibility for implementing the project, and ethical issues related to human subjects protection. A review of the literature is essential for identifying gaps in knowledge and for constructing the hypothesis or research question. Decisions concerning IRB submission, budget allocation, and collection of data must also be considered before implementation of the research design.

  13. EB1 protein alteration characterizes sporadic but not ulcerative colitis associated colorectal cancer.

    PubMed

    Gemoll, Timo; Kollbeck, Sophie L; Karstens, Karl F; Hò, Gia G; Hartwig, Sonja; Strohkamp, Sarah; Schillo, Katharina; Thorns, Christoph; Oberländer, Martina; Kalies, Kathrin; Lehr, Stefan; Habermann, Jens K

    2017-08-15

    While carcinogenesis in Sporadic Colorectal Cancer (SCC) has been thoroughly studied, less is known about Ulcerative Colitis associated Colorectal Cancer (UCC). This study aimed to identify and validate differentially expressed proteins between clinical samples of SCC and UCC to elucidate new insights of UCC/SCC carcinogenesis and progression. Multiplex-fluorescence two-dimensional gel electrophoresis (2-D DIGE) and mass spectrometry identified 67 proteoforms representing 43 distinct proteins. After analysis by Ingenuity Pathway Analysis ® (IPA), subsequent Western blot validation proofed the differential expression of Heat shock 27 kDA protein 1 (HSPB1) and Microtubule-associated protein R/EB family, member 1 (EB1) while the latter one showed also expression differences by immunohistochemistry. Fresh frozen tissue of UCC ( n = 10) matched with SCC ( n = 10) was investigated. Proteins of cancerous intestinal mucosal cells were obtained by Laser Capture Microdissection (LCM) and compared by 2-D DIGE. Significant spots were identified by mass spectrometry. After IPA, three proteins [EB1, HSPB1, and Annexin 5 (ANXA5)] were chosen for further validation by Western blotting and tissue microarray-based immunohistochemistry. This study identified significant differences in protein expression of colorectal carcinoma cells from UCC patients compared to patients with SCC. Particularly, EB1 was validated in an independent clinical cohort.

  14. Research as a standard of care in PICU

    PubMed Central

    Zimmerman, Jerry J.; Anand, Kanwaljeet J. S.; Meert, Kathleen L.; Willson, Douglas F.; Newth, Christopher J. L.; Harrison, Rick; Carcillo, Joseph A.; Berger, John; Jenkins, Tammara L.; Nicholson, Carol; Dean, J. Michael

    2016-01-01

    Background Excellence in clinical care coupled with basic and applied research reflects the maturation of a medical subspecialty, advances that field, and provides objective data for identifying best practices. Pediatric intensive care units (PICU) are uniquely suited for conducting translational and clinical research. Moreover, multiple investigations have reported that a majority of parents are interested in their children’s participation in clinical research, even when the research offers no direct benefit to their child. However, such activity may generate ethical conflict with bedside care providers trying to acutely identify the best approach for an individual critically ill child. Ultimately, this conflict may diminish enthusiasm for the generation of scientific evidence that supports application of evidence-based medicine into PICU clinical standard work. Objective Provide an overview of current state PICU clinical research strengths, liabilities, opportunities, and barriers, and contrast this with an established pediatric hematology-oncology iterative research model that constitutes a learning healthcare system. Design Narrative review of medical literature published in English. Conclusions Currently most PICU therapy is not evidence-based. Developing a learning healthcare system in the PICU integrates clinical research into usual practice and fosters a culture of evidence-based learning and continual care improvement. As PICU mortality has significantly decreased, identification and validation of patient-centered, clinically relevant research outcome measures other than mortality is essential for future clinical trial design. Because most pediatric critical illness may be classified as rare diseases, participation in research networks will facilitate iterative, collaborative, multi-institutional investigations that over time identify best practices to improve PICU outcomes. Despite real ethical challenges, critically ill children and their families should have the opportunity to participate in translational/clinical research whenever feasible. PMID:26513203

  15. Reconciling the professional and student identities of clinical psychology trainees.

    PubMed

    McKenzie, Karen; Cossar, Jill A; Fawns, Tim; Murray, Aja L

    2013-10-01

    The study explored the ways in which qualified and trainee clinical psychologists perceived professional behaviour, as illustrated in a series of short vignettes, in student and clinical practice contexts. Comparisons were made to identify the extent to which ideas of professionalism differed across different learning contexts and between qualified and unqualified staff, with the aim of adding to the literature on which factors influence the development of professional identity in health professionals. An online questionnaire depicting a range of potentially unprofessional behaviours was completed by 265 clinical psychology trainees and 106 qualified clinical psychologists. The data were analysed using a general linear model with simultaneous entry in which rater (trainee vs qualified clinical psychologist), setting (student vs placement) and their interaction predicted acceptability ratings. We found that, in general, trainees and qualified staff agreed on those behaviours that were potentially unprofessional, although where significant differences were found, these were due to trainees rating the same behaviours as more professionally acceptable than qualified clinical psychologists. Despite trainees identifying a range of behaviours as professionally unacceptable, some percentage reported having engaged in a similar behaviour in the past. Irrespective of the status of the rater, the same behaviours tended to be viewed as more professionally unacceptable when in a placement (clinical) setting than in a student (university) setting. Generally, no support was found for a rater by setting interaction. The study suggests that trainee clinical psychologists are generally successful at identifying professional norms, although they do not always act in accordance with these. Conflicting student and professional norms may result in trainees viewing some potentially unprofessional behaviour as less severe than qualified staff. Health professional educators should be aware of this fact and take steps to shape trainee norms to be consistent with that of the professional group.

  16. Genome-wide association study identifies TF as a significant modifier gene of iron metabolism in HFE hemochromatosis.

    PubMed

    de Tayrac, Marie; Roth, Marie-Paule; Jouanolle, Anne-Marie; Coppin, Hélène; le Gac, Gérald; Piperno, Alberto; Férec, Claude; Pelucchi, Sara; Scotet, Virginie; Bardou-Jacquet, Edouard; Ropert, Martine; Bouvet, Régis; Génin, Emmanuelle; Mosser, Jean; Deugnier, Yves

    2015-03-01

    Hereditary hemochromatosis (HH) is the most common form of genetic iron loading disease. It is mainly related to the homozygous C282Y/C282Y mutation in the HFE gene that is, however, a necessary but not a sufficient condition to develop clinical and even biochemical HH. This suggests that modifier genes are likely involved in the expressivity of the disease. Our aim was to identify such modifier genes. We performed a genome-wide association study (GWAS) using DNA collected from 474 unrelated C282Y homozygotes. Associations were examined for both quantitative iron burden indices and clinical outcomes with 534,213 single nucleotide polymorphisms (SNP) genotypes, with replication analyses in an independent sample of 748 C282Y homozygotes from four different European centres. One SNP met genome-wide statistical significance for association with transferrin concentration (rs3811647, GWAS p value of 7×10(-9) and replication p value of 5×10(-13)). This SNP, located within intron 11 of the TF gene, had a pleiotropic effect on serum iron (GWAS p value of 4.9×10(-6) and replication p value of 3.2×10(-6)). Both serum transferrin and iron levels were associated with serum ferritin levels, amount of iron removed and global clinical stage (p<0.01). Serum iron levels were also associated with fibrosis stage (p<0.0001). This GWAS, the largest one performed so far in unselected HFE-associated HH (HFE-HH) patients, identified the rs3811647 polymorphism in the TF gene as the only SNP significantly associated with iron metabolism through serum transferrin and iron levels. Because these two outcomes were clearly associated with the biochemical and clinical expression of the disease, an indirect link between the rs3811647 polymorphism and the phenotypic presentation of HFE-HH is likely. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  17. A systematic review of natural health product treatment for vitiligo

    PubMed Central

    Szczurko, Orest; Boon, Heather S

    2008-01-01

    Background Vitiligo is a hypopigmentation disorder affecting 1 to 4% of the world population. Fifty percent of cases appear before the age of 20 years old, and the disfigurement results in psychiatric morbidity in 16 to 35% of those affected. Methods Our objective was to complete a comprehensive, systematic review of the published scientific literature to identify natural health products (NHP) such as vitamins, herbs and other supplements that may have efficacy in the treatment of vitiligo. We searched eight databases including MEDLINE and EMBASE for vitiligo, leucoderma, and various NHP terms. Prospective controlled clinical human trials were identified and assessed for quality. Results Fifteen clinical trials were identified, and organized into four categories based on the NHP used for treatment. 1) L-phenylalanine monotherapy was assessed in one trial, and as an adjuvant to phototherapy in three trials. All reported beneficial effects. 2) Three clinical trials utilized different traditional Chinese medicine products. Although each traditional Chinese medicine trial reported benefit in the active groups, the quality of the trials was poor. 3) Six trials investigated the use of plants in the treatment of vitiligo, four using plants as photosensitizing agents. The studies provide weak evidence that photosensitizing plants can be effective in conjunction with phototherapy, and moderate evidence that Ginkgo biloba monotherapy can be useful for vitiligo. 4) Two clinical trials investigated the use of vitamins in the therapy of vitiligo. One tested oral cobalamin with folic acid, and found no significant improvement over control. Another trial combined vitamin E with phototherapy and reported significantly better repigmentation over phototherapy only. It was not possible to pool the data from any studies for meta-analytic purposes due to the wide difference in outcome measures and poor quality ofreporting. Conclusion Reports investigating the efficacy of NHPs for vitiligo exist, but are of poor methodological quality and contain significant reporting flaws. L-phenylalanine used with phototherapy, and oral Ginkgo biloba as monotherapy show promise and warrant further investigation. PMID:18498646

  18. The Urinary Microbiome Differs Significantly Between Patients With Chronic Prostatitis/Chronic Pelvic Pain Syndrome and Controls as Well as Between Patients With Different Clinical Phenotypes.

    PubMed

    Shoskes, Daniel A; Altemus, Jessica; Polackwich, Alan S; Tucky, Barbara; Wang, Hannah; Eng, Charis

    2016-06-01

    To study the urinary microbiome of patients with Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) compared with controls. We identified 25 patients with CP/CPPS and 25 men who were either asymptomatic or only had urinary symptoms. Midstream urine was collected. Symptom severity was measured with the National Institutes of Health Chronic Prostatitis Symptom Index and clinical phenotype with UPOINT. Total DNA was extracted from the urine pellet and bacterial-specific 16Sr-DNA-capture identified by MiSeq sequencing. Taxonomic and functional bioinformatic analyses used principal coordinate analysis (PCoA)/MacQIIME, LEfSe, and PiCRUSt algorithms. Patients and controls were similar ages (52.3 vs 57.0 years, P = .27). For patients, median duration was 48 months, mean Chronic Prostatitis Symptom Index was 26.0, and mean UPOINT domains was 3.6. Weighted 3D UniFrac PCoA revealed tighter clustering of controls distinct from the wider clustering of cases (P = .001; α-diversity P = .005). Seventeen clades were overrepresented in patients, for example, Clostridia, and 5 were underrepresented, eg, Bacilli, resulting in predicted perturbations in functional pathways. PiCRUSt inferred differentially regulated pathways between cases and controls that may be of relevance including sporulation, chemotaxis, and pyruvate metabolism. PCoA-derived microbiomic differences were noted for neurologic/systemic domains (P = .06), whereas LEfSe identified differences associated with each of the 6 clinical features. Urinary microbiomes from patients with CP/CPPS have significantly higher alpha(phylogenetic) diversity which cluster differently from controls, and higher counts of Clostridia compared with controls, resulting in predicted perturbations of functional pathways which could suggest metabolite-specific targeted treatment. Several measures of severity and clinical phenotype have significant microbiome differences. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Adolescents with vascular frontal lesion: A neuropsychological follow up case study.

    PubMed

    Chávez, Clara L; Yáñez, Guillermina; Catroppa, Cathy; Rojas, Sulema; Escartin, Erick; Hearps, Stephen J C; García, Antonio

    2016-01-01

    The objective of this research was to identify clinically significant changes in cognitive functions in three adolescents who underwent surgery for resection of a focal vascular lesion in the frontal lobe. Cognitive functions, executive function, behavior regulation, emotion regulation, and social abilities were assessed prior to surgery, six and 24 months post-discharge. Significant clinical changes were observed during all the assessments. Cognitive changes after surgery are not homogeneous. Most of the significant clinical changes were improvements. Especially the significant clinical changes presented in EF domains were only improvements; these results suggest that EF were affected by the vascular lesion and benefitted by the surgery. After resection of a vascular lesion between 15 and 16 years of age the affected executive functions can continue the maturation process. Our results highlight the importance that assessments must include emotional aspects, even if deficits in these domains are not presented in the acute phase. Rehabilitation methods should promote the development of skills that help patients and their families to manage the emotional and behavioral changes that emerge once they are discharged from the hospital. Copyright © 2015 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

  20. Patient-specific parameter estimation in single-ventricle lumped circulation models under uncertainty

    PubMed Central

    Schiavazzi, Daniele E.; Baretta, Alessia; Pennati, Giancarlo; Hsia, Tain-Yen; Marsden, Alison L.

    2017-01-01

    Summary Computational models of cardiovascular physiology can inform clinical decision-making, providing a physically consistent framework to assess vascular pressures and flow distributions, and aiding in treatment planning. In particular, lumped parameter network (LPN) models that make an analogy to electrical circuits offer a fast and surprisingly realistic method to reproduce the circulatory physiology. The complexity of LPN models can vary significantly to account, for example, for cardiac and valve function, respiration, autoregulation, and time-dependent hemodynamics. More complex models provide insight into detailed physiological mechanisms, but their utility is maximized if one can quickly identify patient specific parameters. The clinical utility of LPN models with many parameters will be greatly enhanced by automated parameter identification, particularly if parameter tuning can match non-invasively obtained clinical data. We present a framework for automated tuning of 0D lumped model parameters to match clinical data. We demonstrate the utility of this framework through application to single ventricle pediatric patients with Norwood physiology. Through a combination of local identifiability, Bayesian estimation and maximum a posteriori simplex optimization, we show the ability to automatically determine physiologically consistent point estimates of the parameters and to quantify uncertainty induced by errors and assumptions in the collected clinical data. We show that multi-level estimation, that is, updating the parameter prior information through sub-model analysis, can lead to a significant reduction in the parameter marginal posterior variance. We first consider virtual patient conditions, with clinical targets generated through model solutions, and second application to a cohort of four single-ventricle patients with Norwood physiology. PMID:27155892

  1. Predictors of health-related quality of life changes after lifestyle intervention in persons at risk of type 2 diabetes mellitus.

    PubMed

    Nilsen, Vegard; Bakke, Per Sigvald; Rohde, Gudrun; Gallefoss, Frode

    2014-11-01

    To assess health-related quality of life (HRQOL) of subjects at risk of type 2 diabetes undergoing lifestyle intervention, and predictors for improved HRQOL. The Finnish Diabetes Risk Score was used by general practitioners to identify individuals at risk. Low-intensity interventions with an 18-month follow-up were employed. HRQOL was assessed using the SF-36 at baseline and compared with results from a general Norwegian population survey and further at 6 and 18 months. Simple and multiple linear regression analyses were applied to identify predictors of changes in HRQOL of clinical importance. Two hundred and thirteen participants (50 % women; mean age: 46 years, mean body mass index: 37) were included: 182 returned for 18-month follow-up, of whom 172 completed the HRQOL questionnaire. HRQOL was reduced with clinical significance compared with general Norwegians. The mean changes in HRQOL from the baseline to the follow-up were not of clinical importance. However, one out of three individuals achieved a moderate or large clinical improvement in HRQOL. The best determinant for improved HRQOL was obtained for a composite, clinically significant lifestyle change, i.e. both a weight reduction of at least 5 % and an improvement in exercise capacity of at least 10 %, which was associated with an improvement in five out of the eight SF-36 domains. Subjects at risk of type 2 diabetes report a clinically important reduction in HRQOL compared with general Norwegians. The best predictor of improved HRQOL was a small weight loss combined with a small improvement in aerobic capacity.

  2. Sole Dependence on Urine Testing Strips and the Ability to Identify Clinically Significant Disease: Challenging the Current Paradigm for Heme Detection in General Clinical Situations.

    PubMed

    Rothschild, Bruce

    2016-05-01

    The ability of health care professionals to provide patient care is potentially compromised when predicated on untested, although longstanding, perspectives. One such example is urinalysis testing, which has been currently simplified to use only urine testing strips for detection of microscopic hematuria. To determine whether urine testing strips are sufficient for identification of clinically significant findings in urinalysis. To determine the presence of microscopic hematuria, I examined a collection of urine specimens that had tested heme negative during the 3-month study period. Of the 342 patients from whom urine specimens were examined during this interval, 50 had microscopic hematuria, despite having tested negative for heme via urine testing strip. Also, 30% were not receiving any medication known to produce microscopic hematuria, and 18% had clinically significant pathology. Diagnosis of significant clinical pathologic manifestations would have been compromised had microscopic examination not been performed on the urine specimens from the cohort individuals. Examination of the novel approach of including microscopic examination of specimens in a specific clinical situation challenges the dominant paradigm of reliance on assaying using urine testing strips only, revealing that the current method is not only unreliable for determining microscopic hematuria but also is less than optimal in general clinical practice. The findings of this study provide evidence of the importance of microscopic evaluation as a routine component of urinalysis. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. Histologic prognosticators in feline osteosarcoma: a comparison with phenotypically similar canine osteosarcoma.

    PubMed

    Dimopoulou, Maria; Kirpensteijn, Jolle; Moens, Hester; Kik, Marja

    2008-07-01

    To investigate the histologic characteristics of feline osteosarcoma (OS) and compare the histologic data with phenotypically comparable canine OS. The effects of histologic and clinical variables on survival statistics were evaluated. Retrospective study. Cats (n=62) and dogs (22). Medical records of 62 cats with OS were reviewed for clinically relevant data. Clinical outcome was obtained by telephone interview. Histologic characteristics of OS were classified using a standardized grading system. Histologic characteristics in 22 feline skeletal OS were compared with 22 canine skeletal OS of identical location and subtype. Prognostic variables for clinical outcome were determined using multivariate analysis. Feline OS was characterized by moderate to abundant cellular pleomorphism, low mitotic index, small to moderate amounts of matrix, high cellularity, and a moderate amount of necrosis. There was no significant difference between histologic variables in feline and canine OS. Histologic grade, surgery, and mitotic index significantly influenced clinical outcome as determined by multivariate analysis. Tumor invasion into vessels was not identified as a significant prognosticator. Feline and canine skeletal OS have similar histologic but different prognostic characteristics. Prognosis for cats with OS is related to histologic grade and mitotic index of the tumor.

  4. Undergraduate nursing students' perceptions of the effectiveness of clinical teaching behaviours in Malaysia: A cross-sectional, correlational survey.

    PubMed

    Ludin, Salizar Mohamed; Fathullah, Nik Mohamed Nik

    2016-09-01

    Clinical teachers are a critical determinant of the quality of nursing students' clinical learning experiences. Understanding students' perceptions of clinical teachers' behaviours can provide the basis for recommendations that will help improve the quality of clinical education in clinical settings by developing better clinical teachers. To understand clinical teaching behaviours and their influence on students' learning from the perspective of undergraduate nursing students. A cross-sectional, correlational survey. A nursing faculty in Kuantan, Pahang, Malaysia. A sample of 120/154 (78%) students from Year 2-Year 4 were recruited according to set criteria. A self-administered questionnaire was employed to collect demographic data, and students' perceptions of clinical teaching behaviours and their impact on learning using the Nursing Clinical Teaching Effectiveness Inventory (NCTEI). Year 3 and 4 students perceived faculty clinical teaching behaviours positively. There was a significant association between clinical teaching behaviours and their influence on students' clinical learning. Teachers' competence rated as the most significant influential factor, while teachers' personality rated as least influential. Participants were able to identify the attributes of good clinical teachers and which attributes had the most influence on their learning. Overall, they perceived their teachers as providing good clinical teaching resulting in good clinical learning. Novice clinical teachers and nursing students can use this positive association between teaching behaviours and quality of clinical learning as a guide to clinical teaching and learning. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Genome-wide analysis of pain-, nerve- and neurotrophin -related gene expression in the degenerating human annulus

    PubMed Central

    2012-01-01

    Background In spite of its high clinical relevance, the relationship between disc degeneration and low back pain is still not well understood. Recent studies have shown that genome-wide gene expression studies utilizing ontology searches provide an efficient and valuable methodology for identification of clinically relevant genes. Here we use this approach in analysis of pain-, nerve-, and neurotrophin-related gene expression patterns in specimens of human disc tissue. Control, non-herniated clinical, and herniated clinical specimens of human annulus tissue were studied following Institutional Review Board approval. Results Analyses were performed on more generated (Thompson grade IV and V) discs vs. less degenerated discs (grades I-III), on surgically operated discs vs. control discs, and on herniated vs. control discs. Analyses of more degenerated vs. less degenerated discs identified significant upregulation of well-recognized pain-related genes (bradykinin receptor B1, calcitonin gene-related peptide and catechol-0-methyltransferase). Nerve growth factor was significantly upregulated in surgical vs. control and in herniated vs. control discs. All three analyses also found significant changes in numerous proinflammatory cytokine- and chemokine-related genes. Nerve, neurotrophin and pain-ontology searches identified many matrix, signaling and functional genes which have known importance in the disc. Immunohistochemistry was utilized to confirm the presence of calcitonin gene-related peptide, catechol-0-methyltransferase and bradykinin receptor B1 at the protein level in the human annulus. Conclusions Findings point to the utility of microarray analyses in identification of pain-, neurotrophin and nerve-related genes in the disc, and point to the importance of future work exploring functional interactions between nerve and disc cells in vitro and in vivo. Nerve, pain and neurotrophin ontology searches identified numerous changes in proinflammatory cytokines and chemokines which also have significant relevance to disc biology. Since the degenerating human disc is primarily an avascular tissue site into which disc cells have contributed high levels of proinflammatory cytokines, these substances are not cleared from the tissue and remain there over time. We hypothesize that as nerves grow into the human annulus, they encounter a proinflammatory cytokine-rich milieu which may sensitize nociceptors and exacerbate pain production. PMID:22963171

  6. Clinical features, proximate causes, and consequences of active convulsive epilepsy in Africa.

    PubMed

    Kariuki, Symon M; Matuja, William; Akpalu, Albert; Kakooza-Mwesige, Angelina; Chabi, Martin; Wagner, Ryan G; Connor, Myles; Chengo, Eddie; Ngugi, Anthony K; Odhiambo, Rachael; Bottomley, Christian; White, Steven; Sander, Josemir W; Neville, Brian G R; Newton, Charles R J C; Twine, Rhian; Gómez Olivé, F Xavier; Collinson, Mark; Kahn, Kathleen; Tollman, Stephen; Masanja, Honratio; Mathew, Alexander; Pariyo, George; Peterson, Stefan; Ndyomughenyi, Donald; Bauni, Evasius; Kamuyu, Gathoni; Odera, Victor Mung'ala; Mageto, James O; Ae-Ngibise, Ken; Akpalu, Bright; Agbokey, Francis; Adjei, Patrick; Owusu-Agyei, Seth; Kleinschmidt, Immo; Doku, Victor C K; Odermatt, Peter; Nutman, Thomas; Wilkins, Patricia; Noh, John

    2014-01-01

    Epilepsy is common in sub-Saharan Africa (SSA), but the clinical features and consequences are poorly characterized. Most studies are hospital-based, and few studies have compared different ecological sites in SSA. We described active convulsive epilepsy (ACE) identified in cross-sectional community-based surveys in SSA, to understand the proximate causes, features, and consequences. We performed a detailed clinical and neurophysiologic description of ACE cases identified from a community survey of 584,586 people using medical history, neurologic examination, and electroencephalography (EEG) data from five sites in Africa: South Africa; Tanzania; Uganda; Kenya; and Ghana. The cases were examined by clinicians to discover risk factors, clinical features, and consequences of epilepsy. We used logistic regression to determine the epilepsy factors associated with medical comorbidities. Half (51%) of the 2,170 people with ACE were children and 69% of seizures began in childhood. Focal features (EEG, seizure types, and neurologic deficits) were present in 58% of ACE cases, and these varied significantly with site. Status epilepticus occurred in 25% of people with ACE. Only 36% received antiepileptic drugs (phenobarbital was the most common drug [95%]), and the proportion varied significantly with the site. Proximate causes of ACE were adverse perinatal events (11%) for onset of seizures before 18 years; and acute encephalopathy (10%) and head injury prior to seizure onset (3%). Important comorbidities were malnutrition (15%), cognitive impairment (23%), and neurologic deficits (15%). The consequences of ACE were burns (16%), head injuries (postseizure) (1%), lack of education (43%), and being unmarried (67%) or unemployed (57%) in adults, all significantly more common than in those without epilepsy. There were significant differences in the comorbidities across sites. Focal features are common in ACE, suggesting identifiable and preventable causes. Malnutrition and cognitive and neurologic deficits are common in people with ACE and should be integrated into the management of epilepsy in this region. Consequences of epilepsy such as burns, lack of education, poor marriage prospects, and unemployment need to be addressed. Wiley Periodicals, Inc. © 2013 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of the International League Against Epilepsy.

  7. Implementing clinical guidelines for chronic obstructive pulmonary disease: barriers and solutions

    PubMed Central

    Overington, Jeff D.; Huang, Yao C.; Abramson, Michael J.; Brown, Juliet L.; Goddard, John R.; Bowman, Rayleen V.; Fong, Kwun M.

    2014-01-01

    Chronic obstructive pulmonary disease (COPD) is a complex chronic lung disease characterised by progressive fixed airflow limitation and acute exacerbations that frequently require hospitalisation. Evidence-based clinical guidelines for the diagnosis and management of COPD are now widely available. However, the uptake of these COPD guidelines in clinical practice is highly variable, as is the case for many other chronic disease guidelines. Studies have identified many barriers to implementation of COPD and other guidelines, including factors such as lack of familiarity with guidelines amongst clinicians and inadequate implementation programs. Several methods for enhancing adherence to clinical practice guidelines have been evaluated, including distribution methods, professional education sessions, electronic health records (EHR), point of care reminders and computer decision support systems (CDSS). Results of these studies are mixed to date, and the most effective ways to implement clinical practice guidelines remain unclear. Given the significant resources dedicated to evidence-based medicine, effective dissemination and implementation of best practice at the patient level is an important final step in the process of guideline development. Future efforts should focus on identifying optimal methods for translating the evidence into everyday clinical practice to ensure that patients receive the best care. PMID:25478199

  8. Next generation sequencing of extraskeletal myxoid chondrosarcoma.

    PubMed

    Davis, Elizabeth J; Wu, Yi-Mi; Robinson, Dan; Schuetze, Scott M; Baker, Laurence H; Athanikar, Jyoti; Cao, Xuhong; Kunju, Lakshmi P; Chinnaiyan, Arul M; Chugh, Rashmi

    2017-03-28

    Extraskeletal myxoid chondrosarcoma (EMC) is an indolent translocation-associated soft tissue sarcoma with a high propensity for metastases. Using a clinical sequencing approach, we genomically profiled patients with metastatic EMC to elucidate the molecular biology and identify potentially actionable mutations. We also evaluated potential predictive factors of benefit to sunitinib, a multi-targeted tyrosine kinase inhibitor with reported activity in a subset of EMC patients. Between January 31, 2012 and April 15, 2016, six patients with EMC participated in the clinical sequencing research study. High quality DNA and RNA was isolated and matched normal samples underwent comprehensive next generation sequencing (whole or OncoSeq capture exome of tumor and normal, tumor PolyA+ and capture transcriptome). The expression levels of sunitinib targeted-kinases were measured by transcriptome sequencing for KDR, PDGFRA/B, KIT, RET, FLT1, and FLT4. The previously reported EWSR1-NR4A3 translocation was identified in all patient tumors; however, other recurring genomic abnormalities were not detected. RET expression was significantly greater in patients with EMC relative to other types of sarcomas except for liposarcoma (p<0.0002). The folate receptor was overexpressed in two patients. Our study demonstrated that similar to other translocation-associated sarcomas, the mutational profile of metastatic EMC is limited beyond the pathognomonic translocation. The clinical significance of RET expression in EMC should be explored. Additional pre-clinical investigations of EMC may help elucidate molecular mechanisms contributing to EMC tumorigenesis that could be translated to the clinical setting.

  9. The Portsmouth-based glaucoma refinement scheme: a role for virtual clinics in the future?

    PubMed Central

    Trikha, S; Macgregor, C; Jeffery, M; Kirwan, J

    2012-01-01

    Background Glaucoma referrals continue to impart a significant burden on Hospital Eye Services (HES), with a large proportion of these false positives. Aims To evaluate the Portsmouth glaucoma scheme, utilising virtual clinics, digital technology, and community optometrists to streamline glaucoma referrals. Method The stages of the patient trail were mapped and, at each step of the process, 100 consecutive patient decisions were identified. The diagnostic outcomes of 50 consecutive patients referred from the refinement scheme to the HES were identified. Results A total of 76% of ‘glaucoma' referrals were suitable for the refinement scheme. Overall, 94% of disc images were gradeable in the virtual clinic. In all, 11% of patients ‘attending' the virtual clinic were accepted into HES, with 89% being discharged for community follow-up. Of referrals accepted into HES, the positive predictive value (glaucoma/ocular hypertension/suspect) was 0.78 vs 0.37 in the predating ‘unrefined' scheme (95% CI 0.65–0.87). The scheme has released 1400 clinic slots/year for HES, and has produced a £244 200/year cost saving for Portsmouth Hospitals' Trust. Conclusion The refinement scheme is streamlining referrals and increasing the positive predictive rate in the diagnosis of glaucoma, glaucoma suspect or ocular hypertension. This consultant-led practice-based commissioning scheme, if adopted widely, is likely to incur a significant cost saving while maintaining high quality of care within the NHS. PMID:22766539

  10. Factors related to coping strategies during Japanese physical therapy students' clinical practice.

    PubMed

    Higuchi, Daisuke; Echigo, Ayumi

    2017-08-01

    [Purpose] This study aimed to identify social skills and support that are related to the coping strategies Janpanese physical therapy students use during their clinical practice. [Subjects and Methods] Third-year students who were finished with their clinical practice participated. Self-administered questionnaires were used, including the daily life skill scale, social support scale, and tri-axial coping scale. Spearman's partial correlation coefficients were calculated between social skills, support of daily living, and coping strategies used during the clinical practice, while controlling for gender. [Results] A total of 56 completed questionnaires (median of age: 21 years; 27 males). Social skills during personal situations-knowledge summarization, self-esteem, and positive thinking-were significantly, positively correlated with planning and affirmative interpreting strategies to approach stressors regarding clinical practice, and negatively related to giving up strategies to avoid stressors. Intimacy, leadership, and empathy (social skills during interpersonal situations) were significantly, positively correlated with the following responses to approach stressors: catharsis, information gathering, and affirmative interpreting. Moreover, emotional/companionship social support was significantly, positively correlated with all avoidant coping strategies. [Conclusion] Japanese physical therapy students who had low personal and interpersonal social skills and excess emotional/companionship support in daily life tend to select avoidance, not approach, coping strategies during clinical practice.

  11. Genetics and risk factors for basal cell carcinoma.

    PubMed

    Madan, V; Hoban, P; Strange, R C; Fryer, A A; Lear, J T

    2006-05-01

    Nonmelanoma skin cancer (NMSC) is the commonest cancer in whites and its incidence is increasing worldwide. The prevalence of this cancer is predicted to equal that of all others combined and it was estimated that there were over 2 million cases diagnosed in the U.S.A. in 2004. Patients exhibit marked differences in clinical phenotype with variations in tumour numbers, rate of tumour accrual, site and histological subtype. Furthermore, patients are at increased risk of other cutaneous and noncutaneous cancers. The factors accounting for this variation are complex and still not completely understood. Clearly, ultraviolet light (UV) exposure is a major influence but its relationship to clinical phenotype is not yet clear. In addition, immunosuppression is a significant risk factor. Our group has identified high-risk groups for the development of further basal cell carcinoma (BCC), namely patients with truncal BCC and those presenting with tumour clusters. This presentation will concentrate on these clinical subgroups as well as immunosuppressed patients. These groups represent significant management challenges and are areas where novel, nonsurgical treatment options may make a significant clinical impact in patient care. The risk factors predisposing to these clinical phenotypes will be discussed, including genetic factors and UV exposure. Potential clinical applications, including predictive indices, will be considered.

  12. Valbenazine for Tardive Dyskinesia.

    PubMed

    Freudenreich, Oliver; Remington, Gary

    Tardive dyskinesia (TD) remains a clinical concern for any patient who receives an antipsychotic. While the overall risk of developing TD is lower with newer antipsychotics compared to older agents, a significant number of patients who require long-term treatment will develop TD. Recently, valbenazine (brand name Ingrezza) became the first drug to be approved by the FDA specifically for the treatment of TD. In this New Drug Review, we summarize the basic pharmacology and clinical trial results for valbenazine. Valbenazine is a modified metabolite of the vesicular monoamine transporter 2 (VMAT-2) inhibitor tetrabenazine, which is approved for the treatment of the hyperkinetic movement disorder, Huntington's disease. In short-term clinical trials, valbenazine at a dose of 80 mg/day improved TD, with an effect size that is clinically significant (d=0.90). The effect size for the 40-mg/day dose was lower (d=0.52). Compared to tetrabenazine, valbenazine has better clinical characteristics (i.e., once-a-day dosing, better short-term side effect profile). However, only long-term experience in routine clinical populations can delineate valbenazine's full benefits, optimal dosing, and risks not identified during short-term registration trials.

  13. Factors influencing the severity of acute viral hepatitis A

    PubMed Central

    Kim, Joo Il; Jung, Young Kul; Kwon, Oh Sang; Kim, Yeon Suk; Ku, Yang Suh; Choi, Duck Joo; Kim, Ju Hyun

    2010-01-01

    Background/Aims Most patients with acute viral hepatitis A have a favorable course, but a few of them suffer from severe forms of hepatitis such as fulminant hepatitis. This study was carried out to identify the factors influencing the severity of acute viral hepatitis A. Methods We retrospectively reviewed the medical records of 713 patients with acute hepatitis A, who were divided into two groups: severe hepatitis A (N=87) and non-severe hepatitis A (N=626). Severe hepatitis was defined as fulminant hepatitis or prolongation of prothrombin time (INR≥1.5). Clinical variables were compared between the two groups. Results The incidence of fulminant hepatitis was 1.4% (10/713) in patients with acute hepatitis A. Thirty-three (4.6%) cases exhibited HBsAg positivity. In multivariate analyses, significant alcohol intake and the presence of HBsAg were significant predictive factors of fulminant hepatitis A, and significant alcohol intake and age were significant predictive factors of severe hepatitis A. HBeAg and HBV-DNA status did not affect the clinical course of hepatitis A in chronic hepatitis B carriers. Conclusions While most patients with acute hepatitis A have an uncomplicated clinical course, our data suggest that a more-severe clinical course is correlated with being older, significant alcohol intake, and chronic hepatitis-B-virus infection. PMID:20924212

  14. 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.

  15. PROGNOSTIC SIGNIFICANCE OF CLINICAL, HISTOPATHOLOGICAL, AND MOLECULAR CHARACTERISTICS OF MEDULLOBLASTOMAS IN THE PROSPECTIVE HIT2000 MULTICENTER CLINICAL TRIAL COHORT

    PubMed Central

    Pietsch, Torsten; Schmidt, Rene; Remke, Marc; Korshunov, Andrey; Hovestadt, Volker; Jones, David TW; Felsberg, Jörg; Kaulich, Kerstin; Goschzik, Tobias; Kool, Marcel; Northcott, Paul A.; von Hoff, Katja; von Bueren, André O.; Friedrich, Carsten; Skladny, Heyko; Fleischhack, Gudrun; Taylor, Michael D.; Cremer, Friedrich; Lichter, Peter; Faldum, Andreas; Reifenberger, Guido; Rutkowski, Stefan; Pfister, Stefan M.

    2014-01-01

    BACKGROUND: This study aimed to prospectively evaluate clinical, histopathological and molecular variables for outcome prediction in medulloblastoma patients. METHODS: Patients from the HIT2000 cooperative clinical trial were prospectively enrolled based on the availability of sufficient tumor material and complete clinical information. This revealed a cohort of 184 patients (median age 7.6 years), which was randomly split at a 2:1 ratio into a training (n = 127), and a validation (n = 57) dataset. All samples were subjected to thorough histopathological investigation, CTNNB1 mutation analysis, quantitative PCR, MLPA and FISH analyses for cytogenetic variables, and methylome analysis. RESULTS: By univariable analysis, clinical factors (M-stage), histopathological variables (large cell component, endothelial proliferation, synaptophysin pattern), and molecular features (chromosome 6q status, MYC amplification, TOP2A copy-number, subgrouping) were found to be prognostic. Molecular consensus subgrouping (WNT, SHH, Group 3, Group 4) was validated as an independent feature to stratify patients into different risk groups. When comparing methods for the identification of WNT-driven medulloblastoma, this study identified CTNNB1 sequencing and methylation profiling to most reliably identify these patients. After removing patients with particularly favorable (CTNNB1 mutation, extensive nodularity) or unfavorable (MYC amplification) markers, a risk score for the remaining “intermediate molecular risk” population dependent on age, M-stage, pattern of synaptophysin expression, and MYCN copy-number status was identified and validated, with speckled synaptophysin expression indicating worse outcome. CONCLUSIONS: Methylation subgrouping and CTNNB1 mutation status represent robust tools for the risk-stratification of medulloblastoma. A simple clinico-pathological risk score for “intermediate molecular risk” patients was identified, which deserves further validation. SECONDARY CATEGORY: Pediatrics.

  16. Hospital-Based Clinical Pharmacy Services to Improve Ambulatory Management of Chronic Obstructive Pulmonary Disease

    PubMed Central

    Smith, Amber Lanae; Palmer, Valerie; Farhat, Nada; Kalus, James S.; Thavarajah, Krishna; DiGiovine, Bruno; MacDonald, Nancy C.

    2016-01-01

    Background: No systematic evaluations of a comprehensive clinical pharmacy process measures currently exist to determine an optimal ambulatory care collaboration model for chronic obstructive pulmonary disease (COPD) patients. Objective: Describe the impact of a pharmacist-provided clinical COPD bundle on the management of COPD in a hospital-based ambulatory care clinic. Methods: This retrospective cohort analysis evaluated patients with COPD managed in an outpatient pulmonary clinic. The primary objective of this study was to assess the completion of 4 metrics known to improve the management of COPD: (1) medication therapy management, (2) quality measures including smoking cessation and vaccines, (3) patient adherence, and (4) patient education. The secondary objective was to evaluate the impact of the clinical COPD bundle on clinical and economic outcomes at 30 and 90 days post–initial visit. Results: A total of 138 patients were included in the study; 70 patients served as controls and 68 patients received the COPD bundle from the clinical pharmacist. No patients from the control group had all 4 metrics completed as documented, compared to 66 of the COPD bundle group (P < .0001). Additionally, a statistically significant difference was found in all 4 metrics when evaluated individually. Clinical pharmacy services reduced the number of phone call consults at 90 days (P = .04) but did not have a statistically significant impact on any additional pre-identified clinical outcomes. Conclusion: A pharmacist-driven clinical COPD bundle was associated with significant increases in the completion and documentation of 4 metrics known to improve the outpatient management of COPD.

  17. Alexithymia in eating disorders: Systematic review and meta-analyses of studies using the Toronto Alexithymia Scale.

    PubMed

    Westwood, Heather; Kerr-Gaffney, Jess; Stahl, Daniel; Tchanturia, Kate

    2017-08-01

    The aim of this review was to synthesise the literature on the use of the Toronto Alexithymia Scale (TAS) in eating disorder populations and Healthy Controls (HCs) and to compare TAS scores in these groups. Electronic databases were searched systematically for studies using the TAS and meta-analyses were performed to statistically compare scores on the TAS between individuals with eating disorders and HCs. Forty-eight studies using the TAS with both a clinical eating disorder group and HCs were identified. Of these, 44 were included in the meta-analyses, separated into: Anorexia Nervosa; Anorexia Nervosa, Restricting subtype; Anorexia Nervosa, Binge-Purge subtype, Bulimia Nervosa and Binge Eating Disorder. For all groups, there were significant differences with medium or large effect sizes between the clinical group and HCs, with the clinical group scoring significantly higher on the TAS, indicating greater difficulty with identifying and labelling emotions. Across the spectrum of eating disorders, individuals report having difficulties recognising or describing their emotions. Given the self-report design of the TAS, research to develop and evaluate treatments and clinician-administered assessments of alexithymia is warranted. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Comparison of Three Commercial Systems for Identification of Yeasts Commonly Isolated in the Clinical Microbiology Laboratory

    PubMed Central

    Wadlin, Jill K.; Hanko, Gayle; Stewart, Rebecca; Pape, John; Nachamkin, Irving

    1999-01-01

    We evaluated three commercial systems (RapID Yeast Plus System; Innovative Diagnostic Systems, Norcross, Ga.; API 20C Aux; bioMerieux-Vitek, Hazelwood, Mo.; and Vitek Yeast Biochemical Card, bioMerieux-Vitek) against an auxinographic and microscopic morphologic reference method for the ability to identify yeasts commonly isolated in our clinical microbiology laboratory. Two-hundred one yeast isolates were compared in the study. The RapID Yeast Plus System was significantly better than either API 20C Aux (193 versus 167 correct identifications; P < 0.0001) or the Vitek Yeast Biochemical Card (193 versus 173 correct identifications; P = 0.003) for obtaining correct identifications to the species level without additional testing. There was no significant difference between results obtained with API 20C Aux and the Vitek Yeast Biochemical Card system (P = 0.39). The API 20C Aux system did not correctly identify any of the Candida krusei isolates (n = 23) without supplemental testing and accounted for the major differences between the API 20C Aux and RapID Yeast Plus systems. Overall, the RapID Yeast Plus System was easy to use and is a good system for the routine identification of clinically relevant yeasts. PMID:10325356

  19. Phase 4 Studies in Heart Failure - What is Done and What is Needed?

    PubMed

    Iyngkaran, Pupalan; Liew, Danny; McDonald, Peter; Thomas, Merlin C; Reid, Christopher; Chew, Derek; Hare, David L

    Congestive heart failure (CHF) therapeutics is generated through a well-described evidence generating process. Phases 1 - 3 of this process are required prior to approval and widespread clinical use. Phase 3 in almost all cases is a methodologically sound randomized controlled trial (RCT). After this phase it is generally accepted that the treatment has a significant, independent and prognostically beneficial effect on the pathophysiological process. A major criticism of RCTs is the population to whom the result is applicable. When this population is significantly different from the trial cohort the external validity comes into question. Should the continuation of the evidence generating process continue these problems might be identified. Post marketing surveillance through phase 4 and comparative effectiveness studies through phase 5 trials are often underperformed in comparison to the RCT. These processes can help identify remote adverse events and define new hypotheses for community level benefits. This review is aimed at exploring the post-marketing scene for CHF therapeutics from an Australian health system perspective. We explore the phases of clinical trials, the level of evidence currently available and options for ensuring greater accountability for community level CHF clinical outcomes.

  20. Phase 4 Studies in Heart Failure - What is Done and What is Needed?

    PubMed Central

    Iyngkaran, Pupalan; Liew, Danny; McDonald, Peter; Thomas, Merlin C.; Reid, Christopher; Chew, Derek; Hare, David L.

    2016-01-01

    Congestive heart failure (CHF) therapeutics is generated through a well-described evidence generating process. Phases 1 – 3 of this process are required prior to approval and widespread clinical use. Phase 3 in almost all cases is a methodologically sound randomized controlled trial (RCT). After this phase it is generally accepted that the treatment has a significant, independent and prognostically beneficial effect on the pathophysiological process. A major criticism of RCTs is the population to whom the result is applicable. When this population is significantly different from the trial cohort the external validity comes into question. Should the continuation of the evidence generating process continue these problems might be identified. Post marketing surveillance through phase 4 and comparative effectiveness studies through phase 5 trials are often underperformed in comparison to the RCT. These processes can help identify remote adverse events and define new hypotheses for community level benefits. This review is aimed at exploring the post-marketing scene for CHF therapeutics from an Australian health system perspective. We explore the phases of clinical trials, the level of evidence currently available and options for ensuring greater accountability for community level CHF clinical outcomes. PMID:27280303

  1. New approaches for identifying and testing potential new anti-asthma agents.

    PubMed

    Licari, Amelia; Castagnoli, Riccardo; Brambilla, Ilaria; Marseglia, Alessia; Tosca, Maria Angela; Marseglia, Gian Luigi; Ciprandi, Giorgio

    2018-01-01

    Asthma is a chronic disease with significant heterogeneity in clinical features, disease severity, pattern of underlying disease mechanisms, and responsiveness to specific treatments. While the majority of asthmatic patients are controlled by standard pharmacological strategies, a significant subgroup has limited therapeutic options representing a major unmet need. Ongoing asthma research aims to better characterize distinct clinical phenotypes, molecular endotypes, associated reliable biomarkers, and also to develop a series of new effective targeted treatment modalities. Areas covered: The expanding knowledge on the pathogenetic mechanisms of asthma has allowed researchers to investigate a range of new treatment options matched to patient profiles. The aim of this review is to provide a comprehensive and updated overview of the currently available, new and developing approaches for identifying and testing potential treatment options for asthma management. Expert opinion: Future therapeutic strategies for asthma require the identification of reliable biomarkers that can help with diagnosis and endotyping, in order to determine the most effective drug for the right patient phenotype. Furthermore, in addition to the identification of clinical and inflammatory phenotypes, it is expected that a better understanding of the mechanisms of airway remodeling will likely optimize asthma targeted treatment.

  2. Systematic review: factors contributing to burnout in dentistry.

    PubMed

    Singh, P; Aulak, D S; Mangat, S S; Aulak, M S

    2016-01-01

    Dentists and dental students have been reported to be at high risk of burnout and risk factors have been identified. Despite research into burnout in dentists, only a few papers have identified significantly associated factors. To identify the most significant factors associated with burnout in dentists and dental students in published literature. We systematically searched MEDLINE, EMBASE and HMIC electronic databases to source literature on the factors associated with burnout in dentists. We critically appraised and themed papers using the Critical Appraisal Skills Programme to find the most significant factors. From 115 studies identified by the search string, we deemed 33 papers to be relevant for review. The most prevalent and significant factors associated with burnout were: younger age, male gender, student status, high job-strain/working hours, those enrolled in clinical degree programmes and certain personality types. However, only a limited amount of literature explored the directional relationship between these factors and burnout. This review identified several significant factors contributing to burnout in dentists and dental students. Further longitudinal and prospective studies are required to assess causation. Burnout should be considered a multifactorial phenomenon that can develop early in a dental career. Screening programmes and coping strategies might help to identify and prevent it. © The Author 2015. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. Systemic Lupus Erythematosus with and without Anti-dsDNA Antibodies: Analysis from a Large Monocentric Cohort.

    PubMed

    Conti, Fabrizio; Ceccarelli, Fulvia; Perricone, Carlo; Massaro, Laura; Marocchi, Elisa; Miranda, Francesca; Spinelli, Francesca Romana; Truglia, Simona; Alessandri, Cristiano; Valesini, Guido

    2015-01-01

    The anti-dsDNA antibodies are a marker for Systemic Lupus Erythematosus (SLE) and 70-98% of patients test positive. We evaluated the demographic, clinical, laboratory, and therapeutical features of a monocentric SLE cohort according to the anti-dsDNA status. We identified three groups: anti-dsDNA + (persistent positivity); anti-dsDNA ± (initial positivity and subsequent negativity during disease course); anti-dsDNA - (persistent negativity). Disease activity was assessed by the European Consensus Lupus Activity Measurement (ECLAM). We evaluated 393 patients (anti-dsDNA +: 62.3%; anti-dsDNA ±: 13.3%; anti-dsDNA -: 24.4%). The renal involvement was significantly more frequent in anti-dsDNA + (30.2%), compared with anti-dsDNA ± and anti-dsDNA - (21.1% and 18.7%, resp.; P = 0.001). Serositis resulted significantly more frequent in anti-dsDNA - (82.3%) compared to anti-dsDNA + and anti-dsDNA ± (20.8% and 13.4%, resp.; P < 0.0001). The reduction of C4 serum levels was identified significantly more frequently in anti-dsDNA + and anti-dsDNA ± (40.0% and 44.2%, resp.) compared with anti-dsDNA - (21.8%, P = 0.005). We did not identify significant differences in the mean ECLAM values before and after modification of anti-dsDNA status (P = 0.7). Anti-dsDNA status influences the clinical and immunological features of SLE patients. Nonetheless, it does not appear to affect disease activity.

  4. Does strabismus surgery improve quality and mood, and what factors influence this?

    PubMed

    McBain, H B; MacKenzie, K A; Hancox, J; Ezra, D G; Adams, G G W; Newman, S P

    2016-05-01

    AimsTo establish the impact of adult strabismus surgery on clinical and psychosocial well-being and determine who experiences the greatest benefit from surgery and how one could intervene to improve quality of life post-surgery.MethodsA longitudinal study, with measurements taken pre-surgery and at 3 and 6 months post-surgery. All participants completed the AS-20 a disease specific quality of life scale, along with measures of mood, strabismus and appearance-related beliefs and cognitions and perceived social support. Participants also underwent a full orthoptic assessment at their preoperative visit and again 3 months postoperatively. Clinical outcomes of surgery were classified as success, partial success or failure, using the largest angle of deviation, diplopia and requirement for further therapy.Results210 participants took part in the study. Strabismus surgery led to statistically significant improvements in psychosocial and functional quality of life. Those whose surgery was deemed a partial success did however experience a deterioration in quality of life. A combination of clinical variables, high expectations, and negative beliefs about the illness and appearance pre-surgery were significant predictors of change in quality of life from pre- to post-surgery.ConclusionsStrabismus surgery leads to significant improvements in quality of life up to 6 months postoperatively. There are however a group of patients who do not experience these benefits. A series of clinical and psychosocial factors have now been identified, which will enable clinicians to identify patients who may be vulnerable to poorer outcomes post-surgery and allow for the development of interventions to improve quality of life after surgery.

  5. Clinical scoring system to detect malignant and premalignant vulval lesions.

    PubMed

    Tyagi, Shakun; Tripathi, Reva; Batra, Swaraj

    2014-02-01

    To construct a simple clinical scoring system for evaluation of vulval lesions that will be helpful in clinically detecting the premalignant or malignant lesions of vulva. Seventy women referred for vulval examination at a tertiary care centre in north India were examined over a period of 2 years. Biopsy was performed in 66 consenting women. Association of high-grade vulval lesion with various clinical parameters such as age, duration of symptoms, presenting complaints, the presence of depigmentation, ulceration, hyperkeratosis, acetowhite changes on acetic acid application, asymmetrical distribution of the lesion, surface elevation on naked eye or colposcopy, induration on palpation and toluidine blue stain retention was studied. The significantly associated factors were assigned a value of 0 or 1 depending on whether they were present or absent. Score was then formulated for detection of high-grade lesion defined as moderate to severe dysplasia and early malignancy. Histopathology. Out of the various parameters that were studied, duration of symptoms more than 6 months, hyperkeratosis, asymmetrical distribution of the lesion, surface elevation on naked eye or colposcopy, induration on palpation and positive toluidine blue stain retention of the lesion were found to be significantly associated with a malignant or premalignant lesion. It was found that a score of equal to or greater than 3/6 was significantly associated with a malignant or premalignant lesion. This simple scoring system has a potential to identify the high-grade lesions and can be used to identify the vulval lesion requiring a biopsy or further referral to higher centre.

  6. Estimation of the cure rate in Iranian breast cancer patients.

    PubMed

    Rahimzadeh, Mitra; Baghestani, Ahmad Reza; Gohari, Mahmood Reza; Pourhoseingholi, Mohamad Amin

    2014-01-01

    Although the Cox's proportional hazard model is the popular approach for survival analysis to investigate significant risk factors of cancer patient survival, it is not appropriate in the case of log-term disease free survival. Recently, cure rate models have been introduced to distinguish between clinical determinants of cure and variables associated with the time to event of interest. The aim of this study was to use a cure rate model to determine the clinical associated factors for cure rates of patients with breast cancer (BC). This prospective cohort study covered 305 patients with BC, admitted at Shahid Faiazbakhsh Hospital, Tehran, during 2006 to 2008 and followed until April 2012. Cases of patient death were confirmed by telephone contact. For data analysis, a non-mixed cure rate model with Poisson distribution and negative binomial distribution were employed. All analyses were carried out using a developed Macro in WinBugs. Deviance information criteria (DIC) were employed to find the best model. The overall 1-year, 3-year and 5-year relative survival rates were 97%, 89% and 74%. Metastasis and stage of BC were the significant factors, but age was significant only in negative binomial model. The DIC also showed that the negative binomial model had a better fit. This study indicated that, metastasis and stage of BC were identified as the clinical criteria for cure rates. There are limited studies on BC survival which employed these cure rate models to identify the clinical factors associated with cure. These models are better than Cox, in the case of long-term survival.

  7. Origins of Portal Hypertension in Nonalcoholic Fatty Liver Disease.

    PubMed

    Baffy, Gyorgy

    2018-03-01

    Nonalcoholic fatty liver disease (NAFLD) advanced to cirrhosis is often complicated by clinically significant portal hypertension, which is primarily caused by increased intrahepatic vascular resistance. Liver fibrosis has been identified as a critical determinant of this process. However, there is evidence that portal venous pressure may begin to rise in the earliest stages of NAFLD when fibrosis is far less advanced or absent. The biological and clinical significance of these early changes in sinusoidal homeostasis remains unclear. Experimental and human observations indicate that sinusoidal space restriction due to hepatocellular lipid accumulation and ballooning may impair sinusoidal flow and generate shear stress, increasingly disrupting sinusoidal microcirculation. Sinusoidal endothelial cells, hepatic stellate cells, and Kupffer cells are key partners of hepatocytes affected by NAFLD in promoting endothelial dysfunction through enhanced contractility, capillarization, adhesion and entrapment of blood cells, extracellular matrix deposition, and neovascularization. These biomechanical and rheological changes are aggravated by a dysfunctional gut-liver axis and splanchnic vasoregulation, culminating in fibrosis and clinically significant portal hypertension. We may speculate that increased portal venous pressure is an essential element of the pathogenesis across the entire spectrum of NAFLD. Improved methods of noninvasive portal venous pressure monitoring will hopefully give new insights into the pathobiology of NAFLD and help efforts to identify patients at increased risk for adverse outcomes. In addition, novel drug candidates targeting reversible components of aberrant sinusoidal circulation may prevent progression in NAFLD.

  8. Real-World Clinical Efficacy and Tolerability of Direct-Acting Antivirals in Hepatitis C Monoinfection Compared to Hepatitis C/HIV Coinfection in a Community Care Setting.

    PubMed

    Vijay, Gayam; Rajib, Hossain Muhammad; Mazin, Khalid; Sandipan, Chakaraborty; Osama, Mukhtar; Sumit, Dahal; Amrendra Kumar, Mandal; Arshpal, Gill; Pavani, Garlapati; Ramakrishnaiah, Sreedevi; Khalid, Mowyad; Jagannath, Sherigar; Mohammed, Mansour; Smruti, Mohanty

    2018-06-22

    Limited data exist comparing the safety and efficacy of direct-acting antivirals (DAAs) in hepatitis C virus (HCV) monoinfected and HCV/human immunodeficiency virus (HIV) coinfected patients in the real-world clinic practice setting. All HCV monoinfected and HCV/HIV coinfected patients treated with DAAs between January 2014 and October 2017 in community clinic settings were retrospectively analyzed. Pretreatment baseline patient characteristics, treatment efficacy, factors affecting sustained virologic response at 12 weeks (SVR 12) after treatment, and adverse reactions were compared between the groups. A total of 327 patients were included in the study, of which 253 were HCV monoinfected, and 74 were HCV/HIV coinfected. There was a statistically significant difference observed in SVR 12 when comparing HCV monoinfection and HCV/HIV coinfection (94% and 84%, respectively, p=0.005). However, there were no significant factors identified as a predictor of a reduced response. The most common adverse effect was fatigue (27%). No significant drug interaction was observed between DAA and antiretroviral therapy. None of the patients discontinued the treatment due to adverse events. In a real-world setting, DAA regimens have lower SVR 12 in HCV/HIV coinfection than in HCV monoinfection. Further studies involving a higher number of HCV/HIV coinfected patients are needed to identify real predictors of a reduced response.

  9. Molecular epidemiology and clinical characteristics of drug-resistant Mycobacterium tuberculosis in a tuberculosis referral hospital in China.

    PubMed

    Wang, Qi; Lau, Susanna K P; Liu, Fei; Zhao, Yanlin; Li, Hong Min; Li, Bing Xi; Hu, Yong Liang; Woo, Patrick C Y; Liu, Cui Hua

    2014-01-01

    Despite the large number of drug-resistant tuberculosis (TB) cases in China, few studies have comprehensively analyzed the drug resistance-associated gene mutations and genotypes in relation to the clinical characteristics of M. tuberculosis (Mtb) isolates. We thus analyzed the phenotypic and genotypic drug resistance profiles of 115 Mtb clinical isolates recovered from a tuberculosis referral hospital in Beijing, China. We also performed genotyping by 28 loci MIRU-VNTR analysis. Socio-demographic and clinical data were retrieved from medical records and analyzed. In total, 78 types of mutations (including 42 previously reported and 36 newly identified ones) were identified in 115 Mtb clinical isolates. There was significant correlation between phenotypic and genotypic drug resistance rates for first-line anti-TB drugs (P<0.001). Genotyping revealed 101 MIRU-VNTR types, with 20 isolates (17.4%) being clustered and 95 isolates (82.6%) having unique genotypes. Higher proportion of re-treatment cases was observed among patients with clustered isolates than those with unique MIRU-VNTR genotypes (75.0% vs. 41.1%). Moreover, clinical epidemiological links were identified among patients infected by Mtb strains belonging to the same clusters, suggesting a potential of transmission among patients. Our study provided information on novel potential drug resistance-associated mutations in Mtb. In addition, the genotyping data from our study suggested that enforcement of the implementation of genotyping in diagnostic routines would provide important information for better monitor and control of TB transmission.

  10. Features of asthma which provide meaningful insights for understanding the disease heterogeneity.

    PubMed

    Deliu, M; Yavuz, T S; Sperrin, M; Belgrave, D; Sahiner, U M; Sackesen, C; Kalayci, O; Custovic, A

    2018-01-01

    Data-driven methods such as hierarchical clustering (HC) and principal component analysis (PCA) have been used to identify asthma subtypes, with inconsistent results. To develop a framework for the discovery of stable and clinically meaningful asthma subtypes. We performed HC in a rich data set from 613 asthmatic children, using 45 clinical variables (Model 1), and after PCA dimensionality reduction (Model 2). Clinical experts then identified a set of asthma features/domains which informed clusters in the two analyses. In Model 3, we reclustered the data using these features to ascertain whether this improved the discovery process. Cluster stability was poor in Models 1 and 2. Clinical experts highlighted four asthma features/domains which differentiated the clusters in two models: age of onset, allergic sensitization, severity, and recent exacerbations. In Model 3 (HC using these four features), cluster stability improved substantially. The cluster assignment changed, providing more clinically interpretable results. In a 5-cluster model, we labelled the clusters as: "Difficult asthma" (n = 132); "Early-onset mild atopic" (n = 210); "Early-onset mild non-atopic: (n = 153); "Late-onset" (n = 105); and "Exacerbation-prone asthma" (n = 13). Multinomial regression demonstrated that lung function was significantly diminished among children with "Difficult asthma"; blood eosinophilia was a significant feature of "Difficult," "Early-onset mild atopic," and "Late-onset asthma." Children with moderate-to-severe asthma were present in each cluster. An integrative approach of blending the data with clinical expert domain knowledge identified four features, which may be informative for ascertaining asthma endotypes. These findings suggest that variables which are key determinants of asthma presence, severity, or control may not be the most informative for determining asthma subtypes. Our results indicate that exacerbation-prone asthma may be a separate asthma endotype and that severe asthma is not a single entity, but an extreme end of the spectrum of several different asthma endotypes. © 2017 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.

  11. Exploring clinical wisdom in nursing education.

    PubMed

    McKie, Andrew; Baguley, Fiona; Guthrie, Caitrian; Jackson, Carol; Kirkpatrick, Pamela; Laing, Adele; O'Brien, Stephen; Taylor, Ruth; Wimpenny, Peter

    2012-03-01

    The recent interest in wisdom in professional health care practice is explored in this article. Key features of wisdom are identified via consideration of certain classical, ancient and modern sources. Common themes are discussed in terms of their contribution to 'clinical wisdom' itself and this is reviewed against the nature of contemporary nursing education. The distinctive features of wisdom (recognition of contextual factors, the place of the person and timeliness) may enable their significance for practice to be promoted in more coherent ways in nursing education. Wisdom as practical knowledge (phronesis) is offered as a complementary perspective within the educational preparation and practice of students of nursing. Certain limitations within contemporary UK nursing education are identified that may inhibit development of clinical wisdom. These are: the modularization of programmes in higher education institutions, the division of pastoral and academic support and the relationship between theory and practice.

  12. Identifying transitions in terminal illness trajectories: a critical factor in hospital-based palliative care.

    PubMed

    Dalgaard, Karen Marie; Thorsell, Georg; Delmar, Charlotte

    2010-02-01

    This article describes the significance of the identification and explicit communication of the different clinical phases in incurable illness trajectories in a hospital setting. The article is part of a qualitative study carried out in a Danish haematology department. The data were obtained through a total of 157 hours of participant observation and informal interviews with patients, families, doctors and nurses and four focus group interviews with doctors and nursing staff. Grounded theory was applied for the data analysis. The findings outline how the unpredictability of certain haematological malignancies and barriers in professional practice tended to postpone identifications of transitions between clinical phases. The study has identified ten barriers including personal, professional, time-related, cultural and organizational-for an open dialogue between staff, patients and families about illness progression. The quality of palliative care was affected as different clinical phases require different treatment and care strategies. Complex intervention is called for.

  13. Clinician-scientists in Canada: barriers to career entry and progress.

    PubMed

    Lander, Bryn; Hanley, Gillian E; Atkinson-Grosjean, Janet

    2010-10-04

    Clinician-scientists play an important role in translating between research and clinical practice. Significant concerns about a decline in their numbers have been raised. Potential barriers for career entry and progress are explored in this study. Case-study research methods were used to identify barriers perceived by clinician-scientists and their research teams in two Canadian laboratories. These perceptions were then compared against statistical analysis of data from Canadian Institutes of Health Research (CIHR) databases on grant and award performance of clinician-scientists and non-clinical PhDs for fiscal years 2000 to 2008. Three main barriers were identified through qualitative analysis: research training, research salaries, and research grants. We then looked for evidence of these barriers in the Canada-wide statistical dataset for our study period. Clinician-scientists had a small but statistically significant higher mean number of degrees (3.3) than non-clinical scientists (3.2), potentially confirming the perception of longer training times. But evidence of the other two barriers was equivocal. For example, while overall growth in salary awards was minimal, awards to clinician-scientists increased by 45% compared to 6.3% for non-clinical PhDs. Similarly, in terms of research funding, awards to clinician-scientists increased by more than 25% compared with 5% for non-clinical PhDs. However, clinician-scientist-led grants funded under CIHR's Clinical thematic area decreased significantly from 61% to 51% (p-value<0.001) suggesting that clinician-scientists may be shifting their attention to other research domains. While clinician-scientists continue to perceive barriers to career entry and progress, quantitative results suggest improvements over the last decade. Clinician-scientists are awarded an increasing proportion of CIHR research grants and salary awards. Given the translational importance of this group, however, it may be prudent to adopt specific policy and funding incentives to ensure the ongoing viability of the career path.

  14. ProDisc-L total disc replacement: a comparison of 1-level versus 2-level arthroplasty patients with a minimum 2-year follow-up.

    PubMed

    Hannibal, Matthew; Thomas, Derek J; Low, Jeffrey; Hsu, Ken Y; Zucherman, James

    2007-10-01

    This is a retrospective analysis of data that was collected prospectively from 2 concurrent FDA IDE lumbar arthroplasty clinical trials performed at a single center. To determine if there is a clinical difference between the 1-level ProDisc patients versus the 2-level ProDisc patients at a minimum of 2 years of follow-up. Marnay's work with ProDisc I prompted the U.S. Clinical Trials of the ProDisc II under the direction of the FDA. Disc replacement surgery in the United States has shown promising results for all types of prostheses up to 6 months. Marnay and colleagues showed that their results at 10 years were still promising, and they saw no significant difference between 1-level and multilevel disc replacements. The findings of Ipsen and colleagues suggest that multilevel arthroplasty cases may be less successful than disc replacement at a single level. Patients were part of the FDA clinical trial for the Prodisc II versus circumferential fusion study at a single institution. We identified 27 patients who received ProDisc at 1 level and 32 who received it at 2 levels with at least a 2-year follow-up, for a total of 59 patients. Unpaired t tests were performed on the mean results of Visual Analog Scale, Oswestry Disability Index, SF-36 Healthy Survey Physical Component Summary, and satisfaction using 10-cm line visual scale scores to determine a clinical difference if any between the 2 populations. While patients receiving ProDisc at 2 levels scored marginally lower in all evaluation indexes, score differences in each category were also found to hold no statistical significance. This study was unable to identify a statistically significant difference in outcome between 1- and 2-level ProDisc arthroplasty patients in a cohort from a single center. The equality of clinical effectiveness between 1- and 2-level ProDisc has yet to be determined.

  15. Clinician-Scientists in Canada: Barriers to Career Entry and Progress

    PubMed Central

    Lander, Bryn; Hanley, Gillian E.; Atkinson-Grosjean, Janet

    2010-01-01

    Background Clinician-scientists play an important role in translating between research and clinical practice. Significant concerns about a decline in their numbers have been raised. Potential barriers for career entry and progress are explored in this study. Methods Case-study research methods were used to identify barriers perceived by clinician-scientists and their research teams in two Canadian laboratories. These perceptions were then compared against statistical analysis of data from Canadian Institutes of Health Research (CIHR) databases on grant and award performance of clinician-scientists and non-clinical PhDs for fiscal years 2000 to 2008. Results Three main barriers were identified through qualitative analysis: research training, research salaries, and research grants. We then looked for evidence of these barriers in the Canada-wide statistical dataset for our study period. Clinician-scientists had a small but statistically significant higher mean number of degrees (3.3) than non-clinical scientists (3.2), potentially confirming the perception of longer training times. But evidence of the other two barriers was equivocal. For example, while overall growth in salary awards was minimal, awards to clinician-scientists increased by 45% compared to 6.3% for non-clinical PhDs. Similarly, in terms of research funding, awards to clinician-scientists increased by more than 25% compared with 5% for non-clinical PhDs. However, clinician-scientist-led grants funded under CIHR's Clinical thematic area decreased significantly from 61% to 51% (p-value<0.001) suggesting that clinician-scientists may be shifting their attention to other research domains. Conclusion While clinician-scientists continue to perceive barriers to career entry and progress, quantitative results suggest improvements over the last decade. Clinician-scientists are awarded an increasing proportion of CIHR research grants and salary awards. Given the translational importance of this group, however, it may be prudent to adopt specific policy and funding incentives to ensure the ongoing viability of the career path. PMID:20957175

  16. The role of massage in sports performance and rehabilitation: current evidence and future direction.

    PubMed

    Brummitt, Jason

    2008-02-01

    Massage is a popular treatment choice of athletes, coaches, and sports physical therapists. Despite its purported benefits and frequent use, evidence demonstrating its efficacy is scarce. To identify current literature relating to sports massage and its role in effecting an athlete's psychological readiness, in enhancing sports performance, in recovery from exercise and competition, and in the treatment of sports related musculoskeletal injuries. Electronic databases were used to identify papers relevant to this review. The following keywords were searched: massage, sports injuries, athletic injuries, physical therapy, rehabilitation, delayed onset muscle soreness, sports psychology, sports performance, sports massage, sports recovery, soft tissue mobilization, deep transverse friction massage, pre-event, and post exercise. RESEARCH STUDIES PERTAINING TO THE FOLLOWING GENERAL CATEGORIES WERE IDENTIFIED AND REVIEWED: pre-event (physiological and psychological variables), sports performance, recovery, and rehabilitation. Despite the fact clinical research has been performed, a poor appreciation exists for the appropriate clinical use of sports massage. Additional studies examining the physiological and psychological effects of sports massage are necessary in order to assist the sports physical therapist in developing and implementing clinically significant evidence based programs or treatments.

  17. Factors associated with suicidal risk among a French cohort of problem gamblers seeking treatment.

    PubMed

    Guillou-Landreat, Morgane; Guilleux, Alice; Sauvaget, Anne; Brisson, Lucille; Leboucher, Juliette; Remaud, Manon; Challet-Bouju, Gaëlle; Grall-Bronnec, Marie

    2016-06-30

    Compared to general population, pathological gamblers are 3.4 times more likely to attempt suicide. Our objective was to identify specific profiles of problem gamblers (PGs) with suicidal risk according to sociodemographic, clinical and gambling characteristics. The PGs cohort, called "EVALJEU" , consists in the inclusion of any new PG seeking treatment in our Department. Patients underwent a semi-structured clinical interview and completed self-report questionnaires. The "suicidal risk module" of the Mini International Psychiatric interview (MINI) allowed to constitute two groups of patients that were compared, according to the presence of a suicidal risk. A logistic regression was performed to identify factors related to suicidal risk in PGs. In our sample (N=194), 40.21% presented a suicidal risk. A history of major depression and anxiety disorders were predictors of suicidal risk as well as the perceived inability to stop gambling. Suicidality is a significant clinical concern in PGs. Therefore, three specific predictors, identified by our study, must be assessed. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  18. Detection of Pseudomonas aeruginosa biomarkers from thermally injured mice in situ using imaging mass spectrometry.

    PubMed

    Hamerly, Timothy; Everett, Jake A; Paris, Nina; Fisher, Steve T; Karunamurthy, Arivarasan; James, Garth A; Rumbaugh, Kendra P; Rhoads, Daniel D; Bothner, Brian

    2017-12-15

    Monitoring patients with burn wounds for infection is standard practice because failure to rapidly and specifically identify a pathogen can result in poor clinical outcomes, including death. Therefore, a method that facilitates detection and identification of pathogens in situ within minutes of biopsy would be a significant benefit to clinicians. Mass spectrometry is rapidly becoming a standard tool in clinical settings, capable of identifying specific pathogens from complex samples. Imaging mass spectrometry (IMS) expands the information content by enabling spatial resolution of biomarkers in tissue samples as in histology, without the need for specific stains/antibodies. Herein, a murine model of thermal injury was used to study infection of burn tissue by Pseudomonas aeruginosa. This is the first use of IMS to detect P. aeruginosa infection in situ from thermally injured tissue. Multiple molecular features could be spatially resolved to infected or uninfected tissue. This demonstrates the potential use of IMS in a clinical setting to aid doctors in identifying both presence and species of pathogens in tissue. Copyright © 2017. Published by Elsevier Inc.

  19. Mass Spectrometry in Clinical Laboratory: Applications in Therapeutic Drug Monitoring and Toxicology.

    PubMed

    Garg, Uttam; Zhang, Yan Victoria

    2016-01-01

    Mass spectrometry (MS) has been used in research and specialized clinical laboratories for decades as a very powerful technology to identify and quantify compounds. In recent years, application of MS in routine clinical laboratories has increased significantly. This is mainly due to the ability of MS to provide very specific identification, high sensitivity, and simultaneous analysis of multiple analytes (>100). The coupling of tandem mass spectrometry with gas chromatography (GC) or liquid chromatography (LC) has enabled the rapid expansion of this technology. While applications of MS are used in many clinical areas, therapeutic drug monitoring, drugs of abuse, and clinical toxicology are still the primary focuses of the field. It is not uncommon to see mass spectrometry being used in routine clinical practices for those applications.

  20. What is different about workers' compensation patients? Socioeconomic predictors of baseline disability status among patients with lumbar radiculopathy.

    PubMed

    Atlas, Steven J; Tosteson, Tor D; Hanscom, Brett; Blood, Emily A; Pransky, Glenn S; Abdu, William A; Andersson, Gunnar B; Weinstein, James N

    2007-08-15

    Combined analysis of 2 prospective clinical studies. To identify socioeconomic characteristics associated with workers' compensation in patients with an intervertebral disc herniation (IDH) or spinal stenosis (SpS). Few studies have compared socioeconomic differences between those receiving or not receiving workers' compensation with the same underlying clinical conditions. Patients were identified from the Spine Patient Outcomes Research Trial (SPORT) and the National Spine Network (NSN) practice-based outcomes study. Patients with IDH and SpS within NSN were identified satisfying SPORT eligibility criteria. Information on disability and work status at baseline evaluation was used to categorize patients into 3 groups: workers' compensation, other disability compensation, or work-eligible controls. Enrollment rates of patients with disability in a clinical efficacy trial (SPORT) and practice-based network (NSN) were compared. Independent socioeconomic predictors of baseline workers' compensation status were identified in multivariate logistic regression models controlling for clinical condition, study cohort, and initial treatment designation. Among 3759 eligible patients (1480 in SPORT and 2279 in NSN), 564 (15%) were receiving workers' compensation, 317 (8%) were receiving other disability compensation, and 2878 (77%) were controls. Patients receiving workers' compensation were less common in SPORT than NSN (9.2% vs. 18.8%, P < 0.001), but patients receiving other disability compensation were similarly represented (8.9% vs. 7.7%, P = 0.19). In univariate analyses, many socioeconomic characteristics significantly differed according to baseline workers' compensation status. In multiple logistic regression analyses, gender, educational level, work characteristics, legal action, and expectations about ability to work without surgery were independently associated with receiving workers' compensation. Clinical trials involving conditions commonly seen in patients with workers' compensation may need special efforts to ensure adequate representation. Socioeconomic characteristics markedly differed between patients receiving and not receiving workers' compensation. Identifying the independent effects of workers' compensation on outcomes will require controlling for these baseline characteristics and other clinical features associated with disability status.

  1. Human Leptospirosis on Reunion Island, Indian Ocean: Are Rodents the (Only) Ones to Blame?

    PubMed Central

    Cordonin, Colette; Le Minter, Gildas; Gomard, Yann; Pagès, Frédéric; Jaffar-Bandjee, Marie-Christine; Tortosa, Pablo; Dellagi, Koussay

    2016-01-01

    Background Although leptospirosis is a zoonosis of major concern on tropical islands, the molecular epidemiology of the disease aiming at linking human cases to specific animal reservoirs has been rarely explored within these peculiar ecosystems. Methodology/Principal Findings Five species of wild small mammals (n = 995) as well as domestic animals (n = 101) were screened for Leptospira infection on Reunion Island; positive samples were subsequently genotyped and compared to Leptospira from clinical cases diagnosed in 2012–2013 (n = 66), using MLST analysis. We identified two pathogenic species in human cases, namely Leptospira interrogans and Leptospira borgpetersenii. Leptospira interrogans was by far dominant both in clinical samples (96.6%) and in infected animal samples (95.8%), with Rattus spp and dogs being its exclusive carriers. The genetic diversity within L. interrogans was apparently limited to two sequence types (STs): ST02, identified among most clinical samples and in all rats with complete MLST, and ST34, identified in six humans, but not in rats. Noteworthy, L. interrogans detected in two stray dogs partially matched with ST02 and ST34. Leptospira borgpetersenii was identified in two clinical samples only (3.4%), as well as in cows and mice; four haplotypes were identified, of which two seemingly identical in clinical and animal samples. Leptospira borgpetersenii haplotypes detected in human cases were clearly distinct from the lineage detected so far in the endemic bat species Mormopterus francoismoutoui, thus excluding a role for this volant mammal in the local human epidemiology of the disease. Conclusions/Significance Our data confirm rats as a major reservoir of Leptospira on Reunion Island, but also pinpoint a possible role of dogs, cows and mice in the local epidemiology of human leptospirosis. This study shows that a comprehensive molecular characterization of pathogenic Leptospira in both clinical and animal samples helps to gaining insight into leptospirosis epidemiology within a specific environmental setting. PMID:27294677

  2. What Is Different About Worker’s Compensation Patients?

    PubMed Central

    Atlas, Steven J.; Tosteson, Tor D.; Hanscom, Brett; Blood, Emily A.; Pransky, Glenn S.; Abdu, William A.; Andersson, Gunnar B.; Weinstein, James N.

    2010-01-01

    Study Design Combined analysis of 2 prospective clinical studies. Objective To identify socioeconomic characteristics associated with workers’ compensation in patients with an intervertebral disc herniation (IDH) or spinal stenosis (SpS). Summary of Background Data Few studies have compared socioeconomic differences between those receiving or not receiving workers’ compensation with the same underlying clinical conditions. Methods Patients were identified from the Spine Patient Outcomes Research Trial (SPORT) and the National Spine Network (NSN) practice-based outcomes study. Patients with IDH and SpS within NSN were identified satisfying SPORT eligibility criteria. Information on disability and work status at baseline evaluation was used to categorize patients into 3 groups: workers’ compensation, other disability compensation, or work-eligible controls. Enrollment rates of patients with disability in a clinical efficacy trial (SPORT) and practice-based network (NSN) were compared. Independent socioeconomic predictors of baseline workers’ compensation status were identified in multivariate logistic regression models controlling for clinical condition, study cohort, and initial treatment designation. Results Among 3759 eligible patients (1480 in SPORT and 2279 in NSN), 564 (15%) were receiving workers’ compensation, 317 (8%) were receiving other disability compensation, and 2878 (77%) were controls. Patients receiving workers’ compensation were less common in SPORT than NSN (9.2% vs. 18.8%, P < 0.001), but patients receiving other disability compensation were similarly represented (8.9% vs. 7.7%, P = 0.19). In univariate analyses, many socioeconomic characteristics significantly differed according to baseline workers’ compensation status. In multiple logistic regression analyses, gender, educational level, work characteristics, legal action, and expectations about ability to work without surgery were independently associated with receiving workers’ compensation. Conclusion Clinical trials involving conditions commonly seen in patients with workers’ compensation may need special efforts to ensure adequate representation. Socioeconomic characteristics markedly differed between patients receiving and not receiving workers’ compensation. Identifying the independent effects of workers’ compensation on outcomes will require controlling for these baseline characteristics and other clinical features associated with disability status. PMID:17700451

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

    PubMed

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

    2013-09-01

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

  4. Comparison of methodologies for calculating quality measures based on administrative data versus clinical data from an electronic health record system: implications for performance measures.

    PubMed

    Tang, Paul C; Ralston, Mary; Arrigotti, Michelle Fernandez; Qureshi, Lubna; Graham, Justin

    2007-01-01

    New reimbursement policies and pay-for-performance programs to reward providers for producing better outcomes are proliferating. Although electronic health record (EHR) systems could provide essential clinical data upon which to base quality measures, most metrics in use were derived from administrative claims data. We compared commonly used quality measures calculated from administrative data to those derived from clinical data in an EHR based on a random sample of 125 charts of Medicare patients with diabetes. Using standard definitions based on administrative data (which require two visits with an encounter diagnosis of diabetes during the measurement period), only 75% of diabetics determined by manually reviewing the EHR (the gold standard) were identified. In contrast, 97% of diabetics were identified using coded information in the EHR. The discrepancies in identified patients resulted in statistically significant differences in the quality measures for frequency of HbA1c testing, control of blood pressure, frequency of testing for urine protein, and frequency of eye exams for diabetic patients. New development of standardized quality measures should shift from claims-based measures to clinically based measures that can be derived from coded information in an EHR. Using data from EHRs will also leverage their clinical content without adding burden to the care process.

  5. 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.

  6. Clinical decision support for personalized medicine: an opportunity for pharmacist-physician collaboration.

    PubMed

    Barlow, Jane F

    2012-06-01

    Pharmacogenomics has significant potential to improve the efficacy and safety of medication therapy, but it requires new expertise and adds a new layer of complexity for all healthcare professionals. Pharmacists and pharmacy management systems can play a leading role in providing clinical decision support for the use and interpretation of pharmacogenomic tests. To serve this role effectively, pharmacists will need to expand their expertise in the emerging field of clinical pharmacogenomics. Pharmacy-based clinical programs can expedite the use of pharmacogenomic testing, help physicians interpret the test results and identify future medication risks associated with the patient's phenotype. Over time, some of these functions can be embedded in clinical decision support systems as part of the broader automation of the healthcare system.

  7. Detection and identification of bacteria in clinical samples by 16S rRNA gene sequencing: comparison of two different approaches in clinical practice.

    PubMed

    Jenkins, Claire; Ling, Clare L; Ciesielczuk, Holly L; Lockwood, Julianne; Hopkins, Susan; McHugh, Timothy D; Gillespie, Stephen H; Kibbler, Christopher C

    2012-04-01

    Amplification and sequence analysis of the 16S rRNA gene can be applied to detect and identify bacteria in clinical samples. We examined 75 clinical samples (17 culture-positive, 58 culture-negative) prospectively by two different PCR protocols, amplifying either a single fragment (1343 bp) or two fragments (762/598 bp) of the 16S rRNA gene. The 1343 bp PCR and 762/598 bp PCRs detected and identified the bacterial 16S rRNA gene in 23 (31 %) and 38 (51 %) of the 75 samples, respectively. The 1343 bp PCR identified 19 of 23 (83 %) PCR-positive samples to species level while the 762/598 bp PCR identified 14 of 38 (37 %) bacterial 16S rRNA gene fragments to species level and 24 to the genus level only. Amplification of shorter fragments of the bacterial 16S rRNA gene (762 and 598 bp) resulted in a more sensitive assay; however, analysis of a large fragment (1343 bp) improved species discrimination. Although not statistically significant, the 762/598 bp PCR detected the bacterial 16S rRNA gene in more samples than the 1343 bp PCR, making it more likely to be a more suitable method for the primary detection of the bacterial 16S rRNA gene in the clinical setting. The 1343 bp PCR may be used in combination with the 762/598 bp PCR when identification of the bacterial rRNA gene to species level is required.

  8. Clinical significance of circulating miR-25-3p as a novel diagnostic and prognostic biomarker in osteosarcoma.

    PubMed

    Fujiwara, Tomohiro; Uotani, Koji; Yoshida, Aki; Morita, Takuya; Nezu, Yutaka; Kobayashi, Eisuke; Yoshida, Akihiko; Uehara, Takenori; Omori, Toshinori; Sugiu, Kazuhisa; Komatsubara, Tadashi; Takeda, Ken; Kunisada, Toshiyuki; Kawamura, Machiko; Kawai, Akira; Ochiya, Takahiro; Ozaki, Toshifumi

    2017-05-16

    Emerging evidence has suggested that circulating microRNAs (miRNAs) in body fluids have novel diagnostic and prognostic significance for patients with malignant diseases. The lack of useful biomarkers is a crucial problem of bone and soft tissue sarcomas; therefore, we investigated the circulating miRNA signature and its clinical relevance in osteosarcoma. Global miRNA profiling was performed using patient serum collected from a discovery cohort of osteosarcoma patients and controls and cell culture media. The secretion of the detected miRNAs from osteosarcoma cells and clinical relevance of serum miRNA levels were evaluated using in vitro and in vivo models and a validation patient cohort. Discovery screening identified 236 serum miRNAs that were highly expressed in osteosarcoma patients compared with controls, and eight among these were also identified in the cell culture media. Upregulated expression levels of miR-17-5p and miR-25-3p were identified in osteosarcoma cells, and these were abundantly secreted into the culture media in tumor-derived exosomes. Serum miR-25-3p levels were significantly higher in osteosarcoma patients than in control individuals in the validation cohort, with favorable sensitivity and specificity compared with serum alkaline phosphatase. Furthermore, serum miR-25-3p levels at diagnosis were correlated with patient prognosis and reflected tumor burden in both in vivo models and patients; these associations were more sensitive than those of serum alkaline phosphatase. Serum-based circulating miR-25-3p may serve as a non-invasive blood-based biomarker for tumor monitoring and prognostic prediction in osteosarcoma patients.

  9. Clinical significance of circulating miR-25-3p as a novel diagnostic and prognostic biomarker in osteosarcoma

    PubMed Central

    Fujiwara, Tomohiro; Uotani, Koji; Yoshida, Aki; Morita, Takuya; Nezu, Yutaka; Kobayashi, Eisuke; Yoshida, Akihiko; Uehara, Takenori; Omori, Toshinori; Sugiu, Kazuhisa; Komatsubara, Tadashi; Takeda, Ken; Kunisada, Toshiyuki; Kawamura, Machiko; Kawai, Akira; Ochiya, Takahiro; Ozaki, Toshifumi

    2017-01-01

    Background Emerging evidence has suggested that circulating microRNAs (miRNAs) in body fluids have novel diagnostic and prognostic significance for patients with malignant diseases. The lack of useful biomarkers is a crucial problem of bone and soft tissue sarcomas; therefore, we investigated the circulating miRNA signature and its clinical relevance in osteosarcoma. Methods Global miRNA profiling was performed using patient serum collected from a discovery cohort of osteosarcoma patients and controls and cell culture media. The secretion of the detected miRNAs from osteosarcoma cells and clinical relevance of serum miRNA levels were evaluated using in vitro and in vivo models and a validation patient cohort. Results Discovery screening identified 236 serum miRNAs that were highly expressed in osteosarcoma patients compared with controls, and eight among these were also identified in the cell culture media. Upregulated expression levels of miR-17-5p and miR-25-3p were identified in osteosarcoma cells, and these were abundantly secreted into the culture media in tumor-derived exosomes. Serum miR-25-3p levels were significantly higher in osteosarcoma patients than in control individuals in the validation cohort, with favorable sensitivity and specificity compared with serum alkaline phosphatase. Furthermore, serum miR-25-3p levels at diagnosis were correlated with patient prognosis and reflected tumor burden in both in vivo models and patients; these associations were more sensitive than those of serum alkaline phosphatase. Conclusions Serum-based circulating miR-25-3p may serve as a non-invasive blood-based biomarker for tumor monitoring and prognostic prediction in osteosarcoma patients. PMID:28380419

  10. Predictors of skilled attendance at delivery among antenatal clinic attendants in Ghana: a cross-sectional study of population data.

    PubMed

    Amoakoh-Coleman, Mary; Ansah, Evelyn K; Agyepong, Irene Akua; Grobbee, Diederick E; Kayode, Gbenga A; Klipstein-Grobusch, Kerstin

    2015-05-19

    To identify demographic, maternal and community predictors of skilled attendance at delivery among women who attend antenatal clinic at least once during their pregnancy in Ghana. A cross-sectional study using the 2008 Ghana Demographic and Health Survey (DHS) data. We used frequencies for descriptive analysis, χ(2) test for associations and logistic regression to identify significant predictors. Predictive models were built with estimation of area under the receiver operating characteristic curves (AUC). Ghana. A total of 2041 women who had a live birth in the 5 years preceding the survey, and attended an antenatal clinic having a skilled provider, at least once, during the pregnancy. Skilled attendance at delivery. Overall, 60.5% (1235/2041) of women in our study sample reported skilled attendance at delivery. Significant positive associations existed between skilled attendance at delivery and the variables such as maternal educational level, wealth status class, ever use of contraception, previous pregnancy complications and health insurance coverage (p<0.001). Significant predictors of skilled attendance were wealth status class, residency, previous delivery complication, health insurance coverage and religion in a model with AUC (95% CI) of 0.85 (0.83 to 0.88). Women less likely to have skilled attendance at delivery can be identified during antenatal care by using data on wealth status class, health insurance coverage, residence, history of previous birth complications and religion, and targeted with interventions to improve skilled attendance at delivery. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  11. Management of penile cancer in a Singapore tertiary hospital.

    PubMed

    Tan, Teck Wei; Chia, Sing Joo; Chong, Kian Tai

    2017-06-01

    To present our experience of managing penile squamous cell carcinoma (SCC) in a tertiary hospital in Singapore and to evaluate the prognostic value of the inflammatory markers neutrophil-lymphocyte ratio (NLR) and lymphocyte-monocyte ratio (LMR). We reviewed our prospectively maintained Institutional Review Board-approved urological cancer database to identify men treated for penile SCC at our centre between January 2007 and December 2015. For all the patients identified, we collected epidemiological and clinical data. In all, 39 patients were identified who were treated for penile SCC in our centre. The median [interquartile range (IQR)] follow-up was 34 (16.5-66) months. Although very few (23%) of our patients with high-risk clinical node-negative underwent prophylactic inguinal lymph node dissection (ILND), they still had excellent 5-year recurrence-free survival (RFS; 90%) and cancer-specific survival (CSS; 90%). At multivariate analysis, higher N stage was significantly associated with worse RFS and CSS. Patients with a high NLR (≥2.8) had significantly higher T-stage ( P  = 0.006) and worse CSS ( P  < 0.001) than those with a low NLR. Patients with a low LMR (<3.3) had significantly higher T-stage ( P  = 0.013) and worse RFS ( P  = 0.009) and CSS ( P  < 0.022) than those with a high LMR. Although very few of our patients with intermediate- and high-risk clinical node-negative SCC underwent prophylactic ILND, they still had excellent 5-year RFS and CSS. However, survival was poor in patients with node-positive disease. The pre-treatment NLR and LMR could serve as biomarkers to predict the prognosis of patients with penile cancer.

  12. Genetic neuropathology of obsessive psychiatric syndromes

    PubMed Central

    Jaffe, A E; Deep-Soboslay, A; Tao, R; Hauptman, D T; Kaye, W H; Arango, V; Weinberger, D R; Hyde, T M; Kleinman, J E

    2014-01-01

    Anorexia nervosa (AN), bulimia nervosa (BN) and obsessive-compulsive disorder (OCD) are complex psychiatric disorders with shared obsessive features, thought to arise from the interaction of multiple genes of small effect with environmental factors. Potential candidate genes for AN, BN and OCD have been identified through clinical association and neuroimaging studies; however, recent genome-wide association studies of eating disorders (ED) so far have failed to report significant findings. In addition, few, if any, studies have interrogated postmortem brain tissue for evidence of expression quantitative trait loci (eQTLs) associated with candidate genes, which has particular promise as an approach to elucidating molecular mechanisms of association. We therefore selected single-nucleotide polymorphisms (SNPs) based on candidate gene studies for AN, BN and OCD from the literature, and examined the association of these SNPs with gene expression across the lifespan in prefrontal cortex of a nonpsychiatric control cohort (N=268). Several risk-predisposing SNPs were significantly associated with gene expression among control subjects. We then measured gene expression in the prefrontal cortex of cases previously diagnosed with obsessive psychiatric disorders, for example, ED (N=15) and OCD/obsessive-compulsive personality disorder or tics (OCD/OCPD/Tic; N=16), and nonpsychiatric controls (N=102) and identified 6 and 286 genes that were differentially expressed between ED compared with controls and OCD cases compared with controls, respectively (false discovery rate (FDR) <5%). However, none of the clinical risk SNPs were among the eQTLs and none were significantly associated with gene expression within the broad obsessive cohort, suggesting larger sample sizes or other brain regions may be required to identify candidate molecular mechanisms of clinical association in postmortem brain data sets. PMID:25180571

  13. Genetic neuropathology of obsessive psychiatric syndromes.

    PubMed

    Jaffe, A E; Deep-Soboslay, A; Tao, R; Hauptman, D T; Kaye, W H; Arango, V; Weinberger, D R; Hyde, T M; Kleinman, J E

    2014-09-02

    Anorexia nervosa (AN), bulimia nervosa (BN) and obsessive-compulsive disorder (OCD) are complex psychiatric disorders with shared obsessive features, thought to arise from the interaction of multiple genes of small effect with environmental factors. Potential candidate genes for AN, BN and OCD have been identified through clinical association and neuroimaging studies; however, recent genome-wide association studies of eating disorders (ED) so far have failed to report significant findings. In addition, few, if any, studies have interrogated postmortem brain tissue for evidence of expression quantitative trait loci (eQTLs) associated with candidate genes, which has particular promise as an approach to elucidating molecular mechanisms of association. We therefore selected single-nucleotide polymorphisms (SNPs) based on candidate gene studies for AN, BN and OCD from the literature, and examined the association of these SNPs with gene expression across the lifespan in prefrontal cortex of a nonpsychiatric control cohort (N=268). Several risk-predisposing SNPs were significantly associated with gene expression among control subjects. We then measured gene expression in the prefrontal cortex of cases previously diagnosed with obsessive psychiatric disorders, for example, ED (N=15) and OCD/obsessive-compulsive personality disorder or tics (OCD/OCPD/Tic; N=16), and nonpsychiatric controls (N=102) and identified 6 and 286 genes that were differentially expressed between ED compared with controls and OCD cases compared with controls, respectively (false discovery rate (FDR) <5%). However, none of the clinical risk SNPs were among the eQTLs and none were significantly associated with gene expression within the broad obsessive cohort, suggesting larger sample sizes or other brain regions may be required to identify candidate molecular mechanisms of clinical association in postmortem brain data sets.

  14. Invasive endocervical adenocarcinoma: proposal for a new pattern-based classification system with significant clinical implications: a multi-institutional study.

    PubMed

    Diaz De Vivar, Andrea; Roma, Andres A; Park, Kay J; Alvarado-Cabrero, Isabel; Rasty, Golnar; Chanona-Vilchis, Jose G; Mikami, Yoshiki; Hong, Sung R; Arville, Brent; Teramoto, Norihiro; Ali-Fehmi, Rouba; Rutgers, Joanne K L; Tabassum, Farah; Barbuto, Denise; Aguilera-Barrantes, Irene; Shaye-Brown, Alexandra; Daya, Dean; Silva, Elvio G

    2013-11-01

    The management of endocervical adenocarcinoma is largely based on tumor size and depth of invasion (DOI); however, DOI is difficult to measure accurately. The surgical treatment includes resection of regional lymph nodes, even though most lymph nodes are negative and lymphadenectomies can cause significant morbidity. We have investigated alternative parameters to better identify patients at risk of node metastases. Cases of invasive endocervical adenocarcinoma from 12 institutions were reviewed, and clinical/pathologic features assessed: patients' age, tumor size, DOI, differentiation, lymph-vascular invasion, lymph node metastases, recurrences, and stage. Cases were classified according to a new pattern-based system into Pattern A (well-demarcated glands), B (early destructive stromal invasion arising from well-demarcated glands), and C (diffuse destructive invasion). In total, 352 cases (FIGO Stages I-IV) were identified. Patients' age ranged from 20 to 83 years (mean 45), DOI ranged from 0.2 to 27 mm (mean 6.73), and lymph-vascular invasion was present in 141 cases. Forty-nine (13.9%) demonstrated lymph node metastases. Using this new system, 73 patients (20.7%) with Pattern A tumors (all Stage I) were identified. None had lymph node metastases and/or recurrences. Ninety patients (25.6%) had Pattern B tumors, of which 4 (4.4%) had positive nodes; whereas 189 (53.7%) had Pattern C tumors, of which 45 (23.8%) had metastatic nodes. The proposed classification system can spare 20.7% of patients (Pattern A) of unnecessary lymphadenectomy. Patients with Pattern B rarely present with positive nodes. An aggressive approach is justified in patients with Pattern C. This classification system is simple, easy to apply, and clinically significant.

  15. Adenovirus Respiratory Tract Infections in Peru

    PubMed Central

    Ampuero, Julia S.; Ocaña, Víctor; Gómez, Jorge; Gamero, María E.; Garcia, Josefina; Halsey, Eric S.; Laguna-Torres, V. Alberto

    2012-01-01

    Background Currently, there is a paucity of data regarding human adenovirus (HAdv) circulation in Andean regions of South America. To address this shortcoming, we report the clinical, phylogenetic, and epidemiologic characteristics of HAdv respiratory tract infection from a large sentinel surveillance study conducted among adults and children in Peru. Methods/Principal Findings Oropharyngeal swabs were collected from participants visiting any of 38 participating health centers, and viral pathogens were identified by immunofluorescence assay in cell culture. In addition, molecular characterization was performed on 226 randomly selected HAdv samples. Between 2000 and 2010, a total of 26,375 participants with influenza-like illness (ILI) or severe acute respiratory infection (SARI) were enrolled in the study. HAdv infection was identified in 2.5% of cases and represented 6.2% of all viral pathogens. Co-infection with a heterologous virus was found in 15.5% of HAdv cases. HAdv infection was largely confined to children under the age of 15, representing 88.6% of HAdv cases identified. No clinical characteristics were found to significantly distinguish HAdv infection from other respiratory viruses. Geographically, HAdv infections were more common in sites from the arid coastal regions than in the jungle or highland regions. Co-circulation of subgroups B and C was observed each year between 2006 and 2010, but no clear seasonal patterns of transmission were detected. Conclusions/Significance HAdv accounted for a significant fraction of those presenting with ILI and SARI in Peru and tended to affect the younger population disproportionately. Longitudinal studies will help better characterize the clinical course of patients with HAdv in Peru, as well as determine the role of co-infections in the evolution of illness. PMID:23056519

  16. Detecting ‘Wrong Blood in Tube’ Errors: Evaluation of a Bayesian Network Approach

    PubMed Central

    Doctor, Jason N.; Strylewicz, Greg

    2010-01-01

    Objective In an effort to address the problem of laboratory errors, we develop and evaluate a method to detect mismatched specimens from nationally collected blood laboratory data in two experiments. Methods In Experiment 1 and 2 using blood labs from National Health and Nutrition Examination Survey (NHANES) and values derived from the Diabetes Prevention Program (DPP) respectively, a proportion of glucose and HbA1c specimens were randomly mismatched. A Bayesian network that encoded probabilistic relationships among analytes was used to predict mismatches. In Experiment 1 the performance of the network was compared against existing error detection software. In Experiment 2 the network was compared against 11 human experts recruited from the American Academy of Clinical Chemists. Results were compared via area under the receiver-operating characteristics curves (AUCs) and with agreement statistics. Results In Experiment 1 the network was most predictive of mismatches that produced clinically significant discrepancies between true and mismatched scores ((AUC of 0.87 (±0.04) for HbA1c and 0.83 (±0.02) for glucose), performed well in identifying errors among those self-reporting diabetes (N = 329) (AUC = 0.79 (± 0.02)) and performed significantly better than the established approach it was tested against (in all cases p < .0.05). In Experiment 2 it performed better (and in no case worse) than 7 of the 11 human experts. Average percent agreement was 0.79. and Kappa (κ) was 0.59, between experts and the Bayesian network. Conclusions Bayesian network can accurately identify mismatched specimens. The algorithm is best at identifying mismatches that result in a clinically significant magnitude of error. PMID:20566275

  17. Clinical, radiographic, ultrasonographic and computed tomographic features of nonseptic osteitis of the axial border of the proximal sesamoid bones.

    PubMed

    Vanderperren, K; Bergman, H J; Spoormakers, T J P; Pille, F; Duchateau, L; Puchalski, S M; Saunders, J H

    2014-07-01

    Lysis of the axial aspect of equine proximal sesamoid bones (PSBs) is a rare condition reported to have septic or traumatic origins. Limited information exists regarding imaging of nonseptic axial osteitis of a PSB. To report the clinical, radiographic, ultrasonographic, computed tomographic and intra-arterial contrast-enhanced computed tomographic abnormalities in horses with axial nonseptic osteitis of a PSB. Retrospective clinical study. Eighteen horses diagnosed with nonseptic osteitis of the axial border of a PSB between 2007 and 2012 were reviewed retrospectively. Case details, clinical examination, radiographic, ultrasonographic, computed tomographic and intra-arterial/intra-articular contrast-enhanced computed tomographic features were recorded, when available. Radiographic, ultrasonographic and computed tomographic evaluations of the fetlock region had been performed on 18, 15 and 9 horses, respectively. The effect of the degree of lysis on the grade and duration of lameness was determined. All horses had chronic unilateral lameness, 4 with forelimb and 14 with hindlimb signs. On radiographs, lysis was identified in both PSBs in 14 horses, one PSB in 3 horses and in one horse no lysis was identified. The degree of osteolysis was variable. Ultrasonography identified variably sized irregularities of the bone surface and alteration in echogenicity of the palmar/plantar ligament (PL). All horses undergoing computed tomographic examination (n = 9) had biaxial lysis. The lesions were significantly longer and deeper on computed tomographic images compared with radiographic images. Intra-arterial contrast-enhanced computed tomography may reveal moderate to marked contrast enhancement of the PL. There was no significant effect of the degree of lysis on the grade and duration of lameness. Lesions of nonseptic axial osteitis of a PSB can be identified using a combination of radiography and ultrasonography. Computed tomography provides additional information regarding the extent of the pathology. © 2013 EVJ Ltd.

  18. Different pattern of viral infections and clinical outcomes in patient with acute exacerbation of chronic obstructive pulmonary disease and chronic obstructive pulmonary disease with pneumonia.

    PubMed

    Kim, Ho-Cheol; Choi, Sang-Ho; Huh, Jin-Won; Sung, Heungsup; Hong, Sang Bum; Lim, Chae-Man; Koh, Younsuck

    2016-12-01

    Respiratory viruses are well-known causes of acute exacerbation of chronic obstructive pulmonary disease (AE-COPD) and also important pathogens for concomitant pneumonia in COPD (CP-COPD). However, the differences in a viral infection pattern and clinical impacts of respiratory viruses between the two groups have not been well investigated. The clinical and microbiological data from COPD patients admitted with AE-COPD (n = 281) or CP-COPD (n = 284) between January 2010 and December 2012 were reviewed. After excluding 88 patients (40 with AE-COPD and 48 with CP-COPD) who did not undergo a multiplex RT-PCR test for respiratory viruses, the demographic characteristics, identified viruses, and clinical outcomes of the AE-COPD and CP-COPD groups were compared. Respiratory viruses were identified in 41.9% of AE-COPD group and 33.5% of the CP-COPD groups. The most common virus was influenza virus in the AE-COPD group (33.7%) versus human coronavirus (24.1%) in the CP-COPD group. Influenza virus was significantly more common in the AE-ACOPD group than in the CP-COPD group (P < 0.01). In-hospital mortality of AE-COPD and CP-COPD were 1.2% and 12.3%, respectively (P < 0.01). Among CP-COPD patients, in-hospital mortality of patients with only viral infection group, only bacterial infection group, and viral-bacterial co-infection were 2.6%, 25.8%, and 17.5%, respectively (P = 0.01). Respiratory viruses were commonly identified in both AE-COPD and CP-COPD, influenza virus and human coronavirus were the most common viruses identified in AE-COPD and CP-COPD patients, respectively. The mortality rates of only viral infection group was significantly lower than only bacterial infection or viral-bacterial co-infection group in CP-COPD patients. J. Med. Virol. 88:2092-2099, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  19. Beyond using composite measures to analyze the effect of unmet supportive care needs on caregivers' anxiety and depression.

    PubMed

    Lambert, Sylvie D; Hulbert-Williams, Nicholas; Belzile, Eric; Ciampi, Antonio; Girgis, Afaf

    2018-06-01

    Caregiver research has relied on composite measures (eg, count) of unmet supportive care needs to determine relationships with anxiety and depression. Such composite measures assume that all unmet needs have a similar impact on outcomes. The purpose of this study is to identify individual unmet needs most associated with caregivers' anxiety and depression. Two hundred nineteen caregivers completed the 44-item Supportive Care Needs Survey and the Hospital Anxiety and Depression Scale (minimal clinically important difference = 1.5) at 6 to 8 months and 1, 2, 3.5, and 5 years following the patients' cancer diagnosis. The list of needs was reduced using partial least square regression, and those with a variance importance in projection >1 were analyzed using Bayesian model averaging. Across time, 8 items remained in the top 10 based on prevalence and were labelled "core." Three additional ones were labelled "frequent," as they remained in the top 10 from 1 year onwards. Bayesian model averaging identified a maximum of 3 significant unmet needs per time point-all leading to a difference greater than the minimal clinically important difference. For depression, none of the core unmet needs were significant, rather significance was noted for frequent needs and needs that were not prevalent. For anxiety, 3/8 core and 3/3 frequent unmet needs were significant. Those unmet needs that are most prevalent are not necessarily the most significant ones, and findings provide an evidence-based framework to guide the development of caregiver interventions. A broader contribution is proposing a different approach to identify significant unmet needs. Copyright © 2018 John Wiley & Sons, Ltd.

  20. Nurse-led clinics reduce severity of childhood atopic eczema: a review of the literature.

    PubMed

    Moore, E; Williams, A; Manias, E; Varigos, G

    2006-12-01

    The increasing prevalence and impact of atopic eczema in children in Western countries such as Australia substantiate the need to evaluate the current management of this illness. It has been well documented that the most important aspects in the management of atopic eczema are to allow adequate time for education and demonstration of treatments. However, current models of healthcare funding restrict the opportunity for patient education during medical consultation times. The contribution of nursing to patient care through nurse-led clinics has significant potential in the management of many common chronic illnesses, although atopic eczema has received minimal attention by researchers to date. To discuss the current clinical management of atopic eczema, and to identify the evidence surrounding the benefits of nurse-led clinics in managing patients with chronic illnesses. Systematic searches were undertaken using the Cochrane Library, MedLine, PUBMed and CINAHL from 1995 to 2005. Manual searches of references of retrieved articles identified two additional key studies from 1990 and 1993 which were also included in the review. In total, 22 relevant publications were identified. These included both primary research and descriptive studies that covered the medical management of eczema, patient education and improved patient outcomes. The evidence emerging from the literature indicates that the current management of eczema through doctor-led clinics could be improved, with doctors often lacking the time to offer sufficient patient education to manage chronic illnesses effectively. The literature supports the efficacy of nurse-led clinics in the management of chronic illnesses. The benefits of nurse-led clinics include increased patient satisfaction, longer consultations resulting in improved patient education and similar health outcomes when compared with care from a doctor. No studies were identified comparing nurse-led and doctor-led clinics in the management of eczema. The most effective way to manage atopic eczema is to provide adequate time for education and demonstration of treatments, which the literature suggests can be achieved through nurse-led clinics. The literature review supports an investigation researching the outcomes of a nurse-led clinic on reducing the severity of eczema in children.

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

    PubMed

    Burke, Sarah; Barker, Colin; Marshall, Dianne

    2012-01-01

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

  2. Impact of Ischemic Preconditioning on Outcome in Clinical Liver Surgery: A Systematic Review

    PubMed Central

    Chu, Michael J. J.; Vather, Ryash; Hickey, Anthony J. R.; Phillips, Anthony R. J.; Bartlett, Adam S. J. R.

    2015-01-01

    Background. Ischemia-reperfusion injury is a major cause of post-liver-surgery complications. Ischemic preconditioning (IPC) has been demonstrated to protect against ischemia-reperfusion injury. Clinical studies have examined IPC in liver surgery but with conflicting results. This systematic review aimed to evaluate the effects of IPC on outcome in clinical liver surgery. Methods. An electronic search of OVID Medline and Embase databases was performed to identify studies that reported outcomes in patients undergoing liver surgery subjected to IPC. Basic descriptive statistics were used to summarise data from individual clinical studies. Results. 1093 articles were identified, of which 24 met the inclusion criteria. Seven topics were selected and analysed by subgroup. There were 10 studies in cadaveric liver transplantation, 2 in living-related liver transplantation, and 12 in liver resection. IPC decreases hepatocellular damage in liver surgery as determined by transaminases but does not translate to any significant clinical benefit in orthotopic liver transplant or liver resection. Conclusions. Available clinical evidence does not support routine use of IPC in liver surgery as it does not offer any apparent benefit in perioperative outcome. Further clinical studies will need to be carried out to determine the subset of patients that will benefit from IPC. PMID:25756045

  3. Correlates of immune protection: Standardized and automated assays to interrogate correlates of immunity--Phacilitate Vaccine Forum Washington 2011. The Grand Hyatt, Washington, DC January 24–26, 2011.

    PubMed

    Bolton, Wade

    2011-06-01

    The utility of functional cell mediated immune assays in the assessment of immune response or immunogenicity is increasing significantly as we search for surrogates to determine vaccine efficacy or therapeutic response. No definitive reports to date have demonstrated that CMI assays in human clinical trials correlate with clinical outcome, although animal and non human primate studies have reported surrogacy in varying degrees. This report discusses the approaches identified, their advantages and disadvantages, and their justification for inclusion in the clinical trial setting.

  4. Epigenomic study identifies a novel mesenchyme homeobox2-GLI1 transcription axis involved in cancer drug resistance, overall survival and therapy prognosis in lung cancer patients

    PubMed Central

    Armas-López, Leonel; Piña-Sánchez, Patricia; Arrieta, Oscar; de Alba, Enrique Guzman; Ortiz-Quintero, Blanca; Santillán-Doherty, Patricio; Christiani, David C.; Zúñiga, Joaquín; Ávila-Moreno, Federico

    2017-01-01

    Several homeobox-related gene (HOX) transcription factors such as mesenchyme HOX-2 (MEOX2) have previously been associated with cancer drug resistance, malignant progression and/or clinical prognostic responses in lung cancer patients; however, the mechanisms involved in these responses have yet to be elucidated. Here, an epigenomic strategy was implemented to identify novel MEOX2 gene promoter transcription targets and propose a new molecular mechanism underlying lung cancer drug resistance and poor clinical prognosis. Chromatin immunoprecipitation (ChIP) assays derived from non-small cell lung carcinomas (NSCLC) hybridized on gene promoter tiling arrays and bioinformatics analyses were performed, and quantitative, functional and clinical validation were also carried out. We statistically identified a common profile consisting of 78 gene promoter targets, including Hedgehog-GLI1 gene promoter sequences (FDR≤0.1 and FDR≤0.2). The GLI-1 gene promoter region from −2,192 to −109 was occupied by MEOX2, accompanied by transcriptionally active RNA Pol II and was epigenetically linked to the active histones H3K27Ac and H3K4me3; these associations were quantitatively validated. Moreover, siRNA genetic silencing assays identified a MEOX2-GLI1 axis involved in cellular cytotoxic resistance to cisplatinum in a dose-dependent manner, as well as cellular migration and proliferation. Finally, Kaplan-Maier survival analyses identified significant MEOX2-dependent GLI-1 protein expression associated with clinical progression and poorer overall survival using an independent cohort of NSCLC patients undergoing platinum-based oncological therapy with both epidermal growth factor receptor (EGFR)-non-mutated and EGFR-mutated status. In conclusion, this is the first study to investigate epigenome-wide MEOX2-transcription factor occupation identifying a novel overexpressed MEOX2-GLI1 axis and its clinical association with platinum-based cancer drug resistance and EGFR-tyrosine kinase inhibitor (TKI)-based therapy responses in NSCLC patients. PMID:28978016

  5. Factors influencing acute weight change in patients with schizophrenia treated with olanzapine, haloperidol, or risperidone.

    PubMed

    Basson, B R; Kinon, B J; Taylor, C C; Szymanski, K A; Gilmore, J A; Tollefson, G D

    2001-04-01

    Clinical factors predicting weight change in patients with schizophrenia and related disorders during acute treatment with the antipsychotic drugs olanzapine, risperidone, and haloperidol were sought through retrospective analyses. Six-week body-weight data from 2 trials, study 1 comparing olanzapine and haloperidol (N = 1,369) and study 2 olanzapine and risperidone (N = 268), were analyzed. Effects of 8 clinically relevant covariates--therapy, clinical outcome (Brief Psychiatric Rating Scale), baseline body mass index (BBMI), increased appetite, age, gender, race, and dose--on weight were compared. In study 1, olanzapine (vs. haloperidol) therapy, better clinical outcome, lower BBMI, and nonwhite race significantly affected weight gain. Effects of increased appetite and male gender on weight gain were significant for olanzapine but not for haloperidol. In study 2, better clinical outcome, lower BBMI, and younger age significantly affected weight gain. Increased appetite was more frequent during olanzapine treatment than during haloperidol, but not significantly different from risperidone. Significant differences in effect on weight change were found between olanzapine and haloperidol but not between olanzapine and risperidone. No evidence was found that lower antipsychotic drug doses were associated with lower weight gain. This report identifies predictive factors of acute weight change in patients with schizophrenia. Similar factors across antipsychotic drugs in predicting greater weight gain included better clinical outcome, low BBMI, and nonwhite race. Factors differing between conventional (haloperidol) and atypical (olanzapine) agents included increased appetite and gender. Choice of atypical antipsychotic drug (olanzapine vs. risperidone) was of minor importance with regard to influence on acute weight gain.

  6. A Study to Identify Those Variables Which Contribute to the Utilization of Wellness Clinic Services by Active Duty Army Family Members

    DTIC Science & Technology

    1985-07-01

    utilization of organizational assets. The marketing mix model consisting of the four key vari- ables of price, promotion, product, and place, is commonly...minimal marketing efforts may bring significant increases in useage. The author included some specific recommendations for marketing the Wellness Clinic. 12...care This five factor model indicates that the two major approa- ches to analyzing preventive health care consumer decisionmaking, marketing and health

  7. Opportunities for Cancer-relevant Innovative Technologies with Transformative Potential | Office of Cancer Clinical Proteomics Research

    Cancer.gov

    The National Cancer Institute (NCI) is seeking input from the community on identifying priorities with regards to supporting innovative technology development for cancer-relevant research. While the NCI provides support for technology development through a variety of mechanisms, it is important to understand whether or not these are sufficient for catalyzing and supporting the development of tools with significant potential for advancing important fields of cancer research or clinical care.

  8. The effect of grapefruits (Citrus paradisi) on body weight and cardiovascular risk factors: A systematic review and meta-analysis of randomized clinical trials.

    PubMed

    Onakpoya, Igho; O'Sullivan, Jack; Heneghan, Carl; Thompson, Matthew

    2017-02-11

    The aim of this systematic review was to evaluate the evidence for or against the effectiveness of grapefruits (Citrus paradisi) on body weight, blood pressure, and lipid profile. Electronic searches were conducted in MEDLINE, EMBASE, AMED, and the Cochrane Clinical Trials databases to identify relevant human randomized clinical trials (RCTs). Hand searches of bibliographies were also conducted. Only overweight and obese subjects were included. The reporting quality was assessed using the CONSORT checklist, and the strength of the overall body of evidence was rated based on the GRADE criteria. One hundred and fifty four citations were identified and three RCTs with a total of 250 participants were included. The RCTs were of moderate quality. A meta-analysis for change in body weight failed to reveal a significant difference between grapefruits and controls, MD: -0.45 kg (95% CI: -1.06 to 0.16; I 2 = 53%, but analysis revealed a significant decrease in systolic blood pressure, MD: -2.43 mmHg (95% CI: -4.77 to -0.09; I 2 = 0%). Paucity in the number of RCTs, short durations of interventions, and lack of an established minimum effective dose limit the conclusions that can be drawn about the effects of grapefruit on body weight and metabolic parameters. Further clinical trials evaluating the effects of grapefruit are warranted.

  9. Laypersons' sensitivity for melanoma identification is higher with dermoscopy images than clinical photographs.

    PubMed

    Luttrell, M J; McClenahan, P; Hofmann-Wellenhof, R; Fink-Puches, R; Soyer, H P

    2012-11-01

    Most melanomas are first recognized by patients themselves or by their friends and family. To assess the ability of laypersons to identify melanomas using dermoscopy images. This is an image-based study using laptop computers in the community. Seventeen laypersons were given a one-page educational brochure on the AC Rule for melanoma (asymmetry, colour variation). These laypersons and three expert dermoscopists completed two image sets, each containing a series of 100 pigmented skin lesions. Set 1 contained five melanomas, while set 2 contained 20 melanomas. Participants viewed a clinical image followed by a dermoscopy image for each lesion. For each image a score of 0-10 was assigned for asymmetry and colour, and then an overall assessment was made for suspicion of melanoma. Mean estimates have been calculated for sensitivity and specificity. Laypersons achieved a clinical sensitivity of 91·2% and a significantly higher dermoscopy sensitivity of 94·0%, P = 0·013. This improvement was not associated with a significant change in overall specificity, which for the clinical image was 64·2% and with dermoscopy was 62·0%, P = 0·97. These results indicate that laypersons may be able to use dermoscopy to identify more melanomas than naked eye examination alone. Further study into the practice of dermoscopy by laypersons is warranted. © 2012 The Authors. BJD © 2012 British Association of Dermatologists.

  10. An evidence-based guide to clinical instruction in audiology.

    PubMed

    Mormer, Elaine; Palmer, Catherine; Messick, Cheryl; Jorgensen, Lindsey

    2013-05-01

    A significant portion of the AuD curriculum occurs in clinical settings outside the classroom. Expert clinicians, employed within and outside of the university, are called upon to provide this clinical education. Most have had little or no formal training in clinical teaching yet face pedagogical and logistical challenges when simultaneously providing clinical service and teaching. Training to provide optimal methods and approaches to clinical instruction should be based on research evidence; however, there is a paucity of research in this area within the audiology discipline. This article provides a review of literature supplying evidence for important concepts, elements, and approaches to the clinical instruction process. Additionally, we provide readers with some practical tools with which to facilitate application of optimal clinical teaching principles. We conducted a systematic review of literature on clinical education in audiology and across a wide array of health professions. Through the use of content analysis we identified four elements of the clinical teaching process most critical in examining optimal practices. The elements identified as critical to positive clinical learning outcomes include the establishment of mutual expectations and goals; structured content and delivery of feedback; establishment of a positive instructor/student relationship; and questioning strategies that lead to the development of critical thinking skills. Many disciplines outside of audiology demonstrate robust research activity related to understanding and optimizing the clinical education process. The application of a number of evidence-based clinical teaching principles should allow us to improve student outcomes in audiology. Researchers in our field might consider if and how we should develop our own research literature in clinical education. American Academy of Audiology.

  11. Are there associations between sleep bruxism, chronic stress, and sleep quality?

    PubMed

    Ohlmann, Brigitte; Bömicke, Wolfgang; Habibi, Yasamin; Rammelsberg, Peter; Schmitter, Marc

    2018-07-01

    The purpose of this study was to identify associations between definite sleep bruxism, as defined by the American academy of sleep medicine, and chronic stress and sleep quality. Sleep bruxism was determined by use of questionnaires, assessment of clinical symptoms, and recording of electromyographic and electrocardiographic data (recorded by the Bruxoff ® device). The study included 67 participants. Of these, 38 were identified as bruxers and 29 as non-bruxers. The 38 bruxers were further classified as 17 moderate and 21 intense bruxers. Self-reported stress and self-reported sleep quality were determined by use of the validated questionnaires "Trier Inventory for the Assessment of Chronic Stress" (TICS) and the "Pittsburgh Sleep Quality Index" (PSQI). No statistically significant association was found between sleep bruxism and self-reported stress or sleep quality. However, a significant association between specific items of chronic stress and poor sleep quality was identified. The results of this study indicate an association between subjective sleep quality and subjective chronic stress, irrespective of the presence or absence of sleep bruxism. Chronic stress and sleep quality do not seem to be associated with sleep bruxism. (clinical trial no. NCT03039985). Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. Was it easy to use an Asthma Control Test (ACT) in different clinical practice settings in a tertiary hospital in Singapore?

    PubMed

    Prabhakaran, Lathy; Earnest, Arul; Abisheganaden, John; Chee, Jane

    2009-12-01

    The Asthma Control Test (ACT) is a 5-item self-administered tool designed to assess asthma control. It is said to be simple, easy and can be administered quickly by patients in the clinical practice setting. This stated benefit has yet to be demonstrated in our local clinical practice setting. The aim was to identify factors associated with difficulty in the administration of the ACT in different clinical practice settings in a tertiary hospital in Singapore. This is a prospective study performed from April to June 2008. All patients diagnosed with asthma and referred to an asthma nurse from the in-patient and out-patient clinical practice setting in Tan Tock Seng Hospital were enrolled. Four hundred and thirty-four patients were asked to complete the ACT tool. In the univariate model, we found that age, clinical setting and medical history to be significantly associated with the completion of the ACT. The odds of completion decreased by a factor of 0.92 (95% CI, 0.89 to 0.94) for every year's increase in age, and this was statistically significant (P <0.001). Similarly, the odds ratio of completion for those with more than 3 medical conditions by history were 0.59 (95% CI, 0.48 to 0.71) as compared to those with less than 3 medical conditions by history, and this was also significant (P <0.001). In the multivariate model, we only found age to be an independent and significant factor. After adjusting for age, none of the other variables initially significant in the univariate model remained significant. The results show that the ACT was simple and easy to be administered in younger-aged patients.

  13. Delineating advanced practice nursing in New Zealand: a national survey.

    PubMed

    Carryer, J; Wilkinson, J; Towers, A; Gardner, G

    2018-03-01

    A variety of advanced practice nursing roles and titles have proliferated in response to the changing demands of a population characterized by increasing age and chronic illness. Whilst similarly identified as advanced practice roles, they do not share a common practice profile, educational requirements or legislative direction. The lack of clarity limits comparative research that can inform policy and health service planning. To identify advanced practice roles within nursing titles employed in New Zealand and practice differences between advanced practice and other roles. Replicating recent Australian research, 3255 registered nurses/nurse practitioners in New Zealand completed the amended Advanced Practice Delineation survey tool. The mean domain scores of the predominant advanced practice position were compared with those of other positions. Differences between groups were explored using one-way ANOVA and post hoc between group comparisons. Four nursing position bands were identified: nurse practitioner, clinical nurse specialist, domain-specific and registered nurse. Significant differences between the bands were found on many domain scores. The nurse practitioner and clinical nurse specialist bands had the most similar practice profiles, nurse practitioners being more involved in direct care and professional leadership. Similar to the position of clinical nurse consultant in Australia, those practicing as clinical nurse specialists were deemed to reflect the threshold for advanced practice nursing. The results identified different practice patterns for the identified bands and distinguish the advanced practice nursing roles. By replicating the Australian study of Gardener et al. (2016), this NZ paper extends the international data available to support more evidence-based nursing workforce planning and policy development. © 2017 International Council of Nurses.

  14. Molecular Identification of Unusual Pathogenic Yeast Isolates by Large Ribosomal Subunit Gene Sequencing: 2 Years of Experience at the United Kingdom Mycology Reference Laboratory▿

    PubMed Central

    Linton, Christopher J.; Borman, Andrew M.; Cheung, Grace; Holmes, Ann D.; Szekely, Adrien; Palmer, Michael D.; Bridge, Paul D.; Campbell, Colin K.; Johnson, Elizabeth M.

    2007-01-01

    Rapid identification of yeast isolates from clinical samples is particularly important given their innately variable antifungal susceptibility profiles. We present here an analysis of the utility of PCR amplification and sequence analysis of the hypervariable D1/D2 region of the 26S rRNA gene for the identification of yeast species submitted to the United Kingdom Mycology Reference Laboratory over a 2-year period. A total of 3,033 clinical isolates were received from 2004 to 2006 encompassing 50 different yeast species. While more than 90% of the isolates, corresponding to the most common Candida species, could be identified by using the AUXACOLOR2 yeast identification kit, 153 isolates (5%), comprised of 47 species, could not be identified by using this system and were subjected to molecular identification via 26S rRNA gene sequencing. These isolates included some common species that exhibited atypical biochemical and phenotypic profiles and also many rarer yeast species that are infrequently encountered in the clinical setting. All 47 species requiring molecular identification were unambiguously identified on the basis of D1/D2 sequences, and the molecular identities correlated well with the observed biochemical profiles of the various organisms. Together, our data underscore the utility of molecular techniques as a reference adjunct to conventional methods of yeast identification. Further, we show that PCR amplification and sequencing of the D1/D2 region reliably identifies more than 45 species of clinically significant yeasts and can also potentially identify new pathogenic yeast species. PMID:17251397

  15. Lisdexamfetamine dimesylate in adults with attention-deficit/ hyperactivity disorder who report clinically significant impairment in executive function: results from a randomized, double-blind, placebo-controlled study.

    PubMed

    Adler, Lenard A; Dirks, Bryan; Deas, Patrick F; Raychaudhuri, Aparna; Dauphin, Matthew R; Lasser, Robert A; Weisler, Richard H

    2013-07-01

    Behavioral rating scales that assess impairments in executive function commonly associated with attention-deficit/hyperactivity disorder (ADHD) may offer advantages over neuropsychological testing. The primary objective of this study was to evaluate the efficacy of lisdexamfetamine dimesylate for executive function deficits in adults with ADHD and clinically significant executive function impairment using self-reported Behavior Rating Inventory of Executive Function-Adult version (BRIEF-A) assessments. This randomized double-blind study, conducted between May 2010 and November 2010, screened at least 1 participant at 35 of 39 registered US clinical research sites. Adults (aged 18-55 years) with a primary ADHD diagnosis (meeting full DSM-IV-TR criteria) and executive function deficits (assessed by baseline BRIEF-A Global Executive Composite [GEC] T-scores of at least 65) were randomized to treatment with optimized lisdexamfetamine dimesylate (30 mg/d, 50 mg/d, or 70 mg/d; n = 80) or placebo (n = 81) during a 10-week double-blind treatment period. Outcome measures included the BRIEF-A scales (GEC, index, and clinical subscales). At week 10 or at early termination, lisdexamfetamine dimesylate was associated with significantly greater reductions from baseline in mean BRIEF-A GEC T-scores than placebo (effect size, 0.74; P < .0001) and significantly greater reductions from baseline in mean T-scores for both BRIEF-A index scales (Behavioral Regulation Index and Metacognition Index) and all 9 clinical subscales (P ≤ .0056 for all). At week 10 or at early termination, mean T-scores for BRIEF-A indexes and clinical subscales were below levels of clinically significant executive function deficits (ie, < 65) with lisdexamfetamine dimesylate treatment. The mean (SD) GEC T-score was 57.2 (14.11) for the lisdexamfetamine dimesylate group and 68.3 (17.12) for the placebo group. The safety profile of lisdexamfetamine dimesylate was consistent with other long-acting psychostimulants. Among adults with ADHD and clinically significant executive function deficits, lisdexamfetamine dimesylate was associated with significant improvements in self-reported executive function ratings. ClinicalTrials.gov identifier: NCT01101022. © Copyright 2013 Physicians Postgraduate Press, Inc.

  16. Clinically significant drug-drug interactions involving opioid analgesics used for pain treatment in patients with cancer: a systematic review.

    PubMed

    Kotlinska-Lemieszek, Aleksandra; Klepstad, Pål; Haugen, Dagny Faksvåg

    2015-01-01

    Opioids are the most frequently used drugs to treat pain in cancer patients. In some patients, however, opioids can cause adverse effects and drug-drug interactions. No advice concerning the combination of opioids and other drugs is given in the current European guidelines. To identify studies that report clinically significant drug-drug interactions involving opioids used for pain treatment in adult cancer patients. Systematic review with searches in Embase, MEDLINE, and Cochrane Central Register of Controlled Trials from the start of the databases (Embase from 1980) through January 2014. In addition, reference lists of relevant full-text papers were hand-searched. Of 901 retrieved papers, 112 were considered as potentially eligible. After full-text reading, 17 were included in the final analysis, together with 15 papers identified through hand-searching of reference lists. All of the 32 included publications were case reports or case series. Clinical manifestations of drug-drug interactions involving opioids were grouped as follows: 1) sedation and respiratory depression, 2) other central nervous system symptoms, 3) impairment of pain control and/or opioid withdrawal, and 4) other symptoms. The most common mechanisms eliciting drug-drug interactions were alteration of opioid metabolism by inhibiting the activity of cytochrome P450 3A4 and pharmacodynamic interactions due to the combined effect on opioid, dopaminergic, cholinergic, and serotonergic activity in the central nervous system. Evidence for drug-drug interactions associated with opioids used for pain treatment in cancer patients is very limited. Still, the cases identified in this systematic review give some important suggestions for clinical practice. Physicians prescribing opioids should recognize the risk of drug-drug interactions and if possible avoid polypharmacy.

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

    PubMed Central

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

    2016-01-01

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

  18. Classification of instability after reverse shoulder arthroplasty guides surgical management and outcomes.

    PubMed

    Abdelfattah, Adham; Otto, Randall J; Simon, Peter; Christmas, Kaitlyn N; Tanner, Gregory; LaMartina, Joey; Levy, Jonathan C; Cuff, Derek J; Mighell, Mark A; Frankle, Mark A

    2018-04-01

    Revision of unstable reverse shoulder arthroplasty (RSA) remains a significant challenge. The purpose of this study was to determine the reliability of a new treatment-guiding classification for instability after RSA, to describe the clinical outcomes of patients stabilized operatively, and to identify those with higher risk of recurrence. All patients undergoing revision for instability after RSA were identified at our institution. Demographic, clinical, radiographic, and intraoperative data were collected. A classification was developed using all identified causes of instability after RSA and allocating them to 1 of 3 defined treatment-guiding categories. Eight surgeons reviewed all data and applied the classification scheme to each case. Interobserver and intraobserver reliability was used to evaluate the classification scheme. Preoperative clinical outcomes were compared with final follow-up in stabilized shoulders. Forty-three revision cases in 34 patients met the inclusion for study. Five patients remained unstable after revision. Persistent instability most commonly occurred in persistent deltoid dysfunction and postoperative acromial fractures but also in 1 case of soft tissue impingement. Twenty-one patients remained stable at minimum 2 years of follow-up and had significant improvement of clinical outcome scores and range of motion. Reliability of the classification scheme showed substantial and almost perfect interobserver and intraobserver agreement among all the participants (κ = 0.699 and κ = 0.851, respectively). Instability after RSA can be successfully treated with revision surgery using the reliable treatment-guiding classification scheme presented herein. However, more understanding is needed for patients with greater risk of recurrent instability after revision surgery. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

  19. Radiosensitivity Differences Between Liver Metastases Based on Primary Histology Suggest Implications for Clinical Outcomes After Stereotactic Body Radiation Therapy

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

    Ahmed, Kamran A.; Caudell, Jimmy J.; El-Haddad, Ghassan

    Purpose/Objectives: Evidence from the management of oligometastases with stereotactic body radiation therapy (SBRT) reveals differences in outcomes based on primary histology. We have previously identified a multigene expression index for tumor radiosensitivity (RSI) with validation in multiple independent cohorts. In this study, we assessed RSI in liver metastases and assessed our clinical outcomes after SBRT based on primary histology. Methods and Materials: Patients were identified from our prospective, observational protocol. The previously tested RSI 10 gene assay was run on samples and calculated using the published algorithm. An independent cohort of 33 patients with 38 liver metastases treated with SBRTmore » was used for clinical correlation. Results: A total of 372 unique metastatic liver lesions were identified for inclusion from our prospective, institutional metadata pool. The most common primary histologies for liver metastases were colorectal adenocarcinoma (n=314, 84.4%), breast adenocarcinoma (n=12, 3.2%), and pancreas neuroendocrine (n=11, 3%). There were significant differences in RSI of liver metastases based on histology. The median RSIs for liver metastases in descending order of radioresistance were gastrointestinal stromal tumor (0.57), melanoma (0.53), colorectal neuroendocrine (0.46), pancreas neuroendocrine (0.44), colorectal adenocarcinoma (0.43), breast adenocarcinoma (0.35), lung adenocarcinoma (0.31), pancreas adenocarcinoma (0.27), anal squamous cell cancer (0.22), and small intestine neuroendocrine (0.21) (P<.0001). The 12-month and 24-month Kaplan-Meier rates of local control (LC) for colorectal lesions from the independent clinical cohort were 79% and 59%, compared with 100% for noncolorectal lesions (P=.019), respectively. Conclusions: In this analysis, we found significant differences based on primary histology. This study suggests that primary histology may be an important factor to consider in SBRT radiation dose selection.« less

  20. Frequent attenders without organic disease in a gastroenterology clinic. Patient characteristics and health care use.

    PubMed

    Bass, C; Bond, A; Gill, D; Sharpe, M

    1999-01-01

    We used a hospital computer to identify 50 patients (35 women, 15 men) satisfying research criteria for "frequent attenders" at a gastroenterology outpatient clinic (four or more visits to a general hospital clinic in the previous 12 months). Their mean duration of symptoms was 5 years, and 80% reported fatigue as a significant complaint. Thirteen (37%) of the women were also consulting a gynecologist, and in nine of these their status was normal. Seven (21%) of the 35 women who were interviewed had a history of childhood sexual abuse, and these patients reported significantly more lifetime somatic symptoms (9.7, SD = 3.8) than those without such a history (5.4, SD = 3.5, p = < 0.01). The 50 patients reported high levels of disability and psychological distress, and were more likely to rate the probability of their symptoms as being due to "bowel disease" than to "stress" or "other problems." Forty-five patients had at least one current psychiatric diagnosis and 24 at least two, with somatoform disorders being the most common. Nineteen (38%) reported infrequent panic attacks, but only three had somatization disorder. The mean number of lifetime somatic symptoms was 5.9 (SD = 3.6; range 1-14). Seventeen patients (35%) also satisfied criteria for frequent attending in primary care (> 12 visits over the previous 12 months), and the patients reported a mean number of 5.7 (SD = 2.1) specialist appointments in the previous year. There may be a case for using the hospital computer to identify frequent attenders proactively at an earlier stage of their hospital visits so that appropriate management can be instituted. If such patients can be identified in this way, their assessment and management might be more appropriately supervised in designated clinics by more experienced gastroenterology staff.

  1. Major prognostic role of Ki67 in localized adrenocortical carcinoma after complete resection.

    PubMed

    Beuschlein, Felix; Weigel, Jens; Saeger, Wolfgang; Kroiss, Matthias; Wild, Vanessa; Daffara, Fulvia; Libé, Rosella; Ardito, Arianna; Al Ghuzlan, Abir; Quinkler, Marcus; Oßwald, Andrea; Ronchi, Cristina L; de Krijger, Ronald; Feelders, Richard A; Waldmann, Jens; Willenberg, Holger S; Deutschbein, Timo; Stell, Anthony; Reincke, Martin; Papotti, Mauro; Baudin, Eric; Tissier, Frédérique; Haak, Harm R; Loli, Paola; Terzolo, Massimo; Allolio, Bruno; Müller, Hans-Helge; Fassnacht, Martin

    2015-03-01

    Recurrence of adrenocortical carcinoma (ACC) even after complete (R0) resection occurs frequently. The aim of this study was to identify markers with prognostic value for patients in this clinical setting. From the German ACC registry, 319 patients with the European Network for the Study of Adrenal Tumors stage I-III were identified. As an independent validation cohort, 250 patients from three European countries were included. Clinical, histological, and immunohistochemical markers were correlated with recurrence-free (RFS) and overall survival (OS). Although univariable analysis within the German cohort suggested several factors with potential prognostic power, upon multivariable adjustment only a few including age, tumor size, venous tumor thrombus (VTT), and the proliferation marker Ki67 retained significance. Among these, Ki67 provided the single best prognostic value for RFS (hazard ratio [HR] for recurrence, 1.042 per 1% increase; P < .0001) and OS (HR for death, 1.051; P < .0001) which was confirmed in the validation cohort. Accordingly, clinical outcome differed significantly between patients with Ki67 <10%, 10-19%, and ≥20% (for the German cohort: median RFS, 53.2 vs 31.6 vs 9.4 mo; median OS, 180.5 vs 113.5 vs 42.0 mo). Using the combined cohort prognostic scores including tumor size, VTT, and Ki67 were established. Although these scores discriminated slightly better between subgroups, there was no clinically meaningful advantage in comparison with Ki67 alone. This largest study on prognostic markers in localized ACC identified Ki67 as the single most important factor predicting recurrence in patients following R0 resection. Thus, evaluation of Ki67 indices should be introduced as standard grading in all pathology reports of patients with ACC.

  2. Similar Prevalence of Acetabular Labral Tear in Professional Ballet Dancers and Sporting Participants.

    PubMed

    Mayes, Susan; Ferris, April-Rose; Smith, Peter; Garnham, Andrew; Cook, Jill

    2016-07-01

    To compare the prevalence of acetabular labral tear in male and female professional ballet dancers with age-matched and sex-matched sporting participants and to determine the relationship to clinical findings and cartilage defects. Case-control study. Clinical and radiology practices. Forty-nine (98 hips) male and female professional ballet dancers (current and retired) with median age 30 years (range: 19-64 years) and 49 (98 hips) age-matched and sex-matched sporting participants. Group (ballet or sports), sex, age, hip cartilage defects, history of hip pain, Hip and Groin Outcome Score, passive hip internal rotation (IR), and external rotation range of movement (ROM). Labral tear identified with 3T magnetic resonance imaging (MRI). Labral tears were identified in 51% of all 196 hips. The prevalence did not differ significantly between the ballet and sporting participants (P = 0.41) or between sexes (P = 0.34). Labral tear was not significantly associated with clinical measures, such as pain and function scores or rotation ROM (P > 0.01 for all). Pain provocation test using IR at 90° of hip flexion had excellent specificity [96%, 95% confidence intervals (CIs), 0.77%-0.998%] but poor sensitivity (50%, 95% CI, 0.26%-0.74%) for identifying labral tear in participants reporting hip pain. Older age and cartilage defect presence were independently associated with an increased risk of labral tear (both P < 0.001). The prevalence of labral tear in male and female professional ballet dancers was similar to a sporting population. Labral tears were not associated with clinical findings but were related to cartilage defects, independent of aging. Caution is required when interpreting MRI findings as labral tear may not be the source of the ballet dancer's symptoms.

  3. PRImary care Streptococcal Management (PRISM) study: identifying clinical variables associated with Lancefield group A β-haemolytic streptococci and Lancefield non-Group A streptococcal throat infections from two cohorts of patients presenting with an acute sore throat

    PubMed Central

    Little, Paul; Moore, Michael; Hobbs, F D R; Mant, David; McNulty, Cliodna; Williamson, Ian; Cheng, Edith; Stuart, Beth; Kelly, Joanne; Barnett, Jane; Mullee, Mark

    2013-01-01

    Objective To assess the association between features of acute sore throat and the growth of streptococci from culturing a throat swab. Design Diagnostic cohort. Setting UK general practices. Participants Patients aged 5 or over presenting with an acute sore throat. Patients were recruited for a second cohort (cohort 2, n=517) consecutively after the first (cohort 1, n=606) from similar practices. Main outcome Predictors of the presence of Lancefield A/C/G streptococci. Results The clinical score developed from cohort 1 had poor discrimination in cohort 2 (bootstrapped estimate of area under the receiver operator characteristic (ROC) curve (0.65), due to the poor validity of the individual items in the second data set. Variables significant in multivariate analysis in both cohorts were rapid attendance (prior duration 3 days or less; multivariate adjusted OR 1.92 cohort, 1.67 cohort 2); fever in the last 24 h (1.69, 2.40); and doctor assessment of severity (severely inflamed pharynx/tonsils (2.28, 2.29)). The absence of coryza or cough and purulent tonsils were significant in univariate analysis in both cohorts and in multivariate analysis in one cohort. A five-item score based on Fever, Purulence, Attend rapidly (3 days or less), severely Inflamed tonsils and No cough or coryza (FeverPAIN) had moderate predictive value (bootstrapped area under the ROC curve 0.73 cohort 1, 0.71 cohort 2) and identified a substantial number of participants at low risk of streptococcal infection (38% in cohort 1, 36% in cohort 2 scored ≤1, associated with a streptococcal percentage of 13% and 18%, respectively). A Centor score of ≤1 identified 23% and 26% of participants with streptococcal percentages of 10% and 28%, respectively. Conclusions Items widely used to help identify streptococcal sore throat may not be the most consistent. A modified clinical scoring system (FeverPAIN) which requires further validation may be clinically helpful in identifying individuals who are unlikely to have major pathogenic streptococci. PMID:24163209

  4. PRImary care Streptococcal Management (PRISM) study: identifying clinical variables associated with Lancefield group A β-haemolytic streptococci and Lancefield non-Group A streptococcal throat infections from two cohorts of patients presenting with an acute sore throat.

    PubMed

    Little, Paul; Moore, Michael; Hobbs, F D R; Mant, David; McNulty, Cliodna; Williamson, Ian; Cheng, Edith; Stuart, Beth; Kelly, Joanne; Barnett, Jane; Mullee, Mark

    2013-10-25

    To assess the association between features of acute sore throat and the growth of streptococci from culturing a throat swab. Diagnostic cohort. UK general practices. Patients aged 5 or over presenting with an acute sore throat. Patients were recruited for a second cohort (cohort 2, n=517) consecutively after the first (cohort 1, n=606) from similar practices. Predictors of the presence of Lancefield A/C/G streptococci. The clinical score developed from cohort 1 had poor discrimination in cohort 2 (bootstrapped estimate of area under the receiver operator characteristic (ROC) curve (0.65), due to the poor validity of the individual items in the second data set. Variables significant in multivariate analysis in both cohorts were rapid attendance (prior duration 3 days or less; multivariate adjusted OR 1.92 cohort, 1.67 cohort 2); fever in the last 24 h (1.69, 2.40); and doctor assessment of severity (severely inflamed pharynx/tonsils (2.28, 2.29)). The absence of coryza or cough and purulent tonsils were significant in univariate analysis in both cohorts and in multivariate analysis in one cohort. A five-item score based on Fever, Purulence, Attend rapidly (3 days or less), severely Inflamed tonsils and No cough or coryza (FeverPAIN) had moderate predictive value (bootstrapped area under the ROC curve 0.73 cohort 1, 0.71 cohort 2) and identified a substantial number of participants at low risk of streptococcal infection (38% in cohort 1, 36% in cohort 2 scored ≤1, associated with a streptococcal percentage of 13% and 18%, respectively). A Centor score of ≤1 identified 23% and 26% of participants with streptococcal percentages of 10% and 28%, respectively. Items widely used to help identify streptococcal sore throat may not be the most consistent. A modified clinical scoring system (FeverPAIN) which requires further validation may be clinically helpful in identifying individuals who are unlikely to have major pathogenic streptococci.

  5. Outcomes of febrile children presumed to be immunocompetent who present with leukopenia or neutropenia to an ambulatory setting.

    PubMed

    Serwint, J R; Dias, M M; Chang, H; Sharkey, M; Walker, A R

    2005-09-01

    To determine significant medical outcomes in febrile children presenting to an ambulatory setting with neutropenia and/or leukopenia. Retrospective medical record review conducted on febrile patients who had a blood culture drawn, with white blood cell counts less than 5,000/mm3 and/or an absolute neutrophil count less than 1000/mm3. Ninety-one patients were identified; 5 with positive blood culture results, 13 with significant non-oncologic disease, and 3 patients with leukemia who had involvement of 2 or more cell lines. In the majority of patients, clinical judgment, physical findings, and review of all cell lines of the complete blood cell count identified those with significant disease.

  6. Predictors of temporal patterns of psychiatric distress during 10 years following the nuclear accident at Three Mile Island.

    PubMed

    Dew, M A; Bromet, E J

    1993-04-01

    The present study examines psychiatric symptom levels during a 10-year period in a community sample of mothers of young children. All were identified in the early aftermath of the 1979 Three Mile Island nuclear accident, and followed through the accident's 1989 anniversary. Cluster analysis was used to identify long-term distress profiles during the study period; women's temporal profiles were found to be either (a) stable and at low, clinically nonsignificant levels of distress across all measurement points or (b) at consistently elevated, clinically significant levels that varied with the timing of postaccident events such as the restart of the undamaged reactor and the 10th anniversary. Subsequent multivariate analyses indicated that preaccident characteristics, as well as parameters reflecting respondents' initial involvement with, and reactions to the accident, were important for distinguishing between women within the two temporal profile groups. Implications of the results for both policy formulation and continued research on significant environmental stressors is discussed.

  7. Clinical predictors of quality of life in patients with head and neck cancer.

    PubMed

    Terrell, Jeffrey E; Ronis, David L; Fowler, Karen E; Bradford, Carol R; Chepeha, Douglas B; Prince, Mark E; Teknos, Theodoros N; Wolf, Gregory T; Duffy, Sonia A

    2004-04-01

    To identify clinical predictors of quality of life (QoL) in a head and neck cancer patient population. A convenience sample of 570 patients with upper aerodigestive tract cancers were surveyed at a tertiary care oncology clinic and Veterans Affairs otolaryngology clinic. A self-administered health survey was constructed to collect demographic, health, smoking, alcohol, depression symptom, and QoL information. Tumor site and tumor stage, clinical, and treatment data were abstracted from the patient medical records. Quality of life was assessed using the Medical Outcomes Study Short-Form 36-Item Health Survey (SF-36) and the Head and Neck QoL (HNQoL) instrument. Of the 570 eligible respondents, the presence of a feeding tube had the most negative impact on QoL, with significant decrements in 6 of the 8 SF-36 scales and all 4 HNQoL scales (P<.01). In descending order of severity, medical comorbid conditions, presence of a tracheotomy tube, chemotherapy, and neck dissection were also associated with significant (P<.05) decrements in QoL domains. Patients who took the survey more than 1 year after diagnosis had improved QoL in 7 of 12 domains. Hospital site, age, education level, sex, race, and marital status were also significant predictors of QoL. There are at least 13 demographic and clinical characteristics that are significant predictors of QoL in patients with head and neck cancer, which should be considered when treating patients and conducting QoL studies in the future.

  8. The contribution of psychological factors to recovery after mild traumatic brain injury: is cluster analysis a useful approach?

    PubMed

    Snell, Deborah L; Surgenor, Lois J; Hay-Smith, E Jean C; Williman, Jonathan; Siegert, Richard J

    2015-01-01

    Outcomes after mild traumatic brain injury (MTBI) vary, with slow or incomplete recovery for a significant minority. This study examines whether groups of cases with shared psychological factors but with different injury outcomes could be identified using cluster analysis. This is a prospective observational study following 147 adults presenting to a hospital-based emergency department or concussion services in Christchurch, New Zealand. This study examined associations between baseline demographic, clinical, psychological variables (distress, injury beliefs and symptom burden) and outcome 6 months later. A two-step approach to cluster analysis was applied (Ward's method to identify clusters, K-means to refine results). Three meaningful clusters emerged (high-adapters, medium-adapters, low-adapters). Baseline cluster-group membership was significantly associated with outcomes over time. High-adapters appeared recovered by 6-weeks and medium-adapters revealed improvements by 6-months. The low-adapters continued to endorse many symptoms, negative recovery expectations and distress, being significantly at risk for poor outcome more than 6-months after injury (OR (good outcome) = 0.12; CI = 0.03-0.53; p < 0.01). Cluster analysis supported the notion that groups could be identified early post-injury based on psychological factors, with group membership associated with differing outcomes over time. Implications for clinical care providers regarding therapy targets and cases that may benefit from different intensities of intervention are discussed.

  9. Impact of Stress Cardiac Magnetic Resonance Imaging on Clinical Care

    PubMed Central

    McGraw, Sloane; Romano, Simone; Jue, Jennifer; Bauml, Michael A; Chung, Jaehoon; Farzaneh-Far, Afshin

    2016-01-01

    Given the rising costs of imaging, there is increasing pressure to provide evidence for direct additive impact on clinical care. Appropriate use criteria (AUC) were developed to optimize test-patient selection, and are increasingly used by payers to assess reimbursement. However, these criteria were created by expert consensus with limited systematic validation. The aims of this study were therefore to determine: 1) rates of active clinical change resulting from stress cardiovascular magnetic resonance (CMR) imaging; and 2) whether the AUC can predict these changes. We prospectively enrolled 350 consecutive outpatients referred for stress CMR. Categories of “active changes in clinical care” due to stress CMR were pre-defined. Appropriateness was classified according to the 2013 AUC. Multivariable logistic regression analysis was used to identify factors independently associated with active change. Overall, stress CMR led to an active change in clinical care in about 70% of patients. Rates of change in clinical care did not vary significantly across AUC categories (p=0.767). In a multivariable model adjusting for clinical variables and AUC, only ischemia (OR 6.896, 95% CI 2.637–18.032, p<0.001), known CAD (OR 0.300, 95% CI 0.161–0.559, p<0.001), and age (OR 0.977, 95% CI 0.954–1.000, p=0.050) independently predicted significant clinical change. In conclusion, stress CMR made a significant impact on clinical management, resulting in active change in clinical care in about 70% of patients. AUC categories were not an independent predictor of clinical change. Clinical change was independently associated with presence of ischemia, absence of known CAD, and younger age. PMID:27476576

  10. Computers in medical education 2. Use of a computer package to supplement the clinical experience in a surgical clerkship: an objective evaluation.

    PubMed

    Devitt, P; Cehic, D; Palmer, E

    1998-06-01

    Student teaching of surgery has been devolved from the university in an effort to increase and broaden undergraduate clinical experience. In order to ensure uniformity of learning we have defined learning objectives and provided a computer-based package to supplement clinical teaching. A study was undertaken to evaluate the place of computer-based learning in a clinical environment. Twelve modules were provided for study during a 6-week attachment. These covered clinical problems related to cardiology, neurosurgery and gastrointestinal haemorrhage. Eighty-four fourth-year students undertook a pre- and post-test assessment on these three topics as well as acute abdominal pain. No extra learning material on the latter topic was provided during the attachment. While all students showed significant improvement in performance in the post-test assessment, those who had access to the computer material performed significantly better than did the controls. Within the topics, students in both groups performed equally well on the post-test assessment of acute abdominal pain but the control group's performance was significantly lacking on the topic of gastrointestinal haemorrhage, suggesting that the bulk of learning on this subject came from the computer material and little from the clinical attachment. This type of learning resource can be used to supplement the student's clinical experience and at the same time monitor what they learn during clinical clerkships and identify areas of weakness.

  11. The comparability of solicited versus clinic subjects in alcohol treatment research.

    PubMed

    Pearlman, S; Zweben, A; Li, S

    1989-05-01

    The increasing use of media advertisements to recruit subjects in alcohol treatment research has raised concerns about the comparability of such solicited subjects and subjects drawn from more traditional clinic populations. This paper, based on a study that involved both solicited and clinic subjects, identifies differences between the two types of subjects in terms of sociodemographic variables; pre-treatment drinking and marital adjustment; several dimensions of 'self-definition'; and three outcome measures. These findings suggest that there may be significant differences between solicited and clinic subjects and that these differences should be taken into account in the design of studies utilizing solicited subjects in order to determine the generalizability of the results.

  12. Motor unit number estimates correlate with strength in polio survivors.

    PubMed

    Sorenson, Eric J; Daube, Jasper R; Windebank, Anthony J

    2006-11-01

    Motor unit number estimation (MUNE) has been proposed as an outcome measure in clinical trials for the motor neuron diseases. One major criticism of MUNE is that it may not represent a clinically meaningful endpoint. We prospectively studied a cohort of polio survivors over a period of 15 years with respect to MUNE and strength. We identified a significant association between thenar MUNE and arm strength, extensor digitorum brevis MUNE and leg strength, and the summated MUNE and global strength of the polio survivors. These findings confirm the clinical relevance of MUNE as an outcome measure in the motor neuron diseases and provide further validation for its use in clinical trial research.

  13. Competence profiles in undergraduate dental education: a comparison between theory and reality.

    PubMed

    Koole, Sebastiaan; Van Den Brulle, Shani; Christiaens, Véronique; Jacquet, Wolfgang; Cosyn, Jan; De Bruyn, Hugo

    2017-07-11

    Competence profiles are purposed to provide a blueprint in support to develop and/or benchmark the learning outcomes of undergraduate dental curricula. This study aims to investigate whether a competence profile as proposed by academic- and clinical experts is able to represent the real clinical reality. A questionnaire was developed including questions about gender and age, perception about required competences, and educational organisation and was distributed among Flemish dentists via email and on paper during a symposium. The data was analysed using descriptive statistics, Chi-square and non-parametric Mann-Whitney U-tests. A total of 312 questionnaires were completed (=6.5% of dentist population, with similar gender and age characteristics). All competences in the European competence profile were rated between 7.2 and 9.4 on a 10-point scale. In dentists under 50 years, females rated the importance of identifying/managing anxiety and abnormal patient behaviour; and promoting/improving oral health as significantly higher than males. In dentists of 50 years and above, females rated 8 competences significantly higher than males, including obtaining/recording a complete history; identifying/managing anxiety and abnormal patient behaviour; obtaining/interpreting radiography; identifying temporomandibular and associated disorders; identifying orthodontic needs; awareness of own limitations/when to refer; managing dental urgencies; and basic-life-support/defibrillation. Clinical practice management was most frequently reported as additional competence to address in dental education. Furthermore, the respondents suggested an undergraduate dental curriculum based on 34% theoretical education, 26% preclinical skills training, and 40% clinical education and 86% agreed with a duration of 5 years. Finally, the respondents also illustrated the dynamic nature of dentistry including a reduction of amalgam fillings, a shift from individual practice to group practices, an increased administrative load, and more assertive patients. Findings in the present study suggest the validation of the proposed competences for graduating European dentists within the clinical reality of dental professionals in daily practice. Nevertheless, the results have also demonstrated heterogeneity regarding gender and age within the dentist population and emphasised a continuously evolving dental profession and required competences. Hence, to maintain high quality of dental care, a strategy should be developed in which dental curricula are continuously benchmarked against an evolving clinical reality.

  14. High-heeled shoes and musculoskeletal injuries: a narrative systematic review

    PubMed Central

    Barnish, Maxwell S; Barnish, Jean

    2016-01-01

    Objectives To conduct the first systematic review from an epidemiological perspective regarding the association between high-heeled shoe wear and hallux valgus, musculoskeletal pain, osteoarthritis (OA) and both first-party and second-party injury in human participants without prior musculoskeletal conditions. Setting A systematic review of international peer-reviewed scientific literature across seven major languages. Data sources Searches were conducted on seven major bibliographic databases in July 2015 to initially identify all scholarly articles on high-heeled shoes. Supplementary manual searches were conducted. Titles, abstracts and full-text articles were sequentially screened to identify all articles assessing epidemiological evidence regarding the association between high-heeled shoe wear and hallux valgus, musculoskeletal pain, OA and both first-party and second-party injury in human participants without prior musculoskeletal conditions. Standardised data extraction and quality assessment (Threats to Validity tool) were conducted. Primary and secondary outcome measures Musculoskeletal pain or OA as assessed by clinical diagnosis or clinical assessment tool. First-party or second-party injury. Results 644 unique records were identified, 56 full-text articles were screened and 18 studies included in the review. Four studies assessed the relationship with hallux valgus and three found a significant association. Two studies assessed the association with OA and neither found a significant association. Five studies assessed the association with musculoskeletal pain and three found a significant association. Eight studies assessed first-party injury and seven found evidence of a significant injury toll associated with high-heeled shoes. One study provided data on second-party injury and the injury toll was low. Conclusions High-heeled shoes were shown to be associated with hallux valgus, musculoskeletal pain and first-party injury. No conclusive evidence regarding OA and second-party injury was found. Societal and clinical relevance of these findings is discussed. Concern is expressed about the expectation to wear high-heeled shoes in some work and social situations and access by children. PMID:26769789

  15. Who Is at Risk for Diagnostic Discrepancies? Comparison of Pre- and Postmortal Diagnoses in 1800 Patients of 3 Medical Decades in East and West Berlin

    PubMed Central

    Wittschieber, Daniel; Klauschen, Frederick; Kimmritz, Anna-Christin; von Winterfeld, Moritz; Kamphues, Carsten; Scholman, Hans-Joachim; Erbersdobler, Andreas; Pfeiffer, Heidi; Denkert, Carsten; Dietel, Manfred; Weichert, Wilko

    2012-01-01

    Background Autopsy rates in Western countries consistently decline to an average of <5%, although clinical autopsies represent a reasonable tool for quality control in hospitals, medically and economically. Comparing pre- and postmortal diagnoses, diagnostic discrepancies as uncovered by clinical autopsies supply crucial information on how to improve clinical treatment. The study aimed at analyzing current diagnostic discrepancy rates, investigating their influencing factors and identifying risk profiles of patients that could be affected by a diagnostic discrepancy. Methods and Findings Of all adult autopsy cases of the Charité Institute of Pathology from the years 1988, 1993, 1998, 2003 and 2008, the pre- and postmortal diagnoses and all demographic data were analyzed retrospectively. Based on power analysis, 1,800 cases were randomly selected to perform discrepancy classification (class I-VI) according to modified Goldman criteria. The rate of discrepancies in major diagnoses (class I) was 10.7% (95% CI: 7.7%–14.7%) in 2008 representing a reduction by 15.1%. Subgroup analysis revealed several influencing factors to significantly correlate with the discrepancy rate. Cardiovascular diseases had the highest frequency among class-I-discrepancies. Comparing the 1988-data of East- and West-Berlin, no significant differences were found in diagnostic discrepancies despite an autopsy rate differing by nearly 50%. A risk profile analysis visualized by intuitive heatmaps revealed a significantly high discrepancy rate in patients treated in low or intermediate care units at community hospitals. In this collective, patients with genitourinary/renal or infectious diseases were at particularly high risk. Conclusions This is the current largest and most comprehensive study on diagnostic discrepancies worldwide. Our well-powered analysis revealed a significant rate of class-I-discrepancies indicating that autopsies are still of value. The identified risk profiles may aid both pathologists and clinicians to identify patients at increased risk for a discrepant diagnosis and possibly suboptimal treatment intra vitam. PMID:22629399

  16. Combining clinical variables to optimize prediction of antidepressant treatment outcomes.

    PubMed

    Iniesta, Raquel; Malki, Karim; Maier, Wolfgang; Rietschel, Marcella; Mors, Ole; Hauser, Joanna; Henigsberg, Neven; Dernovsek, Mojca Zvezdana; Souery, Daniel; Stahl, Daniel; Dobson, Richard; Aitchison, Katherine J; Farmer, Anne; Lewis, Cathryn M; McGuffin, Peter; Uher, Rudolf

    2016-07-01

    The outcome of treatment with antidepressants varies markedly across people with the same diagnosis. A clinically significant prediction of outcomes could spare the frustration of trial and error approach and improve the outcomes of major depressive disorder through individualized treatment selection. It is likely that a combination of multiple predictors is needed to achieve such prediction. We used elastic net regularized regression to optimize prediction of symptom improvement and remission during treatment with escitalopram or nortriptyline and to identify contributing predictors from a range of demographic and clinical variables in 793 adults with major depressive disorder. A combination of demographic and clinical variables, with strong contributions from symptoms of depressed mood, reduced interest, decreased activity, indecisiveness, pessimism and anxiety significantly predicted treatment outcomes, explaining 5-10% of variance in symptom improvement with escitalopram. Similar combinations of variables predicted remission with area under the curve 0.72, explaining approximately 15% of variance (pseudo R(2)) in who achieves remission, with strong contributions from body mass index, appetite, interest-activity symptom dimension and anxious-somatizing depression subtype. Escitalopram-specific outcome prediction was more accurate than generic outcome prediction, and reached effect sizes that were near or above a previously established benchmark for clinical significance. Outcome prediction on the nortriptyline arm did not significantly differ from chance. These results suggest that easily obtained demographic and clinical variables can predict therapeutic response to escitalopram with clinically meaningful accuracy, suggesting a potential for individualized prescription of this antidepressant drug. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. Building the Evidence Base for Decision-making in Cancer Genomic Medicine Using Comparative Effectiveness Research

    PubMed Central

    Goddard, Katrina A.B.; Knaus, William A.; Whitlock, Evelyn; Lyman, Gary H.; Feigelson, Heather Spencer; Schully, Sheri D.; Ramsey, Scott; Tunis, Sean; Freedman, Andrew N.; Khoury, Muin J.; Veenstra, David L.

    2013-01-01

    Background The clinical utility is uncertain for many cancer genomic applications. Comparative effectiveness research (CER) can provide evidence to clarify this uncertainty. Objectives To identify approaches to help stakeholders make evidence-based decisions, and to describe potential challenges and opportunities using CER to produce evidence-based guidance. Methods We identified general CER approaches for genomic applications through literature review, the authors’ experiences, and lessons learned from a recent, seven-site CER initiative in cancer genomic medicine. Case studies illustrate the use of CER approaches. Results Evidence generation and synthesis approaches include comparative observational and randomized trials, patient reported outcomes, decision modeling, and economic analysis. We identified significant challenges to conducting CER in cancer genomics: the rapid pace of innovation, the lack of regulation, the limited evidence for clinical utility, and the beliefs that genomic tests could have personal utility without having clinical utility. Opportunities to capitalize on CER methods in cancer genomics include improvements in the conduct of evidence synthesis, stakeholder engagement, increasing the number of comparative studies, and developing approaches to inform clinical guidelines and research prioritization. Conclusions CER offers a variety of methodological approaches to address stakeholders’ needs. Innovative approaches are needed to ensure an effective translation of genomic discoveries. PMID:22516979

  18. The effect of abnormal colour vision on the ability to identify and outline coloured clinical signs and to count stained bacilli in sputum.

    PubMed

    Campbell, John L; Griffin, Lewis; Spalding, J Anthony B; Mir, Fraz A

    2005-11-01

    To determine if medical practitioners with congenital colour vision deficiencies (CCVD) are less able to identify and delineate the extent of coloured abnormal signs than those with normal colour vision. Twenty-two medical practitioners with CCVD and 17 with normal colour vision, matched for age and gender, were shown 10 photographs. They were asked to identify and outline the extent of the clinical sign in eight that were of vomit or stool (six of these showing fresh blood), one of a skin rash and for one to mark the position of bacilli in sputum stained by the Ziehl-Neelsen method. There were statistically significant differences between the CCVD practitioners and those with normal colour vision in their ability to outline abnormalities in five of the six photographs that showed fresh blood, in the photograph of a rash and in marking the position of bacilli in the photograph of a stained slide. Medical practitioners with CCVD are handicapped in their evaluation of the presence and extent of coloured clinical signs. Medical schools should ensure that students with CCVD are aware of their deficiency and know its severity, so they can take special care in clinical practice.

  19. The Molecular Phenotype of Endocapillary Proliferation: Novel Therapeutic Targets for IgA Nephropathy

    PubMed Central

    John, Rohan; Grone, Elisabeth; Porubsky, Stefan; Gröne, Hermann-Josef; Herzenberg, Andrew M.; Scholey, James W.; Hladunewich, Michelle; Cattran, Daniel C.

    2014-01-01

    IgA nephropathy (IgAN) is a clinically and pathologically heterogeneous disease. Endocapillary proliferation is associated with higher risk of progressive disease, and clinical studies suggest that corticosteroids mitigate this risk. However, corticosteroids are associated with protean cellular effects and significant toxicity. Furthermore the precise mechanism by which they modulate kidney injury in IgAN is not well delineated. To better understand molecular pathways involved in the development of endocapillary proliferation and to identify novel specific therapeutic targets, we evaluated the glomerular transcriptome of microdissected kidney biopsies from 22 patients with IgAN. Endocapillary proliferation was defined according to the Oxford scoring system independently by 3 nephropathologists. We analyzed mRNA expression using microarrays and identified transcripts differentially expressed in patients with endocapillary proliferation compared to IgAN without endocapillary lesions. Next, we employed both transcription factor analysis and in silico drug screening and confirmed that the endocapillary proliferation transcriptome is significantly enriched with pathways that can be impacted by corticosteroids. With this approach we also identified novel therapeutic targets and bioactive small molecules that may be considered for therapeutic trials for the treatment of IgAN, including resveratrol and hydroquinine. In summary, we have defined the distinct molecular profile of a pathologic phenotype associated with progressive renal insufficiency in IgAN. Exploration of the pathways associated with endocapillary proliferation confirms a molecular basis for the clinical effectiveness of corticosteroids in this subgroup of IgAN, and elucidates new therapeutic strategies for IgAN. PMID:25133636

  20. Clinical and histopathologic independent prognostic factors in oral squamous cell carcinoma: a retrospective study of 334 cases.

    PubMed

    Arduino, Paolo G; Carrozzo, Marco; Chiecchio, Andrea; Broccoletti, Roberto; Tirone, Federico; Borra, Eleonora; Bertolusso, Giorgio; Gandolfo, Sergio

    2008-08-01

    This retrospective hospital-based study reviewed and evaluated the outcome of patients with oral squamous cell carcinoma (OSCC) with the aim of identifying factors affecting the clinical course and survival rate. Patients with a follow-up of at least 12 months were included. The data collected were statistically analyzed for the presence of factors valuable for prognosis; survival curves were processed in accordance with the Kaplan-Meier method. Differences in the expression of variables in different grading levels were investigated. Cox's proportional hazard model for Z(i) covariates (grading, age, T, N) also was calculated. Mean patient age was 67.7 years in women (n = 152) and 62.4 years in men (n = 182). A total of 98 patients were identified with Broder's/World Health Organization grade 1 histology, 176 with grade 2, and 55 with grade 3; 5 patients were identified as grade 4 (carcinoma in situ). Gender and risk factors seemed to be unrelated to prognosis, whereas a significant increase in mortality was seen in patients over age 70. Histological grading, tumor size, and neck involvement were related, as independent factors, in predicting survival in patients with OSCC (QM-H > 3.9). Gender, age, and risk factors had no statistical relationship with cancer histological differentiation. Our analysis reveals a statistically significant relationship among histological Broder's grading of malignancy, tumor size, locoregional involvement, and survival rates, underscoring the utility of tumor differentiation in predicting the clinical course and outcome of OSCC.

  1. 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.

  2. Characterization of Change and Significance for Clinical Findings in Radiology Reports Through Natural Language Processing.

    PubMed

    Hassanpour, Saeed; Bay, Graham; Langlotz, Curtis P

    2017-06-01

    We built a natural language processing (NLP) method to automatically extract clinical findings in radiology reports and characterize their level of change and significance according to a radiology-specific information model. We utilized a combination of machine learning and rule-based approaches for this purpose. Our method is unique in capturing different features and levels of abstractions at surface, entity, and discourse levels in text analysis. This combination has enabled us to recognize the underlying semantics of radiology report narratives for this task. We evaluated our method on radiology reports from four major healthcare organizations. Our evaluation showed the efficacy of our method in highlighting important changes (accuracy 99.2%, precision 96.3%, recall 93.5%, and F1 score 94.7%) and identifying significant observations (accuracy 75.8%, precision 75.2%, recall 75.7%, and F1 score 75.3%) to characterize radiology reports. This method can help clinicians quickly understand the key observations in radiology reports and facilitate clinical decision support, review prioritization, and disease surveillance.

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

    PubMed

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

    2016-11-30

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

  4. Aspects of postoperative magnetic resonance imaging of patients with avascular necrosis of the femoral head, treated by advanced core decompression.

    PubMed

    Lazik, Andrea; Landgraeber, Stefan; Claßen, Tim; Kraff, Oliver; Lauenstein, Thomas C; Theysohn, Jens M

    2015-10-01

    To analyze remodeling processes after advanced core decompression (ACD) in patients with avascular femoral head necrosis by means of 3T MRI and to identify indicators for clinical outcome considering the defect size and characteristics of the bone graft and of the neighboring regeneration tissue. Thirty-four hips, with preexisting preoperative MRIs in 21 cases, were examined 1-34 months (mean 12.7) postoperatively by 3T MRI. The volume of necrosis was measured manually pre- and postoperatively to calculate absolute as well as percentage necrosis reduction. The signal intensity of the bone graft was quantified using a 4-point scale. Border phenomena between the bone graft and bone were described and classified into groups. Wilcoxon sign-rank test was used to identify correlations between the analyzed items and clinical signs of femoral head collapse after a mean follow-up time of 28.6 months (10.4-46.8). Mean percentage reduction of necrosis was significantly higher in asymptomatic patients (59.36%) compared to patients with signs of femoral head collapse (28.78%, p = 0.008). Signal intensity of the bone graft increased in T1w and T2w TIRM sequences over time after surgery and was significantly higher in asymptomatic patients. Five border phenomena between the bone graft and healthy bone were identified. Among them, the so-called "rail sign" representing three layers of remodeling tissue correlated with the histological observations. A variety of border phenomena representing remodeling processes have been described using 3T MRI. Beneath the percentage amount of necrosis reduction, we identified the signal intensity of the bone graft as an indicator for clinical outcome.

  5. Array-Based Comparative Genomic Hybridization Analysis Reveals Chromosomal Copy Number Aberrations Associated with Clinical Outcome in Canine Diffuse Large B-Cell Lymphoma

    PubMed Central

    Bresolin, Silvia; Marconato, Laura; Comazzi, Stefano; Te Kronnie, Geertruy; Aresu, Luca

    2014-01-01

    Canine Diffuse Large B-cell Lymphoma (cDLBCL) is an aggressive cancer with variable clinical response. Despite recent attempts by gene expression profiling to identify the dog as a potential animal model for human DLBCL, this tumor remains biologically heterogeneous with no prognostic biomarkers to predict prognosis. The aim of this work was to identify copy number aberrations (CNAs) by high-resolution array comparative genomic hybridization (aCGH) in 12 dogs with newly diagnosed DLBCL. In a subset of these dogs, the genetic profiles at the end of therapy and at relapse were also assessed. In primary DLBCLs, 90 different genomic imbalances were counted, consisting of 46 gains and 44 losses. Two gains in chr13 were significantly correlated with clinical stage. In addition, specific regions of gains and losses were significantly associated to duration of remission. In primary DLBCLs, individual variability was found, however 14 recurrent CNAs (>30%) were identified. Losses involving IGK, IGL and IGH were always found, and gains along the length of chr13 and chr31 were often observed (>41%). In these segments, MYC, LDHB, HSF1, KIT and PDGFRα are annotated. At the end of therapy, dogs in remission showed four new CNAs, whereas three new CNAs were observed in dogs at relapse compared with the previous profiles. One ex novo CNA, involving TCR, was present in dogs in remission after therapy, possibly induced by the autologous vaccine. Overall, aCGH identified small CNAs associated with outcome, which, along with future expression studies, may reveal target genes relevant to cDLBCL. PMID:25372838

  6. Molecular and Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry-Based Characterization of Clinically Significant Melanized Fungi in India.

    PubMed

    Singh, Ashutosh; Singh, Pradeep Kumar; Kumar, Anil; Chander, Jagdish; Khanna, Geetika; Roy, Pradip; Meis, Jacques F; Chowdhary, Anuradha

    2017-04-01

    Melanized or black fungi are a heterogeneous group of fungi causing cutaneous to systemic diseases with high mortality. These fungi are rarely reported as agents of human infections, primarily due to difficulties in their classical identification. In this study, we examined, using molecular methods and matrix-assisted laser desorption ioniazation-time of flight mass spectrometry (MALDI-TOF MS), the diversity of melanized fungi (MF) isolated from patients in 19 medical centers in India. Overall, during a 4-year period, 718 (5.3%) clinical specimens yielded MF. Of these, 72 (10%) isolates had clinical significance and were identified primarily by sequencing the internal transcribed spacer and large subunit (LSU) regions. MF represented 21 genera comprising 29 species, the majority of them belonging to the orders Pleosporales (50%) and Chaetothyriales (22%). Among the 29 fungal species identified in this study, only 6 (20%) species were identified by the MALDI-TOF MS due to the limited commercial database of Bruker Daltonics for MF. However, a 100% identification rate of 20 additional species identified in this study was obtained by constructing an in-house database using 24- to 96-h-old liquid cultures. Further, the CLSI broth microdilution method revealed low MICs for posaconazole (≤1 μg/ml) and voriconazole (≤2 μg/ml) in 96% and 95% of isolates, respectively. Skin/subcutaneous and sino-nasal and pulmonary phaeohyphomycosis due to MF were diagnosed in 21.4% ( n = 15) and 28.5% ( n = 20) of cases. Also, 10% of patients had central nervous system involvement ( n = 7), and 3 cases of fungal osteomyelitis due to Cladophialophora bantiana and Corynespora spp. were observed. Copyright © 2017 American Society for Microbiology.

  7. 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.

  8. Polygenic hazard scores in preclinical Alzheimer disease.

    PubMed

    Tan, Chin Hong; Hyman, Bradley T; Tan, Jacinth J X; Hess, Christopher P; Dillon, William P; Schellenberg, Gerard D; Besser, Lilah M; Kukull, Walter A; Kauppi, Karolina; McEvoy, Linda K; Andreassen, Ole A; Dale, Anders M; Fan, Chun Chieh; Desikan, Rahul S

    2017-09-01

    Identifying asymptomatic older individuals at elevated risk for developing Alzheimer disease (AD) is of clinical importance. Among 1,081 asymptomatic older adults, a recently validated polygenic hazard score (PHS) significantly predicted time to AD dementia and steeper longitudinal cognitive decline, even after controlling for APOE ɛ4 carrier status. Older individuals in the highest PHS percentiles showed the highest AD incidence rates. PHS predicted longitudinal clinical decline among older individuals with moderate to high Consortium to Establish a Registry for Alzheimer's Disease (amyloid) and Braak (tau) scores at autopsy, even among APOE ɛ4 noncarriers. Beyond APOE, PHS may help identify asymptomatic individuals at highest risk for developing Alzheimer neurodegeneration. Ann Neurol 2017;82:484-488. © 2017 American Neurological Association.

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

    PubMed

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

    2015-01-01

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

  10. Systematic review and network meta-analysis comparing clinical outcomes and effectiveness of surgical treatments for haemorrhoids.

    PubMed

    Simillis, C; Thoukididou, S N; Slesser, A A P; Rasheed, S; Tan, E; Tekkis, P P

    2015-12-01

    The aim was to compare the clinical outcomes and effectiveness of surgical treatments for haemorrhoids. Randomized clinical trials were identified by means of a systematic review. A Bayesian network meta-analysis was performed using the Markov chain Monte Carlo method in WinBUGS. Ninety-eight trials were included with 7827 participants and 11 surgical treatments for grade III and IV haemorrhoids. Open, closed and radiofrequency haemorrhoidectomies resulted in significantly more postoperative complications than transanal haemorrhoidal dearterialization (THD), LigaSure™ and Harmonic® haemorrhoidectomies. THD had significantly less postoperative bleeding than open and stapled procedures, and resulted in significantly fewer emergency reoperations than open, closed, stapled and LigaSure™ haemorrhoidectomies. Open and closed haemorrhoidectomies resulted in more pain on postoperative day 1 than stapled, THD, LigaSure™ and Harmonic® procedures. After stapled, LigaSure™ and Harmonic® haemorrhoidectomies patients resumed normal daily activities earlier than after open and closed procedures. THD provided the earliest time to first bowel movement. The stapled and THD groups had significantly higher haemorrhoid recurrence rates than the open, closed and LigaSure™ groups. Recurrence of haemorrhoidal symptoms was more common after stapled haemorrhoidectomy than after open and LigaSure™ operations. No significant difference was identified between treatments for anal stenosis, incontinence and perianal skin tags. Open and closed haemorrhoidectomies resulted in more postoperative complications and slower recovery, but fewer haemorrhoid recurrences. THD and stapled haemorrhoidectomies were associated with decreased postoperative pain and faster recovery, but higher recurrence rates. The advantages and disadvantages of each surgical treatment should be discussed with the patient before surgery to allow an informed decision to be made. © 2015 BJS Society Ltd Published by John Wiley & Sons Ltd.

  11. 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.

  12. Predictors of clinical outcome following lumbar disc surgery: the value of historical, physical examination, and muscle function variables.

    PubMed

    Hebert, Jeffrey J; Fritz, Julie M; Koppenhaver, Shane L; Thackeray, Anne; Kjaer, Per

    2016-01-01

    Explore the relationships between preoperative findings and clinical outcome following lumbar disc surgery, and investigate the prognostic value of physical examination findings after accounting for information acquired from the clinical history. We recruited 55 adult patients scheduled for first time, single-level lumbar discectomy. Participants underwent a standardized preoperative evaluation including real-time ultrasound imaging assessment of lumbar multifidus function, and an 8-week postoperative rehabilitation programme. Clinical outcome was defined by change in disability, and leg and low back pain (LBP) intensity at 10 weeks. Linear regression models were used to identify univariate and multivariate predictors of outcome. Univariate predictors of better outcome varied depending on the outcome measure. Clinical history predictors included a greater proportion of leg pain to LBP, pain medication use, greater time to surgery, and no history of previous physical or injection therapy. Physical examination predictors were a positive straight or cross straight leg raise test, diminished lower extremity strength, sensation or reflexes, and the presence of postural abnormality or pain peripheralization. Preoperative pain peripheralization remained a significant predictor of improved disability (p = 0.04) and LBP (p = 0.02) after accounting for information from the clinical history. Preoperative lumbar multifidus function was not associated with clinical outcome. Information gleaned from the clinical history and physical examination helps to identify patients more likely to succeed with lumbar disc surgery. While this study helps to inform clinical practice, additional research confirming these results is required prior to confident clinical implementation.

  13. Clinical significance of preoperative carcinoembryonic antigen level in patients with clinical stage IA non-small cell lung cancer.

    PubMed

    Maeda, Ryo; Suda, Takashi; Hachimaru, Ayumi; Tochii, Daisuke; Tochii, Sachiko; Takagi, Yasushi

    2017-01-01

    The objective of this study was to assess the preoperative serum carcinoembryonic antigen (CEA) level in patients with clinical stage IA non-small cell lung cancer (NSCLC) and to evaluate its clinical significance. Between January 2005 and December 2014, a total of 378 patients with clinical stage IA NSCLC underwent complete resection with systematic node dissection. The survival rate was estimated starting from the date of surgery to the date of either death or the last follow-up by the Kaplan-Meier method. Univariate analyses by log-rank tests were used to determine prognostic factors. Cox proportional hazards ratios were used to identify independent predictors of poor prognosis. Clinicopathological predictors of lymph node metastases were evaluated by logistic regression analyses. The 5-year survival rate of patients with an elevated preoperative serum CEA level was significantly lower than that of patients with a normal CEA level (75.5% vs. 87.7%; P=0.02). However, multivariate analysis did not show the preoperative serum CEA level to be an independent predictor of poor prognosis. Postoperative pathological factors, including lymphatic permeation, visceral pleural invasion, and lymph node metastases, tended to be positive in patients with an elevated preoperative serum CEA level. In addition, the CEA level was a statistically significant independent clinical predictor of lymph node metastases. The preoperative serum CEA level was not an independent predictor of poor prognosis in patients with pathological stage IA NSCLC but was an important clinical predictor of tumor invasiveness and lymph node metastases in patients with clinical stage IA NSCLC. Therefore, measurement of the preoperative serum CEA level should be considered even for patients with early-stage NSCLC.

  14. Patient safety culture in Norwegian primary care: a study in out-of-hours casualty clinics and GP practices.

    PubMed

    Bondevik, Gunnar Tschudi; Hofoss, Dag; Hansen, Elisabeth Holm; Deilkås, Ellen Catharina Tveter

    2014-09-01

    This study aimed to investigate patient safety attitudes amongst health care providers in Norwegian primary care by using the Safety Attitudes Questionnaire, in both out-of-hours (OOH) casualty clinics and GP practices. The questionnaire identifies five major patient safety factors: Teamwork climate, Safety climate, Job satisfaction, Perceptions of management, and Working conditions. Cross-sectional study. Statistical analysis included multiple linear regression and independent samples t-tests. Seven OOH casualty clinics and 17 GP practices in Norway. In October and November 2012, 510 primary health care providers working in OOH casualty clinics and GP practices (316 doctors and 194 nurses) were invited to participate anonymously. To study whether patterns in patient safety attitudes were related to professional background, gender, age, and clinical setting. The overall response rate was 52%; 72% of the nurses and 39% of the doctors answered the questionnaire. In the OOH clinics, nurses scored significantly higher than doctors on Safety climate and Job satisfaction. Older health care providers scored significantly higher than younger on Safety climate and Working conditions. In GP practices, male health professionals scored significantly higher than female on Teamwork climate, Safety climate, Perceptions of management and Working conditions. Health care providers in GP practices had significant higher mean scores on the factors Safety climate and Working conditions, compared with those working in the OOH clinics. Our study showed that nurses scored higher than doctors, older health professionals scored higher than younger, male GPs scored higher than female GPs, and health professionals in GP practices scored higher than those in OOH clinics - on several patient safety factors.

  15. A clinical knowledge measurement tool to assess the ability of community pharmacists to detect drug-related problems.

    PubMed

    Williams, Mackenzie; Peterson, Gregory M; Tenni, Peter C; Bindoff, Ivan K

    2012-08-01

    Drug-related problems (DRPs) are associated with significant morbidity and mortality, with most DRPs thought to be preventable. Community pharmacists can detect and either prevent or resolve many of these DRPs. A survey-based clinical knowledge measurement tool was designed and validated to estimate a community pharmacist's clinical knowledge and ability to detect and appropriately resolve DRPs. Nine clinical cases with seven multiple-choice statements (63 statements in total) were constructed, based on scenarios that were found to occur frequently in Australian community pharmacies. The statements aimed to assess a pharmacist's ability to identify, gather relevant information about and make appropriate recommendations to resolve, a DRP. The survey was pilot tested with 18 academics at three Australian pharmacy schools, resulting in the removal of 23 statements. The survey was then administered to undergraduate pharmacy students (28 fourth-year, 41 third-year and 42 first-year students) and to 433 Australian community pharmacists who were participating in an intervention documentation trial. The pharmacists' resultant survey scores were correlated against their actual rate of documenting clinical interventions. The tool had relatively good internal consistency. Significant differences were seen between the three groups of students (P < 0.01). Community pharmacists with additional clinical qualifications had a significantly higher score than other participating pharmacists (P < 0.01). A moderate, but significant, correlation was seen between the pharmacists' survey score and their clinical intervention rate in practice during the trial (P < 0.01). The clinical knowledge measurement tool appeared to estimate a pharmacist's ability to detect and resolve DRPs within the community pharmacy environment. © 2012 The Authors. IJPP © 2012 Royal Pharmaceutical Society.

  16. Patient phenotypes associated with outcomes after aneurysmal subarachnoid hemorrhage: a principal component analysis.

    PubMed

    Ibrahim, George M; Morgan, Benjamin R; Macdonald, R Loch

    2014-03-01

    Predictors of outcome after aneurysmal subarachnoid hemorrhage have been determined previously through hypothesis-driven methods that often exclude putative covariates and require a priori knowledge of potential confounders. Here, we apply a data-driven approach, principal component analysis, to identify baseline patient phenotypes that may predict neurological outcomes. Principal component analysis was performed on 120 subjects enrolled in a prospective randomized trial of clazosentan for the prevention of angiographic vasospasm. Correlation matrices were created using a combination of Pearson, polyserial, and polychoric regressions among 46 variables. Scores of significant components (with eigenvalues>1) were included in multivariate logistic regression models with incidence of severe angiographic vasospasm, delayed ischemic neurological deficit, and long-term outcome as outcomes of interest. Sixteen significant principal components accounting for 74.6% of the variance were identified. A single component dominated by the patients' initial hemodynamic status, World Federation of Neurosurgical Societies score, neurological injury, and initial neutrophil/leukocyte counts was significantly associated with poor outcome. Two additional components were associated with angiographic vasospasm, of which one was also associated with delayed ischemic neurological deficit. The first was dominated by the aneurysm-securing procedure, subarachnoid clot clearance, and intracerebral hemorrhage, whereas the second had high contributions from markers of anemia and albumin levels. Principal component analysis, a data-driven approach, identified patient phenotypes that are associated with worse neurological outcomes. Such data reduction methods may provide a better approximation of unique patient phenotypes and may inform clinical care as well as patient recruitment into clinical trials. http://www.clinicaltrials.gov. Unique identifier: NCT00111085.

  17. Characteristics of respiratory outbreaks in care homes during four influenza seasons, 2011-2015.

    PubMed

    Gallagher, N; Johnston, J; Crookshanks, H; Nugent, C; Irvine, N

    2018-06-01

    Influenza and other respiratory infections can spread rapidly and cause severe morbidity and mortality in care home settings. This study describes the characteristics of respiratory outbreaks in care homes in Northern Ireland during a four-year period, and aims to identify factors that predict which respiratory outbreaks are more likely to be positively identified as influenza. Epidemiological, virological, and clinical characteristics of outbreaks during the study period were described. Variables collected at notification were compared to identify predictors for an outbreak testing positive for influenza. t-Tests and χ 2 -tests were used to compare means and proportions respectively; significance level was set at 95%. During the four seasons, 95 respiratory outbreaks were reported in care homes, 70 of which were confirmed as influenza. More than 1000 cases were reported, with 135 associated hospitalizations and 22 deaths. Vaccination uptake in residents was consistently high (mean: 86%); however, in staff it was poorly reported, and, when reported, consistently low (mean: 14%). Time to notification and number of cases at notification were both higher than expected according to national recommendations for reporting outbreaks. No clinically significant predictors of a positive influenza outbreak were identified. Respiratory outbreaks in care homes were associated with significant morbidity and mortality, despite high vaccination uptake. The absence of indicators at notification of an outbreak to accurately predict influenza infection highlights the need for prompt reporting and laboratory testing. Raising staff awareness, training in the management of respiratory outbreaks in accordance with national guidance, and improvement of staff vaccination uptake are recommended. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  18. Retrospective Analysis of 255 Papillary Thyroid Carcinomas ≤2 cm: Clinicohistological Features and Prognostic Factors.

    PubMed

    Marques, Pedro; Leite, Valeriano; Bugalho, Maria João

    2014-12-01

    Papillary thyroid carcinoma (PTC) is the most common thyroid cancer. The widespread use of neck ultrasound (US) and US-guided fine-needle aspiration cytology is triggering an overdiagnosis of PTC. To evaluate clinical behavior and outcomes of patients with PTCs ≤2 cm, seeking for possible prognostic factors. Clinical records of cases with histological diagnosis of PTC ≤2 cm followed at the Endocrine Department of Instituto Português de Oncologia, Lisbon between 2002 and 2006 were analyzed retrospectively. We identified 255 PTCs, 111 were microcarcinomas. Most patients underwent near-total thyroidectomy, with lymph node dissections in 55 cases (21.6%). Radioiodine therapy was administered in 184 patients. At the last evaluation, 38 (14.9%) had evidence of disease. Two deaths were attributed to PTC. Median (±SD) follow-up was 74 (±23) months. Multivariate analysis identified vascular invasion, lymph node and systemic metastases significantly associated with recurrence/persistence of disease. In addition, lymph node involvement was significantly associated with extrathyroidal extension and angioinvasion. Median (±SD) disease-free survival (DFS) was estimated as 106 (±3) months and the 5-year DFS rate was 87.5%. Univariate Cox analysis identified some relevant parameters for DFS, but multivariate regression only identified lymph node and systemic metastases as significant independent factors. The median DFS estimated for lymph node and systemic metastases was 75 and 0 months, respectively. In the setting of small PTCs, vascular invasion, extrathyroidal extension and lymph node and/or systemic metastases may confer worse prognosis, perhaps justifying more aggressive therapeutic and follow-up approaches in such cases.

  19. Willingness to Participate in Clinical Trials among Patients of Chinese Heritage: A Meta-Synthesis

    PubMed Central

    Limkakeng, Alexander; Phadtare, Amruta; Shah, Jatin; Vaghasia, Meenakshi; Wei, Ding Ying; Shah, Anand; Pietrobon, Ricardo

    2013-01-01

    Background Subjects of Chinese heritage have been found to participate in clinical research at lower rates than other groups despite growing in numbers as a population. While much research has examined research participants' motivation, there has not been a comprehensive synthesis of this information with respect to participants of Chinese descent. We sought to identify the factors that promote and hinder participation in clinical research among participants of Chinese heritage. Methodology/Principal Findings We conducted a systematic review of the literature in Pubmed, OpenJGATE, SCIRUS, and COCHRANE databases and performed a meta-synthesis of retrieved articles. We extracted qualitative data, such as quotes to identify emerging themes. We identified five studies that met our selection criteria. Of them, only one (1/5) was conducted in China while other studies involved Chinese emigrants in USA (3/5) and Singapore (1/5). Participants from China were similar to emigrants with regard to factors that either promoted or decreased research participation. Four studies reported data exclusively on Chinese subjects. Three of the five studies involved qualitative interviews while the others were conducted using a survey design. Six themes favoring research participation were identified: Personal Benefit to Participants, Financial Incentives, Participant Sense of Altruism, Family or Physician Recommendations, Advertisements, and Convenience to the Participant. Five factors were seen as a barrier to participation in clinical trials: Mistrust of Researchers, Language Barrier, Lack of Financial and Other Support, Cultural and Social Barriers, Lack of Knowledge about Clinical Trials. Conclusions/Significance Chinese heritage clinical research participants value personal benefit, financial incentives, the ability to help others, recommendations of others, advertisements, and convenience when considering clinical research participation. In addition, the establishment of trust and addressing knowledge deficits are important factors to them. Investigators seeking to optimize enrolment in these populations should incorporate these findings into their study design and subject handouts. PMID:23349672

  20. The role of emotion in clinical decision making: an integrative literature review.

    PubMed

    Kozlowski, Desirée; Hutchinson, Marie; Hurley, John; Rowley, Joanne; Sutherland, Joanna

    2017-12-15

    Traditionally, clinical decision making has been perceived as a purely rational and cognitive process. Recently, a number of authors have linked emotional intelligence (EI) to clinical decision making (CDM) and calls have been made for an increased focus on EI skills for clinicians. The objective of this integrative literature review was to identify and synthesise the empirical evidence for a role of emotion in CDM. A systematic search of the bibliographic databases PubMed, PsychINFO, and CINAHL (EBSCO) was conducted to identify empirical studies of clinician populations. Search terms were focused to identify studies reporting clinician emotion OR clinician emotional intelligence OR emotional competence AND clinical decision making OR clinical reasoning. Twenty three papers were retained for synthesis. These represented empirical work from qualitative, quantitative, and mixed-methods approaches and comprised work with a focus on experienced emotion and on skills associated with emotional intelligence. The studies examined nurses (10), physicians (7), occupational therapists (1), physiotherapists (1), mixed clinician samples (3), and unspecified infectious disease experts (1). We identified two main themes in the context of clinical decision making: the subjective experience of emotion; and, the application of emotion and cognition in CDM. Sub-themes under the subjective experience of emotion were: emotional response to contextual pressures; emotional responses to others; and, intentional exclusion of emotion from CDM. Under the application of emotion and cognition in CDM, sub-themes were: compassionate emotional labour - responsiveness to patient emotion within CDM; interdisciplinary tension regarding the significance and meaning of emotion in CDM; and, emotion and moral judgement. Clinicians' experienced emotions can and do affect clinical decision making, although acknowledgement of that is far from universal. Importantly, this occurs in the in the absence of a clear theoretical framework and educational preparation may not reflect the importance of emotional competence to effective CDM.

  1. Genomic analysis of diffuse pediatric low-grade gliomas identifies recurrent oncogenic truncating rearrangements in the transcription factor MYBL1

    PubMed Central

    Ramkissoon, Lori A.; Horowitz, Peleg M.; Craig, Justin M.; Ramkissoon, Shakti H.; Rich, Benjamin E.; Schumacher, Steven E.; McKenna, Aaron; Lawrence, Michael S.; Bergthold, Guillaume; Brastianos, Priscilla K.; Tabak, Barbara; Ducar, Matthew D.; Van Hummelen, Paul; MacConaill, Laura E.; Pouissant-Young, Tina; Cho, Yoon-Jae; Taha, Hala; Mahmoud, Madeha; Bowers, Daniel C.; Margraf, Linda; Tabori, Uri; Hawkins, Cynthia; Packer, Roger J.; Hill, D. Ashley; Pomeroy, Scott L.; Eberhart, Charles G.; Dunn, Ian F.; Goumnerova, Liliana; Getz, Gad; Chan, Jennifer A.; Santagata, Sandro; Hahn, William C.; Stiles, Charles D.; Ligon, Azra H.; Kieran, Mark W.; Beroukhim, Rameen; Ligon, Keith L.

    2013-01-01

    Pediatric low-grade gliomas (PLGGs) are among the most common solid tumors in children but, apart from BRAF kinase mutations or duplications in specific subclasses, few genetic driver events are known. Diffuse PLGGs comprise a set of uncommon subtypes that exhibit invasive growth and are therefore especially challenging clinically. We performed high-resolution copy-number analysis on 44 formalin-fixed, paraffin-embedded diffuse PLGGs to identify recurrent alterations. Diffuse PLGGs exhibited fewer such alterations than adult low-grade gliomas, but we identified several significantly recurrent events. The most significant event, 8q13.1 gain, was observed in 28% of diffuse astrocytoma grade IIs and resulted in partial duplication of the transcription factor MYBL1 with truncation of its C-terminal negative-regulatory domain. A similar recurrent deletion-truncation breakpoint was identified in two angiocentric gliomas in the related gene v-myb avian myeloblastosis viral oncogene homolog (MYB) on 6q23.3. Whole-genome sequencing of a MYBL1-rearranged diffuse astrocytoma grade II demonstrated MYBL1 tandem duplication and few other events. Truncated MYBL1 transcripts identified in this tumor induced anchorage-independent growth in 3T3 cells and tumor formation in nude mice. Truncated transcripts were also expressed in two additional tumors with MYBL1 partial duplication. Our results define clinically relevant molecular subclasses of diffuse PLGGs and highlight a potential role for the MYB family in the biology of low-grade gliomas. PMID:23633565

  2. Knowledge of neonatal danger signs among mothers attending well baby clinic in Nakuru Central District, Kenya: cross sectional descriptive study.

    PubMed

    Kibaru, Elizabeth Gathoni; Otara, Amos Magembe

    2016-10-25

    Neonatal mortality has remained high in Kenya despite various efforts being applied to reduce this negative trend. Early detection of neonatal illness is an important step towards improving new born survival. Toward this end there is need for the mothers to be able to identify signs in neonates that signifies severe neonatal illnesses. The objective of the study was to determine the level of knowledge of mothers attending well baby clinics on postnatal neonatal danger signs and determine the associated factors. Cross sectional descriptive study. Purposive sampling of Health care facilities that provide antenatal, delivery and postnatal services were identified. In each of the selected health facility structured questionnaires were administered to mothers with children aged six weeks to nine months attending well baby clinics. Frequencies, Chi square and multivariate logistic regression were determined using the SPSS software (version 20). During the period of study 414 mothers attending well baby clinics were interviewed. Information on neonatal dangers was not provided to 237 (57.2%) of the postnatal mothers during their antenatal clinic attendance by the health care providers. Majority of mothers 350 (84.5%) identified less than three neonatal danger signs. Hotness of the body (fever) was the commonly recognized danger sign by 310 (74.9%) postnatal mothers. Out of 414 mothers 193 (46.6%), 166 (40.1%), 146 (35.3%) and 24 (5.8%) identified difficulty in breathing, poor sucking, jaundice and lethargy/unconsciousness as new born danger signs respectively. Only 46 (11.1%) and 40 (9.7%) identified convulsion and hypothermia as new born danger signs respectively. Education Level, PNC accompaniment by Spouse, Danger signs information to Mother, Explanation of MCH booklet by Care provider during ANC and Mother read MCH Booklet were factors positively associated with improved knowledge of neonatal danger sign. In multivariate logistic regression none of the factors tested were statistically significant in relation to level of knowledge. Knowledge of neonatal danger signs was low among mothers attending well baby clinic despite the information being available in the MCH booklets provided to the mothers during antenatal clinics.

  3. Tibiofemoral Osteoarthritis and Varus-Valgus Laxity

    PubMed Central

    Freisinger, Gregory M.; Schmitt, Laura C.; Wanamaker, Andrea B.; Siston, Robert A.; Chaudhari, Ajit M. W.

    2017-01-01

    The purpose of this study was to systematically review and synthesize the literature measuring varus-valgus laxity in individuals with tibiofemoral osteoarthritis (OA). Specifically, we aimed to identify varus-valgus laxity differences between persons with OA and controls, by radiographic disease severity, by frontal plane knee alignment, and by sex. We also aimed to identify if there was a relationship between varus-valgus laxity and clinical performance and self-reported function. We systematically searched for peer-reviewed original research articles in PubMed, Scopus, and CINAHL to identify all existing literature regarding knee OA and objective measurement of varus-valgus laxity in vivo. Forty articles were identified that met the inclusion criteria and data were extracted. Varus-valgus laxity was significantly greater in individuals with OA compared with controls in a majority of studies, while no study found laxity to be significantly greater in controls. Varus-valgus laxity of the knee was reported in persons with OA and varying degrees of frontal plane alignment, disease severity, clinical performance, and self-reported function but no consensus finding could be identified. Females with knee OA appear to have more varus-valgus laxity than males. Meta-analysis was not possible due to the heterogeneity of the subject populations and differences in laxity measurement devices, applied loading, and laxity definitions. Increased varus-valgus laxity is a characteristic of knee joints with OA. Large variances exist in reported varus-valgus laxity and may be due to differences in measurement devices. Prospective studies on joint laxity are needed to identify if increased varus-valgus laxity is a causative factor in OA incidence and progression. PMID:27680888

  4. Comparison of glaucoma knowledge and referral practices among family physicians with ophthalmologists' expectations.

    PubMed

    Basilious, Alfred; Cheng, Jason; Buys, Yvonne M

    2015-06-01

    To compare family physicians' glaucoma knowledge and clinical skills with ophthalmologists' expectations. An electronic cross-sectional survey of family physicians and ophthalmologists. Participants included members of the Canadian Ophthalmological Society, Canadian Glaucoma Society, and the American Glaucoma Society, as well as family physicians in the Canadian Medical Directory and the Society of Rural Physicians of Canada listserv. Two complementary surveys were developed to evaluate family physicians' glaucoma knowledge and basic examination skills, and ophthalmologists' expected level of family physician clinical knowledge and skills. χ(2) tests identified differences between family physician and ophthalmologist responses. Differences in family physician knowledge based on practice location and frequency of patient visits with a diagnosis of glaucoma were also evaluated. A total of 142 ophthalmologists and 110 family physicians completed the survey. The majority (82%) of family physicians reported seeing patients with diagnosed glaucoma weekly, monthly, or semiannually. Significantly fewer family physicians than expected (p < 0.001) identified African descent (46%) and corticosteroid use (84%) as glaucoma risk factors. Family physicians were significantly less likely to refer based on risk factors (72%) than expected by ophthalmologists (91%; p < 0.001). Only 28% of family physicians were comfortable performing direct ophthalmoscopy, and 37% were comfortable checking for a relative afferent pupillary defect. A significant percentage of family physicians lacked knowledge of glaucoma medications (30%) and side effects (57%). This study revealed significant disparities in family physician glaucoma knowledge, clinical examination skills, and referral practices. Educational materials should target these knowledge gaps. Copyright © 2015 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.

  5. Homozygosity for the WRN Helicase-Inactivating Variant, R834C, does not confer a Werner syndrome clinical phenotype

    PubMed Central

    Kamath-Loeb, Ashwini S.; Zavala-van Rankin, Diego G.; Flores-Morales, Jeny; Emond, Mary J.; Sidorova, Julia M.; Carnevale, Alessandra; Cárdenas-Cortés, Maria del Carmen; Norwood, Thomas H.; Monnat, Raymond J.; Loeb, Lawrence A.; Mercado-Celis, Gabriela E.

    2017-01-01

    Loss-of-function mutations in the WRN helicase gene cause Werner syndrome- a progeroid syndrome with an elevated risk of cancer and other age-associated diseases. Large numbers of single nucleotide polymorphisms have been identified in WRN. We report here the organismal, cellular, and molecular phenotypes of variant rs3087425 (c. 2500C > T) that results in an arginine to cysteine substitution at residue 834 (R834C) and up to 90% reduction of WRN helicase activity. This variant is present at a high (5%) frequency in Mexico, where we identified 153 heterozygous and three homozygous individuals among 3,130 genotyped subjects. Family studies of probands identified ten additional TT homozygotes. Biochemical analysis of WRN protein purified from TT lymphoblast cell lines confirmed that the R834C substitution strongly and selectively reduces WRN helicase, but not exonuclease activity. Replication track analyses showed reduced replication fork progression in some homozygous cells following DNA replication stress. Among the thirteen TT homozygotes, we identified a previously unreported and statistically significant gender bias in favor of males (p = 0.0016), but none of the clinical findings associated with Werner syndrome. Our results indicate that WRN helicase activity alone is not rate-limiting for the development of clinical WS. PMID:28276523

  6. Attachment in psychosis: A latent profile analysis of attachment styles and association with symptoms in a large psychosis cohort.

    PubMed

    Bucci, Sandra; Emsley, Richard; Berry, Katherine

    2017-01-01

    Attachment has been identified as one of various possible mechanisms involved in understanding models of psychosis, but measures that reliably and validly assess attachment styles in psychosis are limited. The aim of this study was to identify attachment patterns in psychosis and examine demographic and clinical correlates across attachment groups. Latent profile analysis on attachment data from 588 participants who met criteria for non-affective psychosis was used to classify people into attachment classes. Four latent classes of attachment were identified: secure, insecure-anxious, insecure-avoidant and disorganised. Secure attachment was the most common attachment style, suggesting that a significant number of clients with psychosis are inherently resilient. Disorganised attachment was associated with a higher proportion of sexual and physical abuse and more severe positive symptoms compared to other attachment classes. This is not only the largest study to examine attachment styles, their demographic and clinical profile, and the clinical profile of disorganised attachment more specifically, in psychosis, but also the first study to use a validated self-report measure of attachment in psychosis to identify four classes of attachment style. Findings advance developmental models of attachment and psychosis; participants with disorganised attachment report more frequent trauma history and more severe psychotic symptoms. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Intimate partner violence against Japanese and non-Japanese women in Japan: a cross-sectional study in the perinatal setting.

    PubMed

    Inami, Eriko; Kataoka, Yaeko; Eto, Hiromi; Horiuchi, Shigeko

    2010-06-01

    To identify the prevalence of intimate partner violence (IPV) against Japanese women (JW) and non-Japanese women (NJW) in a perinatal setting. Additional purposes were to identify the associated factors of IPV, describe the characteristics of IPV against NJW, and assess the acceptability of the Violence Against Women Screen (VAWS) instrument as a screening tool. A cross-sectional survey was conducted from September to November 2007 in an urban hospital maternity clinic in Tokyo, Japan. Women who attended the maternity clinic received the VAWS instrument, which was translated into four languages (Japanese with Kanji and Hiragana, English, Chinese, and Tagalog) and was used to identify IPV. A total of 400 women participated in the study: 357 were JW and 43 were NJW. The prevalence rate of IPV among the JW was 31.4% and 21.4% among the NJW. There was no statistical significance between the two groups. A multiple logistic regression with adjusted odds ratio identified two associated factors for IPV: being multipara and previous experience of physical violence from a partner. The prevalence of IPV was not statistically different among JW and NJW. Screening for IPV, early intervention, and support should be expanded in hospitals and maternity clinics in Japan.

  8. Clinical evaluation of the Vitek ANI card for identification of anaerobic bacteria.

    PubMed Central

    Schreckenberger, P C; Celig, D M; Janda, W M

    1988-01-01

    An evaluation of the Vitek Anaerobe Identification (ANI) card was performed with 341 bacterial isolates, including 313 clinical isolates and 28 stock strains of anaerobic microorganisms. Identifications obtained with the ANI card were compared with those determined by conventional methods. The card identified 73.2% of 149 anaerobic gram-negative bacilli, 63.6% of 44 Clostridium spp., 65.8% of 38 anaerobic nonsporeforming gram-positive bacilli, and 69.1% of 110 anaerobic cocci, with no further testing required. When genus-level identifications were included, 83.9% of the anaerobic gram-negative bacilli, 70.5% of Clostridium spp., 73.7% of the anaerobic nonsporeforming gram-positive bacilli, and 73.6% of the anaerobic cocci were identified. Nineteen isolates (5.6%) produced identifications of good confidence but marginal separation or questionable biotype, in which the correct identification was listed with one or two other possible choices and extra tests were required and suggested. A total of 28 (8.2%) were not identified and 29 isolates (8.5%) were misidentified by the ANI card. Among the commonly isolated clinically significant anaerobes, the ANI card identified 100% of 55 Bacteroides fragilis and 100% of 8 Clostridium perfringens. Use of supplemental tests and expansion of the data base to include additional strains of organisms that are difficult to separate even with conventional methods may improve the accuracy of the ANI card as a method for identification of anaerobic bacteria in the clinical laboratory. PMID:3343321

  9. GATA3 expression in clinically useful groups of breast carcinoma: a comparison with GCDFP15 and mammaglobin for identifying paired primary and metastatic tumors.

    PubMed

    Yang, Yuqiong; Lu, Shanming; Zeng, Wenqin; Xie, Shoucheng; Xiao, Shengjun

    2017-02-01

    GATA3 has been recognized as the novel marker for identifying primary and metastatic breast carcinomas, consistently showing that GATA3 was significantly more sensitive than traditional markers gross cystic disease fluid protein 15 (GCDFP15) and mammaglobin (MGB). However, clinically useful groups of breast carcinomas status were not identified, which were determining appropriate treatment strategy, affecting the prognosis. In this study, we undertook a comparative study of the marker GATA3 and GCDFP15 and MGB in clinically useful groups of paired primary and metastatic breast cancer. We retrieved 64 cases of matched primary and metastatic breast cancer from the surgical pathology archive at our institution. According to the emerging 2015 St. Gallen Consensus, the clinically useful groups were divided into ER and/or PR (+), HER2 (-), abbreviated as A; ER and/or PR (+), HER2 (+), abbreviated as B; ER and PR (-), HER2 (+), abbreviated as C; ER, PR and HER2 (-), abbreviated as D; each group contained 16 cases (n=16). Tissue microarrays were created, with three 1-mm punch specimens from each case. The tissue microarrays were cut at 4-μm thickness and stained with monoclonal antibodies to GATA3, GCDFP15, and MGB. Staining intensity (0-3+) and extent (0%-100%) were scored with an H-score calculated (range, 0-300). Sensitivities by varying H-score cutoffs (any; ≥50; ≥150) for a positive result in the clinically useful groups of matched primary or metastatic breast cancer among GATA3, GCDFP15, and MGB. GATA3 was significantly more sensitive than GCDFP15 and MGB A and B groups (P<.05) rather than C and D groups (P>.05). However, GATA3 in conjunction with GCDFP15 and MGB detection could improve the sensitivity of C group (P<.05) rather than D group (P>.05). Significantly, good coincidence was observed between primary and metastatic tumor GATA3 expression (κ value = 0.826 >0.75) as compared with the coincidence of GCDFP15 (κ value =0.492 <0.75) and MGB (κ value =0.593 <0.75) (both P<.05). In conclusion, GATA3 expression did not show the same sensitivity for the clinically useful groups of breast cancer. GATA3 expression is positively correlated with ER-positive, PR-positive, and HER2-positive carcinomas. In addition, the matched primary and metastatic tumor expression of GATA3 shows good coincidence. We propose the careful selection of GATA3 for identifying hormone receptor negativity of breast cancer, especially in the case of triple-negative breast cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Posturography and locomotor tests of dynamic balance after long-duration spaceflight.

    PubMed

    Cohen, Helen S; Kimball, Kay T; Mulavara, Ajitkumar P; Bloomberg, Jacob J; Paloski, William H

    2012-01-01

    The currently approved objective clinical measure of standing balance in astronauts after space flight is the Sensory Organization Test battery of computerized dynamic posturography. No tests of walking balance are currently approved for standard clinical testing of astronauts. This study determined the sensitivity and specificity of standing and walking balance tests for astronauts before and after long-duration space flight. Astronauts were tested on an obstacle avoidance test known as the Functional Mobility Test (FMT) and on the Sensory Organization Test using sway-referenced support surface motion with eyes closed (SOT 5) before and six months after (n=15) space flight on the International Space Station. They were tested two to seven days after landing. Scores on SOT tests decreased and scores on FMT increased significantly from pre- to post-flight. In other words, post-flight scores were worse than pre-flight scores. SOT and FMT scores were not significantly related. ROC analyses indicated supra-clinical cut-points for SOT 5 and for FMT. The standard clinical cut-point for SOT 5 had low sensitivity to post-flight astronauts. Higher cut-points increased sensitivity to post-flight astronauts but decreased specificity to pre-flight astronauts. Using an FMT cut-point that was moderately highly sensitive and highly specific plus SOT 5 at the standard clinical cut-point was no more sensitive than SOT 5, alone. FMT plus SOT 5 at higher cut-points was more specific and more sensitive. The total correctly classified was highest for FMT, alone, and for FMT plus SOT 5 at the highest cut-point. These findings indicate that standard clinical comparisons are not useful for identifying problems. Testing both standing and walking balance will be more likely to identify balance deficits.

  11. Dental Students' Clinical Expectations and Experiences Treating Persons with Disabilities.

    PubMed

    Perusini, Darsi J; Llacuachaqui, Marcia; Sigal, Michael J; Dempster, Laura J

    2016-03-01

    Persons with disabilities (PWDs) have a disproportionate level of dental disease relative to the general population. Access to care is a cause along with dentists' willingness to treat PWDs. The aim of this study was to investigate the expectations and experiences of dental students in providing treatment to these patients in a hospital-based dental clinic for PWDs. Senior dental students at the Faculty of Dentistry, University of Toronto (n=92) were surveyed prior to (Phase I) and at the end of (Phase II) mandatory clinical rotations at the Mount Sinai Hospital's Dentistry Clinic for Persons with Special Needs. Response rates were 88% for Phase I and 58% for Phase II. Before the rotations, 70% of the respondents reported little or no experience with PWDs, and 46% said they did not feel comfortable providing basic dental treatment to PWDs. However, in Phase II, significantly more students reported being comfortable than in Phase I (p=0.001). Overall, the majority of respondents (Phase I 95%; Phase II 98%) indicated they would at least attempt to provide basic dental care to PWDs after graduation. The majority also identified the opportunity to provide care and interact with PWDs as the most enjoyable aspect of their experience at the clinic. They reported that the experience helped reduce their concerns about treating PWDs including being more realistic about the time required and ideal quality of the treatment they could provide. These results suggest that their experience in the clinic significantly increased students' comfort in treating PWDs. The respondents expressed a willingness to treat PWDs once graduated and generally identified their experience as being more positive than their expectations.

  12. Dolichoectatic aneurysms of the vertebrobasilar system: clinical and radiographic factors that predict poor outcomes.

    PubMed

    Xu, David S; Levitt, Michael R; Kalani, M Yashar S; Rangel-Castilla, Leonardo; Mulholland, Celene B; Abecassis, Isaac J; Morton, Ryan P; Nerva, John D; Siddiqui, Adnan H; Levy, Elad I; Spetzler, Robert F; Albuquerque, Felipe C; McDougall, Cameron G

    2018-02-01

    OBJECTIVE Fusiform dolichoectatic vertebrobasilar aneurysms are rare, challenging lesions. The natural history of these lesions and medium- and long-term patient outcomes are poorly understood. The authors sought to evaluate patient prognosis after diagnosis of fusiform dolichoectatic vertebrobasilar aneurysms and to identify clinical and radiographic predictors of neurological deterioration. METHODS The authors reviewed multiple, prospectively maintained, single-provider databases at 3 large-volume cerebrovascular centers to obtain data on patients with unruptured, fusiform, basilar artery dolichoectatic aneurysms diagnosed between January 1, 2000, and January 1, 2015. RESULTS A total of 50 patients (33 men, 17 women) were identified; mean clinical follow-up was 50.1 months and mean radiographic follow-up was 32.4 months. At last follow-up, 42% (n = 21) of aneurysms had progressed and 44% (n = 22) of patients had deterioration of their modified Rankin Scale scores. When patients were dichotomized into 2 groups- those who worsened and those who did not-univariate analysis showed 5 variables to be statistically significantly different: sex (p = 0.007), radiographic brainstem compression (p = 0.03), clinical posterior fossa compression (p < 0.001), aneurysmal growth on subsequent imaging (p = 0.001), and surgical therapy (p = 0.006). A binary logistic regression was then created to evaluate these variables. The only variable found to be a statistically significant predictor of clinical worsening was clinical symptoms of posterior fossa compression at presentation (p = 0.01). CONCLUSIONS Fusiform dolichoectatic vertebrobasilar aneurysms carry a poor prognosis, with approximately one-half of the patients deteriorating or experiencing progression of their aneurysm within 5 years. Despite being high risk, intervention-when carefully timed (before neurological decline)-may be beneficial in select patients.

  13. Cognitive processing therapy for posttraumatic stress disorder delivered to rural veterans via telemental health: a randomized noninferiority clinical trial.

    PubMed

    Morland, Leslie A; Mackintosh, Margaret-Anne; Greene, Carolyn J; Rosen, Craig S; Chard, Kathleen M; Resick, Patricia; Frueh, B Christopher

    2014-05-01

    To compare clinical and process outcomes of cognitive processing therapy-cognitive only version (CPT-C) delivered via videoteleconferencing (VTC) to in-person in a rural, ethnically diverse sample of veterans with posttraumatic stress disorder (PTSD). A randomized clinical trial with a noninferiority design was used to determine if providing CPT-C via VTC is effective and "as good as" in-person delivery. The study took place between March 2009 and June 2013. PTSD was diagnosed per DSM-IV. Participants received 12 sessions of CPT-C via VTC (n = 61) or in-person (n = 64). Assessments were administered at baseline, midtreatment, immediately posttreatment, and 3 and 6 months posttreatment. The primary clinical outcome was posttreatment PTSD severity, as measured by the Clinician-Administered PTSD Scale. Clinical and process outcomes found VTC to be noninferior to in-person treatment. Significant reductions in PTSD symptoms were identified at posttreatment (Cohen d = 0.78, P < .05) and maintained at 3- and 6-month follow-up (d = 0.73, P < .05 and d = 0.76, P < .05, respectively). High levels of therapeutic alliance, treatment compliance, and satisfaction and moderate levels of treatment expectancies were reported, with no differences between groups (for all comparisons, F < 1.9, P > .17). Providing CPT-C to rural residents with PTSD via VTC produced outcomes that were "as good as" in-person treatment. All participants demonstrated significant reductions in PTSD symptoms posttreatment and at follow-up. Results indicate that VTC can offer increased access to specialty mental health care for residents of rural or remote areas. ClinicalTrials.gov identifier: NCT00879255. © Copyright 2014 Physicians Postgraduate Press, Inc.

  14. Outbreak of Pneumocystis jirovecii Infection among Heart Transplant Recipients: Molecular Investigation and Management of an Inter-human Transmission.

    PubMed

    Vindrios, William; Argy, Nicolas; Le Gal, Solène; Lescure, François-Xavier; Massias, Laurent; Le, Minh Patrick; Wolff, Michel; Yazdanpanah, Yazdan; Nevez, Gilles; Houze, Sandrine; Dorent, Richard; Lucet, Jean-Christophe

    2017-05-26

    An outbreak of Pneumocystis jirovecii pneumonia (PCP) occurred among heart transplant recipients (HTR) at the outpatient clinic of a university hospital, from March to September 2015. Clinical, therapeutic, biological and molecular data were analyzed to determine its origin and control the outbreak. Clinical and biological data regarding all HTR followed in the outpatient clinic were collected. PCP diagnosis was based on microscopy and real-time PCR. Investigations were performed by building a transmission map, completed by genotyping Pneumocystis isolates and by a control of chemoprophylaxis observance. Asymptomatic exposed patients were screened for colonisation using real-time PCR. Among 124 HTR, 7 PCP cases were confirmed. Screening identified three additional patients colonized by Pneumocystis jirovecii. All patients were cured and no further cases were identified after that trimethoprim-sulfamethoxazole prophylaxis was introduced in the entire cohort. Genotyping demonstrated the same strain in all PCP cases and colonized patients. All cases were linked with possible transmission chains from 2 possible index patients. Inter-human transmission was significantly associated with more frequent visits in the outpatient clinic. Six cases were receiving atovaquone as a prophylaxis. The occurrence of PCP was significantly associated with atovaquone prophylaxis. This is the first outbreak with detailed molecular analysis in HTR so far. Genotyping and transmission chain confirmed the inter-human transmission in all colonized/infected PCP cases. Outpatient clinic layout and high encounters probably caused this PCP cluster, which was controlled after systematic trimethoprim-sulfamethoxazole prophylaxis in exposed patients. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  15. Suicide Prevention in Special Populations.

    ERIC Educational Resources Information Center

    Bogdaniak, Roman C.; Coronado, Maria G.

    Suicide prevention techniques, from a clinical perspective, need to be as diversified as the population they serve. In certain special population groups, suicide has reached epidemic proportions, and there is a significant public health need for specific suicide prevention strategies. Special populations need to be identified and their suicide…

  16. [Clinical presentation of different severities of hemorrhagic fever with renal syndrome: how to recognise it].

    PubMed

    Lausević, Mirjana; Lausević, Zeljko; Stojimirović, Biljana

    2012-07-01

    Besides viral serotype, HLA haplotype and cytokine genes polymorphism are associated with clinical presentation of hemorrhagic fever with renal syndrome. Since these analyses are unavailable in routine clinical practice, the aim of this study was to assess clinical, laboratory and radiographic findings associated with clinical presentation of disease severity. A total of 30 patients (27 men and 3 women), average age 40 +/- 14.9 years, treated for hemorrhagic fever with renal syndrome from January 1, 1999 to December 31, 2009 in Clinical Center of Serbia, were included in the study. Nine patients (30%) had mild, 14 (46.7%) moderate and 7 (23.3%) severe form of the disease; 24 (800%) recovered, 6 (20%) died in the acute phase of the illness, and 19 patients (63.3%) required hemodialysis. The average titer of antiviral antibodies in patients infected with Belgrade serotype virus were significantly higher in those with severe clinical presentation. Hypotension, anuria, macrohaematuria, pulmonary infiltration, pleural effusion, hepatomegalia and positive meningeal signs were more frequent in the patients with severe form of the disease. Statistically significant differences between groups with mild, moderate and severe clinical picture were found in serum total protein, albumin, calcium, glutamate pyruvate and glutamate oxaloacetate transaminase on admittance; serum creatinine and phosphorus concentration on day 14 and day 21; serum sodium and calciums on day 14; hemoglobine concentration on day 21. A statistically significant correlation was found between clinical presentation of the disease severity and platelet count, white blood cell count, hemoglobine concentration, serum calcium and serum transaminases on admittance. Multivariate analysis identified variables' combinations associated with clinical presentation of the disease. Our study confirmed that we can distinguish patients who will manifest different severities of the disease on the basis of careful consideration of laboratory and clinical findings on admission.

  17. Healthcare students' evaluation of the clinical learning environment and supervision - a cross-sectional study.

    PubMed

    Pitkänen, Salla; Kääriäinen, Maria; Oikarainen, Ashlee; Tuomikoski, Anna-Maria; Elo, Satu; Ruotsalainen, Heidi; Saarikoski, Mikko; Kärsämänoja, Taina; Mikkonen, Kristina

    2018-03-01

    The purpose of clinical placements and supervision is to promote the development of healthcare students´ professional skills. High-quality clinical learning environments and supervision were shown to have significant influence on healthcare students´ professional development. This study aimed to describe healthcare students` evaluation of the clinical learning environment and supervision, and to identify the factors that affect these. The study was performed as a cross-sectional study. The data (n = 1973) were gathered through an online survey using the Clinical Learning Environment, Supervision and Nurse Teacher scale during the academic year 2015-2016 from all healthcare students (N = 2500) who completed their clinical placement at a certain university hospital in Finland. The data were analysed using descriptive statistics and binary logistic regression analysis. More than half of the healthcare students had a named supervisor and supervision was completed as planned. The students evaluated the clinical learning environment and supervision as 'good'. The students´ readiness to recommend the unit to other students and the frequency of separate private unscheduled sessions with the supervisor were the main factors that affect healthcare students` evaluation of the clinical learning environment and supervision. Individualized and goal-oriented supervision in which the student had a named supervisor and where supervision was completed as planned in a positive environment that supported learning had a significant impact on student's learning. The clinical learning environment and supervision support the development of future healthcare professionals' clinical competence. The supervisory relationship was shown to have a significant effect on the outcomes of students' experiences. We recommend the planning of educational programmes for supervisors of healthcare students for the enhancement of supervisors' pedagogical competencies in supervising students in the clinical practice. Copyright © 2018 Elsevier Ltd. All rights reserved.

  18. Impact of Patient Reminders on Papanicolaou Test Completion for High-Risk Patients Identified by a Clinical Decision Support System.

    PubMed

    MacLaughlin, Kathy L; Kessler, Maya E; Komandur Elayavilli, Ravikumar; Hickey, Branden C; Scheitel, Marianne R; Wagholikar, Kavishwar B; Liu, Hongfang; Kremers, Walter K; Chaudhry, Rajeev

    2018-05-01

    A clinical decision support system (CDSS) for cervical cancer screening identifies patients due for routine cervical cancer screening. Yet, high-risk patients who require more frequent screening or earlier follow-up to address past abnormal results are not identified. We aimed to assess the effect of a complex CDSS, incorporating national guidelines for high-risk patient screening and abnormal result management, its implementation to identify patients overdue for testing, and the outcome of sending a targeted recommendation for follow-up. At three primary care clinics affiliated with an academic medical center, a reminder recommending an appointment for Papanicolaou (Pap) testing or Pap and human papillomavirus cotesting was sent to high-risk women aged 18 through 65 years (intervention group) identified by CDSS as overdue for testing. Historical control patients, who did not receive a reminder, were identified by CDSS 1 year before the date when reminders were sent to the intervention group. Test completion rates were compared between the intervention and control groups through a generalized estimating equation extension. Across the three sites, the average completion rate of recommended follow-up testing was significantly higher in the intervention group at 23.7% (61/257) than the completion rate at 3.3% (17/516) in the control group (p < 0.001). A CDSS with enhanced capabilities to identify high-risk women due for cervical cancer testing beyond routine screening intervals, with subsequent patient notification, has the potential to decrease cervical precancer and cancer by improving adherence to guideline-compliant follow-up and needed treatment.

  19. BRCA1 and BRCA2 genetic testing—pitfalls and recommendations for managing variants of uncertain clinical significance

    PubMed Central

    Eccles, D. M.; Mitchell, G.; Monteiro, A. N. A.; Schmutzler, R.; Couch, F. J.; Spurdle, A. B.; Gómez-García, E. B.

    2015-01-01

    Background Increasing use of BRCA1/2 testing for tailoring cancer treatment and extension of testing to tumour tissue for somatic mutation is moving BRCA1/2 mutation screening from a primarily prevention arena delivered by specialist genetic services into mainstream oncology practice. A considerable number of gene tests will identify rare variants where clinical significance cannot be inferred from sequence information alone. The proportion of variants of uncertain clinical significance (VUS) is likely to grow with lower thresholds for testing and laboratory providers with less experience of BRCA. Most VUS will not be associated with a high risk of cancer but a misinterpreted VUS has the potential to lead to mismanagement of both the patient and their relatives. Design Members of the Clinical Working Group of ENIGMA (Evidence-based Network for the Interpretation of Germline Mutant Alleles) global consortium (www.enigmaconsortium.org) observed wide variation in practices in reporting, disclosure and clinical management of patients with a VUS. Examples from current clinical practice are presented and discussed to illustrate potential pitfalls, explore factors contributing to misinterpretation, and propose approaches to improving clarity. Results and conclusion Clinicians, patients and their relatives would all benefit from an improved level of genetic literacy. Genetic laboratories working with clinical geneticists need to agree on a clinically clear and uniform format for reporting BRCA test results to non-geneticists. An international consortium of experts, collecting and integrating all available lines of evidence and classifying variants according to an internationally recognized system, will facilitate reclassification of variants for clinical use. PMID:26153499

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

    PubMed Central

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

    2008-01-01

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

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