Statistical approaches for evaluating body composition markers in clinical cancer research.

Science.gov (United States)

Bayar, Mohamed Amine; Antoun, Sami; Lanoy, Emilie

2017-04-01

The term 'morphomics' stands for the markers of body composition in muscle and adipose tissues. in recent years, as part of clinical cancer research, several associations between morphomics and outcome or toxicity were found in different treatment settings leading to a growing interest. we aim to review statistical approaches used to evaluate these markers and suggest practical statistical recommendations. Area covered: We identified statistical methods used recently to take into account properties of morphomics measurements. We also reviewed adjustment methods on major confounding factors such as gender and approaches to model morphomic data, especially mixed models for repeated measures. Finally, we focused on methods for determining a cut-off for a morphomic marker that could be used in clinical practice and how to assess its robustness. Expert commentary: From our review, we proposed 13 key points to strengthen analyses and reporting of clinical research assessing associations between morphomics and outcome or toxicity.

Angiographic Guidewire with Measuring Markers: Design and Clinical Experience

International Nuclear Information System (INIS)

Kamei, Seiji; Ishiguchi, Tsuneo; Murata, Katsuhito; Matsuda, Joe; Ohno, Ryota; Kimura, Junko; Nakamura, Atsushi; Ohno, Kazuko; Kawamura, Toshiki; Ikeda, Mitsuru

2006-01-01

Purpose. We have developed an angiographic guidewire with measuring markers to determine accurately how far a guidewire is inserted within a catheter. We investigated whether use of this guidewire reduces the risk of vascular injury and the fluoroscopic time during guidewire manipulations. Methods. Four markers were put on the surface of the guidewire at 80, 100, 110, and 120 cm from the tip. The actual lengths of 54 catheters from seven manufacturers were measured and compared with the nominal lengths. Sixty consecutive patients who underwent angiography were randomized into two groups: in one group guidewires with surface markers were used (marker group) and in the other group, conventional guidewires (control group). For each guidewire insertion, the fluoroscopic time before the guidewire was pushed forward into the vessel lumen was recorded. The number of occasions on which unintentionally the guidewire had already been pushed out of the catheter at the start of fluoroscopy was also evaluated. Results. The actual lengths of all catheters were greater than the nominal lengths by 1.0-11.0 cm. Mean fluoroscopic time for each guidewire insertion was 3.3 sec in the marker group and 5.7 sec in the control group (p < 0.05). Guidewires were unintentionally pushed out of the catheters without fluoroscopy three times (3.6%), in each case in the control group. Conclusion. The guidewire with measuring markers is effective for enhancing safety and in reducing fluoroscopic radiation during angiographic procedures. It is recommended that operators be aware that actual lengths of catheters may vary significantly from the nominal lengths listed; they should be aware of this with any guidewire, but particularly with the angiographic measuring guidewire

Patient safety trilogy: perspectives from clinical engineering.

Science.gov (United States)

Gieras, Izabella; Sherman, Paul; Minsent, Dennis

2013-01-01

This article examines the role a clinical engineering or healthcare technology management (HTM) department can play in promoting patient safety from three different perspectives: a community hospital, a national government health system, and an academic medical center. After a general overview, Izabella Gieras from Huntington Hospital in Pasadena, CA, leads off by examining the growing role of human factors in healthcare technology, and describing how her facility uses clinical simulations in medical equipment evaluations. A section by Paul Sherman follows, examining patient safety initiatives from the perspective of the Veterans Health Administration with a focus on hazard alerts and recalls. Dennis Minsent from Oregon Health & Science University writes about patient safety from an academic healthcare perspective, and details how clinical engineers can engage in multidisciplinary safety opportunities.

A combination of molecular markers and clinical features improve the classification of pancreatic cysts.

Science.gov (United States)

Springer, Simeon; Wang, Yuxuan; Dal Molin, Marco; Masica, David L; Jiao, Yuchen; Kinde, Isaac; Blackford, Amanda; Raman, Siva P; Wolfgang, Christopher L; Tomita, Tyler; Niknafs, Noushin; Douville, Christopher; Ptak, Janine; Dobbyn, Lisa; Allen, Peter J; Klimstra, David S; Schattner, Mark A; Schmidt, C Max; Yip-Schneider, Michele; Cummings, Oscar W; Brand, Randall E; Zeh, Herbert J; Singhi, Aatur D; Scarpa, Aldo; Salvia, Roberto; Malleo, Giuseppe; Zamboni, Giuseppe; Falconi, Massimo; Jang, Jin-Young; Kim, Sun-Whe; Kwon, Wooil; Hong, Seung-Mo; Song, Ki-Byung; Kim, Song Cheol; Swan, Niall; Murphy, Jean; Geoghegan, Justin; Brugge, William; Fernandez-Del Castillo, Carlos; Mino-Kenudson, Mari; Schulick, Richard; Edil, Barish H; Adsay, Volkan; Paulino, Jorge; van Hooft, Jeanin; Yachida, Shinichi; Nara, Satoshi; Hiraoka, Nobuyoshi; Yamao, Kenji; Hijioka, Susuma; van der Merwe, Schalk; Goggins, Michael; Canto, Marcia Irene; Ahuja, Nita; Hirose, Kenzo; Makary, Martin; Weiss, Matthew J; Cameron, John; Pittman, Meredith; Eshleman, James R; Diaz, Luis A; Papadopoulos, Nickolas; Kinzler, Kenneth W; Karchin, Rachel; Hruban, Ralph H; Vogelstein, Bert; Lennon, Anne Marie

2015-11-01

The management of pancreatic cysts poses challenges to both patients and their physicians. We investigated whether a combination of molecular markers and clinical information could improve the classification of pancreatic cysts and management of patients. We performed a multi-center, retrospective study of 130 patients with resected pancreatic cystic neoplasms (12 serous cystadenomas, 10 solid pseudopapillary neoplasms, 12 mucinous cystic neoplasms, and 96 intraductal papillary mucinous neoplasms). Cyst fluid was analyzed to identify subtle mutations in genes known to be mutated in pancreatic cysts (BRAF, CDKN2A, CTNNB1, GNAS, KRAS, NRAS, PIK3CA, RNF43, SMAD4, TP53, and VHL); to identify loss of heterozygozity at CDKN2A, RNF43, SMAD4, TP53, and VHL tumor suppressor loci; and to identify aneuploidy. The analyses were performed using specialized technologies for implementing and interpreting massively parallel sequencing data acquisition. An algorithm was used to select markers that could classify cyst type and grade. The accuracy of the molecular markers was compared with that of clinical markers and a combination of molecular and clinical markers. We identified molecular markers and clinical features that classified cyst type with 90%-100% sensitivity and 92%-98% specificity. The molecular marker panel correctly identified 67 of the 74 patients who did not require surgery and could, therefore, reduce the number of unnecessary operations by 91%. We identified a panel of molecular markers and clinical features that show promise for the accurate classification of cystic neoplasms of the pancreas and identification of cysts that require surgery. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

CLINICAL APPLICATION OF TUMOUR MARKERS: A REvIEw

African Journals Online (AJOL)

2009-12-02

Dec 2, 2009 ... for use in treatment monitoring of colorectal, hepatocellular, prostatic, ovarian and pancreatic carcinomas ... for cancer in the clinical setting (1,3-6). Primary ... presentation is one of the determinants of prognosis in cancer. If a tumour marker concentration is related to the tumour size then it may be useful for.

National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for use of tumor markers in clinical practice

DEFF Research Database (Denmark)

Sturgeon, Catharine M; Hoffman, Barry R; Chan, Daniel W

2008-01-01

BACKGROUND: This report presents updated National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines summarizing quality requirements for the use of tumor markers. METHODS: One subcommittee developed guidelines for analytical quality relevant to serum and tissue-based tumor...... questions to ensure selection of the appropriate test, adherence to good clinical and laboratory practices (e.g., minimization of the risk of incorrect patient and/or specimen identification, tube type, or timing), use of internationally standardized and well-characterized methods, careful adherence...... records. Also mandatory is extensive validation encompassing all stages of analysis before introduction of new technologies such as microarrays and mass spectrometry. Provision of high-quality tumor marker services is facilitated by dialogue involving researchers, diagnostic companies, clinical...

Clinical Relevance of Prognostic and Predictive Molecular Markers in Gliomas.

Science.gov (United States)

Siegal, Tali

2016-01-01

Sorting and grading of glial tumors by the WHO classification provide clinicians with guidance as to the predicted course of the disease and choice of treatment. Nonetheless, histologically identical tumors may have very different outcome and response to treatment. Molecular markers that carry both diagnostic and prognostic information add useful tools to traditional classification by redefining tumor subtypes within each WHO category. Therefore, molecular markers have become an integral part of tumor assessment in modern neuro-oncology and biomarker status now guides clinical decisions in some subtypes of gliomas. The routine assessment of IDH status improves histological diagnostic accuracy by differentiating diffuse glioma from reactive gliosis. It carries a favorable prognostic implication for all glial tumors and it is predictive for chemotherapeutic response in anaplastic oligodendrogliomas with codeletion of 1p/19q chromosomes. Glial tumors that contain chromosomal codeletion of 1p/19q are defined as tumors of oligodendroglial lineage and have favorable prognosis. MGMT promoter methylation is a favorable prognostic marker in astrocytic high-grade gliomas and it is predictive for chemotherapeutic response in anaplastic gliomas with wild-type IDH1/2 and in glioblastoma of the elderly. The clinical implication of other molecular markers of gliomas like mutations of EGFR and ATRX genes and BRAF fusion or point mutation is highlighted. The potential of molecular biomarker-based classification to guide future therapeutic approach is discussed and accentuated.

IMMUNOLOGICAL MARKERS OF DIABETES MELLITUS IN VARIOUS CLINICAL VARIANTS OF THE DISORDER

OpenAIRE

G. G. Baiburina

2011-01-01

Abstract. We studied immune markers of diabetes mellitus, as well as their relations to clinical features at the onset of disease. The patients with newly diagnosed diabetes were examined. Antibodies to glutamate decarboxylase, islet-cell cytoplasm antigen, along with antibodies to insulin and basal C-peptide were tested. Immunological markers of type 1 diabetes mellitus have been identified in 58% of cases. The immune markers of type 2 diabetes mellitus have been discovered in 47.5% of cases...

Oligonucleotide-based pharmaceuticals: Non-clinical and clinical safety signals and non-clinical testing strategies.

Science.gov (United States)

Mustonen, Enni-Kaisa; Palomäki, Tiina; Pasanen, Markku

2017-11-01

Antisense oligonucleotides, short interfering RNAs (siRNAs) and aptamers are oligonucleotide-based pharmaceuticals with a promising role in targeted therapies. Currently, five oligonucleotide-based pharmaceuticals have achieved marketing authorization in Europe or USA and many more are undergoing clinical testing. However, several safety concerns have been raised in non-clinical and clinical studies. Oligonucleotides share properties with both chemical and biological pharmaceuticals and therefore they pose challenges also from the regulatory point of view. We have analyzed the safety data of oligonucleotides and evaluated the applicability of current non-clinical toxicological guidelines for assessing the safety of oligonucleotide-based pharmaceuticals. Oligonucleotide-based pharmaceuticals display a similar toxicological profile, exerting adverse effects on liver and kidney, evoking hematological alterations, as well as causing immunostimulation and prolonging the coagulation time. It is possible to extrapolate some of these effects from non-clinical studies to humans. However, evaluation strategies for genotoxicity testing of "non-natural" oligonucleotides should be revised. Additionally, the selective use of surrogates and prediction of clinical endpoints for non-clinically observed immunostimulation is complicated by its multiple potential manifestations, demanding improvements in the testing strategies. Utilizing more relevant and mechanistic-based approaches and taking better account of species differences, could possibly improve the prediction of relevant immunological/proinflammatory effects in humans. Copyright © 2017 Elsevier Inc. All rights reserved.

Clinical usefulness of bone turnover marker concentrations in osteoporosis

DEFF Research Database (Denmark)

Morris, H A; Eastell, R; Jorgensen, N R

2017-01-01

Current evidence continues to support the potential for bone turnover markers (BTM) to provide clinically useful information particularly for monitoring the efficacy of osteoporosis treatment. Many of the limitations identified earlier remain, principally in regard to the relationship between BTM...... of combining such data for meta-analyses. Harmonization of units for reporting serum/plasma CTX (ng/L) and PINP (μg/L) is recommended. The development of international collaborations continues with an important initiative to combine BTM results from clinical trials in osteoporosis in a meta...

Safety and Efficacy of Ultrasound-Guided Fiducial Marker Implantation for CyberKnife Radiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Kim, Jae Hyun; Hong, Seong; Sook; Kim, Jung Hoon; Park, Hyun Jeong; Chang, Yun Woo; Chang, A Ram [Soonchunhyang University Seoul Hospital, Seoul (Korea, Republic of); Kwon, Seok Beom [Hallym University College of Medicine, Chuncheon (Korea, Republic of)

2012-06-15

To evaluate the safety and technical success rate of an ultrasound-guided fiducial marker implantation in preparation for CyberKnife radiation therapy. We retrospectively reviewed 270 percutaneous ultrasound-guided fiducial marker implantations in 77 patients, which were performed from June 2008 through March 2011. Of 270 implantations, 104 were implanted in metastatic lymph nodes, 96 were in the liver, 39 were in the pancreas, and 31 were in the prostate. During and after the implantation, major and minor procedure-related complications were documented. We defined technical success as the implantation enabling adequate treatment planning and CT simulation. The major and minor complication rates were 1% and 21%, respectively. One patient who had an implantation in the liver suffered severe abdominal pain, biloma, and pleural effusion, which were considered as major complication. Abdominal pain was the most common complication in 11 patients (14%). Among nine patients who had markers inserted in the prostate, one had transient hematuria for less than 24 hours, and the other experienced transient voiding difficulty. Of the 270 implantations, 261 were successful (97%). The reasons for unsuccessful implantations included migration of fiducial markers (five implantations, 2%) and failure to discriminate the fiducial markers (three implantations, 1%). Among the unsuccessful implantation cases, six patients required additional procedures (8%). The symptomatic complications following ultrasound-guided percutaneous implantation of fiducial markers are relatively low. However, careful consideration of the relatively higher rate of migration and discrimination failure is needed when performing ultrasound-guided percutaneous implantations of fiducial markers.

Comparison of clinical and biochemical markers of dehydration with the clinical dehydration scale in children: a case comparison trial.

Science.gov (United States)

Tam, Ron K; Wong, Hubert; Plint, Amy; Lepage, Nathalie; Filler, Guido

2014-06-16

The clinical dehydration scale (CDS) is a quick, easy-to-use tool with 4 clinical items and a score of 1-8 that serves to classify dehydration in children with gastroenteritis as no, some or moderate/severe dehydration. Studies validating the CDS (Friedman JN) with a comparison group remain elusive. We hypothesized that the CDS correlates with a wide spectrum of established markers of dehydration, making it an appropriate and easy-to-use clinical tool. This study was designed as a prospective double-cohort trial in a single tertiary care center. Children with diarrhea and vomiting, who clinically required intravenous fluids for rehydration, were compared with minor trauma patients who required intravenous needling for conscious sedation. We compared the CDS with clinical and urinary markers (urinary electrolytes, proteins, ratios and fractional excretions) for dehydration in both groups using receiver operating characteristic (ROC) curves to determine the area under the curve (AUC). We enrolled 73 children (male = 36) in the dehydration group and 143 (male = 105) in the comparison group. Median age was 32 months (range 3-214) in the dehydration and 96 months (range 2.6-214 months, p dehydration group and 0 in the comparison group (p dehydrated group: difference in heart rate, diastolic blood pressure, urine sodium/potassium ratio, urine sodium, fractional sodium excretion, serum bicarbonate, and creatinine measurements. The best markers for dehydration were urine Na and serum bicarbonate (ROC AUC = 0.798 and 0.821, respectively). CDS was most closely correlated with serum bicarbonate (Pearson r = -0.3696, p = 0.002). Although serum bicarbonate is not the gold standard for dehydration, this study provides further evidence for the usefulness of the CDS as a dehydration marker in children. Registered at ClinicalTrials.gov (NCT00462527) on April 18, 2007.

Percutaneous fiducial marker placement prior to stereotactic body radiotherapy for malignant liver tumors: an initial experience

International Nuclear Information System (INIS)

Ohta, Kengo; Shimohira, Masashi; Murai, Taro; Nishimura, Junichi; Iwata, Hiromitsu; Ogino, Hiroyuki; Hashizume, Takuya; Shibamoto, Yuta

2016-01-01

The aim of this study was to describe our initial experience with a gold flexible linear fiducial marker and to evaluate the safety and technical and clinical efficacy of stereotactic body radiotherapy using this marker for malignant liver tumors. Between July 2012 and February 2015, 18 patients underwent percutaneous fiducial marker placement before stereotactic body radiotherapy for malignant liver tumors. We evaluated the technical and clinical success rates of the procedure and the associated complications. Technical success was defined as successful placement of the fiducial marker at the target site, and clinical success was defined as the completion of stereotactic body radiotherapy without the marker dropping out of position. All 18 fiducial markers were placed successfully, so the technical success rate was 100% (18/18). All 18 patients were able to undergo stereotactic body radiotherapy without marker migration. Thus, the clinical success rate was 100% (18/18). Slight pneumothorax occurred as a minor complication in one case. No major complications such as coil migration or bleeding were observed. The examined percutaneous fiducial marker was safely placed in the liver and appeared to be useful for stereotactic body radiotherapy for malignant liver tumors

Health and safety in clinical laboratories in developing countries: safety considerations.

Science.gov (United States)

Ejilemele, A A; Ojule, A C

2004-01-01

Clinical laboratories are potentially hazardous work areas. Health and safety in clinical laboratories is becoming an increasingly important subject as a result of the emergence of highly infectious diseases such as hepatitis and HIV. This is even more so in developing countries where health and safety have traditionally been regarded as low priority issues, considering the more important health problems confronting the health authorities in these countries. We conducted a literature search using the medical subheadings titles on the INTERNET over a period of twenty years and summarized our findings. This article identifies hazards in the laboratories and highlights measures to make the laboratory a safer work place. It also emphasizes the mandatory obligations of employers and employees towards the attainment of acceptable safety standards in clinical laboratories in Third World countries in the face of the current HIV/AIDS epidemic in many of these developing countries especially in the sub-Saharan Africa while accommodating the increasing work load in these laboratories. Both the employer and the employee have major roles to play in the maintenance of a safe working environment. This can be achieved if measures discussed are incorporated into everyday laboratory practice.

Genomic markers for decision making: what is preventing us from using markers?

Science.gov (United States)

Coyle, Vicky M; Johnston, Patrick G

2010-02-01

The advent of novel genomic technologies that enable the evaluation of genomic alterations on a genome-wide scale has significantly altered the field of genomic marker research in solid tumors. Researchers have moved away from the traditional model of identifying a particular genomic alteration and evaluating the association between this finding and a clinical outcome measure to a new approach involving the identification and measurement of multiple genomic markers simultaneously within clinical studies. This in turn has presented additional challenges in considering the use of genomic markers in oncology, such as clinical study design, reproducibility and interpretation and reporting of results. This Review will explore these challenges, focusing on microarray-based gene-expression profiling, and highlights some common failings in study design that have impacted on the use of putative genomic markers in the clinic. Despite these rapid technological advances there is still a paucity of genomic markers in routine clinical use at present. A rational and focused approach to the evaluation and validation of genomic markers is needed, whereby analytically validated markers are investigated in clinical studies that are adequately powered and have pre-defined patient populations and study endpoints. Furthermore, novel adaptive clinical trial designs, incorporating putative genomic markers into prospective clinical trials, will enable the evaluation of these markers in a rigorous and timely fashion. Such approaches have the potential to facilitate the implementation of such markers into routine clinical practice and consequently enable the rational and tailored use of cancer therapies for individual patients.

Clinical Trial Electronic Portals for Expedited Safety Reporting: Recommendations from the Clinical Trials Transformation Initiative Investigational New Drug Safety Advancement Project.

Science.gov (United States)

Perez, Raymond P; Finnigan, Shanda; Patel, Krupa; Whitney, Shanell; Forrest, Annemarie

2016-12-15

Use of electronic clinical trial portals has increased in recent years to assist with sponsor-investigator communication, safety reporting, and clinical trial management. Electronic portals can help reduce time and costs associated with processing paperwork and add security measures; however, there is a lack of information on clinical trial investigative staff's perceived challenges and benefits of using portals. The Clinical Trials Transformation Initiative (CTTI) sought to (1) identify challenges to investigator receipt and management of investigational new drug (IND) safety reports at oncologic investigative sites and coordinating centers and (2) facilitate adoption of best practices for communicating and managing IND safety reports using electronic portals. CTTI, a public-private partnership to improve the conduct of clinical trials, distributed surveys and conducted interviews in an opinion-gathering effort to record investigator and research staff views on electronic portals in the context of the new safety reporting requirements described in the US Food and Drug Administration's final rule (Code of Federal Regulations Title 21 Section 312). The project focused on receipt, management, and review of safety reports as opposed to the reporting of adverse events. The top challenge investigators and staff identified in using individual sponsor portals was remembering several complex individual passwords to access each site. Also, certain tasks are time-consuming (eg, downloading reports) due to slow sites or difficulties associated with particular operating systems or software. To improve user experiences, respondents suggested that portals function independently of browsers and operating systems, have intuitive interfaces with easy navigation, and incorporate additional features that would allow users to filter, search, and batch safety reports. Results indicate that an ideal system for sharing expedited IND safety information is through a central portal used by

A methodological study to compare survey-based and observation-based evaluations of organisational and safety cultures and then compare both approaches with markers of the quality of care.

Science.gov (United States)

Freeth, D; Sandall, J; Allan, T; Warburton, F; Berridge, E J; Mackintosh, N; Rogers, M; Abbott, S

2012-05-01

Patient safety concerns have focused attention on organisational and safety cultures, in turn directing attention to the measurement of organisational and safety climates. First, to compare levels of agreement between survey- and observation-based measures of organisational and safety climates/cultures and to compare both measures with criterion-based audits of the quality of care, using evidence-based markers drawn from national care standards relating to six common clinical conditions. (This required development of an observation-based instrument.) Second, to examine whether observation-based evaluations could replace or augment survey measurements to mitigate concerns about declining response rates and increasing social desirability bias. Third, to examine mediating factors in safety and organisational climate scores. The study had three strands: (A) a postal questionnaire survey to elicit staff perceptions of organisational and safety climates, using six prevalidated scales; (B) semistructured non-participant observation of clinical teams; and (C) a retrospective criterion-based audit carried out by non-clinical auditors to minimise hindsight bias. Standardised summary scores were created for each strand, and pairs of measurements were compared (strand A with strand B, strand A with strand C, and strand B with strand C) using Bland-Altman plots to evaluate agreement. Correlations were also examined. Multilevel modelling of Strand A scores explored mediating factors. Eight emergency departments and eight maternity units in England, UK. None. Examination of feasibility, correlation and agreement. Strand A: the overall response rate was 27.6%, whereas site-specific rates ranged from 9% to 47%. We identified more mediating factors than previous studies; variable response rates had little effect on the results. Organisational and safety climate scores were strongly correlated (r = 0.845) and exhibited good agreement [standard deviation (SD) differences 0.449; 14 (88

76 FR 36318 - Safety Zone; Waterway Closure, Morgan City-Port Allen Route From Mile Marker 0 to Port Allen Lock

Science.gov (United States)

2011-06-22

... Executive Order 13045, Protection of Children from Environmental Health Risks and Safety Risks. This rule is not an economically significant rule and does not create an environmental risk to health or risk to...-AA00 Safety Zone; Waterway Closure, Morgan City-Port Allen Route From Mile Marker 0 to Port Allen Lock...

Safety Culture and Senior Leadership Behavior: Using Negative Safety Ratings to Align Clinical Staff and Senior Leadership.

Science.gov (United States)

O'Connor, Shawn; Carlson, Elizabeth

2016-04-01

This report describes how staff-designed behavior changes among senior leaders can have a positive impact on clinical nursing staff and enhance the culture of safety in a community hospital. A positive culture of safety in a hospital improves outcomes for patients and staff. Senior leaders are accountable for developing an environment that supports a culture of safety. At 1 community hospital, surveys demonstrated that staff members did not view senior leaders as supportive of or competent in creating a culture of safety. After approval from the hospital's institutional review board was obtained, clinical nurses generated and selected ideas for senior leader behavior change. The new behaviors were assessed by a convenience sample survey of clinical nurses. In addition, culture of safety survey results were compared. Risk reports and harm events were also measured before and after behavior changes. The volume of risk and near-miss reports increased, showing that clinical staff were more inclined to report events after senior leader communication, access, and visibility increased. Harm events went down. The culture of safety survey demonstrated an improvement in the senior leadership domain in 4 of 6 units. The anonymous convenience survey demonstrated that staff members recognized changes that senior leaders had made and felt that these changes positively impacted the culture of safety. By developing skills in communication, advocacy, visibility, and access, senior leaders can enhance a hospital's culture of safety and create stronger ties with clinical staff.

Molecular and protein markers for clinical decision making in breast cancer: today and tomorrow.

Science.gov (United States)

Harbeck, Nadia; Sotlar, Karl; Wuerstlein, Rachel; Doisneau-Sixou, Sophie

2014-04-01

In early breast cancer (eBC), established clinicopathological factors are not sufficient for clinical decision making particularly regarding adjuvant chemotherapy since substantial over- or undertreatment may occur. Thus, novel protein- and molecular markers have been put forward as decision aids. Since these potential prognosis and/or predictive tests differ substantially regarding their methodology, analytical and clinical validation, this review attempts to summarize the essential facts for clinicians. This review focuses on those markers which are the most advanced so far in their development towards routine clinical application, i.e. two protein markers (i.e. uPA/PAI-1 and IHC4) and six molecular multigene tests (i.e. Mammaprint®, Oncotype DX®, PAM50, Endopredict®, the 97-gene genomic grade, and 76 gene Rotterdam signatures). Next to methodological aspects, we summarized the clinical evidences, in particular the main prospective clinical trials which have already been fully recruited (i.e. MINDACT, TAILORx, WSG PLAN B) or are still ongoing (i.e. RxPONDER/SWOG S1007, WSG-ADAPT). Last but not least, this review points out the key elements for clinicians to select one test among the wide panel of proposed assays, for a specific population of patients in term of level of evidence, analytical and clinical validity as well as cost effectiveness. Copyright © 2013 Elsevier Ltd. All rights reserved.

Autism and genetics: Clinical approach and association study with two markers of HRAS gene

Energy Technology Data Exchange (ETDEWEB)

Herault, J.; Petit, E.; Cherpi, C. [Laboratoire de Biochimie Medicale, Tours (France)] [and others

1995-08-14

Twin studies and familial aggregation studies indicate that genetic factors could play a role in infantile autism. In an earlier study, we identified a possible positive association between autism and a c-Harvey-ras (HRAS) oncogene marker at the 3{prime} end of the coding region. In an attempt to confirm this finding, we studied a larger population, well-characterized clinically and genetically. We report a positive association between autism and two HRAS markers, the 3{prime} marker used in the initial study and an additional marker in exon 1. 46 refs., 1 fig., 2 tabs.

Lipid storage myopathy with clinical markers of Marfan syndrome: A rare association

Directory of Open Access Journals (Sweden)

Subasree Ramakrishnan

2012-01-01

Full Text Available Disorders of lipid metabolism can cause variable clinical presentations, often involving skeletal muscle, alone or together with other tissues. A 19-year-old boy presented with a 2-year history of muscle pain, cramps, exercise intolerance and progressive weakness of proximal lower limbs. Examination revealed skeletal markers of Marfan syndrome in the form of increased arm span compared with height, Kyphoscoliois, moderate pectus excavatum, high arched palate and wrist sign. He also had mild neck flexor weakness and proximal lower limb weakness with areflexia. Pathologic findings revealed lipid-laden fine vacuoles in the muscle fibers. Possibility of carnitine deficiency myopathy was considered and the patient was started on carnitine and Co Q. The patient made remarkable clinical improvement over the next 2 months. This case is reported for rarity of the association of clinical markers of Marfan syndrome and lipid storage myopathy and sparse literature on lipid storage myopathy in the Indian context.

What is Clinical Safety in Electronic Health Care Record Systems?

Science.gov (United States)

Davies, George

There is mounting public awareness of an increasing number of adverse clinical incidents within the National Health Service (NHS), but at the same time, large health care projects like the National Programme for IT (NPFIT) are claiming that safer care is one of the benefits of the project and that health software systems in particular have the potential to reduce the likelihood of accidental or unintentional harm to patients. This paper outlines the approach to clinical safety management taken by CSC, a major supplier to NPFIT; discusses acceptable levels of risk and clinical safety as an end-to-end concept; and touches on the future for clinical safety in health systems software.

A new fiducial marker for Image-guided radiotherapy of prostate cancer: Clinical experience

Energy Technology Data Exchange (ETDEWEB)

Carl, Jesper; Nielsen, Jane; Holmberg, Mats; Hoejkjaer Larsen, Erik; Fabrin, Knud; Fisker, Rune V. (Dept. of Medical Physics, Oncology, Aalborg Hospital (Denmark))

2008-08-15

Background. A new fiducial marker for image guided radiotherapy (IGRT) based on a removable prostate stent made of Ni Ti has been developed during two previous clinical feasibility studies. The marker is currently being evaluated for IGRT treatment in a third clinical study. Method. The new marker is used to co-register MR and planning CT scans with high accuracy in the region around the prostate. The co-registered MR-CT volumes are used for delineation of GTV before planning. In each treatment session the IGRT system is used to position the patient before treatment. The IGRT system use a stereo pair of kV images matched to corresponding Digital Reconstructed Radiograms (DRR) from the planning CT scan. The match is done using mutual gray scale information. The pair of DRR's for positioning is created in the IGRT system with a threshold in the Look Up Table (LUT). The resulting match provides the necessary shift in couch coordinates to position the stent with an accuracy of 1-2 mm within the planned position. Results. At the present time 39 patients have received the new marker. Of the 39 one has migrated to the bladder. Deviations of more than 5 mm between CTV outlined on CT and MR are seen in several cases and in anterior-posterior (AP), left-right (LR) and cranial-caudal (CC) directions. Intra-fraction translation movements up to +/- 3 mm are seen as well. As the stent is also clearly visible on images taken with high voltage x-rays using electronic portal images devices (EPID), the positioning has been verified independently of the IGRT system. Discussion. The preliminary result of an on going clinical study of a Ni Ti prostate stent, potentially a new fiducial marker for image guided radiotherapy, looks promising. The risk of migration appears to be much lower compared to previous designs

A new fiducial marker for Image-guided radiotherapy of prostate cancer: clinical experience.

Science.gov (United States)

Carl, Jesper; Nielsen, Jane; Holmberg, Mats; Højkjaer Larsen, Erik; Fabrin, Knud; Fisker, Rune V

2008-01-01

A new fiducial marker for image guided radiotherapy (IGRT) based on a removable prostate stent made of Ni Ti has been developed during two previous clinical feasibility studies. The marker is currently being evaluated for IGRT treatment in a third clinical study. The new marker is used to co-register MR and planning CT scans with high accuracy in the region around the prostate. The co-registered MR-CT volumes are used for delineation of GTV before planning. In each treatment session the IGRT system is used to position the patient before treatment. The IGRT system use a stereo pair of kV images matched to corresponding Digital Reconstructed Radiograms (DRR) from the planning CT scan. The match is done using mutual gray scale information. The pair of DRR's for positioning is created in the IGRT system with a threshold in the Look Up Table (LUT). The resulting match provides the necessary shift in couch coordinates to position the stent with an accuracy of 1-2 mm within the planned position. At the present time 39 patients have received the new marker. Of the 39 one has migrated to the bladder. Deviations of more than 5 mm between CTV outlined on CT and MR are seen in several cases and in anterior-posterior (AP), left-right (LR) and cranial-caudal (CC) directions. Intra-fraction translation movements up to +/- 3 mm are seen as well. As the stent is also clearly visible on images taken with high voltage x-rays using electronic portal images devices (EPID), the positioning has been verified independently of the IGRT system. The preliminary result of an on going clinical study of a Ni Ti prostate stent, potentially a new fiducial marker for image guided radiotherapy, looks promising. The risk of migration appears to be much lower compared to previous designs.

A new fiducial marker for Image-guided radiotherapy of prostate cancer: Clinical experience

International Nuclear Information System (INIS)

Carl, Jesper; Nielsen, Jane; Holmberg, Mats; Hoejkjaer Larsen, Erik; Fabrin, Knud; Fisker, Rune V.

2008-01-01

Background. A new fiducial marker for image guided radiotherapy (IGRT) based on a removable prostate stent made of Ni Ti has been developed during two previous clinical feasibility studies. The marker is currently being evaluated for IGRT treatment in a third clinical study. Method. The new marker is used to co-register MR and planning CT scans with high accuracy in the region around the prostate. The co-registered MR-CT volumes are used for delineation of GTV before planning. In each treatment session the IGRT system is used to position the patient before treatment. The IGRT system use a stereo pair of kV images matched to corresponding Digital Reconstructed Radiograms (DRR) from the planning CT scan. The match is done using mutual gray scale information. The pair of DRR's for positioning is created in the IGRT system with a threshold in the Look Up Table (LUT). The resulting match provides the necessary shift in couch coordinates to position the stent with an accuracy of 1-2 mm within the planned position. Results. At the present time 39 patients have received the new marker. Of the 39 one has migrated to the bladder. Deviations of more than 5 mm between CTV outlined on CT and MR are seen in several cases and in anterior-posterior (AP), left-right (LR) and cranial-caudal (CC) directions. Intra-fraction translation movements up to +/- 3 mm are seen as well. As the stent is also clearly visible on images taken with high voltage x-rays using electronic portal images devices (EPID), the positioning has been verified independently of the IGRT system. Discussion. The preliminary result of an on going clinical study of a Ni Ti prostate stent, potentially a new fiducial marker for image guided radiotherapy, looks promising. The risk of migration appears to be much lower compared to previous designs

Chronic Kidney Disease Awareness Among Individuals with Clinical Markers of Kidney Dysfunction

Science.gov (United States)

Plantinga, Laura C.; Hsu, Chi-yuan; Jordan, Regina; Burrows, Nilka Ríos; Hedgeman, Elizabeth; Yee, Jerry; Saran, Rajiv; Powe, Neil R.

2011-01-01

Summary Background and objectives Awareness of chronic kidney disease (CKD) among providers and patients is low. Whether clinical cues prompt recognition of CKD is unknown. We examined whether markers of kidney disease that should trigger CKD recognition among providers are associated with higher individual CKD awareness. Design, setting, participants, & measurements CKD awareness was assessed in 1852 adults with an estimated GFR kidneys?” Participants were grouped by distribution of the following abnormal markers of CKD: hyperkalemia, acidosis, hyperphosphatemia, elevated blood urea nitrogen, anemia, albuminuria, and uncontrolled hypertension. Odds of CKD awareness associated with each abnormal marker and groupings of markers were estimated by multivariable logistic regression. Results Among individuals with kidney disease, only those with albuminuria had greater odds of CKD awareness (adjusted odds ratio, 4.0, P disease. Conclusions Although individuals who manifest many markers of kidney dysfunction are more likely to be aware of their CKD, their CKD awareness remains low. A better understanding of mechanisms of awareness is required to facilitate earlier detection of CKD and implement therapy to minimize associated complications. PMID:21784832

7T: Physics, safety, and potential clinical applications.

Science.gov (United States)

Kraff, Oliver; Quick, Harald H

2017-12-01

With more than 60 installed magnetic resonance imaging (MRI) systems worldwide operating at a magnetic field strength of 7T or higher, ultrahigh-field (UHF) MRI has been established as a platform for clinically oriented research in recent years. Profound technical and methodological developments have helped overcome the inherent physical challenges of UHF radiofrequency (RF) signal homogenization in the human body. The ongoing development of dedicated RF coil arrays was pivotal in realizing UHF body MRI, beyond mere brain imaging applications. Another precondition to clinical application of 7T MRI is the safety testing of implants and the establishment of safety concepts. Against this backdrop, 7T MRI and MR spectroscopy (MRS) recently have demonstrated capabilities and potentials for clinical diagnostics in a variety of studies. This article provides an overview of the immanent physical challenges of 7T UHF MRI and discusses recent technical solutions and safety concepts. Furthermore, recent clinically oriented studies are highlighted that span a broad application spectrum from 7T UHF brain to body MRI. 4 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1573-1589. © 2017 International Society for Magnetic Resonance in Medicine.

Suitability of miniature inductively coupled RF coils as MR-visible markers for clinical purposes.

Science.gov (United States)

Garnov, Nikita; Thormer, Gregor; Trampel, Robert; Grunder, Wilfried; Kahn, Thomas; Moche, Michael; Busse, Harald

2011-11-01

MR-visible markers have already been used for various purposes such as image registration, motion detection, and device tracking. Inductively coupled RF (ICRF) coils, in particular, provide a high contrast and do not require connecting wires to the scanner, which makes their application highly flexible and safe. This work aims to thoroughly characterize the MR signals of such ICRF markers under various conditions with a special emphasis on fully automatic detection. The small markers consisted of a solenoid coil that was wound around a glass tube containing the MR signal source and tuned to the resonance frequency of a 1.5 T MRI. Marker imaging was performed with a spoiled gradient echo sequence (FLASH) and a balanced steady-state free precession (SSFP) sequence (TrueFISP) in three standard projections. The signal intensities of the markers were recorded for both pulse sequences, three source materials (tap water, distilled water, and contrast agent solution), different flip angles and coil alignments with respect to the B(0) direction as well as for different marker positions in the entire imaging volume (field of view, FOV). Heating of the ICRF coils was measured during 10-min RF expositions to three conventional pulse sequences. Clinical utility of the markers was assessed from their performance in computer-aided detection and in defining double oblique scan planes. For almost the entire FOV (±215 mm) and an estimated 82% of all possible RF coil alignments with respect to B(0), the ICRF markers generated clearly visible MR signals and could be reliably localized over a large range of flip angles, in particular with the TrueFISP sequence (0.3°-4.0°). Generally, TrueFISP provided a higher marker contrast than FLASH. RF exposition caused a moderate heating (≤5 °C) of the ICRF coils only. Small ICRF coils, imaged at low flip angles with a balanced SSFP sequence showed an excellent performance under a variety of experimental conditions and therefore make for a

Patient Safety Culture in Slovenian out-of-hours Primary Care Clinics.

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Klemenc-Ketiš, Zalika; Deilkås, Ellen Tveter; Hofoss, Dag; Bondevik, Gunnar Tschudi

2017-10-01

Patient safety culture is a concept which describes how leader and staff interaction, attitudes, routines and practices protect patients from adverse events in healthcare. We aimed to investigate patient safety culture in Slovenian out-of-hours health care (OOHC) clinics, and determine the possible factors that might be associated with it. This was a cross-sectional study, which took place in Slovenian OOHC, as part of the international study entitled Patient Safety Culture in European Out-of-Hours Services (SAFE-EUR-OOH). All the OOHC clinics in Slovenia (N=60) were invited to participate, and 37 agreed to do so; 438 employees from these clinics were invited to participate. We used the Slovenian version of the Safety Attitudes Questionnaire - an ambulatory version (SAQAV) to measure the climate of safety. Out of 438 invited participants, 250 answered the questionnaire (57.1% response rate). The mean overall score ± standard deviation of the SAQ was 56.6±16.0 points, of Perceptions of Management 53.6±19.6 points, of Job Satisfaction 48.5±18.3 points, of Safety Climate 59.1±22.1 points, of Teamwork Climate 72.7±16.6, and of Communication 51.5±23.4 points. Employees working in the Ravne na Koroškem region, employees with variable work shifts, and those with full-time jobs scored significantly higher on the SAQ-AV. The safety culture in Slovenian OOHC clinics needs improvement. The variations in the safety culture factor scores in Slovenian OOHC clinics point to the need to eliminate variations and improve working conditions in Slovenian OOHC clinics.

Inherited Genetic Markers for Thrombophilia in Northeastern Iran (a Clinical-Based Report

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Fatemeh Keify

2014-05-01

Full Text Available Background: Thrombophilia is a main predisposition to thrombosis due to a procoagulant state. Several point mutations play key roles in blood-clotting disorders, which are grouped under the term thrombophilia. These thrombophilic mutations are methylenetetrahydrofolate reductase (MTHFR, C677T, and A1298C, factor V Leiden (G1691A, prothrombin gene mutation (factor II, G20210A, and plasminogen activator inhibitor (PAI. In the present study, we assessed the prevalence of the above thrombophilia markers in patients with recurrent pregnancy loss or first and second trimester abortions, infertility, and failed in vitro fertilization (IVF. Methods: This study was conducted among 457 cases those were referred to detect the inherited genetic markers for thrombophilia. Markers for MTHFR, Factor II, and Factor V were assessed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP, and PAI was assessed by Amplification Refractory Mutation System (ARMS-PCR. Results: Two hundred sixty cases (56.89% were diagnosed as having at least one thrombophilia marker, whereas 197 cases (43.11% had no thrombophilia markers and were normal. Conclusion: According to the current study, the pattern of abnormal genetic markers for thrombophilia in northeastern Iran demonstrates the importance of genetic evaluations in patients who show clinical abnormalities with recurrent spontaneous abortion (RSA or other serious obstetric complications.

Injection safety knowledge and practices among clinical health care ...

African Journals Online (AJOL)

Injection safety is therefore critical in preventing occupational exposure and infection from blood borne pathogens, hence prevention is a vital part of any ... safety among clinical healthcare workers at the Garissa Provincial General Hospital.

Socioeconomic inequalities in prognostic markers of non-Hodgkin lymphoma: analysis of a national clinical database

DEFF Research Database (Denmark)

Frederiksen, Birgitte Lidegaard; Brown, Peter de Nully; Dalton, Susanne Oksbjerg

2011-01-01

in histological subgroups reflecting aggressiveness of disease among the social groups. One of the most likely mechanisms of the social difference is longer delay in those with low socioeconomic position. The findings of social inequality in prognostic markers in non-Hodgkin lymphoma (NHL) patients could already......The survival of non-Hodgkin lymphoma patients strongly depends on a range of prognostic factors. This registry-based clinical cohort study investigates the relation between socioeconomic position and prognostic markers in 6234 persons included in a national clinical database in 2000-2008, Denmark....... Several measures of individual socioeconomic position were achieved from Statistics Denmark. The risk of being diagnosed with advanced disease, as expressed by the six prognostic markers (Ann Arbor stage III or IV, more than one extranodal lesion, elevated serum lactate dehydrogenase (LDH), performance...

Safety and effectiveness considerations for clinical studies of visual prosthetic devices

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Cohen, Ethan D.

2007-03-01

With the advent of new designs of visual prostheses for the blind, FDA is faced with developing guidance for evaluating their engineering, safety and patient performance. Visual prostheses are considered significant risk medical devices, and their use in human clinical trials must be approved by FDA under an investigation device exemption (IDE). This paper contains a series of test topics and design issues that sponsors should consider in order to assess the safety and efficacy of their device. The IDE application includes a series of pre-clinical and clinical data sections. The pre-clinical section documents laboratory, animal and bench top performance tests of visual prostheses safety and reliability to support a human clinical trial. The materials used in constructing the implant should be biocompatible, sterile, corrosion resistant, and able to withstand any forces exerted on it during normal patient use. The clinical data section is composed of items related to patient-related evaluation of device performance. This section documents the implantation procedure, trial design, statistical analysis and how visual performance is assessed. Similar to cochlear implants, a visual prosthesis is expected to last in the body for many years, and good pre-clinical and clinical testing will help ensure its safety, durability and effectiveness.

Transarterial Fiducial Marker Placement for Image-guided Proton Therapy for Malignant Liver Tumors

Energy Technology Data Exchange (ETDEWEB)

Ohta, Kengo, E-mail: yesterday.is.yesterday@gmail.com; Shimohira, Masashi, E-mail: mshimohira@gmail.com [Nagoya City University Graduate School of Medical Sciences, Department of Radiology (Japan); Sasaki, Shigeru, E-mail: ssasaki916@yahoo.co.jp; Iwata, Hiromitsu, E-mail: h-iwa-ncu@nifty.com; Nishikawa, Hiroko, E-mail: piroko1018@gmail.com; Ogino, Hiroyuki, E-mail: oginogio@gmail.com; Hara, Masaki, E-mail: mhara@med.nagoya-cu.ac.jp [Nagoya City West Medical Center, Department of Radiation Oncology, Nagoya Proton Therapy Center (Japan); Hashizume, Takuya, E-mail: tky300@gmail.com; Shibamoto, Yuta, E-mail: yshiba@med.nagoya-cu.ac.jp [Nagoya City University Graduate School of Medical Sciences, Department of Radiology (Japan)

2015-10-15

PurposeThe aim of this study is to analyze the technical and clinical success rates and safety of transarterial fiducial marker placement for image-guided proton therapy for malignant liver tumors.Methods and MaterialsFifty-five patients underwent this procedure as an interventional treatment. Five patients had 2 tumors, and 4 tumors required 2 markers each, so the total number of procedures was 64. The 60 tumors consisted of 46 hepatocellular carcinomas and 14 liver metastases. Five-mm-long straight microcoils of 0.018 inches in diameter were used as fiducial markers and placed in appropriate positions for each tumor. We assessed the technical and clinical success rates of transarterial fiducial marker placement, as well as the complications associated with it. Technical success was defined as the successful delivery and placement of the fiducial coil, and clinical success was defined as the completion of proton therapy.ResultsAll 64 fiducial coils were successfully installed, so the technical success rate was 100 % (64/64). Fifty-four patients underwent proton therapy without coil migration. In one patient, proton therapy was not performed because of obstructive jaundice due to bile duct invasion by hepatocellular carcinoma. Thus, the clinical success rate was 98 % (54/55). Slight bleeding was observed in one case, but it was stopped immediately and then observed. None of the patients developed hepatic infarctions due to fiducial marker migration.ConclusionTransarterial fiducial marker placement appears to be a useful and safe procedure for proton therapy for malignant liver tumors.

Transarterial Fiducial Marker Placement for Image-guided Proton Therapy for Malignant Liver Tumors

International Nuclear Information System (INIS)

Ohta, Kengo; Shimohira, Masashi; Sasaki, Shigeru; Iwata, Hiromitsu; Nishikawa, Hiroko; Ogino, Hiroyuki; Hara, Masaki; Hashizume, Takuya; Shibamoto, Yuta

2015-01-01

PurposeThe aim of this study is to analyze the technical and clinical success rates and safety of transarterial fiducial marker placement for image-guided proton therapy for malignant liver tumors.Methods and MaterialsFifty-five patients underwent this procedure as an interventional treatment. Five patients had 2 tumors, and 4 tumors required 2 markers each, so the total number of procedures was 64. The 60 tumors consisted of 46 hepatocellular carcinomas and 14 liver metastases. Five-mm-long straight microcoils of 0.018 inches in diameter were used as fiducial markers and placed in appropriate positions for each tumor. We assessed the technical and clinical success rates of transarterial fiducial marker placement, as well as the complications associated with it. Technical success was defined as the successful delivery and placement of the fiducial coil, and clinical success was defined as the completion of proton therapy.ResultsAll 64 fiducial coils were successfully installed, so the technical success rate was 100 % (64/64). Fifty-four patients underwent proton therapy without coil migration. In one patient, proton therapy was not performed because of obstructive jaundice due to bile duct invasion by hepatocellular carcinoma. Thus, the clinical success rate was 98 % (54/55). Slight bleeding was observed in one case, but it was stopped immediately and then observed. None of the patients developed hepatic infarctions due to fiducial marker migration.ConclusionTransarterial fiducial marker placement appears to be a useful and safe procedure for proton therapy for malignant liver tumors

Electronic clinical safety reporting system: a benefits evaluation.

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Elliott, Pamela; Martin, Desmond; Neville, Doreen

2014-06-11

Eastern Health, a large health care organization in Newfoundland and Labrador (NL), started a staged implementation of an electronic occurrence reporting system (used interchangeably with "clinical safety reporting system") in 2008, completing Phase One in 2009. The electronic clinical safety reporting system (CSRS) was designed to replace a paper-based system. The CSRS involves reporting on occurrences such as falls, safety/security issues, medication errors, treatment and procedural mishaps, medical equipment malfunctions, and close calls. The electronic system was purchased from a vendor in the United Kingdom that had implemented the system in the United Kingdom and other places, such as British Columbia. The main objective of the new system was to improve the reporting process with the goal of improving clinical safety. The project was funded jointly by Eastern Health and Canada Health Infoway. The objectives of the evaluation were to: (1) assess the CSRS on achieving its stated objectives (particularly, the benefits realized and lessons learned), and (2) identify contributions, if any, that can be made to the emerging field of electronic clinical safety reporting. The evaluation involved mixed methods, including extensive stakeholder participation, pre/post comparative study design, and triangulation of data where possible. The data were collected from several sources, such as project documentation, occurrence reporting records, stakeholder workshops, surveys, focus groups, and key informant interviews. The findings provided evidence that frontline staff and managers support the CSRS, identifying both benefits and areas for improvement. Many benefits were realized, such as increases in the number of occurrences reported, in occurrences reported within 48 hours, in occurrences reported by staff other than registered nurses, in close calls reported, and improved timelines for notification. There was also user satisfaction with the tool regarding ease of use

GOLIMUMAB SAFETY ACCORDING TO CLINICAL FINDINGS

Directory of Open Access Journals (Sweden)

G. V. Lukina

2015-01-01

Full Text Available                                                      The review analyzes trials dealing with the safety of golimumab (GLM  used in rheumatology.  This drug was the latest Contact: Galina Lukina;gvl3@yandex.ru Поступила 12.05.14tumor necrosis factor α (TNF-α inhibitor introduced  into clinical practice and therefore the estimation of its tolerability is particularly relevant. The data obtained in large-scale clinical trials suggest that GLM has a good safety profile. The most common  adverse events (AE were infections, more often mild. The rate of infections was higher with the use of GLM 100 mg than with that of 50 mg. The overall cancer rate did not increase during a follow-up of less than 160 weeks. However, the rate of lymphomas in patients receiving GLM 100 mg proved to be higher than in those taking GLM 50 mg, in the general population, and in the placebo group in particular. AE were evenly distributed among patients with rheumatoid  arthritis, psoriatic arthritis, or ankylosing spondylitis. Overall, the findings are in agreement with the data on the safety of previously used TNF-α inhibitors. No fundamentally new AE have been encountered. It is necessary to accumulate  data on the use of GLM in real clinical practice, which will be able to more objectively define its place in the current therapy of rheumatic diseases.

Markers of neuroinflammation and neuronal injury in bipolar disorder: Relation to prospective clinical outcomes.

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Isgren, Anniella; Sellgren, Carl; Ekman, Carl-Johan; Holmén-Larsson, Jessica; Blennow, Kaj; Zetterberg, Henrik; Jakobsson, Joel; Landén, Mikael

2017-10-01

Neuroimmune mechanisms have been linked to the pathophysiology of bipolar disorder based on studies of biomarkers in plasma, cerebrospinal fluid (CSF), and postmortem brain tissue. There are, however, no longitudinal studies investigating if CSF markers of neuroinflammation and neuronal injury predict clinical outcomes in patients with bipolar disorder. We have in previous studies found higher CSF concentrations of interleukin-8 (IL-8), monocyte chemoattractant protein 1 (MCP-1/CCL-2), chitinase-3-like protein 1 (CHI3L1/YKL-40), and neurofilament light chain (NF-L) in euthymic patients with bipolar disorder compared with controls. Here, we investigated the relationship of these CSF markers of neuroinflammation and neuronal injury with clinical outcomes in a prospective study. 77 patients with CSF analyzed at baseline were followed for 6-7years. Associations of baseline biomarkers with clinical outcomes (manic/hypomanic and depressive episodes, suicide attempts, psychotic symptoms, inpatient care, GAF score change) were investigated. Baseline MCP-1 concentrations were positively associated with manic/hypomanic episodes and inpatient care during follow-up. YKL-40 concentrations were negatively associated with manic/hypomanic episodes and with occurrence of psychotic symptoms. The prospective negative association between YKL-40 and manic/hypomanic episodes survived multiple testing correction. Concentrations of IL-8 and NF-L were not associated with clinical outcomes. High concentrations of these selected CSF markers of neuroinflammation and neuronal injury at baseline were not consistently associated with poor clinical outcomes in this prospective study. The assessed proteins may be involved in adaptive immune processes or reflect a state of vulnerability for bipolar disorder rather than being of predictive value for disease progression. Copyright © 2017 Elsevier Inc. All rights reserved.

Safety culture perceptions of pharmacists in Malaysian hospitals and health clinics: a multicentre assessment using the Safety Attitudes Questionnaire

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Samsuri, Srima Elina; Pei Lin, Lua; Fahrni, Mathumalar Loganathan

2015-01-01

Objective To assess the safety attitudes of pharmacists, provide a profile of their domains of safety attitude and correlate their attitudes with self-reported rates of medication errors. Design A cross-sectional study utilising the Safety Attitudes Questionnaire (SAQ). Setting 3 public hospitals and 27 health clinics. Participants 117 pharmacists. Main outcome measure(s) Safety culture mean scores, variation in scores across working units and between hospitals versus health clinics, predictors of safety culture, and medication errors and their correlation. Results Response rate was 83.6% (117 valid questionnaires returned). Stress recognition (73.0±20.4) and working condition (54.8±17.4) received the highest and lowest mean scores, respectively. Pharmacists exhibited positive attitudes towards: stress recognition (58.1%), job satisfaction (46.2%), teamwork climate (38.5%), safety climate (33.3%), perception of management (29.9%) and working condition (15.4%). With the exception of stress recognition, those who worked in health clinics scored higher than those in hospitals (psafety culture. As perceptions improved, the number of medication errors reported decreased. Group-specific interventions that target specific domains are necessary to improve the safety culture. PMID:26610761

Prediction of Clinically Relevant Safety Signals of Nephrotoxicity through Plasma Metabolite Profiling

Directory of Open Access Journals (Sweden)

W. B. Mattes

2013-01-01

Full Text Available Addressing safety concerns such as drug-induced kidney injury (DIKI early in the drug pharmaceutical development process ensures both patient safety and efficient clinical development. We describe a unique adjunct to standard safety assessment wherein the metabolite profile of treated animals is compared with the MetaMap Tox metabolomics database in order to predict the potential for a wide variety of adverse events, including DIKI. To examine this approach, a study of five compounds (phenytoin, cyclosporin A, doxorubicin, captopril, and lisinopril was initiated by the Technology Evaluation Consortium under the auspices of the Drug Safety Executive Council (DSEC. The metabolite profiles for rats treated with these compounds matched established reference patterns in the MetaMap Tox metabolomics database indicative of each compound’s well-described clinical toxicities. For example, the DIKI associated with cyclosporine A and doxorubicin was correctly predicted by metabolite profiling, while no evidence for DIKI was found for phenytoin, consistent with its clinical picture. In some cases the clinical toxicity (hepatotoxicity, not generally seen in animal studies, was detected with MetaMap Tox. Thus metabolite profiling coupled with the MetaMap Tox metabolomics database offers a unique and powerful approach for augmenting safety assessment and avoiding clinical adverse events such as DIKI.

Sources of Safety Data and Statistical Strategies for Design and Analysis: Clinical Trials.

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Zink, Richard C; Marchenko, Olga; Sanchez-Kam, Matilde; Ma, Haijun; Jiang, Qi

2018-03-01

There has been an increased emphasis on the proactive and comprehensive evaluation of safety endpoints to ensure patient well-being throughout the medical product life cycle. In fact, depending on the severity of the underlying disease, it is important to plan for a comprehensive safety evaluation at the start of any development program. Statisticians should be intimately involved in this process and contribute their expertise to study design, safety data collection, analysis, reporting (including data visualization), and interpretation. In this manuscript, we review the challenges associated with the analysis of safety endpoints and describe the safety data that are available to influence the design and analysis of premarket clinical trials. We share our recommendations for the statistical and graphical methodologies necessary to appropriately analyze, report, and interpret safety outcomes, and we discuss the advantages and disadvantages of safety data obtained from clinical trials compared to other sources. Clinical trials are an important source of safety data that contribute to the totality of safety information available to generate evidence for regulators, sponsors, payers, physicians, and patients. This work is a result of the efforts of the American Statistical Association Biopharmaceutical Section Safety Working Group.

MR arthrography: pharmacology, efficacy and safety in clinical trials

International Nuclear Information System (INIS)

Schulte-Altedorneburg, G.; Gebhard, M.; Wohlgemuth, W.A.; Fischer, W.; Zentner, J.; Bohndorf, K.; Wegener, R.; Balzer, T.

2003-01-01

A meta-analysis was carried out of clinical trials published between 1987 and 2001 in respect of the clinical pharmacology and safety as well as the diagnostic efficacy of gadolinium-DTPA (Gd-DTPA) for direct intra-articular injection before MRI examination.Design. Scientific papers (clinical, postmortem and experimental studies) and information from the manufacturer regarding intra-articular injection of Gd-DTPA that addressed questions of mode of action, optimal concentration and dose, elimination and safety were reviewed. Clinical studies were classified according to their study design. The sensitivity, specificity and accuracy of MR arthrography (MRA) were compared with a ''gold standard'' (arthroscopy, arthrotomy) and other radiological evidence for different joints.Results. Fifty-two clinical studies of the overall 112 studies addressed aspects of diagnostic efficacy of MRA in patients or in healthy volunteers. The shoulder was the most assessed joint (29 of 52 studies). Good (>80%) or even excellent (90-100%) sensitivity, specificity and accuracy were found for MRA in most indications, especially for the shoulder and knee joints and induced extension of rotator cuff lesions, labrum abnormalities and postoperative meniscal tears. Two millimoles per liter has proven to be the best concentration for intra-articular administration of Gd-DTPA. After passive complete diffusion from the joint within 6-24 h, complete and rapid renal elimination takes place after intra-articular injection. Local safety proved to be excellent after intra-articular administration of Gd-DTPA. Regarding systemic tolerance almost no side effects have been reported, but the same safety considerations apply for intra-articular administration of Gd-DTPA as for intravenous injection.Conclusions. The diagnostic efficacy of intra-articular MRA in most clinical conditions affecting major joints is greater than that of plain MRI. In some diagnostic problems MRA achieves almost the same

Safety culture perceptions of pharmacists in Malaysian hospitals and health clinics: a multicentre assessment using the Safety Attitudes Questionnaire.

Science.gov (United States)

Samsuri, Srima Elina; Pei Lin, Lua; Fahrni, Mathumalar Loganathan

2015-11-26

To assess the safety attitudes of pharmacists, provide a profile of their domains of safety attitude and correlate their attitudes with self-reported rates of medication errors. A cross-sectional study utilising the Safety Attitudes Questionnaire (SAQ). 3 public hospitals and 27 health clinics. 117 pharmacists. Safety culture mean scores, variation in scores across working units and between hospitals versus health clinics, predictors of safety culture, and medication errors and their correlation. Response rate was 83.6% (117 valid questionnaires returned). Stress recognition (73.0±20.4) and working condition (54.8±17.4) received the highest and lowest mean scores, respectively. Pharmacists exhibited positive attitudes towards: stress recognition (58.1%), job satisfaction (46.2%), teamwork climate (38.5%), safety climate (33.3%), perception of management (29.9%) and working condition (15.4%). With the exception of stress recognition, those who worked in health clinics scored higher than those in hospitals (pculture. As perceptions improved, the number of medication errors reported decreased. Group-specific interventions that target specific domains are necessary to improve the safety culture. 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/

Mathematical modeling of efficacy and safety for anticancer drugs clinical development.

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Lavezzi, Silvia Maria; Borella, Elisa; Carrara, Letizia; De Nicolao, Giuseppe; Magni, Paolo; Poggesi, Italo

2018-01-01

Drug attrition in oncology clinical development is higher than in other therapeutic areas. In this context, pharmacometric modeling represents a useful tool to explore drug efficacy in earlier phases of clinical development, anticipating overall survival using quantitative model-based metrics. Furthermore, modeling approaches can be used to characterize earlier the safety and tolerability profile of drug candidates, and, thus, the risk-benefit ratio and the therapeutic index, supporting the design of optimal treatment regimens and accelerating the whole process of clinical drug development. Areas covered: Herein, the most relevant mathematical models used in clinical anticancer drug development during the last decade are described. Less recent models were considered in the review if they represent a standard for the analysis of certain types of efficacy or safety measures. Expert opinion: Several mathematical models have been proposed to predict overall survival from earlier endpoints and validate their surrogacy in demonstrating drug efficacy in place of overall survival. An increasing number of mathematical models have also been developed to describe the safety findings. Modeling has been extensively used in anticancer drug development to individualize dosing strategies based on patient characteristics, and design optimal dosing regimens balancing efficacy and safety.

Biochemical markers of bone turnover in the clinical development of drugs for osteoporosis and metastatic bone disease: potential uses and pitfalls.

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Cremers, Serge; Garnero, Patrick

2006-01-01

Biochemical markers of bone turnover are used increasingly during the clinical development of drugs for the treatment of metabolic bone diseases such as Paget's disease, osteoporosis and cancer that has metastasised to the bone. However, assessing the optimal value of these markers is often complicated, and such an assessment is an obvious prerequisite for rational use of the markers and, consequently, potential improvement of clinical drug development. Biochemical markers of bone turnover are substances in the blood or urine that are produced or released during bone remodelling. They provide semiquantitative information on bone remodelling, and are often the most adequate tool to describe the pharmacodynamics of the drug. Their use has increased considerably because of dose-effect relationships that have been seen with certain drugs, but also because they have proven relationships with clinical outcomes in several metabolic bone diseases. However, there is a lack of information on the kinetics of these markers, and the immunoassays that are frequently used in their monitoring often measure a mixture of fragments rather than a single molecular entity. For drug development it should also be realised that different markers, but also different assays for the same marker, may provide different results, considerably limiting the ability to compare results. In postmenopausal osteoporosis, relationships have been shown between several biochemical markers of bone turnover, and either fracture risk and/or the antifracture efficacy of drugs. Such relationships can be used for the development of drugs with similar mechanisms of action, but also for the development of these drugs for closely related indications, such as corticosteroid-induced osteoporosis. In both of these instances, data on effects on biochemical markers of bone turnover are usually employed in combination with information about effects on bone mineral density. However, the relationships of these parameters

Tumor markers in colorectal cancer

OpenAIRE

Fernandes, Luís César [UNIFESP; Matos, Delcio [UNIFESP

2002-01-01

Colorectal cancer is a clinical entity of a persistent relevance in clinical practice and its early diagnosis is a determinant factor to obtain better therapeutic results. Tumor markers are helpful means for a better approach to individuals with such neoplasm. In the present review, the authors analyze the phases in which surgical-clinical treatment markers must be used: diagnosis, determination of tumor stage, establishment of prognosis and detection of recurrence. Current and future markers...

Grammar Clinical Marker Yields Substantial Heritability for Language Impairments in 16-Year-Old Twins.

Science.gov (United States)

Dale, Philip S; Rice, Mabel L; Rimfeld, Kaili; Hayiou-Thomas, Marianna E

2018-01-22

There is a need for well-defined language phenotypes suitable for adolescents in twin studies and other large-scale research projects. Rice, Hoffman, and Wexler (2009) have developed a grammatical judgment measure as a clinical marker of language impairment, which has an extended developmental range to adolescence. We conducted the first twin analysis, along with associated phenotypic analyses of validity, of an abridged, 20-item version of this grammatical judgment measure (GJ-20), based on telephone administration using prerecorded stimuli to 405 pairs of 16-year-olds (148 monozygotic and 257 dizygotic) drawn from the Twins Early Development Study (Haworth, Davis, & Plomin, 2012). The distribution of scores is markedly skewed negatively, as expected for a potential clinical marker. Low performance on GJ-20 is associated with lower maternal education, reported learning disability (age 7 years), and low scores on language tests administered via the Twins Early Development Study (age 16 years) as well as General Certificate of Secondary Education English and Math examination performance (age 16 years). Liability threshold estimates for the genetic influence on low performance on GJ-20 are substantial, ranging from 36% with a lowest 10% criterion to 74% for a lowest 5% criterion. The heritability of GJ-20 scores, especially at more extreme cutoffs, along with the score distribution and association with other indicators of language impairments, provides additional evidence for the potential value of this measure as a clinical marker of specific language impairment.

Improving diabetic foot care in a nurse-managed safety-net clinic.

Science.gov (United States)

Peterson, Joann M; Virden, Mary D

2013-05-01

This article is a description of the development and implementation of a Comprehensive Diabetic Foot Care Program and assessment tool in an academically affiliated nurse-managed, multidisciplinary, safety-net clinic. The assessment tool parallels parameters identified in the Task Force Foot Care Interest Group of the American Diabetes Association's report published in 2008, "Comprehensive Foot Examination and Risk Assessment." Review of literature, Silver City Health Center's (SCHC) 2009 Annual Report, retrospective chart review. Since the full implementation of SCHC's Comprehensive Diabetic Foot Care Program, there have been no hospitalizations of clinic patients for foot-related complications. The development of the Comprehensive Diabetic Foot Assessment tool and the implementation of the Comprehensive Diabetic Foot Care Program have resulted in positive outcomes for the patients in a nurse-managed safety-net clinic. This article demonstrates that quality healthcare services can successfully be developed and implemented in a safety-net clinic setting. ©2012 The Author(s) Journal compilation ©2012 American Association of Nurse Practitioners.

Undergraduate medical students' perceptions and intentions regarding patient safety during clinical clerkship.

Science.gov (United States)

Lee, Hoo-Yeon; Hahm, Myung-Il; Lee, Sang Gyu

2018-04-04

The purpose of this study was to examine undergraduate medical students' perceptions and intentions regarding patient safety during clinical clerkships. Cross-sectional study administered in face-to-face interviews using modified the Medical Student Safety Attitudes and Professionalism Survey (MSSAPS) from three colleges of medicine in Korea. We assessed medical students' perceptions of the cultures ('safety', 'teamwork', and 'error disclosure'), 'behavioural intentions' concerning patient safety issues and 'overall patient safety'. Confirmatory factor analysis and Spearman's correlation analyses was performed. In total, 194(91.9%) of the 211 third-year undergraduate students participated. 78% of medical students reported that the quality of care received by patients was impacted by teamwork during clinical rotations. Regarding error disclosure, positive scores ranged from 10% to 74%. Except for one question asking whether the disclosure of medical errors was an important component of patient safety (74%), the percentages of positive scores for all the other questions were below 20%. 41.2% of medical students have intention to disclose it when they saw a medical error committed by another team member. Many students had difficulty speaking up about medical errors. Error disclosure guidelines and educational efforts aimed at developing sophisticated communication skills are needed. This study may serve as a reference for other institutions planning patient safety education in their curricula. Assessing student perceptions of safety culture can provide clerkship directors and clinical service chiefs with information that enhances the educational environment and promotes patient safety.

[Clinical governance and patient safety culture in clinical laboratories in the Spanish National Health System].

Science.gov (United States)

Giménez-Marín, Á; Rivas-Ruiz, F

To conduct a situational analysis of patient safety culture in public laboratories in the Spanish National Health System and to determine the clinical governance variables that most strongly influence patient safety. A descriptive cross-sectional study was carried out, in which a Survey of Patient Safety in Clinical Laboratories was addressed to workers in 26 participating laboratories. In this survey, which consisted of 45 items grouped into 6 areas, scores were assigned on a scale from 0 to 100 (where 0 is the lowest perception of patient safety). Laboratory managers were asked specific questions about quality management systems and technology. The mean scores for the 26 participating hospitals were evaluated, and the following results observed: in 4of the 6areas, the mean score was higher than 70 points. In the third area (equipment and resources) and the fourth area (working conditions), the scores were lower than 60 points. Every hospital had a digital medical record system. This 100% level of provision was followed by that of an electronic request management system, which was implemented in 82.6% of the hospitals. The results obtained show that the culture of security is homogeneous and of high quality in health service laboratories, probably due to the steady improvement observed. However, in terms of clinical governance, there is still some way to go, as shown by the presence of weaknesses in crucial dimensions of safety culture, together with variable levels of implementation of fail-safe technologies and quality management systems. Copyright © 2017 SECA. Publicado por Elsevier España, S.L.U. All rights reserved.

Clinical usefulness of CEA, CA19-9, and CYFRA 21-1 as tumor markers for urothelial bladder carcinoma.

Science.gov (United States)

Washino, Satoshi; Hirai, Masaru; Matsuzaki, Atsushi; Kobayashi, Yutaka

2011-01-01

To evaluate the usefulness of measuring serum CEA, CA19-9, and CYFRA 21-1 levels for the diagnosis and monitoring of bladder cancer. Serum levels of CEA, CA19-9, and CYFRA 21-1 were measured in 85 patients with bladder cancer. The absolute level of each marker and the positive rate were compared with the clinical stage and histological grade of the tumor. Changes of the markers were assessed in patients with or without disease progression, and the correlations between survival and positivity/negativity of these markers were also evaluated. A higher serum level of CYFRA 21-1 was significantly correlated with higher tumor stage (p CEA and CA19-9 levels did not differ significantly among each stage and grade. The CYFRA 21-1 level increased significantly along with disease progression (from 7.33 ± 13.3 to 55.9 ± 127 ng/ml, p marker of advanced- and high-grade urothelial carcinoma of the bladder. It is useful for monitoring this disease and for predicting the prognosis. In contrast, the clinical usefulness of CEA and CA19-9 as tumor markers was not demonstrated. Copyright © 2011 S. Karger AG, Basel.

Platelet indices as markers of platelet turnover and aggregation: pathophysiological interpretation, clinical impact, perspectives in research

Directory of Open Access Journals (Sweden)

Malinova L.I.

2017-12-01

Full Text Available The purpose of the review is to characterize existing in open access bibliographical databases such as eLibrary and PubMed evidence on clinical impact of morphometric platelet indices as markers of platelet aggregation ability and turnover as a methodology and theoretical framework of further investigation. Studies results were pooled from open access bibliographic databases (eLibrary, and PubMed according to modified PRISMA algorithm. Relevant studies were identified by systematic searches of the original studies published during the last 10 years in the Russian and English languages. Results of 96 original studies in accordance with inclusion criteria were published during the last 10 years in scientific journals indexed in eLibrary, and PubMed. The majority of publications (64.58% consist of evidence pro diagnostic and prognostic significance of platelet indices. Studies demonstrating the significance of platelet indices as possible risk markers of thrombotic events in cardiovascular patients were predominating among "pro" publications. In 15.63% published results contradict concept of platelet indices usefulness as diagnostic and prognostic markers in clinical practice. Morphometric platelet indices can be considered as useful diagnostic and prognostic markers of thrombotic events in cardiovascular patients. Existing gaps in evidence suggest the need of further investigations.

Conducting Clinically Based Intimate Partner Violence Research: Safety Protocol Recommendations.

Science.gov (United States)

Anderson, Jocelyn C; Glass, Nancy E; Campbell, Jacquelyn C

Maintaining safety is of utmost importance during research involving participants who have experienced intimate partner violence (IPV). Limited guidance on safety protocols to protect participants is available, particularly information related to technology-based approaches to informed consent, data collection, and contacting participants during the course of a study. The purpose of the article is to provide details on the safety protocol developed and utilized with women receiving care at an urban HIV clinic and who were taking part in an observational study of IPV, mental health symptoms, and substance abuse and their relationship to HIV treatment adherence. The protocol presents the technological strategies to promote safety and allow autonomy in participant decision-making throughout the research process, including Voice over Internet Protocol telephone numbers, and tablet-based eligibility screening and data collection. Protocols for management of participants at risk for suicide and/or intimate partner homicide that included automated high-risk messaging to participants and research staff and facilitated disclosure of risk to clinical staff based on participant preferences are discussed. Use of technology and partnership with clinic staff helped to provide an environment where research regarding IPV could be conducted without undue burden or risk to participants. Utilizing tablet-based survey administration provided multiple practical and safety benefits for participants. Most women who screened into high-risk categories for suicide or intimate partner homicide did not choose to have their results shared with their healthcare providers, indicating the importance of allowing participants control over information sharing whenever possible.

[Establish research model of post-marketing clinical safety evaluation for Chinese patent medicine].

Science.gov (United States)

Zheng, Wen-ke; Liu, Zhi; Lei, Xiang; Tian, Ran; Zheng, Rui; Li, Nan; Ren, Jing-tian; Du, Xiao-xi; Shang, Hong-cai

2015-09-01

The safety of Chinese patent medicine has become a focus of social. It is necessary to carry out work on post-marketing clinical safety evaluation for Chinese patent medicine. However, there have no criterions to guide the related research, it is urgent to set up a model and method to guide the practice for related research. According to a series of clinical research, we put forward some views, which contained clear and definite the objective and content of clinical safety evaluation, the work flow should be determined, make a list of items for safety evaluation project, and put forward the three level classification of risk control. We set up a model of post-marketing clinical safety evaluation for Chinese patent medicine. Based this model, the list of items can be used for ranking medicine risks, and then take steps for different risks, aims to lower the app:ds:risksrisk level. At last, the medicine can be managed by five steps in sequence. The five steps are, collect risk signal, risk recognition, risk assessment, risk management, and aftereffect assessment. We hope to provide new ideas for the future research.

Clinical risk management and patient safety education for nurses: a critique.

Science.gov (United States)

Johnstone, Megan-Jane; Kanitsaki, Olga

2007-04-01

Nurses have a pivotal role to play in clinical risk management (CRM) and promoting patient safety in health care domains. Accordingly, nurses need to be prepared educationally to manage clinical risk effectively when delivering patient care. Just what form the CRM and safety education of nurses should take, however, remains an open question. A recent search of the literature has revealed a surprising lack of evidence substantiating models of effective CRM and safety education for nurses. In this paper, a critical discussion is advanced on the question of CRM and safety education for nurses and the need for nurse education in this area to be reviewed and systematically researched as a strategic priority, nationally and internationally. It is a key contention of this paper that without 'good' safety education research it will not be possible to ensure that the educational programs that are being offered to nurses in this area are evidence-based and designed in a manner that will enable nurses to develop the capabilities they need to respond effectively to the multifaceted and complex demands that are inherent in their ethical and professional responsibilities to promote and protect patient safety and quality care in health care domains.

Tumor microenvironment in head and neck squamous cell carcinomas: predictive value and clinical relevance of hypoxic markers. A review.

Science.gov (United States)

Hoogsteen, Ilse J; Marres, Henri A M; Bussink, Johan; van der Kogel, Albert J; Kaanders, Johannes H A M

2007-06-01

Hypoxia and tumor cell proliferation are important factors determining the treatment response of squamous cell carcinomas of the head and neck. Successful approaches have been developed to counteract these resistance mechanisms although usually at the cost of increased short- and long-term side effects. To provide the best attainable quality of life for individual patients and the head and neck cancer patient population as a whole, it is of increasing importance that tools be developed that allow a better selection of patients for these intensified treatments. A literature review was performed with special focus on the predictive value and clinical relevance of endogenous hypoxia-related markers. New methods for qualitative and quantitative assessment of functional microenvironmental parameters such as hypoxia, proliferation, and vasculature have identified several candidate markers for future use in predictive assays. Hypoxia-related markers include hypoxia inducible factor (HIF)-1alpha, carbonic anhydrase IX, glucose transporters, erythropoietin receptor, osteopontin, and others. Although several of these markers and combinations of markers are associated with treatment outcome, their clinical value as predictive factors remains to be established. A number of markers and marker profiles have emerged that may have potential as a predictive assay. Validation of these candidate assays requires testing in prospective trials comparing standard treatment against experimental treatments targeting the related microregional constituent. (c) 2007 Wiley Periodicals, Inc. Head Neck, 2007.

A patient safety objective structured clinical examination.

Science.gov (United States)

Singh, Ranjit; Singh, Ashok; Fish, Reva; McLean, Don; Anderson, Diana R; Singh, Gurdev

2009-06-01

There are international calls for improving education for health care workers around certain core competencies, of which patient safety and quality are integral and transcendent parts. Although relevant teaching programs have been developed, little is known about how best to assess their effectiveness. The objective of this work was to develop and implement an objective structured clinical examination (OSCE) to evaluate the impact of a patient safety curriculum. The curriculum was implemented in a family medicine residency program with 47 trainees. Two years after commencing the curriculum, a patient safety OSCE was developed and administered at this program and, for comparison purposes, to incoming residents at the same program and to residents at a neighboring residency program. All 47 residents exposed to the training, all 16 incoming residents, and 10 of 12 residents at the neighboring program participated in the OSCE. In a standardized patient case, error detection and error disclosure skills were better among trained residents. In a chart-based case, trained residents showed better performance in identifying deficiencies in care and described more appropriate means of addressing them. Third year residents exposed to a "Systems Approach" course performed better at system analysis and identifying system-based solutions after the course than before. Results suggest increased systems thinking and inculcation of a culture of safety among residents exposed to a patient safety curriculum. The main weaknesses of the study are its small size and suboptimal design. Much further investigation is needed into the effectiveness of patient safety curricula.

Marker for the pre-clinical development of bone substitute materials

Directory of Open Access Journals (Sweden)

de Wild Michael

2017-09-01

Full Text Available Thin mechanically stable Ti-cages have been developed for the in-vivo application as X-ray and histology markers for the optimized evaluation of pre-clinical performance of bone graft materials. A metallic frame defines the region of interest during histological investigations and supports the identification of the defect site. This standardization of the procedure enhances the quality of pre-clinical experiments. Different models of thin metallic frameworks were designed and produced out of titanium by additive manufacturing (Selective Laser Melting. The productibility, the mechanical stability, the handling and suitability of several frame geometries were tested during surgery in artificial and in ex-vivo bone before a series of cages was preclinically investigated in the female Göttingen minipigs model. With our novel approach, a flexible process was established that can be adapted to the requirements of any specific animal model and bone graft testing.

Evaluation of clinical and laboratory markers of cardiometabolic risk in overweight and obese children and adolescents

Directory of Open Access Journals (Sweden)

Heloísa Marcelina da Cunha Palhares

Full Text Available OBJECTIVE: This study analyzed the frequency of cardiometabolic risk markers and metabolic syndrome occurrence in overweight and obese children and adolescents. METHODS: The participants included 161 overweight (n=65 and obese (n=96 individuals aged between 5 and 19 years. Clinical markers were assessed (body mass index, body fat percentage, waist circumference, acanthosis, systolic and diastolic blood pressures, laboratory parameters [glucose, insulin, cholesterol (total and fractions and triglyceride levels and homeostasis model assessment of insulin resistance (HOMA-IR index] and leptin and adiponectin levels. The frequency of changes, odds ratios and correlations among markers were determined. Metabolic syndrome was assessed according to International Diabetes Federation criteria. RESULTS: A high frequency of acanthosis (51.6%; increased waist circumference (45.4%, systolic blood pressure / diastolic blood pressure (8.1% / 9.3%, glucose (10%, insulin (36.9% and HOMA-IR (44.3% values; and reduced high-density lipoprotein levels (47.2% were observed. Leptin levels were increased in 95% of obese and in 66% of overweight subjects. Adiponectin was decreased in 29.5% of obese and in 34% of overweight subjects. An odd ratio analysis revealed a greater probability of increased waist circumference (9.0, systolic blood pressure (4.1, triglyceride (2.3 and insulin (2.9 levels and HOMA-IR (3.0 in the obese group than in the overweight group. The clinical and laboratory parameters and leptin levels exhibited significant correlations, whereas adiponectin was negatively correlated with systolic blood pressure. The occurrence rate of metabolic syndrome was 13.6%. CONCLUSIONS: The high frequency of changes in clinical, laboratory and adipokine markers indicates the need for early interventions aimed at preventing cardiometabolic complications in adulthood.

Patient safety and quality of care: how may clinical simulation contribute?

DEFF Research Database (Denmark)

Jensen, Sanne

2015-01-01

The usability of health information technology (IT) is increasingly recognized as critically important to the development of systems that ensure patient safety and quality of care. The substantial complexity of organizations, work practice and physical environments within the healthcare sector...... influences the development and application of health IT. When health IT is introduced in local clinical work practices, potential patient safety hazards and insufficient support of work practices need to be examined. Qualitative methods, such as clinical simulation, may be used to evaluate new technology...

Clinical safety and professional liability claims in Ophthalmology.

Science.gov (United States)

Dolz-Güerri, F; Gómez-Durán, E L; Martínez-Palmer, A; Castilla Céspedes, M; Arimany-Manso, J

2017-11-01

Patient safety is an international public health priority. Ophthalmology scientific societies and organisations have intensified their efforts in this field. As a tool to learn from errors, these efforts have been linked to the management of medical professional liability insurance through the analysis of claims. A review is performed on the improvements in patient safety, as well as professional liability issues in Ophthalmology. There is a high frequency of claims and risk of economic reparation of damage in the event of a claim in Ophthalmology. Special complaints, such as wrong surgery or lack of information, have a high risk of financial compensation and need strong efforts to prevent these potentially avoidable events. Studies focused on pathologies or specific procedures provide information of special interest to sub-specialists. The specialist in Ophthalmology, like any other doctor, is subject to the current legal provisions and appropriate mandatory training in the medical-legal aspects of health care is essential. Professionals must be aware of the fundamental aspects of medical professional liability, as well as specific aspects, such as defensive medicine and clinical safety. The understanding of these medical-legal aspects in the routine clinical practice can help to pave the way towards a satisfactory and safe professional career, and help in increasing patient safety. The aim of this review is to contribute to this training, for the benefit of professionals and patients. Copyright © 2017 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

Prediction of clinical infection in women with preterm labour with intact membranes: a score based on ultrasonographic, clinical and biological markers.

Science.gov (United States)

Kayem, Gilles; Maillard, Françoise; Schmitz, Thomas; Jarreau, Pierre H; Cabrol, Dominique; Breart, Gérard; Goffinet, François

2009-07-01

To predict maternal and neonatal clinical infection at admission in women hospitalized for preterm labour (PTL) with intact membranes. Prospective study of 371 women hospitalized for preterm labour with intact membranes. The primary outcome was clinical infection, defined by clinical chorioamnionitis at delivery or early-onset neonatal infection. Clinical infection was identified in 21 cases (5.7%) and was associated with earlier gestational age at admission for PTL, elevated maternal C-reactive protein (CRP) and white blood cell count (WBC), shorter cervical length, and a cervical funnelling on ultrasound. We used ROC curves to determine the cut-off values that minimized the number of false positives and false negatives. The cut-off points chosen were 30 weeks for gestational age at admission, 25 mm for cervical length, 8 mg/l for CRP and 12,000 c/mm(3) for WBC. Each of these variables was assigned a weight on the basis of the adjusted odds ratios in a clinical infection risk score (CIRS). We set a threshold corresponding to a specificity close to 90%, and calculated the positive and negative predictive values and likelihood ratios of each marker and of the CIRS. The CIRS had a sensitivity of 61.9%, while the sensitivity of the other markers ranged from 19.0% to 42.9%. Internal cross-validation was used to estimate the performance of the CIRS in new subjects. The diagnostic values found remained close to the initial values. A clinical infection risk score built from data known at admission for preterm labour helps to identify women and newborns at high risk of clinical infection.

Clinical usefulness of biochemical markers of liver fibrosis in patients with nonalcoholic fatty liver disease

Institute of Scientific and Technical Information of China (English)

Hiroshi Sakugawa; Fukunori Kinjo; Atsushi Saito; Tomofumi Nakayoshi; Kasen Kobashigawa; Tsuyoshi Yamashiro; Tatsuji Maeshiro; Satoru Miyagi; Joji Shiroma; Akiyo Toyama; Tomokuni Nakayoshi

2005-01-01

AIM: Nonalcoholic steatohepatitis (NASH) is a severe form of nonalcoholic fatty liver disease (NAFLD), and progresses to the end stage of liver disease. Biochemical markers of liver fibrosis are strongly associated with the degree of histological liver fibrosis in patients with chronic liver disease.However, data are few on the usefulness of markers in NAFLD patients. The aim of this study was to identify better noninvasive predictors of hepatic fibrosis, with special focus on markers of liver fibrosis, type Ⅵ collagen 7S domain and hyaluronic acid.METHODS: One hundred and twelve patients with histologically proven NAFLD were studied.RESULTS: The histological stage of NAFLD correlated with several clinical and biochemical variables, the extent of hepatic fibrosis and the markers of liver fibrosis were relatively strong associated. The best cutoff values to detect NASH were assessed by using receiver operating characteristic analysis: type Ⅵ collagen 7S domain ≥5.0 ng/mL, hyaluronic acid ≥43 ng/mL. Both markers had a high positive predictive value: type Ⅵ collagen 7S domain, 86% and hyaluronic acid,92%. Diagnostic accuracies of these markers were evaluated to detect severe fibrosis. Both markers showed high negative predictive values: type Ⅵ collagen 7S domain (≥5.0 ng/mL),84% and hyaluronic acid (≥50 ng/mL), 78%, and were significantly and independently associated with the presence of NASH or severe fibrosis by logistic regression analysis.CONCLUSION: Both markers of liver fibrosis are useful in discriminating NASH from fatty liver alone or patients with severe fibrosis from patients with non-severe fibrosis.

A Randomized, Controlled Clinical Trial Comparing Efficacy, Safety ...

African Journals Online (AJOL)

A Randomized, Controlled Clinical Trial Comparing Efficacy, Safety and Cost Effectiveness of Lornoxicam with Diclofenac Sodium in Patients of Osteoarthritis Knee. ... All patients were assessed with visual analogue scale and 100 meter walking test before starting of therapy, at 15 days and at 1, 2 and 3 months of therapy.

Factors shaping effective utilization of health information technology in urban safety-net clinics.

Science.gov (United States)

George, Sheba; Garth, Belinda; Fish, Allison; Baker, Richard

2013-09-01

Urban safety-net clinics are considered prime targets for the adoption of health information technology innovations; however, little is known about their utilization in such safety-net settings. Current scholarship provides limited guidance on the implementation of health information technology into safety-net settings as it typically assumes that adopting institutions have sufficient basic resources. This study addresses this gap by exploring the unique challenges urban resource-poor safety-net clinics must consider when adopting and utilizing health information technology. In-depth interviews (N = 15) were used with key stakeholders (clinic chief executive officers, medical directors, nursing directors, chief financial officers, and information technology directors) from staff at four clinics to explore (a) nonhealth information technology-related clinic needs, (b) how health information technology may provide solutions, and (c) perceptions of and experiences with health information technology. Participants identified several challenges, some of which appear amenable to health information technology solutions. Also identified were requirements for effective utilization of health information technology including physical infrastructural improvements, funding for equipment/training, creation of user groups to share health information technology knowledge/experiences, and specially tailored electronic billing guidelines. We found that despite the potential benefit that can be derived from health information technologies, the unplanned and uninformed introduction of these tools into these settings might actually create more problems than are solved. From these data, we were able to identify a set of factors that should be considered when integrating health information technology into the existing workflows of low-resourced urban safety-net clinics in order to maximize their utilization and enhance the quality of health care in such settings.

Advancing medication infusion safety through the clinical integration of technology.

Science.gov (United States)

Gerhart, Donald; O'Shea, Kristen; Muller, Sharon

2013-01-01

Adverse drug events resulting from errors in prescribing or administering medications are preventable. Within a hospital system, numerous technologies are employed to address the common sources of medication error, including the use of electronic medical records, physician order entry, smart infusion pumps, and barcode medication administration systems. Infusion safety is inherently risky because of the high-risk medications administered and the lack of integration among the stand-alone systems in most institutions. Intravenous clinical integration (IVCI) is a technology that connects electronic medical records, physician order entry, smart infusion pumps, and barcode medication administration systems. It combines the safety features of an automatically programmed infusion pump (drug, concentration, infusion rate, and patient weight, all auto-programmed into the device) with software that provides visibility to real-time clinical infusion data. Our article describes the characteristics of IVCI at WellSpan Health and its impact on patient safety. The integrated infusion system has the capability of reducing medication errors, improving patient care, reducing in-facility costs, and supporting asset management. It can enhance continuous quality improvement efforts and efficiency of clinical work flow. After implementing IVCI, the institution realized a safer patient environment and a more streamlined work flow for pharmacy and nursing.

Radiation safety considerations and compliance within equine veterinary clinics: Results of an Australian survey

International Nuclear Information System (INIS)

Surjan, Y.; Ostwald, P.; Milross, C.; Warren-Forward, H.

2015-01-01

Objective: To examine current knowledge and the level of compliance of radiation safety principles in equine veterinary clinics within Australia. Method: Surveys were sent to equine veterinary surgeons working in Australia. The survey was delivered both online and in hardcopy format; it comprised 49 questions, 15 of these directly related to radiation safety. The participants were asked about their current and previous use of radiation-producing equipment. Information regarding their level of knowledge and application of radiation safety principles and practice standards was collected and analysed. Results: The use of radiation-producing equipment was evident in 94% of responding clinics (a combination of X-ray, CT and/or Nuclear Medicine Cameras). Of those with radiation-producing equipment, 94% indicated that they hold a radiation licence, 78% had never completed a certified radiation safety course and 19% of participants did not use a personal radiation monitor. In 14% of cases, radiation safety manuals or protocols were not available within clinics. Conclusions: The study has shown that knowledge and application of guidelines as provided by the Code of Practice for Radiation Protection in Veterinary Medicine (2009) is poorly adhered to. The importance of compliance with regulatory requirements is pivotal in minimising occupational exposure to ionising radiation in veterinary medicine, thus there is a need for increased education and training in the area. - Highlights: • Application of the Code of Practice for Veterinary Medicine is poorly adhered to. • Majority of veterinary clinics had not completed certified radiation safety course. • One-fifth of participants did not use personal radiation monitoring. • Increased education and training in area of radiation safety and protection required to generate compliance in clinics

Clinically Meaningful Use of Blood Tumor Markers in Oncology.

Science.gov (United States)

Holdenrieder, Stefan; Pagliaro, Lance; Morgenstern, David; Dayyani, Farshid

2016-01-01

Before the introduction of modern imaging techniques and the recent developments in molecular diagnosis, tumor markers (TMs) were among the few available diagnostic tools for the management of cancer patients. Easily obtained from serum or plasma samples, TMs are minimally invasive and convenient, and the associated costs are low. Single TMs were traditionally used but these have come under scrutiny due to their low sensitivity and specificity when used, for example, in a screening setting. However, recent research has shown superior performance using a combination of multiple TMs as a panel for assessment, or as part of validated algorithms that also incorporate other clinical factors. In addition, newer TMs have been discovered that have an increased sensitivity and specificity profile for defined malignancies. The aim of this review is to provide a concise overview of the appropriate uses of both traditional and newer TMs and their roles in diagnosis, prognosis, and the monitoring of patients in current clinical practice. We also look at the future direction of TMs and their integration with other diagnostic modalities and other emerging serum based biomarkers, such as circulating nucleic acids, to ultimately advance diagnostic performance and improve patient management.

Clinically Meaningful Use of Blood Tumor Markers in Oncology

Directory of Open Access Journals (Sweden)

Stefan Holdenrieder

2016-01-01

Full Text Available Before the introduction of modern imaging techniques and the recent developments in molecular diagnosis, tumor markers (TMs were among the few available diagnostic tools for the management of cancer patients. Easily obtained from serum or plasma samples, TMs are minimally invasive and convenient, and the associated costs are low. Single TMs were traditionally used but these have come under scrutiny due to their low sensitivity and specificity when used, for example, in a screening setting. However, recent research has shown superior performance using a combination of multiple TMs as a panel for assessment, or as part of validated algorithms that also incorporate other clinical factors. In addition, newer TMs have been discovered that have an increased sensitivity and specificity profile for defined malignancies. The aim of this review is to provide a concise overview of the appropriate uses of both traditional and newer TMs and their roles in diagnosis, prognosis, and the monitoring of patients in current clinical practice. We also look at the future direction of TMs and their integration with other diagnostic modalities and other emerging serum based biomarkers, such as circulating nucleic acids, to ultimately advance diagnostic performance and improve patient management.

Marker-based or model-based RSA for evaluation of hip resurfacing arthroplasty? A clinical validation and 5-year follow-up.

Science.gov (United States)

Lorenzen, Nina Dyrberg; Stilling, Maiken; Jakobsen, Stig Storgaard; Gustafson, Klas; Søballe, Kjeld; Baad-Hansen, Thomas

2013-11-01

The stability of implants is vital to ensure a long-term survival. RSA determines micro-motions of implants as a predictor of early implant failure. RSA can be performed as a marker- or model-based analysis. So far, CAD and RE model-based RSA have not been validated for use in hip resurfacing arthroplasty (HRA). A phantom study determined the precision of marker-based and CAD and RE model-based RSA on a HRA implant. In a clinical study, 19 patients were followed with stereoradiographs until 5 years after surgery. Analysis of double-examination migration results determined the clinical precision of marker-based and CAD model-based RSA, and at the 5-year follow-up, results of the total translation (TT) and the total rotation (TR) for marker- and CAD model-based RSA were compared. The phantom study showed that comparison of the precision (SDdiff) in marker-based RSA analysis was more precise than model-based RSA analysis in TT (p CAD RSA analysis (p = 0.002), but showed no difference between the marker- and CAD model-based RSA analysis regarding the TR (p = 0.91). Comparing the mean signed values regarding the TT and the TR at the 5-year follow-up in 13 patients, the TT was lower (p = 0.03) and the TR higher (p = 0.04) in the marker-based RSA compared to CAD model-based RSA. The precision of marker-based RSA was significantly better than model-based RSA. However, problems with occluded markers lead to exclusion of many patients which was not a problem with model-based RSA. HRA were stable at the 5-year follow-up. The detection limit was 0.2 mm TT and 1° TR for marker-based and 0.5 mm TT and 1° TR for CAD model-based RSA for HRA.

Understanding of safety monitoring in clinical trials by individuals with CF or their parents: A qualitative analysis.

Science.gov (United States)

Kern-Goldberger, Andrew S; Hessels, Amanda J; Saiman, Lisa; Quittell, Lynne M

2018-03-14

Recruiting both pediatric and adult participants for clinical trials in CF is currently of paramount importance as numerous new therapies are being developed. However, recruitment is challenging as parents of children with CF and adults with CF cite safety concerns as a principal barrier to enrollment. In conjunction with the CF Foundation (CFF) Data Safety Monitoring Board (DSMB), a pilot brochure was developed to inform patients and parents of the multiple levels of safety monitoring; the CFF simultaneously created an infographic representing the safety monitoring process. This study explores the attitudes and beliefs of CF patients and families regarding safety monitoring and clinical trial participation, and elicits feedback regarding the educational materials. Semi-structured interviews were conducted using a pre-tested interview guide and audio-recorded during routine CF clinic visits. Participants included 5 parents of children with CF quotations: attitudes toward clinical trials, safety values, conceptualizing the safety monitoring process, and priorities for delivery of patient education. Participant feedback was used to revise the pilot brochure; text was shortened, unfamiliar words clarified (e.g., "pipeline"), abbreviations eliminated, and redundancy avoided. Qualitative analysis of CF patient and family interviews provided insights into barriers to participation in clinical trials, safety concerns, perspectives on safety monitoring and educational priorities. We plan a multicenter study to determine if the revised brochure reduces knowledge, attitude and practice barriers regarding participation in CF clinical trials. Copyright © 2018 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Manual Dexterity in Schizophrenia—A Neglected Clinical Marker?

Directory of Open Access Journals (Sweden)

Maxime Térémetz

2017-07-01

dexterity may represent a useful clinical marker in schizophrenia.

[Biological markers for the status of vitamins B12 and D: the importance of some analytical aspects in relation to clinical interpretation of results].

Science.gov (United States)

Boulat, O; Rey, F; Mooser, V

2012-10-31

Biological markers for the status of vitamins B12 and D: the importance of some analytical aspects in relation to clinical interpretation of results When vitamin B12 deficiency is expressed clinically, the diagnostic performance of total cobalamin is identical to that of holotranscobalamin II. In subclinical B12 deficiency, the two aforementioned markers perform less well. Additional analysis of a second, functional marker (methylmalonate or homocysteine) is recommended. Different analytical approaches for 25-hydroxyvitamin D quantification, the marker of vitamin D deficiency, are not yet standardized. Measurement biases of up to +/- 20% compared with the original method used to establish threshold values are still observed.

Patient safety and quality of care: How may clinical simulation contribute?

Directory of Open Access Journals (Sweden)

Sanne Jensen

2015-09-01

Full Text Available The usability of health information technology (IT is increasingly recognized as critically important to the development of systems that ensure patient safety and quality of care. The substantial complexity of organizations, work practice and physical environments within the healthcare sector influences the development and application of health IT. When health IT is introduced in local clinical work practices, potential patient safety hazards and insufficient support of work practices need to be examined. Qualitative methods, such as clinical simulation, may be used to evaluate new technology in correlation with the clinical context and to study the interaction between users, technology and work practice. Compared with the “classic” methods, such as heuristic inspection and usability testing, clinical simulation takes the clinical context into account. Clinical simulation can be useful in many processes in the human-centred design cycle. In the requirement specification, clinical simulation can be useful to analyze user requirements and work practice as well to evaluate requirements. In the design of health IT, clinical simulation can be used to evaluate clinical information systems and serve as common ground to help to achieve a shared understanding between various communities of practice. In a public procurement process, a clinical simulation-based assessment can help give insight into different solutions and how they support work practice. Before organizational implementation, clinical simulation is a very suitable means, by which to assess an application in connection with work practice.

Tumour markers in urology

International Nuclear Information System (INIS)

Schmid, L.; Fornara, P.; Fabricius, P.G.

1988-01-01

The same applies essentially also for the bladder carcinomas: There is no reliable marker for these cancers which would be useful for clinical purposes. TPA has proven to be too non-specific in malignoma-detection and therefore hardly facilitates clinical decision-making in individual cases. The CEA is not sensitive enough to be recommendable for routine application. However, in advanced stages a CEA examination may be useful if applied within the scope of therapeutic efforts made to evaluate efficacy. In cases of carcinomas of the prostate the sour prostate-specific phosphatase (SPP) and, more recently, especially the prostate-specific antigen (PSA) have proven in follow-up and therapy monitoring, whereby the PSA is superior to the SPP. Nevertheless, both these markers should be employed in therapy monitoring because differences in behaviour will be observed when the desired treatment effect is only achieved in one of the two markers producing tumour cell clonuses. Both markers, but especially the PSA, are quite reliably in agreement with the result of the introduced chemo-/hormone therapy, whereby an increase may be a sure indicator of relapse several months previous to clinical symptoms, imaging procedures, so-called routine laboratory results and subjective complaints. However, none of the 2 markers is appropriate for the purposes of screening or early diagnosis of carcinomas of the prostate. (orig.) [de

Safety measurement and monitoring in healthcare: a framework to guide clinical teams and healthcare organisations in maintaining safety

Science.gov (United States)

Vincent, Charles; Burnett, Susan; Carthey, Jane

2014-01-01

Patients, clinicians and managers all want to be reassured that their healthcare organisation is safe. But there is no consensus about what we mean when we ask whether a healthcare organisation is safe or how this is achieved. In the UK, the measurement of harm, so important in the evolution of patient safety, has been neglected in favour of incident reporting. The use of softer intelligence for monitoring and anticipation of problems receives little mention in official policy. The Francis Inquiry report into patient treatment at the Mid Staffordshire NHS Foundation Trust set out 29 recommendations on measurement, more than on any other topic, and set the measurement of safety an absolute priority for healthcare organisations. The Berwick review found that most healthcare organisations at present have very little capacity to analyse, monitor or learn from safety and quality information. This paper summarises the findings of a more extensive report and proposes a framework which can guide clinical teams and healthcare organisations in the measurement and monitoring of safety and in reviewing progress against safety objectives. The framework has been used so far to promote self-reflection at both board and clinical team level, to stimulate an organisational check or analysis in the gaps of information and to promote discussion of ‘what could we do differently’. PMID:24764136

Prediction of Driving Safety in Individuals with Homonymous Hemianopia and Quadrantanopia from Clinical Neuroimaging

Directory of Open Access Journals (Sweden)

Michael S. Vaphiades

2014-01-01

Full Text Available Background. This study aimed to determine whether it is possible to predict driving safety of individuals with homonymous hemianopia or quadrantanopia based upon a clinical review of neuroimages that are routinely available in clinical practice. Methods. Two experienced neuroophthalmologists viewed a summary report of the CT/MRI scans of 16 participants with homonymous hemianopic or quadrantanopic field defects which indicated the site and extent of the lesion and they made predictions regarding whether participants would be safe/unsafe to drive. Driving safety was independently defined at the time of the study using state-recorded motor vehicle crashes (all crashes and at-fault for the previous 5 years and ratings of driving safety determined through a standardized on-road driving assessment by a certified driving rehabilitation specialist. Results. The ability to predict driving safety was highly variable regardless of the driving safety measure, ranging from 31% to 63% (kappa levels ranged from −0.29 to 0.04. The level of agreement between the neuroophthalmologists was only fair (kappa = 0.28. Conclusions. Clinical evaluation of summary reports of currently available neuroimages by neuroophthalmologists is not predictive of driving safety. Future research should be directed at identifying and/or developing alternative tests or strategies to better enable clinicians to make these predictions.

Prediction of driving safety in individuals with homonymous hemianopia and quadrantanopia from clinical neuroimaging.

Science.gov (United States)

Vaphiades, Michael S; Kline, Lanning B; McGwin, Gerald; Owsley, Cynthia; Shah, Ritu; Wood, Joanne M

2014-01-01

Background. This study aimed to determine whether it is possible to predict driving safety of individuals with homonymous hemianopia or quadrantanopia based upon a clinical review of neuroimages that are routinely available in clinical practice. Methods. Two experienced neuroophthalmologists viewed a summary report of the CT/MRI scans of 16 participants with homonymous hemianopic or quadrantanopic field defects which indicated the site and extent of the lesion and they made predictions regarding whether participants would be safe/unsafe to drive. Driving safety was independently defined at the time of the study using state-recorded motor vehicle crashes (all crashes and at-fault) for the previous 5 years and ratings of driving safety determined through a standardized on-road driving assessment by a certified driving rehabilitation specialist. Results. The ability to predict driving safety was highly variable regardless of the driving safety measure, ranging from 31% to 63% (kappa levels ranged from -0.29 to 0.04). The level of agreement between the neuroophthalmologists was only fair (kappa = 0.28). Conclusions. Clinical evaluation of summary reports of currently available neuroimages by neuroophthalmologists is not predictive of driving safety. Future research should be directed at identifying and/or developing alternative tests or strategies to better enable clinicians to make these predictions.

Evaluating the Clinical Learning Environment: Resident and Fellow Perceptions of Patient Safety Culture.

Science.gov (United States)

Bump, Gregory M; Calabria, Jaclyn; Gosman, Gabriella; Eckart, Catherine; Metro, David G; Jasti, Harish; McCausland, Julie B; Itri, Jason N; Patel, Rita M; Buchert, Andrew

2015-03-01

The Accreditation Council for Graduate Medical Education has begun to evaluate teaching institutions' learning environments with Clinical Learning Environment Review visits, including trainee involvement in institutions' patient safety and quality improvement efforts. We sought to address the dearth of metrics that assess trainee patient safety perceptions of the clinical environment. Using the Hospital Survey on Patient Safety Culture (HSOPSC), we measured resident and fellow perceptions of patient safety culture in 50 graduate medical education programs at 10 hospitals within an integrated health system. As institution-specific physician scores were not available, resident and fellow scores on the HSOPSC were compared with national data from 29 162 practicing providers at 543 hospitals. Of the 1337 residents and fellows surveyed, 955 (71.4%) responded. Compared with national practicing providers, trainees had lower perceptions of patient safety culture in 6 of 12 domains, including teamwork within units, organizational learning, management support for patient safety, overall perceptions of patient safety, feedback and communication about error, and communication openness. Higher perceptions were observed for manager/supervisor actions promoting patient safety and for staffing. Perceptions equaled national norms in 4 domains. Perceptions of patient safety culture did not improve with advancing postgraduate year. Trainees in a large integrated health system have variable perceptions of patient safety culture, as compared with national norms for some practicing providers. Administration of the HSOPSC was feasible and acceptable to trainees, and may be used to track perceptions over time.

Safety and usefulness of outreach clinic conducted by pediatric echosonographers

International Nuclear Information System (INIS)

Al Harbi, Badr; Al Akhfash, Ali A.; Al Ghamdi, Abdullah; Al-Mesned, Abdulrahman

2012-01-01

Outreach echocardiographic services led by cardiac sonographers may help district level hospitals in the management of patients suspected to have cardiac anomalies. However, the safety and utility of such an approach is not tested. We retrospectively reviewed our experience of patients seen in the outreach visits by the echocardiographers alone and subsequently reviewed in the pediatric cardiology clinic. Comparison between the diagnosis made by the echocardiographer and the consultant pediatric cardiologist were done. We defined safety as no change in patient management plan between the outreach evaluation and the pediatric cardiology clinic evaluation, and we defined usefulness as being beneficial, serviceable and of practical use. Two senior echocardiographic technicians did 41 clinic visits and over a period of 17 months, 623 patients were seen. Patients less than 3 months of age constitute 63% of the total patients seen. Normal echocardiographic examinations were found in 342 (55%) of patients. These patients were not seen in our cardiology clinic. Abnormal echocardiographic examinations were found in 281 (45%) of patients. Among the 281 patients with abnormal echos in the outreach visits, 251 patients (89.3%) were seen in the pediatric cardiology clinic. Comparing the results of the outreach clinic evaluation to that of the pediatric cardiology clinic, 73 patients (29%) diagnosed to have a minor CHD turned to have normal echocardiographic examinations. In all patients seen in both the outreach clinics and the pediatric tertiary cardiac clinics there was no change in patient's management plan. Outreach clinic conducted by pediatric echo sonographers could be useful and safe. It may help in reducing unnecessary visits to pediatric cardiology clinics, provide parental reassurance, and help in narrowing the differential diagnosis in critically ill patient unable to be transferred to tertiary cardiac centers provided it is done by experienced echosonographers

Effects of an onion by-product on bioactivity and safety markers in healthy rats

DEFF Research Database (Denmark)

Roldan-Marin, Eduvigis; Krath, Britta; Poulsen, Morten

2009-01-01

Onions are excellent sources of bioactive compounds including fructo-oligosaccharides (FOS) and polyphenols. An onion by-product was characterised in order to be developed as a potentially bioactive food ingredient. Our main aim was to investigate whether the potential health and safety effects...... of this onion by-product were shared by either of two derived fractions, an extract containing the onion FOS and polyphenols and a residue fraction containing mainly cell wall materials. We report here on the effects of feeding these products on markers of potential toxicity, protective enzymes and gut...... environment in healthy rats. Rats were fed during 4 weeks with a diet containing the products or a control feed balanced in carbohydrate. The onion by-product and the extract caused anaemia as expected in rodents for Allium products. No other toxicity was observed, including genotoxicity. Glutathione...

Evaluation of features to support safety and quality in general practice clinical software

Science.gov (United States)

2011-01-01

Background Electronic prescribing is now the norm in many countries. We wished to find out if clinical software systems used by general practitioners in Australia include features (functional capabilities and other characteristics) that facilitate improved patient safety and care, with a focus on quality use of medicines. Methods Seven clinical software systems used in general practice were evaluated. Fifty software features that were previously rated as likely to have a high impact on safety and/or quality of care in general practice were tested and are reported here. Results The range of results for the implementation of 50 features across the 7 clinical software systems was as follows: 17-31 features (34-62%) were fully implemented, 9-13 (18-26%) partially implemented, and 9-20 (18-40%) not implemented. Key findings included: Access to evidence based drug and therapeutic information was limited. Decision support for prescribing was available but varied markedly between systems. During prescribing there was potential for medicine mis-selection in some systems, and linking a medicine with its indication was optional. The definition of 'current medicines' versus 'past medicines' was not always clear. There were limited resources for patients, and some medicines lists for patients were suboptimal. Results were provided to the software vendors, who were keen to improve their systems. Conclusions The clinical systems tested lack some of the features expected to support patient safety and quality of care. Standards and certification for clinical software would ensure that safety features are present and that there is a minimum level of clinical functionality that clinicians could expect to find in any system.

Sudden cardiac death and pump failure death prediction in chronic heart failure by combining ECG and clinical markers in an integrated risk model

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Orini, Michele; Mincholé, Ana; Monasterio, Violeta; Cygankiewicz, Iwona; Bayés de Luna, Antonio; Martínez, Juan Pablo

2017-01-01

Background Sudden cardiac death (SCD) and pump failure death (PFD) are common endpoints in chronic heart failure (CHF) patients, but prevention strategies are different. Currently used tools to specifically predict these endpoints are limited. We developed risk models to specifically assess SCD and PFD risk in CHF by combining ECG markers and clinical variables. Methods The relation of clinical and ECG markers with SCD and PFD risk was assessed in 597 patients enrolled in the MUSIC (MUerte Súbita en Insuficiencia Cardiaca) study. ECG indices included: turbulence slope (TS), reflecting autonomic dysfunction; T-wave alternans (TWA), reflecting ventricular repolarization instability; and T-peak-to-end restitution (ΔαTpe) and T-wave morphology restitution (TMR), both reflecting changes in dispersion of repolarization due to heart rate changes. Standard clinical indices were also included. Results The indices with the greatest SCD prognostic impact were gender, New York Heart Association (NYHA) class, left ventricular ejection fraction, TWA, ΔαTpe and TMR. For PFD, the indices were diabetes, NYHA class, ΔαTpe and TS. Using a model with only clinical variables, the hazard ratios (HRs) for SCD and PFD for patients in the high-risk group (fifth quintile of risk score) with respect to patients in the low-risk group (first and second quintiles of risk score) were both greater than 4. HRs for SCD and PFD increased to 9 and 11 when using a model including only ECG markers, and to 14 and 13, when combining clinical and ECG markers. Conclusion The inclusion of ECG markers capturing complementary pro-arrhythmic and pump failure mechanisms into risk models based only on standard clinical variables substantially improves prediction of SCD and PFD in CHF patients. PMID:29020031

[Validation of a questionnaire to evaluate patient safety in clinical laboratories].

Science.gov (United States)

Giménez Marín, Ángeles; Rivas-Ruiz, Francisco

2012-01-01

The aim of this study was to prepare, pilot and validate a questionnaire to evaluate patient safety in the specific context of clinical laboratories. A specific questionnaire on patient safety in the laboratory, with 62 items grouped into six areas, was developed, taking into consideration the diverse human and laboratory contextual factors which may contribute to producing errors. A pilot study of 30 interviews was carried out, including validity and reliability analyses using principal components factor analysis and Cronbach's alpha. Subsequently, 240 questionnaires were sent to 21 hospitals, followed by a test-retest of 41 questionnaires with the definitive version. The sample analyzed was composed of 225 questionnaires (an overall response rate of 80%). Of the 62 items initially assessed, 17 were eliminated due to non-compliance with the criteria established before the principal components factor analysis was performed. For the 45 remaining items, 12 components were identified, with an cumulative variance of 69.5%. In seven of the 10 components with two or more items, Cronbach's alpha was higher than 0.7. The questionnaire items assessed in the test-retest were found to be stable. We present the first questionnaire with sufficiently proven validity and reliability for evaluating patient safety in the specific context of clinical laboratories. This questionnaire provides a useful instrument to perform a subsequent macrostudy of hospital clinical laboratories in Spain. The questionnaire can also be used to monitor and promote commitment to patient safety within the search for continuous quality improvement. Copyright © 2011 SESPAS. Published by Elsevier Espana. All rights reserved.

Fire safety in dental clinics: Basics for dentists and dental students

Directory of Open Access Journals (Sweden)

Kalyana Chakravarthy Pentapati

2015-01-01

Full Text Available Fire safety is essential component and requirement in health care sector. It includes components like emergency exits, manual call outs, different types of fire extinguishers, safe assembly area, fire hydrant system with water sprinkler systems etc. We attempt to provide some basics about fire and fire safety that are prerequisite for safe working environment in dental clinics along with some recommendations that can be incorporated in the curriculum.

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

Science.gov (United States)

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

2012-07-01

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

Clinical and atopic parameters and airway inflammatory markers in childhood asthma: a factor analysis

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Leung, T; Wong, G; Ko, F; Lam, C; Fok, T

2005-01-01

Background: Recent studies have repeatedly shown weak correlations among lung function parameters, atopy, exhaled nitric oxide level (FeNO), and airway inflammatory markers, suggesting that they are non-overlapping characteristics of asthma in adults. A study was undertaken to determine, using factor analysis, whether the above features represent separate dimensions of childhood asthma. Methods: Clinically stable asthmatic patients aged 7–18 years underwent spirometric testing, methacholine bronchial challenge, blood sampling for atopy markers and chemokine levels (macrophage derived chemokine (MDC), thymus and activation regulated chemokine (TARC), and eotaxin), FeNO, and chemokines (MDC and eotaxin) and leukotriene B4 measurements in exhaled breath condensate (EBC). Results: The mean (SD) forced expiratory volume in 1 second (FEV1) and FeNO of 92 patients were 92.1 (15.9)% predicted and 87.3 (65.7) ppb, respectively. 59% of patients received inhaled corticosteroids. Factor analysis selected four different factors, explaining 55.5% of total variance. The Kaiser-Meyer-Olkin measure of sampling adequacy was 0.587. Plasma total and specific IgE levels, peripheral blood eosinophil percentage, and FeNO loaded on factor 1; plasma TARC and MDC concentrations on factor 2; MDC, eotaxin and leukotriene B4 concentrations in EBC on factor 3; and plasma eotaxin concentration together with clinical indices including body mass index and disease severity score loaded on factor 4. Post hoc factor analyses revealed similar results when outliers were excluded. Conclusions: The results suggest that atopy related indices and airway inflammation are separate dimensions in the assessment of childhood asthma, and inflammatory markers in peripheral blood and EBC are non-overlapping factors of asthma. PMID:16055623

75 FR 47602 - Clinical Studies of Safety and Effectiveness of Orphan Products Research Project Grant (R01)

Science.gov (United States)

2010-08-06

...] Clinical Studies of Safety and Effectiveness of Orphan Products Research Project Grant (R01) AGENCY: Food... (OPD) grant program. The goal of FDA's OPD grant program is to support the clinical development of... product will be superior to the existing therapy. FDA provides grants for clinical studies on safety and...

The subject-fixated coaxially sighted corneal light reflex: a clinical marker for centration of refractive treatments and devices.

Science.gov (United States)

Chang, Daniel H; Waring, George O

2014-11-01

To describe the inconsistencies in definition, application, and usage of the ocular reference axes (optical axis, visual axis, line of sight, pupillary axis, and topographic axis) and angles (angle kappa, lambda, and alpha) and to propose a precise, reproducible, clinically defined reference marker and axis for centration of refractive treatments and devices. Perspective. Literature review of papers dealing with ocular reference axes, angles, and centration. The inconsistent definitions and usage of the current ocular axes, as derived from eye models, limit their clinical utility. With a clear understanding of Purkinje images and a defined alignment of the observer, light source/fixation target, and subject eye, the subject-fixated coaxially sighted corneal light reflex can be a clinically useful reference marker. The axis formed by connecting the subject-fixated coaxially sighted corneal light reflex and the fixation point, the subject-fixated coaxially sighted corneal light reflex axis, is independent of pupillary dilation and phakic status of the eye. The relationship of the subject-fixated coaxially sighted corneal light reflex axis to a refined definition of the visual axis without reference to nodal points, the foveal-fixation axis, is discussed. The displacement between the subject-fixated coaxially sighted corneal light reflex and pupil center is described not by an angle, but by a chord, here termed chord mu. The application of the subject-fixated coaxially sighted corneal light reflex to the surgical centration of refractive treatments and devices is discussed. As a clinically defined reference marker, the subject-fixated coaxially sighted corneal light reflex avoids the shortcomings of current ocular axes for clinical application and may contribute to better consensus in the literature and improved patient outcomes. Copyright © 2014 Elsevier Inc. All rights reserved.

Time since start of first-line therapy as a predictive clinical marker for nintedanib in patients with previously treated non-small cell lung cancer

DEFF Research Database (Denmark)

Gaschler-Markefski, Birgit; Sikken, Patricia; Heymach, John V

2017-01-01

INTRODUCTION: No predictive clinical or genetic markers have been identified or validated for antiangiogenic agents in lung cancer. We aimed to identify a predictive clinical marker of benefit for nintedanib, an angiokinase inhibitor, using data from two large second-line non-small cell lung cancer...... Phase III trials (LUME-Lung 1 ([LL1] and LUME-Lung 2). METHODS: Predictive marker identification was conducted in a multi-step process using data from both trials; a hypothesis was generated, confirmed and validated. Statistical analyses included a stepwise selection approach, a recursive partitioning...... method and the evaluation of HRs, including treatment-by-covariate interactions. The marker was finally validated using a prospectively defined hierarchical testing procedure and treatment-by-covariate interaction for overall survival (OS) based on LL1. RESULTS: Time since start of first-line therapy...

Clinical use of serum TRA-1-60 as tumor marker in patients with germ cell cancer

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Lajer, Henrik; Daugaard, Gedske; Andersson, Anna-Maria

2002-01-01

TRA-1-60 antigen has been related to the presence of embryonal germ cell carcinoma (EC) and carcinoma in situ. Our study further investigated the clinical efficacy of TRA-1-60 as a serum tumor marker for germ cell cancer in the testis. Three groups of patients with germ cell tumors were included:...

A multidisciplinary three-phase approach to improve the clinical utility of patient safety indicators.

Science.gov (United States)

Najjar, Peter; Kachalia, Allen; Sutherland, Tori; Beloff, Jennifer; David-Kasdan, Jo Ann; Bates, David W; Urman, Richard D

2015-01-01

The AHRQ Patient Safety Indicators (PSIs) are used for calculation of risk-adjusted postoperative rates for adverse events. The payers and quality consortiums are increasingly requiring public reporting of hospital performance on these metrics. We discuss processes designed to improve the accuracy and clinical utility of PSI reporting in practice. The study was conducted at a 793-bed tertiary care academic medical center where PSI processes have been aggressively implemented to track patient safety events at discharge. A three-phased approach to improving administrative data quality was implemented. The initiative consisted of clinical review of all PSIs, documentation improvement, and provider outreach including active querying for patient safety events. This multidisciplinary effort to develop a streamlined process for PSI calculation reduced the reporting of miscoded PSIs and increased the clinical utility of PSI monitoring. Over 4 quarters, 4 of 41 (10%) PSI-11 and 9 of 138 (7%) PSI-15 errors were identified on review of clinical documentation and appropriate adjustments were made. A multidisciplinary, phased approach leveraging existing billing infrastructure for robust metric coding, ongoing clinical review, and frontline provider outreach is a novel and effective way to reduce the reporting of false-positive outcomes and improve the clinical utility of PSIs.

Frailty Markers and Treatment Decisions in Patients Seen in Oncogeriatric Clinics: Results from the ASRO Pilot Study.

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Farcet, Anaïs; de Decker, Laure; Pauly, Vanessa; Rousseau, Frédérique; Bergman, Howard; Molines, Catherine; Retornaz, Frédérique

2016-01-01

Comprehensive Geriatric Assessment (CGA) is the gold standard to help oncologists select the best cancer treatment for their older patients. Some authors have suggested that the concept of frailty could be a more useful approach in this population. We investigated whether frailty markers are associated with treatment recommendations in an oncogeriatric clinic. This prospective study included 70 years and older patients with solid tumors and referred for an oncogeriatric assessment. The CGA included nine domains: autonomy, comorbidities, medication, cognition, nutrition, mood, neurosensory deficits, falls, and social status. Five frailty markers were assessed (nutrition, physical activity, energy, mobility, and strength). Patients were categorized as Frail (three or more frailty markers), pre-frail (one or two frailty markers), or not-frail (no frailty marker). Treatment recommendations were classified into two categories: standard treatment with and without any changes and supportive/palliative care. Multiple logistic regression models were used to analyze factors associated with treatment recommendations. 217 patients, mean age 83 years (± Standard deviation (SD) 5.3), were included. In the univariate analysis, number of frailty markers, grip strength, physical activity, mobility, nutrition, energy, autonomy, depression, Eastern Cooperative Oncology Group Scale of Performance Status (ECOG-PS), and falls were significantly associated with final treatment recommendations. In the multivariate analysis, the number of frailty markers and basic Activities of Daily Living (ADL) were significantly associated with final treatment recommendations (pmarkers are associated with final treatment recommendations in older cancer patients. Longitudinal studies are warranted to better determine their use in a geriatric oncology setting.

Somatostatin receptor scintigraphy in sarcoidosis: relation to selected clinical and laboratory markers.

Science.gov (United States)

Piotrowski, Wojciech J; Bieńkiewicz, Małgorzata; Frieske, Izabella; Marczak, Jerzy; Antczak, Adam; Górski, Paweł; Kuśmierek, Jacek; Płachcińska, Anna

2012-01-01

Discriminating between active and inactive sarcoidosis may be problematic in everyday clinical practice. There are numerous biochemical markers used in the diagnosis and monitoring of sarcoidosis. Somatostatin receptor (SR) scintigraphy with the use of 99mTc-octreotide may be used to estimate disease activity. The aim of the paper was to assess the value of traditional biomarkers (serum angiotensin-converting enzyme [SACE], C-reactive protein, markers of calcium metabolism, bronchoalveolar lavage fluid [BALF] lymphocytes) and a novel biomarker, 8-isoprostane (8-IP) in exhaled breath condensate (EBC), in the assessment of sarcoidosis activity in relation to somatostatin receptor scintigraphy. The study included 32 patients with sarcoidosis. Scintigraphy was performed using somatostatin analogue, 99mTc-HYNIC-TOC; planar and SPECT/CT images were recorded. The study group was divided into a subgroup with positive radiotracer uptake (n = 20) and without a visible uptake (n = 12). 8-IP levels were measured in EBC by an immunoenzymatic assay. RESULTS We observed a significantly higher EBC 8-IP levels in the subgroup with positive uptake compared with those with negative uptake (19.1 ± 19.8 vs. 5.4 ± 3.5 pg/ml, P = 0.02). The levels of SACE and the percentage of BALF lymphocytes were also nonsignificantly elevated. In the group of patients with positive scintigraphy results, a positive correlation was observed between the uptake ratio and SACE (r = 0.44, P = 0.041). The results indicate low value of biochemical markers in the assessment of disease activity. SR scintigraphy may have practical usefulness in the monitoring of sarcoidosis.

Is a comparative clinical trial for breast cancer tumor markers to monitor disease recurrence warranted? A value of information analysis.

Science.gov (United States)

Thariani, Rahber; Henry, Norah Lynn; Ramsey, Scott D; Blough, David K; Barlow, Bill; Gralow, Julie R; Veenstra, David L

2013-05-01

Breast cancer tumor markers are used by some clinicians to screen for disease recurrence risk. Since there is limited evidence of benefit, additional research may be warranted. To assess the potential value of a randomized clinical trial of breast tumor marker testing in routine follow-up of high-risk, stage II-III breast cancer survivors. We developed a decision-analytic model of tumor marker testing plus standard surveillance every 3-6 months for 5 years. The expected value of sample information was calculated using probabilistic simulations and was a function of: the probability of selecting the optimal monitoring strategy with current versus future information; the impact of choosing the nonoptimal strategy; and the size of the population affected. The value of information for a randomized clinical trial involving 9000 women was US$214 million compared with a cost of US$30-60 million to conduct such a trial. The probability of making an alternate, nonoptimal decision and choosing testing versus no testing was 32% with current versus future information from the trial. The impact of a nonoptimal decision was US$2150 and size of population impacted over 10 years was 308,000. The value of improved information on overall survival was US$105 million, quality of life US$37 million and test performance US$71 million. Conducting a randomized clinical trial of breast cancer tumor markers appears to offer a good societal return on investment. Retrospective analyses to assess test performance and evaluation of patient quality of life using tumor markers may also offer valuable areas of research. However, alternative investments may offer even better returns in investments and, as such, the trial concept deserves further study as part of an overall research-portfolio evaluation.

Assessment of patient safety culture in clinical laboratories in the Spanish National Health System.

Science.gov (United States)

Giménez-Marín, Angeles; Rivas-Ruiz, Francisco; García-Raja, Ana M; Venta-Obaya, Rafael; Fusté-Ventosa, Margarita; Caballé-Martín, Inmaculada; Benítez-Estevez, Alfonso; Quinteiro-García, Ana I; Bedini, José Luis; León-Justel, Antonio; Torra-Puig, Montserrat

2015-01-01

There is increasing awareness of the importance of transforming organisational culture in order to raise safety standards. This paper describes the results obtained from an evaluation of patient safety culture in a sample of clinical laboratories in public hospitals in the Spanish National Health System. A descriptive cross-sectional study was conducted among health workers employed in the clinical laboratories of 27 public hospitals in 2012. The participants were recruited by the heads of service at each of the participating centers. Stratified analyses were performed to assess the mean score, standardized to a base of 100, of the six survey factors, together with the overall patient safety score. 740 completed questionnaires were received (88% of the 840 issued). The highest standardized scores were obtained in Area 1 (individual, social and cultural) with a mean value of 77 (95%CI: 76-78), and the lowest ones, in Area 3 (equipment and resources), with a mean value of 58 (95%CI: 57-59). In all areas, a greater perception of patient safety was reported by the heads of service than by other staff. We present the first multicentre study to evaluate the culture of clinical safety in public hospital laboratories in Spain. The results obtained evidence a culture in which high regard is paid to safety, probably due to the pattern of continuous quality improvement. Nevertheless, much remains to be done, as reflected by the weaknesses detected, which identify areas and strategies for improvement.

De novo sequencing of circulating miRNAs identifies novel markers predicting clinical outcome of locally advanced breast cancer

Directory of Open Access Journals (Sweden)

Wu Xiwei

2012-03-01

Full Text Available Abstract Background MicroRNAs (miRNAs have been recently detected in the circulation of cancer patients, where they are associated with clinical parameters. Discovery profiling of circulating small RNAs has not been reported in breast cancer (BC, and was carried out in this study to identify blood-based small RNA markers of BC clinical outcome. Methods The pre-treatment sera of 42 stage II-III locally advanced and inflammatory BC patients who received neoadjuvant chemotherapy (NCT followed by surgical tumor resection were analyzed for marker identification by deep sequencing all circulating small RNAs. An independent validation cohort of 26 stage II-III BC patients was used to assess the power of identified miRNA markers. Results More than 800 miRNA species were detected in the circulation, and observed patterns showed association with histopathological profiles of BC. Groups of circulating miRNAs differentially associated with ER/PR/HER2 status and inflammatory BC were identified. The relative levels of selected miRNAs measured by PCR showed consistency with their abundance determined by deep sequencing. Two circulating miRNAs, miR-375 and miR-122, exhibited strong correlations with clinical outcomes, including NCT response and relapse with metastatic disease. In the validation cohort, higher levels of circulating miR-122 specifically predicted metastatic recurrence in stage II-III BC patients. Conclusions Our study indicates that certain miRNAs can serve as potential blood-based biomarkers for NCT response, and that miR-122 prevalence in the circulation predicts BC metastasis in early-stage patients. These results may allow optimized chemotherapy treatments and preventive anti-metastasis interventions in future clinical applications.

Genome-Wide DNA Copy Number Analysis of Acute Lymphoblastic Leukemia Identifies New Genetic Markers Associated with Clinical Outcome.

Directory of Open Access Journals (Sweden)

Maribel Forero-Castro

Full Text Available Identifying additional genetic alterations associated with poor prognosis in acute lymphoblastic leukemia (ALL is still a challenge.To characterize the presence of additional DNA copy number alterations (CNAs in children and adults with ALL by whole-genome oligonucleotide array (aCGH analysis, and to identify their associations with clinical features and outcome. Array-CGH was carried out in 265 newly diagnosed ALLs (142 children and 123 adults. The NimbleGen CGH 12x135K array (Roche was used to analyze genetic gains and losses. CNAs were analyzed with GISTIC and aCGHweb software. Clinical and biological variables were analyzed. Three of the patients showed chromothripsis (cth6, cth14q and cth15q. CNAs were associated with age, phenotype, genetic subtype and overall survival (OS. In the whole cohort of children, the losses on 14q32.33 (p = 0.019 and 15q13.2 (p = 0.04 were related to shorter OS. In the group of children without good- or poor-risk cytogenetics, the gain on 1p36.11 was a prognostic marker independently associated with shorter OS. In adults, the gains on 19q13.2 (p = 0.001 and Xp21.1 (p = 0.029, and the loss of 17p (p = 0.014 were independent markers of poor prognosis with respect to OS. In summary, CNAs are frequent in ALL and are associated with clinical parameters and survival. Genome-wide DNA copy number analysis allows the identification of genetic markers that predict clinical outcome, suggesting that detection of these genetic lesions will be useful in the management of patients newly diagnosed with ALL.

Clinical efficacy and safety of edaravone therapy in acute cerebral ...

African Journals Online (AJOL)

Purpose: To evaluate the clinical efficacy and safety of edaravone in the treatment of acute cerebral haemorrhage (ACH). Methods: This study recruited 120 patients who developed ACH. The patients were divided into control and treatment groups with 60 patients per group. The control group underwent conventional ...

Multiple large solar lentigos on the upper back as clinical markers of past severe sunburn: a case-control study.

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Derancourt, C; Bourdon-Lanoy, E; Grob, J-J; Guillaume, J-C; Bernard, P; Bastuji-Garin, S

2007-01-01

Multiple solar lentigos commonly seen on the upper back and shoulders of adults are classically considered as a sign of photodamage, although epidemiological studies are scarce. To assess whether these lesions are clinical markers of past severe sunburn. A case-control study in two outpatient dermatology clinics in French university hospitals. Past episodes of moderate and severe sunburn were compared between 145 adult patients with multiple solar lentigos on the upper back and 145 matched controls. In multivariate analysis adjusted for potential confounders, recalled episodes of sunburn during childhood, adolescence and adulthood were independently associated with the presence of multiple solar lentigos (adjusted odds ratios, 95% confidence intervals: 2.3 (1.1-5.2) and 28.1 (10.4-75.6) for moderate and severe sunburn, respectively). Multiple solar lentigos on the upper back and shoulders of adults are potential clinical markers of past severe sunburn which may thus be used to identify a population at higher risk of developing cutaneous malignant melanoma.

Study on the clinical value of combined determination of six tumor marker for diagnosis of pulmonary carcinoma

International Nuclear Information System (INIS)

Chen Zhong; Liu Yun; Liu Li; Lu Xiaopeng; Zhang Jun; Li Jiangang; Zhu Zili

2006-01-01

Objective: To study the clinical applicability of single/combined determination of six tumor markers (CEA, CA125, CA50, CA19-9, CA153, CYFRA21-1) for diagnosis of pulmonary carcinoma. Methods: Serum contents of these six tumor markers were determined with RIA in 130 patients with pulmonary carcinoma, 40 patients with various benign pulmonary disorders, and 45 controls. Results: (1) Only two false positive cases were found in the 40 patients with benign pulmonary disorders (CA125, n=1, CA153 n=1). (2) Positive rate of single marker in patients with pulmonary cancer: CYFRA21-1 (79.23%)>CA153 (61.53%) > CA125(58.46%)> CA19-9(57.69%) > CEA(46.92%) > CA50(43.84%). (3) Combined determination of CYFRA21-1 with any one of the other 5 markers would increase the positive rate to 86.15%-89.23%. (4) Mean value of any marker in the malignant cases were over 4 folds of that in the benign cases-high diagnostic credibility. (5) Histology of the malignancy (squamous cell carcinoma or adenocarcinoma) made no difference on the positive rate of the markers with the exception of a slight higher positive rate of CA19-9 in adenocarcinomas. Conclusion: The authors believe that combined determination of CYFRA21-1 with CA153 would be the first choice for diagnosis of pulmonary carcinoma, followed by CYFRA21-1 + CA125 or CA19-9. (authors)

Tumors markers

International Nuclear Information System (INIS)

Yamaguchi-Mizumoto, N.H.

1989-01-01

In order to study blood and cell components alterations (named tumor markers) that may indicate the presence of a tumor, several methods are presented. Aspects as diagnostic, prognostic, therapeutic value and clinical evaluation are discussed. (M.A.C.)

Clinical significance of serum tumor markers for gastric cancer: a systematic review of literature by the Task Force of the Japanese Gastric Cancer Association.

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Shimada, Hideaki; Noie, Tamaki; Ohashi, Manabu; Oba, Koji; Takahashi, Yutaka

2014-01-01

The aim of this review was to evaluate the clinical significance of serum tumor markers, particularly CEA, CA19-9, and CA72-4, in patients with gastric cancer. A systematic literature search was performed using PubMed/MEDLINE with the keywords "gastric cancer" and "tumor marker," to select 4,925 relevant reports published before the end of November 2012. A total of 187 publications contained data for CEA and CA19-9, and 19 publications contained data related to all three tumor markers. The positive rates were 21.1 % for CEA, 27.8 % for CA19-9, and 30.0 % for CA72-4. These three markers were significantly associated with tumor stage and patient survival. Serum markers are not useful for early cancer, but they are useful for detecting recurrence and distant metastasis, predicting patient survival, and monitoring after surgery. Tumor marker monitoring may be useful for patients after surgery because the positive conversion of tumor markers usually occurs 2-3 months before imaging abnormalities. Among other tumor markers, alpha-fetoprotein (AFP) is useful for detecting and predicting liver metastases. Moreover, CA125 and sialyl Tn antigens (STN) are useful for detecting peritoneal metastases. Although no prospective trial has yet been completed to evaluate the clinical significance of these serum markers, this literature survey suggests that combinations of CEA, CA19-9, and CA72-4 are the most effective ways for staging before surgery or chemotherapy. In particular, monitoring tumor markers that were elevated before surgery or chemotherapy could be useful for detection of recurrence or evaluation of the response.

A 2-year study of patient safety competency assessment in 29 clinical laboratories.

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Reed, Robyn C; Kim, Sara; Farquharson, Kara; Astion, Michael L

2008-06-01

Competency assessment is critical for laboratory operations and is mandated by the Clinical Laboratory Improvement Amendments of 1988. However, no previous reports describe methods for assessing competency in patient safety. We developed and implemented a Web-based tool to assess performance of 875 laboratory staff from 29 laboratories in patient safety. Question categories included workplace culture, categorizing error, prioritization of patient safety interventions, strength of specific interventions, and general patient safety concepts. The mean score was 85.0%, with individual scores ranging from 56% to 100% and scores by category from 81.3% to 88.6%. Of the most difficult questions (laboratory technologists. Computer-based competency assessments help laboratories identify topics for continuing education in patient safety.

Clinical Significance of Tumor Marker Detection in Patients 
with Advanced Squamous Cell Carcimoma of the Lung

Directory of Open Access Journals (Sweden)

Ping LIANG

2016-10-01

Full Text Available Background and objective Due to it's concealment and no obvious symptoms, lung squamous carcimoma often has advanced disease when diagnosed. The aims of this study were to describe the characteristics of the disease, to evaluate the clinical importance of detection of multiple tumor markers in patients with squamous cell carcinoma of the lung. Methods The characteristics of all patients with advanced squamous cell lung cancer treated in Beijing Cancer Hospital of Chinese Academy of Medical Sciences during Jan. 2011 to Dec. 2015 were identified by cases reviewing and data extracting. The characteristics, detection levels and sensitivity of multiple tumor makers among patients were described. Results The 260 patients were treated with mean age of (59.4±9.2 years, 85.8% (n=223 of them were male, 14.2% (n=37 of them were female. 78.1% (n=203 of all were smokers and 3.1% (n=8 of patients had family history of tumor. The positive rate of cytokerantin 19 fragment (CYFRA21-1 was 71.2%, which was the highest among five tumor markers. The five tumor markers median level had no statistical significance between different tumor (T stages and node (N stages (all P>0.05, only the positive rate of SCC had statistical significance between different T stages (P=0.035. The combination measurement of CYFRA21-1+carcinogen-embryonic antigen (CEA, CYFRA21-1+CEA+cancer antigen (CA125, CA125+CYFRA21-1+CEA+neuron specific enolase (NSE, and CA125+CYFRA21-1+NSE+CEA+squamous cell carcinoma antigen (SCC were better and had higher clinical values, the positive rates were 82.7%, 84.6%, 85.0% and 86.2%, respectively. Conclusion The positive rate of CYFRA21-1 was the highest and the sensitivity of single test of five tumor markers was low, the combination of multiple tumor markers increased the sensitivity of diagnosis of SQCLC, the combination of CA125, CYFRA21-1 and CEA was the best choice.

Effects of a vildagliptin/metformin combination on markers of atherosclerosis, thrombosis, and inflammation in diabetic patients with coronary artery disease

Directory of Open Access Journals (Sweden)

Klempfner Robert

2012-06-01

Full Text Available Abstract Background Diabetic patients present with an accelerated atherosclerotic process and an increased risk for future cardiovascular events. In addition to the risk imposed by the disease itself, pharmacological treatment adds also a sizable risk, especially if certain classes of antidiabetic drugs are employed. Animal evidence indicates that dipeptidyl peptidase-4 inhibitors have anti-atherosclerotic effects, yet clinical data are scarcely available. Design We plan to prospectively investigate the effects of dipeptidyl peptidase-4 inhibition with vildagliptin on a number of atherothrombotic markers and adipokines in patients with proven atherosclerosis and type 2 diabetes. The selected markers are: interleukin-6, high sensitivity C reactive protein, interleukin 1-beta, total adiponectin levels, matrix metallo-proteinase 9 and platelet reactivity testing. Sixty eligible patients will be randomized in a 2:1 ratio to vildagliptin/metformin or metformin only treatment, for a 3-month duration treatment. Blood sampling for the proposed investigations will be taken at enrollment and immediately after completion of the study period. Discussion Demonstrating antiatherothrombotic properties of dipeptidyl peptidase-4 inhibitors on proven markers is of substantial clinical significance. Coupled with their proven good safety profile these findings could translate into a significant clinical benefit.

What is the clinical value of cancer stem cell markers in gliomas?

DEFF Research Database (Denmark)

Dahlrot, Rikke Hedegaard; Hermansen, Simon Kjær; Hansen, Steinbjørn

2013-01-01

. This review summarizes current reports on putative glioma CSC markers and reviews the prognostic value of the individual immunohistochemical markers reported in the literature. Using the Pubmed database, twenty-seven CSC studies looking at membrane markers (CD133, podoplanin, CD15, and A2B5), filament markers...

Clinical value of combined detection of tumor markers in effusion fluid for diagnosis of malignant pleural effusion and ascites

International Nuclear Information System (INIS)

Li Jiangang; Ji Zhigu; Cui Xuejun; Zhu Zili

2010-01-01

Objective: To study the clinical usefulness of combined detection of tumor markers in effusion fluid in patients with malignant pleural effusion or ascites. Methods: Combined detection of six tumor markers (CA125, CA50, CA15-3, CYFRA21-1, βHCG, HCG) in effusion fluid was performed in 92 patients with malignant pleural effusion and 78 patients with malignant ascites as well as 100 control benign specimens. These tumor markers were examined with CLIA, except CA50, which was examined with RIA. Exfoliative cytology was also examined in the malignant specimens. Results: The positive rate of these markers was highest with CA125, followed by CA50, CA15-3, CYFRA21-1, βHCG and HCG in order. βHCG and HCG, though with quite low positive rate, were still useful markers due to the almost zero false-positive rate, i.e. very high specificity. For combined determination of two markers, CA15 + CYFRA21-1 or CA125 + CA50 would result in the highest positive rate. For highly suspected but undetermined cases, the following criteria for malignancy would be helpful: (1) two or more positive among CA125, CA50, CA15-3, CYFRA21-1 (2) One of the four CAs positive + either βHCG or HCG (3) Both βHCG and HCG positive. Tumor markers positiveness would be supplementary to doubtful cytological studies. Conclusion: Combined detection of tumor markers in effusion fluid would be very helpful for diagnosis of malignancy. (authors)

Clinical Implications of Intestinal Stem Cell Markers in Colorectal Cancer

DEFF Research Database (Denmark)

Espersen, Maiken Lise Marcker; Olsen, Jesper; Linnemann, Dorte

2015-01-01

Colorectal cancer (CRC) still has one of the highest incidence and mortality rate among cancers. Therefore, improved differential diagnostics and personalized treatment are still needed. Several intestinal stem cell markers have been found to be associated with CRC and might have a prognostic...... and predictive significance in CRC patients. This review provides an overview of the intestinal stem cell markers leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5), B cell–specific Moloney murine leukemia virus insertion site 1 (BMI1), Musashi1 (MSI1), and sex-determining region y-box 9 (SOX9......) and their implications in human CRC. The exact roles of the intestinal stem cell markers in CRC development and progression remain unclear; however, high expression of these stem cell markers have a potential prognostic significance and might be implicated in chemotherapy resistance...

Non-clinical studies in the process of new drug development - Part II: Good laboratory practice, metabolism, pharmacokinetics, safety and dose translation to clinical studies.

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Andrade, E L; Bento, A F; Cavalli, J; Oliveira, S K; Schwanke, R C; Siqueira, J M; Freitas, C S; Marcon, R; Calixto, J B

2016-12-12

The process of drug development involves non-clinical and clinical studies. Non-clinical studies are conducted using different protocols including animal studies, which mostly follow the Good Laboratory Practice (GLP) regulations. During the early pre-clinical development process, also known as Go/No-Go decision, a drug candidate needs to pass through several steps, such as determination of drug availability (studies on pharmacokinetics), absorption, distribution, metabolism and elimination (ADME) and preliminary studies that aim to investigate the candidate safety including genotoxicity, mutagenicity, safety pharmacology and general toxicology. These preliminary studies generally do not need to comply with GLP regulations. These studies aim at investigating the drug safety to obtain the first information about its tolerability in different systems that are relevant for further decisions. There are, however, other studies that should be performed according to GLP standards and are mandatory for the safe exposure to humans, such as repeated dose toxicity, genotoxicity and safety pharmacology. These studies must be conducted before the Investigational New Drug (IND) application. The package of non-clinical studies should cover all information needed for the safe transposition of drugs from animals to humans, generally based on the non-observed adverse effect level (NOAEL) obtained from general toxicity studies. After IND approval, other GLP experiments for the evaluation of chronic toxicity, reproductive and developmental toxicity, carcinogenicity and genotoxicity, are carried out during the clinical phase of development. However, the necessity of performing such studies depends on the new drug clinical application purpose.

Molecular markers in bladder cancer: Novel research frontiers.

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Sanguedolce, Francesca; Cormio, Antonella; Bufo, Pantaleo; Carrieri, Giuseppe; Cormio, Luigi

2015-01-01

Bladder cancer (BC) is a heterogeneous disease encompassing distinct biologic features that lead to extremely different clinical behaviors. In the last 20 years, great efforts have been made to predict disease outcome and response to treatment by developing risk assessment calculators based on multiple standard clinical-pathological factors, as well as by testing several molecular markers. Unfortunately, risk assessment calculators alone fail to accurately assess a single patient's prognosis and response to different treatment options. Several molecular markers easily assessable by routine immunohistochemical techniques hold promise for becoming widely available and cost-effective tools for a more reliable risk assessment, but none have yet entered routine clinical practice. Current research is therefore moving towards (i) identifying novel molecular markers; (ii) testing old and new markers in homogeneous patients' populations receiving homogeneous treatments; (iii) generating a multimarker panel that could be easily, and thus routinely, used in clinical practice; (iv) developing novel risk assessment tools, possibly combining standard clinical-pathological factors with molecular markers. This review analyses the emerging body of literature concerning novel biomarkers, ranging from genetic changes to altered expression of a huge variety of molecules, potentially involved in BC outcome and response to treatment. Findings suggest that some of these indicators, such as serum circulating tumor cells and tissue mitochondrial DNA, seem to be easily assessable and provide reliable information. Other markers, such as the phosphoinositide-3-kinase (PI3K)/AKT (serine-threonine kinase)/mTOR (mammalian target of rapamycin) pathway and epigenetic changes in DNA methylation seem to not only have prognostic/predictive value but also, most importantly, represent valuable therapeutic targets. Finally, there is increasing evidence that the development of novel risk assessment tools

Unremitted hyperthyroidism following 131I treatment: an analysis of clinical markers in 48 patients

International Nuclear Information System (INIS)

Fang Yi; Zhang Xiuli; Liu Jianfeng; Zhang Youren

2002-01-01

Objective: To evaluate changes in clinical markers of unremitted hyperthyroidism patients after the first 131 I treatment. Methods: Forth eight unremitted hyperthyroidism patients were selected. Their thyroid function, the peak of 131 I uptake rate and thyroid weight before and after 131 I treatment were compared. Results: TT 3 , TT 4 , TSH were relatively stable and the peak of 131 I uptake rate and thyroid weight were reduced after 131 I treatment. Conclusions: Thyroid volume was reduced after 131 I treatment even if patients' clinical symptoms still existed; the peak of 131 I uptake rate was reduced after 131 I treatment, suggesting that their sensibility to 131 I decreased, so the absorbed dose should be adjusted when the 131 I dosage of second treatment is calculated

[Clinical usefulness of bone turnover markers in the management of osteoporosis].

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Yano, Shozo

2013-09-01

Osteoporosis is a state of elevated risk for bone fracture due to depressed bone strength, which is considered to be the sum of bone mineral density and bone quality. Since a measure of bone quality has not been established, bone mineral density and bone turnover markers are the only way to evaluate bone strength. Bone turnover markers are classified into bone formation marker and resorption marker, which are correlated with the bone formation rate and resorption rate, respectively, and bone matrix-related marker. Bone is always metabolized; old tissue is resorbed by acids and proteases derived from osteoclasts, whereas new bone is produced by osteoblasts. Bone formation and resorption rates should be balanced (also called coupled). When the bone resorption rate exceeds the formation rate(uncoupled state), bone volume will be reduced. Thus, we can comprehend bone metabolism by measuring both formation and resorption markers at the same time. Increased fracture risk is recognized by elevated bone resorption markers and undercarboxylated osteocalcin, which reflects vitamin K insufficiency and bone turnover. These values and the time course give us helpful information to choose medicine suitable for the patients and to judge the responsiveness. If the value is extraordinarily high without renal failure, metabolic bone disorder or bone metastatic tumor should be considered. Bone quality may be assessed by measuring bone matrix-related markers such as homocystein and pentosidine. Since recent studies indicate that the bone is a hormone-producing organ, it is possible that glucose metabolism or an unknown mechanism could be assessed in the future.

Clinical performance of LOCI™-based tumor marker assays for tumor markers CA 15-3, CA 125, CEA, CA 19-9 and AFP in gynecological cancers.

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Dolscheid-Pommerich, Ramona C; Keyver-Paik, Mignon; Hecking, Thomas; Kuhn, Walther; Hartmann, Gunther; Stoffel-Wagner, Birgit; Holdenrieder, Stefan

2017-10-01

Evidence is sparse regarding the clinical performance of luminescent oxygen channeling immunoassays-based tumor marker assays in gynecological cancer. Analyzing serum samples of 336 patients with Dimension™Vista1500, we investigated the diagnostic power of carbohydrate antigen 15-3, carbohydrate antigen 125, carcinoembryonic antigen, carbohydrate antigen 19-9, and alpha-fetoprotein in patients suffering from different types of gynecological cancer and precancerous gynecological diseases and compared findings to appropriate control groups. The cohort comprised 177 female patients with gynecological cancers (73 breast, 22 cervical, 16 endometrial, 17 vulva, and 49 ovarian cancers), 26 patients with precancerous gynecological diseases (11 vulva, 4 cervical, and 10 breast), 109 patients with benign gynecological diseases, and 24 healthy controls. Discriminative power was assessed by areas under the curve in receiver operating characteristic curves, and sensitivities were determined at a fixed specificity of 95%. Levels of biomarkers in healthy controls were in the expected ranges and a discriminative power between gynecological cancers and healthy controls was observed for several tumor markers. Established tumor type-associated markers were elevated in specific gynecological cancers and benign controls as well as within precancerous gynecological diseases and healthy control group. In ovarian cancer, carbohydrate antigen 125 and carbohydrate antigen 15-3 were significantly elevated compared to the respective benign diseases. Carbohydrate antigen 125 was the most conclusive marker (area under the curve = 0.86% and 77.6% sensitivity at 95% specificity). In breast cancer, carcinoembryonic antigen and carbohydrate antigen 15-3 were significantly higher than in the respective benign diseases. Carcinoembryonic antigen achieved the most conclusive area under the curve (0.65) with 31.5% sensitivity at 95% specificity. None of the investigated markers was found to be of

SAFETY: an integrated clinical reasoning and reflection framework for undergraduate nursing students.

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Hicks Russell, Bedelia; Geist, Melissa J; House Maffett, Jenny

2013-01-01

Nurse educators can no longer focus on imparting to students knowledge that is merely factual and content specific. Activities that provide students with opportunities to apply concepts in real-world scenarios can be powerful tools. Nurse educators should take advantage of student-patient interactions to model clinical reasoning and allow students to practice complex decision making throughout the entire curriculum. In response to this change in nursing education, faculty in a pediatric course designed a reflective clinical reasoning activity based on the SAFETY template, which is derived from the National Council of State Boards of Nursing RN practice analysis. Students were able to prioritize key components of nursing care, as well as integrate practice issues such as delegation, Health Insurance Portability and Accountability Act violations, and questioning the accuracy of orders. SAFETY is proposed as a framework for integration of content knowledge, clinical reasoning, and reflection on authentic professional nursing concerns. Copyright 2012, SLACK Incorporated.

Exploration of Disease Markers under Translational Medicine Model

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Rajagopal Krishnamoorthy

2015-06-01

Full Text Available Disease markers are defined as the biomarkers with specific characteristics during the general physical, pathological or therapeutic process, the detection of which can inform the progression of present biological process of organisms. However, the exploration of disease markers is complicated and difficult, and only a few markers can be used in clinical practice and there is no significant difference in the mortality of cancers before and after biomarker exploration. Translational medicine focuses on breaking the blockage between basic medicine and clinical practice. In addition, it also establishes an effective association between researchers engaged on basic scientific discovery and clinical physicians well informed of patients' requirements, and gives particular attentions on how to translate the basic molecular biological research to the most effective and appropriate methods for the diagnosis, treatment and prevention of diseases, hoping to translate basic research into the new therapeutic methods in clinic. Therefore, this study mainly summarized the exploration of disease markers under translational medicine model so as to provide a basis for the translation of basic research results into clinical application.

Clinical value of multi-tumor markers detection with (CEA, CA19-9, CA72-4) for diagnosis of gastric malignancy

International Nuclear Information System (INIS)

Liu Yun; Li Jiangang

2007-01-01

Objective: To assess the clinical value of multi-tumor markers detection with (CEA, CA19-9, CA72-4) for diagnosis of gastric malignancy. Methods: Serum CEA, CA19-9, CA72-4 contents were measured with IRMA in 228 patients with gastric malignancies, 152 patients with benign gastric disorders and 200 controls. Results: The positive rates of single marker detection were all above 70% and that of CA72-4 was the highest (84.21%), next was CA19-9 (75.43%). Three tumor markers were all negative in only 4 cases (false negative rate was 1.75% ). So combined detection of 3 tumor markers could improve the positive rate to 98.25%. With combined determination of two markers, double positive rate for different sets of combinations was: 61.84% for CA72-4 + CA19-9, 51.31% for CA72-4 + CEA and 48.24% for CEA + CA19-9. Conclusion: It was suggested that for screening, CA72-4 was the first choice in single marker detections, and CA72-4 + CA19-9 was the first choice for combined detections of two markers. For follow-up, a combination of 2 markers with highest positive rate for the specific histopathologic type (i. e. carcinoma, leiomyosarcoma or lymphosarcoma) should be used throughout the study. (authors)

A randomized clinical trial comparing embryo culture in a conventional incubator with a time-lapse incubator

DEFF Research Database (Denmark)

Kirkegaard, Kirstine; Hindkjaer, Johnny Juhl; Grøndahl, Marie Louise

2012-01-01

Time-lapse monitoring allows for a flexible embryo evaluation and potentially provides new dynamic markers of embryo competence. Before introducing time-lapse monitoring in a clinical setting, the safety of the instrument must be properly documented. Accordingly, the aim of this study...

Double blind clinical trail comparing the safety and efficacy of ...

African Journals Online (AJOL)

Double blind clinical trail comparing the safety and efficacy of nimesulide (100g) and diclofenac in osteoarthrosis of the hip and knee joints. ... A significant proportion of the patients in the diclofenac group (50% vs 17.6%) had break through pain that warranted the use of at least two tablets of 500mg of paracetamol per week ...

The macrophage activation marker sCD163 combined with markers of the Enhanced Liver Fibrosis (ELF) score predicts clinically significant portal hypertension in patients with cirrhosis

DEFF Research Database (Denmark)

Sandahl, T D; McGrail, R; Møller, H J

2016-01-01

BACKGROUND: Noninvasive identification of significant portal hypertension in patients with cirrhosis is needed in hepatology practice. AIM: To investigate whether the combination of sCD163 as a hepatic inflammation marker and the fibrosis markers of the Enhanced Liver Fibrosis score (ELF) can...... predict portal hypertension in patients with cirrhosis. METHODS: We measured sCD163 and the ELF components (hyaluronic acid, tissue inhibitor of metalloproteinase-1 and procollagen-III aminopeptide) in two separate cohorts of cirrhosis patients that underwent hepatic vein catheterisation. To test...... the predictive accuracy we developed a CD163-fibrosis portal hypertension score in an estimation cohort (n = 80) and validated the score in an independent cohort (n = 80). A HVPG ≥10 mmHg was considered clinically significant. RESULTS: Both sCD163 and the ELF components increased in a stepwise manner...

Markers of Collagen Remodeling Detect Clinically Significant Fibrosis in Chronic Hepatitis C Patients

DEFF Research Database (Denmark)

Nielsen, Mette J; Kazankov, Konstantin; Leeming, Diana J

2015-01-01

as potential biomarkers for clinically significant and advanced fibrosis. METHODS: Specific protein fragments of matrix metalloprotease degraded type I, III, IV and VI collagen (C1M, C3M, C4M, C6M) and type III and IV collagen formation (Pro-C3 and P4NP7S) were assessed in plasma from 403 chronic hepatitis C...... patients by specific ELISAs. Patients were stratified according to Metavir Fibrosis stage; F0 (n = 46), F1 (n = 161), F2 (n = 95), F3 (n = 44) and F4 (n = 33) based on liver biopsy. RESULTS: Pro-C3 was significantly elevated in patients with significant fibrosis (≥F2) compared to F0-F1 (p... the markers C3M, C4M, C6M and P4NP7S were significantly elevated in patients with advanced fibrosis (≥F3) compared to F0-F2 (pC1M showed no difference between fibrosis stages. Using Receiver Operating Characteristics analysis, the best marker for detecting ≥F2 and ≥F3 was Pro-C3 with AUC = 0...

Monitoring antimalarial safety and tolerability in clinical trials: A case study from Uganda

Directory of Open Access Journals (Sweden)

Mpimbaza Arthur

2008-06-01

Full Text Available Abstract Background New antimalarial regimens, including artemisinin-based combination therapies (ACTs, have been adopted widely as first-line treatment for uncomplicated malaria. Although these drugs appear to be safe and well-tolerated, experience with their use in Africa is limited and continued assessment of safety is a priority. However, no standardized guidelines for evaluating drug safety and tolerability in malaria studies exist. A system for monitoring adverse events in antimalarial trials conducted in Uganda was developed. Here the reporting system is described, and difficulties faced in analysing and interpreting the safety results are illustrated, using data from the trials. Case description Between 2002 and 2007, eleven randomized, controlled clinical trials were conducted to compare the efficacy, safety, and tolerability of different antimalarial regimens for treatment of uncomplicated malaria in Uganda. The approach to adverse event monitoring was similar in all studies. A total of 5,614 treatments were evaluated in 4,876 patients. Differences in baseline characteristics and patterns of adverse event reporting were noted between the sites, which limited the ability to pool and analyse data. Clinical failure following antimalarial treatment confounded associations between treatment and adverse events that were also common symptoms of malaria, particularly in areas of lower transmission intensity. Discussion and evaluation Despite prospectively evaluating for adverse events, limitations in the monitoring system were identified. New standardized guidelines for monitoring safety and tolerability in antimalarial trials are needed, which should address how to detect events of greatest importance, including serious events, those with a causal relationship to the treatment, those which impact on adherence, and events not previously reported. Conclusion Although the World Health Organization has supported the development of

Assessing the Clinical Role of Genetic Markers of Early-Onset Prostate Cancer Among High-Risk Men Enrolled in Prostate Cancer Early Detection

Science.gov (United States)

Hughes, Lucinda; Zhu, Fang; Ross, Eric; Gross, Laura; Uzzo, Robert G.; Chen, David Y. T.; Viterbo, Rosalia; Rebbeck, Timothy R.; Giri, Veda N.

2011-01-01

Background Men with familial prostate cancer (PCA) and African American men are at risk for developing PCA at younger ages. Genetic markers predicting early-onset PCA may provide clinically useful information to guide screening strategies for high-risk men. We evaluated clinical information from six polymorphisms associated with early-onset PCA in a longitudinal cohort of high-risk men enrolled in PCA early detection with significant African American participation. Methods Eligibility criteria include ages 35–69 with a family history of PCA or African American race. Participants undergo screening and biopsy per study criteria. Six markers associated with early-onset PCA (rs2171492 (7q32), rs6983561 (8q24), rs10993994 (10q11), rs4430796 (17q12), rs1799950 (17q21), and rs266849 (19q13)) were genotyped. Cox models were used to evaluate time to PCA diagnosis and PSA prediction for PCA by genotype. Harrell’s concordance index was used to evaluate predictive accuracy for PCA by PSA and genetic markers. Results 460 participants with complete data and ≥1 follow-up visit were included. 56% were African American. Among African American men, rs6983561 genotype was significantly associated with earlier time to PCA diagnosis (p=0.005) and influenced prediction for PCA by the PSA (p<0.001). When combined with PSA, rs6983561 improved predictive accuracy for PCA compared to PSA alone among African American men (PSA= 0.57 vs. PSA+rs6983561=0.75, p=0.03). Conclusions Early-onset marker rs6983561 adds potentially useful clinical information for African American men undergoing PCA risk assessment. Further study is warranted to validate these findings. Impact Genetic markers of early-onset PCA have potential to refine and personalize PCA early detection for high-risk men. PMID:22144497

[Prognostic and predictive molecular markers for urologic cancers].

Science.gov (United States)

Hartmann, A; Schlomm, T; Bertz, S; Heinzelmann, J; Hölters, S; Simon, R; Stoehr, R; Junker, K

2014-04-01

Molecular prognostic factors and genetic alterations as predictive markers for cancer-specific targeted therapies are used today in the clinic for many malignancies. In recent years, many molecular markers for urogenital cancers have also been identified. However, these markers are not clinically used yet. In prostate cancer, novel next-generation sequencing methods revealed a detailed picture of the molecular changes. There is growing evidence that a combination of classical histopathological and validated molecular markers could lead to a more precise estimation of prognosis, thus, resulting in an increasing number of patients with active surveillance as a possible treatment option. In patients with urothelial carcinoma, histopathological factors but also the proliferation of the tumor, mutations in oncogenes leading to an increasing proliferation rate and changes in genes responsible for invasion and metastasis are important. In addition, gene expression profiles which could distinguish aggressive tumors with high risk of metastasis from nonmetastasizing tumors have been recently identified. In the future, this could potentially allow better selection of patients needing systemic perioperative treatment. In renal cell carcinoma, many molecular markers that are associated with metastasis and survival have been identified. Some of these markers were also validated as independent prognostic markers. Selection of patients with primarily organ-confined tumors and increased risk of metastasis for adjuvant systemic therapy could be clinically relevant in the future.

Bone markers during acute burn care: Relevance to clinical practice?

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Rousseau, Anne-Françoise; Damas, Pierre; Delanaye, Pierre; Cavalier, Etienne

2017-02-01

Bone changes are increasingly described after burn. How bone markers could help to detect early bone changes or to screen burn patients at higher risk of demineralization is still not made clear. We performed an observational study assessing the changes in serum bone markers after moderate burn. Adults admitted in the first 24h following burn extended on >10% body surface area were included. Serum levels of collagen type 1 cross-linked C-telopeptide (CTX), tartrate-resistant acid phosphatase 5b (TRAP), type 1 procollagen N-terminal (P1NP) and bone alkaline phosphatase (b-ALP) were measured at admission and every week during the first month. Data are expressed as median [min-max]. Bone markers were measured in 20 patients: 18 men, 2 women (including one post-menopausal). Age was 46 [19-86] years old, burn surface area reached 15 [7-85] %. Twelve patients completed the study. All biomarkers mainly remained into normal ranges during evolution. A huge variability was observed regarding biomarkers evolution. Patient's evolution was not linear and could fluctuate from a decrease to an increase of blood concentrations. There was not necessarily a consistency between the two formation or the two resorption markers. Variations observed between two consecutive measurements were lesser than the accepted critical difference in almost one third of the cases. Considering available data, role and interest of bone markers in management of burn related bone disease remain unclear. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

Clinical significance of biochemical markers of bone metabolism in patients with type 2 diabetes mellitus

International Nuclear Information System (INIS)

Zhang Bashan; Zeng Longhong; Lai Fudi

2004-01-01

Objective: To investigate the clinical significance of changes of levels of biochemical markers of bone metabolism in patients with type 2 diabetes mellitus. Methods: Serum osteocalcin (BGP, with RIA), Ca alkaline phosphatase (ALP) and random specimen urinary deoxypyridinoline (DPD, with chemiluminescence assay), Ca, creatinine levels were measured in 40 patients with type 2 diabetes mellitus and 31 controls. Results: Serum BGP levels in diabetic patients were much lower than those in the controls (P<0.05); while urinary DPD/Cr ratio and Ca/Cr ratio were significantly higher in the patients than those in the controls (P<0.05, P<0.05). Serum Ca and ALP levels were about the same in the two groups. Conclusion: Loss of bone mass in diabetic patients are due to both decreased bone formation and increased bone resorption. Determination of the levels of the biochemical markers of bone metabolism (BGP, DPD......) could be applied for early detection of osteoporosis. (authors)

Have the Findings from Clinical Risk Prediction and Trials Any Key Messages for Safety Pharmacology?

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Jem D. Lane

2017-11-01

Full Text Available Anti-arrhythmic drugs are a mainstay in the management of symptoms related to arrhythmias, and are adjuncts in prevention and treatment of life-threatening ventricular arrhythmias. However, they also have the potential for pro-arrhythmia and thus the prediction of arrhythmia predisposition and drug response are critical issues. Clinical trials are the latter stages in the safety testing and efficacy process prior to market release, and as such serve as a critical safeguard. In this review, we look at some of the lessons to be learned from approaches to arrhythmia prediction in patients, clinical trials of drugs used in the treatment of arrhythmias, and the implications for the design of pre-clinical safety pharmacology testing.

Preclinical and phase 1 clinical safety of Setarud (IMOD™, a novel immunomodulator

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P Khairandish

2009-10-01

Full Text Available "n "n  Background: A new herbal drug, Setarud (IMODTM that has been shown to have beneficial immune effects was tested to determine its acute and chronic toxicity in animals and to establish its intravenous form maximum tolerated dose (MTD in an open-labeled phase I clinical trial. Methods: BALB/c and C57BL/6 mice and Wistar rats were monitored for general state and biochemical markers for chronic test. At the end of chronic test, animals examined macroscopically and histologically. HIV-infected asymptomatic male patients with CD4 counts more than 200, were enrolled in the trial. Baseline dose was calculated from the 10% lethal dose (LD10 established in laboratory animal studies. Dose escalation was performed in four cohorts of 3 patients receiving IMODTM intravenously at a cohort-specific dose of 2, 4, 6.7, and 10 ml daily for 4 weeks. Patients were clinically examined at days of 1, 2, 3 and then weekly; and the safety was assessed on the basis of reports of adverse events, laboratory-test data and toxicity signs. Results: LD50 values in acute toxicity test were 42-66 and 50-56 ml/kg in i.m. and i.p. injections, respectively. Total scores of embryotoxicity during pregnancy were significantly lower in the Setarud group (p < 0.05. Pre-implantational deaths in the Setarud group were significantly higher, but post-implantational deaths level was lower than those in the control group. Inhibition of ossification in the skeletons of the fetuses and incidence of still birth were significantly higher while body weight of new-born rats of treatment group in the first month of their lifes were lower than those of the control group.In all four cohorts, there were no major side effects or dose-limiting toxicity, except for a mild sweating and weight loss in two patients from the first group that was reversed without discontinuation of the treatment. No clinically relevant trends in laboratory test results or ECG changes were noted. No adverse effect due to

Changes of serum tumor markers, immunoglobulins, TNF-α and hs-CRP levels in patients with breast cancer and its clinical significance

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Jian-Gang Dai; Yong-Feng Wu; Mei Li

2017-01-01

Objective: To study the serum tumor markers, immunoglobulin, TNF-α and hs-CRP in breast cancer in different pathological stages of the concentration, and to analyze the clinical significance of early diagnosis of breast cancer. Methods: A total of 130 patients with breast cancer were divided into stage I, II, III and IV according to clinical pathology. In addition, 40 patients with benign breast disease and 35 healthy subjects were selected as benign breast disease group and control group. Serum tumor markers, immunoglobulins, TNF-αand hs-CRP concentrations were measured and compared of all subjects. Results: There were no significant difference in serum tumor markers, immunoglobulin and inflammatory factors between the control group and the benign breast cancer group. The level of serum tumor markers in breast cancer group was significantly higher than that in control group and benign breast cancer group. The levels of serum CA125, CA153 and CEA were gradually increased with the severity enhancing from stage I and IV of breast cancer, and he difference was statistically significant. The level of serum immunoglobulin in breast cancer group was significantly higher than that in control group and benign breast cancer group. The levels of serum IgG and IgM increased gradually severity enhancing from stage I and IV of breast cancer, and the difference was statistically significant. The level of serum TNF-α and hs-CRP in serum of breast cancer group was significantly higher than that of control group and benign breast cancer group. The serum levels of TNF-α and hs-CRP increased gradually with severity enhancing from stage I and IV of breast cancer, and the difference was statistically significant. Conclusion: The level of serum tumor markers in breast cancer patients is increasing. Humoral and inflammatory responses are activated to varying degrees and increase with the aggregation of disease. They may involve regulating the occurrence and metastasis of breast

OS090. Performance of candidate clinical and biochemical markers in screening early in pregnancy to detect women at high risk to develop preeclampsia.

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Forest, J-C; Massé, J; Bujold, E; Rousseau, F; Charland, M; Thériault, S; Lafond, J; Giguère, Y

2012-07-01

The advent of early preventive measures, such as low-dose aspirin targeting women at high risk of preeclampsia (PE), emphasizes the need for better detection. Despite the emergence of promising biochemical markers linked to the pathophysiological processes, systematic reviews have shown that, until now, no single tests fulfill the criteria set by WHO for biomarkers to screen for a disease. However, recent literature reveals that by combining various clinical, biophysical and biochemical markers into multivariate algorithms, one can envisage to estimate the risk of PE with a performance that would reach clinical utility and cost-effectiveness, but this remains to be demonstrated in various environments and health care settings. To investigate, in a prospective study, the clinical utility of candidate biomarkers and clinical data to detect, early in pregnancy, women at risk to develop PE and to propose a multivariate prediction algorithm combining clinical parameters to biochemical markers. 7929 pregnant women prospectively recruited at the first prenatal visit, provided blood samples, clinical and sociodemographic information. 214 pregnant women developed hypertensive disorders of pregnancy (HDP) of which 88 had PE (1.2%), including 44 with severe PE (0.6%). A nested case-control study was performed including for each case of HDP two normal pregnancies matched for maternal age, gestational age at recruitment, ethnicity, parity, and smoking status. Based on the literature we selected the most promising markers in a multivariate logistic regression model: mean arterial pressure (MAP), BMI, placental growth factor (PlGF), soluble Flt-1, inhibin A and PAPP-A. Biomarker results measured between 10-18 weeks gestation were expressed as multiples of the median. Medians were determined for each gestational week. When combined with MAP at the time of blood sampling and BMI at the beginning of pregnancy, the four biochemical markers discriminate normal pregnancies from those

Clinical Trial of a Home Safety Toolkit for Alzheimer’s Disease

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Kathy J. Horvath

2013-01-01

Full Text Available This randomized clinical trial tested a new self-directed educational intervention to improve caregiver competence to create a safer home environment for persons with dementia living in the community. The sample included 108 patient/caregiver dyads: the intervention group (n=60 received the Home Safety Toolkit (HST, including a new booklet based on health literacy principles, and sample safety items to enhance self-efficacy to make home safety modifications. The control group (n=48 received customary care. Participants completed measures at baseline and at twelve-week follow-up. Multivariate Analysis of Covariance (MANCOVA was used to test for significant group differences. All caregiver outcome variables improved in the intervention group more than in the control. Home safety was significant at P≤0.001, caregiver strain at P≤0.001, and caregiver self-efficacy at P=0.002. Similarly, the care receiver outcome of risky behaviors and accidents was lower in the intervention group (P≤0.001. The self-directed use of this Home Safety Toolkit activated the primary family caregiver to make the home safer for the person with dementia of Alzheimer's type (DAT or related disorder. Improving the competence of informal caregivers is especially important for patients with DAT in light of all stakeholders reliance on their unpaid care.

Perceptions of clinical safety climate of the multicultural nursing workforce in Saudi Arabia: a cross-sectional survey.

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Almutairi, Adel F; Gardner, Glenn; McCarthy, Alexandra

2013-01-01

The purpose of this study is to explore the safety climate perceptions of the multicultural nursing workforce, and to investigate the influence of diversity of the multicultural nursing workforce on clinical safety in a large tertiary hospital in Saudi Arabia. Working in a multicultural environment is challenging. Each culture has its own unique characteristics and dimensions that shape the language, lifestyle, beliefs, values, customs, traditions, and patterns of behaviour, which expatriate nurses must come to terms with. However, cultural diversity in the health care environment can potentially affect the quality of care and patient safety. A mixed-method case study (survey, interview and document analysis) was employed. A primary study phase entailed the administration of the Safety Climate Survey (SCS). A population sampling strategy was used and 319 nurses participated, yielding a 76.8% response rate. Descriptive and inferential statistics (Kruskal-Wallis test) were used to analyse survey data. The data revealed the nurses' perceptions of the clinical safety climate in this multicultural environment was unsafe, with a mean score of 3.9 out of 5. No significant difference was found between the age groups, years of nursing experience and their perceptions of the safety climate in this context. A significant difference was observed between the national background categories of nurses and perceptions of safety climate. Cultural diversity within the nursing workforce could have a significant influence on perceptions of clinical safety. These findings have the potential to inform policy and practice related to cultural diversity in Saudi Arabia.

Identified metabolic signature for assessing red blood cell unit quality is associated with endothelial damage markers and clinical outcomes

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Bordbar, Aarash; Johansson, Pär I.; Paglia, Giuseppe

2016-01-01

shown no difference of clinical outcome for patients receiving old or fresh RBCs. An overlooked but essential issue in assessing RBC unit quality and ultimately designing the necessary clinical trials is a metric for what constitutes an old or fresh RBC unit. STUDY DESIGN AND METHODS: Twenty RBC units...... years and endothelial damage markers in healthy volunteers undergoing autologous transfusions. CONCLUSION: The state of RBC metabolism may be a better indicator of cellular quality than traditional hematologic variables....

Methylphenidate dose optimization for ADHD treatment: review of safety, efficacy, and clinical necessity

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Huss M

2017-07-01

Full Text Available Michael Huss,1 Praveen Duhan,2 Preetam Gandhi,3 Chien-Wei Chen,4 Carsten Spannhuth,3 Vinod Kumar5 1Child and Adolescent Psychiatry, University Medicine, Mainz, Germany; 2Global Medical Affairs, Novartis Healthcare Pvt. Ltd., Hyderabad, India; 3Development Franchise, Established Medicine Neuroscience, Novartis Pharma AG, Basel, Switzerland; 4Biostatistics Cardio-Metabolic & Established Medicine, Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 5Established Medicines, Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA Abstract: Attention-deficit/hyperactivity disorder (ADHD is a chronic psychiatric disorder characterized by hyperactivity and/or inattention and is often associated with a substantial impact on psychosocial functioning. Methylphenidate (MPH, a central nervous system stimulant, is commonly used for pharmacological treatment of adults and children with ADHD. Current practice guidelines recommend optimizing MPH dosage to individual patient needs; however, the clinical benefits of individual dose optimization compared with fixed-dose regimens remain unclear. Here we review the available literature on MPH dose optimization from clinical trials and real-world experience on ADHD management. In addition, we report safety and efficacy data from the largest MPH modified-release long-acting Phase III clinical trial conducted to examine benefits of dose optimization in adults with ADHD. Overall, MPH is an effective ADHD treatment with a good safety profile; data suggest that dose optimization may enhance the safety and efficacy of treatment. Further research is required to establish the extent to which short-term clinical benefits of MPH dose optimization translate into improved long-term outcomes for patients with ADHD. Keywords: methylphenidate, dose optimization, attention-deficit/hyperactivity disorder, ADHD

Rapid Generation of Multiple Loci-Engineered Marker-free Poxvirus and Characterization of a Clinical-Grade Oncolytic Vaccinia Virus

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Zong Sheng Guo

2017-12-01

Full Text Available Recombinant poxviruses, utilized as vaccine vectors and oncolytic viruses, often require manipulation at multiple genetic loci in the viral genome. It is essential for viral vectors to possess no adventitious mutations and no (antibiotic selection marker in the final product for human patients in order to comply with the guidance from the regulatory agencies. Rintoul et al. have previously developed a selectable and excisable marker (SEM system for the rapid generation of recombinant vaccinia virus. In the current study, we describe an improved methodology for rapid creation and selection of recombinant poxviruses with multiple genetic manipulations solely based on expression of a fluorescent protein and with no requirement for drug selection that can lead to cellular stress and the risk of adventitious mutations throughout the viral genome. Using this improved procedure combined with the SEM system, we have constructed multiple marker-free oncolytic poxviruses expressing different cytokines and other therapeutic genes. The high fidelity of inserted DNA sequences validates the utility of this improved procedure for generation of therapeutic viruses for human patients. We have created an oncolytic poxvirus expressing human chemokine CCL5, designated as vvDD-A34R-hCCL5, with manipulations at two genetic loci in a single virus. Finally, we have produced and purified this virus in clinical grade for its use in a phase I clinical trial and presented data on initial in vitro characterization of the virus.

Molecular markers in glioma.

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Ludwig, Kirsten; Kornblum, Harley I

2017-09-01

Gliomas are the most malignant and aggressive form of brain tumors, and account for the majority of brain cancer related deaths. Malignant gliomas, including glioblastoma are treated with radiation and temozolomide, with only a minor benefit in survival time. A number of advances have been made in understanding glioma biology, including the discovery of cancer stem cells, termed glioma stem cells (GSC). Some of these advances include the delineation of molecular heterogeneity both between tumors from different patients as well as within tumors from the same patient. Such research highlights the importance of identifying and validating molecular markers in glioma. This review, intended as a practical resource for both clinical and basic investigators, summarizes some of the more well-known molecular markers (MGMT, 1p/19q, IDH, EGFR, p53, PI3K, Rb, and RAF), discusses how they are identified, and what, if any, clinical relevance they may have, in addition to discussing some of the specific biology for these markers. Additionally, we discuss identification methods for studying putative GSC's (CD133, CD15, A2B5, nestin, ALDH1, proteasome activity, ABC transporters, and label-retention). While much research has been done on these markers, there is still a significant amount that we do not yet understand, which may account for some conflicting reports in the literature. Furthermore, it is unlikely that the investigator will be able to utilize one single marker to prospectively identify and isolate GSC from all, or possibly, any gliomas.

Comparative usefulness of inflammatory markers to indicate bacterial infection-analyzed according to blood culture results and related clinical factors.

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Nishikawa, Hirokazu; Shirano, Michinori; Kasamatsu, Yu; Morimura, Ayumi; Iida, Ko; Kishi, Tomomi; Goto, Tetsushi; Okamoto, Saki; Ehara, Eiji

2016-01-01

To assess relationships of inflammatory markers and 2 related clinical factors with blood culture results, we retrospectively investigated inpatients' blood culture and blood chemistry findings that were recorded from January to December 2014 using electronic medical records and analyzed the data of 852 subjects (426 culture-positive and 426 culture-negative). Results suggested that the risk of positive blood culture statistically increased as inflammatory marker levels and the number of related factors increased. Concerning the effectiveness of inflammatory markers, when the outcome definition was also changed for C-reactive protein (CRP), the odds ratio had a similar value, whereas when the outcome definition of blood culture positivity was used for procalcitonin (PCT), the greatest effectiveness of that was detected. Therefore, the current results suggest that PCT is more useful than CRP as an auxiliary indication of bacterial infection. Copyright © 2016 Elsevier Inc. All rights reserved.

Clinical reactivations of herpes simplex virus type 2 infection and human immunodeficiency virus disease progression markers.

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Bulbulgul Aumakhan

Full Text Available BACKGROUND: The natural history of HSV-2 infection and role of HSV-2 reactivations in HIV disease progression are unclear. METHODS: Clinical symptoms of active HSV-2 infection were used to classify 1,938 HIV/HSV-2 co-infected participants of the Women's Interagency HIV Study (WIHS into groups of varying degree of HSV-2 clinical activity. Differences in plasma HIV RNA and CD4+ T cell counts between groups were explored longitudinally across three study visits and cross-sectionally at the last study visit. RESULTS: A dose dependent association between markers of HIV disease progression and degree of HSV-2 clinical activity was observed. In multivariate analyses after adjusting for baseline CD4+ T cell levels, active HSV-2 infection with frequent symptomatic reactivations was associated with 21% to 32% increase in the probability of detectable plasma HIV RNA (trend p = 0.004, an average of 0.27 to 0.29 log10 copies/ml higher plasma HIV RNA on a continuous scale (trend p<0.001 and 51 to 101 reduced CD4+ T cells/mm(3 over time compared to asymptomatic HSV-2 infection (trend p<0.001. CONCLUSIONS: HIV induced CD4+ T cell loss was associated with frequent symptomatic HSV-2 reactivations. However, effect of HSV-2 reactivations on HIV disease progression markers in this population was modest and appears to be dependent on the frequency and severity of reactivations. Further studies will be necessary to determine whether HSV-2 reactivations contribute to acceleration of HIV disease progression.

In vitro and in vivo applications of tumor markers

International Nuclear Information System (INIS)

Chatal, J.F.; Ricolleau, G.; Fumoleau, P.; Vuillez, J.P.H.; Chetanneau, A.; Peltier, P.; Lacroix, H.

1988-01-01

In vitro and in vivo applications of tumor markers are reviewed. Concerning in vitro applications, the following topics are developed: ideal marker criterion; present availability of markers; immunoassay methodology; clinical applications; future prospects (oncogenes). In vivo applications deal with immunoscintigraphy a new imaging technique, different from conventional morphological methods, based on specific recognition of antigenic target and involving many immunologic, hemodynamic and methodologic parameters. These various parameters are presented and clinical applications and future prospects of immunoscintigraphy are evaluated [fr

Using clinical supervision to improve the quality and safety of patient care: a response to Berwick and Francis.

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Tomlinson, Jonathon

2015-06-11

After widely publicised investigations into excess patient deaths at Mid Staffordshire hospital the UK government commissioned reports from Robert Francis QC and Professor Don Berwick. Among their recommendations to improve the quality and safety of patient care were lifelong learning, professional support and 'just culture'. Clinical supervision is in an excellent position to support these activities but opportunities are in danger of being squeezed out by regulatory and managerial demands. Doctors who have completed their training are responsible for complex professional judgements for which narrative supervision is particularly helpful. With reference to the literature and my own practice I propose that all practicing clinicians should have regular clinical supervision. Clinical supervision has patient-safety and the quality of patient care as its primary purposes. After training is completed, doctors may practice for the rest of their career without any clinical supervision, the implication being that the difficulties dealt with in clinical supervision are no longer difficulties, or are better dealt with some other way. Clinical supervision is sufficiently flexible to be adapted to the needs of experienced clinicians as its forms can be varied, though its functions remain focused on patient safety, good quality clinical care and professional wellbeing. The evidence linking clinical supervision to the quality and safety of patient care reveals that supervision is most effective when its educational and supportive functions are separated from its managerial and evaluative functions. Among supervision's different forms, narrative-based-supervision is particularly useful as it has been developed for clinicians who have completed their training. It provides ways to explore the complexity of clinical judgements and encourages doctors to question one another's authority in a supportive culture. To be successful, supervision should also be professionally led and

A Quality Model to Select Patients in Cupping Therapy Clinics: A New Tool for Ensuring Safety in Clinical Practice.

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Aboushanab, Tamer; AlSanad, Saud

2018-06-08

Cupping therapy is a popular treatment in various countries and regions, including Saudi Arabia. Cupping therapy is regulated in Saudi Arabia by the National Center for Complementary and Alternative Medicine (NCCAM), Ministry of Health. The authors recommend that this quality model for selecting patients in cupping clinics - first version (QMSPCC-1) - be used routinely as part of clinical practice and quality management in cupping clinics. The aim of the quality model is to ensure the safety of patients and to introduce and facilitate quality and auditing processes in cupping therapy clinics. Clinical evaluation of this tool is recommended. Continued development, re-evaluation and reassessment of this tool are important. Copyright © 2018. Published by Elsevier B.V.

Four small supernumerary marker chromosomes derived from chromosomes 6, 8, 11 and 12 in a patient with minimal clinical abnormalities: a case report

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Hamid Ahmed B

2010-08-01

Full Text Available Abstract Introduction Small supernumerary marker chromosomes are still a problem in cytogenetic diagnostic and genetic counseling. This holds especially true for the rare cases with multiple small supernumerary marker chromosomes. Most such cases are reported to be clinically severely affected due to the chromosomal imbalances induced by the presence of small supernumerary marker chromosomes. Here we report the first case of a patient having four different small supernumerary marker chromosomes which, apart from slight developmental retardation in youth and non-malignant hyperpigmentation, presented no other clinical signs. Case presentation Our patient was a 30-year-old Caucasian man, delivered by caesarean section because of macrosomy. At birth he presented with bilateral cryptorchidism but no other birth defects. At age of around two years he showed psychomotor delay and a bilateral convergent strabismus. Later he had slight learning difficulties, with normal social behavior and now lives an independent life as an adult. Apart from hypogenitalism, he has multiple hyperpigmented nevi all over his body, short feet with pes cavus and claw toes. At age of 30 years, cytogenetic and molecular cytogenetic analysis revealed a karyotype of 50,XY,+min(6(:p11.1-> q11.1:,+min(8(:p11.1->q11.1:,+min(11(:p11.11->q11:,+min(12(:p11.2~12->q10:, leading overall to a small partial trisomy in 12p11.1~12.1. Conclusions Including this case, four single case reports are available in the literature with a karyotype 50,XN,+4mar. For prenatally detected multiple small supernumerary marker chromosomes in particular we learn from this case that such a cytogenetic condition may be correlated with a positive clinical outcome.

National Academy of Clinical Biochemistry laboratory medicine practice guidelines for use of tumor markers in testicular, prostate, colorectal, breast, and ovarian cancers

DEFF Research Database (Denmark)

Sturgeon, Catharine M.; Duffy, Michael J.; Stenman, Ulf-Håkan

2008-01-01

BACKGROUND: Updated National Academy of Clinical Biochemistry (NACB) Laboratory Medicine Practice Guidelines for the use of tumor markers in the clinic have been developed. METHODS: Published reports relevant to use of tumor markers for 5 cancer sites--testicular, prostate, colorectal, breast...... for differential diagnosis of nonseminomatous and seminomatous germ cell tumors. Prostate-specific antigen (PSA) is not recommended for prostate cancer screening, but may be used for detecting disease recurrence and monitoring therapy. Free PSA measurement data are useful for distinguishing malignant from benign...... prostatic disease when total PSA is cancer, carcinoembryonic antigen is recommended (with some caveats) for prognosis determination, postoperative surveillance, and therapy monitoring in advanced disease. Fecal occult blood testing may be used for screening asymptomatic adults 50...

Surrogate end points in clinical research: hazardous to your health.

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Grimes, David A; Schulz, Kenneth F

2005-05-01

Surrogate end points in clinical research pose real danger. A surrogate end point is an outcome measure, commonly a laboratory test, that substitutes for a clinical event of true importance. Resistance to activated protein C, for example, has been used as a surrogate for venous thrombosis in women using oral contraceptives. Other examples of inappropriate surrogate end points in contraception include the postcoital test instead of pregnancy to evaluate new spermicides, breakage and slippage instead of pregnancy to evaluate condoms, and bone mineral density instead of fracture to assess the safety of depo-medroxyprogesterone acetate. None of these markers captures the effect of the treatment on the true outcome. A valid surrogate end point must both correlate with and accurately predict the outcome of interest. Although many surrogate markers correlate with an outcome, few have been shown to capture the effect of a treatment (for example, oral contraceptives) on the outcome (venous thrombosis). As a result, thousands of useless and misleading reports on surrogate end points litter the medical literature. New drugs have been shown to benefit a surrogate marker, but, paradoxically, triple the risk of death. Thousands of patients have died needlessly because of reliance on invalid surrogate markers. Researchers should avoid surrogate end points unless they have been validated; that requires at least one well done trial using both the surrogate and true outcome. The clinical maxim that "a difference to be a difference must make a difference" applies to research as well. Clinical research should focus on outcomes that matter.

Circulating fibrosis markers, eosinophil cationic protein and eosinophil protein X in patients with Wuchereria bancrofti infection: association with clinical status

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Esterre P.

2006-06-01

Full Text Available We measured the concentrations of several circulating fibrosis markers (type I collagen I, type III procollagen, hyaluronan and eosinophil granule proteins (ECP and EPX in lymphatic filariasis patients to investigate their relationship with clinical, parasitological and immunological data. This study was conducted in Polynesian patients with various stages of the disease (acute lymphangitis, chyluria, hydrocoele, elephantiasis, a closely related microbial lymphangitis and endemic controls. We observed modifications of the different markers in this pathology. Serum type I collagen and PIIINP were decreased. Serum hyaluronan, linked to perilymphatic granulomatous inflammation, was significantly increased in acute lymphangitis and elephantiasis patients. Serum ECP was also increased, at the limit of significance in our sample, in elephantiasis patients. These two last markers, already validated in another helminth disease, schistosomiasis, have potential interest in terms of follow-up of morbidity in these parasitic diseases.

Measures to Improve Diagnostic Safety in Clinical Practice.

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Singh, Hardeep; Graber, Mark L; Hofer, Timothy P

2016-10-20

Timely and accurate diagnosis is foundational to good clinical practice and an essential first step to achieving optimal patient outcomes. However, a recent Institute of Medicine report concluded that most of us will experience at least one diagnostic error in our lifetime. The report argues for efforts to improve the reliability of the diagnostic process through better measurement of diagnostic performance. The diagnostic process is a dynamic team-based activity that involves uncertainty, plays out over time, and requires effective communication and collaboration among multiple clinicians, diagnostic services, and the patient. Thus, it poses special challenges for measurement. In this paper, we discuss how the need to develop measures to improve diagnostic performance could move forward at a time when the scientific foundation needed to inform measurement is still evolving. We highlight challenges and opportunities for developing potential measures of "diagnostic safety" related to clinical diagnostic errors and associated preventable diagnostic harm. In doing so, we propose a starter set of measurement concepts for initial consideration that seem reasonably related to diagnostic safety and call for these to be studied and further refined. This would enable safe diagnosis to become an organizational priority and facilitate quality improvement. Health-care systems should consider measurement and evaluation of diagnostic performance as essential to timely and accurate diagnosis and to the reduction of preventable diagnostic harm.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Safety and clinical efficacy of golimumab in the treatment of arthritides

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Ismail Simsek

2010-09-01

Full Text Available Ismail Simsek, Yusuf YaziciNew York University School of Medicine, NYU Hospital for Joint Diseases, New York, USAAbstract: Golimumab is a human anti-tumor necrosis factor (TNF-alpha monoclonal antibody that was recently approved for the treatment of patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. This review covers the published clinical trial data on the use of golimumab for the approved indications mentioned above with respect to efficacy and safety. The various ongoing trials for golimumab have yielded promising results in terms of efficacy and safety in methotrexate-naive and -resistant patients with rheumatoid arthritis, as well as in patients who were previously treated with other anti-TNF agents. In addition, the efficacy of golimumab in psoriatic arthritis and ankylosing spondylitis has also been demonstrated. The real safety information will be available only once the drug has been used in many more patients, who frequently have comorbid conditions.Keywords: arthritis, rheumatoid, psoriatic arthritis, ankylosing spondylitis

Clinical manifestation, serology marker & microscopic agglutination test (MAT) to mortality in human leptospirosis

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Perdhana, S. A. P.; Susilo, R. S. B.; Arifin; Redhono, D.; Sumandjar, T.

2018-03-01

Leptospirosis is a potentially fatal zoonosis that is endemic in many tropical regions and causes large epidemics after heavy rainfall and flooding. Severe disease is estimated 5–15% of all human infections. Its mortality rate is 5-40%. MAT, isolation of the organism, or leptospiral DNA in PCR are used to confirm Leptospirosis. This cross-sectional analytic study recruited 26 hospitalized leptospirosis patients admitted to Dr. Moewardi Hospital Surakarta. The diagnosis was based on clinical, laboratory and epidemiological findings. The onset of the disease was the date when the first symptom started, and the end of the analysis was the date when the patient died or discharged. Modified Faine’s score ≥ 25 tend to die (45.5%) while modified Faine’s score 20 – 24 tend to heal (60%) (OR 1.250; CI 0.259-6.029; p=1.0). Seropositive IgM predicts mortality 7.8 times higher than seronegative IgM (OR 7.800; CI 1.162-52.353; p=0.038). MAT positive predict mortality 10.667 times higher than MAT negative (OR 10.667; CI 1.705-66.720; p=0.015). Clinical manifestation, MAT, and serologic marker are all correlated with mortality in Leptospirosis. However, statistically, clinical manifestation has an insignificant correlation.

Frequency of hepatitis B (HBV) viral markers in sixth year dental students after three years clinical exposure

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Buxt, P; Fairbairn, P J.M.; Stern, S R; Treisman, B [University of the Witwatersrand, Johannesburg (South Africa). Dept. of Oral Pathology

1981-08-01

The frequency of Hepatitis B viral markers was studied in 40 6th year dental students at the University of the Witwatersrand, Johannesburg, after three years clinical exposure, using the radioimmunoassay technique. Three were anti-HBs positive; none was HBsAg positive. The frequency of the anti-HBs positive cases did not differ significantly from a group of blood donors, nor were there any statistically significant associated risk factors.

Use of wand markers on the pelvis in three dimensional gait analysis

DEFF Research Database (Denmark)

Smith, Martin; Curtis, Derek; Bencke, Jesper

2013-01-01

During clinical gait analysis, surface markers are placed over the anterior superior iliac spines (ASIS) of the pelvis. However, this can be problematic in overweight or obese subjects, where excessive adipose tissue can obscure the markers and prevent accurate tracking. A novel solution to this ......During clinical gait analysis, surface markers are placed over the anterior superior iliac spines (ASIS) of the pelvis. However, this can be problematic in overweight or obese subjects, where excessive adipose tissue can obscure the markers and prevent accurate tracking. A novel solution...... to this problem has previously been proposed and tested on a limited sample of healthy, adult subjects. This involves use of wand markers on the pelvis, to virtually recreate the ASIS markers. The method was tested here on 20 typical subjects presenting for clinical gait analysis (adults and children, including...

A clinical study of dermatoses in diabetes to establish its markers

Directory of Open Access Journals (Sweden)

Dependra Kumar Timshina

2012-01-01

Full Text Available Background: Cutaneous manifestations of diabetes mellitus generally appear subsequent to the development of the disease, but they may be the first presenting signs and in some cases they may precede the primary disease manifestation by many years. Aims : T0 he aim of our study was to study the spectrum of dermatoses in diabetics, to know the frequency of dermatoses specific to diabetes mellitus (DM, and to establish the mucocutaneous markers of DM. Material and Methods: The study was conducted at a diabetic clinic and our department between September 2008 and June 2010. Two hundred and twenty-four diabetic patients were included in the study group and those with gestational diabetes were excluded. Healthy age- and sex-matched individuals were taken as controls. Results: The male to female ratio was 1 : 1.21. Type 2 DM was seen in 89.7% and type 1 DM in 10.3% of the patients. Dermatoses were seen in 88.3% of the diabetics compared to 36% in non-diabetic controls (P<0.05. Cutaneous infections were the most common dermatoses followed by acanthosis nigricans and xerosis in diabetics. Type 2 DM was found to have an increased risk of complications than type 1 DM. Complications of diabetes were seen in 43.7% of the diabetic cases. Diabetic dermopathy, loss of hair over the legs, diabetic foot ulcer, and so on, were found to be the cutaneous markers of DM in our group of cases. Conclusion: Dermatoses were more common in diabetics than non-diabetics. Cutaneous infections formed the largest group of dermatoses in DM.

Clinical use of computed tomography and surface markers to assist internal fixation within the equine hoof.

Science.gov (United States)

Gasiorowski, Janik C; Richardson, Dean W

2015-02-01

To describe clinical use of computed tomography (CT) and hoof surface markers to facilitate internal fixation within the confines of the hoof wall. Retrospective case series. Horses (n = 16) that had CT-guided internal fixation of the distal phalanx (DP) or distal sesamoid bone (DSB). Drill bit entry point and direction were planned from CT image series performed on hooves with grids of barium paste dots at proposed entry and projected exit sites. Post-implantation CT images were obtained to check screw position and length as well as fracture reduction. Imaging, reduction, and surgical and general anesthesia times were evaluated. Outcome was recorded. Screw position and length were considered near optimal in all horses, with no consequential malposition of bits or screws. Fracture reduction was evident in all cases. Preoperative planning times (at least 2 CT image acquisitions and grid creation) ranged from 10 to 20 minutes. Surgery time ranged from 45 to 90 minutes (mean, 61 minutes) and general anesthesia time ranged from 115 to 220 minutes (mean, 171 minutes). The combination of CT and surface marker grids allowed accurate positioning of screws in clinical DP and DSB fractures. The technique was simple and rapid. An aiming device is useful for the technique. © Copyright 2014 by The American College of Veterinary Surgeons.

Breath acetone as a potential marker in clinical practice.

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Ruzsányi, Veronika; Péter Kalapos, Miklós

2017-06-01

In recent decades, two facts have changed the opinion of researchers about the function of acetone in humans. Firstly, it has turned out that acetone cannot be regarded as simply a waste product of metabolism, because there are several pathways in which acetone is produced or broken down. Secondly, methods have emerged making possible its detection in exhaled breath, thereby offering an attractive alternative to investigation of blood and urine samples. From a clinical point of view the measurement of breath acetone levels is important, but there are limitations to its wide application. These limitations can be divided into two classes, technical and biological limits. The technical limits include the storage of samples, detection threshold, standardization of clinical settings, and the price of instruments. When considering the biological ranges of acetone, personal factors such as race, age, gender, weight, food consumption, medication, illicit drugs, and even profession/class have to be taken into account to use concentration information for disorders. In some diseases such as diabetes mellitus and lung cancer, as well as in nutrition-related behavior such as starvation and ketogenic diet, breath acetone has been extensively examined. At the same time, there is a lack of investigations in other cases in which ketosis is also evident, such as in alcoholism or an inborn error of metabolism. In summary, the detection of acetone in exhaled breath is a useful and promising tool for diagnosis and it can be used as a marker to follow the effectiveness of treatments in some disorders. However, further endeavors are needed for clarification of the exact distribution of acetone in different body compartments and evaluation of its complex role in humans, especially in those cases in which a ketotic state also occurs.

Increased serum ß2-microglobulin is associated with clinical and immunological markers of disease activity in systemic lupus erythematosus patients

DEFF Research Database (Denmark)

Hermansen, M-L F; Hummelshøj, L; Lundsgaard, Dorte

2012-01-01

The objective of this study was to explore the relationship between serum levels of ß2-microglobulin (ß2MG), which some studies suggest reflect disease activity in systemic lupus erythematosus (SLE), and various clinical and immunological markers of disease activity in SLE. Twenty-six SLE patients...

Non-clinical models: validation, study design and statistical consideration in safety pharmacology.

Science.gov (United States)

Pugsley, M K; Towart, R; Authier, S; Gallacher, D J; Curtis, M J

2010-01-01

The current issue of the Journal of Pharmacological and Toxicological Methods (JPTM) focuses exclusively on safety pharmacology methods. This is the 7th year the Journal has published on this topic. Methods and models that specifically relate to methods relating to the assessment of the safety profile of a new chemical entity (NCE) prior to first in human (FIH) studies are described. Since the Journal started publishing on this topic there has been a major effort by safety pharmacologists, toxicologists and regulatory scientists within Industry (both large and small Pharma as well as Biotechnology companies) and also from Contract Research Organizations (CRO) to publish the surgical details of the non-clinical methods utilized but also provide important details related to standard and non-standard (or integrated) study models and designs. These details from core battery and secondary (or ancillary) drug safety assessment methods used in drug development programs have been the focus of these special issues and have been an attempt to provide validation of methods. Similarly, the safety pharmacology issues of the Journal provide the most relevant forum for scientists to present novel and modified methods with direct applicability to determination of drug safety-directly to the safety pharmacology scientific community. The content of the manuscripts in this issue includes the introduction of additional important surgical methods, novel data capture and data analysis methods, improved study design and effects of positive control compounds with known activity in the model. Copyright 2010 Elsevier Inc. All rights reserved.

Omega-3 supplementation on inflammatory markers in patients with chronic Chagas cardiomyopathy: a randomized clinical study.

Science.gov (United States)

Silva, Paula Simplício da; Mediano, Mauro Felippe Felix; Silva, Gilberto Marcelo Sperandio da; Brito, Patricia Dias de; Cardoso, Claudia Santos de Aguiar; Almeida, Cristiane Fonseca de; Sangenis, Luiz Henrique Conde; Pinheiro, Roberta Olmo; Hasslocher-Moreno, Alejandro Marcel; Brasil, Pedro Emmanuel Alvarenga Americano do; Sousa, Andrea Silvestre de

2017-06-09

Several studies have been focusing on the effect of omega-3 polyunsaturated fatty acids on modulation of inflammatory markers in several cardiopathies. Although immunoregulatory dysfunction has been associated to the chronic cardiac involvement in Chagas disease, there is no study examining the effects of omega-3 supplementation in these patients. We investigated the effects of omega-3 PUFAs on markers of inflammation and lipid profile in chronic Chagas cardiomyopathy patients. The present study was a single-center double-blind clinical trial including patients with chronic Chagas cardiomyopathy. Patients were randomly assigned to receive omega-3 PUFAs capsules (1.8g EPA and 1.2g DHA) or placebo (corn oil) during an 8-week period. Cytokines, fasting glucose, lipid, and anthropometric profiles were evaluated. Forty-two patients (23 women and 19 men) were included in the study and there were only two losses to follow-up during the 8-week period. Most of sociodemographic and clinical characteristics were similar between the groups at baseline, except for the cytokines IL-1β, IL-6, IL-8, IL-10, IL-17α, and IFNγ. The omega-3 PUFAs group demonstrated greater improvements in serum triglycerides (-21.1 vs. -4.1; p = 0.05) and IL-10 levels (-10.6 vs. -35.7; p = 0.01) in comparison to controls after 8 weeks of intervention. No further differences were observed between groups. Omega-3 PUFAs supplementation may favorably affect lipid and inflammatory profile in chronic Chagas cardiomyopathy patients, demonstrated by a decrease in triglycerides and improvements on IL-10 concentration. Further studies examining the clinical effects of omega-3 fatty acids supplementation in chronic Chagas cardiomyopathy are necessary. NCT01863576.

Biochemical markers of bone turnover

International Nuclear Information System (INIS)

Kim, Deog Yoon

1999-01-01

Biochemical markers of bone turnover has received increasing attention over the past few years, because of the need for sensitivity and specific tool in the clinical investigation of osteoporosis. Bone markers should be unique to bone, reflect changes of bone less, and should be correlated with radiocalcium kinetics, histomorphometry, or changes in bone mass. The markers also should be useful in monitoring treatment efficacy. Although no bone marker has been established to meet all these criteria, currently osteocalcin and pyridinium crosslinks are the most efficient markers to assess the level of bone turnover in the menopausal and senile osteoporosis. Recently, N-terminal telopeptide (NTX), C-terminal telopeptide (CTX) and bone specific alkaline phosphatase are considered as new valid markers of bone turnover. Recent data suggest that CTX and free deoxypyridinoline could predict the subsequent risk of hip fracture of elderly women. Treatment of postmenopausal women with estrogen, calcitonin and bisphosphonates demonstrated rapid decrease of the levels of bone markers that correlated with the long-term increase of bone mass. Factors such as circadian rhythms, diet, age, sex, bone mass and renal function affect the results of biochemical markers and should be appropriately adjusted whenever possible. Each biochemical markers of bone turnover may have its own specific advantages and limitations. Recent advances in research will provide more sensitive and specific assays

FDA drug safety communications: a narrative review and clinical considerations for older adults.

Science.gov (United States)

Marcum, Zachary A; Vande Griend, Joseph P; Linnebur, Sunny A

2012-08-01

The US Food and Drug Administration (FDA) has new regulatory authorities intended to enhance drug safety monitoring in the postmarketing period. This has resulted in an increase in communication from the FDA in recent years about the safety profile of certain drugs. It is important to stay abreast of the current literature on drug risks to effectively communicate these risks to patients, other health care providers, and the general public. To summarize 4 new FDA drug safety communications by describing the evidence supporting the risks and the clinical implications for older adults. The FDA Web site was reviewed for new drug safety communications from May 2011 to April 2012 that would be relevant to older adults. Approved labeling for each drug or class was obtained from the manufacturer, and PubMed was searched for primary literature that supported the drug safety concern. FDA drug safety communications for 4 drugs were chosen because of the potential clinical importance in older adults. A warning for citalopram was made because of potential problems with QT prolongation in patients taking less than 40 mg per day. The evidence suggests minor changes in QT interval. Given the flat dose-response curve in treating depression with citalopram, the new 20-mg/d maximum dose in older adults is sensible. Another warning was made for proton pump inhibitors (PPIs) and an increased risk of Clostridium difficile infection. A dose-response relationship was found for this drug risk. With C. difficile infections on the rise in older adults, along with other safety risks of PPI therapy, PPIs should only be used in older adults indicated for therapy for the shortest duration possible. In addition, a warning about dabigatran was made. There is strong evidence from a large clinical trial, as well as case reports, of increased bleeding risk in older adults taking dabigatran, especially in older adults with decreased renal function. This medication should be used with caution in older

Clinical significance of determination of 3 tumor markers in bronchoalveolar lavage fluid

International Nuclear Information System (INIS)

Chen Rui; Hu Huacheng; Hu Yunzhu

2003-01-01

Objective: To investigate the value of 3 tumor markers in bronchoalveolar lavage fluid (BALF) for diagnosis and evaluation of disease extent in patients with lung cancer. Methods: The level of CEA, CYFRA21-1 and NSE in BALF was measured in 92 patients with lung cancer and 40 patients with benign lung diseases by using chemoluminescence, RIA and ELISA methods respectively. Results: The level of all 3 tumor markers measured in BALF was much higher in lung cancer group than that in benign lung disease group (P<0.01 or P<0.05), and it was higher in patients with advanced disease (stage III and IV) than that in stage I and II. These tumor markers increased in different degrees among the patients in various pathological classifications. It was also found the level of these tumor markers was higher and more sensitive in BALF than that in serum. Conclusion: The measurement of the tumor markers in BALF has more significant value than the measurement in serum, which contribute to the early diagnosis, pathological classification and prognosis evaluation of lung cancer

Systematic evaluation of candidate blood markers for detecting ovarian cancer.

Directory of Open Access Journals (Sweden)

Chana Palmer

2008-07-01

Full Text Available Epithelial ovarian cancer is a significant cause of mortality both in the United States and worldwide, due largely to the high proportion of cases that present at a late stage, when survival is extremely poor. Early detection of epithelial ovarian cancer, and of the serous subtype in particular, is a promising strategy for saving lives. The low prevalence of ovarian cancer makes the development of an adequately sensitive and specific test based on blood markers very challenging. We evaluated the performance of a set of candidate blood markers and combinations of these markers in detecting serous ovarian cancer.We selected 14 candidate blood markers of serous ovarian cancer for which assays were available to measure their levels in serum or plasma, based on our analysis of global gene expression data and on literature searches. We evaluated the performance of these candidate markers individually and in combination by measuring them in overlapping sets of serum (or plasma samples from women with clinically detectable ovarian cancer and women without ovarian cancer. Based on sensitivity at high specificity, we determined that 4 of the 14 candidate markers--MUC16, WFDC2, MSLN and MMP7--warrant further evaluation in precious serum specimens collected months to years prior to clinical diagnosis to assess their utility in early detection. We also reported differences in the performance of these candidate blood markers across histological types of epithelial ovarian cancer.By systematically analyzing the performance of candidate blood markers of ovarian cancer in distinguishing women with clinically apparent ovarian cancer from women without ovarian cancer, we identified a set of serum markers with adequate performance to warrant testing for their ability to identify ovarian cancer months to years prior to clinical diagnosis. We argued for the importance of sensitivity at high specificity and of magnitude of difference in marker levels between cases and

Comparative Studies of Collaborative Team Depression Care Adoption in Safety Net Clinics

Science.gov (United States)

Ell, Kathleen; Wu, Shinyi; Guterman, Jeffrey; Schulman, Sandra-Gross; Sklaroff, Laura; Lee, Pey-Jiuan

2018-01-01

Purpose: To evaluate three approaches adopting collaborative depression care model in Los Angeles County safety net clinics with predominantly Latino type 2 diabetes patients. Methods: Pre-post differences in treatment rates and symptom reductions were compared between baseline, 6-month, and 12-month follow-ups for each approach: (a) Multifaceted…

The marker: A precious link between generations and a part of the long-term safety story

International Nuclear Information System (INIS)

Massart, Cecile

2014-01-01

High-level radioactive waste brings us face to face with a social, emotional, ethical, political and environmental situation at the heart of which lies the security of the living world. From now on, mankind has to make commitments to protect itself. Building an artistic device, a continuous creation that links and reveals the situation will inform and shed some light on the objectives. In co-operation with industries that manage geological repositories, the installation of markers above ground introduces non-technical aspects that can increase safety. In the art world, many works of art produced throughout the 20. century associate art with waste as vestiges for keeping. The use of waste has shaken the nature of art since Marcel Duchamp, the eye of Man Ray as well as the definition of the artist. The waste recycling industry has modified the way we see it. For what is waste? It embodies above all the imperfect and also a 'time capsule'. In the case that concerns us, waste stays buried in our doubt, secured by our current financial means that are substantial. The notion of time for its decay is calculated and, at the end, it vanishes. Its visibility is next to nil, whereas its presence remains very powerful and thrills the imagination. The hosting community is permeated with it. At the same time the laboratory at the disposal facility provides economic dynamism, an analysis of upheavals in this territory, an exhibition of artistic devices and an awareness of danger. The proposals that are described here are the result of a decade of research. It seems that from the beginning there has been negligence on the part of the nuclear industry regarding the storage of high-level radioactive waste. The general public is not very knowledgeable about the subject. Projects for geological disposal often give the local population the feeling of an ablation of a piece of territory. To sum it up, in the long run, we consider the study of two barriers for the safety of high

Clinical Usefulness of Implanted Fiducial Markers for Hypofractionated Radiotherapy of Prostate Cancer

International Nuclear Information System (INIS)

Choi, Young Min; Ahn, Sung Hwan; Lee, Hyung Hwan; Lee, Hyung Sik; Hur, Woo Joo; Yoon, Jin Han; Kim, Tae Hyo; Kim, Soo Dong; Yun, Seong Guk

2011-01-01

To assess the usefulness of implanted fiducial markers in the setup of hypofractionated radiotherapy for prostate cancer patients by comparing a fiducial marker matched setup with a pelvic bone match. Four prostate cancer patients treated with definitive hypofractionated radiotherapy between September 2009 and August 2010 were enrolled in this study. Three gold fiducial markers were implanted into the prostate and through the rectum under ultrasound guidance around a week before radiotherapy. Glycerin enemas were given prior to each radiotherapy planning CT and every radiotherapy session. Hypofractionated radiotherapy was planned for a total dose of 59.5 Gy in daily 3.5 Gy with using the Novalis system. Orthogonal kV X-rays were taken before radiotherapy. Treatment positions were adjusted according to the results from the fusion of the fiducial markers on digitally reconstructed radiographs of a radiotherapy plan with those on orthogonal kV X-rays. When the difference in the coordinates from the fiducial marker fusion was less than 1 mm, the patient position was approved for radiotherapy. A virtual bone matching was carried out at the fiducial marker matched position, and then a setup difference between the fiducial marker matching and bone matching was evaluated. Three patients received a planned 17-fractionated radiotherapy and the rest underwent 16 fractionations. The setup error of the fiducial marker matching was 0.94±0.62 mm (range, 0.09 to 3.01 mm; median, 0.81 mm), and the means of the lateral, craniocaudal, and anteroposterior errors were 0.39±0.34 mm, 0.46±0.34 mm, and 0.57±0.59 mm, respectively. The setup error of the pelvic bony matching was 3.15±2.03 mm (range, 0.25 to 8.23 mm; median, 2.95 mm), and the error of craniocaudal direction (2.29±1.95 mm) was significantly larger than those of anteroposterior (1.73±1.31 mm) and lateral directions (0.45±0.37 mm), respectively (p< 0.05). Incidences of over 3 mm and 5 mm in setup difference among the

Recommendations for Clinical Pathology Data Generation, Interpretation, and Reporting in Target Animal Safety Studies for Veterinary Drug Development.

Science.gov (United States)

Siska, William; Gupta, Aradhana; Tomlinson, Lindsay; Tripathi, Niraj; von Beust, Barbara

Clinical pathology testing is routinely performed in target animal safety studies in order to identify potential toxicity associated with administration of an investigational veterinary pharmaceutical product. Regulatory and other testing guidelines that address such studies provide recommendations for clinical pathology testing but occasionally contain outdated analytes and do not take into account interspecies physiologic differences that affect the practical selection of appropriate clinical pathology tests. Additionally, strong emphasis is often placed on statistical analysis and use of reference intervals for interpretation of test article-related clinical pathology changes, with limited attention given to the critical scientific review of clinically, toxicologically, or biologically relevant changes. The purpose of this communication from the Regulatory Affairs Committee of the American Society for Veterinary Clinical Pathology is to provide current recommendations for clinical pathology testing and data interpretation in target animal safety studies and thereby enhance the value of clinical pathology testing in these studies.

Clinical impact of [18F]FDG-PET in patients with suspected recurrent breast cancer based on asymptomatically elevated tumor marker serum levels. A preliminary report

International Nuclear Information System (INIS)

Liu, Chiu-Shong; Lin, Cheng-Chieh; Kao, Chia-Hung; Yen, Ruoh-Fang

2002-01-01

The purpose of this study was to evaluate retrospectively the impact of [ 18 F]fluorodeoxyglucose positron emission tomography (FDG-PET) on the detection of recurrent breast cancer based on asymptomatically elevated tumor markers levels. Whole-body FDG-PET was performed in 30 patients with suspected recurrent breast cancer and asymptomatic tumor marker increase but negative or equivocal other imaging modality results. A blood sample was drawn in each case for marker assay (CA 15-3 and CEA) on the same day as the FDG-PET. All of these 30 asymptomatic patients had either CA 15-3>32 U/ml or CEA>5 ng/ml. The final diagnosis of recurrent breast cancer was established by operation/biopsy histopathological findings or clinical follow-up for >1 year by additional morphological imaging techniques. Among the 30 patients, the final diagnosis of recurrent breast cancer was established in 38 sites in 28 patients. FDG-PET accurately detected 35/38 sites in 25/28 patients with recurrence. The diagnostic sensitivity and accuracy of FDG-PET in patients with suspected recurrent breast cancer and asymptomatically elevated tumor markers were 96 and 90%, respectively. FDG-PET is a useful technique for detecting recurrent breast cancer suspected from asymptomatically elevated tumor markers levels and has an important clinical impact on the management of these patients. (author)

MRI with cardiac pacing devices – Safety in clinical practice

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Kaasalainen, Touko, E-mail: touko.kaasalainen@hus.fi [HUS Medical Imaging Center, Helsinki University Central Hospital, POB 340 (Haartmaninkatu 4), 00290 Helsinki (Finland); Department of Physics, University of Helsinki (Finland); Pakarinen, Sami, E-mail: sami.pakarinen@hus.fi [HUS Department of Cardiology, Helsinki University Central Hospital, POB 340 (Haartmaninkatu 4), 00290 Helsinki (Finland); Kivistö, Sari, E-mail: sari.kivisto@hus.fi [HUS Medical Imaging Center, Helsinki University Central Hospital, POB 340 (Haartmaninkatu 4), 00290 Helsinki (Finland); Holmström, Miia, E-mail: miia.holmstrom@hus.fi [HUS Medical Imaging Center, Helsinki University Central Hospital, POB 340 (Haartmaninkatu 4), 00290 Helsinki (Finland); Hänninen, Helena, E-mail: helena.hanninen@hus.fi [HUS Department of Cardiology, Helsinki University Central Hospital, POB 340 (Haartmaninkatu 4), 00290 Helsinki (Finland); Peltonen, Juha, E-mail: juha.peltonen@hus.fi [HUS Medical Imaging Center, Helsinki University Central Hospital, POB 340 (Haartmaninkatu 4), 00290 Helsinki (Finland); Department of Biomedical Engineering and Computational Science, School of Science, Aalto University, Helsinki (Finland); Lauerma, Kirsi, E-mail: kirsi.lauerma@hus.fi [HUS Medical Imaging Center, Helsinki University Central Hospital, POB 340 (Haartmaninkatu 4), 00290 Helsinki (Finland); Sipilä, Outi, E-mail: outi.sipila@hus.fi [HUS Medical Imaging Center, Helsinki University Central Hospital, POB 340 (Haartmaninkatu 4), 00290 Helsinki (Finland)

2014-08-15

Objectives: The aim of this study was to introduce a single centre “real life” experience of performing MRI examinations in clinical practice on patients with cardiac pacemaker systems. Additionally, we aimed to evaluate the safety of using a dedicated safety protocol for these patients. Materials and methods: We used a 1.5 T MRI scanner to conduct 68 MRI scans of different body regions in patients with pacing systems. Of the cardiac devices, 32% were MR-conditional, whereas the remaining 68% were MR-unsafe. We recorded the functional parameters of the devices prior, immediately after, and approximately one month after the MRI scanning, and compared the device parameters to the baseline values. Results: All MRI examinations were completed safely, and each device could be interrogated normally following the MRI. We observed no changes in the programmed parameters of the devices. For most of the participants, the distributions of the immediate and one-month changes in the device parameters were within 20% of the baseline values, although some changes approached clinically important thresholds. Furthermore, we observed no differences in the variable changes between MR-conditional and MR-unsafe pacing systems, or between scans of the thorax area and other scanned areas. Conclusion: MRI in patients with MR-conditional pacing systems and selected MR-unsafe systems could be performed safely under strict conditions in this study.

[Analysis of patient complaints in Primary Care: An opportunity to improve clinical safety].

Science.gov (United States)

Añel-Rodríguez, R M; Cambero-Serrano, M I; Irurzun-Zuazabal, E

2015-01-01

To determine the prevalence and type of the clinical safety problems contained in the complaints made by patients and users in Primary Care. An observational, descriptive, cross-sectional study was conducted by analysing both the complaint forms and the responses given to them in the period of one year. At least 4.6% of all claims analysed in this study contained clinical safety problems. The family physician is the professional who received the majority of the complaints (53.6%), and the main reason was the problems related to diagnosis (43%), mainly the delay in diagnosis. Other variables analysed were the severity of adverse events experienced by patients (in 68% of cases the patient suffered some harm), the subsequent impact on patient care, which was affected in 39% of cases (7% of cases even requiring hospital admission), and the level of preventability of adverse events (96% avoidable) described in the claims. Finally the type of response issued to each complaint was analysed, being purely bureaucratic in 64% of all cases. Complaints are a valuable source of information about the deficiencies identified by patients and healthcare users. There is considerable scope for improvement in the analysis and management of claims in general, and those containing clinical safety issues in particular. To date, in our area, there is a lack of appropriate procedures for processing these claims. Likewise, we believe that other pathways or channels should be opened to enable communication by patients and healthcare users. Copyright © 2015 SECA. Published by Elsevier Espana. All rights reserved.

Safety and function of a new clinical intracerebral microinjection instrument for stem cells and therapeutics examined in the Göttingen minipig

DEFF Research Database (Denmark)

Bjarkam, Carsten R; GLUD, AN; Margolin, Lee

2010-01-01

Safety and function of a new clinical intracerebral microinjection instrument for stem cells and therapeutics examined in the Göttingen minipig......Safety and function of a new clinical intracerebral microinjection instrument for stem cells and therapeutics examined in the Göttingen minipig...

Safety and clinical efficacy of some radiation-sterilized medical products and pharmaceuticals

International Nuclear Information System (INIS)

Kulkarni, R.D.; Gopal, N.G.S.

1975-01-01

Medical products and pharmaceuticals must conform to certain minimum physico-chemical microbiological and biological requirements. The biological requirements comprise principally testing for toxicity, safety, and pyrogens. Besides the above-mentioned criteria, there are two other important characteristics, viz. clinical efficacy and tolerance in animal and/or human beings. These latter requirements, expected from the final product released for general human use, are not carried out routinely. In the present-day pharmaceutical and medical technology, numerous mew products are appearing, many of them requiring radiation sterilization as they are not stable towards the other conventional methods of sterilization. While the post-irradiation physicochemical changes in a product may not be significant, the bio-availability or biological activity of the product may be affected to a more significant extent. Some evidence of this has recently been reported. Hence, it is desirable to carry out studies on safety as well as clinical efficacy on irradiated products. This paper describes some studies on plastic-based medical products, a pharmaceutical raw material, a typical infusion fluid such as normal saline, antibiotics and their ointments. (author)

3D marker-controlled watershed for kidney segmentation in clinical CT exams.

Science.gov (United States)

Wieclawek, Wojciech

2018-02-27

Image segmentation is an essential and non trivial task in computer vision and medical image analysis. Computed tomography (CT) is one of the most accessible medical examination techniques to visualize the interior of a patient's body. Among different computer-aided diagnostic systems, the applications dedicated to kidney segmentation represent a relatively small group. In addition, literature solutions are verified on relatively small databases. The goal of this research is to develop a novel algorithm for fully automated kidney segmentation. This approach is designed for large database analysis including both physiological and pathological cases. This study presents a 3D marker-controlled watershed transform developed and employed for fully automated CT kidney segmentation. The original and the most complex step in the current proposition is an automatic generation of 3D marker images. The final kidney segmentation step is an analysis of the labelled image obtained from marker-controlled watershed transform. It consists of morphological operations and shape analysis. The implementation is conducted in a MATLAB environment, Version 2017a, using i.a. Image Processing Toolbox. 170 clinical CT abdominal studies have been subjected to the analysis. The dataset includes normal as well as various pathological cases (agenesis, renal cysts, tumors, renal cell carcinoma, kidney cirrhosis, partial or radical nephrectomy, hematoma and nephrolithiasis). Manual and semi-automated delineations have been used as a gold standard. Wieclawek Among 67 delineated medical cases, 62 cases are 'Very good', whereas only 5 are 'Good' according to Cohen's Kappa interpretation. The segmentation results show that mean values of Sensitivity, Specificity, Dice, Jaccard, Cohen's Kappa and Accuracy are 90.29, 99.96, 91.68, 85.04, 91.62 and 99.89% respectively. All 170 medical cases (with and without outlines) have been classified by three independent medical experts as 'Very good' in 143

Clinical Significance of Immuno phenotypic Markers in Pediatric T-cell Acute Lymphoblastic Leukemia

International Nuclear Information System (INIS)

SIDHOM, I.; SHAABAN, Kh.; SOLIMAN, S.; HAMDY, N.; YASSIN, D.; SALEM, Sh.; HASSANEIN, H.; MANSOUR, M.T.; EZZAT, S.; EL-ANWAR, W.

2008-01-01

Background: Cell-marker profiling has led to conflicting conclusions about its prognostic significance in T-ALL. Aim: To investigate the prevalence of the expression of CD34, CD10 and myeloid associated antigens (CD13/ CD33) in childhood T-ALL and to relate their presence to initial clinical and biologic features and early response to therapy. Patients and Methods: This study included 67 consecutive patients with newly diagnosed T-ALL recruited from the Children's Cancer Hospital in Egypt during the time period from July 2007 to June 2008. Immuno phenotypic markers and minimal residual disease (MRD) were studied by five-color flow cytometry. Results: The frequency of CD34 was 34.9%, CD10 33.3%, while CD13/CD33 was 18.8%. No significant association was encountered between CD34, CD10 or myeloid antigen positivity and the presenting clinical features as age, sex, TLC and CNS leukemia. Only CD10+ expression had significant association with initial CNS involvement (p=0.039). CD34 and CD13/CD33 expression was significantly associated with T-cell maturation stages (p<0.05). No relationship was observed for age, TLC, gender, NCI risk or CNS involvement with early response to therapy illustrated by BM as well as MRD day 15 and day 42. CD34+, CD13/CD33+ and early T-cell stage had high MRD levels on day 15 that was statistically highly significant (p<0.01), but CD10+ had statistically significant lower MRD level on day 15 (p=0.049). However, only CD34 retained its significance at an MRD cut-off level of 0.01%. Conclusion: CD34, CD10, CD13/CD33 expression, as well as T-cell maturation stages, may have prognostic significance in pediatric T-ALL as they have a significant impact on early clearance of leukemic cells detected by MRD day 15.

The frequency of hepatitis B (HBV) viral markers in sixth year dental students after three years clinical exposure

International Nuclear Information System (INIS)

Buxt, P.; Fairbairn, P.J.M.; Stern, S.R.; Treisman, B.

1981-01-01

The frequency of Hepatitis B viral markers was studied in 40 6th year dental students at the University of the Witwatersrand, Johannesburg, after three years clinical exposure, using the radioimmunoassay technique. Three were anti-HBs positive; none was HBsAg positive. The frequency of the anti-HBs positive cases did not differ significantly from a group of blood donors, nor were there any statistically significant associated risk factors [af

Safety, correlative markers, and clinical results of adjuvant nivolumab in combination with vaccine in resected high-risk metastatic melanoma.

Science.gov (United States)

Gibney, Geoffrey T; Kudchadkar, Ragini R; DeConti, Ronald C; Thebeau, Melissa S; Czupryn, Maria P; Tetteh, Leticia; Eysmans, Cabell; Richards, Allison; Schell, Michael J; Fisher, Kate J; Horak, Christine E; Inzunza, H David; Yu, Bin; Martinez, Alberto J; Younos, Ibrahim; Weber, Jeffrey S

2015-02-15

The anti-programmed death-1 (PD-1) antibody nivolumab (BMS-936558) has clinical activity in patients with metastatic melanoma. Nivolumab plus vaccine was investigated as adjuvant therapy in resected stage IIIC and IV melanoma patients. HLA-A*0201 positive patients with HMB-45, NY-ESO-1, and/or MART-1 positive resected tumors received nivolumab (1 mg/kg, 3 mg/kg, or 10 mg/kg i.v.) with a multi-peptide vaccine (gp100, MART-1, and NY-ESO-1 with Montanide ISA 51 VG) every 2 weeks for 12 doses followed by nivolumab maintenance every 12 weeks for 8 doses. Primary objective was safety and determination of a maximum tolerated dose (MTD). Secondary objectives included relapse-free survival (RFS), overall survival (OS), and immunologic correlative studies. Thirty-three patients were enrolled. Median age was 47 years; 55% were male. Two patients had stage IIIC disease; 31 patients had stage IV disease. Median follow-up was 32.1 months. MTD was not reached. Most common related adverse events (>40%) were vaccine injection site reaction, fatigue, rash, pruritus, nausea, and arthralgias. Five related grade 3 adverse events [hypokalemia (1), rash (1), enteritis (1), and colitis (2)] were observed. Ten of 33 patients relapsed. Estimated median RFS was 47.1 months; median OS was not reached. Increases in CTLA-4(+)/CD4(+), CD25(+)Treg/CD4(+), and tetramer specific CD8(+) T-cell populations were observed with treatment (P < 0.05). Trends for lower baseline myeloid-derived suppressor cell and CD25(+)Treg/CD4(+) populations were seen in nonrelapsing patients; PD-L1 tumor status was not significantly associated with RFS. Nivolumab with vaccine is well tolerated as adjuvant therapy and demonstrates immunologic activity with promising survival in high-risk resected melanoma, justifying further study. ©2014 American Association for Cancer Research.

Clinical Safety and Tolerability of Vildagliptin - Insights from Randomised Trials, Observational Studies and Post-marketing Surveillance.

Science.gov (United States)

Mathieu, Chantal; Kozlovski, Plamen; Paldánius, Päivi M; Foley, James E; Modgill, Vikas; Evans, Marc; Serban, Carmen

2017-08-01

Vildagliptin is one of the most extensively studied dipeptidyl peptidase-4 (DPP-4) inhibitors in terms of its clinical utility. Over the last decade, a vast panorama of evidence on the benefit-risk profile of vildagliptin has been generated in patients with type 2 diabetes mellitus (T2DM). In this article, we review the cumulative evidence on the safety of vildagliptin from the clinical development programme, as well as reports of rare adverse drug reactions detected during the post-marketing surveillance of the drug. Across clinical studies, the overall safety and tolerability profile of vildagliptin was similar to placebo, and it was supported by real-world data in a broad population of patients with T2DM, making DPP-4 inhibitors, like vildagliptin, a safe option for managing patients with T2DM.

The effect of periodontal therapy on cardiovascular risk markers: a 6-month randomized clinical trial.

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Caúla, André Luis; Lira-Junior, Ronaldo; Tinoco, Eduardo Muniz Barretto; Fischer, Ricardo Guimarães

2014-09-01

To determine the influence of non-surgical mechanical periodontal treatment on inflammatory markers related to risk for cardiovascular disease. A total of 64 patients with severe chronic periodontitis was randomly subjected to immediately periodontal treatment (test group, n = 32) or delayed periodontal treatment, without treatment during the study period (control group, n = 32). Clinical periodontal and laboratory examinations were performed at baseline (T0), 2 months (T2), and 6 months (T6) after the initial examinations (Control group) or completion of periodontal treatment (Test group). After 2 months of periodontal treatment there was a significant reduction of erythrocyte sedimentation rate (ESR) and triglycerides (p = 0.002, p = 0.004, respectively) in the test group. Median values of C-reactive protein, ESR, total cholesterol, and triglycerides were reduced after 6 month of periodontal treatment in the test group (p periodontal treatment was effective in reducing the levels of systemic inflammation markers and improved the lipid profile in subjects with severe chronic periodontitis. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effects of metformin on markers of oxidative stress and antioxidant reserve in patients with newly diagnosed type 2 diabetes: A randomized clinical trial

Directory of Open Access Journals (Sweden)

Yu V Pankratova

2012-09-01

Full Text Available Реферат по статье: Effects of metformin on markers of oxidative stress and antioxidant reserve in patients with newly diagnosed type 2 diabetes: A randomized clinical trial Alireza Esteghamati, Delaram Eskandari, Hossein Mirmiranpour, Sina Noshad, Mostafa Mousavizadeh, Mehdi Hedayati, Manouchehr Nakhjavan//Clinical Nutrition xxx (2012 1-7 Tehran, Iran

Established and emerging biological activity markers of inflammatory bowel disease

DEFF Research Database (Denmark)

Nielsen, O H; Vainer, B; Madsen, S M

2000-01-01

Assessment of disease activity in inflammatory bowel disease (IBD), i.e., ulcerative colitis (UC) and Crohn's disease (CD), is done using clinical parameters and various biological disease markers. Ideally, a disease marker must: be able to identify individuals at risk of a given disorder......, be disease specific, mirror the disease activity and, finally, be easily applicable for routine clinical purposes. However, no such disease markers have yet been identified for IBD. In this article, classical disease markers including erythrocyte sedimentation rate, acute phase proteins (especially...... orosomucoid and CRP), leukocyte and platelet counts, albumin, neopterin, and beta2-microglobulin will be reviewed together with emerging disease markers such as antibodies of the ANCA/ASCA type, cytokines (e.g., IL-1, IL-2Ralpha, IL-6, IL-8, TNF-alpha, and TNF-alpha receptors) and with various adhesion...

Established and emerging biological activity markers of inflammatory bowel disease

DEFF Research Database (Denmark)

Nielsen, O H; Vainer, B; Madsen, S M

2000-01-01

orosomucoid and CRP), leukocyte and platelet counts, albumin, neopterin, and beta2-microglobulin will be reviewed together with emerging disease markers such as antibodies of the ANCA/ASCA type, cytokines (e.g., IL-1, IL-2Ralpha, IL-6, IL-8, TNF-alpha, and TNF-alpha receptors) and with various adhesion......Assessment of disease activity in inflammatory bowel disease (IBD), i.e., ulcerative colitis (UC) and Crohn's disease (CD), is done using clinical parameters and various biological disease markers. Ideally, a disease marker must: be able to identify individuals at risk of a given disorder......, be disease specific, mirror the disease activity and, finally, be easily applicable for routine clinical purposes. However, no such disease markers have yet been identified for IBD. In this article, classical disease markers including erythrocyte sedimentation rate, acute phase proteins (especially...

DNM3, p65 and p53 from exosomes represent potential clinical diagnosis markers for glioblastoma multiforme

Science.gov (United States)

Yang, Jian-kai; Song, Jian; Huo, Hao-ran; Zhao, Yin-long; Zhang, Guang-yu; Zhao, Zong-mao; Sun, Guo-zhu; Jiao, Bao-hua

2017-01-01

Background: Glioblastoma multiforme (GBM) is the most aggressive and deadly primary brain cancer that arises from astrocytes and classified as grade IV. Recently, exosomes have been reported as an essential mediator in diverse cancer carcinogenesis and metastasis. However, their role in GBM is still unclear. In this study, we aimed to investigate whether blood exosomes can be potential clinical diagnostic markers for GBM. Methods: We used a xenograft orthotopic mouse model to detect the differentially expressed genes in the brain and blood exosomes of original/recurrent GBM. Results: We found that recurrent GBM had stronger growth capacity and lethality than original GBM in the mouse model. A gene microarray of original tumors and blood exosomes from GBM orthotopic xenografts results showed that DNM3, p65 and CD117 expressions increased, whereas PTEN and p53 expressions decreased in both original tumors and blood exosomes. In the recurrent GBM tumor model, DNM3 and p65 showed increased expressions, whereas ST14 and p53 showed decreased expressions in tumor and blood exosomes of the recurrent GBM mouse model. Conclusion: In summary, we found that DNM3, p65 and p53 had a similar trend in brain and blood exosomes both for original and recurrent GBM, and could serve as potential clinical diagnostic markers for GBM. PMID:29449895

77 FR 46764 - Clinical Studies of Safety and Effectiveness of Orphan Products Research Project Grant (R01)

Science.gov (United States)

2012-08-06

...] Clinical Studies of Safety and Effectiveness of Orphan Products Research Project Grant (R01) AGENCY: Food... per year. B. Research Objectives The goal of FDA's OPD grant program is to support the clinical... (OPD) grant program. The goal of FDA's OPD grant program is to support the clinical development of...

Clinical value of assays of multiple serum tumor markers in conjunction with 18F-FDG SPECT for discriminating malignant from benign lung disorders

International Nuclear Information System (INIS)

Zhang Chunyan; Wang Linglong; Tu Liping; Yu Yuefang; Zhu Weijie; Cai Ao; Gao Shuxing

2006-01-01

Objective: To evaluate the clinical value of assays of multiple tumor markers in conjunction with 18 F-FDG SPECT for discriminating malignant from benign lung disorders. Methods: A total of 62 patients with malignant and benign lung diseases un- derwent 18 F-FDG SPECT examination and tests for serum tumor markers CEA, CA50, CA199 and CA242, alone or combined. The sensitivity, specificity, accuracy of these tests were examined. Results: The sensitivity, specificity accuracy of 18 F-FDG SPECT for the diagnosis of malignant lung tumors were 85.7 (30/35), 59.3 (16/27) and 74.2(46/62) respectively, those of each of serum CEA, CA199, CA50, CA242 levels in diagnosing malignant lung tumors were 22.9(8/35), 92.6(25/27), 59.7(33/62), 14.3(5/35), 100(27/27), 51.6 (32/62), 34.3 (12/35), 85.2 (23/27), 56.5 (35/62), 28.6 (10/35), 85.2 (23/27) and 53.2 (33/62) respectively, those of assays of multiple serum tumor markers for diagnosis of malignant lung tumors were 85.7 (30/35), 85.2 (23/27) and 85.5 (53/62) respectively, those of assays of multiple tumor markers in conjunction with 18 F-FDG SPECT for discriminating malignant from benign lung nodules were 88.6(31/35), 85.2(23/27) and 87.1 (54/62) respectively. Conclusion: Assays of multiple serum tumor markers in conjunction with 18 F-FDG SPECT for discriminating malignant from benign lung disorders can yield higher sensitivity, specialty and accuracy, making a significant contribution to clinical application. (authors)

Clinical laboratory markers of inflammation as determinants of chronic graft-versus-host disease activity and NIH global severity.

Science.gov (United States)

Grkovic, L; Baird, K; Steinberg, S M; Williams, K M; Pulanic, D; Cowen, E W; Mitchell, S A; Hakim, F T; Martires, K J; Avila, D N; Taylor, T N; Salit, R B; Rowley, S D; Zhang, D; Fowler, D H; Bishop, M R; Gress, R E; Pavletic, S Z

2012-04-01

Chronic graft-versus-host disease (cGVHD) remains a major cause of non-relapse morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Currently there are no accepted measures of cGVHD activity to aid in clinical management and disease staging. We analyzed clinical markers of inflammation in the sera of patients with established cGVHD and correlated those with definitions of disease activity. In all, 189 adults with cGVHD (33% moderate and 66% severe according to National Institutes of Health (NIH) global scoring) were consecutively enrolled onto a cross-sectional prospective cGVHD natural history study. At the time of evaluation, 80% were receiving systemic immunosuppression and failed a median of four prior systemic therapies (PST) for their cGVHD. Lower albumin (P<0.0001), higher C-reactive protein (P = 0.043), higher platelets (P = 0.030) and higher number of PST (P<0.0001) were associated with active disease defined as clinician's intention to intensify or alter systemic therapy due to the lack of response. Higher platelet count (P = 0.021) and higher number of PST (P<0.0001) were associated with more severe diseased defined by NIH global score. This study identified common laboratory indicators of inflammation that can serve as markers of cGVHD activity and severity.

A meta-model for computer executable dynamic clinical safety checklists.

Science.gov (United States)

Nan, Shan; Van Gorp, Pieter; Lu, Xudong; Kaymak, Uzay; Korsten, Hendrikus; Vdovjak, Richard; Duan, Huilong

2017-12-12

Safety checklist is a type of cognitive tool enforcing short term memory of medical workers with the purpose of reducing medical errors caused by overlook and ignorance. To facilitate the daily use of safety checklists, computerized systems embedded in the clinical workflow and adapted to patient-context are increasingly developed. However, the current hard-coded approach of implementing checklists in these systems increase the cognitive efforts of clinical experts and coding efforts for informaticists. This is due to the lack of a formal representation format that is both understandable by clinical experts and executable by computer programs. We developed a dynamic checklist meta-model with a three-step approach. Dynamic checklist modeling requirements were extracted by performing a domain analysis. Then, existing modeling approaches and tools were investigated with the purpose of reusing these languages. Finally, the meta-model was developed by eliciting domain concepts and their hierarchies. The feasibility of using the meta-model was validated by two case studies. The meta-model was mapped to specific modeling languages according to the requirements of hospitals. Using the proposed meta-model, a comprehensive coronary artery bypass graft peri-operative checklist set and a percutaneous coronary intervention peri-operative checklist set have been developed in a Dutch hospital and a Chinese hospital, respectively. The result shows that it is feasible to use the meta-model to facilitate the modeling and execution of dynamic checklists. We proposed a novel meta-model for the dynamic checklist with the purpose of facilitating creating dynamic checklists. The meta-model is a framework of reusing existing modeling languages and tools to model dynamic checklists. The feasibility of using the meta-model is validated by implementing a use case in the system.

Dosimetric implications of inter- and intrafractional prostate positioning errors during tomotherapy : Comparison of gold marker-based registrations with native MVCT.

Science.gov (United States)

Wust, Peter; Joswig, Marc; Graf, Reinhold; Böhmer, Dirk; Beck, Marcus; Barelkowski, Thomasz; Budach, Volker; Ghadjar, Pirus

2017-09-01

For high-dose radiation therapy (RT) of prostate cancer, image-guided (IGRT) and intensity-modulated RT (IMRT) approaches are standard. Less is known regarding comparisons of different IGRT techniques and the resulting residual errors, as well as regarding their influences on dose distributions. A total of 58 patients who received tomotherapy-based RT up to 84 Gy for high-risk prostate cancer underwent IGRT based either on daily megavoltage CT (MVCT) alone (n = 43) or the additional use of gold markers (n = 15) under routine conditions. Planned Adaptive (Accuray Inc., Madison, WI, USA) software was used for elaborated offline analysis to quantify residual interfractional prostate positioning errors, along with systematic and random errors and the resulting safety margins after both IGRT approaches. Dosimetric parameters for clinical target volume (CTV) coverage and exposition of organs at risk (OAR) were also analyzed and compared. Interfractional as well as intrafractional displacements were determined. Particularly in the vertical direction, residual interfractional positioning errors were reduced using the gold marker-based approach, but dosimetric differences were moderate and the clinical relevance relatively small. Intrafractional prostate motion proved to be quite high, with displacements of 1-3 mm; however, these did not result in additional dosimetric impairments. Residual interfractional positioning errors were reduced using gold marker-based IGRT; however, this resulted in only slightly different final dose distributions. Therefore, daily MVCT-based IGRT without markers might be a valid alternative.

Clinical impact of [{sup 18}F]FDG-PET in patients with suspected recurrent breast cancer based on asymptomatically elevated tumor marker serum levels. A preliminary report

Energy Technology Data Exchange (ETDEWEB)

Liu, Chiu-Shong; Lin, Cheng-Chieh; Kao, Chia-Hung [China Medical Coll., Taichung, Taiwan (China). Hospital; Shen, Yeh-You [Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan (China); Yen, Ruoh-Fang [National Taiwan Univ., Taipei, Taiwan (China). Hospital

2002-07-01

The purpose of this study was to evaluate retrospectively the impact of [{sup 18}F]fluorodeoxyglucose positron emission tomography (FDG-PET) on the detection of recurrent breast cancer based on asymptomatically elevated tumor markers levels. Whole-body FDG-PET was performed in 30 patients with suspected recurrent breast cancer and asymptomatic tumor marker increase but negative or equivocal other imaging modality results. A blood sample was drawn in each case for marker assay (CA 15-3 and CEA) on the same day as the FDG-PET. All of these 30 asymptomatic patients had either CA 15-3>32 U/ml or CEA>5 ng/ml. The final diagnosis of recurrent breast cancer was established by operation/biopsy histopathological findings or clinical follow-up for >1 year by additional morphological imaging techniques. Among the 30 patients, the final diagnosis of recurrent breast cancer was established in 38 sites in 28 patients. FDG-PET accurately detected 35/38 sites in 25/28 patients with recurrence. The diagnostic sensitivity and accuracy of FDG-PET in patients with suspected recurrent breast cancer and asymptomatically elevated tumor markers were 96 and 90%, respectively. FDG-PET is a useful technique for detecting recurrent breast cancer suspected from asymptomatically elevated tumor markers levels and has an important clinical impact on the management of these patients. (author)

Multiplex Polymerase Chain Reaction for Identification of Shigellae and Four Shigella Species Using Novel Genetic Markers Screened by Comparative Genomics.

Science.gov (United States)

Kim, Hyun-Joong; Ryu, Ji-Oh; Song, Ji-Yeon; Kim, Hae-Yeong

2017-07-01

In the detection of Shigella species using molecular biological methods, previously known genetic markers for Shigella species were not sufficient to discriminate between Shigella species and diarrheagenic Escherichia coli. The purposes of this study were to screen for genetic markers of the Shigella genus and four Shigella species through comparative genomics and develop a multiplex polymerase chain reaction (PCR) for the detection of shigellae and Shigella species. A total of seven genomic DNA sequences from Shigella species were subjected to comparative genomics for the screening of genetic markers of shigellae and each Shigella species. The primer sets were designed from the screened genetic markers and evaluated using PCR with genomic DNAs from Shigella and other bacterial strains in Enterobacteriaceae. A novel Shigella quintuplex PCR, designed for the detection of Shigella genus, S. dysenteriae, S. boydii, S. flexneri, and S. sonnei, was developed from the evaluated primer sets, and its performance was demonstrated with specifically amplified results from each Shigella species. This Shigella multiplex PCR is the first to be reported with novel genetic markers developed through comparative genomics and may be a useful tool for the accurate detection of the Shigella genus and species from closely related bacteria in clinical microbiology and food safety.

Circulating Markers of Vascular Injury and Angiogenesis in ANCA-Associated Vasculitis

Science.gov (United States)

Monach, Paul A; Tomasson, Gunnar; Specks, Ulrich; Stone, John H; Cuthbertson, David; Krischer, Jeffrey; Ding, Linna; Fervenza, Fernando C; Fessler, Barri J; Hoffman, Gary S; Ikle, David; Kallenberg, Cees GM; Langford, Carol A; Mueller, Mark; Seo, Philip; St.Clair, E William; Spiera, Robert; Tchao, Nadia; Ytterberg, Steven R; Gu, Yi-Zhong; Snyder, Ronald D; Merkel, Peter A

2011-01-01

Objective To identify biomarkers that distinguish between active ANCA-associated vasculitis (AAV) and remission in a manner superior or complementary to established markers of systemic inflammation. Methods Markers of vascular injury and angiogenesis were measured before and after treatment in a large clinical trial in AAV. 163 subjects enrolled in the Rituximab in ANCA-Associated Vasculitis (RAVE) trial were studied. Serum levels of E-selectin, ICAM-3, MMP1, MMP3, MMP9, P-selectin, thrombomodulin, and VEGF were measured at study screening (time of active disease) and at month 6. ESR and CRP levels had been measured at the time of the clinical visit. The primary outcome was the difference in marker level between screening and month 6 among patients in remission (BVAS/WG score of 0) at month 6. Results All subjects had severe active vasculitis (mean BVAS/WG score 8.6 +/− 3.2 SD) at screening. Among the 123 subjects clinically in remission at month 6, levels of all markers except E-selectin showed significant declines. MMP3 levels were also higher among the 23 subjects with active disease at month 6 than among the 123 subjects in remission. MMP3 levels correlated weakly with ESR and CRP. Conclusion Many markers of vascular injury and angiogenesis are elevated in severe active AAV and decline with treatment, but MMP3 appears to distinguish active AAV from remission better than the other markers studied. Further study of MMP3 is warranted to determine its clinical utility in combination with conventional markers of inflammation and ANCA titers. PMID:21953143

Preoperative Molecular Markers in Thyroid Nodules.

Science.gov (United States)

Sahli, Zeyad T; Smith, Philip W; Umbricht, Christopher B; Zeiger, Martha A

2018-01-01

The need for distinguishing benign from malignant thyroid nodules has led to the pursuit of differentiating molecular markers. The most common molecular tests in clinical use are Afirma ® Gene Expression Classifier (GEC) and Thyroseq ® V2. Despite the rapidly developing field of molecular markers, several limitations exist. These challenges include the recent introduction of the histopathological diagnosis "Non-Invasive Follicular Thyroid neoplasm with Papillary-like nuclear features", the correlation of genetic mutations within both benign and malignant pathologic diagnoses, the lack of follow-up of molecular marker negative nodules, and the cost-effectiveness of molecular markers. In this manuscript, we review the current published literature surrounding the diagnostic value of Afirma ® GEC and Thyroseq ® V2. Among Afirma ® GEC studies, sensitivity (Se), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV) ranged from 75 to 100%, 5 to 53%, 13 to 100%, and 20 to 100%, respectively. Among Thyroseq ® V2 studies, Se, Sp, PPV, and NPV ranged from 40 to 100%, 56 to 93%, 13 to 90%, and 48 to 97%, respectively. We also discuss current challenges to Afirma ® GEC and Thyroseq ® V2 utility and clinical application, and preview the future directions of these rapidly developing technologies.

Clinical utility of autoantibodies and biologic markers in rheumatoid ...

African Journals Online (AJOL)

Objective: To review the current and emerging auto-antibodies and biologic markers in rheumatoid arthritis. Data source: Published original research work and reviews were searched in English related to pathophysiology, diagnosis and auto antibodies in rheumatoid arthritis. Study design: Only articles that emphasis on ...

Clinical Introduction of a Novel Liquid Fiducial Marker for Breathing Adapted Radiotherapy of Non-Small Cell Lung Cancer

DEFF Research Database (Denmark)

Rydhog, Jonas Scherman

delivery, e.g. breathing related tumour motion and anatomical changes during treatment. To ensure dose delivery to the target, a safety margin is added to the tumour. A large treatment volume, however, can be problematic due to the proximity of vital anatomical structures in the chest region, e...... for the tumour position in lung cancer patients. Furthermore, we evaluated the potential benefit of a breathing adaptation technique, where patients hold their breath during treatment delivery. We found that this technique reduced both tumour motion and doses to risk organs. Finally, we investigated...... the potential of measuring radiation doses from an activated liquid silver marker, via photon-nuclear reactions in-situ, using positron emission-tomography and proved a clear correlation between delivered radiation dose and measured induced activity....

Study of skin markers for magnetic resonance imaging examinations

International Nuclear Information System (INIS)

Takatsu, Yasuo; Umezaki, Yoshie; Miyati, Tosiaki; Yamamura, Kenichirou

2013-01-01

In magnetic resonance imaging (MRI), skin markers are used as a landmark in order to make plans for examinations. However, there isn't a lot of research about the material and shape of skin markers. The skin marker's essential elements are safety, good cost performance, high signal intensity for T 1 weighted image (T 1 WI) and T 2 weighted image (T 2 WI), and durable. In order to get a high signal-to-noise ratio (SNR) of T 1 WI and T 2 WI, baby oil, salad oil and olive oil were chosen, because these materials were easy to obtain and safe for the skin. The SNR of baby oil was the best. Baby oil was injected into the infusion tube, and the tube was solvent welded and cut by a heat sealer. In order to make ring shaped skin markers, both ends of the tube were stuck with adhesive tape. Three different diameters of markers were made (3, 5, 10 cmφ). Ring shaped skin markers were put on to surround the examination area, therefore, the edge of the examination area could be seen at every cross section. Using baby oil in the ring shaped infusion tube is simple, easy, and a highly useful skin marker. (author)

The need for radio-opaque side markers on CT of the paranasal sinuses

International Nuclear Information System (INIS)

Nandi, R.; Luk, T.L.; Henson, J.

2003-01-01

AIM: To audit the presence of a radio-opaque 'side marker' routinely placed on the right side of the face of all patients undergoing computed tomography (CT) of the paranasal sinuses in our hospital and to audit awareness levels amongst ear, nose and throat (ENT) clinical and theatre staff regarding the 'marker'. MATERIALS AND METHODS: An audit of 100 CT studies of the paranasal sinuses was carried out with regard to the presence or absence of the marker. A further audit was conducted relating to the awareness amongst ENT clinical staff and theatre nurses regarding the marker. Re-audit of a second cohort of 100 sinus CT studies was carried out after implementing changes indicated by the first audit cycle. Awareness amongst staff concerned was similarly re-audited. RESULTS: In audit cycle I the side marker was positively identified in 85% of the CT examinations and were deemed absent in 15%. Of the clinical staff interviewed, only 30% were aware of the presence of the 'marker' and it's significance. In audit cycle II the 'side marker' was positively identified in 100% of the scans reviewed. Awareness of the presence of the 'marker' amongst clinical staff was found to be 90%. CONCLUSIONS: The routine placement of a radio-opaque side marker on the right zygoma of all patients undergoing CT of paranasal sinuses is a simple yet effective additional means of denoting the correct side whilst interpreting such images. This has important implications regarding surgery. The audit has shown an improvement in both the placement of the side marker as well as in awareness levels amongst staff involved to ensure best practice

Safety of an alkalinizing buffer designed for inhaled medications in humans.

Science.gov (United States)

Davis, Michael D; Walsh, Brian K; Dwyer, Scott T; Combs, Casey; Vehse, Nico; Paget-Brown, Alix; Pajewski, Thomas; Hunt, John F

2013-07-01

Airway acidification plays a role in disorders of the pulmonary tract. We hypothesized that the inhalation of alkalinized glycine buffer would measurably alkalinize the airways without compromising lung function or causing adverse events. We evaluated the safety of an inhaled alkaline glycine buffer in both healthy subjects and in subjects with stable obstructive airway disease. This work includes 2 open-label safety studies. The healthy controls were part of a phase 1 safety study of multiple inhalations of low-dose alkaline glycine buffer; nebulized saline was used as a comparator in 8 of the healthy controls. Subsequently, a phase 2 study in subjects with stable obstructive airway disease was completed using a single nebulized higher-dose strategy of the alkaline inhalation. We studied 20 non-smoking adults (10 healthy controls and 10 subjects with obstructive airway disease), both at baseline and after inhalation of alkaline buffer. We used spirometry and vital signs as markers of clinical safety. We used changes in fraction of exhaled nitric oxide (NO) and exhaled breath condensate (EBC) pH as surrogate markers of airway pH modification. Alkaline glycine inhalation was tolerated by all subjects in both studies, with no adverse effects on spirometric parameters or vital signs. Airway alkalinization was confirmed by a median increase in EBC pH of 0.235 pH units (IQR 0.56-0.03, P = .03) in subjects after inhalation of the higher-dose alkaline buffer (2.5 mL of 100 mmol/L glycine). Alkalinization of airway lining fluid is accomplished with inhalation of alkaline glycine buffer and causes no adverse effects on pulmonary function or vital signs.

Diffusion-weighted and dynamic contrast-enhanced imaging as markers of clinical behavior in children with optic pathway glioma

International Nuclear Information System (INIS)

Jost, Sarah C.; Ackerman, Joseph W.; Garbow, Joel R.; Manwaring, Linda P.; Gutmann, David H.; McKinstry, Robert C.

2008-01-01

Optic pathway gliomas (OPGs) are common pediatric brain tumors that pose significant clinical challenges with regard to predicting which tumors are likely to become symptomatic and require treatment. These tumors can arise sporadically or in the context of the inherited cancer predisposition syndrome neurofibromatosis type 1 (NF1). Few studies have suggested biological or imaging markers that predict the clinical course of this disease. In this cross-sectional study, we hypothesized that the clinical behavior of OPGs in children can be differentiated by diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) MRI. A total of 27 children with OPG were studied using DW and DCE MRI protocols. Diffusivity and permeability were calculated and correlated with the clinical behavior the OPG. Mean diffusivity values of 1.39 μm 2 /ms and mean permeability values of 2.10 ml/min per 100 cm 3 of tissue were measured. Clinically aggressive OPGs had significantly higher mean permeability values (P = 0.05) than clinically stable tumors. In addition, there was a strong correlation between clinical aggressiveness and the absence of NF1 (P < 0.01). These results suggest that DCE MRI might be a useful biomarker for clinically aggressive OPG, which should be confirmed in larger prospective longitudinal studies. (orig.)

Drug Safety

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... over-the-counter drug. The FDA evaluates the safety of a drug by looking at Side effects ... clinical trials The FDA also monitors a drug's safety after approval. For you, drug safety means buying ...

Skin autofluorescence, a novel marker for glycemic and oxidative stress-derived advanced glycation endproducts : An overview of current clinical studies, evidence, and limitations

NARCIS (Netherlands)

Mulder, Douwe J.; Van de Water, Tara; Lutgers, Helen L.; Graaff, Reindert; Gans, Rijk O.; Zijlstra, Felix; Smit, Andries J.

2006-01-01

Background: Advanced glycation endproducts (AGES) predict long-term complications in age-related diseases. However, there are no clinically applicable markers for measuring AGES in vivo. Methods: We have recently introduced the AGE-Reader (DiagnOptics B.V., Groningen, The Netherlands) to

Acute Coronary Syndromes: From The Laboratory Markers To The Coronary Vessels

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Palazzuoli Alberto

2006-01-01

Full Text Available A number of "interesting" risk markers have been proposed as providing prognostic information in acute coronary syndromes (ACS. Elevation in plasma inflammatory and necrosis biomarkers have been related to future cardiovascular events in individuals with or without prior myocardial infarction. Recently BNP and pro-BNP are entered in clinical practice to recognize patients at major risk, providing incremental information respect to the traditional markers. Together with these laboratory indexes, a few of promising laboratory markers once easily available, could become useful in identification of patients at high risk. Several studies evaluated many markers of platelet aggregation, endothelial dysfunction and vascular thrombosis, but it is not yet clear whether each of the proposed markers may provide incremental predictive information. We describe, following the most studies reported in literature, the laboratory markers with potential clinical and prognostic power that could early help physicians in the identifi cation of patients with impaired coronary disease and more narrowed coronary arteries.

Serum tumor markers in pediatric osteosarcoma: a summary review

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Savitskaya Yulia A

2012-03-01

Full Text Available Abstract Osteosarcoma is the most common primary high-grade bone tumor in both adolescents and children. Early tumor detection is key to ensuring effective treatment. Serum marker discovery and validation for pediatric osteosarcoma has accelerated in recent years, coincident with an evolving understanding of molecules and their complex interactions, and the compelling need for improved pediatric osteosarcoma outcome measures in clinical trials. This review gives a short overview of serological markers for pediatric osteosarcoma, and highlights advances in pediatric osteosarcoma-related marker research within the past year. Studies in the past year involving serum markers in patients with pediatric osteosarcoma can be assigned to one of four categories, i.e., new approaches and new markers, exploratory studies in specialized disease subsets, large cross-sectional validation studies, and longitudinal studies, with and without an intervention. Most of the studies have examined the association of a serum marker with some aspect of the natural history of pediatric osteosarcoma. As illustrated by the many studies reviewed, several serum markers are emerging that show a credible association with disease modification. The expanding pool of informative osteosarcoma-related markers is expected to impact development of therapeutics for pediatric osteosarcoma positively and, it is hoped, ultimately clinical care. Combinations of serum markers of natural immunity, thyroid hormone homeostasis, and bone tumorigenesis may be undertaken together in patients with pediatric osteosarcoma. These serum markers in combination may do better. The potential effect of an intrinsic dynamic balance of tumor angiogenesis residing within a single hormone (tri-iodothyronine is an attractive concept for regulation of vascularization in pediatric osteosarcoma.

Clinical applicability of determination of serum tumor markers (CEA, CA15-3 and CA125) levels changes for assessment of efficacy of chemotherapy in patients with breast cancer

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Xu Junying; Liu Chaoying; Li Jiang; Hu Hong; Wang Runjie

2009-01-01

Objective: To study the usefulness of monitoring changes of serum levels of tumor markers (CEA, CA15-3 and CA125) for assessment of efficacy of chemotherapy in patients with breast cancer. Methods: Serum CEA, CA15-3 and CA125 levels were measured with CLIA three days before beginning 1st course of appropriate chemotherapy and 3 weeks after completing 2nd course of treatment in 45 patients with advanced breast cancer (TNM stage III, n=20, stage IV n=25). Results: Expressed as CR, PR, SD and PD as defined by the changes of serum tumor markers levels (according to Bac D.J. et al) were compared with clinically observed ones (WHO standard). The serum levels of Cea, CA15-3 decreased markedly in the CR and PR groups of patients but increased markedly in PD patients (P 0.05). The coincidence rate between the results observed clinically and results derived from tumor marker changes was 50.0% for CEA, 55.6% for CA15-3, 31.1% for CA125 and 73% for three markers combined. Conclusion: Combined determination of the changes of serum levels of three tumor marker would help to make a reasonably satisfactory assessment of efficacy of chemotherapy in patients with breast cancer. (authors)

Efficacy and Safety of Rituximab in Children with Refractory Nephrotic Syndrome; A Multicenter Clinical Trial

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Yo Han Ahn

2014-06-01

Conclusions: In this interim analysis of clinical trial to evaluate the efficacy and safety of RTX in children with refractory NS, RTX treatment for refractory NS was safe and effective, especially in patients with DNS.

Changes in markers associated with dendritic cells driving the differentiation of either TH2 cells or regulatory T cells correlate with clinical benefit during allergen immunotherapy.

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Gueguen, Claire; Bouley, Julien; Moussu, Hélène; Luce, Sonia; Duchateau, Magalie; Chamot-Rooke, Julia; Pallardy, Marc; Lombardi, Vincent; Nony, Emmanuel; Baron-Bodo, Véronique; Mascarell, Laurent; Moingeon, Philippe

2016-02-01

Regulatory dendritic cell (DC) markers, such as C1Q, are upregulated in PBMCs of patients with grass pollen allergy exhibiting clinical benefit during allergen immunotherapy (AIT). We sought to define markers differentially expressed in human monocyte-derived DCs differentiated toward a proallergic (DCs driving the differentiation of TH2 cells [DC2s]) phenotype and investigate whether changes in such markers in the blood correlate with AIT efficacy. Transcriptomes and proteomes of monocyte-derived DCs polarized toward DCs driving the differentiation of TH1 cells (DC1s), DC2s, or DCs driving the differentiation of regulatory T cells (DCreg cells) profiles were compared by using genome-wide cDNA microarrays and label-free quantitative proteomics, respectively. Markers differentially regulated in DC2s and DCreg cells were assessed by means of quantitative PCR in PBMCs from 80 patients with grass pollen allergy before and after 2 or 4 months of sublingual AIT in parallel with rhinoconjunctivitis symptom scores. We identified 20 and 26 new genes/proteins overexpressed in DC2s and DCreg cells, respectively. At an individual patient level, DC2-associated markers, such as CD141, GATA3, OX40 ligand, and receptor-interacting serine/threonine-protein kinase 4 (RIPK4), were downregulated after a 4-month sublingual AIT course concomitantly with an upregulation of DCreg cell-associated markers, including complement C1q subcomponent subunit A (C1QA), FcγRIIIA, ferritin light chain (FTL), and solute carrier organic anion transporter family member 2B1 (SLCO2B1), in the blood of clinical responders as opposed to nonresponders. Changes in such markers were better correlated with clinical benefit than alterations of allergen-specific CD4(+) T-cell or IgG responses. A combination of 5 markers predominantly expressed by blood DCs (ie, C1Q and CD141) or shared with lymphoid cells (ie, FcγRIIIA, GATA3, and RIPK4) reflecting changes in the balance of regulatory/proallergic responses

Metallothionein, a marker of antiapoptosis, is associated with clinical forms of oral lichen planus.

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Allon, Irit; Ofir, Merav; Vered, Hanna; Hirshberg, Abraham

2014-11-01

To investigate the expression of anti- and proapoptosis markers, metallothionein (MT), and caspase-2, in the epithelial and inflammatory cells of oral lichen planus (OLP) patients, and to investigate the association with clinical parameters. Included were biopsies of 70 OLP patients. The clinical data were collected from patients' charts. The expression of MT and caspase-2 was immunomorphometrically analyzed in the epithelial and inflammatory cells, and the results were correlated with the clinical presentation. The epithelial and inflammatory cells expressed MT (10.2 ± 5.75 and 0.68 ± 0.86) and caspase-2 (1.54 ± 2.6 and 0.98 ± 1.15) which show a trend toward an inverse expression. The expression of MT in the epithelium was significantly higher in patients presenting with keratotic lichen planus than in patients with the atrophic and erosive forms (P = 0.0008). In the inflammatory cells, the expression of MT was inversely correlated with increasing age (R = 0.34, P = 0.0069). The pattern of expression of MT and caspase-2 in OLP suggests an extensive antiapoptotic response in the keratotic form of the disease. Symptomatic patients may benefit from therapy targeted to apoptosis in the future. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Clinical values of detection of multiple tumor markers in pleural fluid for diagnosis malignancy

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Xiao Chuangqing; Jiang Li; Zhou Guanghua; He Yunnan

2005-01-01

Objective: To improve the diagnostic accuracy for the differentiation of malignant from tuberculous pleural effusion with determination of multiple tumor markers in pleural fluid. Methods: With a multiple tumor markers combined protein chip diagnostic system, contents of twelve common tumor markers were detected in the chest fluid from 60 patients with malignant pleural effusion and 30 patients with tuberculous pleural effusion. Results: For pulmonary carcinoma related pleural effusion, the contents of four common tumor markers (CEA, NSE, SF, CA125) in chest fluid were significantly higher those in tuberculous related chest fluid. The diagnostic positive rate of combined test of these four marker for malignancy could be as high as 96.7%. Conclusion: Combined determination of chest fluid CEA, NSE, SF, CA125 contents was very sensitive and accurate for differentiation of malignant from tuberculous pleural effusion. (authors)

Biochemical Markers in Neurocritical Care

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Omidvar Rezae

2016-07-01

Full Text Available During the past two decades, a variety of serum or cerebrospinal fluid (CSF biochemical markers in daily clinical practice have been recommended to diagnose and monitor diverse diseases or pathologic situations. It will be essential to develop a panel of biomarkers, to be suitable for evaluation of treatment efficacy, representing distinct phases of injury and recovery and consider the temporal profile of those. Among the possible and different biochemical markers, S100b appeared to fulfill many of optimized criteria of an ideal marker. S100b, a cytosolic low molecular weight dimeric calciumbinding protein from chromosome 21, synthesized in glial cells throughout the CNS, an homodimeric diffusible, belongs to a family of closely related protein, predominantly expressed by astrocytes and Schwann cells and a classic immunohistochemical marker for these cells, is implicated in brain development and neurophysiology. Of the 3 isoforms of S-100, the BB subunit (S100B is present in high concentrations in central and peripheral glial and Schwann cells, Langerhans and anterior pituitary cells, fat, muscle, and bone marrow tissues. The biomarker has shown to be a sensitive marker of clinical and subclinical cerebral damage, such as stroke, traumatic brain injury, and spinal cord injury. Increasing evidence suggests that the biomarker plays a double function as an intracellular regulator and an extracellular signal of the CNS. S100b is found in the cytoplasm in a soluble form and also is associated with intracellular membranes, centrosomes, microtubules, and type III intermediate filaments. Their genomic organization now is known, and many of their target proteins have been identified, although the mechanisms of regulating S100b secretion are not completely understood and appear to be related to many factors, such as the proinflammatory cytokines, tumor necrosis factor alpha (TNF-a, interleukin (IL-1b, and metabolic stress. 

Patient safety in the clinical laboratory: a longitudinal analysis of specimen identification errors.

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Wagar, Elizabeth A; Tamashiro, Lorraine; Yasin, Bushra; Hilborne, Lee; Bruckner, David A

2006-11-01

Patient safety is an increasingly visible and important mission for clinical laboratories. Attention to improving processes related to patient identification and specimen labeling is being paid by accreditation and regulatory organizations because errors in these areas that jeopardize patient safety are common and avoidable through improvement in the total testing process. To assess patient identification and specimen labeling improvement after multiple implementation projects using longitudinal statistical tools. Specimen errors were categorized by a multidisciplinary health care team. Patient identification errors were grouped into 3 categories: (1) specimen/requisition mismatch, (2) unlabeled specimens, and (3) mislabeled specimens. Specimens with these types of identification errors were compared preimplementation and postimplementation for 3 patient safety projects: (1) reorganization of phlebotomy (4 months); (2) introduction of an electronic event reporting system (10 months); and (3) activation of an automated processing system (14 months) for a 24-month period, using trend analysis and Student t test statistics. Of 16,632 total specimen errors, mislabeled specimens, requisition mismatches, and unlabeled specimens represented 1.0%, 6.3%, and 4.6% of errors, respectively. Student t test showed a significant decrease in the most serious error, mislabeled specimens (P patient safety projects. Trend analysis demonstrated decreases in all 3 error types for 26 months. Applying performance-improvement strategies that focus longitudinally on specimen labeling errors can significantly reduce errors, therefore improving patient safety. This is an important area in which laboratory professionals, working in interdisciplinary teams, can improve safety and outcomes of care.

Salivary pH and Buffering Capacity as Risk Markers for Early Childhood Caries: A Clinical Study.

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Jayaraj, D; Ganesan, S

2015-01-01

The diagnostic utility of saliva is currently being explored in various branches of dentistry, remarkably in the field of caries research. This study was aimed to determine if assessment of salivary pH and buffering capacity would serve as reliable tools in risk prediction of early childhood caries (ECC). Paraffin-stimulated salivary samples were collected from 50 children with ECC (group I) and 50 caries free children (group II). Salivary pH and buffering capacity (by titration with 0.1 N hydrochloric acid) were assessed using a handheld digital pH meter in both groups. The data obtained were subjected to statistical analysis. Statistically, no significant difference was observed between both the groups for all salivary parameters assessed, except for the buffering capacity level at 150 μl titration of 0.1 N hydrochloric acid (p = 0.73; significant at 1% level). Salivary pH and buffering capacity may not serve as reliable markers for risk prediction of ECC. How to cite this article: Jayaraj D, Ganesan S. Salivary pH and Buffering Capacity as Risk Markers for Early Childhood Caries: A Clinical Study. Int J Clin Pediatr Dent 2015;8(3):167-171.

Tumor markers in pancreatic cancer: a European Group on Tumor Markers (EGTM) status report.

LENUS (Irish Health Repository)

Duffy, M J

2012-02-01

Pancreatic ductal adenocarcinoma is one of the most difficult malignancies to diagnose and treat. The aim of this article is to review how tumor markers can aid the diagnosis and management of patients with this malignancy. The most widely used and best validated marker for pancreatic cancer is CA 19-9. Inadequate sensitivity and specificity limit the use of CA 19-9 in the early diagnosis of pancreatic cancer. In non-jaundiced patients, however, CA 19-9 may complement other diagnostic procedures. In patients with resectable pancreatic cancer, presurgical and postresection CA 19-9 levels correlate with overall survival. In advanced disease, elevated pretreatment levels of CA 19-9 are associated with adverse patient outcome and thus may be combined with other factors for risk stratification. Most, but not all, reports indicate that serial levels of CA 19-9 correlate with response to systemic therapy. Use of CA 19-9 kinetics in conjunction with imaging is therefore recommended in monitoring therapy. Although several potential serum and tissue markers for pancreatic cancer are currently undergoing evaluation, none are sufficiently validated for routine clinical use. CA 19-9 thus remains the serum pancreatic cancer marker against which new markers for this malignancy should be judged.

Corpus callosum atrophy as a marker of clinically meaningful cognitive decline in secondary progressive multiple sclerosis. Impact on employment status.

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Papathanasiou, Athanasios; Messinis, Lambros; Zampakis, Petros; Papathanasopoulos, Panagiotis

2017-09-01

Cognitive impairment in Multiple Sclerosis (MS) is more frequent and pronounced in secondary progressive MS (SPMS). Cognitive decline is an important predictor of employment status in patients with MS. Magnetic Resonance Imaging (MRI) markers have been used to associate tissue damage with cognitive dysfunction. The aim of the study was to designate the MRI marker that predicts cognitive decline in SPMS and explore its effect on employment status. 30 SPMS patients and 30 healthy participants underwent neuropsychological assessment using the Trail Making Test (TMT) parts A and B, semantic and phonological verbal fluency task and a computerized cognitive screening battery (Central Nervous System Vital Signs). Employment status was obtained as a quality of life measure. Brain MRI was performed in all participants. We measured total lesion volume, third ventricle width, thalamic and corpus callosum atrophy. The frequency of cognitive decline for our SPMS patients was 80%. SPMS patients differed significantly from controls in all neuropsychological measures. Corpus callosum area was correlated with cognitive flexibility, processing speed, composite memory, executive functions, psychomotor speed, reaction time and phonological verbal fluency task. Processing speed and composite memory were the most sensitive markers for predicting employment status. Corpus callosum area was the most sensitive MRI marker for memory and processing speed. Corpus callosum atrophy predicts a clinically meaningful cognitive decline, affecting employment status in our SPMS patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Clinical Utility and Safety of a Model-Based Patient-Tailored Dose of Vancomycin in Neonates.

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Leroux, Stéphanie; Jacqz-Aigrain, Evelyne; Biran, Valérie; Lopez, Emmanuel; Madeleneau, Doriane; Wallon, Camille; Zana-Taïeb, Elodie; Virlouvet, Anne-Laure; Rioualen, Stéphane; Zhao, Wei

2016-04-01

Pharmacokinetic modeling has often been applied to evaluate vancomycin pharmacokinetics in neonates. However, clinical application of the model-based personalized vancomycin therapy is still limited. The objective of the present study was to evaluate the clinical utility and safety of a model-based patient-tailored dose of vancomycin in neonates. A model-based vancomycin dosing calculator, developed from a population pharmacokinetic study, has been integrated into the routine clinical care in 3 neonatal intensive care units (Robert Debré, Cochin Port Royal, and Clocheville hospitals) between 2012 and 2014. The target attainment rate, defined as the percentage of patients with a first therapeutic drug monitoring serum vancomycin concentration achieving the target window of 15 to 25 mg/liter, was selected as an endpoint for evaluating the clinical utility. The safety evaluation was focused on nephrotoxicity. The clinical application of the model-based patient-tailored dose of vancomycin has been demonstrated in 190 neonates. The mean (standard deviation) gestational and postnatal ages of the study population were 31.1 (4.9) weeks and 16.7 (21.7) days, respectively. The target attainment rate increased from 41% to 72% without any case of vancomycin-related nephrotoxicity. This proof-of-concept study provides evidence for integrating model-based antimicrobial therapy in neonatal routine care. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

SU-D-201-07: A Survey of Radiation Oncology Residents’ Training and Preparedness to Lead Patient Safety Programs in Clinics

International Nuclear Information System (INIS)

Spraker, M; Nyflot, M; Ford, E; Kane, G; Zeng, J; Hendrickson, K

2016-01-01

Purpose: Safety and quality has garnered increased attention in radiation oncology, and physicians and physicists are ideal leaders of clinical patient safety programs. However, it is not clear whether residency programs incorporate formal patient safety training and adequately equip residents to assume this leadership role. A national survey was conducted to evaluate medical and physics residents’ exposure to safety topics and their confidence with the skills required to lead clinical safety programs. Methods: Radiation oncology residents were identified in collaboration with ARRO and AAPM. The survey was released in February 2016 via email using REDCap. This included questions about exposure to safety topics, confidence leading safety programs, and interest in training opportunities (i.e. workshops). Residents rated their exposure, skills, and confidence on 4 or 5-point scales. Medical and physics residents responses were compared using chi-square tests. Results: Responses were collected from 56 of 248 (22%) physics and 139 of 690 (20%) medical residents. More than two thirds of all residents had no or only informal exposure to incident learning systems (ILS), root cause analysis (RCA), failure mode and effects analysis (FMEA), and the concept of human factors engineering (HFE). Likewise, 63% of residents had not heard of RO-ILS. Response distributions were similar, however more physics residents had formal exposure to FMEA (p<0.0001) and felt they were adequately trained to lead FMEAs in clinic (p<0.001) than medical residents. Only 36% of residents felt their patient safety training was adequate, and 58% felt more training would benefit their education. Conclusion: These results demonstrate that, despite increasing desire for patient safety training, medical and physics residents’ exposure to relevant concepts is low. Physics residents had more exposure to FMEA than medical residents, and were more confident in leading FMEA. This suggests that increasing

SU-D-201-07: A Survey of Radiation Oncology Residents’ Training and Preparedness to Lead Patient Safety Programs in Clinics

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Spraker, M; Nyflot, M; Ford, E; Kane, G; Zeng, J; Hendrickson, K [University of Washington, Seattle, WA (United States)

2016-06-15

Purpose: Safety and quality has garnered increased attention in radiation oncology, and physicians and physicists are ideal leaders of clinical patient safety programs. However, it is not clear whether residency programs incorporate formal patient safety training and adequately equip residents to assume this leadership role. A national survey was conducted to evaluate medical and physics residents’ exposure to safety topics and their confidence with the skills required to lead clinical safety programs. Methods: Radiation oncology residents were identified in collaboration with ARRO and AAPM. The survey was released in February 2016 via email using REDCap. This included questions about exposure to safety topics, confidence leading safety programs, and interest in training opportunities (i.e. workshops). Residents rated their exposure, skills, and confidence on 4 or 5-point scales. Medical and physics residents responses were compared using chi-square tests. Results: Responses were collected from 56 of 248 (22%) physics and 139 of 690 (20%) medical residents. More than two thirds of all residents had no or only informal exposure to incident learning systems (ILS), root cause analysis (RCA), failure mode and effects analysis (FMEA), and the concept of human factors engineering (HFE). Likewise, 63% of residents had not heard of RO-ILS. Response distributions were similar, however more physics residents had formal exposure to FMEA (p<0.0001) and felt they were adequately trained to lead FMEAs in clinic (p<0.001) than medical residents. Only 36% of residents felt their patient safety training was adequate, and 58% felt more training would benefit their education. Conclusion: These results demonstrate that, despite increasing desire for patient safety training, medical and physics residents’ exposure to relevant concepts is low. Physics residents had more exposure to FMEA than medical residents, and were more confident in leading FMEA. This suggests that increasing

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

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

2014-01-01

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

Translational safety biomarkers of colonic barrier integrity in the rat.

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Erkens, Tim; Bueters, Ruud; van Heerden, Marjolein; Cuyckens, Filip; Vreeken, Rob; Goeminne, Nick; Lammens, Lieve

2018-05-20

The intestinal barrier controls intestinal permeability, and its disruption has been associated with multiple diseases. Therefore, preclinical safety biomarkers monitoring barrier integrity are essential during the development of drugs targeting the intestines, particularly if starting treatment early after onset of disease. Classical toxicology endpoints are not sensitive enough and therefore our objective was to identify non-invasive markers enabling early in vivo detection of colonic barrier perturbation. Male Sprague-Dawley rats were dosed intracolonically via the rectum, using sodium caprate or ibuprofen as tool compounds to alter barrier integrity. Several potentially translational biomarkers and probe molecules related to permeability, inflammation or tissue damage were evaluated, using various analytical platforms, including immunoassays, targeted metabolomics and highly sensitive ultra-performance liquid chromatography-tandem mass spectrometry. Several markers were identified that allow early in vivo detection of colonic barrier integrity changes, before histopathological evidence of tissue damage. The most promising permeability markers identified were plasma fluorescein isothiocyanate-dextran 4000 and a lactulose/mannitol/sucralose mixture in urine. These markers showed maximum increases over 100-fold or approximately 10-50-fold, respectively. Intracolonic administration of the above probe molecules outperformed oral administration and inflammatory or other biomarkers, such as α 2 -macroglobulin, calprotectin, cytokines, prostaglandins and a panel of metabolic molecules to identify early and subtle changes in barrier integrity. However, optimal timing of probe administration and sample collection is important for all markers evaluated. Inclusion of these probe molecules in preclinical toxicity studies might aid in risk assessment and the design of a clinical biomarker plan, as several of these markers have translational potential. Copyright © 2018 John

Oral candidiasis as a clinical marker of highly active antiretroviral treatment failure in HIV-infected patients

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Sandra Lopez-Verdin

Full Text Available Introduction: Oral candidiasis is an opportunistic infection that is readily detectable in the clinic. It has been used to assess the immune status of HIV patients as well as the effectiveness of highly active antiretroviral therapy. Objective: To determine the frequency of oral candidiasis infection among various indicators associated with antiretroviral therapy effectiveness. Material and methods: Cross-sectional and analytical study, in which groups were initially created based on the use or not of antiretroviral therapy. Participants were subjected to questions on factors related to Candida infection, salivary flow measurements and a clinical examination of the oral cavity to determine the frequency of candidiasis Results: The difference in the frequency of oral candidiasis between groups with and without antiretroviral therapy was significant (OR 2.6 IC95% 1.5-4.4. There were also a significant association with decreased number of CD4 lymphocytes.. Discussion: Resistance to anti-retroviral therapy constitutes one of the fundamental barriers to a successful treatment in patients infected with the human immunodeficiency virus, as do toxicities and adherence problems. Clinical markers such oral candidiasis is an easily and accesible parameter for the early detection of treatment failure.

Variable expression of molecular markers in juvenile nasopharyngeal angiofibroma.

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Mishra, A; Pandey, A; Mishra, S C

2017-09-01

Molecular categorisation may explain the wide variation in the clinical characteristics of juvenile nasopharyngeal angiofibroma. Variations in molecular markers in juvenile nasopharyngeal angiofibroma in an Indian population were investigated and compared with global reports. Variable molecular marker expression was demonstrated at the regional and global levels. A wide variation in molecular characteristics is evident. Molecular data have been reported for only 11 countries, indicating a clear geographical bias. Only 58 markers have been studied, and most are yet to be validated. Research into the molecular epidemiology of juvenile nasopharyngeal angiofibroma is still in its infancy. Although the molecular variation is not well understood, data obtained so far have prompted important research questions. Hence, multicentre collaborative molecular studies are needed to establish the aetiopathogenesis and establish molecular surrogates for clinical characteristics.

Undergraduate baccalaureate nursing students' self-reported confidence in learning about patient safety in the classroom and clinical settings: an annual cross-sectional study (2010-2013).

Science.gov (United States)

Lukewich, Julia; Edge, Dana S; Tranmer, Joan; Raymond, June; Miron, Jennifer; Ginsburg, Liane; VanDenKerkhof, Elizabeth

2015-05-01

Given the increasing incidence of adverse events and medication errors in healthcare settings, a greater emphasis is being placed on the integration of patient safety competencies into health professional education. Nurses play an important role in preventing and minimizing harm in the healthcare setting. Although patient safety concepts are generally incorporated within many undergraduate nursing programs, the level of students' confidence in learning about patient safety remains unclear. Self-reported patient safety competence has been operationalized as confidence in learning about various dimensions of patient safety. The present study explores nursing students' self-reported confidence in learning about patient safety during their undergraduate baccalaureate nursing program. Cross-sectional study with a nested cohort component conducted annually from 2010 to 2013. Participants were recruited from one Canadian university with a four-year baccalaureate of nursing science program. All students enrolled in the program were eligible to participate. The Health Professional Education in Patient Safety Survey was administered annually. The Health Professional Education in Patient Safety Survey captures how the six dimensions of the Canadian Patient Safety Institute Safety Competencies Framework and broader patient safety issues are addressed in health professional education, as well as respondents' self-reported comfort in speaking up about patient safety issues. In general, nursing students were relatively confident in what they were learning about the clinical dimensions of patient safety, but they were less confident about the sociocultural aspects of patient safety. Confidence in what they were learning in the clinical setting about working in teams, managing adverse events and responding to adverse events declined in upper years. The majority of students did not feel comfortable speaking up about patient safety issues. The nested cohort analysis confirmed these

The accuracy of CT and tumor markers in the detection of a recurrent ovarian carcinoma

International Nuclear Information System (INIS)

Wakabayashi, Yukari; Ishida, Jiro; Kotake, Fumio; Hirose, Masahiro; Kawana, Koji; Abe, Kimihiko; Amino, Saburo; Negishi, Yoshiyuki; Akiya, Kiyoshi

1989-01-01

Twenty-three patients previously diagnosed as having ovarian cancer were examined with both serum tumor markers (CA 125, CA 19-9, TPA, IAP, AFP) and a pelvic CT scan. The tumor markers predict the clinical outcome more accurately than the CT scan. Further, the tumor markers showed a clear correlation with the clinical course. But in one case, however, the tumor markers were seen to reduce below the normal level from chemotherapy, while the CT scan showed a tumor mass. Thus, both, a CT scan and tumor marker assays are felt to be indispensable for detecting the recurrence of an ovarian cancer. (author)

Feasibility of magnetic marker localisation for non-palpable breast cancer.

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Schermers, B; van der Hage, J A; Loo, C E; Vrancken Peeters, M T F D; Winter-Warnars, H A O; van Duijnhoven, F; Ten Haken, B; Muller, S H; Ruers, T J M

2017-06-01

Accurate tumour localisation is essential for breast-conserving surgery of non-palpable tumours. Current localisation technologies are associated with disadvantages such as logistical challenges and migration issues (wire guided localisation) or legislative complexities and high administrative burden (radioactive localisation). We present MAgnetic MArker LOCalisation (MaMaLoc), a novel technology that aims to overcome these disadvantages using a magnetic marker and a magnetic detection probe. This feasibility study reports on the first experience with this new technology for breast cancer localisation. Fifteen patients with unifocal, non-palpable breast cancer were recruited. They received concurrent placement of the magnetic marker in addition to a radioactive iodine seed, which is standard of care in our clinic. In a subset of five patients, migration of the magnetic marker was studied. During surgery, a magnetic probe and gammaprobe were alternately used to localise the markers and guide surgery. The primary outcome parameter was successful transcutaneous identification of the magnetic marker. Additionally, data on radiologist and surgeon satisfaction were collected. Magnetic marker placement was successful in all cases. Radiologists could easily adapt to the technology in the clinical workflow. Migration of the magnetic marker was negligible. The primary endpoint of the study was met with an identification rate of 100%. Both radiologists and surgeons reflected that the technology was intuitive to use and that it was comparable to radioactive iodine seed localisation. Magnetic marker localisation for non-palpable breast cancer is feasible and safe, and may be a viable non-radioactive alternative to current localisation technologies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparison between low-cost marker-less and high-end marker-based motion capture systems for the computer-aided assessment of working ergonomics.

Science.gov (United States)

Patrizi, Alfredo; Pennestrì, Ettore; Valentini, Pier Paolo

2016-01-01

The paper deals with the comparison between a high-end marker-based acquisition system and a low-cost marker-less methodology for the assessment of the human posture during working tasks. The low-cost methodology is based on the use of a single Microsoft Kinect V1 device. The high-end acquisition system is the BTS SMART that requires the use of reflective markers to be placed on the subject's body. Three practical working activities involving object lifting and displacement have been investigated. The operational risk has been evaluated according to the lifting equation proposed by the American National Institute for Occupational Safety and Health. The results of the study show that the risk multipliers computed from the two acquisition methodologies are very close for all the analysed activities. In agreement to this outcome, the marker-less methodology based on the Microsoft Kinect V1 device seems very promising to promote the dissemination of computer-aided assessment of ergonomics while maintaining good accuracy and affordable costs. PRACTITIONER’S SUMMARY: The study is motivated by the increasing interest for on-site working ergonomics assessment. We compared a low-cost marker-less methodology with a high-end marker-based system. We tested them on three different working tasks, assessing the working risk of lifting loads. The two methodologies showed comparable precision in all the investigations.

Ghost marker detection and elimination in marker-based optical tracking systems for real-time tracking in stereotactic body radiotherapy

International Nuclear Information System (INIS)

Yan, Guanghua; Li, Jonathan; Huang, Yin; Mittauer, Kathryn; Lu, Bo; Liu, Chihray

2014-01-01

uncertainties, and marker displacement. Results: The sensor positions and the limit for the CWL condition were measured with excellent reproducibility (standard deviation ≤ 0.39 mm). The ghost marker detection algorithm had perfect detection accuracy for both the jig (1544 samples) and the anthropomorphic phantom (2045 samples). Pattern matching was successful for all samples from both phantoms as well as the 40 patient marker patterns. Conclusions: The authors proposed a simple model to explain the origin of ghost markers and identified the CWL condition as the necessary condition for ghost marker occurrence. The retrospective ghost marker detection and elimination algorithms guarantee complete ghost marker elimination while providing the users with maximum flexibility in selecting the number of markers and their configuration to meet their clinic needs

Ghost marker detection and elimination in marker-based optical tracking systems for real-time tracking in stereotactic body radiotherapy

Energy Technology Data Exchange (ETDEWEB)

Yan, Guanghua, E-mail: yan@ufl.edu; Li, Jonathan; Huang, Yin; Mittauer, Kathryn; Lu, Bo; Liu, Chihray [Department of Radiation Oncology, University of Florida, Gainesville, Florida 32610 (United States)

2014-10-15

uncertainties, and marker displacement. Results: The sensor positions and the limit for the CWL condition were measured with excellent reproducibility (standard deviation ≤ 0.39 mm). The ghost marker detection algorithm had perfect detection accuracy for both the jig (1544 samples) and the anthropomorphic phantom (2045 samples). Pattern matching was successful for all samples from both phantoms as well as the 40 patient marker patterns. Conclusions: The authors proposed a simple model to explain the origin of ghost markers and identified the CWL condition as the necessary condition for ghost marker occurrence. The retrospective ghost marker detection and elimination algorithms guarantee complete ghost marker elimination while providing the users with maximum flexibility in selecting the number of markers and their configuration to meet their clinic needs.

Clinical significance of nailfold capillaroscopy in systemic lupus erythematosus: correlation with endothelial cell activation markers and disease activity.

Science.gov (United States)

Kuryliszyn-Moskal, A; Ciolkiewicz, M; Klimiuk, P A; Sierakowski, S

2009-01-01

To evaluate whether nailfold capillaroscopy (NC) changes are associated with the main serum endothelial cell activation markers and the disease activity of systemic lupus erythematosus (SLE). Serum levels of vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), soluble E-selectin (sE-selectin), and soluble thrombomodulin (sTM) were determined by an enzyme-linked immunosorbent assay (ELISA) in 80 SLE patients and 33 healthy controls. Nailfold capillary abnormalities were seen in 74 out of 80 (92.5%) SLE patients. A normal capillaroscopic pattern or mild changes were found in 33 (41.25%) and moderate/severe abnormalities in 47 (58.75%) of all SLE patients. In SLE patients a capillaroscopic score >1 was more frequently associated with the presence of internal organ involvement (p 1 and controls. SLE patients with severe/moderate capillaroscopic abnormalities showed significantly higher VEGF serum levels than patients with mild changes (p < 0.001). Moreover, there was a significant positive correlation between the severity of capillaroscopic changes and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) (p < 0.005) as well as between capillaroscopic score and VEGF serum levels (p < 0.001). Our findings confirm the usefulness of NC as a non-invasive technique for the evaluation of microvascular involvement in SLE patients. A relationship between changes in NC, endothelial cell activation markers and clinical features of SLE suggest an important role for microvascular abnormalities in clinical manifestation of the disease.

Evaluation of clinical value of combined tumor markers detection in diagnosis of lung cancer

International Nuclear Information System (INIS)

Zhang Guangming; Deng Shouzhen; Wang Yun; Xu Lianqin; He Wanting; Gao Quan; Lin Xiangtong

2002-01-01

To evaluate clinical value of single or combined tumor marker detection CY21-1, CEA, CA15-3 and SCC in the diagnosis of lung cancer. There was retrospective analysis of 87 lung cancer inpatients, all of them was confirmed by pathology. Results showed: (1) Sensitivity of CY21-1, CEA, CA15-3 and SCC by single detection in diagnosing lung cancer was 59.8%, 39.1%, 44.8%, 18.4%, respectively. (2) Sensitivity of group I (CY21-1 + CEA) was 78.2%; sensitivity of group II (CY21-1 + CEA + CA15-3) was 88.5%; sensitivity of group III (CY21-1 + CEA + CA15-3 + SCC) was the same as group II. In the diagnosis of lung cancer, the combined detection with CY21-1, CEA, CA15-3 was an ideal selective combination

Cognitive and imaging markers in non-demented subjects attending a memory clinic: study design and baseline findings of the MEMENTO cohort.

Science.gov (United States)

Dufouil, Carole; Dubois, Bruno; Vellas, Bruno; Pasquier, Florence; Blanc, Frédéric; Hugon, Jacques; Hanon, Olivier; Dartigues, Jean-François; Harston, Sandrine; Gabelle, Audrey; Ceccaldi, Mathieu; Beauchet, Olivier; Krolak-Salmon, Pierre; David, Renaud; Rouaud, Olivier; Godefroy, Olivier; Belin, Catherine; Rouch, Isabelle; Auguste, Nicolas; Wallon, David; Benetos, Athanase; Pariente, Jérémie; Paccalin, Marc; Moreaud, Olivier; Hommet, Caroline; Sellal, François; Boutoleau-Bretonniére, Claire; Jalenques, Isabelle; Gentric, Armelle; Vandel, Pierre; Azouani, Chabha; Fillon, Ludovic; Fischer, Clara; Savarieau, Helen; Operto, Gregory; Bertin, Hugo; Chupin, Marie; Bouteloup, Vincent; Habert, Marie-Odile; Mangin, Jean-François; Chêne, Geneviève

2017-08-29

The natural history and disease mechanisms of Alzheimer's disease and related disorders (ADRD) are still poorly understood. Very few resources are available to scrutinise patients as early as needed and to use integrative approaches combining standardised, repeated clinical investigations and cutting-edge biomarker measurements. In the nationwide French MEMENTO cohort study, participants were recruited in memory clinics and screened for either isolated subjective cognitive complaints (SCCs) or mild cognitive impairment (MCI; defined as test performance 1.5 SD below age, sex and education-level norms) while not demented (Clinical Dementia Rating [CDR] <1). Baseline data collection included neurological and physical examinations as well as extensive neuropsychological testing. To be included in the MEMENTO cohort, participants had to agree to undergo both brain magnetic resonance imaging (MRI) and blood sampling. Cerebral 18 F-fluorodeoxyglucose positon emission tomography and lumbar puncture were optional. Automated analyses of cerebral MRI included assessments of volumes of whole-brain, hippocampal and white matter lesions. The 2323 participants, recruited from April 2011 to June 2014, were aged 71 years, on average (SD 8.7), and 62% were women. CDR was 0 in 40% of participants, and 30% carried at least one apolipoprotein E ε4 allele. We observed that more than half (52%) of participants had amnestic mild cognitive impairment (17% single-domain aMCI), 32% had non-amnestic mild cognitive impairment (16.9% single-domain naMCI) and 16% had isolated SCCs. Multivariable analyses of neuroimaging markers associations with cognitive categories showed that participants with aMCI had worse levels of imaging biomarkers than the others, whereas participants with naMCI had markers at intermediate levels between SCC and aMCI. The burden of white matter lesions tended to be larger in participants with aMCI. Independently of CDR, all neuroimaging and neuropsychological markers

Early detection of clinically significant prostate cancer at diagnosis: a prospective study using a novel panel of TMPRSS2:ETS fusion gene markers

International Nuclear Information System (INIS)

Chan, Sam W.; Nguyen, Phuong-Nam; Violette, Philippe; Brimo, Fadi; Taguchi, Yosh; Aprikian, Armen; Chen, Junjian Z.

2013-01-01

We explore noninvasive clinical applications of multiple disease-specific fusion markers recently discovered in prostate cancer to predict the risk of cancer occurrence and aggressiveness at diagnosis. A total of 92 men who were prostate-specific antigen (PSA) screened and scheduled for diagnostic biopsy were enrolled for this study. Prospectively collected urine was blind coded for laboratory tests. RNA from urine sediments was analyzed using a panel of 6 TMPRSS2:ETS fusion markers with a sensitive quantitative PCR platform. The pathology reported 39 biopsy-positive cases from 92 patients (42.4%). In urine test, 10 unique combinations of fusion types were detected in 32 of 92 (34.8%) prebiopsy samples. A novel combination of fusion markers, termed Fx (III, IV, ETS), was identified with a sensitivity of 51.3% and an odds ratio of 10.1 in detecting cancer on biopsy. Incorporating a categorical variable of Fx (III, IV, ETS) with urine PCA3 and serum PSA, a regression model was developed to predict biopsy outcomes with an overall accuracy of 77%. Moreover, the overexpression of Fx (III, IV, or ETS) was shown to be an independent predictor to the high-grade cancer, with a predictive accuracy of 80% when coupled with PSA density. The individualized risk scores further stratified a high-risk group that is composed of 92% high-grade cancers and a low-risk group that harbors mainly clinically insignificant cancers. In conclusion, we have identified a novel combination of fusion types very specific to the clinically significant prostate cancer and developed effective regression models to predict biopsy outcomes and aggressive cancers at diagnosis

Development and testing of an objective structured clinical exam (OSCE) to assess socio-cultural dimensions of patient safety competency

Science.gov (United States)

Ginsburg, Liane R; Tregunno, Deborah; Norton, Peter G; Smee, Sydney; de Vries, Ingrid; Sebok, Stefanie S; VanDenKerkhof, Elizabeth G; Luctkar-Flude, Marian; Medves, Jennifer

2015-01-01

Background Patient safety (PS) receives limited attention in health professional curricula. We developed and pilot tested four Objective Structured Clinical Examination (OSCE) stations intended to reflect socio-cultural dimensions in the Canadian Patient Safety Institute's Safety Competency Framework. Setting and participants 18 third year undergraduate medical and nursing students at a Canadian University. Methods OSCE cases were developed by faculty with clinical and PS expertise with assistance from expert facilitators from the Medical Council of Canada. Stations reflect domains in the Safety Competency Framework (ie, managing safety risks, culture of safety, communication). Stations were assessed by two clinical faculty members. Inter-rater reliability was examined using weighted κ values. Additional aspects of reliability and OSCE performance are reported. Results Assessors exhibited excellent agreement (weighted κ scores ranged from 0.74 to 0.82 for the four OSCE stations). Learners’ scores varied across the four stations. Nursing students scored significantly lower (p<0.05) than medical students on three stations (nursing student mean scores=1.9, 1.9 and 2.7; medical student mean scores=2.8, 2.9 and 3.5 for stations 1, 2 and 3, respectively where 1=borderline unsatisfactory, 2=borderline satisfactory and 3=competence demonstrated). 7/18 students (39%) scored below ‘borderline satisfactory’ on one or more stations. Conclusions Results show (1) four OSCE stations evaluating socio-cultural dimensions of PS achieved variation in scores and (2) performance on this OSCE can be evaluated with high reliability, suggesting a single assessor per station would be sufficient. Differences between nursing and medical student performance are interesting; however, it is unclear what factors explain these differences. PMID:25398630

Review on the efficacy, safety and clinical applications of polihexanide, a modern wound antiseptic.

Science.gov (United States)

Hübner, N-O; Kramer, A

2010-01-01

Infected wounds are still one of the great challenges in medicine. In the last decade, it has become increasingly clear that antimicrobial chemotherapy is limited by the spread of antimicrobial resistance. Fortunately, new, highly effective antiseptic substances with a broad antimicrobial spectrum are available, so local treatment is expected to get increasingly more important in wound therapy. This paper reviews the antiseptic agent polihexanide (polyhexamethylene biguanide, PHMB), one of the most promising substances available today, from a clinical point of view, focusing on efficacy, safety and clinical applications. Copyright © 2010 S. Karger AG, Basel.

Exploring the Q-marker of "sweat soaking method" processed radix Wikstroemia indica: Based on the "effect-toxicity-chemicals" study.

Science.gov (United States)

Feng, Guo; Chen, Yun-Long; Li, Wei; Li, Lai-Lai; Wu, Zeng-Guang; Wu, Zi-Jun; Hai, Yue; Zhang, Si-Chao; Zheng, Chuan-Qi; Liu, Chang-Xiao; He, Xin

2018-06-01

Radix Wikstroemia indica (RWI), named "Liao Ge Wang" in Chinese, is a kind of toxic Chinese herbal medicine (CHM) commonly used in Miao nationality of South China. "Sweat soaking method" processed RWI could effectively decrease its toxicity and preserve therapeutic effect. However, the underlying mechanism of processing is still not clear, and the Q-markers database for processed RWI has not been established. Our study is to investigate and establish the quality evaluation system and potential Q-markers based on "effect-toxicity-chemicals" relationship of RWI for quality/safety assessment of "sweat soaking method" processing. The variation of RWI in efficacy and toxicity before and after processing was investigated by pharmacological and toxicological studies. Cytotoxicity test was used to screen the cytotoxicity of components in RWI. The material basis in ethanol extract of raw and processed RWI was studied by UPLC-Q-TOF/MS. And the potential Q-markers were analyzed and predicted according to "effect-toxicity-chemical" relationship. RWI was processed by "sweat soaking method", which could preserve efficacy and reduce toxicity. Raw RWI and processed RWI did not show significant difference on the antinociceptive and anti-inflammatory effect, however, the injury of liver and kidney by processed RWI was much weaker than that by raw RWI. The 20 compounds were identified from the ethanol extract of raw product and processed product of RWI using UPLC-Q-TOF/MS, including daphnoretin, emodin, triumbelletin, dibutyl phthalate, Methyl Paraben, YH-10 + OH and matairesinol, arctigenin, kaempferol and physcion. Furthermore, 3 diterpenoids (YH-10, YH-12 and YH-15) were proved to possess the high toxicity and decreased by 48%, 44% and 65%, respectively, which could be regarded as the potential Q-markers for quality/safety assessment of "sweat soaking method" processed RWI. A Q-marker database of processed RWI by "sweat soaking method" was established according to the results

Clinical Evaluation of Tumor Markers for Diagnosis in Patients with Non-small Cell Lung Cancer in China.

Science.gov (United States)

Ma, Li; Xie, Xiao-Wei; Wang, Hai-Yan; Ma, Ling-Yun; Wen, Zhong-Guang

2015-01-01

To evaluate the value of combined detection of serum carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1), and carbohydrateantigen 125 (CA125) for the clinical diagnosis of non- small cell lung cancer (NSCLC). Serum CEA, CYFRA21-1 and CA125 were assessed in 140 patients with NSCLC, 90 patients with benign lung disease and 90 normal control subjects, and differences of expression were compared in each group, and joint effects of these tumor markers in the diagnosis of NSCLC were analyzed. Serum CEA, CYFRA21-1 and CA125 in patients with NSCLC were significantly higher than those with benign lung disease and normal controls (PCEA, CYFRA21-1 and CA125 were 49.45%, 59.67%, and 44.87% respectively. As expected, combinations of these tumor markers improved their sensitivity for NSCLC. The combined detection of CEA+CYFRA21-1 was the most cost-effective combination which had higher sensitivity and specificity in NSCLC. Elevation of serum CEA and CYFRA21-1 was significantly associated with pathological types (PCEA, CYFRA21-1 and CA125 was significantly associated with TNM staging (PCEA, CYFRA21-1 and CA125 is of diagnostic value in the diagnosis of lung cancer, and a joint detection of these three tumor markers, could greatly improve the sensitivity of diagnosis on NSCLC. Combined detection of CEA+CYFRA21-1 proved to be the most economic and practical strategy in diagnosis of NSCLC, which can be used to screen the high-risk group.

Adapting Cognitive Task Analysis to Investigate Clinical Decision Making and Medication Safety Incidents.

Science.gov (United States)

Russ, Alissa L; Militello, Laura G; Glassman, Peter A; Arthur, Karen J; Zillich, Alan J; Weiner, Michael

2017-05-03

Cognitive task analysis (CTA) can yield valuable insights into healthcare professionals' cognition and inform system design to promote safe, quality care. Our objective was to adapt CTA-the critical decision method, specifically-to investigate patient safety incidents, overcome barriers to implementing this method, and facilitate more widespread use of cognitive task analysis in healthcare. We adapted CTA to facilitate recruitment of healthcare professionals and developed a data collection tool to capture incidents as they occurred. We also leveraged the electronic health record (EHR) to expand data capture and used EHR-stimulated recall to aid reconstruction of safety incidents. We investigated 3 categories of medication-related incidents: adverse drug reactions, drug-drug interactions, and drug-disease interactions. Healthcare professionals submitted incidents, and a subset of incidents was selected for CTA. We analyzed several outcomes to characterize incident capture and completed CTA interviews. We captured 101 incidents. Eighty incidents (79%) met eligibility criteria. We completed 60 CTA interviews, 20 for each incident category. Capturing incidents before interviews allowed us to shorten the interview duration and reduced reliance on healthcare professionals' recall. Incorporating the EHR into CTA enriched data collection. The adapted CTA technique was successful in capturing specific categories of safety incidents. Our approach may be especially useful for investigating safety incidents that healthcare professionals "fix and forget." Our innovations to CTA are expected to expand the application of this method in healthcare and inform a wide range of studies on clinical decision making and patient safety.

Emerging Role of Endothelial and Inflammatory Markers in Preeclampsia

Directory of Open Access Journals (Sweden)

Menha Swellam

2009-01-01

Full Text Available Objectives: Endothelial disturbance and excess inflammatory response are pathogenic mechanisms in pre-eclampsia (PE. Authors determine the clinical diagnostic role for thrombomodulin (TM, plasminogen activator inhibitor-1 (PAI-1 as endothelial markers and C-reactive protein (CRP, and interlukin-6 (IL-6 as inflammatory markers when tested independently or in combinations.

Biosafety considerations for selectable and scorable markers used in cassava (Manihot esculenta Crantz) biotechnology.

Science.gov (United States)

Petersen, William; Umbeck, Paul; Hokanson, Karen; Halsey, Mark

2005-01-01

Cassava is an important subsistence crop grown only in the tropics, and represents a major source of calories for many people in developing countries. Improvements in the areas of resistance to insects and viral diseases, enhanced nutritional qualities, reduced cyanogenic content and modified starch characteristics are urgently needed. Traditional breeding is hampered by the nature of the crop, which has a high degree of heterozygosity, irregular flowering, and poor seed set. Biotechnology has the potential to enhance crop improvement efforts, and genetic engineering techniques for cassava have thus been developed over the past decade. Selectable and scorable markers are critical to efficient transformation technology, and must be evaluated for biosafety, as well as efficiency and cost-effectiveness. In order to facilitate research planning and regulatory submission, the literature on biosafety aspects of the selectable and scorable markers currently used in cassava biotechnology is surveyed. The source, mode of action and current use of each marker gene is described. The potential for toxicity, allergenicity, pleiotropic effects, horizontal gene transfer, and the impact of these on food or feed safety and environmental safety is evaluated. Based on extensive information, the selectable marker genes nptII, hpt, bar/pat, and manA, and the scorable marker gene uidA, all have little risk in terms of biosafety. These appear to represent the safest options for use in cassava biotechnology available at this time.

Elevated tumour marker: an indication for imaging?

LENUS (Irish Health Repository)

McMahon, Colm J

2012-02-01

INTRODUCTION: The purpose of this study was to evaluate the utility of imaging examinations in patients with elevated tumour markers when (a) the tumour marker is not validated for as a primary diagnostic test; (b) the patient had no personal history of cancer and (c) the patient had no other imaging indication. MATERIALS AND METHODS: Patients without known cancer who had abnormal carcinoembryonic antigen, CA19-9, CA125 and\\/or CA15-3 serology over a one-year period were included. A retrospective medical record review was performed to assess the number of these cases who underwent imaging because of \\'elevated tumour marker\\' in the absence of a clinical indication for imaging. The number and result of these imaging studies were evaluated. RESULTS: Eight hundred and nineteen patients were included. Of those, 25 patients (mean age: 67.8 [range 41-91] y), were imaged to evaluate: \\'elevated tumour marker\\'. They underwent 29 imaging studies (mean [+\\/-standard deviation (SD)] per patient = 1.2 [+\\/-0.4]), and had 42 elevated tumour marker serology tests (mean [+\\/-SD] per patient = 1.7 [+\\/-0.7]). Four patients had >1 imaging test. No patient had an imaging study which diagnosed a malignancy or explained the elevated tumour marker. CONCLUSION: The non-judicious use of tumour markers can prompt further unnecessary investigations including imaging. In this study, there was no positive diagnostic yield for imaging performed for investigation of \\'elevated tumour marker\\'. \\'Elevated tumour marker\\

Rethinking the therapeutic misconception: social justice, patient advocacy, and cancer clinical trial recruitment in the US safety net.

Science.gov (United States)

Burke, Nancy J

2014-09-20

Approximately 20% of adult cancer patients are eligible to participate in a clinical trial, but only 2.5-9% do so. Accrual is even less for minority and medically underserved populations. As a result, critical life-saving treatments and quality of life services developed from research studies may not address their needs. This study questions the utility of the bioethical concern with therapeutic misconception (TM), a misconception that occurs when research subjects fail to distinguish between clinical research and ordinary treatment, and therefore attribute therapeutic intent to research procedures in the safety net setting. This paper provides ethnographic insight into the ways in which research is discussed and related to standard treatment. In the course of two years of ethnographic fieldwork in a safety net hospital, I conducted clinic observations (n=150 clinic days) and in-depth in-person qualitative interviews with patients (n=37) and providers (n=15). I used standard qualitative methods to organize and code resulting fieldnote and interview data. Findings suggest that TM is limited in relevance for the interdisciplinary context of cancer clinical trial recruitment in the safety net setting. Ethnographic data show the value of the discussions that happen prior to the informed consent, those that introduce the idea of participation in research. These preliminary discussions are elemental especially when recruiting underserved and vulnerable patients for clinical trial participation who are often unfamiliar with medical research and how it relates to medical care. Data also highlight the multiple actors involved in research discussions and the ethics of social justice and patient advocacy they mobilize, suggesting that class, inequality, and dependency influence the forms of ethical engagements in public hospital settings. On the ground ethics of social justice and patient advocacy are more relevant than TM as guiding ethical principles in the context of

Serum tumor markers in chronic kidney disease: as clinical tool in diagnosis, treatment and prognosis of cancers.

Science.gov (United States)

Amiri, Fateme Shamekhi

2016-01-01

Cancer is singled out as the biggest cause of death in the world, predicted to reach 13.1 million cancer-related deaths by the year 2030. Although there are no specific tumor markers used in cancer screening, some markers can be used to assist in making a diagnosis and determining a prognosis. They can be used to follow in cases where the diagnosis is cancer through monitoring of the disease recurrence and/or evaluating the response to therapy. These markers are not specific as the number increases in multiple cases of cancer. Some markers are positive in a single type of cancer; others are detectable in more than one type. An ideal tumor marker should be highly sensitive, specific, and reliable with high prognostic value. Other characteristics of an ideal tumor marker are organ specificity and correlation of it with tumor stages. However, none of the tumor markers reported to date has all these characteristics. Influence of different stages of chronic kidney function on serum tumor markers is variable. Furthermore, hemodialysis, peritoneal dialysis, and kidney transplantation affect on tumor markers differently. Sometimes, no study has been found in the literature review. Combined serum tumor markers may also be valuable. This literature review points the role of serum tumor markers in screening, diagnosis, and follow-up of cancer patients in chronic kidney disease patients and renal allograft recipients. In addition, impact of chronic kidney disease and kidney transplantation on different serum tumor markers is briefly explored.

[Biochemical markers of bone remodeling: pre-analytical variations and guidelines for their use. SFBC (Société Française de Biologie Clinique) Work Group. Biochemical markers of bone remodeling].

Science.gov (United States)

Garnero, P; Bianchi, F; Carlier, M C; Genty, V; Jacob, N; Kamel, S; Kindermans, C; Plouvier, E; Pressac, M; Souberbielle, J C

2000-01-01

Biochemical markers of bone turnover have been developed over the past 20 years that are more specific for bone tissue than conventional ones such as total alkaline phosphatase and urinary hydroxyproline. They have been widely used in clinical research and in clinical trials of new therapies as secondary end points of treatment efficacy. Most of the interest has been devoted to their use in postmenopausal osteoporosis, a condition characterized by subtle modifications of bone metabolism that cannot be detected readily by conventional markers of bone turnover. Although several recent studies have suggested that biochemical markers may be used for the management of the individual patient in routine clinical practice, this has not been clearly defined and is a matter of debate. Because of the crucial importance to clarify this issue, the Société Francaise de Biologie Clinique prompted an expert committee to summarize the available data and to make recommendations. The following paper includes a review on the biochemical and analytical aspects of the markers of bone formation and resorption and on the sources of variability such as sex, age, menstrual cycle, pregnancy and lactation, physical activity, seasonal variation and effects of diseases and treatments. We will also describe the effects of pre-analytical factors on the measurements of the different markers. Finally based on that review, we will make practical recommendations for the use of these markers in order to minimize the variability of the measurements and improve the clinical interpretation of the data.

[Clinical safety and professional liability claims in Orthopaedic Surgery and Traumatology].

Science.gov (United States)

Bori, G; Gómez-Durán, E L; Combalia, A; Trilla, A; Prat, A; Bruguera, M; Arimany-Manso, J

2016-01-01

The specialist in orthopaedic and traumatological surgery, like any other doctor, is subject to the current legal provisions while exercising their profession. Mandatory training in the medical-legal aspects of health care is essential. Claims against doctors are a reality, and orthopaedic and traumatological surgery holds first place in terms of frequency of claims according to the data from the General Council of Official Colleges of Doctors of Catalonia. Professionals must be aware of the fundamental aspects of medical professional liability, as well as specific aspects, such as defensive medicine and clinical safety. The understanding of these medical-legal aspects in the routine clinical practice can help to pave the way towards a satisfactory and safe professional career. The aim of this review is to contribute to this training, for the benefit of professionals and patients. Copyright © 2015 SECOT. Published by Elsevier Espana. All rights reserved.

Clinical value of combined detection of serum tumor markers and whole body bone scan for diagnosis of bone metastases from breast cancer

International Nuclear Information System (INIS)

Gao Chao; Zhao Jing; Liu Desheng; Zhang Jingchuan; Ji Xuejing; Hou Xiancun

2007-01-01

Objective: To study the clinical value of serum tumor marker determination and whole body bone scan for diagnosis of bone metastases from breast cancer. Methods: Serum tumor markers (CA15-3, CEA, TSGF)were detected with GLIA and whole body bone scan were investigated by SPECT in 124 breast cancer patients. Results: In 124 patients, 38 patients were diagnosed as positive for bone metastases with whole body bone scan. The positive predicting values of CA15-3, CEA, TSGF were 76.78%, 80% and 82.14%, and the negative predicting values of CA15-3, GEA, TSGF were 82.41%, 86.74% and 84.29% respectively. The levels of CA15-3, CEA, TSGF in patients with bone metastases were significantly higher than those in patients without metastasis and the controls (P<0.01). Conclusion: Determination of levels of serum tumor markers CA15-3, CEA, TSGF is helpful for diagnosis of bone metastases from breast cancer. Combined detection of GA15-3, CEA, TSGF could increase the sensitivity and accuracy of diagnosing bone metastases. (authors)

Interpreting and Integrating Clinical and Anatomic Pathology Results.

Science.gov (United States)

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

2017-01-01

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

Heartburn during sleep: a clinical marker of gastro-oesophageal reflux disease in morbidly obese patients.

Science.gov (United States)

Fornari, F; Madalosso, C A S; Callegari-Jacques, S M; Gurski, R R

2009-02-01

Gastro-oesophageal reflux disease (GORD) and morbid obesity are entities with increasing prevalence. New clinical strategies are cornerstones for their management. The aim of this study was to assess the prevalence of heartburn during sleep (HDS) and whether this symptom predicts the presence of objective GORD parameters and increased heartburn perception in morbidly obese patients. Ninety-one consecutive morbidly obese patients underwent clinical evaluation, upper gastrointestinal endoscopy and oesophageal pH monitoring. HDS was characterized when patients replied positively to the question, 'Does heartburn wake you from sleep?'. A General Score for Heartburn (GSH) ranging between 0 and 5 was assessed with the question 'How bad is your heartburn?'. HDS was reported by 33 patients (36%). More patients with HDS had abnormal acid contact time or reflux oesophagitis than patients without HDS (94%vs 57%, P heartburn preceded by acid reflux in diurnal (39%vs 9%; P heartburn. HDS occurs in a significant minority of patients with morbid obesity and has high positive predictive value for GORD. Symptomatic reflux during the sleep seems to be a marker of increased heartburn perception in this population.

Identify super quality markers from prototype-based pharmacokinetic markers of Tangzhiqing tablet (TZQ) based on in vitro dissolution/ permeation and in vivo absorption correlations.

Science.gov (United States)

Li, Ziqiang; Liu, Jia; Li, Yazhuo; Du, Xi; Li, Yanfen; Wang, Ruihua; Lv, Chunxiao; He, Xin; Wang, Baohe; Huang, Yuhong; Zhang, Deqin

2018-06-01

A quality marker (Q-marker) is defined as an inherent chemical compound that is used for the quality control of a drug. Its biological activities are closely related to safety and therapeutic effects. Generally, a multiple-component herbal medicine may have many Q-markers. We therefore proposed a concept of "super Q-marker" satisfying both the criterion of Q-markers and PK-markers to be used in more effective quality control of herbal medicine. The first aim was to find suitable prototype-based PK-markers from Tangzhiqing tablets (TZQ), a Chinese patent medicine. Then super Q-markers were expected to be identified from the prototype-based PK-markers based on an in vitro-in vivo correlation study. Potentially eligible prototype-based PK-markers were identified in a single- and multiple-dose pharmacokinetic study on TZQ in 30 healthy volunteers. The in vitro dissolution and permeation profiles of the prototype-based PK-markers of TZQ were evaluated by the physiologically-based drug dissolution/absorption simulating system (DDASS). An in vitro-in vivo correlation analysis was conducted between the dissolution/permeation behaviors in DDASS and the actual absorption profiles in human to test the transferability and traceability of the promising super Q-markers for TZQ. In human, plasma paeoniflorin and nuciferine as prototype-based PK-markers exhibited the appropriate pharmacokinetic properties, including dose-dependent systemic exposure (AUC, C max ) and a proper elimination half-life (1∼3h). In DDASS, it was predicted that paeoniflorin and nuciferine are highly permeable but the absorption rates are primarily limited by the dissolution rates. Moreover, the established in vitro-in vivo correlations of paeoniflorin and nuciferine were in support of the super Q-markers features. Paeoniflorin and nuciferine are identified as the super Q-markers from the prototype-based PK-markers of TZQ based on findings from a combination of in vitro, in vivo, and in vitro-in vivo

BOVINE PLASMA FIBRINOGEN AS MARKER IN CLINICAL AND SUB-CLINICAL MASTITIS

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R. Ali

2018-06-01

Full Text Available Plasma samples were collected from healthy as well as clinical and sub-clinical mastitis affected cows from Barasat, West Bengal, India. Plasma samples, after ammonium sulphate precipitation, were dialyzed against several changes of PBS (pH 7.2 to remove the excess ammonium sulphate. Then plasma fibrinogens were purified by gel filtration chromatography on Sephacryl S-200 HR. SDS-PAGE (10% of purified fibrinogen from plasma of healthy cow revealed polypeptide bands of 74, 67 and 57 kDa which represent the α (alpha, β (beta and γ (gamma- chains respectively. On the other hand, purified fibrinogen from plasma of sub-clinical and clinical mastitis affected cow revealed polypeptide bands of 73 (α-chain, 68 kDa (β-chain and 72 (γ-chain, 68 kDa (β-chain respectively. The SDS-PAGE analysis showed the absence of gamma (γ- chain of fibrinogen in both the samples of sub-clinical and clinical mastitis positive cow. Single precipitin line was observed in double immunodiffusion test when purified fibrinogen from healthy, clinical and subclinical mastitis positive cows reacted with hyper immune sera raised in rabbit. No precipitin line was found against the normal control serum. These purified fibrinogens also showed cross reactivity against antibody raised in rabbit when analyzed by western blot technique.

A new method for the assessment of patient safety competencies during a medical school clerkship using an objective structured clinical examination

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Renata Mahfuz Daud-Gallotti

2011-01-01

Full Text Available INTRODUCTION: Patient safety is seldom assessed using objective evaluations during undergraduate medical education. OBJECTIVE: To evaluate the performance of fifth-year medical students using an objective structured clinical examination focused on patient safety after implementation of an interactive program based on adverse events recognition and disclosure. METHODS: In 2007, a patient safety program was implemented in the internal medicine clerkship of our hospital. The program focused on human error theory, epidemiology of incidents, adverse events, and disclosure. Upon completion of the program, students completed an objective structured clinical examination with five stations and standardized patients. One station focused on patient safety issues, including medical error recognition/disclosure, the patient-physician relationship and humanism issues. A standardized checklist was completed by each standardized patient to assess the performance of each student. The student's global performance at each station and performance in the domains of medical error, the patient-physician relationship and humanism were determined. The correlations between the student performances in these three domains were calculated. RESULTS: A total of 95 students participated in the objective structured clinical examination. The mean global score at the patient safety station was 87.59 ± 1.24 points. Students' performance in the medical error domain was significantly lower than their performance on patient-physician relationship and humanistic issues. Less than 60% of students (n = 54 offered the simulated patient an apology after a medical error occurred. A significant correlation was found between scores obtained in the medical error domains and scores related to both the patient-physician relationship and humanistic domains. CONCLUSIONS: An objective structured clinical examination is a useful tool to evaluate patient safety competencies during the medical

Myocardial Contrast Agents – Safety Considerations and Clinical Efficacy in Stress Echocardiography

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Maier Anca

2016-11-01

Full Text Available Transthoracic echocardiographic examination is known to be a safe, non-invasive and reproducible method, used in every day clinical practice to obtain important information about cardiac structure and function. Unfortunately, a significant proportion of studies have highlighted the considerable technically difficultly in producing diagnostic images due to a poor acoustic window and more than 33% of patients undergoing stress echocardiography have suboptimal echocardiographic images. All these limitations have led to the use of contrast agents to improve the quality of standard ultrasound examination to provide a better delineation of left ventricle endocardial borders or to obtain information that cannot be achieved by using standard echocardiography, such as assessing myocardial microcirculation and therefore perfusion. This paper sought to review the clinical efficacy and safety of ultrasound contrast agents focusing on stress echocardiography.

Clinical impact of concomitant immunomodulators on biologic therapy: Pharmacokinetics, immunogenicity, efficacy and safety.

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Xu, Zhenhua; Davis, Hugh M; Zhou, Honghui

2015-03-01

Immune-mediated inflammatory diseases encompass a variety of different clinical syndromes, manifesting as either common diseases such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD) and psoriasis, or rare diseases such as cryopyrin-associated periodic syndromes. The therapy for these diseases often involves the use of a wide range of drugs including nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, immunomodulators, and biologic therapies. Due to the abundance of relevant clinical data, this article provides a general overview on the clinical impact of the concomitant use of immunomodulators and biologic therapies, with a focus on anti-tumor necrosis factor-α agents (anti-TNFα), for the treatment of RA and Crohn's disease (CD). Compared to biologic monotherapy, concomitant use of immunomodulators (methotrexate, azathioprine, and 6-mercaptopurine) often increases the systemic exposure of the anti-TNFα agent and decreases the formation of antibodies to the anti-TNFα agent, consequently enhancing clinical efficacy. Nevertheless, long-term combination therapy with immunomodulators and anti-TNFα agents may be associated with increased risks of serious infections and malignancies. Therefore, the determination whether combination therapy is suitable for a patient should always be based on an individualized benefit-risk evaluation. More research should be undertaken to identify and validate prognostic markers for predicting patients who would benefit the most and those who are at greater risk from combination therapy with immunomodulators and anti-TNFα agents. © 2015, The American College of Clinical Pharmacology.

INFLAMMATORY MARKERS IN ACUTE ISCHAEMIC STROKE IN RELATION TO CLINICAL SEVERITY AND EARLY OUTCOME

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S. Gopi

2018-01-01

Full Text Available BACKGROUND Biochemical markers of inflammation could be useful to predict severity of stroke in acute phase. Stroke is the third cause of mortality and the first cause of disability. Recent literature have demonstrated that inflammation contributes to all phases of atherosclerosis. The results of researchers suggest that atherosclerosis is an inflammatory disease. The aim of the study is to assess the1. Level of peripheral inflammatory markers in acute ischaemic stroke and their relation to severity of acute stroke. 2. Value of inflammatory markers in predicting the short-term outcome and disability at the end of six months. MATERIALS AND METHODS This is a prospective case control study for 6 months done from September 2014 to August 2016 in 100 patients of acute ischaemic stroke within first 5 days of symptom onset in comparison >18 years of age with 50 age and sex matched controls. Blood samples for all cases and controls were sent for erythrocyte sedimentation rate, Neutrophil-to-Lymphocyte Ratio (NLR, hs-C-reactive protein, mean platelet volume, serum ferritin, serum albumin and S. gamma-glutamyl transferase at admission. RESULTS The mean values of ESR, NLR, hs-CRP in all the cases are higher when compared to the controls and are statistically significant, whereas the mean values of MPV, S. ferritin, S. albumin and GGT in cases are lower when compared to controls, but are within normal range and difference is statistically significant except ferritin. ESR, hs-CRP has significant correlation with severity of acute ischaemic stroke. The mean values of these markers increased with increase in severity. Serum albumin has significant correlation with severity of acute ischaemic stroke with mean values of these markers decreasing with increase in severity of stroke. There is no significant correlation of the inflammatory markers in present study with the short-term outcome. CONCLUSION Inflammation plays an important role in the pathogenesis of non

Effects of an onion by-product on bioactivity and safety markers in healthy rats.

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Roldán-Marín, Eduvigis; Krath, Britta N; Poulsen, Morten; Binderup, Mona-Lise; Nielsen, Tom H; Hansen, Max; Barri, Thaer; Langkilde, Søren; Cano, M Pilar; Sánchez-Moreno, Concepción; Dragsted, Lars O

2009-12-01

Onions are excellent sources of bioactive compounds including fructo-oligosaccharides (FOS) and polyphenols. An onion by-product was characterised in order to be developed as a potentially bioactive food ingredient. Our main aim was to investigate whether the potential health and safety effects of this onion by-product were shared by either of two derived fractions, an extract containing the onion FOS and polyphenols and a residue fraction containing mainly cell wall materials. We report here on the effects of feeding these products on markers of potential toxicity, protective enzymes and gut environment in healthy rats. Rats were fed during 4 weeks with a diet containing the products or a control feed balanced in carbohydrate. The onion by-product and the extract caused anaemia as expected in rodents for Allium products. No other toxicity was observed, including genotoxicity. Glutathione reductase (GR) and glutathione peroxidase (GPx1) activities in erythrocytes increased when rats were fed with the onion extract. Hepatic gene expression of Gr, Gpx1, catalase, 5-aminolevulinate synthase and NAD(P)H:quinone oxidoreductase was not altered in any group of the onion fed rats. By contrast, gamma-glutamate cysteine ligase catalytic subunit gene expression was upregulated but only in rats given the onion residue. The onion by-products as well as the soluble and insoluble fractions had prebiotic effects as evidenced by decreased pH, increased butyrate production and altered gut microbiota enzyme activities. In conclusion, the onion by-products have no in vivo genotoxicity, may support in vivo antioxidative defence and alter the functionality of the rat gut microbiota.

Effectiveness and safety of probiotic preparations in clinical treatment of inflammatory bowel disease

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Ewa Wasilewska

2018-03-01

Full Text Available Inflammatory bowel disease (IBD is characterized by an aggressive immune response to luminal antigens including those of commensal microbiota, which are essential for intestinal homeostasis and appear to play a role in tolerance and immunity. Its disturbances can result in intestinal dysbiosis and the development of disease. The precise role of luminal bacteria in the pathogenesis of IBD has yet to be elucidated; however, considerable evidence implicates changes to bacterial communities associated with the gut mucosa in the disease state. It is also well known that beneficial microbes can confer a functional health benefit to the host. We analysed the effectiveness of probiotics to relieve symptoms in patients suffering from IBD. Using the Medline database and manually searching articles, we reviewed clinical trials performed with probiotics and lactic acid bacteria as supportive or alternative IBD treatments. The article summarizes IBD microenvironment and the efficiency of probiotic preparations in attenuating the symptoms of Crohn’s disease, ulcerative colitis, and pouchitis. The safety of probiotic intake is also analyzed based on existing outcomes of clinical trials and case reports. Strong evidence exists that probiotics are effective as supportive therapy for IBD; however, only a few preparations have well documented efficiency and safety. Clinical studies demonstrated that probiotics were more effective in preventing recurrence of the disease symptoms than in the management of its active stage. Some products may increase the risk of complications in specific patient groups; therefore, the use of probiotics should be considered with caution in the case of severe active IBD, especially with disrupted mucosa.

Ethics of safety reporting of a clinical trial

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Amrita Sil

2017-01-01

Full Text Available Clinical trial related injury and serious adverse events (SAE are a major area of concern. In all such scenarios the investigator is responsible for medical care of the trial participant and also ethically bound to report the event to all the stakeholders of the clinical trial. The trial sponsor is responsible for ongoing safety evaluation of the investigational product, reporting and compensating the participant in case of any SAE. The Ethics Committee and regulatory body of the country are to uphold the ethical principles of beneficence, justice, non-maleficence in such cases. Any unwanted and noxious effect of a drug when used in recommended doses is an adverse drug reaction (ADR whereas if causal association is not yet established it is termed adverse event (AE. An AE or ADR that is associated with death, in-patient hospitalization, prolongation of hospitalization, persistent or significant disability or incapacity, a congenital anomaly, or is otherwise life threatening is termed as an SAE. The principal investigator reports the event to the licensing authority (DCGI, sponsor and Chairperson of the Ethics Committee (EC within 24 hours of occurrence of the SAE. This report is furthered by a detailed report by both the investigator and the EC and given to the DCGI who then gives a final decision on the amount of compensation to be given by the sponsor or the sponsor's representative to the grieving party.

Non-clinical safety evaluation of intranasal iota-carrageenan.

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Hebar, Alexandra; Koller, Christiane; Seifert, Jan-Marcus; Chabicovsky, Monika; Bodenteich, Angelika; Bernkop-Schnürch, Andreas; Grassauer, Andreas; Prieschl-Grassauer, Eva

2015-01-01

Carrageenan has been widely used as food additive for decades and therefore, an extended oral data set is available in the public domain. Less data are available for other routes of administration, especially intranasal administration. The current publication describes the non-clinical safety and toxicity of native (non-degraded) iota-carrageenan when applied intranasally or via inhalation. Intranasally applied iota-carrageenan is a topically applied, locally acting compound with no need of systemic bioavailability for the drug's action. Animal experiments included repeated dose local tolerance and toxicity studies with intranasally applied 0.12% iota-carrageenan for 7 or 28 days in New Zealand White rabbits and nebulized 0.12% iota-carrageenan administered to F344 rats for 7 days. Permeation studies revealed no penetration of iota-carrageenan across nasal mucosa, demonstrating that iota-carrageenan does not reach the blood stream. Consistent with this, no relevant toxic or secondary pharmacological effects due to systemic exposure were observed in the rabbit or rat repeated dose toxicity studies. Data do not provide any evidence for local intolerance or toxicity, when carrageenan is applied intranasally or by inhalation. No signs for immunogenicity or immunotoxicity have been observed in the in vivo studies. This is substantiated by in vitro assays showing no stimulation of a panel of pro-inflammatory cytokines by iota-carrageenan. In conclusion, 0.12% iota-carrageenan is safe for clinical use via intranasal application.

Non-clinical safety evaluation of intranasal iota-carrageenan.

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Alexandra Hebar

Full Text Available Carrageenan has been widely used as food additive for decades and therefore, an extended oral data set is available in the public domain. Less data are available for other routes of administration, especially intranasal administration. The current publication describes the non-clinical safety and toxicity of native (non-degraded iota-carrageenan when applied intranasally or via inhalation. Intranasally applied iota-carrageenan is a topically applied, locally acting compound with no need of systemic bioavailability for the drug's action. Animal experiments included repeated dose local tolerance and toxicity studies with intranasally applied 0.12% iota-carrageenan for 7 or 28 days in New Zealand White rabbits and nebulized 0.12% iota-carrageenan administered to F344 rats for 7 days. Permeation studies revealed no penetration of iota-carrageenan across nasal mucosa, demonstrating that iota-carrageenan does not reach the blood stream. Consistent with this, no relevant toxic or secondary pharmacological effects due to systemic exposure were observed in the rabbit or rat repeated dose toxicity studies. Data do not provide any evidence for local intolerance or toxicity, when carrageenan is applied intranasally or by inhalation. No signs for immunogenicity or immunotoxicity have been observed in the in vivo studies. This is substantiated by in vitro assays showing no stimulation of a panel of pro-inflammatory cytokines by iota-carrageenan. In conclusion, 0.12% iota-carrageenan is safe for clinical use via intranasal application.

Usefulness of molecular markers in the diagnosis of occupational and recreational histoplasmosis outbreaks.

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Frías-De-León, María Guadalupe; Ramírez-Bárcenas, José Antonio; Rodríguez-Arellanes, Gabriela; Velasco-Castrejón, Oscar; Taylor, Maria Lucia; Reyes-Montes, María Del Rocío

2017-03-01

Histoplasmosis is considered the most important systemic mycosis in Mexico, and its diagnosis requires fast and reliable methodologies. The present study evaluated the usefulness of PCR using Hcp100 and 1281-1283 (220) molecular markers in detecting Histoplasma capsulatum in occupational and recreational outbreaks. Seven clinical serum samples of infected individuals from three different histoplasmosis outbreaks were processed by enzyme-linked immunosorbent assay (ELISA) to titre anti-H. capsulatum antibodies and to extract DNA. Fourteen environmental samples were also processed for H. capsulatum isolation and DNA extraction. Both clinical and environmental DNA samples were analysed by PCR with Hcp100 and 1281-1283 (220) markers. Antibodies to H. capsulatum were detected by ELISA in all serum samples using specific antigens, and in six of these samples, the PCR products of both molecular markers were amplified. Four environmental samples amplified one of the two markers, but only one sample amplified both markers and an isolate of H. capsulatum was cultured from this sample. All PCR products were sequenced, and the sequences for each marker were analysed using the Basic Local Alignment Search Tool (BLASTn), which revealed 95-98 and 98-100 % similarities with the reference sequences deposited in the GenBank for Hcp100 and 1281-1283 (220) , respectively. Both molecular markers proved to be useful in studying histoplasmosis outbreaks because they are matched for pathogen detection in either clinical or environmental samples.

Bipolar disorder and complementary medicine: current evidence, safety issues, and clinical considerations.

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Sarris, Jerome; Lake, James; Hoenders, Rogier

2011-10-01

Bipolar disorder (BD) is a debilitating syndrome that is often undiagnosed and undertreated. Population surveys show that persons with BD often self-medicate with complementary and alternative medicine (CAM) or integrative therapies in spite of limited research evidence supporting their use. To date, no review has focused specifically on nonconventional treatments of BD. The study objectives were to present a review of nonconventional (complementary and integrative) interventions examined in clinical trials on BD, and to offer provisional guidelines for the judicious integrative use of CAM in the management of BD. PubMed, CINAHL,(®) Web of Science, and Cochrane Library databases were searched for human clinical trials in English during mid-2010 using Bipolar Disorder and CAM therapy and CAM medicine search terms. Effect sizes (Cohen's d) were also calculated where data were available. Several positive high-quality studies on nutrients in combination with conventional mood stabilizers and antipsychotic medications in BD depression were identified, while branched-chain amino acids and magnesium were effective (small studies) in attenuating mania in BD. In the treatment of bipolar depression, evidence was mixed regarding omega-3, while isolated studies provide provisional support for a multinutrient formula, n-acetylcysteine, and l-tryptophan. In one study, acupuncture was found to have favorable but nonsignificant effects on mania and depression outcomes. Current evidence supports the integrative treatment of BD using combinations of mood stabilizers and select nutrients. Other CAM or integrative modalities used to treat BD have not been adequately explored to date; however, some early findings are promising. Select CAM and integrative interventions add to established conventional treatment of BD and may be considered when formulating a treatment plan. It is hoped that the safety issues and clinical considerations addressed in this article may encourage the practice

Corneal markers of diabetic neuropathy.

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Pritchard, Nicola; Edwards, Katie; Shahidi, Ayda M; Sampson, Geoff P; Russell, Anthony W; Malik, Rayaz A; Efron, Nathan

2011-01-01

Diabetic neuropathy is a significant clinical problem that currently has no effective therapy, and in advanced cases, leads to foot ulceration and lower limb amputation. The accurate detection, characterization and quantification of this condition are important in order to define at-risk patients, anticipate deterioration, monitor progression, and assess new therapies. This review evaluates novel corneal methods of assessing diabetic neuropathy. Two new noninvasive corneal markers have emerged, and in cross-sectional studies have demonstrated their ability to stratify the severity of this disease. Corneal confocal microscopy allows quantification of corneal nerve parameters and noncontact corneal esthesiometry, the functional correlate of corneal structure, assesses the sensitivity of the cornea. Both these techniques are quick to perform, produce little or no discomfort for the patient, and are suitable for clinical settings. Each has advantages and disadvantages over traditional techniques for assessing diabetic neuropathy. Application of these new corneal markers for longitudinal evaluation of diabetic neuropathy has the potential to reduce dependence on more invasive, costly, and time-consuming assessments, such as skin biopsy.

Clinically Meaningful Use of Blood Tumor Markers in Oncology

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Holdenrieder, Stefan; Pagliaro, Lance; Morgenstern, David; Dayyani, Farshid

2016-01-01

Before the introduction of modern imaging techniques and the recent developments in molecular diagnosis, tumor markers (TMs) were among the few available diagnostic tools for the management of cancer patients. Easily obtained from serum or plasma samples, TMs are minimally invasive and convenient, and the associated costs are low. Single TMs were traditionally used but these have come under scrutiny due to their low sensitivity and specificity when used, for example, in a screening setting. H...

Polyphenols as Possible Markers of Botanical Origin of Honey.

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Gašić, Uroš M; Milojković-Opsenica, Dušanka M; Tešić, Živoslav Lj

2017-07-01

In recent years, the botanical and geographical origin of food has become an important topic in the context of food quality and safety, as well as consumer protection, in accordance with international standards. Finding chemical markers, especially phytochemicals, characteristic for some kind of food is the subject of interest of a significant number of researchers in the world. This paper is focused on the use of polyphenols as potential markers for the determination of botanical origin of honey. It includes a review of the polyphenols present in various honey samples and the methods for their separation and identification. Special emphasis in this paper is placed on the identification of honey polyphenols using advanced LC-MS techniques in order to find specific markers of botanical origin of honey. In this regard, this study gives an overview of the literature that describes the use of LC-MS techniques for the isolation and determination of honey polyphenols. This review focuses on the research performed in the past two decades.

Evolution of hepatitis B serological markers in HIV coinfected patients: a case study

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Ana Luiza de Castro Conde Toscano

Full Text Available ABSTRACT OBJECTIVE To describe the evolution of serological markers among HIV and hepatitis B coinfected patients, with emphasis on evaluating the reactivation or seroreversion of these markers. METHODS The study population consisted of patients met in an AIDS Outpatient Clinic in São Paulo State, Brazil. We included in the analysis all HIV-infected and who underwent at least two positive hepatitis B surface antigen serological testing during clinical follow up, with tests taken six months apart. Patients were tested with commercial kits available for hepatitis B serological markers by microparticle enzyme immunoassay. Clinical variables were collected: age, sex, CD4+ T-cell count, HIV viral load, alanine aminotransferase level, exposure to antiretroviral drugs including lamivudine and/or tenofovir. RESULTS Among 2,242 HIV positive patients, we identified 105 (4.7% patients with chronic hepatitis B. Follow up time for these patients varied from six months to 20.5 years. All patients underwent antiretroviral therapy during follow-up. Among patients with chronic hepatitis B, 58% were hepatitis B “e” antigen positive at the first assessment. Clearance of hepatitis B surface antigen occurred in 15% (16/105 of patients with chronic hepatitis B, and 50% (8/16 of these patients presented subsequent reactivation or seroreversion of hepatitis B surface antigen. Among hepatitis B “e” antigen positive patients, 57% (35/61 presented clearance of this serologic marker. During clinical follow up, 28.5% (10/35 of those who initially cleared hepatitis B “e” antigen presented seroreversion or reactivation of this marker. CONCLUSIONS Among HIV coinfected patients under antiretroviral therapy, changes of HBV serological markers were frequently observed. These results suggest that frequent monitoring of these serum markers should be recommended.

[Immunological Markers in Organ Transplantation].

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Beckmann, J H; Heits, N; Braun, F; Becker, T

2017-04-01

The immunological monitoring in organ transplantation is based mainly on the determination of laboratory parameters as surrogate markers of organ dysfunction. Structural damage, caused by alloreactivity, can only be detected by invasive biopsy of the graft, which is why inevitably rejection episodes are diagnosed at a rather progressive stage. New non-invasive specific markers that enable transplant clinicians to identify rejection episodes at an earlier stage, on the molecular level, are needed. The accurate identification of rejection episodes and the establishment of operational tolerance permit early treatment or, respectively, a controlled cessation of immunosuppression. In addition, new prognostic biological markers are expected to allow a pre-transplant risk stratification thus having an impact on organ allocation and immunosuppressive regimen. New high-throughput screening methods allow simultaneous examination of hundreds of characteristics and the generation of specific biological signatures, which might give concrete information about acute rejection, chronic dysfunction as well as operational tolerance. Even though multiple studies and a variety of publications report about important advances on this subject, almost no new biological marker has been implemented in clinical practice as yet. Nevertheless, new technologies, in particular analysis of the genome, transcriptome, proteome and metabolome will make personalised transplantation medicine possible and will further improve the long-term results and graft survival rates. This article gives a survey of the limitations and possibilities of new immunological markers in organ transplantation. Georg Thieme Verlag KG Stuttgart · New York.

Patient safety climate and worker safety behaviours in acute hospitals in Scotland.

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Agnew, Cakil; Flin, Rhona; Mearns, Kathryn

2013-06-01

To obtain a measure of hospital safety climate from a sample of National Health Service (NHS) acute hospitals in Scotland and to test whether these scores were associated with worker safety behaviors, and patient and worker injuries. Data were from 1,866 NHS clinical staff in six Scottish acute hospitals. A Scottish Hospital Safety Questionnaire measured hospital safety climate (Hospital Survey on Patient Safety Culture), worker safety behaviors, and worker and patient injuries. The associations between the hospital safety climate scores and the outcome measures (safety behaviors, worker and patient injury rates) were examined. Hospital safety climate scores were significantly correlated with clinical workers' safety behavior and patient and worker injury measures, although the effect sizes were smaller for the latter. Regression analyses revealed that perceptions of staffing levels and managerial commitment were significant predictors for all the safety outcome measures. Both patient-specific and more generic safety climate items were found to have significant impacts on safety outcome measures. This study demonstrated the influences of different aspects of hospital safety climate on both patient and worker safety outcomes. Moreover, it has been shown that in a hospital setting, a safety climate supporting safer patient care would also help to ensure worker safety. The Scottish Hospital Safety Questionnaire has proved to be a usable method of measuring both hospital safety climate as well as patient and worker safety outcomes. Copyright © 2013 National Safety Council and Elsevier Ltd. Published by Elsevier Ltd. All rights reserved.

Clinically isolated syndrome. Prognostic markers for conversion to multiple sclerosis and initiation of disease-modifying therapy

International Nuclear Information System (INIS)

Kohriyama, Tatsuo

2011-01-01

Eighty-five percent of patients with multiple sclerosis (MS) initially present with a single demyelinating event, referred to as a clinically isolated syndrome (CIS) of the optic nerves, brainstem, or spinal cord. Following the onset of CIS, 38 to 68% of patients develop clinically definite MS (CDMS). Clinically silent brain lesions are seen on MRI in 50 to 80% of patients with CIS at first clinical presentation and 56 to 88% of CIS patients with abnormal MRI are at high risk of conversion to CDMS. Axonal damage, that is considered to underlie the development of persistent disability in MS, occurs in the CIS stage. Treatment with disease-modifying therapies (DMTs), that might prevent axonal damage and result in slowing the progression of disability, should be initiated early during the disease course. Clinical trials demonstrated that early treatment of CIS patients with the standard dose of interferon beta (IFNβ) significantly reduced the risk of progression to CDMS by 44 to 50%. After 5 years of follow-up, the results of the IFNβ treatment extension studies confirmed that the risk of conversion to CDMS was significantly reduced by 35 to 37% in patients receiving early treatment compared to that in those receiving delayed treatment. However, not every patient with CIS will progress to CDMS; the IFNβ treatment is appropriately indicated for CIS patients who are diagnosed with MS by McDonald diagnostic criteria based on MRI findings of dissemination in space and time and are at high risk for conversion to CDMS. Development of more reliable prognostic markers will enable DMTs to be targeted for those who are most likely to benefit. (author)

National survey on internal quality control for tumour markers in clinical laboratories in China.

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Wang, Wei; Zhong, Kun; Yuan, Shuai; He, Falin; Du, Yuxuan; Hu, Zhehui; Wang, Zhiguo

2018-06-15

This survey was initiated to obtain knowledge on the current situation of internal quality control (IQC) practice for tumour markers (TMs) in China. Additionally, we tried to acquire the most appropriate quality specifications. This survey was a current status survey. The IQC information had been collected via online questionnaires. All of 1821 clinical laboratories which participated in the 2016 TMs external quality assessment (EQA) programme had been enrolled. The imprecision evaluation criteria were the minimal, desirable, and optimal allowable imprecisions based on biological variations, and 1/3 total allowable error (TEa) and 1/4 TEa. A total of 1628 laboratories answered the questionnaires (89%). The coefficients of variation (CVs) of the IQC of participant laboratories varied greatly from 1% (5 th percentile) to 13% (95 th percentile). More than 82% (82 - 91%) of participant laboratories two types of CVs met 1/3 TEa except for CA 19-9. The percentiles of current CVs were smaller than cumulative CVs. A number of 1240 laboratories (76%) reported their principles and systems used. The electrochemiluminescence was the most used principle (45%) and had the smallest CVs. The performance of laboratories for TMs IQC has yet to be improved. On the basis of the obtained results, 1/3 TEa would be realistic and attainable quality specification for TMs IQC for clinical laboratories in China.

Are HPV vaccination services accessible to high-risk communities? A spatial analysis of HPV-associated cancer and Chlamydia rates and safety-net clinics.

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Tsui, Jennifer; Rodriguez, Hector P; Gee, Gilbert C; Escobedo, Loraine A; Kominski, Gerald F; Bastani, Roshan

2013-12-01

While HPV vaccines can greatly benefit adolescents and young women from high-risk areas, little is known about whether safety-net immunization services are geographically accessible to communities at greatest risk for HPV-associated diseases. We explore the spatial relationship between areas with high HPV risk and proximity to safety-net clinics from an ecologic perspective. We used cancer registry data and Chlamydia surveillance data to identify neighborhoods within Los Angeles County with high risk for HPV-associated cancers. We examined proximity to safety-net clinics among neighborhoods with the highest risk. Proximity was measured as the shortest distance between each neighborhood center and the nearest clinic and having a clinic within 3 miles of each neighborhood center. The average 5-year non-age-adjusted rates were 1,940 cases per 100,000 for Chlamydia and 60 per 100,000 for HPV-associated cancers. A large majority, 349 of 386 neighborhoods with high HPV-associated cancer rates and 532 of 537 neighborhoods with high Chlamydia rates, had a clinic within 3 miles of the neighborhood center. Clinics were more likely to be located within close proximity to high-risk neighborhoods in the inner city. High-risk neighborhoods outside of this urban core area were less likely to be near accessible clinics. The majority of high-risk neighborhoods were geographically near safety-net clinics with HPV vaccination services. Due to low rates of vaccination, these findings suggest that while services are geographically accessible, additional efforts are needed to improve uptake. Programs aimed to increase awareness about the vaccine and to link underserved groups to vaccination services are warranted.

Selection of chemical markers for the quality control of medicinal plants of the genus Cecropia.

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Rivera-Mondragón, Andrés; Ortíz, Orlando O; Bijttebier, Sebastiaan; Vlietinck, Arnold; Apers, Sandra; Pieters, Luc; Caballero-George, Catherina

2017-12-01

Several Cecropia (Cecropiaceae) species are traditionally used in Latin America for the treatment of a variety of diseases including diabetes, arterial hypertension, asthma, bronchitis, anxiety, and inflammation. At present, a number of commercial products based on these plants have been introduced into the market with very little information on methods for guaranteeing their quality and safety. This work proposes potential chemical markers for the quality control of the raw materials of Cecropia obtusifolia Bertol., Cecropia peltata L., Cecropia glaziovii Snethl., Cecropia pachystachya Trécul, and Cecropia hololeuca Miq. The Herbal Chemical Marker Ranking System (Herb MaRS) developed by the National Institute of Complementary Medicine (NICM) at the University of Western Sydney was used for selecting chemical markers for the quality control of selected medicinal species of Cecropia. This review covers the period from 1982 to 2016. Chlorogenic acid, flavonoidal glycosides (orientin, isoorientin, vitexin, isovitexin, and rutin), catechin, epicatechin, procyanidins (B2, B5, and C1), steroids (β-sitosterol), and triterpenoids (α-amyrin, pomolic, tormentic and ursolic acids) were selected as chemical markers for the quality control of the leaves. It is necessary to establish comprehensive standards for guaranteeing quality, safety and efficacy of herbal drugs. The selection of adequate chemical markers for quality control purposes requires a good knowledge about the chemical composition of medicinal plants and their associated biological properties. To the best of our knowledge this review article is the first to address the identification and quantitative determination of the chemical markers for the genus Cecropia.

Typing clinical and animal environment Aspergillus fumigatus gliotoxin producer strains isolated from Brazil by PCR-RFLP markers.

Science.gov (United States)

Soleiro, C A; Pena, G A; Cavaglieri, L R; Coelho, I; Keller, L M; Dalcero, A M; Rosa, C A R

2013-12-01

Aspergillus fumigatus, a well-known human and animal pathogen causing aspergillosis, has been historically identified by morphological and microscopic features. However, recent studies have shown that species identification on the basis of morphology alone is problematic. The aim of this work was to confirm the taxonomic state at specie level of a set of clinical (human and animal) and animal environment A. fumigatus strains identified by morphological criteria applying a PCR-RFLP assay by an in silico and in situ analysis with three restriction enzymes. The A. fumigatus gliotoxin-producing ability was also determined. Previous to the in situ PCR-RFLP analysis, an in silico assay with BccI, MspI and Sau3AI restriction enzymes was carried out. After that, these enzymes were used for in situ assay. All A. fumigatus strains isolated from corn silage, human aspergillosis and bovine mastitis and high per cent of the strains isolated from cereals, animal feedstuff and sorghum silage were able to produce high gliotoxin levels. Also, all these strains identified by morphological criteria as A. fumigatus, regardless of its isolation source, had band patterns according to A. fumigatus sensu stricto by PCR-RFLP markers. Aspergillus fumigatus is a well-known human and animal pathogen causing aspergillosis. In this study, clinical (human and animal) and animal environment strains were able to produce high gliotoxin levels and had band profiles according to A. fumigatus sensu stricto by PCR-RFLP markers. The results obtained here suggest that strains involved in human and animal aspergillosis could come from the animal environment in which A. fumigatus is frequently found. Its presence in animal environments could affect animal health and productivity; in addition, there are risks of contamination for rural workers during handling and storage of animal feedstuffs. © 2013 The Society for Applied Microbiology.

Health IT for Patient Safety and Improving the Safety of Health IT.

Science.gov (United States)

Magrabi, Farah; Ong, Mei-Sing; Coiera, Enrico

2016-01-01

Alongside their benefits health IT applications can pose new risks to patient safety. Problems with IT have been linked to many different types of clinical errors including prescribing and administration of medications; as well as wrong-patient, wrong-site errors, and delays in procedures. There is also growing concern about the risks of data breach and cyber-security. IT-related clinical errors have their origins in processes undertaken to design, build, implement and use software systems in a broader sociotechnical context. Safety can be improved with greater standardization of clinical software and by improving the quality of processes at different points in the technology life cycle, spanning design, build, implementation and use in clinical settings. Oversight processes can be set up at a regional or national level to ensure that clinical software systems meet specific standards. Certification and regulation are two mechanisms to improve oversight. In the absence of clear standards, guidelines are useful to promote safe design and implementation practices. Processes to identify and mitigate hazards can be formalised via a safety management system. Minimizing new patient safety risks is critical to realizing the benefits of IT.

A protein-based set of reference markers for liver tissues and hepatocellular carcinoma

International Nuclear Information System (INIS)

Sun, Stella; Yi, Xin; Poon, Ronnie TP; Yeung, Chun; Day, Philip JR; Luk, John M

2009-01-01

During the last decade, investigations have focused on revealing genes or proteins that are involved in HCC carcinogenesis using either genetic or proteomic techniques. However, these studies are overshadowed by a lack of good internal reference standards. The need to identify 'housekeeping' markers, whose expression is stable in various experimental and clinical conditions, is therefore of the utmost clinical relevance in quantitative studies. This is the first study employed 2-DE analysis to screen for potential reference markers and aims to correlate the abundance of these proteins with their level of transcript expression. A Chinese cohort of 224 liver tissues samples (105 cancerous, 103 non-tumourous cirrhotic, and 16 normal) was profiled using 2-DE analysis. Expression of the potential reference markers was confirmed by western blot, immunohistochemistry and real-time quantitative PCR. geNorm algorithm was employed for gene stability measure of the identified reference markers. The expression levels of three protein markers beta-actin (ACTB), heat shock protein 60 (HSP60), and protein disulphide isomerase (PDI) were found to be stable using p-values (p > 0.99) as a ranking tool in all 224 human liver tissues examined by 2-DE analysis. Of high importance, ACTB and HSP 60 were successfully validated at both protein and mRNA levels in human hepatic tissues by western blot, immunohistochemistry and real-time quantitative PCR. In addition, no significant correlation of these markers with any clinicopathological features of HCC and cirrhosis was found. Gene stability measure of these two markers with other conventionally applied housekeeping genes was assessed by the geNorm algorithm, which ranked ACTB and HSP60 as the most stable genes among this cohort of clinical samples. Our findings identified 2 reference markers that exhibited stable expression across human liver tissues with different conditions thus should be regarded as reliable reference

Identification and validation of multiple cell surface markers of clinical-grade adipose-derived mesenchymal stromal cells as novel release criteria for good manufacturing practice-compliant production

NARCIS (Netherlands)

Camilleri, Emily T.; Gustafson, Michael P.; Dudakovic, Amel; Riester, Scott M.; Garces, Catalina Galeano; Paradise, Christopher R.; Takai, Hideki; Karperien, Marcel; Cool, Simon; Sampen, Hee Jeong Im; Larson, A. Noelle; Qu, Wenchun; Smith, Jay; Dietz, Allan B.; van Wijnen, Andre J.

2016-01-01

Background: Clinical translation of mesenchymal stromal cells (MSCs) necessitates basic characterization of the cell product since variability in biological source and processing of MSCs may impact therapeutic outcomes. Although expression of classical cell surface markers (e.g., CD90, CD73, CD105,

[Preliminary results of an open-label observational study evaluating the efficacy and safety of Prolia used in women with postmenopausal osteoporosis].

Science.gov (United States)

Ershova, O B; Lesniak, O M; Belova, K Iu; Nazarova, A V; Manovitskaia, A V; Musaeva, T M; Musraev, R M; Nurlygaianov, R Z; Rozhinskaia, L Ia; Skripnikova, I A; Toroptsova, N V

2014-01-01

To evaluate the efficacy and safety of Denosumab (Prolia), a first-line osteoporosis (OP) medication that is a fully human monoclonal antibody to the receptor activator of nuclear factor xB ligand (RANKL), within an open-label observational study. Patients aged 50 years or older with postmenopausal OP, who were treated with Prolia in clinical practice, were examined. The concentrations of the bone resorption (BR) marker of C-terminal telopeptide and other laboratory indicators (total serum calcium, total alkaline phosphatase, and creatinine) were measured following 3 months. Adverse drug reactions were recorded. Three months after initiation of the investigation, there was a significant decrease in the BR marker C-terminal telopeptide (by 89%; p<0.0001). There were rare adverse reactions: hypocalcemia in 3 (5.9%) patients, arthralgias in 2 (3.9%), and eczema in 1 (1.9%). There were neither serious adverse events nor study withdrawal cases. The preliminary results of the open-label study of Prolia in postmenopausal OP suggest that the significantly lower BR activity determines the efficacy of this drug and its high safety.

ASSESSMENT OF RELATED ANAMNESTIC AND CLINICAL FACTORS ON EFFICACY AND SAFETY OF ANTI-HELICOBACTER PYLORI THERAPY

Directory of Open Access Journals (Sweden)

D. N. Andreev

2016-01-01

Full Text Available The article presents the results of a prospective clinical study in which 100 patients with H. pylori-associated peptic ulcer disease of stomach/duodenum were examined. The aim of the study was to assess the effect of concomitant anamnestic and clinical factors on the efficacy and safety of eradication therapy (ET. Type 2 diabetes mellitus is a factor that significantly reduces the efficiency of ET with OR 0.21 (95% CI 0,06-0,69, p = 0,0102. Using a macrolide antibiotics prior to ET during the previous 12 months is associated with a reduction in the effectiveness of H. pylori eradication with OR 0.27 (95% CI 0,08-0,90, p = 0,0342. Despite the lack of statistical significance observed negative effect on the efficiency of ET factors such as smoking and increased BMI. Smoking, female gender, age over 50 years and the presence of type 2 diabetes mellitus had no significant impact on the safety profile of ET. 

Clinical relevance of nine transcriptional molecular markers for the diagnosis of head and neck squamous cell carcinoma in tissue and saliva rinse

International Nuclear Information System (INIS)

Lallemant, Benjamin; Hollande, Frédéric; Lallemant, Jean-Gabriel; Lumbroso, Serge; Brouillet, Jean-Paul; Evrard, Alexandre; Combescure, Christophe; Chapuis, Heliette; Chambon, Guillaume; Raynal, Caroline; Reynaud, Christophe; Sabra, Omar; Joubert, Dominique

2009-01-01

Analysis of 23 published transcriptome studies allowed us to identify nine genes displaying frequent alterations in HNSCC (FN1, MMP1, PLAU, SPARC, IL1RN, KRT4, KRT13, MAL, and TGM3). We aimed to independently confirm these dysregulations and to identify potential relationships with clinical data for diagnostic, staging and prognostic purposes either at the tissue level or in saliva rinse. For a period of two years, we systematically collected tumor tissue, normal matched mucosa and saliva of patients diagnosed with primary untreated HNSCC. Expression levels of the nine genes of interest were measured by RT-qPCR in tumor and healthy matched mucosa from 46 patients. MMP1 expression level was measured by RT-qPCR in the salivary rinse of 51 HNSCC patients and 18 control cases. Dysregulation of the nine genes was confirmed by the Wilcoxon test. IL1RN, MAL and MMP1 were the most efficient diagnostic markers of HNSCC, with ROC AUC > 0.95 and both sensitivity and specificity above 91%. No clinically relevant correlation was found between gene expression level in tumor and T stage, N stage, tumor grade, global survival or disease-free survival. Our preliminary results suggests that with 100% specificity, MMP1 detection in saliva rinse is potentially useful for non invasive diagnosis of HNSCC of the oral cavity or oropharynx, but technical improvement is needed since sensitivity was only 20%. IL1RN, MAL and MMP1 are prospective tumor diagnostic markers for HNSCC. MMP1 overexpression is the most promising marker, and its detection could help identify tumor cells in tissue or saliva

Predicting refeeding hypophosphataemia: insulin growth factor 1 (IGF-1) as a diagnostic biochemical marker for clinical practice.

Science.gov (United States)

Goyale, Atul; Ashley, Sarah L; Taylor, David R; Elnenaei, Manal O; Alaghband-Zadeh, Jamshid; Sherwood, Roy A; le Roux, Carel W; Vincent, Royce P

2015-01-01

Refeeding syndrome (RS) is a potentially fatal condition that can occur following the re-introduction of nutrition after a period of starvation. Hypophosphataemia following the reintroduction of nutrition is often the only reliable biochemical marker of RS. Refeeding index (RI) generated from baseline insulin-like growth factor-1 (IGF-1) and leptin has been proposed as a useful biochemical marker for the identification of patients at risk of developing refeeding hypophosphataemia (RH). A prospective study included 52 patients referred for parenteral nutrition (PN). The sensitivity and specificity of IGF-1 measured using a sensitive assay was compared to the RI in predicting the development of RH (a ≥ 30% drop in PO4 during the first 36-h of PN administration). Leptin and IGF-1 were analysed on baseline samples using a quantitative enzyme-linked immunoassay. Daily blood samples were collected from all patients for routine biochemistry for the full duration of PN administration. High sensitivity IGF-1 measurement alone was comparable with the RI, using receiver-operating characteristic (ROC) curve analysis, with areas under the curve being 0.79 and 0.80, respectively, and superior to leptin alone (0.72) for predicting ≥ 30% drop in PO4. The cut-off value for IGF-1 that gave best sensitivity (91% [95% CI 75-98%]) and specificity (65% [95% CI 41-85%]) was 63.7 µg/L, with a likelihood ratio of 2.59. Baseline IGF-1 is an objective, sensitive and specific biochemical marker in identifying patients who are at high risk of developing RH prior to PN administration and therefore may have a role in clinical practice. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Improvement in Interobserver Accuracy in Delineation of the Lumpectomy Cavity Using Fiducial Markers

International Nuclear Information System (INIS)

Shaikh, Talha; Chen Ting; Khan, Atif; Yue, Ning J.; Kearney, Thomas; Cohler, Alan; Haffty, Bruce G.; Goyal, Sharad

2010-01-01

Purpose: To determine, whether the presence of gold fiducial markers would improve the inter- and intraphysician accuracy in the delineation of the surgical cavity compared with a matched group of patients who did not receive gold fiducial markers in the setting of accelerated partial-breast irradiation (APBI). Methods and Materials: Planning CT images of 22 lumpectomy cavities were reviewed in a cohort of 22 patients; 11 patients received four to six gold fiducial markers placed at the time of surgery. Three physicians categorized the seroma cavity according to cavity visualization score criteria and delineated each of the 22 seroma cavities and the clinical target volume. Distance between centers of mass, percentage overlap, and average surface distance for all patients were assessed. Results: The mean seroma volume was 36.9 cm 3 and 34.2 cm 3 for fiducial patients and non-fiducial patients, respectively (p = ns). Fiducial markers improved the mean cavity visualization score, to 3.6 ± 1.0 from 2.5 ± 1.3 (p < 0.05). The mean distance between centers of mass, average surface distance, and percentage overlap for the seroma and clinical target volume were significantly improved in the fiducial marker patients as compared with the non-fiducial marker patients (p < 0.001). Conclusions: The placement of gold fiducial markers placed at the time of lumpectomy improves interphysician identification and delineation of the seroma cavity and clinical target volume. This has implications in radiotherapy treatment planning for accelerated partial-breast irradiation and for boost after whole-breast irradiation.

Safety evaluation of saffron stigma (Crocus sativus L. aqueous extract and crocin in patients with schizophrenia

Directory of Open Access Journals (Sweden)

Bentolhoda Mousavi

2015-08-01

Full Text Available Objectives: Saffron is the stigma of Crocus sativus L., which has the potentials to play a role in the treatment of many diseases. Although many researches are now going on this precious spice, there are few data on saffron safety in human, especially in patients with chronic mental illnesses. This study aimed to evaluate the short-term safety and tolerability of both saffron and crocin (its major constituent in adult patients with schizophrenia. Materials and Methods: The capsules of saffron aqueous extract (SAE and crocin were used to evaluate short-term safety and tolerability in patients with schizophrenia. A double-blind, placebo-controlled study was performed on patients with schizophrenia. The patients were all male and were divided into three 22-patient groups. While receiving their normal treatment, they also received a 12 week treatment with SAE (15 mg twice daily, crocin (15 mg twice daily or placebo. Results: A total of 61 patients completed the trial; none of them reported a serious side effect. WBC count increased significantly in patients receiving saffron aqua extract (SAE, but it was within the normal range and had no clinical significance. Other hematologic components, markers of thyroid, liver and kidney or inflammation markers had no statistically significant difference among the groups. Conclusions: This study showed that SAE and crocin in doses of 15 mg twice daily were safely tolerated in patients with schizophrenia.

Secondhand Smoke Exposure and Preclinical Markers of Cardiovascular Risk in Toddlers.

Science.gov (United States)

Groner, Judith A; Huang, Hong; Joshi, Mandar S; Eastman, Nicholas; Nicholson, Lisa; Bauer, John Anthony

2017-10-01

To investigate relationships between secondhand smoke exposure in young children and several preclinical markers of cardiovascular risk that have been established as relevant to adult populations. There were 139 children, 2-5 years of age, enrolled in a cross-sectional study. Secondhand smoke exposure was objectively determined by hair nicotine level; a comprehensive panel of clinical markers (morning blood pressure, fasting glucose and insulin, lipid profiles, inflammation) and research markers (markers of oxidation, endothelial stress, and endothelial repair) of cardiovascular risk status were assessed. Univariate and multivariate linear regression were used to evaluate relationships between secondhand smoke exposure and cardiovascular risk markers. Hair nicotine levels were correlated directly with blood pressure and serum C-reactive protein, and inversely correlated with serum high-density lipoprotein cholesterol and endothelial cell progenitor cell prevalence. In multivariate analyses, these relationships remained when controlled for age, sex, body mass index z-score, maternal education, and method of payment. Additionally, in multivariate analyses, hair nicotine level was significantly negatively correlated with total antioxidant capacity. These results support the view that secondhand smoke exposure in the very young has a detectable relationship with several markers of cardiovascular risk, long before the emergence of clinical disease. Further studies to define mechanisms and strategies to prevent and mitigate these risks early in life are warranted. Copyright © 2017 Elsevier Inc. All rights reserved.

Impact of a Simulated Clinical Day With Peer Coaching and Deliberate Practice: Promoting a Culture of Safety.

Science.gov (United States)

Badowski, Donna M; Oosterhouse, Kimberly J

Nursing education is challenged to shift from task-based proficiencies to higher level competencies with patient safety as a priority. Using a quasi-experimental pretest/posttest design, a simulation-based, peer-coached, deliberate practice clinical substitution was implemented to compare nursing students' knowledge, skills, and attitudes for promoting safety. Our findings demonstrated improved knowledge and skill acquisition in the intervention and control groups. The former trended toward improved team communication attitudes and enteral medication skill performance. Additional research with larger samples is needed to further investigate this innovative strategy.

Workplace Re-organization and Changes in Physiological Stress Markers

DEFF Research Database (Denmark)

Carlsson, Rikke Hinge; Hansen, Åse Marie; Kristiansen, Jesper

2014-01-01

The aim of this study was to investigate changes in physiological stress markers as a consequence of workplace reorganization. Moreover, we aimed to investigate changes in the psychosocial work environment (job strain, effortreward imbalance (ERI), in psychological distress (stress symptoms......, perceived stress) and the mediating effect of these factors on changes in physiological stress markers. We used data from a longitudinal study that studied the health consequences of a major reorganization of non-state public offices executed in Denmark on 1 January 2007. Collection of clinical...... and questionnaire data was in 2006 and 2008, and in this sub-study we included 359 participants. To reflect stress reactions of the autonomic nervous system, the endocrine system and the immune system, we included 13 physiological markers. We observed significant change in several physiological stress markers...

Myostatin as a Marker for Doxorubicin Induced Cardiac Damage.

Science.gov (United States)

Kesik, Vural; Honca, Tevfik; Gulgun, Mustafa; Uysal, Bulent; Kurt, Yasemin Gulcan; Cayci, Tuncer; Babacan, Oguzhan; Gocgeldi, Ercan; Korkmazer, Nadir

2016-01-01

Doxorubicin (DXR) is an effective chemotherapeutic agent but causes severe cardiac failure over known doses. Thus, early detection and prevention of cardiac damage is important. Various markers have been tested for early detection of cardiac damage. Myostatin is a protein produced in skeletal muscle cells inhibits muscle differentiation and growth during myogenesis. We evaluated the role of myostatin as a marker for showing DXR induced cardiac damage and compared with well known cardiac markers like NT-proBNP, hs-TnT and CK in a rat model of chronic DXR cardiotoxicity. Myostatin, NT-proBNP, and hs-TnT but not CK rose significantly during DXR treatment. Myostatin can be used as an early marker of DXR induced cardiotoxicity. © 2016 by the Association of Clinical Scientists, Inc.

'Impulsive compulsivity' in obsessive-compulsive disorder: a phenotypic marker of patients with poor clinical outcome.

Science.gov (United States)

Kashyap, Himani; Fontenelle, Leonardo F; Miguel, Euripedes C; Ferrão, Ygor A; Torres, Albina R; Shavitt, Roseli G; Ferreira-Garcia, Rafael; do Rosário, Maria C; Yücel, Murat

2012-09-01

Although traditionally obsessive-compulsive disorder (OCD) and impulse control disorders (ICD) have represented opposing ends of a continuum, recent research has demonstrated a frequent co-occurrence of impulsive and compulsive behaviours, which may contribute to a worse clinical picture of some psychiatric disorders. We hypothesize that individuals with 'impulsive' OCD as characterized by poor insight, low resistance, and reduced control towards their compulsions will have a deteriorative course, greater severity of hoarding and/or symmetry/ordering symptoms, and comorbid ICD and/or substance use disorders (SUD). The sample consisted of 869 individuals with a minimum score of 16 on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Of these, 65 had poor insight, low resistance, and reduced control towards compulsions ('poor IRC') and 444 had preserved insight, greater resistance and better control over compulsions ('good IRC'). These two groups were compared on a number of clinical and demographic variables. Individuals with poor IRC were significantly more likely to have a deteriorative course (p disorder (p = 0.026), trichotillomania (p = 0.014) and compulsive buying (p = 0.040). Regression analysis revealed that duration of obsessions (p = 0.037) and hoarding severity (p = 0.005) were significant predictors of poor IRC. In the absence of specific measures for impulsivity in OCD, the study highlights the utility of simple measures such as insight, resistance and control over compulsions as a phenotypic marker of a subgroup of OCD with impulsive features demonstrating poor clinical outcome. Copyright © 2012 Elsevier Ltd. All rights reserved.

Practice-based evidence: profiling the safety of cilostazol by text-mining of clinical notes.

Science.gov (United States)

Leeper, Nicholas J; Bauer-Mehren, Anna; Iyer, Srinivasan V; Lependu, Paea; Olson, Cliff; Shah, Nigam H

2013-01-01

Peripheral arterial disease (PAD) is a growing problem with few available therapies. Cilostazol is the only FDA-approved medication with a class I indication for intermittent claudication, but carries a black box warning due to concerns for increased cardiovascular mortality. To assess the validity of this black box warning, we employed a novel text-analytics pipeline to quantify the adverse events associated with Cilostazol use in a clinical setting, including patients with congestive heart failure (CHF). We analyzed the electronic medical records of 1.8 million subjects from the Stanford clinical data warehouse spanning 18 years using a novel text-mining/statistical analytics pipeline. We identified 232 PAD patients taking Cilostazol and created a control group of 1,160 PAD patients not taking this drug using 1:5 propensity-score matching. Over a mean follow up of 4.2 years, we observed no association between Cilostazol use and any major adverse cardiovascular event including stroke (OR = 1.13, CI [0.82, 1.55]), myocardial infarction (OR = 1.00, CI [0.71, 1.39]), or death (OR = 0.86, CI [0.63, 1.18]). Cilostazol was not associated with an increase in any arrhythmic complication. We also identified a subset of CHF patients who were prescribed Cilostazol despite its black box warning, and found that it did not increase mortality in this high-risk group of patients. This proof of principle study shows the potential of text-analytics to mine clinical data warehouses to uncover 'natural experiments' such as the use of Cilostazol in CHF patients. We envision this method will have broad applications for examining difficult to test clinical hypotheses and to aid in post-marketing drug safety surveillance. Moreover, our observations argue for a prospective study to examine the validity of a drug safety warning that may be unnecessarily limiting the use of an efficacious therapy.

Practice-based evidence: profiling the safety of cilostazol by text-mining of clinical notes.

Directory of Open Access Journals (Sweden)

Nicholas J Leeper

Full Text Available Peripheral arterial disease (PAD is a growing problem with few available therapies. Cilostazol is the only FDA-approved medication with a class I indication for intermittent claudication, but carries a black box warning due to concerns for increased cardiovascular mortality. To assess the validity of this black box warning, we employed a novel text-analytics pipeline to quantify the adverse events associated with Cilostazol use in a clinical setting, including patients with congestive heart failure (CHF.We analyzed the electronic medical records of 1.8 million subjects from the Stanford clinical data warehouse spanning 18 years using a novel text-mining/statistical analytics pipeline. We identified 232 PAD patients taking Cilostazol and created a control group of 1,160 PAD patients not taking this drug using 1:5 propensity-score matching. Over a mean follow up of 4.2 years, we observed no association between Cilostazol use and any major adverse cardiovascular event including stroke (OR = 1.13, CI [0.82, 1.55], myocardial infarction (OR = 1.00, CI [0.71, 1.39], or death (OR = 0.86, CI [0.63, 1.18]. Cilostazol was not associated with an increase in any arrhythmic complication. We also identified a subset of CHF patients who were prescribed Cilostazol despite its black box warning, and found that it did not increase mortality in this high-risk group of patients.This proof of principle study shows the potential of text-analytics to mine clinical data warehouses to uncover 'natural experiments' such as the use of Cilostazol in CHF patients. We envision this method will have broad applications for examining difficult to test clinical hypotheses and to aid in post-marketing drug safety surveillance. Moreover, our observations argue for a prospective study to examine the validity of a drug safety warning that may be unnecessarily limiting the use of an efficacious therapy.

Time since onset of disease and individual clinical markers associate with transcriptional changes in uncomplicated dengue.

Directory of Open Access Journals (Sweden)

Cornelia A M van de Weg

2015-03-01

Full Text Available BACKGROUND: Dengue virus (DENV infection causes viral haemorrhagic fever that is characterized by extensive activation of the immune system. The aim of this study is to investigate the kinetics of the transcriptome signature changes during the course of disease and the association of genes in these signatures with clinical parameters. METHODOLOGY/PRINCIPLE FINDINGS: Sequential whole blood samples from DENV infected patients in Jakarta were profiled using affymetrix microarrays, which were analysed using principal component analysis, limma, gene set analysis, and weighted gene co-expression network analysis. We show that time since onset of disease, but not diagnosis, has a large impact on the blood transcriptome of patients with non-severe dengue. Clinical diagnosis (according to the WHO classification does not associate with differential gene expression. Network analysis however, indicated that the clinical markers platelet count, fibrinogen, albumin, IV fluid distributed per day and liver enzymes SGOT and SGPT strongly correlate with gene modules that are enriched for genes involved in the immune response. Overall, we see a shift in the transcriptome from immunity and inflammation to repair and recovery during the course of a DENV infection. CONCLUSIONS/SIGNIFICANCE: Time since onset of disease associates with the shift in transcriptome signatures from immunity and inflammation to cell cycle and repair mechanisms in patients with non-severe dengue. The strong association of time with blood transcriptome changes hampers both the discovery as well as the potential application of biomarkers in dengue. However, we identified gene expression modules that associate with key clinical parameters of dengue that reflect the systemic activity of disease during the course of infection. The expression level of these gene modules may support earlier detection of disease progression as well as clinical management of dengue.

NABIC marker database: A molecular markers information network of agricultural crops.

Science.gov (United States)

Kim, Chang-Kug; Seol, Young-Joo; Lee, Dong-Jun; Jeong, In-Seon; Yoon, Ung-Han; Lee, Gang-Seob; Hahn, Jang-Ho; Park, Dong-Suk

2013-01-01

In 2013, National Agricultural Biotechnology Information Center (NABIC) reconstructs a molecular marker database for useful genetic resources. The web-based marker database consists of three major functional categories: map viewer, RSN marker and gene annotation. It provides 7250 marker locations, 3301 RSN marker property, 3280 molecular marker annotation information in agricultural plants. The individual molecular marker provides information such as marker name, expressed sequence tag number, gene definition and general marker information. This updated marker-based database provides useful information through a user-friendly web interface that assisted in tracing any new structures of the chromosomes and gene positional functions using specific molecular markers. The database is available for free at http://nabic.rda.go.kr/gere/rice/molecularMarkers/

Translating self-persuasion into an adolescent HPV vaccine promotion intervention for parents attending safety-net clinics.

Science.gov (United States)

Baldwin, Austin S; Denman, Deanna C; Sala, Margarita; Marks, Emily G; Shay, L Aubree; Fuller, Sobha; Persaud, Donna; Lee, Simon Craddock; Skinner, Celette Sugg; Wiebe, Deborah J; Tiro, Jasmin A

2017-04-01

Self-persuasion is an effective behavior change strategy, but has not been translated for low-income, less educated, uninsured populations attending safety-net clinics or to promote human papillomavirus (HPV) vaccination. We developed a tablet-based application (in English and Spanish) to elicit parental self-persuasion for adolescent HPV vaccination and evaluated its feasibility in a safety-net population. Parents (N=45) of age-eligible adolescents used the self-persuasion application. Then, during cognitive interviews, staff gathered quantitative and qualitative feedback on the self-persuasion tasks including parental decision stage. The self-persuasion tasks were rated as easy to complete and helpful. We identified six question prompts rated as uniformly helpful, not difficult to answer, and generated non-redundant responses from participants. Among the 33 parents with unvaccinated adolescents, 27 (81.8%) reported deciding to get their adolescent vaccinated after completing the self-persuasion tasks. The self-persuasion application was feasible and resulted in a change in parents' decision stage. Future studies can now test the efficacy of the tablet-based application on HPV vaccination. The self-persuasion application facilitates verbalization of reasons for HPV vaccination in low literacy, safety-net settings. This self-administered application has the potential to be more easily incorporated into clinical practice than other patient education approaches. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Biomolecular Markers in Cancer of the Tongue

Directory of Open Access Journals (Sweden)

Daris Ferrari

2009-01-01

Full Text Available The incidence of tongue cancer is increasing worldwide, and its aggressiveness remains high regardless of treatment. Genetic changes and the expression of abnormal proteins have been frequently reported in the case of head and neck cancers, but the little information that has been published concerning tongue tumours is often contradictory. This review will concentrate on the immunohistochemical expression of biomolecular markers and their relationships with clinical behaviour and prognosis. Most of these proteins are associated with nodal stage, tumour progression and metastases, but there is still controversy concerning their impact on disease-free and overall survival, and treatment response. More extensive clinical studies are needed to identify the patterns of molecular alterations and the most reliable predictors in order to develop tailored anti-tumour strategies based on the targeting of hypoxia markers, vascular and lymphangiogenic factors, epidermal growth factor receptors, intracytoplasmatic signalling and apoptosis.

Clinical Trials

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Full Text Available ... needed. For safety purposes, clinical trials start with small groups of patients to find out whether a ... phase I clinical trials test new treatments in small groups of people for safety and side effects. ...

The predictive effect of inflammatory markers and lipid accumulation product index on clinical symptoms associated with polycystic ovary syndrome in nonobese adolescents and younger aged women.

Science.gov (United States)

Tola, Esra Nur; Yalcin, Serenat Eris; Dugan, Nadiye

2017-07-01

The aim of our study is to analyse the inflammatory markers and lipid accumulation product (LAP) index in nonobese adolescents and younger aged women with polycystic ovary syndrome (PCOS) compared with age and body mass index (BMI)-matched healthy controls and to determine whether the investigated parameters are potential markers for the etiopathogenesis of PCOS. We also aim to determine whether these inflammatory markers are predictive for developing some clinical implications, such as cardiovascular disease (CVD) and insulin resistance (IR), associated with PCOS. A total of 34 adolescents and younger aged females with PCOS, and 33 age and BMI-matched healthy controls were recruited for our study. All participants were nonobese (BMIpredictive effect of investigated inflammatory markers and LAP index on CVD risk among PCOS patients after adjustment for abdominal obesity. We also found a positive predictive effect of WBC and a negative predictive effect of lymphocytes on IR in PCOS patients after adjustment for abdominal obesity. We did not find any predictor effect of NEO on IR, but it was a positive predictive marker for an elevated HOMA-IR index. Elevated NEO, CRP levels and LAP index could have potential roles in the etiopathogenesis of PCOS in nonobese adolescents and younger aged females,NEO could be a predictive marker for elevated HOMA-IR index, and WBC and lymphocytes could be predictive for the development of IR among nonobese adolescents and younger aged females with PCOS. Copyright © 2017 Elsevier B.V. All rights reserved.

Research advances in tumor markers for the diagnosis of hepatocellular carcinoma

Directory of Open Access Journals (Sweden)

YANG Guimin

2018-01-01

Full Text Available Hepatocellular carcinoma (HCC is a malignant tumor with a high fatality rate in the world, and alpha-fetoprotein (AFP is the most commonly used tumor marker for HCC diagnosis. However, AFP does not have a satisfactory sensitivity or specificity and may lead to missed diagnosis when the tumor is small in the early stage of HCC. This article summarizes the clinical value of new tumor markers in the diagnosis, treatment monitoring, and prognosis judgment of HCC and analyzes the future prospects of the measurement of tumor markers for HCC. It is pointed out that combined determination of several tumor markers helps to improve the sensitivity and specificity of HCC diagnosis, and the screening and optimization of combined determination of tumor markers, noninvasive and efficient tumor markers, and individualized treatment are research hotspots in future.

Hidden marker position estimation during sit-to-stand with walker.

Science.gov (United States)

Yoon, Sang Ho; Jun, Hong Gul; Dan, Byung Ju; Jo, Byeong Rim; Min, Byung Hoon

2012-01-01

Motion capture analysis of sit-to-stand task with assistive device is hard to achieve due to obstruction on reflective makers. Previously developed robotic system, Smart Mobile Walker, is used as an assistive device to perform motion capture analysis in sit-to-stand task. All lower limb markers except hip markers are invisible through whole session. The link-segment and regression method is applied to estimate the marker position during sit-to-stand. Applying a new method, the lost marker positions are restored and the biomechanical evaluation of the sit-to-stand movement with a Smart Mobile Walker could be carried out. The accuracy of the marker position estimation is verified with normal sit-to-stand data from more than 30 clinical trials. Moreover, further research on improving the link segment and regression method is addressed.

Prognostic factors in non-muscle-invasive bladder tumors - I. Clinical prognostic factors: A review of the experience of the EORTC genito-urinary group - II. Biologic prognostic markers

NARCIS (Netherlands)

Kurth, Karl-Heinz; Sylvester, Richard J.

2007-01-01

Objectives: To summarize the most important clinical prognostic factors of non-muscle-invasive bladder cancer, as assessed by the European organization for Research and Treatment of Cancer (EORTC) Genito-Urinary Group, to present biologic markers involved in urothelial cell carcinoma, and to address

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

Science.gov (United States)

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

Use of the false discovery rate for evaluating clinical safety data.

Science.gov (United States)

Mehrotra, Devan V; Heyse, Joseph F

2004-06-01

Clinical adverse experience (AE) data are routinely evaluated using between group P values for every AE encountered within each of several body systems. If the P values are reported and interpreted without multiplicity considerations, there is a potential for an excess of false positive findings. Procedures based on confidence interval estimates of treatment effects have the same potential for false positive findings as P value methods. Excess false positive findings can needlessly complicate the safety profile of a safe drug or vaccine. Accordingly, we propose a novel method for addressing multiplicity in the evaluation of adverse experience data arising in clinical trial settings. The method involves a two-step application of adjusted P values based on the Benjamini and Hochberg false discovery rate (FDR). Data from three moderate to large vaccine trials are used to illustrate our proposed 'Double FDR' approach, and to reinforce the potential impact of failing to account for multiplicity. This work was in collaboration with the late Professor John W. Tukey who coined the term 'Double FDR'.

Clinical Significance on the Serologic Profiles of HBV Markers in Various Liver Diseases

Energy Technology Data Exchange (ETDEWEB)

Yu, Byung Hee; Lee, Choong Kyu; Kim, Jong Hwa; Kim, Kwang Ill; Lee, Chong Suk [National Medical Canter, Seoul (Korea, Republic of)

1983-09-15

By radioimmunoassay, serologic markers of Hepatitis B Virus were studied in 44 patients with acute viral hepatitis, 10 patients with chronic persistent hepatitis, 10 patients with chronic active hepatitis, 44 patients with liver cirrhosis and 25 patients with primary hepatocellular carcinoma. The results were follows: 1) HBsAg was present in 77.2% of AVH, 40% of CPH, 80% of CAH, 55.1% of LC and 68% of PHC. In this HBsAg positive groups, all but one in liver cirrhosis had Anti-HBc. 2) Anti-HBs was most commonly detected in CPH and accompanied by Anti-HBc except one case in AVH. 3) Anti-HBc was the only marker detected in 11.4% of AVH, 20% of CPH, 20% of CAH, 16.3% of LC and 8% of PHC. 4) HBeAg was most commonly found in HBsAg-positive CPH but Anti-HBe was most frequently detected in PHC. 5) The absence of HBV markers was noted in 2.3% of AVH, 10% of CPH, 8% of PHC except CAH and LC.

Safety and Efficacy of Catheter Direct Thrombolysis in Management of Acute Iliofemoral Deep Vein Thrombosis: A Systematic Review.

Science.gov (United States)

Elbasty, Ahmed; Metcalf, James

2017-12-01

Catheter direct thrombolysis (CDT) has been shown to be an effective treatment for deep venous thrombosis. The objective of the review is to improve safety and efficacy of the CDT by using ward based protocol, better able to predict complications and treatment outcome through monitoring of haemostatic parameters and clinical observation during thrombolysis procedure. MEDLINE, EMBASE, CENTRAL and Web of Science were searched for all articles on deep venous thrombosis, thrombolysis and correlations of clinical events (bleeding, successful thrombolysis) during thrombolysis with hemostatic parameters to March 2016. The risk of bias in included studies was assessed by Cochrane Collaboration's tool and Cochrane Risk of Bias Assessment Tool: for Non-Randomized Studies of Interventions. Twenty-four studies were included in the review and we found that improving safety and efficacy of CDT by using ward based protocol depending on eight factors; strict patient selection criteria, types of fibrinolytic drugs, mode of fibrinolytic drug injection, biochemical markers monitoring (fibrinogen, D-dimer, activated partial thromboplastin time, plasminogen activator inhibitor-1), timing of intervention, usage of intermittent pneumatic calf, ward monitoring and thrombolysis imaging assessment (intravascular ultrasound). These factors may help to improve safety and efficacy by reducing total thrombolytic drug dosage and at the same time ensure successful lysis. There is a marked lack of randomized controlled trials discussing the safety and efficacy of catheter direct thrombolysis. CDT can be performed safely and efficiently in clinical ward, providing that careful nursing, biochemical monitoring, proper selection and mode of infusion of fibrinolytic drugs, usage of Intermittent pneumatic calf and adequate thrombolysis imaging assessment are ensured.

75 FR 53701 - Clinical Studies of Safety and Effectiveness of Orphan Products Research Project Grant (R01...

Science.gov (United States)

2010-09-01

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0394] Clinical Studies of Safety and Effectiveness of Orphan Products Research Project Grant (R01); Correction AGENCY: Food and Drug Administration, HHS. ACTION: Notice; correction. SUMMARY: The Food and Drug...

Vitamin E supplementation in canine atopic dermatitis: improvement of clinical signs and effects on oxidative stress markers.

Science.gov (United States)

Plevnik Kapun, A; Salobir, J; Levart, A; Tavčar Kalcher, G; Nemec Svete, A; Kotnik, T

2014-12-06

Low levels of plasma vitamin E concentrations were found in canine atopic dermatitis (CAD). The present study was aimed at determining the effect of an eight-week vitamin E supplementation on clinical response (Canine Atopic Dermatitis Extent and Severity Index (CADESI-03) scores and pruritus intensity) in dogs with atopic dermatitis. Levels of oxidative stress markers (plasma malondialdehyde and total antioxidant capacity (TAC), blood glutathione peroxidase and erythrocyte superoxide dismutase, plasma and skin vitamin E concentrations) were also determined. Twenty-nine dogs with CAD were included in the study. Fourteen received vitamin E (8.1 IU/kg once daily, orally) and 15 received mineral oil as placebo (orally). All dogs were treated with antihistamine fexofenadine. Levels of oxidative stress markers (with the exception of skin vitamin E), CADESI-03 and pruritus intensity were determined at the beginning, then every two weeks. Skin vitamin E was determined at the beginning and at the end of the treatment. Significantly higher plasma levels of vitamin E and TAC were observed in the vitamin E group than in the placebo group. CADESI-03 scores determined throughout the treatment in the vitamin E group were significantly lower than in the placebo group. The findings of this study support the supplementation of vitamin E in dogs with atopic dermatitis. British Veterinary Association.

Safety, tolerability, and risks associated with first- and second-generation antipsychotics: a state-of-the-art clinical review

Science.gov (United States)

Solmi, Marco; Murru, Andrea; Pacchiarotti, Isabella; Undurraga, Juan; Veronese, Nicola; Fornaro, Michele; Stubbs, Brendon; Monaco, Francesco; Vieta, Eduard; Seeman, Mary V; Correll, Christoph U; Carvalho, André F

2017-01-01

Since the discovery of chlorpromazine (CPZ) in 1952, first-generation antipsychotics (FGAs) have revolutionized psychiatric care in terms of facilitating discharge from hospital and enabling large numbers of patients with severe mental illness (SMI) to be treated in the community. Second-generation antipsychotics (SGAs) ushered in a progressive shift from the paternalistic management of SMI symptoms to a patient-centered approach, which emphasized targets important to patients – psychosocial functioning, quality of life, and recovery. These drugs are no longer limited to specific Diagnostic and Statistical Manual of Mental Disorders (DSM) categories. Evidence indicates that SGAs show an improved safety and tolerability profile compared with FGAs. The incidence of treatment-emergent extrapyramidal side effects is lower, and there is less impairment of cognitive function and treatment-related negative symptoms. However, treatment with SGAs has been associated with a wide range of untoward effects, among which treatment-emergent weight gain and metabolic abnormalities are of notable concern. The present clinical review aims to summarize the safety and tolerability profile of selected FGAs and SGAs and to link treatment-related adverse effects to the pharmacodynamic profile of each drug. Evidence, predominantly derived from systematic reviews, meta-analyses, and clinical trials of the drugs amisulpride, aripiprazole, asenapine, brexpiprazole, cariprazine, clozapine, iloperidone, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, sertindole, ziprasidone, CPZ, haloperidol, loxapine, and perphenazine, is summarized. In addition, the safety and tolerability profiles of antipsychotics are discussed in the context of the “behavioral toxicity” conceptual framework, which considers the longitudinal course and the clinical and therapeutic consequences of treatment-emergent side effects. In SMI, SGAs with safer metabolic profiles should ideally be prescribed

Clinical safety of a polyvalent F(ab')2 equine antivenom in 223 African snake envenomations : a field trial in Cameroon

OpenAIRE

Chippaux, Jean-Philippe; Lang, J.; Amadi Eddine, S; Fagot, P.; Rage, V.; Peyrieux, J.C.; Le Mener, V.

1998-01-01

A large-scale clinical trial was conducted, according to World Health Organization Good Clinical Practice guidelines, in 7 centres in North Cameroon to determine the safety and efficacy of a polyvalent antivenom composed of purified F(ab')2. This study included 223 patients presenting clinically with an obvious snake bite, predominantly due to #Echis ocellatus$ (viper), the most abundant species in this savannah region. Clinical surveillance was maintained for 5 d in all patients and until th...

Part of tumor markers in the evaluation of tumor response to irradiation

International Nuclear Information System (INIS)

Deckers, C.; Desmedt, M.

1994-01-01

When present, the tumor markers reflect the clinical evolution of the malignant lesions. We present here their variations in relation to the antitumor treatment and demonstrate that the marker reflects quite well the tumor response and constitutes an additional monitoring for the clinician. (authors). 11 refs., 2 figs

Molecular markers: Implications for cytopathology and specimen collection.

Science.gov (United States)

VanderLaan, Paul A

2015-08-01

Cytologic specimens obtained through minimally invasive biopsy techniques are increasingly being used as principle diagnostic specimens for tumors arising in multiple sites. The number and scope of ancillary tests performed on these specimens have grown substantially over the past decade, including many molecular markers that not only can aid in formulating accurate and specific diagnoses but also can provide prognostic or therapeutic information to help direct clinical decisions. Thus, the cytopathologist needs to ensure that adequate material is collected and appropriately processed for the study of relevant molecular markers, many of which are specific to tumor site. This brief review covers considerations for effective cytologic specimen collection and processing to ensure diagnostic and testing success. In addition, a general overview is provided of molecular markers pertinent to tumors from a variety of sites. The recognition of these established and emerging molecular markers by cytopathologists is an important step toward realizing the promise of personalized medicine. © 2015 American Cancer Society.

Antibiotic Resistance Genetic Markers and Integrons in White Soft Cheese: Aspects of Clinical Resistome and Potentiality of Horizontal Gene Transfer.

Science.gov (United States)

de Paula, Ana Caroline L; Medeiros, Julliane D; de Azevedo, Analice C; de Assis Chagas, Jéssica M; da Silva, Vânia L; Diniz, Cláudio G

2018-02-19

Antibiotic resistance poses an important threat to global public health and has become a challenge to modern medicine. The occurrence of antibiotic-resistant bacteria in a broad range of foods has led to a growing concern about the impact that food may have as a reservoir of antibiotic resistance genes. Considering Minas Frescal Cheese (MFC)-a typical Brazilian white soft cheese-and its economic and cultural values, in this study, medically relevant antimicrobial-resistance genetic markers (AR genes) were screened, and the occurrence of integrons were evaluated in manufactured MFC using culture-independent approaches. Through a fingerprinting analysis, the tested MFCs were brand-clustered, indicating reproducibility along the production chain. A common core of resistance markers in all brands evaluated and related antimicrobials such as β-lactams, tetracyclines, quinolones, and sulfonamide was detected. Several other markers, including efflux pumps and aminoglycosides-resistance were distributed among brands. Class 1 and 2 integrons were observed, respectively, in 77% and 97% of the samples. The presence of AR genes is of special interest due to their clinical relevance. Taken together, the data may suggest that the production chain of MFC might contribute to the spread of putative drug-resistant bacteria, which could greatly impact human health. Furthermore, detection of class 1 and class 2 integrons in MFC has led to discussions about resistance gene spread in this traditional cheese, providing evidence of potential horizontal transfer of AR genes to human gut microbiota.

Antibiotic Resistance Genetic Markers and Integrons in White Soft Cheese: Aspects of Clinical Resistome and Potentiality of Horizontal Gene Transfer

Directory of Open Access Journals (Sweden)

Ana Caroline L. de Paula

2018-02-01

Full Text Available Antibiotic resistance poses an important threat to global public health and has become a challenge to modern medicine. The occurrence of antibiotic-resistant bacteria in a broad range of foods has led to a growing concern about the impact that food may have as a reservoir of antibiotic resistance genes. Considering Minas Frescal Cheese (MFC—a typical Brazilian white soft cheese—and its economic and cultural values, in this study, medically relevant antimicrobial-resistance genetic markers (AR genes were screened, and the occurrence of integrons were evaluated in manufactured MFC using culture-independent approaches. Through a fingerprinting analysis, the tested MFCs were brand-clustered, indicating reproducibility along the production chain. A common core of resistance markers in all brands evaluated and related antimicrobials such as β-lactams, tetracyclines, quinolones, and sulfonamide was detected. Several other markers, including efflux pumps and aminoglycosides-resistance were distributed among brands. Class 1 and 2 integrons were observed, respectively, in 77% and 97% of the samples. The presence of AR genes is of special interest due to their clinical relevance. Taken together, the data may suggest that the production chain of MFC might contribute to the spread of putative drug-resistant bacteria, which could greatly impact human health. Furthermore, detection of class 1 and class 2 integrons in MFC has led to discussions about resistance gene spread in this traditional cheese, providing evidence of potential horizontal transfer of AR genes to human gut microbiota.

Significance Of Immunohistochemical Markers In Diagnostics Of Urinary Bladder Cancer

Directory of Open Access Journals (Sweden)

A.V. Medvedeva

2009-12-01

Full Text Available On the basis of surgical and biopsy material 106 patients with diseases of urinary bladder have been under study. They received treatment at Scientific Research Institute of Fundamental and Clinical Uronephrology of Saratov State Medical University. 13 immunohistochemical markers have been evaluated: markers of proliferative activity - Ki-67, PCNA, p63, suppressor of tumor growth - p53, markers of apoptosis - Bcl-2, Bax, receptor of epidermal growth factors - EGFR, cytokeratin profile - (CK7, CK8, CK10/13, CK 17, CK18, CK19, as well as their diagnostic significance for identifying the urinary bladder cancer

Quality Markers in Cardiology. Main Markers to Measure Quality of Results (Outcomes) and Quality Measures Related to Better Results in Clinical Practice (Performance Metrics). INCARDIO (Indicadores de Calidad en Unidades Asistenciales del Área del Corazón): A SEC/SECTCV Consensus Position Paper.

Science.gov (United States)

López-Sendón, José; González-Juanatey, José Ramón; Pinto, Fausto; Cuenca Castillo, José; Badimón, Lina; Dalmau, Regina; González Torrecilla, Esteban; López-Mínguez, José Ramón; Maceira, Alicia M; Pascual-Figal, Domingo; Pomar Moya-Prats, José Luis; Sionis, Alessandro; Zamorano, José Luis

2015-11-01

Cardiology practice requires complex organization that impacts overall outcomes and may differ substantially among hospitals and communities. The aim of this consensus document is to define quality markers in cardiology, including markers to measure the quality of results (outcomes metrics) and quality measures related to better results in clinical practice (performance metrics). The document is mainly intended for the Spanish health care system and may serve as a basis for similar documents in other countries. Copyright © 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Overexpression of endothelin B receptor in glioblastoma: a prognostic marker and therapeutic target?

KAUST Repository

Vasaikar, Suhas

2018-02-06

BackgroundGlioblastoma (GBM) is the most common malignant brain tumor with median survival of 12-15 months. Owing to uncertainty in clinical outcome, additional prognostic marker(s) apart from existing markers are needed. Since overexpression of endothelin B receptor (ETBR) has been demonstrated in gliomas, we aimed to test whether ETBR is a useful prognostic marker in GBM and examine if the clinically available endothelin receptor antagonists (ERA) could be useful in the disease treatment.MethodsData from The Cancer Genome Atlas and the Gene Expression Omnibus database were analyzed to assess ETBR expression. For survival analysis, glioblastoma samples from 25 Swedish patients were immunostained for ETBR, and the findings were correlated with clinical history. The druggability of ETBR was assessed by protein-protein interaction network analysis. ERAs were analyzed for toxicity in in vitro assays with GBM and breast cancer cells.ResultsBy bioinformatics analysis, ETBR was found to be upregulated in glioblastoma patients, and its expression levels were correlated with reduced survival. ETBR interacts with key proteins involved in cancer pathogenesis, suggesting it as a druggable target. In vitro viability assays showed that ERAs may hold promise to treat glioblastoma and breast cancer.ConclusionsETBR is overexpressed in glioblastoma and other cancers and may be a prognostic marker in glioblastoma. ERAs may be useful for treating cancer patients.

Molecular markers in the epidemiology and diagnosis of coccidioidomycosis.

Science.gov (United States)

Duarte-Escalante, Esperanza; Frías-De-León, María Guadalupe; Zúñiga, Gerardo; Martínez-Herrera, Erick; Acosta-Altamirano, Gustavo; Reyes-Montes, María Del Rocío

2014-01-01

The prevalence of coccidioidomycosis in endemic areas has been observed to increase daily. To understand the causes of the spread of the disease and design strategies for fungal detection in clinical and environmental samples, scientists have resorted to molecular tools that allow fungal detection in a natural environment, reliable identification in clinical cases and the study of biological characteristics, such as reproductive and genetic structure, demographic history and diversification. We conducted a review of the most important molecular markers in the epidemiology of Coccidioides spp. and the diagnosis of coccidioidomycosis. A literature search was performed for scientific publications concerning the application of molecular tools for the epidemiology and diagnosis of coccidioidomycosis. The use of molecular markers in the epidemiological study and diagnosis of coccidioidomycosis has allowed for the typing of Coccidioides spp. isolates, improved understanding of their mode of reproduction, genetic variation and speciation and resulted in the development specific, rapid and sensitive strategies for detecting the fungus in environmental and clinical samples. Molecular markers have revealed genetic variability in Coccidioides spp. This finding influences changes in the epidemiology of coccidioidomycosis, such as the emergence of more virulent or antifungal resistant genotypes. Furthermore, the molecular markers currently used to identify Coccidioides immitis and Coccidioides posadasii are specific and sensitive. However, they must be validated to determine their application in diagnosis. This manuscript is part of the series of works presented at the "V International Workshop: Molecular genetic approaches to the study of human pathogenic fungi" (Oaxaca, Mexico, 2012). Copyright © 2013 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.

[Innovation in healthcare processes and patient safety using clinical simulation].

Science.gov (United States)

Rojo, E; Maestre, J M; Díaz-Mendi, A R; Ansorena, L; Del Moral, I

2016-01-01

Many excellent ideas are never implemented or generalised by healthcare organisations. There are two related paradigms: thinking that individuals primarily change through accumulating knowledge, and believing that the dissemination of that knowledge within the organisation is the key element to facilitate change. As an alternative, a description and evaluation of a simulation-based inter-professional team training program conducted in a Regional Health Service to promote and facilitate change is presented. The Department of Continuing Education completed the needs assessment using the proposals presented by clinical units and management. Skills and behaviors that could be learned using simulation were selected, and all personnel from the units participating were included. Experiential learning principles based on clinical simulation and debriefing, were used for the instructional design. The Kirkpatrick model was used to evaluate the program. Objectives included: a) decision-making and teamwork skills training in high prevalence diseases with a high rate of preventable complications; b) care processes reorganisation to improve efficiency, while maintaining patient safety; and, c) implementation of new complex techniques with a long learning curve, and high preventable complications rate. Thirty clinical units organised 39 training programs in the 3 public hospitals, and primary care of the Regional Health Service during 2013-2014. Over 1,559 healthcare professionals participated, including nursing assistants, nurses and physicians. Simulation in healthcare to train inter-professional teams can promote and facilitate change in patient care, and organisational re-engineering. Copyright © 2016 SECA. Publicado por Elsevier España, S.L.U. All rights reserved.

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

Science.gov (United States)

Pountos, Ippokratis; Giannoudis, Peter V

2018-03-01

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

Serotonin, neural markers and memory

Directory of Open Access Journals (Sweden)

Alfredo eMeneses

2015-07-01

Full Text Available Diverse neuropsychiatric disorders present dysfunctional memory and no effective treatment exits for them; likely as result of the absence of neural markers associated to memory. Neurotransmitter systems and signaling pathways have been implicated in memory and dysfunctional memory; however, their role is poorly understood. Hence, neural markers and cerebral functions and dysfunctions are revised. To our knowledge no previous systematic works have been published addressing these issues. The interactions among behavioral tasks, control groups and molecular changes and/or pharmacological effects are mentioned. Neurotransmitter receptors and signaling pathways, during normal and abnormally functioning memory with an emphasis on the behavioral aspects of memory are revised. With focus on serotonin, since as it is a well characterized neurotransmitter, with multiple pharmacological tools, and well characterized downstream signaling in mammals’ species. 5-HT1A, 5-HT4, 5-HT5, 5-HT6 and 5-HT7 receptors as well as SERT (serotonin transporter seem to be useful neural markers and/or therapeutic targets. Certainly, if the mentioned evidence is replicated, then the translatability from preclinical and clinical studies to neural changes might be confirmed. Hypothesis and theories might provide appropriate limits and perspectives of evidence

Prognostic DNA Methylation Markers for Prostate Cancer

Directory of Open Access Journals (Sweden)

Siri H. Strand

2014-09-01

Full Text Available Prostate cancer (PC is the most commonly diagnosed neoplasm and the third most common cause of cancer-related death amongst men in the Western world. PC is a clinically highly heterogeneous disease, and distinction between aggressive and indolent disease is a major challenge for the management of PC. Currently, no biomarkers or prognostic tools are able to accurately predict tumor progression at the time of diagnosis. Thus, improved biomarkers for PC prognosis are urgently needed. This review focuses on the prognostic potential of DNA methylation biomarkers for PC. Epigenetic changes are hallmarks of PC and associated with malignant initiation as well as tumor progression. Moreover, DNA methylation is the most frequently studied epigenetic alteration in PC, and the prognostic potential of DNA methylation markers for PC has been demonstrated in multiple studies. The most promising methylation marker candidates identified so far include PITX2, C1orf114 (CCDC181 and the GABRE~miR-452~miR-224 locus, in addition to the three-gene signature AOX1/C1orf114/HAPLN3. Several other biomarker candidates have also been investigated, but with less stringent clinical validation and/or conflicting evidence regarding their possible prognostic value available at this time. Here, we review the current evidence for the prognostic potential of DNA methylation markers in PC.

High Retention and Safety of Percutaneously Implanted Endovascular Embolization Coils as Fiducial Markers for Image-Guided Stereotactic Ablative Radiotherapy of Pulmonary Tumors

International Nuclear Information System (INIS)

Hong, Julian C.; Yu Yao; Rao, Aarti K.; Dieterich, Sonja; Maxim, Peter G.; Le, Quynh-Thu; Diehn, Maximilian; Sze, Daniel Y.; Kothary, Nishita; Loo, Billy W.

2011-01-01

Purpose: To compare the retention rates of two types of implanted fiducial markers for stereotactic ablative radiotherapy (SABR) of pulmonary tumors, smooth cylindrical gold 'seed' markers ('seeds') and platinum endovascular embolization coils ('coils'), and to compare the complication rates associated with the respective implantation procedures. Methods and Materials: We retrospectively analyzed the retention of percutaneously implanted markers in 54 consecutive patients between January 2004 and June 2009. A total of 270 markers (129 seeds, 141 coils) were implanted in or around 60 pulmonary tumors over 59 procedures. Markers were implanted using a percutaneous approach under computed tomography (CT) guidance. Postimplantation and follow-up imaging studies were analyzed to score marker retention relative to the number of markers implanted. Markers remaining near the tumor were scored as retained. Markers in a distant location (e.g., pleural space) were scored as lost. CT imaging artifacts near markers were quantified on radiation therapy planning scans. Results: Immediately after implantation, 140 of 141 coils (99.3%) were retained, compared to 110 of 129 seeds (85.3%); the difference was highly significant (p < 0.0001). Of the total number of lost markers, 45% were reported lost during implantation, but 55% were lost immediately afterwards. No additional markers were lost on longer-term follow-up. Implanted lesions were peripherally located for both seeds (mean distance, 0.33 cm from pleural surface) and coils (0.34 cm) (p = 0.96). Incidences of all pneumothorax (including asymptomatic) and pneumothorax requiring chest tube placement were lower in implantation of coils (23% and 3%, respectively) vs. seeds (54% and 29%, respectively; p = 0.02 and 0.01). The degree of CT artifact was similar between marker types. Conclusions: Retention of CT-guided percutaneously implanted coils is significantly better than that of seed markers. Furthermore, implanting coils is at

Cellular normoxic biophysical markers of hydroxyurea treatment in sickle cell disease.

Science.gov (United States)

Hosseini, Poorya; Abidi, Sabia Z; Du, E; Papageorgiou, Dimitrios P; Choi, Youngwoon; Park, YongKeun; Higgins, John M; Kato, Gregory J; Suresh, Subra; Dao, Ming; Yaqoob, Zahid; So, Peter T C

2016-08-23

Hydroxyurea (HU) has been used clinically to reduce the frequency of painful crisis and the need for blood transfusion in sickle cell disease (SCD) patients. However, the mechanisms underlying such beneficial effects of HU treatment are still not fully understood. Studies have indicated a weak correlation between clinical outcome and molecular markers, and the scientific quest to develop companion biophysical markers have mostly targeted studies of blood properties under hypoxia. Using a common-path interferometric technique, we measure biomechanical and morphological properties of individual red blood cells in SCD patients as a function of cell density, and investigate the correlation of these biophysical properties with drug intake as well as other clinically measured parameters. Our results show that patient-specific HU effects on the cellular biophysical properties are detectable at normoxia, and that these properties are strongly correlated with the clinically measured mean cellular volume rather than fetal hemoglobin level.

EPID detection of radio-opaque markers for the evaluation of prostate position during megavoltage irradiation: a clinical study

International Nuclear Information System (INIS)

Vigneault, E.; Pouliot, J.; Laverdiere, J.; Roy, J.

1995-01-01

Purpose: To assess daily prostatic apex motion relative to pelvic bone structures during megavoltage irradiation. Materials and Methods: Radio-opaque markers were implanted under ultrasound guidance near the prostatic apex of ten patients with localized prostatic carcinoma. Patients were subsequently treated with four field box technique at a beam energy of 23 MV. During treatment, on-line images were obtained with an Electronic Portal Imaging Device (EPID) for each field and fraction. The marker was easily identified, even on unprocessed images and the distance between the marker and a bony landmark was measured. Timelapse movie for the complete treatment of each patient were also reviewed. After the completion of treatment, a transrectal ultrasound examination was performed to verify the position of the marker relative to the apex. Results: Over 1000 digital portal images were acquired. Antero-posterior and lateral views of each fraction were analysed. The quality of portal images obtained with megavoltage irradiation was good. Even without image histogram equalization it was possible to evaluate pelvic bone structures. Moreover, the radio-opaque marker was easily visible on every on-line portal image. Qualitatively, the review of timelapse movies showed important interfraction motions of the marker while bone structures remained stable. Quantitatively, the position of the marker were measured for each fraction. Marker displacements of up to 1,4 cm were measured between two consecutive days of treatment. Important marker motions were predominately in the antero-posterior and cephalo-caudal directions. Position of the markers relative to the prostatic apex were verified with ultrasound at the end of the treatments and were found to remain globaly at their original position. Intratreatment images were reviewed in two cases and no change in marker positions was observed. Our results, obtained during the treatment courses, indicate similar or larger prostate motions

The evaluation of diagnostic value of the tumor markers: CCSA-2 and CEA in colorectal cancer.

Science.gov (United States)

Knychalski, Bartłomiej; Lukieńczuk, Tadeusz

2012-02-01

Finding the biomarker or biomarkers with high sensitivity and specificity in colorectal cancer, and thus a high diagnostic value will determine their clinical usefulness in clinical practice. An effective noninvasive blood test would be an ideal method to detect colorectal cancer. Discovered in 2007 a novel tumor marker CCSA-2 showes a promising results in patients with colorectal cancer. THE AIM OF THE STUDY was the evaluation of diagnostic and clinical value of a novel marker - colon cancer specific antigen-2 (CCSA-2) in colorectal adenocarcinoma in comparison to carcinoembryonic antigen (CEA) in patients operated during the years 2008 to 2010 at Wrocław Medical University 1st Department and Clinic of General, Gastroenterological and Endocrinologic Surgery. The study was performed on 40 patients with colorectal cancer and 40 patients in control group consisted of healthy subjects who had colonoscopy examinations with negative results (no pathology in the colon was found). The obtained results were statistically analyzed using nonparametric tests - Mann Whitney U and Kruskal-Wallis and Spearman's rank correlation coefficients. To determine the clinical value of CCSA-2 and CEA in those groups, their sensitivity and specifity was evaluated using ROC analysis. This analysis determines the accuracy and diagnostic value of both tests. There was a positive correlation between markers in patients with colorectal cancer and a statistically significant relationship according to which respondents with higher concentrations of CCSA-2 also have higher concentrations of CEA (R=0.754, ptumor markers increase and correlate with the clinical progression of the disease. Accuracy of CCSA-2 test using ROC analysis showed a slightly lower measurement of antigen CCSA-2 as diagnostic value in colorectal cancer in comparison to measurement of antigen CEA (accuracy of tests: CCSA-2 - 52%, CEA - 60%). CCSA-2 as a single tumor marker has a low diagnostic value in colorectal cancer because

Multiple Brain Markers are Linked to Age-Related Variation in Cognition

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Hedden, Trey; Schultz, Aaron P.; Rieckmann, Anna; Mormino, Elizabeth C.; Johnson, Keith A.; Sperling, Reisa A.; Buckner, Randy L.

2016-01-01

Age-related alterations in brain structure and function have been challenging to link to cognition due to potential overlapping influences of multiple neurobiological cascades. We examined multiple brain markers associated with age-related variation in cognition. Clinically normal older humans aged 65–90 from the Harvard Aging Brain Study (N = 186) were characterized on a priori magnetic resonance imaging markers of gray matter thickness and volume, white matter hyperintensities, fractional anisotropy (FA), resting-state functional connectivity, positron emission tomography markers of glucose metabolism and amyloid burden, and cognitive factors of processing speed, executive function, and episodic memory. Partial correlation and mediation analyses estimated age-related variance in cognition shared with individual brain markers and unique to each marker. The largest relationships linked FA and striatum volume to processing speed and executive function, and hippocampal volume to episodic memory. Of the age-related variance in cognition, 70–80% was accounted for by combining all brain markers (but only ∼20% of total variance). Age had significant indirect effects on cognition via brain markers, with significant markers varying across cognitive domains. These results suggest that most age-related variation in cognition is shared among multiple brain markers, but potential specificity between some brain markers and cognitive domains motivates additional study of age-related markers of neural health. PMID:25316342

The Affordability of Providing Sexually Transmitted Disease Services at a Safety-net Clinic.

Science.gov (United States)

Dean, Lorraine T; Montgomery, Madeline C; Raifman, Julia; Nunn, Amy; Bertrand, Thomas; Almonte, Alexi; Chan, Philip A

2018-04-01

Sexually transmitted diseases continue to increase in the U.S. There is a growing need for financially viable models to ensure the longevity of safety-net sexually transmitted disease clinics, which provide testing and treatment to high-risk populations. This micro-costing analysis estimated the number of visits required to balance cost and revenue of a sexually transmitted disease clinic in a Medicaid expansion state. In 2017, actual and projected cost and revenues were estimated from the Rhode Island sexually transmitted disease clinic in 2015. Projected revenues for a hypothetical clinic offering a standard set of sexually transmitted disease services were based on Medicaid; private ("commercial") insurance; and institutional ("list price") reimbursement rates. The number of visits needed to cover clinic costs at each rate was assessed. Total operating cost for 2,153 clinic visits was estimated at $255,769, or $119 per visit. Laboratory testing and salaries each accounted for 44% of operating costs, medications for treatment 7%, supplies 5%, and 28% of visits used insurance. For a standard clinic offering a basic set of sexually transmitted disease services to break even, a projected 73% of visits need to be covered at the Medicaid rate, 38% at private rate, or 11% at institutional rate. Sexually transmitted disease clinics may be financially viable when a majority of visits are billed at a Medicaid rate; however, mixed private/public models may be needed if not all visits are billed. In this manner, sexually transmitted disease clinics can be solvent even if not all visits are billed to insurance, thus ensuring access to uninsured or underinsured patients. Copyright © 2018 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Biochemical Markers for Osteoarthritis: Is There any Promising Candidate?

Directory of Open Access Journals (Sweden)

Elif Aydın

2016-04-01

Full Text Available Osteoarthritis (OA is the most common degenerative joint disease. OA affects millions of individuals each year and becoming the most important cause of pain in geriatric population. Progressive destruction of articular cartilage is one of the prominent features of the disease. The diagnosis of OA is generally based on clinical and radiographical findings, which are insufficient to determine early-stage OA and predict disease course. There is a need for biomarkers that help clinicians early diagnose, assess disease activity, predict prognosis and monitor response to therapy. There are a growing number of publications regarding candidate markers in this field. The aim of this paper was to review recent studies on biochemical markers that reflect cartilage, synovial and bone turnover and their clinical use in patients with OA.

Reference values of thirty-one frequently used laboratory markers for 75-year-old males and females

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Ryden, Ingvar; Lind, Lars

2012-01-01

Background We have previously reported reference values for common clinical chemistry tests in healthy 70-year-old males and females. We have now repeated this study 5 years later to establish reference values also at the age of 75. It is important to have adequate reference values for elderly patients as biological markers may change over time, and adequate reference values are essential for correct clinical decisions. Methods We have investigated 31 frequently used laboratory markers in 75-year-old males (n = 354) and females (n = 373) without diabetes. The 2.5 and 97.5 percentiles for these markers were calculated according to the recommendations of the International Federation of Clinical Chemistry. Results Reference values are reported for 75-year-old males and females for 31 frequently used laboratory markers. Conclusion There were minor differences between reference intervals calculated with and without individuals with cardiovascular diseases. Several of the reference intervals differed from Scandinavian reference intervals based on younger individuals (Nordic Reference Interval Project). PMID:22300333

[Knowledge and adherence to bio-safety measures and biological accidents by nursing students during their clinical practice].

Science.gov (United States)

Merino-de la Hoz, Felicitas; Durá-Ros, María Jesús; Rodríguez-Martín, Elías; González-Gómez, Silvia; Mariano López-López, Luis; Abajas-Bustillo, Rebeca; de la Horra-Gutiérrez, Inmaculada

2010-01-01

To identify the degree of knowledge and performance of bio-safety measures by nursing students and knowing the type of biological accidents suffered during their clinical practice. A cross-sectional study was conducted on the students of three Nursing courses held in May of 2008. Data was collected by an anonymous self-administered questionnaire, with a return of 54%. A total of 97% of students seemed to know the standard biosafety measures, and all of them (100%) stated that those measures must be applied to every patient. However, the reality of clinical practice shows that biosafety measures are only partially applied. An average of 60.2% implement the personal hygiene measures, 66.1% use physical barriers, and 44% use sharp materials safely. Around 32.25% of the students have suffered some biological accident, with a greater incidence in the second year: administering injections (24%), drawing blood samples with Venojet needles (18%) and recapping used needles (17%). The high level of knowledge shown by the students on standard precautions is not always shown in clinical practice. There are significant deficiencies in student safety practices: recapping of used needles continues to be one of the most common risk practices carried out. Copyright (c) 2009 Elsevier España, S.L. All rights reserved.

Safety of 13-valent pneumococcal conjugate vaccine in infants and children: meta-analysis of 13 clinical trials in 9 countries.

Science.gov (United States)

Thompson, Allison; Gurtman, Alejandra; Patterson, Scott; Juergens, Christine; Laudat, France; Emini, Emilio A; Gruber, William C; Scott, Daniel A

2013-10-25

Meta-analyses enable summarization and interpretation of data across clinical trials. When applied to safety data they allow for detection of rare events. Recently, a 13-valent pneumococcal conjugate vaccine (PCV13) was approved in multiple countries worldwide for routine immunization of infants and young children. This meta-analysis was conducted to identify potentially clinically important rare safety events associated with PCV13. To summarize the safety of PCV13 compared with 7-valent pneumococcal conjugate vaccine (PCV7) administered to infants and toddlers. A meta-analysis was performed of integrated safety data from 13 infant studies (PCV13 n=4729 and PCV7 n=2760) conducted in 9 North American, European, and Asian countries. Local reactions at the vaccine injection site and systemic events were collected for 4-7 days after each dose into electronic diaries. Adverse events (AEs) were collected after each vaccination. Overall, rates of local reactions after any dose of the infant series were similar between PCV13 and PCV7 groups: tenderness (46.7% vs 44.8%, respectively); swelling (28.5% vs 26.9%); and redness (36.4% vs 33.9%). After the toddler dose, tenderness was significantly higher among PCV7 subjects than PCV13 subjects (54.4% vs 48.8%; P=0.005). Frequencies of fever (≥38°C) were similar in both groups and mostly mild (≤39°C); incidence of moderate fever (>39°C to ≤40°C) with PCV13 was ≤2.8% after any infant dose and 5.0% after the toddler dose, compared with ≤2.6% and 7.3%, respectively, with PCV7. Fever >40°C was uncommon in both groups. Frequencies of decreased appetite, irritability, and sleep disturbances were similar in both groups. AEs were the types of conditions and symptoms expected in infants and children, and clinically significant differences between vaccine groups were not observed. PCV13 has a favorable safety profile similar to that of PCV7, a vaccine for which there is >10 years clinical experience. Copyright © 2013

Role of Phosphorylated Neurofilament H as a diagnostic and prognostic marker in traumatic brain injury

Directory of Open Access Journals (Sweden)

Moh Omar Ghonemi

2013-09-01

Conclusion: Phosphorylated Neurofilament H can be used as a diagnostic and prognostic marker in patients with TBI as seen by the presence of significant correlations between the marker levels and different clinical and radiological tools.

Use of Tumor Markers in Gastrointestinal Cancers: Surgeon Perceptions and Cost-Benefit Trade-Off Analysis.

Science.gov (United States)

Acharya, Amish; Markar, Sheraz R; Matar, Michael; Ni, Melody; Hanna, George B

2017-05-01

Gastrointestinal cancers constitute the third most common cancers worldwide. Tumor markers have long since been used in the postoperative surveillance of these malignancies; however, the true value in clinical practice remains undetermined. This study aimed to evaluate the clinical utility of three tumor markers in colorectal and esophagogastric cancer. A systematic review of the literature was undertaken to elicit the sensitivity, specificity, statistical heterogeneity and ability to predict recurrence and metastases for carcinoembryonic antigen (CEA), cancer antigen (CA) 19-9 and CA125. European surgeons were surveyed to assess their current practice and the characteristics of tumor markers they most valued. Data from the included studies and survey were combined in a cost-benefit trade-off analysis to assess which tumor markers are of most use in clinical practice. Diagnostic sensitivity and specificity were ranked the most desirable characteristics of a tumor marker by those surveyed. Overall, 156 studies were included to inform the cost-benefit trade-off. The cost-benefit trade-off showed that CEA outperformed both CA19-9 and CA125, with lower financial cost and a higher sensitivity, and diagnostic accuracy for metastases at presentation (area under the curve [AUC] 0.70 vs. 0.61 vs. 0.46), as well as similar diagnostic accuracy for recurrence (AUC 0.46 vs. 0.48). Cost-benefit trade-off analysis identified CEA to be the best performing tumor marker. Further studies should seek to evaluate new tumor markers, with investigation tailored to factors that meet the requirements of practicing clinicians.

Identification of laboratory markers of disease activity in rheumatoid arthritis abstract objective

International Nuclear Information System (INIS)

Naqi, N.; Ahmed, T.A.; Malik, J.M.

2012-01-01

To identify the laboratory markers of disease activity, by finding relationship of biochemical markers with clinical disease activity measurement in patients suffering from rheumatoid arthritis (RA). Study Design: Cross sectional analytical study. Place and duration of study: Department of Immunology, Armed Forces Institute of Pathology (AFIP), Rawalpindi from January 2009 to January 2010 in collaboration with Fauji Foundation Hospital and Military Hospital Rawalpindi. Patients and Methods: One hundred patients diagnosed as having rheumatoid arthritis (RA) as per American college of Rheumatology (ACR) revised criteria 1987 and fulfilling the study's inclusion criteria were studied. These patients were assessed clinically according to Simplified Disease Activity Index (SDAI) and divided into three groups which were mild, moderate and severe based on disease activity. These three groups were then assessed for disease activity by Rheumatoid factor (RA factor), Anti Cyclic Citrullinated Peptide antibodies (anti CCP antibodies), Erythrocyte Sedimentation Rate (ESR) and C- Reactive Proteins (CRP). The association of these laboratory markers with three groups of disease activity was analyzed to detect most sensitive disease activity markers for RA. Results: All the assessed laboratory markers that are RA factor, anti CCP antibodies, ESR and CRP are directly related with RA disease activity and any of them can be used to assess disease activity in RA. However a combination of the tests, analyzed in this study markers maybe used for better prediction of disease activity Conclusion: The identification of the laboratory markers of disease activity may help physician to diagnose aggressive disease early and evaluate prognosis in RA patients. (author)

Utility of CEA and CA 19-9 tumor markers in diagnosis and prognostic assessment of mucinous epithelial cancers of the appendix.

Science.gov (United States)

Carmignani, C Pablo; Hampton, Regina; Sugarbaker, Christina E; Chang, David; Sugarbaker, Paul H

2004-09-15

Tumor markers are a clinical tool frequently used in oncology in association with other clinical and radiologic information. For gastrointestinal cancer, carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) tumor markers have found selected clinical application. The use of these tumor markers in mucinous epithelial tumors of the appendix has not been previously determined. In patients with peritoneal dissemination of a mucinous epithelial malignancy of the appendix, tumor markers CEA and CA 19-9 were prospectively recorded preoperatively within 1 week prior to definitive treatment. Also, if the appendiceal tumor recurred, the tumor marker was determined. The accuracy of these two tumor markers in the management of this disease was determined for these two specific clinical situations. CEA was elevated in 56% of 532 patients and CA 19-9 was elevated in 67.1% of these patients. Although the absolute level of tumor marker did not correlate with prognosis, a normal value indicated an improved survival. CEA was elevated in 35.2% of 110 patients determined to have recurrent disease; CA 19-9 was elevated in 62.9% and at least one of the tumor markers was elevated in 68.2% of patients. An elevated CEA tumor marker at the time of recurrence indicated a reduced prognosis. Both CEA and CA 19-9 tumor markers were elevated in a majority of these patients and should be a valuable diagnostic tool previously underutilized in this group of patients. These tumor markers were also of benefit in the assessment of prognosis in that a normal level indicated an improved prognosis. At the time of a reoperative procedure, CEA and CA 19-9 tumor markers gave information regarding the progression of disease. These tumor markers have practical value in the management of epithelial appendiceal malignancy with peritoneal dissemination. Copyright 2004 Wiley-Liss, Inc.

Measurement of some tumor markers by IRMA in vietnam

International Nuclear Information System (INIS)

Tran Xuan Truong

2004-01-01

As we known that a perfect tumor markers could be used in five different ways : for population screening, for diagnose, for monitoring therapy and for follow-up early evidence of cancer recurrence. In order to achieve perfect status a tumor markers would require total negativity in healthy subject, total positivity for single tumor type and close correlation between plasma tumor marker concentration and tumor size . The advance of monoclonal antibodies has had dramatic impact in oncology, where new tumor markers have been discovered and assay methods for all tumor markers have been improved commercially . Analytical performance of these new methods are potentially as good as that of the best Immunoradiometric assay for others analytes. In Vietnam, the first time we use immunoradiometric assay (IRMA) for the measurement of some tumor markers in normal subject and cancer diseases. These are Thyroglobulin (TG) of thyroid cancer, cancer-antigen 15-3 (CA15-3) of breast cancer and cancer-antigen 72-4 (CA72-4) of stomach cancer. We would like applying the CA72-4 in the indication of stomach cancer, CA15-3 in the differential diagnosis of breast cancer, and TG in the differential diagnosis of thyroid cancer. And all of these tumor markers were also used in the clinical follow-up and early detection of recurrence and metastatic Cancer of them. We could try researching on them much more. (authors)

Unlicensed pharmaceutical preparations for clinical patient care: Ensuring safety.

Science.gov (United States)

de Wilde, Sofieke; de Jong, Maria G H; Le Brun, Paul P H; Guchelaar, Henk-Jan; Schimmel, Kirsten J M

2018-01-01

Most medicinal products dispensed to patients have marketing authorization (MA) to ensure high quality of the product, safety, and efficacy. However, in daily practice, to treat patients adequately, there is a medical need for drugs that do not hold MA. To meet this medical need, medicinal products are used in clinical care without MA (unlicensed), such as products prepared by (local) pharmacies: the pharmaceutical preparations. Three types of pharmaceutical preparations are distinguished: (i) reconstitution in excess of summary of product characteristics; (ii) adaptation of a licensed medicinal product (outside its official labeling); (iii) medicinal products from an active pharmaceutical ingredient. Although unlicensed, patients may expect the same quality for these unlicensed pharmaceutical preparations as for the licensed medicinal products. To assure this quality, a proper risk-benefit assessment and proper documentation in (centralized) patient registries and linking to a national pharmacovigilance database should be in place. Based on a risk assessment matrix, requirements for quality assurance can be determined, which has impact on the level of documentation of a pharmaceutical preparation. In this paper, the approach for good documentation including quality assurance and benefit-risk assessment will be discussed and possibilities for patient registries are described to make these crucial preparations available for regular patient care. KEY POINTS Ensuring pharmaceutical quality and performing a proper benefit-risk assessment will guarantee safe use of pharmaceutical preparations. Good documentation of (ultra-)orphan treatments can be collected in centralized patient registries and should be combined with existing information in (inter)national databases and self-reflection of patients. Linking patient registries to a centralized database for adverse drug events is highly recommended as it increases safety control of the (ultra) orphan pharmaceutical

Surrogate marker analysis in cancer clinical trials through time-to-event mediation techniques.

Science.gov (United States)

Vandenberghe, Sjouke; Duchateau, Luc; Slaets, Leen; Bogaerts, Jan; Vansteelandt, Stijn

2017-01-01

The meta-analytic approach is the gold standard for validation of surrogate markers, but has the drawback of requiring data from several trials. We refine modern mediation analysis techniques for time-to-event endpoints and apply them to investigate whether pathological complete response can be used as a surrogate marker for disease-free survival in the EORTC 10994/BIG 1-00 randomised phase 3 trial in which locally advanced breast cancer patients were randomised to either taxane or anthracycline based neoadjuvant chemotherapy. In the mediation analysis, the treatment effect is decomposed into an indirect effect via pathological complete response and the remaining direct effect. It shows that only 4.2% of the treatment effect on disease-free survival after five years is mediated by the treatment effect on pathological complete response. There is thus no evidence from our analysis that pathological complete response is a valuable surrogate marker to evaluate the effect of taxane versus anthracycline based chemotherapies on progression free survival of locally advanced breast cancer patients. The proposed analysis strategy is broadly applicable to mediation analyses of time-to-event endpoints, is easy to apply and outperforms existing strategies in terms of precision as well as robustness against model misspecification.

Robustness and precision of an automatic marker detection algorithm for online prostate daily targeting using a standard V-EPID.

Science.gov (United States)

Aubin, S; Beaulieu, L; Pouliot, S; Pouliot, J; Roy, R; Girouard, L M; Martel-Brisson, N; Vigneault, E; Laverdière, J

2003-07-01

An algorithm for the daily localization of the prostate using implanted markers and a standard video-based electronic portal imaging device (V-EPID) has been tested. Prior to planning, three gold markers were implanted in the prostate of seven patients. The clinical images were acquired with a BeamViewPlus 2.1 V-EPID for each field during the normal course radiotherapy treatment and are used off-line to determine the ability of the automatic marker detection algorithm to adequately and consistently detect the markers. Clinical images were obtained with various dose levels from ranging 2.5 to 75 MU. The algorithm is based on marker attenuation characterization in the portal image and spatial distribution. A total of 1182 clinical images were taken. The results show an average efficiency of 93% for the markers detected individually and 85% for the group of markers. This algorithm accomplishes the detection and validation in 0.20-0.40 s. When the center of mass of the group of implanted markers is used, then all displacements can be corrected to within 1.0 mm in 84% of the cases and within 1.5 mm in 97% of cases. The standard video-based EPID tested provides excellent marker detection capability even with low dose levels. The V-EPID can be used successfully with radiopaque markers and the automatic detection algorithm to track and correct the daily setup deviations due to organ motions.

Efficacy, Safety, and Feasibility of the Morphine Microdose Method in Community-Based Clinics.

Science.gov (United States)

Wilkes, Denise M; Orillosa, Susan J; Hustak, Erik C; Williams, Courtney G; Doulatram, Gulshan R; Solanki, Daneshvari R; Garcia, Eduardo A; Huang, Li-Yen M

2017-06-13

The goal of this study was to assess the success of the morphine microdose method in a community pain clinic setting by monitoring follow-up frequency, dose escalation, and monotherapy/polytherapy ratio. The morphine microdose method involves a pretrial reduction or elimination of systemic opioids followed by a period of abstinence. Intrathecal (IT) morphine is then started at doses of less than 0.2 mg per day. Systemic opioid abstinence is then continued after pump implant and IT morphine monotherapy. Retrospective review of medical records. Private and academic pain clinic practices. Chronic noncancer pain patients. We reviewed the charts of 60 patients who had completed a microdose regimen and had an IT pump implanted between June 11, 2008, and October 11, 2014. During IT therapy, dose change over time, pain scores, side effects, max dose, and duration were recorded. The majority of patients (35/60, 58%) were successfully managed solely on morphine microdose monotherapy. These patients did not require additional oral therapy. There was a significant reduction in mean pain scores, from 7.4 ± 0.32 before microdose therapy to 4.8 ± 0.3 after microdose therapy. Microdose therapy achieved analgesia, improved safety, and avoided systemic side effects. The safety of IT therapy was increased by using a lower concentration (2 mg/mL) and lower daily doses (microdose therapy was feasible, safe, and cost-effective in the outpatient setting. 2017 American Academy of Pain Medicine. This work is written by US Government employees and is in the public domain in the US.

Sensitivity of the Oxford Foot Model to marker misplacement: A systematic single-case investigation.

Science.gov (United States)

Carty, Christopher P; Walsh, Henry P J; Gillett, Jarred G

2015-09-01

The purpose of this paper was to systematically assess the effect of Oxford Foot Model (OFM) marker misplacement on hindfoot relative to tibia, and forefoot relative to hindfoot kinematic calculations during the stance phase of gait. Marker trajectories were recorded with an 8-camera motion analysis system (Vicon Motion Systems Ltd., UK) and ground reaction forces were recorded from three force platforms (AMTI, USA). A custom built marker cluster consisting of 4 markers in a square arrangement (diagonal distance 2 cm) was used to assess the effect of marker misplacement in the superior, inferior, anterior and posterior direction for the sustentaculum tali (STL), the proximal 1st metatarsal (P1M), distal 5th metatarsal (D5M), proximal 5th metatarsal (P5M) and lateral calcaneus (LCA) markers. In addition manual movement of the heel complex 1 cm superiorly, inferiorly, medially and laterally, and also an alignment error of 10° inversion and 10° eversion was assessed. Clinically meaningful effects of marker misplacement were determined using a threshold indicating the minimal clinically important difference. Misplacement of the heel-wand complex had the most pronounced effect on mean kinematic profiles during the stance phase across all degrees-of-freedom with respect to hindfoot-tibia and forefoot-hindfoot angles. Vertical marker misplacement of the D5M and P5M markers affected the sagittal plane, and to a lesser extent frontal plane, forefoot-hindfoot kinematics. In conclusion, the OFM is highly sensitive to misplacement of the heel-wand complex in all directions and the P5M marker in the vertical direction. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

Safety Profile of Good Manufacturing Practice Manufactured Interferon γ-Primed Mesenchymal Stem/Stromal Cells for Clinical Trials.

Science.gov (United States)

Guess, Adam J; Daneault, Beth; Wang, Rongzhang; Bradbury, Hillary; La Perle, Krista M D; Fitch, James; Hedrick, Sheri L; Hamelberg, Elizabeth; Astbury, Caroline; White, Peter; Overolt, Kathleen; Rangarajan, Hemalatha; Abu-Arja, Rolla; Devine, Steven M; Otsuru, Satoru; Dominici, Massimo; O'Donnell, Lynn; Horwitz, Edwin M

2017-10-01

Mesenchymal stem/stromal cells (MSCs) are widely studied by both academia and industry for a broad array of clinical indications. The collective body of data provides compelling evidence of the clinical safety of MSC therapy. However, generally accepted proof of therapeutic efficacy has not yet been reported. In an effort to generate a more effective therapeutic cell product, investigators are focused on modifying MSC processing protocols to enhance the intrinsic biologic activity. Here, we report a Good Manufacturing Practice-compliant two-step MSC manufacturing protocol to generate MSCs or interferon γ (IFNγ) primed MSCs which allows freshly expanded cells to be infused in patients on a predetermined schedule. This protocol eliminates the need to infuse cryopreserved, just thawed cells which may reduce the immune modulatory activity. Moreover, using (IFNγ) as a prototypic cytokine, we demonstrate the feasibility of priming the cells with any biologic agent. We then characterized MSCs and IFNγ primed MSCs prepared with our protocol, by karyotype, in vitro potential for malignant transformation, biodistribution, effect on engraftment of transplanted hematopoietic cells, and in vivo toxicity in immune deficient mice including a complete post-mortem examination. We found no evidence of toxicity attributable to the MSC or IFNγ primed MSCs. Our data suggest that the clinical risk of infusing MSCs or IFNγ primed MSCs produced by our two-step protocol is not greater than MSCs currently in practice. While actual proof of safety requires phase I clinical trials, our data support the use of either cell product in new clinical studies. Stem Cells Translational Medicine 2017;6:1868-1879. © 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Effect of steroids on inflammatory markers and clinical parameters in congenital open heart surgery: a randomised controlled trial.

Science.gov (United States)

Amanullah, Muhammad M; Hamid, Mohammad; Hanif, Hashim M; Muzaffar, Marium; Siddiqui, Maria T; Adhi, Fatima; Ahmad, Khabir; Khan, Shahjahan; Hasan, Zahra

2016-03-01

Cardiopulmonary bypass is associated with systemic inflammatory response. Steroids suppress this response, although the therapeutic evidence remains controversial. We hypothesised that intravenous steroids in children undergoing open-heart surgery would decrease inflammation leading to better early post-operative outcomes. We conducted a randomised controlled trial to evaluate the trends in the levels of immunomodulators and their effects on clinical parameters. To assess the effects of intravenous steroids on early post-operative inflammatory markers and clinical parameters in children undergoing open-heart surgery. A randomised controlled trial involving 152 patients, from one month up to 18 years of age, who underwent open-heart surgery for congenital heart disease from April 2010-2012 was carried out. Patients were randomised and administered either three scheduled intravenous pulse doses of dexamethasone (1 mg/kg) or placebo. Blood samples were drawn at four time intervals and serum levels of inflammatory cytokines - Interleukin-6, 8, 10, 18, and tumour necrosis factor-alpha - were measured. Clinical parameters were also assessed. Blood cytokine levels were compared between the dexamethasone (n=65) and placebo (n=64) groups. Interleukin-6 levels were lower at 6 and 24 hours post-operatively (p<0.001), and Interleukin-10 levels were higher 6 hours post-operatively (p<0.001) in the steroid group. Interleukin-8, 18, and tumour necrosis factor-alpha levels did not differ between the groups at any time intervals. The clinical parameters were similar in both the groups. Dexamethasone caused quantitative suppression of Interleukin-6 and increased Interleukin-10 activation, contributing to reduced immunopathology, but it did not translate into clinical benefit in the short term.

A novel method for monitoring high-risk breast cancer with tumor markers

DEFF Research Database (Denmark)

Sölétormos, G; Nielsen, D; Schiøler, V

1993-01-01

cancer. METHODS: Ninety females with high-risk breast cancer were included in the study. Response evaluation was based upon clinical examination, x-rays or histology and elaborated marker criteria. RESULTS: During the marker monitoring period, metastases in four patients were confined to skin or lymph......BACKGROUND: An early and reliable diagnosis of metastatic spread has increased interest in serum tumor markers. This study investigated the ability of CA 15.3, CEA, and TPA to identify, predict, and exclude metastases in bone/viscera during adjuvant treatment and follow-up of high-risk breast...

Cellular normoxic biophysical markers of hydroxyurea treatment in sickle cell disease

OpenAIRE

Hosseini, Poorya; Abidi, Sabia Z.; Du, E; Papageorgiou, Dimitrios P.; Choi, Youngwoon; Park, YongKeun; Higgins, John M.; Kato, Gregory J.; Suresh, Subra; Dao, Ming; Yaqoob, Zahid; So, Peter T. C.

2016-01-01

There exists a critical need for developing biomarkers reflecting clinical outcomes and for evaluating the effectiveness of treatments for sickle cell disease patients. Prior attempts to find such patient-specific markers have mostly relied upon chemical biomarkers or biophysical properties at hypoxia with limited success. We introduce unique biomarkers based on characterization of cellular biophysical properties at normoxia and show that these markers correlate sensitively with treatment usi...

Patient participation in patient safety still missing: Patient safety experts' views.

Science.gov (United States)

Sahlström, Merja; Partanen, Pirjo; Rathert, Cheryl; Turunen, Hannele

2016-10-01

The aim of this study was to elicit patient safety experts' views of patient participation in promoting patient safety. Data were collected between September and December in 2014 via an electronic semi-structured questionnaire and interviews with Finnish patient safety experts (n = 21), then analysed using inductive content analysis. Patient safety experts regarded patients as having a crucial role in promoting patient safety. They generally deemed the level of patient safety as 'acceptable' in their organizations, but reported that patient participation in their own safety varied, and did not always meet national standards. Management of patient safety incidents differed between organizations. Experts also suggested that patient safety training should be increased in both basic and continuing education programmes for healthcare professionals. Patient participation in patient safety is still lacking in clinical practice and systematic actions are needed to create a safety culture in which patients are seen as equal partners in the promotion of high-quality and safe care. © 2016 John Wiley & Sons Australia, Ltd.

Oxidative Stress Markers and Genetic Polymorphisms of Glutathione ...

African Journals Online (AJOL)

Hence, we evaluated the serum levels of oxidative stress markers and investigated genetic polymorphisms of glutathione S-transferase associated with autism. Materials and Methods: Forty-two children clinically diagnosed with ASD using the Diagnostic and Statistical Manual for Mental Disorders (DSM-5) criteria and a ...

Implications of Artefacts Reduction in the Planning CT Originating from Implanted Fiducial Markers

International Nuclear Information System (INIS)

Kassim, Iskandar; Joosten, Hans; Barnhoorn, Jaco C.; Heijmen, Ben J.M.; Dirkx, Maarten L.P.

2011-01-01

The efficacy of metal artefact reduction (MAR) software to suppress artefacts in reconstructed computed tomography (CT) images originating from small metal objects, like tumor markers and surgical clips, was evaluated. In addition, possible implications of using digital reconstructed radiographs (DRRs), based on the MAR CT images, for setup verification were analyzed. A phantom and 15 patients with different tumor sites and implanted markers were imaged with a multislice CT scanner. The raw image data was reconstructed both with the clinically used filtered-backprojection (FBP) and with the MAR software. Using the MAR software, improvements in image quality were often observed in CT slices with markers or clips. Especially when several markers were located near to each other, fewer streak artefacts were observed than with the FBP algorithm. In addition, the shape and size of markers could be identified more accurately, reducing the contoured marker volumes by a factor of 2. For the phantom study, the CT numbers measured near to the markers corresponded more closely to the expected values. However, the MAR images were slightly more smoothed compared with the images reconstructed with FBP. For 8 prostate cancer patients in this study, the interobserver variation in 3D marker definition was similar (<0.4 mm) when using DRRs based on either FBP or MAR CT scans. Automatic marker matches also showed a similar success rate. However, differences in automatic match results up to 1 mm, caused by differences in the marker definition, were observed, which turned out to be (borderline) statistically significant (p = 0.06) for 2 patients. In conclusion, the MAR software might improve image quality by suppressing metal artefacts, probably allowing for a more reliable delineation of structures. When implanted markers or clips are used for setup verification, the accuracy may slightly be improved as well, which is relevant when using very tight clinical target volume (CTV) to

Safety and pharmacodynamics of dalazatide, a Kv1.3 channel inhibitor, in the treatment of plaque psoriasis: A randomized phase 1b trial.

Directory of Open Access Journals (Sweden)

Eric J Tarcha

Full Text Available Dalazatide is a specific inhibitor of the Kv1.3 potassium channel. The expression and function of Kv1.3 channels are required for the function of chronically activated memory T cells, which have been shown to be key mediators of autoimmune diseases, including psoriasis.The primary objective was to evaluate the safety of repeat doses of dalazatide in adult patients with mild-to-moderate plaque psoriasis. Secondary objectives were to evaluate clinical proof of concept and the effects of dalazatide on mediators of inflammation in the blood and on chronically activated memory T cell populations.Patients (n = 24 were randomized 5:5:2 to receive dalazatide at 30 mcg/dose, 60 mcg/dose, or placebo twice weekly by subcutaneous injection (9 doses total. Safety was assessed on the basis of physical and neurological examination and laboratory testing. Clinical assessments included body-surface area affected, Psoriasis Area and Severity Index (PASI, and investigator and patient questionnaires.The most common adverse events were temporary mild (Grade 1 hypoesthesia (n = 20; 75% placebo, 85% dalazatide and paresthesia (n = 15; 25% placebo, 70% dalazatide involving the hands, feet, or perioral area. Nine of 10 patients in the 60 mcg/dose group had a reduction in their PASI score between baseline and Day 32, and the mean reduction in PASI score was significant in this group (P < 0.01. Dalazatide treatment reduced the plasma levels of multiple inflammation markers and reduced the expression of T cell activation markers on peripheral blood memory T cells.The study was small and drug treatment was for a short duration (4 weeks.This study indicates that dalazatide is generally well tolerated and can improve psoriatic skin lesions by modulating T cell surface and activation marker expression and inhibiting mediators of inflammation in the blood. Larger studies of longer duration are warranted.

Internet access and online cancer information seeking among Latino immigrants from safety net clinics.

Science.gov (United States)

Selsky, Claire; Luta, George; Noone, Anne-Michelle; Huerta, Elmer E; Mandelblatt, Jeanne S

2013-01-01

Internet use is widespread, but little is known about Internet use for cancer information among Latinos, especially those who rely on safety net clinics. The authors investigated access to and intended use of the Internet for cancer information among low income, immigrant Latinos predominately from Central and South America. A cross-sectional study of 1,273 Latinos 21 years and older attending safety net clinics or health fairs was conducted from June 2007 to November 2008. The authors used logistic regression models to evaluate associations of age, acculturation, psychosocial factors and other covariates with Internet access and intended use of the Internet for cancer information among those with access. Of the sample, 44% reported Internet access. Higher information self-efficacy and greater trust in the Internet were independently associated with Internet access (p = .05 and p Internet use for cancer information, considering covariates. In addition, those with high (vs. low) perceived risk of cancer (OR = 1.76; 95% CI [1.14, 2.73]; p = .01) and higher levels of trust in online health information (OR = 1.47 per one-point increase; 95% [CI 1.19, 1.82]; p = .0004) were more likely to intend to seek cancer information online. These findings that Internet access is fairly high in the immigrant Latino population and that the Internet is a trusted source of cancer information suggest that the Internet may be a channel for cancer control interventions.

Assessing medical students' perceptions of patient safety: the medical student safety attitudes and professionalism survey.

Science.gov (United States)

Liao, Joshua M; Etchegaray, Jason M; Williams, S Tyler; Berger, David H; Bell, Sigall K; Thomas, Eric J

2014-02-01

To develop and test the psychometric properties of a survey to measure students' perceptions about patient safety as observed on clinical rotations. In 2012, the authors surveyed 367 graduating fourth-year medical students at three U.S. MD-granting medical schools. They assessed the survey's reliability and construct and concurrent validity. They examined correlations between students' perceptions of organizational cultural factors, organizational patient safety measures, and students' intended safety behaviors. They also calculated percent positive scores for cultural factors. Two hundred twenty-eight students (62%) responded. Analyses identified five cultural factors (teamwork culture, safety culture, error disclosure culture, experiences with professionalism, and comfort expressing professional concerns) that had construct validity, concurrent validity, and good reliability (Cronbach alphas > 0.70). Across schools, percent positive scores for safety culture ranged from 28% (95% confidence interval [CI], 13%-43%) to 64% (30%-98%), while those for teamwork culture ranged from 47% (32%-62%) to 74% (66%-81%). They were low for error disclosure culture (range: 10% [0%-20%] to 27% [20%-35%]), experiences with professionalism (range: 7% [0%-15%] to 23% [16%-30%]), and comfort expressing professional concerns (range: 17% [5%-29%] to 38% [8%-69%]). Each cultural factor correlated positively with perceptions of overall patient safety as observed in clinical rotations (r = 0.37-0.69, P safety behavioral intent item. This study provided initial evidence for the survey's reliability and validity and illustrated its applicability for determining whether students' clinical experiences exemplify positive patient safety environments.

Cerebrospinal fluid inflammatory markers in patients with multiple sclerosis: a pilot study.

Science.gov (United States)

Matejčíková, Z; Mareš, J; Přikrylová Vranová, H; Klosová, J; Sládková, V; Doláková, J; Zapletalová, J; Kaňovský, P

2015-02-01

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. Autoimmune inflammation is common in the early stages of MS. This stage is followed by the neurodegenerative process. The result of these changes is axon and myelin breakdown. Although MS is according to McDonald's revised diagnostic criteria primarily a clinical diagnosis, paraclinical investigation methods are an important part in the diagnosis of MS. In common practice, magnetic resonance imaging of the brain and spinal cord, examination of cerebrospinal fluid (CSF) and examination of visual evoked potentials are used. There are an increasing number of studies dealing with biomarkers in CSF and their role in the diagnosis and treatment of MS. We hypothesized that the levels of some markers could be changed in MS in comparison with controls. We studied five inflammatory markers [interleukin-6 (IL-6), interleukin-8, interleukin-10 (IL-10), beta-2-microglobulin, orosomucoid]. CSF and serum levels of inflammatory markers were assessed in 38 patients with newly diagnosed MS meeting McDonald's revised diagnostic criteria and in 28 subjects as a control group (CG). Levels of beta-2-microglobulin and interleukin-8 in CSF were found to be significantly higher in MS patients in comparison to CG (p < 0.001 resp. p = 0.007). No differences in other CSF markers (IL-6, IL-10 and orosomucoid) and serum levels of all markers between both groups were found. The levels of two studied inflammatory markers were found to be increased at the time of first clinical symptoms of MS. Research on the role of inflammatory and neurodegenerative markers in MS should continue.

Five-year safety and performance results from the Argus II Retinal Prosthesis System clinical trial

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da Cruz, Lyndon; Dorn, Jessy D.; Humayun, Mark S.; Dagnelie, Gislin; Handa, James; Barale, Pierre-Olivier; Sahel, José-Alain; Stanga, Paulo E.; Hafezi, Farhad; Safran, Avinoam B.; Salzmann, Joel; Santos, Arturo; Birch, David; Spencer, Rand; Cideciyan, Artur V.; de Juan, Eugene; Duncan, Jacque L.; Eliott, Dean; Fawzi, Amani; Olmos de Koo, Lisa C.; Ho, Allen C.; Brown, Gary; Haller, Julia; Regillo, Carl; Del Priore, Lucian V.; Arditi, Aries; Greenberg, Robert J.

2016-01-01

Purpose The Argus® II Retinal Prosthesis System (Second Sight Medical Products, Inc., Sylmar, CA) was developed to restore some vision to patients blind from retinitis pigmentosa (RP) or outer retinal degeneration. A clinical trial was initiated in 2006 to study the long-term safety and efficacy of the Argus II System in patients with bare or no light perception due to end-stage RP. Design The study is a prospective, multicenter, single-arm, clinical trial. Within-patient controls included the non-implanted fellow eye and patients' native residual vision compared to their vision when using the System. Subjects There were 30 subjects in 10 centers in the U.S. and Europe. Methods The worse-seeing eye of blind patients was implanted with the Argus II System. Patients wore glasses mounted with a small camera and a video processor that converted images into stimulation patterns sent to the electrode array on the retina. Main Outcome Measures The primary outcome measures were safety (the number, seriousness, and relatedness of adverse events) and visual function, as measured by three computer-based, objective tests. Secondary measures included functional vision performance on objectively-scored real-world tasks. Results Twenty-four out of 30 patients remained implanted with functioning Argus II Systems at 5 years post-implant. Only one additional serious adverse event was experienced since the 3-year time point. Patients performed significantly better with the System ON than OFF on all visual function tests and functional vision tasks. Conclusions The five-year results of the Argus II trial support the long-term safety profile and benefit of the Argus II System for patients blind from RP. The Argus II is the first and only retinal implant to have market approval in the European Economic Area, the United States, and Canada. PMID:27453256

Five-Year Safety and Performance Results from the Argus II Retinal Prosthesis System Clinical Trial.

Science.gov (United States)

da Cruz, Lyndon; Dorn, Jessy D; Humayun, Mark S; Dagnelie, Gislin; Handa, James; Barale, Pierre-Olivier; Sahel, José-Alain; Stanga, Paulo E; Hafezi, Farhad; Safran, Avinoam B; Salzmann, Joel; Santos, Arturo; Birch, David; Spencer, Rand; Cideciyan, Artur V; de Juan, Eugene; Duncan, Jacque L; Eliott, Dean; Fawzi, Amani; Olmos de Koo, Lisa C; Ho, Allen C; Brown, Gary; Haller, Julia; Regillo, Carl; Del Priore, Lucian V; Arditi, Aries; Greenberg, Robert J

2016-10-01

The Argus II Retinal Prosthesis System (Second Sight Medical Products, Inc, Sylmar, CA) was developed to restore some vision to patients blind as a result of retinitis pigmentosa (RP) or outer retinal degeneration. A clinical trial was initiated in 2006 to study the long-term safety and efficacy of the Argus II System in patients with bare or no light perception resulting from end-stage RP. Prospective, multicenter, single-arm clinical trial. Within-patient controls included the nonimplanted fellow eye and patients' native residual vision compared with their vision with the Argus II. Thirty participants in 10 centers in the United States and Europe. The worse-seeing eye of blind patients was implanted with the Argus II. Patients wore glasses mounted with a small camera and a video processor that converted images into stimulation patterns sent to the electrode array on the retina. The primary outcome measures were safety (the number, seriousness, and relatedness of adverse events) and visual function, as measured by 3 computer-based, objective tests. Secondary measures included functional vision performance on objectively scored real-world tasks. Twenty-four of 30 patients remained implanted with functioning Argus II Systems at 5 years after implantation. Only 1 additional serious adverse event was experienced after the 3-year time point. Patients performed significantly better with the Argus II on than off on all visual function tests and functional vision tasks. The 5-year results of the Argus II trial support the long-term safety profile and benefit of the Argus II System for patients blind as a result of RP. The Argus II is the first and only retinal implant to have market approval in the European Economic Area, the United States, and Canada. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Vedolizumab Effectiveness and Safety Over the First Year of Use in an IBD Clinical Practice.

Science.gov (United States)

Vivio, Emily E; Kanuri, Navya; Gilbertsen, Joanna J; Monroe, Kelly; Dey, Neelendu; Chen, Chien-Huan; Gutierrez, Alexandra M; Ciorba, Matthew A

2016-04-01

Vedolizumab inhibits leucocyte vascular adhesion and migration into the gastrointestinal tract through α4β7 integrin blockade. This agent became available in mid-2014 for the treatment of moderate to severe Crohn's disease (CD) and UC (UC). The aim of this study was to assess the patterns of use, effectiveness and safety of vedolizumab in an inflammatory bowel disease (IBD) clinical practice. Patients beginning vedolizumab were enrolled with informed consent. A prospective cohort was followed with laboratory, disease activity and quality-of-life assessments made during infusion visits up to week 14. Duration of vedolizumab use, mucosal healing and safety were analysed retrospectively for all patients not captured in the prospective component of this study. One hundred and two patients started vedolizumab, with 51 patients (30 CD, 21 UC) followed prospectively. The CD patients exhibited a significant decrease in Crohn's Disease Activity Index (p = 0.04) and Harvey-Bradshaw index (p < 0.01) by week 14. The UC patients demonstrated improved partial Mayo scores at weeks 6 (p < 0.01) and 14 (p < 0.001). Ninety percent of all CD and UC patients remained on vedolizumab up to week 14. IBD-related quality of life was improved by week 6 in CD and UC cohorts (p = 0.02 and p < 0.01 respectively). Colectomy for lack of response and systemic histoplamosis were notable reasons for early discontinuation of vedolizumab, which was otherwise well tolerated. Vedolizumab was efficacious and a high percentage of patients continued this therapy beyond induction dosing. Observed safety signals may be attributed to the refractory IBD disease state of this early-adopting clinical cohort. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Clinical efficacy and safety of polyethylene glycol 3350 versus liquid paraffin in the treatment of pediatric functional constipation.

Science.gov (United States)

Rafati, Mr; Karami, H; Salehifar, E; Karimzadeh, A

2011-01-01

Functional constipation is prevalent in children. Recently polyethylene glycol has been introduced as an effective and safe drug to treat chronic constipation. There are only a few clinical trials on comparison of PEG and liquid paraffin in childhood constipation. The purpose of this study was to evaluate clinical efficacy and safety of PEG 3350 solution and liquid paraffin in the treatment of children with functional constipation in Sari Toba clinic during the period of 2008-2009. Children with a history of functional constipation were subjects of this study. One hundred and sixty children of 2-12 years old with functional constipation were randomized in two PEG and paraffin treatment groups. Patients received either 1.0-1.5 g/kg/day PEG 3350 or 1.0-1.5 ml/kg/day liquid paraffin for 4 months. Clinical efficacy was evaluated by stool and encopresis frequency/week and overall treatment success rate was compared in two groups. Compared with the baseline, defecation frequency/ week increased significantly and encopresis frequency meaningfully decreased in two groups during the period of the study. Patients using PEG 3350 had more success rate (mean: 95.3%±3.7) compared with the patients in paraffin group (mean: 87.2%±7.1) (p=0.087). Administration of PEG 3350 were associated with less adverse events than liquid paraffin. In conclusion in treatment of pediatric functional constipation, regarding clinical efficacy and safety, PEG 3350 were at least as effective as liquid paraffin and but less adverse drug events.

Patients' perceptions of safety and quality of maternity clinical handover

Directory of Open Access Journals (Sweden)

Chin Georgiana SM

2011-08-01

Full Text Available Abstract Background Maternity clinical handover serves to address the gaps in knowledge existing when transitions between individuals or groups of clinicians occur throughout the antenatal, intra-partum and postnatal period. There are limited published studies on maternity handover and a paucity of information about patients' perceptions of the same. This paper reports postnatal patients' perceptions of how maternity handover contributes to the quality and safety of maternity care. Methods This paper reports on a mixed-methods study consisting of qualitative interviews and quantitative medical record analysis. Thirty English-speaking postnatal patients who gave birth at an Australian tertiary maternity hospital participated in a semi-structured interview prior to discharge from hospital. Interview data were coded thematically using the constant comparative method and managed via NVivo software; this data set was supplemented by medical record data analysed using STATA. Results Almost half of the women were aware of a handover process. Clinician awareness of patient information was seen as evidence that handover had taken place and was seen as representing positive aspects of teamwork, care and communication by participants, all important factors in the perception of quality health care. Collaborative cross-checking, including the use of cognitive artefacts such as hand held antenatal records and patient-authored birth plans, and the involvement of patients and their support people in handover were behaviours described by participants to be protective mechanisms that enhanced quality and safety of care. These human factors also facilitated team situational awareness (TSA, shared decision making and patient motivation in labour. Conclusions This study illustrates that many patients are aware of handover processes. For some patients, evidence of handover, through clinician awareness of information, represented positive aspects of teamwork, care and

Validation of systems biology derived molecular markers of renal donor organ status associated with long term allograft function.

Science.gov (United States)

Perco, Paul; Heinzel, Andreas; Leierer, Johannes; Schneeberger, Stefan; Bösmüller, Claudia; Oberhuber, Rupert; Wagner, Silvia; Engler, Franziska; Mayer, Gert

2018-05-03

Donor organ quality affects long term outcome after renal transplantation. A variety of prognostic molecular markers is available, yet their validity often remains undetermined. A network-based molecular model reflecting donor kidney status based on transcriptomics data and molecular features reported in scientific literature to be associated with chronic allograft nephropathy was created. Significantly enriched biological processes were identified and representative markers were selected. An independent kidney pre-implantation transcriptomics dataset of 76 organs was used to predict estimated glomerular filtration rate (eGFR) values twelve months after transplantation using available clinical data and marker expression values. The best-performing regression model solely based on the clinical parameters donor age, donor gender, and recipient gender explained 17% of variance in post-transplant eGFR values. The five molecular markers EGF, CD2BP2, RALBP1, SF3B1, and DDX19B representing key molecular processes of the constructed renal donor organ status molecular model in addition to the clinical parameters significantly improved model performance (p-value = 0.0007) explaining around 33% of the variability of eGFR values twelve months after transplantation. Collectively, molecular markers reflecting donor organ status significantly add to prediction of post-transplant renal function when added to the clinical parameters donor age and gender.

Molecular Strain Typing of Clinical Isolates, Trichophyton rubrum using Non Transcribed Spacer (NTS) Region as a Molecular Marker.

Science.gov (United States)

Ramaraj, Vijayakumar; Vijayaraman, Rajyoganandh S; Elavarashi, Elangovan; Rangarajan, Sudha; Kindo, Anupma Jyoti

2017-05-01

Dermatophytes are a group of fungi which infect keratinized tissues and causes superficial mycoses in humans and animals. The group comprises of three major genera, Trichophyton , Microsporum and Epidermophyton . Among them Trichophyton rubrum is a predominant anthropophilic fungi which causes chronic infections. Although, the infection is superficial and treatable, reinfection/coinfection causes inflation in the treatment cost. Identifying the source and mode of transmission is essential to prevent its transmission. Accurate discrimination is required to understand the clinical (relapse or reinfection) and epidemiological implications of the genetic heterogeneity of this species. Polymorphism in the Non Transcribed Spacer (NTS) region of ribosomal DNA (rDNA) clusters renders an effective way to discriminate strains among T. rubrum . To carry out the strain typing of the clinical isolates, Trichophyton rubrum using NTS as a molecular marker. Seventy T.rubrum clinical isolates obtained from April-2011-March 2013, from Sri Ramachandra Medical Centre, Chennai, Tamil Nadu, India, were identified by conventional phenotypic methods and included in this prospective study. The isolates were then subjected to Polymerase Chain Reaction (PCR) targeting two subrepeat elements (SREs), TRS-1 and TRS-2 of the NTS region. Strain-specific polymorphism was observed in both subrepeat loci. Total, nine different strains were obtained on combining both TRS-1 and TRS-2, SREs. The outcome has given a strong representation for using NTS region amplification in discriminating the T. rubrum clinical isolates. The method can be adapted as a tool for conducting epidemiology and population based study in T. rubrum infections. This will help in future exploration of the epidemiology of T. rubrum .

Clinical utility of a combination of tumour markers in the diagnosis of malignant pleural effusions.

Science.gov (United States)

Gaspar, M J; De Miguel, J; García Díaz, J D; Díez, M

2008-01-01

The aim of the present study was to evaluate the diagnostic value of the tumour markers carcinoembryonic antigen (CEA), carbohydrate antigens CA 125, CA 15.3, CA 19.9 and tumor-associated glycoprotein 72 (TAG 72) in the pleural fluid (PF) of patients with pleural effusions of different etiologies. One hundred and fifty-five patients with pleural effusions (40 malignant, 84 benign and 31 paraneoplastic) were studied prospectively. The concentration of the tumour markers in serum and PF were measured by magnetic particle enzyme immunoassay. The PF to serum (PF/S) concentration ratios were calculated. The concentrations of CEA, CA 15.3, CA 19.9 and TAG 72 in PF and the PF/serum ratios were significantly higher in effusions of malignant and paraneoplastic origin than in those of benign origin. The receiver operating characteristic (ROC) curves were calculated for each marker and the diagnostic cut-off point was selected as the value that offered a specificity of 100% (CEA: 6.5 ng/ml; CA 15.3:62.4 IU/l; TAG 72:10.9 IU/l). CEA presented the greatest sensitivity [45% in the malignant group, 38.7% in the paraneoplastic group, and 41.4% in the pooled group (combined malignant and paraneoplastic)]. TAG 72 presented the largest area under the curve (0.89 in the malignant group and 0.80 in the pooled group). The diagnostic efficacy of the PF/S ratios was not better than measurement of the tumour markers in pleural fluid. The highest diagnostic accuracy for the diagnosis of malignant pleural effusions was achieved by grouping the markers in a panel comprising CEA, CA 15.3 and TAG 72; this showed a sensitivity of 75% and a negative predictive value of 79.1% . In the subgroup of patients with negative cytology, the sensitivity was 41.2% for CEA, 35.5% for CA 15.3 and 33.3% for TAG 72. The combination of these three markers achieved a sensitivity of 84.6%. The combined measurement of CEA, CA 15.3 and TAG 72 in pleural fluid is a useful complementary test in the differential

TH-C-18C-01: MRI Safety

Energy Technology Data Exchange (ETDEWEB)

Pooley, R [Mayo Clinic, Jacksonville, FL (United States); Bernstein, M; Shu, Y; Gorny, K; Felmlee, J [Mayo Clinic, Rochester, MN (United States); Panda, A [Mayo Clinic, Arizona, Scottsdale, AZ (United States)

2014-06-15

Clinical diagnostic medical physicists may be responsible for implementing and maintaining a comprehensive MR safety program. Accrediting bodies including the ACR, IAC, Radsite and The Joint Commission each include aspects of MR Safety into their imaging accreditation programs; MIPPA regulations further raise the significance of non-compliance. In addition, The Joint Commission recently announced New and Revised Diagnostic Imaging Standards for accredited health care organizations which include aspects of MR Safety. Hospitals and clinics look to the physicist to understand guidelines, regulations and accreditation requirements related to MR safety. The clinical medical physicist plays a significant role in a clinical practice by understanding the physical basis for the risks and acting as a facilitator to successfully implement a safety program that provides well-planned siting, allows for the safe scanning of certain implanted devices, and helps radiologists manage specific patient exams. The MRI scanning of specific devices will be discussed including cardiac pacemakers and neurostimulators such as deep brain stimulators. Furthermore for sites involved in MR guided interventional procedures, the MR physicist plays an essential role to establish safe practices. Creating a framework for a safe MRI practice includes the review of actual safety incidents or close calls to determine methods for prevention in the future. Learning Objectives: Understand the requirements and recommendations related to MR safety from accrediting bodies and federal regulations. Understand the Medical Physicist's roles to ensure MR Safety. Identify best practices for dealing with implanted devices, including pacemakers and deep brain stimulators. Review aspects of MR safety involved in an MR guided interventional environment. Understand the important MR safety aspects in actual safety incidents or near misses.

Global Distribution of Human-Associated Fecal Genetic Markers in Reference Samples from Six Continents.

Science.gov (United States)

Mayer, René E; Reischer, Georg H; Ixenmaier, Simone K; Derx, Julia; Blaschke, Alfred Paul; Ebdon, James E; Linke, Rita; Egle, Lukas; Ahmed, Warish; Blanch, Anicet R; Byamukama, Denis; Savill, Marion; Mushi, Douglas; Cristóbal, Héctor A; Edge, Thomas A; Schade, Margit A; Aslan, Asli; Brooks, Yolanda M; Sommer, Regina; Masago, Yoshifumi; Sato, Maria I; Taylor, Huw D; Rose, Joan B; Wuertz, Stefan; Shanks, Orin C; Piringer, Harald; Mach, Robert L; Savio, Domenico; Zessner, Matthias; Farnleitner, Andreas H

2018-05-01

Numerous bacterial genetic markers are available for the molecular detection of human sources of fecal pollution in environmental waters. However, widespread application is hindered by a lack of knowledge regarding geographical stability, limiting implementation to a small number of well-characterized regions. This study investigates the geographic distribution of five human-associated genetic markers (HF183/BFDrev, HF183/BacR287, BacHum-UCD, BacH, and Lachno2) in municipal wastewaters (raw and treated) from 29 urban and rural wastewater treatment plants (750-4 400 000 population equivalents) from 13 countries spanning six continents. In addition, genetic markers were tested against 280 human and nonhuman fecal samples from domesticated, agricultural and wild animal sources. Findings revealed that all genetic markers are present in consistently high concentrations in raw (median log 10 7.2-8.0 marker equivalents (ME) 100 mL -1 ) and biologically treated wastewater samples (median log 10 4.6-6.0 ME 100 mL -1 ) regardless of location and population. The false positive rates of the various markers in nonhuman fecal samples ranged from 5% to 47%. Results suggest that several genetic markers have considerable potential for measuring human-associated contamination in polluted environmental waters. This will be helpful in water quality monitoring, pollution modeling and health risk assessment (as demonstrated by QMRAcatch) to guide target-oriented water safety management across the globe.

Chromogranin A as circulating marker for diagnosis and management of neuroendocrine neoplasms: more flaws than fame.

Science.gov (United States)

Marotta, Vincenzo; Zatelli, Maria Chiara; Sciammarella, Concetta; Ambrosio, Maria Rosaria; Bondanelli, Marta; Colao, Annamaria; Faggiano, Antongiulio

2018-01-01

Owing to the heterogeneity of neuroendocrine neoplasms (NENs), the availability of reliable circulating markers is critical for improving diagnostics, prognostic stratification, follow-up and definition of treatment strategy. This review is focused on chromogranin A (CgA), a hydrophilic glycoprotein present in large dense core vesicles of neuroendocrine cells. Despite being long identified as the most useful NEN-related circulating marker, clinical application of CgA is controversial. CgA assays still lack standardization, thus hampering not only clinical management but also the comparison between different analyses. In the diagnostic setting, clinical utility of CgA is limited as hampered by (a) the variety of oncological and non-oncological conditions affecting marker levels, which impairs specificity; (b) the fact that 30-50% of NENs show normal CgA, which impairs sensitivity. Regarding the prognostic phase, there is prospective evidence which demonstrates that advanced NENs secreting CgA have poorer outcome, as compared with those showing non-elevated marker levels. Although the identification of cut-offs allowing a proper risk stratification of CgA-secreting patients has not been performed, this represents the most important clinical application of the marker. By contrast, based on prospective studies, the trend of elevated circulating CgA does not represent a valid indicator of morphological evolution and has therefore no utility for the follow-up phase. Ultimately, current knowledge about the role of the marker for the definition of treatment strategy is poor and is limited by the small number of available studies, their prevalent retrospective nature and the absence of control groups of untreated subjects. © 2018 Society for Endocrinology.

Improved Pancreatic Adenocarcinoma Diagnosis in Jaundiced and Non-Jaundiced Pancreatic Adenocarcinoma Patients through the Combination of Routine Clinical Markers Associated to Pancreatic Adenocarcinoma Pathophysiology.

Science.gov (United States)

Ferri, María José; Saez, Marc; Figueras, Joan; Fort, Esther; Sabat, Miriam; López-Ben, Santiago; de Llorens, Rafael; Aleixandre, Rosa Núria; Peracaula, Rosa

2016-01-01

There is still no reliable biomarker for the diagnosis of pancreatic adenocarcinoma. Carbohydrate antigen 19-9 (CA 19-9) is a tumor marker only recommended for pancreatic adenocarcinoma follow-up. One of the clinical problems lies in distinguishing between this cancer and other benign pancreatic diseases such as chronic pancreatitis. In this study we will assess the value of panels of serum molecules related to pancreatic cancer physiopathology to determine whether alone or in combination could help to discriminate between these two pathologies. CA 19-9, carcinoembryonic antigen (CEA), C-reactive protein, albumin, insulin growth factor-1 (IGF-1) and IGF binding protein-3 were measured using routine clinical analyzers in a cohort of 47 pancreatic adenocarcinoma, 20 chronic pancreatitis and 15 healthy controls. The combination of CA 19-9, IGF-1 and albumin resulted in a combined area under the curve (AUC) of 0.959 with 93.6% sensitivity and 95% specificity, much higher than CA 19-9 alone. An algorithm was defined to classify the patients as chronic pancreatitis or pancreatic cancer with the above specificity and sensitivity. In an independent validation group of 20 pancreatic adenocarcinoma and 13 chronic pancreatitis patients, the combination of the four molecules classified correctly all pancreatic adenocarcinoma and 12 out of 13 chronic pancreatitis patients. Although this panel of markers should be validated in larger cohorts, the high sensitivity and specificity values and the convenience to measure these parameters in clinical laboratories shows great promise for improving pancreatic adenocarcinoma diagnosis.

Improved Pancreatic Adenocarcinoma Diagnosis in Jaundiced and Non-Jaundiced Pancreatic Adenocarcinoma Patients through the Combination of Routine Clinical Markers Associated to Pancreatic Adenocarcinoma Pathophysiology.

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María José Ferri

Full Text Available There is still no reliable biomarker for the diagnosis of pancreatic adenocarcinoma. Carbohydrate antigen 19-9 (CA 19-9 is a tumor marker only recommended for pancreatic adenocarcinoma follow-up. One of the clinical problems lies in distinguishing between this cancer and other benign pancreatic diseases such as chronic pancreatitis. In this study we will assess the value of panels of serum molecules related to pancreatic cancer physiopathology to determine whether alone or in combination could help to discriminate between these two pathologies.CA 19-9, carcinoembryonic antigen (CEA, C-reactive protein, albumin, insulin growth factor-1 (IGF-1 and IGF binding protein-3 were measured using routine clinical analyzers in a cohort of 47 pancreatic adenocarcinoma, 20 chronic pancreatitis and 15 healthy controls.The combination of CA 19-9, IGF-1 and albumin resulted in a combined area under the curve (AUC of 0.959 with 93.6% sensitivity and 95% specificity, much higher than CA 19-9 alone. An algorithm was defined to classify the patients as chronic pancreatitis or pancreatic cancer with the above specificity and sensitivity. In an independent validation group of 20 pancreatic adenocarcinoma and 13 chronic pancreatitis patients, the combination of the four molecules classified correctly all pancreatic adenocarcinoma and 12 out of 13 chronic pancreatitis patients.Although this panel of markers should be validated in larger cohorts, the high sensitivity and specificity values and the convenience to measure these parameters in clinical laboratories shows great promise for improving pancreatic adenocarcinoma diagnosis.

The application of the psychological contract to workplace safety.

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Walker, Arlene; Hutton, Dorothy M

2006-01-01

Psychological contracts of safety are conceptualized as the beliefs of individuals about reciprocal safety obligations inferred from implicit or explicit promises. Although the literature on psychological contracts is growing, the existence of psychological contracts in relation to safety has not been established. The research sought to identify psychological contracts in the conversations of employees about safety, by demonstrating reciprocity in relation to employer and employee safety obligations. The identified safety obligations were used to develop a measure of psychological contracts of safety. The participants were 131 employees attending safety training sessions in retail and manufacturing organizations. Non-participant observation was used to collect the data during safety training sessions. Content analysis was used to analyze the data. Categories for coding were established through identification of language markers that demonstrated contingencies or other implied obligations. Direct evidence of reciprocity between employer safety obligations and employee safety obligations was found in statements from the participants demonstrating psychological contracts. A comprehensive list of perceived employer and employee safety obligations was compiled and developed into a measure of psychological contracts of safety. A small sample of 33 safety personnel was used to validate the safety obligations. CONCLUSIONS AND IMPACT ON INDUSTRY: Implications of these findings for safety and psychological contract research are discussed.

Molecular epidemiology of malaria in Cameroon. XXX. sequence analysis of Plasmodium falciparum ATPase 6, dihydrofolate reductase, and dihydropteroate synthase resistance markers in clinical isolates from children treated with an artesunate-sulfadoxine-pyrimethamine combination.

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Menemedengue, Virginie; Sahnouni, Khalifa; Basco, Leonardo; Tahar, Rachida

2011-07-01

Plasmodium falciparum dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) genes are reliable molecular markers for antifolate resistance. The P. falciparum ATPase 6 (pfatp6) gene has been proposed to be a potential marker for artemisinin resistance. In our previous clinical study, we showed that artesunate-sulfadoxine-pyrimethamine is highly effective against uncomplicated malaria in Yaoundé, Cameroon. In the present study, dhfr, dhps, and pfatp6 mutations in P. falciparum isolates obtained from children treated with artesunate-sulfadoxine-pyrimethamine were determined. All 61 isolates had wild-type Pfatp6 263, 623, and 769 alleles, and 11 (18%) had a single E431K substitution. Three additional mutations, E643Q, E432K, and E641Q, were detected. The results did not indicate any warning signal of serious concern (i.e., no parasites were seen with quintuple dhfr-dhps, DHFR Ile164Leu, or pfatp6 mutations), as confirmed by the high clinical efficacy of artesunate-sulfadoxine-pyrimethamine. Further studies are required to identify a molecular marker that reliably predicts artemisinin resistance.

Immunogenetic markers of Crohn's disease in adults population of the Moscow region

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Stavtsev D.S.

2014-12-01

Full Text Available Aim: to study immunogenetic markers of predisposition to the development and protection for Crohn's disease in adults population of the Moscow region. Material and methods. The study included 53 samples of peripheral blood of patients with Crohn's disease in the Moscow region. The control group was represented by 1,700 samples of umbilical cord blood is healthy newborns. Revealing HLA antigens at low level performed by SSO method on DynalRELI 48 processor. The results received with ambiguous interpretation was using PCR-SSP method (Ivitrogen. Results. Were found the positive and negative associations of groups of HLA alleles with clinical form, the course of Crohn's disease and response to steroid treatment, in particular revealed that, predisposition to the development for Crohn's disease in women and with sensitivity to steroid treatment in this disease associated allele group C*12, to the characteristic restricting markers such as Crohn's disease include the В 38 and A*11 markers nonrestricting, nonpenetrating noninflammatory type groups are alleles B*56 and C*14 and C*14 is also associated with the risk of Crohn's disease in men, characteristic markers of protection to the development of the disease crown with chronic relapsing and severe clinical course are DQB1*02 and DQB1*03, respectively. Conclusion. These results demonstrate the need for studies of gene polymorphism HLA-system, not only in relation to the disease in general, but in selected patients with clinical groups.

The Royal College of Pathologists of Australasia Quality Assurance Program: Immunohistochemistry Breast Marker Audit Overview 2005-2015.

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Haffajee, Zenobia Ayesha Mohamed; Kumar, Beena; Francis, Glenn; Peck, Martyn; Badrick, Tony

2017-11-20

The Royal College of Pathologists of Australasia Quality Assurance Program (RCPAQAP) Anatomical Pathology provides a comprehensive External Quality Assurance (EQA) exercise to review the reporting of immunohistochemistry (IHC) and in-situ hybridization (ISH) breast markers through an audit of clinical results. The aim of this exercise was to provide information regarding the quality of breast marker testing within clinical laboratories from 2005 to 2015. This comprehensive audit included estrogen, progesterone, and HER2 marker reporting. This was an important quality assurance activity established in response to ongoing difficulties experienced in laboratories in this area of testing.

Clinical efficacy, safety, and tolerability of fingolimod for the treatment of relapsing-remitting multiple sclerosis

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Gajofatto A

2015-12-01

Full Text Available Alberto Gajofatto,1,2 Marco Turatti,2 Salvatore Monaco,1,2 Maria Donata Benedetti2 1Department of Neurological, Biomedical and Movement Sciences, University of Verona, Verona, Italy; 2Division of Neurology B, Verona University Hospital, Verona, Italy Abstract: Fingolimod is a selective immunosuppressive agent approved worldwide for the treatment of relapsing-remitting multiple sclerosis (MS, a chronic and potentially disabling neurological condition. Randomized double-blind clinical trials have shown that fingolimod significantly reduces relapse rate and ameliorates a number of brain MRI measures, including cerebral atrophy, compared to both placebo and intramuscular interferon-1a. The effect on disability progression remains controversial, since one Phase III trial showed a significant benefit of treatment while two others did not. Although fingolimod has a very convenient daily oral dosing, the possibility of serious cardiac, ocular, infectious, and other rare adverse events justified the decision of the European Medicines Agency to approve the drug as a second-line treatment for MS patients not responsive to first-line therapy, or those with rapidly evolving course. In the United States, fingolimod is instead authorized as a first-line treatment. The aim of this review is to describe and discuss the characteristics of fingolimod concerning its efficacy, safety, and tolerability in the clinical context of multiple sclerosis management. Keywords: multiple sclerosis, fingolimod, safety, tolerability, efficacy

Markers

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Healthy Schools Network, Inc., 2011

2011-01-01

Dry erase whiteboards come with toxic dry erase markers and toxic cleaning products. Dry erase markers labeled "nontoxic" are not free of toxic chemicals and can cause health problems. Children are especially vulnerable to environmental health hazards; moreover, schools commonly have problems with indoor air pollution, as they are more densely…

Evaluation of Serum CEA, CA19-9, CA72-4, CA125 and Ferritin as Diagnostic Markers and Factors of Clinical Parameters for Colorectal Cancer

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Gao, Yanfeng; Wang, Jinping; Zhou, Yue; Sheng, Sen; Qian, Steven Y.; Huo, Xiongwei

2018-01-01

Blood-based protein biomarkers have recently shown as simpler diagnostic modalities for colorectal cancer, while their association with clinical pathological characteristics is largely unknown. In this study, we not only examined the sensitivity and reliability of single/multiple serum markers for diagnosis, but also assessed their connection with pathological parameters from a total of 279 colorectal cancer patients. Our study shown that glycoprotein carcinoembryonic antigen (CEA) owns the h...

Simulated settings; powerful arenas for learning patient safety practices and facilitating transference to clinical practice. A mixed method study.

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Reime, Marit Hegg; Johnsgaard, Tone; Kvam, Fred Ivan; Aarflot, Morten; Breivik, Marit; Engeberg, Janecke Merethe; Brattebø, Guttorm

2016-11-01

Poor teamwork is an important factor in the occurrence of critical incidents because of a lack of non-technical skills. Team training can be a key to prevent these incidents. The purpose of this study was to explore the experience of nursing and medical students after a simulation-based interprofessional team training (SBITT) course and its impact on professional and patient safety practices, using a concurrent mixed-method design. The participants (n = 262) were organized into 44 interprofessional teams. The results showed that two training sequences the same day improved overall team performance. Making mistakes during SBITT appeared to improve the quality of patient care once the students returned to clinical practice as it made the students more vigilant. Furthermore, the video-assisted oral debriefing provided an opportunity to strengthen interprofessional teamwork and share situational awareness. SBITT gave the students an opportunity to practice clinical reasoning skills and to share professional knowledge. The students conveyed the importance of learning to speak up to ensure safe patient practices. Simulated settings seem to be powerful arenas for learning patient safety practices and facilitating transference of this awareness to clinical practice. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparison between clinical significance of serum proinflammatory proteins (IL-6 and CRP) and classic tumor markers (CEA and CA 19-9) in gastric cancer.

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Lukaszewicz-Zając, Marta; Mroczko, Barbara; Gryko, Mariusz; Kędra, Bogusław; Szmitkowski, Maciej

2011-06-01

Gastric cancer (GC) is a second most common cause of cancer-related death and represents an inflammation-driven malignancy. It has been suggested that interleukin 6 (IL-6) and C-reactive protein (CRP) play a potential role in the growth and progression of GC. The aim of the present study was to compare clinical significance of IL-6 and CRP with classic tumor markers-carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9) in GC patients. The study included 92 patients with GC and 70 healthy subjects. The serum concentrations of IL-6, CEA and CA 19-9 were determined using immunoenzyme assays, whereas CRP using immunoturbidimetric method. We defined the diagnostic criteria and prognostic value for proteins tested. In GC patients, the serum concentrations of all the proteins tested were significantly higher than in healthy subjects. The IL-6, CEA and CA 19-9 levels correlated with nodal metastases, while CRP with tumor stage, gastric wall invasion, presence of nodal and distant metastases. Diagnostic sensitivity of IL-6 was higher (85%) than those of other markers (CRP 66%, CA 19-9 34%, CEA 22%) and increased in combined use with CRP or CEA (88%). The area under ROC curve for IL-6 was larger than those of CRP and classic tumor markers (CEA and CA 19-9). None of the proteins tested was independent prognostic factor for the survival of GC patients. Our findings indicate better usefulness of serum proinflammatory proteins-IL-6 and CRP than classic tumor markers-CEA and CA 19-9 in the diagnosis of GC.

Effects of intermittent fasting on body composition and clinical health markers in humans.

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Tinsley, Grant M; La Bounty, Paul M

2015-10-01

Intermittent fasting is a broad term that encompasses a variety of programs that manipulate the timing of eating occasions by utilizing short-term fasts in order to improve body composition and overall health. This review examines studies conducted on intermittent fasting programs to determine if they are effective at improving body composition and clinical health markers associated with disease. Intermittent fasting protocols can be grouped into alternate-day fasting, whole-day fasting, and time-restricted feeding. Alternate-day fasting trials of 3 to 12 weeks in duration appear to be effective at reducing body weight (≈3%-7%), body fat (≈3-5.5 kg), total cholesterol (≈10%-21%), and triglycerides (≈14%-42%) in normal-weight, overweight, and obese humans. Whole-day fasting trials lasting 12 to 24 weeks also reduce body weight (≈3%-9%) and body fat, and favorably improve blood lipids (≈5%-20% reduction in total cholesterol and ≈17%-50% reduction in triglycerides). Research on time-restricted feeding is limited, and clear conclusions cannot be made at present. Future studies should examine long-term effects of intermittent fasting and the potential synergistic effects of combining intermittent fasting with exercise. © The Author(s) 2015. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Molecular tissue changes in early myocardial ischemia: from pathophysiology to the identification of new diagnostic markers.

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Aljakna, Aleksandra; Fracasso, Tony; Sabatasso, Sara

2018-03-01

Diagnosing early myocardial ischemia (the initial 4 to 6 h after interruption of blood flow to part of the myocardium) remains a challenge for clinical and forensic pathologists. Several immunohistochemical markers have been proposed for improving postmortem detection of early myocardial ischemia; however, no single marker appears to be both sufficiently specific as well as sensitive. This review summarizes the diverse categories of molecular tissue markers that have been investigated in human autopsy samples with acute myocardial infarction as well as in the well-established and widely used in vivo animal model of early myocardial ischemia (permanent ligation of the coronary artery). Recently identified markers appearing during the initial 2 h of myocardial ischemia are highlighted. Among them, only six were tested for specificity (C5b-9, hypoxia-inducible factor 1-alpha, vascular endothelial growth factor, heart fatty acid binding protein, connexin 43, and JunB). Despite the discovery of several potentially promising markers (in terms of early expression and specificity), many of them remain to be tested and validated for application in routine diagnostics in clinical and forensic pathology. In particular, research investigating the postmortem stability of these markers is required before any might be implemented into routine diagnostics. Establishing a standardized panel of immunohistochemical markers may be more useful for improving sensitivity and specificity than searching for a single marker.

Electronic portal imaging device detection of radioopaque markers for the evaluation of prostate position during megavoltage irradiation: a clinical study

International Nuclear Information System (INIS)

Vigneault, Eric; Pouliot, Jean; Laverdiere, Jacques; Roy, Jean; Dorion, Marc

1997-01-01

Purpose: This study was designed to assess daily prostatic apex motion relative to pelvic bone structures during megavoltage irradiation. Methods and Materials: Radioopaque markers were implanted under ultrasound guidance near the prostatic apex of 11 patients with localized prostatic carcinoma. Patients were subsequently treated with a four field-box technique at a beam energy of 23 MV. During treatment, on-line images were obtained with an electronic portal imaging device (EPID). The marker was easily identified, even on unprocessed images, and the distance between the marker and a bony landmark was measured. Timelapse movies were also reviewed. After the completion of treatment, a transcrectal ultrasound examination was performed in 8 of 11 patients, to verify the position of the marker. Results: We acquired over 900 digital portal images and analyzed posterioanterior and right lateral views. The quality of portal images obtained with megavoltage irradiation was good. It was possible to evaluate pelvic bone structures even without image histogram equalization. Moreover, the radioopaque marker was easily visible on every online portal image. The review of timelapse movies showed important interfraction motion of the marker while bone structures remained stable. We measured the position of the marker for each fraction. Marker displacements up to 1.6 cm were measured between 2 consecutive days of treatment. Important marker motions were predominantly in the posteroanterior and cephalocaudal directions. In eight patients, we verified the position of the marker relative to the prostatic apex with ultrasound at the end of the treatments. The marker remained in the trapezoid zone. Intratreatment images reviewed in two cases showed no change in marker position. Our results, obtained during the treatment courses, indicate similar or larger prostate motions than previously observed in studies that used intertreatment x-ray films and CT images. Marker implantation under

Correlation of plasma B-type natriuretic peptide levels with metabolic risk markers.

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Ahued-Ortega, José Armando; León-García, Plácido Enrique; Hernández-Pérez, Elizabeth

2018-04-17

Natriuretic peptide type B (BNP) is a marker of myocardium injury. This peptide has been associated with metabolic risk markers, although controversy exists in this regard. The aim of the present study was to determine the correlation of plasma BNP levels with metabolic risk parameters. A retrospective, observational study that included 152 patients, who were classified according to their clinical diagnosis as patients with metabolic syndrome. Plasma BNP levels and clinical metabolic parameters were assessed by using Spearmańs rank correlation coefficient. A significant inverse association with weight (r=-.408; p<.0001) and BMI (r=-.443; p<.001) was obtained. While a positive significant association with systolic pressure (r=.324; p<.001) was observed. A significant decrease was found in BNP levels and components of metabolic syndrome. (p<.05). Based on the results from this study, we can conclude that BNP determination could be an adequate metabolic marker. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

Markers of stem cells in human ovarian granulosa cells: is there a clinical significance in ART?

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Varras Michail

2012-11-01

Full Text Available Abstract Background The purpose of the study was to determine the incidence of gene expression of Oct-4 and DAZL, which are typical markers for stem cells, in human granulosa cells during ovarian stimulation in women with normal FSH levels undergoing IVF or ICSI and to discover any clinical significance of such expression in ART. Methods Twenty one women underwent ovulation induction for IVF or ICSI and ET with standard GnRH analogue-recombinant FSH protocol. Infertility causes were male and tubal factor. Cumulus–mature oocyte complexes were denuded separately and granulosa cells were analyzed for each patient separately using quantitative reverse-transcription–polymerase chain reaction analysis for Oct-4 and DAZL gene expression with G6PD gene as internal standard. Results G6PD and Oct-4 mRNA was detected in the granulosa cells in 47.6% (10/21. The median of Oct-4 mRNA/G6PD mRNA was 1.75 with intra-quarteral range from 0.10 to 98.21. The OCT-4 mRNA expression was statistically significantly correlated with the number of oocytes retrieved; when the Oct-4 mRNA expression was higher, then more than six oocytes were retrieved (p=0.037, Wilcoxon rank-sum. No detection of DAZL mRNA was found in granulosa cells. There was no additional statistically significant correlation between the levels of Oct-4 expression and FSH basal levels or estradiol peak levels or dosage of FSH for ovulation induction. No association was found between the presence or absence of Oct-4 mRNA expression in granulosa cells and ovarian response to gonadotropin stimulation. Also, no influence on pregnancy was observed between the presence or absence of Oct-4 mRNA expression in granulosa cells or to its expression levels accordingly. Conclusions Expression of OCT-4 mRNA, which is a typical stem cell marker and absence of expression of DAZL mRNA, which is a typical germ cell marker, suggest that a subpopulation of luteinized granulosa cells in healthy ovarian follicles (47

PAM50 Breast Cancer Subtyping by RT-qPCR and Concordance with Standard Clinical Molecular Markers

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Bastien Roy RL

2012-10-01

Full Text Available Abstract Background Many methodologies have been used in research to identify the “intrinsic” subtypes of breast cancer commonly known as Luminal A, Luminal B, HER2-Enriched (HER2-E and Basal-like. The PAM50 gene set is often used for gene expression-based subtyping; however, surrogate subtyping using panels of immunohistochemical (IHC markers are still widely used clinically. Discrepancies between these methods may lead to different treatment decisions. Methods We used the PAM50 RT-qPCR assay to expression profile 814 tumors from the GEICAM/9906 phase III clinical trial that enrolled women with locally advanced primary invasive breast cancer. All samples were scored at a single site by IHC for estrogen receptor (ER, progesterone receptor (PR, and Her2/neu (HER2 protein expression. Equivocal HER2 cases were confirmed by chromogenic in situ hybridization (CISH. Single gene scores by IHC/CISH were compared with RT-qPCR continuous gene expression values and “intrinsic” subtype assignment by the PAM50. High, medium, and low expression for ESR1, PGR, ERBB2, and proliferation were selected using quartile cut-points from the continuous RT-qPCR data across the PAM50 subtype assignments. Results ESR1, PGR, and ERBB2 gene expression had high agreement with established binary IHC cut-points (area under the curve (AUC ≥ 0.9. Estrogen receptor positivity by IHC was strongly associated with Luminal (A and B subtypes (92%, but only 75% of ER negative tumors were classified into the HER2-E and Basal-like subtypes. Luminal A tumors more frequently expressed PR than Luminal B (94% vs 74% and Luminal A tumors were less likely to have high proliferation (11% vs 77%. Seventy-seven percent (30/39 of ER-/HER2+ tumors by IHC were classified as the HER2-E subtype. Triple negative tumors were mainly comprised of Basal-like (57% and HER2-E (30% subtypes. Single gene scoring for ESR1, PGR, and ERBB2 was more prognostic than the corresponding IHC markers as

Safety in cardiac surgery

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Siregar, S.

2013-01-01

The monitoring of safety in cardiac surgery is a complex process, which involves many clinical, practical, methodological and statistical issues. The objective of this thesis was to measure and to compare safety in cardiac surgery in The Netherlands using the Netherlands Association for

meta-analysis of Serum Tumor Markers in Lung Cancer

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Xianfeng LU

2010-12-01

Full Text Available Background and objective The detection of serum tumor markers is of great value for early diagnosis of lung cancer. The aim of this study is to summarize the clinic significance characteristics of serum markers contributing to the detection of lung cancer. Methods References about serum markers of lung cancer were estimated using meta-analysis method. 712 references which included more than 20 cases, 20 controls, the serum markers of 52 832 patients with malignancies and 32 037 patients as controls were evaluated. Results Overall the detection of 13 markers play a significant part in lung cancer diagnosis. The sensitivity of CEA, CA125, CYFRA21-1, TPA, SCCAg, DKK1, NSE, ProGRP in the patients’ serum with lung cancer were 47.50%, 50.11%, 57.00%, 50.93%, 49.00%, 69.50%, 39.73%, 51.48% and the specificity were 92.34%, 80.19%, 90.16%, 88.41%, 91.07%, 92.20%, 89.11%, 94.89%. In the combined analysis of tumor markers: the sensitivity, specificity of NSE+ProGRP were 88.90% and 72.82% in diagnosis of small cell lung cancer, respectively. In diagnosis of squamous corcinoma, the sensitivity and specificity of TSGF+SCCAg+CYFRA21-1 were 95.30% and 74.20%. The the sensitivity and specificity of CA153+Ferrtin+CEA were 91.90% and 44.00% in diagnosis of lung cancer. Conclusion Although the assay of tumor markers in serum is useful for diagnosis of early lung cancer, the sensitivity and specificity are low. Combined detection of these tumor markers could increase sensitivity and specificity.

Safety and efficacy of endovascular therapy and gamma knife surgery for brain arteriovenous malformations in China: Study protocol for an observational clinical trial

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Hengwei Jin

2017-09-01

Full Text Available Introduction: Brain arteriovenous malformations (BAVMs are associated with high morbidity and mortality. The treatment of BAVM remains controversial. Microinvasive treatment, including endovascular therapy and gamma knife surgery, has been the first choice in many conditions. However, the overall clinical outcome of microinvasive treatment remains unknown and a prospective trial is needed. Methods: This is a prospective, non-randomized, and multicenter observational registry clinical trial to evaluate the safety and efficacy of microinvasive treatment for BAVMs. The study will require up to 400 patients in approximately 12 or more centers in China, followed for 2 years. Main subjects of this study are BAVM patients underwent endovascular therapy and/or gamma knife surgery. The trial will not affect the choice of treatment modality. The primary outcomes are perioperative complications (safety, and postoperative hemorrhage incidence rate and complete occlusion rate (efficacy. Secondary outcomes are elimination of hemorrhage risk factors (coexisting aneurysms and arteriovenous fistula, volume reduction and remission of symptoms. Safety and efficacy of endovascular therapy, gamma knife surgery, and various combination modes of the two modalities will be compared. Operative complications and outcomes at pretreatment, post-treatment, at discharge and at 3 months, 6 months and 2 years follow-up intervals will be analyzed using the modified Rankin Scale (mRS. Discussion: The most confusion on BAVM treatment is whether to choose interventional therapy or medical therapy, and the choice of interventional therapy modes. This study will provide evidence for evaluating the safety and efficacy of microinvasive treatment in China, to characterize the microinvasive treatment strategy for BAVMs. Keywords: Brain arteriovenous malformation, Clinical trial, Endovascular therapy, Gamma knife, Safety, Efficacy

State and trait olfactory markers of major depression.

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Marine Naudin

Full Text Available Nowadays, depression is a major issue in public health. Because of the partial overlap between the brain structures involved in depression, olfaction and emotion, the study of olfactory function could be a relevant way to find specific cognitive markers of depression. This study aims at determining whether the olfactory impairments are state or trait markers of major depressive episode (MDE through the study of the olfactory parameters involving the central olfactory pathway. In a pilot study, we evaluated prospectively 18 depressed patients during acute episodes of depression and 6 weeks after antidepressant treatment (escitalopram against 54 healthy volunteers, matched by age, gender and smoking status. We investigated the participants' abilities to identify odors (single odors and in binary mixture, to evaluate and discriminate the odors' intensity, and determine the hedonic valence of odors. The results revealed an "olfactory anhedonia" expressed by decrease of hedonic score for high emotional odorant as potential state marker of MDE. Moreover, these patients experienced an "olfactory negative alliesthesia", during the odor intensity evaluation, and failed to identify correctly two odorants with opposite valences in a binary iso-mixture, which constitute potential trait markers of the disease. This study provides preliminary evidence for olfactory impairments associated with MDE (state marker that are persistent after the clinical improvement of depressive symptoms (trait marker. These results could be explained by the chronicity of depression and/or by the impact of therapeutic means used (antidepressant treatment. They need to be confirmed particularly the ones obtained in complex olfactory environment which corresponds a more objective daily life situation.

Pharmacogenetic markers to predict the clinical response to methotrexate in south Indian Tamil patients with psoriasis.

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Indhumathi, S; Rajappa, Medha; Chandrashekar, Laxmisha; Ananthanarayanan, P H; Thappa, D M; Negi, V S

2017-08-01

Despite the advent of several new systemic therapies, methotrexate remains the gold standard for the treatment of moderate to severe psoriasis. However, there exists a significant heterogeneity in individual response to methotrexate. There are no consistently reliable markers to predict methotrexate treatment response till date. We aimed to demonstrate the association of certain genetic variants in the HLA (HLA-A2, HLA-B17, and HLA-Cw6) and the non-HLA genes including T-helper (Th)-1, Th-2, Th-17 cytokine genes (IFN-γ, IL-2, IL-4, IL-10, IL-12B, and IL-23R), and T-regulatory gene (FOXP3) with the methotrexate treatment response in South Indian Tamil patients with psoriasis. Of the 360 patients recruited, 189 patients with moderate to severe psoriasis were treated with methotrexate. Of the 189 patients, 132 patients responded to methotrexate and the remaining 57 patients were non-responders. We analyzed the association of aforesaid polymorphisms with the methotrexate treatment outcome using binary logistic regression. We observed that there were significant differences between genotype frequencies of HLA-Cw6 and FOXP3 (rs3761548) among the responders compared to non-responders, with conservative estimation. We observed that pro-inflammatory cytokines such as IFN-γ, IL-2, IL-12, and IL-23 were markedly reduced with the use of methotrexate, in comparison to the baseline levels, while the plasma IL-4 levels were increased posttreatment. Our results serve as preliminary evidence for the clinical use of genetic markers as predictors of response to methotrexate in psoriasis. This might aid in the future in the development of a point-of-care testing (POCT) gene chip, to predict optimal treatment response in patients with psoriasis, based on their individual genotypic profile.

Clinical efficacy and safety of polyethylene glycol 3350 versus liquid paraffin in the treatment of pediatric functional constipation

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E Salehifar

2011-05-01

Full Text Available "nBackground and the purpose of the study: Functional constipation is prevalent in children. Recently has been introduced as an effective and safe drug to treat chronic constipation. There are only a few clinical trials on comparison of PEG and liquid paraffin in childhood constipation. The purpose of this study was to evaluate clinical efficacy and safety of PEG 3350 solution and liquid paraffin in the treatment of children with functional constipation in Sari Toba clinic during the period of 2008-2009. "nMethods: Children with a history of functional constipation were subjects of this study. One hundred and sixty children of 2-12 years old with functional constipation were randomized in two PEG and paraffin treatment groups. Patients received either 1.0-1.5 g/kg/day PEG 3350 or 1.0-1.5 ml/kg/day liquid paraffin for 4 months. Clinical efficacy was evaluated by stool and encopresis frequency/week and overall treatment success rate was compared in two groups. "nResults and major conclusion: Compared with the baseline, defecation frequency/ week increased significantly and encopresis frequency meaningfully decreased in two groups during the period of the study. Patients using PEG 3350 had more success rate (mean: 95.3%±3.7 compared with the patients in paraffin group (mean: 87.2%±7.1 (p=0.087. Administration of PEG 3350 was associated with less adverse events than liquid paraffin. In conclusion in treatment of pediatric functional constipation , regarding clinical efficacy and safety, PEG 3350 were at least as effective as liquid paraffin and but less adverse drug events.

Clinical efficacy and safety of polyethylene glycol 3350 versus liquid paraffin in the treatment of pediatric functional constipation

Science.gov (United States)

Rafati, MR.; Karami, H.; Salehifar, E.; Karimzadeh, A.

2011-01-01

Background and the purpose of the study Functional constipation is prevalent in children. Recently polyethylene glycol has been introduced as an effective and safe drug to treat chronic constipation. There are only a few clinical trials on comparison of PEG and liquid paraffin in childhood constipation. The purpose of this study was to evaluate clinical efficacy and safety of PEG 3350 solution and liquid paraffin in the treatment of children with functional constipation in Sari Toba clinic during the period of 2008–2009. Methods Children with a history of functional constipation were subjects of this study. One hundred and sixty children of 2–12 years old with functional constipation were randomized in two PEG and paraffin treatment groups. Patients received either 1.0–1.5 g/kg/day PEG 3350 or 1.0–1.5 ml/kg/day liquid paraffin for 4 months. Clinical efficacy was evaluated by stool and encopresis frequency/week and overall treatment success rate was compared in two groups. Results and major conclusion Compared with the baseline, defecation frequency/ week increased significantly and encopresis frequency meaningfully decreased in two groups during the period of the study. Patients using PEG 3350 had more success rate (mean: 95.3%±3.7) compared with the patients in paraffin group (mean: 87.2%±7.1) (p=0.087). Administration of PEG 3350 were associated with less adverse events than liquid paraffin. In conclusion in treatment of pediatric functional constipation, regarding clinical efficacy and safety, PEG 3350 were at least as effective as liquid paraffin and but less adverse drug events. PMID:22615652

Modulation of Brain Activity with Noninvasive Transcranial Direct Current Stimulation (tDCS): Clinical Applications and Safety Concerns

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Zhao, Haichao; Qiao, Lei; Fan, Dongqiong; Zhang, Shuyue; Turel, Ofir; Li, Yonghui; Li, Jun; Xue, Gui; Chen, Antao; He, Qinghua

2017-01-01

Transcranial direct current stimulation (tDCS) is a widely-used tool to induce neuroplasticity and modulate cortical function by applying weak direct current over the scalp. In this review, we first introduce the underlying mechanism of action, the brief history from discovery to clinical scientific research, electrode positioning and montages, and parameter setup of tDCS. Then, we review tDCS application in clinical samples including people with drug addiction, major depression disorder, Alzheimer's disease, as well as in children. This review covers the typical characteristics and the underlying neural mechanisms of tDCS treatment in such studies. This is followed by a discussion of safety, especially when the current intensity is increased or the stimulation duration is prolonged. Given such concerns, we provide detailed suggestions regarding safety procedures for tDCS operation. Lastly, future research directions are discussed. They include foci on the development of multi-tech combination with tDCS such as with TMS and fMRI; long-term behavioral and morphological changes; possible applications in other research domains, and more animal research to deepen the understanding of the biological and physiological mechanisms of tDCS stimulation. PMID:28539894

Safety evaluation of phytosterols in laying hens: effects on laying performance, clinical blood parameters, and organ development.

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Shi, S R; Shen, Y R; Chang, L L; Zhou, C J; Bo, Z; Wang, Z Y; Tong, H B; Zou, J M

2014-03-01

Phytosterols are intended for use as a novel food ingredient with plasma cholesterol-lowering activity. Although phytosterols are naturally present in the normal diet, daily consumption is insufficient to ensure plasma cholesterol-lowering levels. Therefore, phytosterols may be added to the diets to achieve the desired cholesterol-lowering activity. A subchronic laying hen safety study was conducted to examine if high-dose phytosterols could affect the safety of hens. Three hundred sixty 21-wk-old Hy-Line Brown laying hens were randomly assigned to 5 groups with 6 replicates of 12 birds each; after 3 wk, birds were fed diets supplemented with 0, 20, 80, 400, and 800 mg/kg of phytosterols for 12 wk. Throughout the study, clinical observations and laying performance were measured. At the end of the study, birds were subjected to a full postmortem examination: blood samples were taken for clinical pathology, selected organs were weighed, and specified tissues were taken for subsequent histological examination. No treatment-related changes that were considered to be of toxicological significance were observed. Therefore, a nominal phytosterol concentration of 800 mg/kg was considered to be the no-observed-adverse-effect level.

Interlinkage among cardio-metabolic disease markers in an urban poor setting in Nairobi, Kenya

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Tilahun Nigatu Haregu

2016-02-01

Full Text Available Introduction: The main cardio-metabolic diseases – mostly cardiovascular diseases such as stroke and ischemic heart disease – share common clinical markers such as raised blood pressure and blood glucose. The pathways of development of many of these conditions are also interlinked. In this regard, a higher level of co-occurrence of the main cardio-metabolic disease markers is expected. Evidence about the patterns of occurrence of cardio-metabolic markers and their interlinkage in the sub-Saharan African setting is inadequate. Objective: The goal of the study was to describe the interlinkage among common cardio-metabolic disease markers in an African setting. Design: We used data collected in a cross-sectional study from 5,190 study participants as part of cardiovascular disease risk assessment in the urban slums of Nairobi, Kenya. Five commonly used clinical markers of cardio-metabolic conditions were considered in this analysis. These markers were waist circumference, blood pressure, random blood glucose, total blood cholesterol, and triglyceride levels. Patterns of these markers were described using means, standard deviations, and proportions. The associations between the markers were determined using odds ratios. Results: The weighted prevalence of central obesity, hypertension, hyperglycemia, hypercholesterolemia, and hypertriglyceridemia were 12.3%, 7.0%, 2.5%, 10.3%, and 17.3%, respectively. Women had a higher prevalence of central obesity and hypercholesterolemia as compared to men. Blood glucose was strongly associated with central obesity, blood pressure, and triglyceride levels, whereas the association between blood glucose and total blood cholesterol was not statistically significant. Conclusions: This study shows that most of the common cardio-metabolic markers are interlinked, suggesting a higher probability of comorbidity due to cardio-metabolic conditions and thus the need for integrated approaches.

Gadobutrol for contrast-enhanced magnetic resonance imaging in elderly patients: review of the safety profile from clinical trial, post-marketing surveillance, and pharmacovigilance data

International Nuclear Information System (INIS)

Endrikat, J.; Schwenke, C.; Prince, M.R.

2015-01-01

Aim: To assess the safety of gadobutrol administration in elderly patients (≥65 years) by comparing the incidence of adverse drug reactions (ADRs) following gadobutrol-enhanced magnetic resonance imaging (MRI) procedures in elderly patients with that in adults aged 18–64 years. Materials and methods: Safety data on gadobutrol administration from clinical trials, post-marketing surveillance (PMS) studies, and pharmacovigilance reports were collected in three databases. In each dataset, absolute and relative frequencies of ADRs between age groups were analysed, along with odds ratios and 95% confidence intervals. Logistic regression was used to identify significant influencing factors on ADRs in the PMS and pharmacovigilance data. Results: Rates of reported ADRs were lower in elderly patients versus adults aged <65 years due to a reduced incidence of non-serious ADRs; this was statistically significant for the clinical trials and pharmacovigilance populations, with a trend in the PMS database. Serious ADRs occurred infrequently in the clinical trials and PMS populations (too low for statistical comparison), and pharmacovigilance data demonstrated a low incidence (<0.005%) in both age groups. Conclusions: This evaluation involving three large databases demonstrated no greater incidence of ADRs following gadobutrol-enhanced MRI in elderly patients (≥65 years) compared with younger adults, with gadobutrol having a favourable safety profile in both age groups. -- Highlights: •First dedicated safety study of an extracellular contrast agent in the elderly. •Elderly patients experience fewer non-serious ADRs than younger adults. •Gadobutrol has a favourable safety profile in both age groups

Molecular markers in well-differentiated thyroid cancer.

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D'Cruz, Anil K; Vaish, Richa; Vaidya, Abhishek; Nixon, Iain J; Williams, Michelle D; Vander Poorten, Vincent; López, Fernando; Angelos, Peter; Shaha, Ashok R; Khafif, Avi; Skalova, Alena; Rinaldo, Alessandra; Hunt, Jennifer L; Ferlito, Alfio

2018-06-01

Thyroid nodules are of common occurrence in the general population. About a fourth of these nodules are indeterminate on aspiration cytology placing many a patient at risk of unwanted surgery. The purpose of this review is to discuss various molecular markers described to date and place their role in proper perspective. This review covers the fundamental role of the signaling pathways and genetic changes involved in thyroid carcinogenesis. The current literature on the prognostic significance of these markers is also described. PubMed was used to search relevant articles. The key terms "thyroid nodules", "thyroid cancer papillary", "carcinoma papillary follicular", "carcinoma papillary", "adenocarcinoma follicular" were searched in MeSH, and "molecular markers", "molecular testing", mutation, BRAF, RAS, RET/PTC, PAX 8, miRNA, NIFTP in title and abstract fields. Multiple combinations were done and a group of experts in the subject from the International Head and Neck Scientific Group extracted the relevant articles and formulated the review. There has been considerable progress in the understanding of thyroid carcinogenesis and the emergence of numerous molecular markers in the recent years with potential to be used in the diagnostic algorithm of these nodules. However, their precise role in routine clinical practice continues to be a contentious issue. Majority of the studies in this context are retrospective and impact of these mutations is not independent of other prognostic factors making the interpretation difficult. The prevalence of these mutations in thyroid nodule is high and it is a continuously evolving field. Clinicians should stay informed as recommendation on the use of these markers is expected to evolve.

Tackling Cancer Resistance by Immunotherapy: Updated Clinical Impact and Safety of PD-1/PD-L1 Inhibitors

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Shifaa M. Abdin

2018-01-01

Full Text Available Cancer therapy has been constantly evolving with the hope of finding the most effective agents with the least toxic effects to eradicate tumors. Cancer immunotherapy is currently among the most promising options, fulfilling this hope in a wide range of tumors. Immunotherapy aims to activate immunity to fight cancer in a very specific and targeted manner; however, some abnormal immune reactions known as immune-related adverse events (IRAEs might occur. Therefore, many researchers are aiming to define the most proper protocols for managing these complications without interfering with the anticancer effect. One of these targeted approaches is the inhibition of the interaction between the checkpoint protein, programmed death-receptor 1 (PD-1, and its ligand, programmed death-ligand 1 (PD-L1, via a class of antibodies known as PD-1/PD-L1 inhibitors. These antibodies achieved prodigious success in a wide range of malignancies, including those where optimal treatment is not yet fully identified. In this review, we have critically explored and discussed the outcome of the latest PD-1 and PD-L1 inhibitor studies in different malignancies compared to standard chemotherapeutic alternatives with a special focus on the clinical efficacy and safety. The approval of the clinical applications of nivolumab, pembrolizumab, atezolizumab, avelumab, and durvalumab in the last few years clearly highlights the hopeful future of PD-1/PD-L1 inhibitors for cancer patients. These promising results of PD-1/PD-L1 inhibitors have encouraged many ongoing preclinical and clinical trials to explore the extent of antitumor activity, clinical efficacy and safety as well as to extend their applications.

Tackling Cancer Resistance by Immunotherapy: Updated Clinical Impact and Safety of PD-1/PD-L1 Inhibitors.

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Abdin, Shifaa M; Zaher, Dana M; Arafa, El-Shaimaa A; Omar, Hany A

2018-01-25

Cancer therapy has been constantly evolving with the hope of finding the most effective agents with the least toxic effects to eradicate tumors. Cancer immunotherapy is currently among the most promising options, fulfilling this hope in a wide range of tumors. Immunotherapy aims to activate immunity to fight cancer in a very specific and targeted manner; however, some abnormal immune reactions known as immune-related adverse events (IRAEs) might occur. Therefore, many researchers are aiming to define the most proper protocols for managing these complications without interfering with the anticancer effect. One of these targeted approaches is the inhibition of the interaction between the checkpoint protein, programmed death-receptor 1 (PD-1), and its ligand, programmed death-ligand 1 (PD-L1), via a class of antibodies known as PD-1/PD-L1 inhibitors. These antibodies achieved prodigious success in a wide range of malignancies, including those where optimal treatment is not yet fully identified. In this review, we have critically explored and discussed the outcome of the latest PD-1 and PD-L1 inhibitor studies in different malignancies compared to standard chemotherapeutic alternatives with a special focus on the clinical efficacy and safety. The approval of the clinical applications of nivolumab, pembrolizumab, atezolizumab, avelumab, and durvalumab in the last few years clearly highlights the hopeful future of PD-1/PD-L1 inhibitors for cancer patients. These promising results of PD-1/PD-L1 inhibitors have encouraged many ongoing preclinical and clinical trials to explore the extent of antitumor activity, clinical efficacy and safety as well as to extend their applications.

Daily Prostate Volume and Position Monitoring Using Implanted Gold Markers and On-Board Imaging during Radiotherapy

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Linda Kašaová

2011-01-01

Full Text Available Purpose: This study aimed to evaluate prostate volume changes and prostate motions during radiotherapy. Methods: In 2010, twenty-five patients were treated for prostate cancer by external beam radiotherapy with implanted fiducial markers. Coordinates of three gold markers on kilovoltage images were calculated daily. Volume changes in target structure were observed through changes in intermarker distances. Differences in patient position between laser-tattoo alignment and gold marker localization were evaluated. Intrafraction motion was assessed by measuring marker displacement on kilovoltage images acquired before and after fraction delivery. Results: Prostate shrinkage was observed in 60% of patients. The average shrinkage was 7% of the prostate’s initial volume. Corrections after laser-tattoo alignment remained mostly below 1 cm. The difference between marker centroid position on the actual images and the planning images was 2 ± 1 mm on average. The extension of intrafraction movements was 7.6 ± 0.2 mm on average. Conclusions: In our retrospective study, the possibility for prostate volume changes during radiotherapy was revealed. Intrafraction movements turned out to be the limiting factor in safety margin reduction.

Procalcitonin: A Reliable Marker for the Diagnosis of Neonatal Sepsis

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Adib, Minoo; Bakhshiani, Zahra; Navaei, Fakhri; Saheb Fosoul, Fereshteh; Fouladi, Salomeh; Kazemzadeh, Hamidreza

2012-01-01

Objective(s) In the last few years, serum procalcitonin has been proposed as an early marker of infections in neonates, with varying results. In this study, we aimed to investigate the value of procalcitonin, and C- reactive protein in establishing the diagnosis of neonatal sepsis. Materials and Methods Blood samples were collected at admission from 69 neonates with suspected infection (admitted to the Neonatal Intensive Care Units at Alzahra and Dr Beheshti Hospital in and Fatema-Zahra in Najafabad from May 2005 to April 2006). Patients were categorized in different groups according to clinical symptoms of sepsis, bacteriological and laboratory results. Group I consisted of 20 newborns with positive blood cultures and other biological tests which suggested infection. Group II consisted of 49 neonates with negative blood cultures but had two or three of clinical signs of sepsis. The control group included 18 healthy neonates with physiological hyperbilirubinemia and no clinical and biological data of infection, referred to the hospital for bilirubin determination. Procalcitonin and C-reactive protein (CRP) were determined by immunoluminometric assay and nephlometry method respectively. Results Mean levels of procalcitonin and CRP in septic neonates (group I) were significantly higher than the other two groups (P< 0.005). Sensitivity, specificity, positive predictive value and negative predictive value were determined for all markers and compared with each other. Conclusion We conclude that procalcitonin is a better marker than CRP in the diagnosis of neonatal sepsis. PMID:23493845

Expediting Clinician Adoption of Safety Practices: The UCSF Venous Access Patient Safety Interdisciplinary Education Project

National Research Council Canada - National Science Library

Donaldson, Nancy E; Plank, Rosemary K; Williamson, Ann; Pearl, Jeffrey; Kellogg, Jerry; Ryder, Marcia

2005-01-01

...) Venous Access Device (VAD) Patient Safety Interdisciplinary Education Project was to develop a 30-hour/one clinical academic unit VAD patient safety course with the aim of expediting clinician adoption of critical concepts...

Effect of Non-Surgical Periodontal Treatment on Clinical and Biochemical Risk Markers of Cardiovascular Disease: A Randomized Trial.

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Hada, Divya Singh; Garg, Subhash; Ramteke, Girish B; Ratre, Madhu Singh

2015-11-01

Various studies have shown periodontal disease is one of the risk factors for coronary heart disease (CHD), and periodontal treatment of patients with CHD has also been correlated with reduction in systemic markers of CHD. The aim of this study is to evaluate the effect of non-surgical periodontal treatment (NSPT) on the cardiovascular clinical and biochemical status of patients with CHD. Seventy known patients with CHD were allocated randomly to either a control group (C; no periodontal therapy) (n = 35) or an experimental group (E; NSPT in the form of scaling and root planing [SRP]) (n = 35). Cardiovascular status was assessed using clinical parameters such as pulse, respiratory rate, blood pressure (BP), and biochemical parameters, such as high-sensitivity C-reactive protein (hsCRP), lipid profile, and white blood cell (WBC) count, at baseline and 1, 3, and 6 months. Intergroup and intragroup comparisons were performed using Student t test, and P C, n = 25; group E, n = 30). Highly statistically significant reduction was observed in systolic BP (7.1 mm Hg) and very-low-density lipoproteins (VLDLs; 5.16 mg/dL) in group E. Changes were also observed in other cardiovascular biochemical and clinical parameters but were not statistically significant. NSPT (in the form of SRP) positively affects limited cardiovascular (clinical and biochemical) status of patients with CHD. Reduction in triglyceride, VLDL, total WBC, lymphocyte, and neutrophil counts and increase in hsCRP, total cholesterol, high-density lipoprotein, and low-density lipoprotein levels were observed. Highly significant reduction in VLDL cholesterol levels and systolic BP was observed among the various parameters measured.

Can urinary exosomes act as treatment response markers in prostate cancer?

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Tabi Zsuzsanna

2009-01-01

Full Text Available Abstract Background Recently, nanometer sized vesicles (termed exosomes have been described as a component of urine. Such vesicles may be a useful non-invasive source of markers in renal disease. Their utility as a source of markers in urological cancer remains unstudied. Our aim in this study was to investigate the feasibility and value of analysing urinary exosomes in prostate cancer patients undergoing standard therapy. Methods Ten patients (with locally advanced PCa provided spot urine specimens at three time points during standard therapy. Patients received 3–6 months neoadjuvant androgen deprivation therapy prior to radical radiotherapy, comprising a single phase delivering 55 Gy in 20 fractions to the prostate and 44 Gy in 20 fractions to the pelvic nodes. Patients were continued on adjuvant ADT according to clinical need. Exosomes were purified, and the phenotype compared to exosomes isolated from the prostate cancer cell line LNcaP. A control group of 10 healthy donors was included. Serum PSA was used as a surrogate treatment response marker. Exosomes present in urine were quantified, and expression of prostate markers (PSA and PSMA and tumour-associated marker 5T4 was examined. Results The quantity and quality of exosomes present in urine was highly variable, even though we handled all materials freshly and used methods optimized for obtaining highly pure exosomes. There was approx 2-fold decrease in urinary exosome content following 12 weeks ADT, but this was not sustained during radiotherapy. Nevertheless, PSA and PSMA were present in 20 of 24 PCa specimens, and not detected in healthy donor specimens. There was a clear treatment-related decrease in exosomal prostate markers in 1 (of 8 patient. Conclusion Evaluating urinary-exosomes remains difficult, given the variability of exosomes in urine specimens. Nevertheless, this approach holds promise as a non-invasive source of multiple markers of malignancy that could provide

Clinical procedure for colon carcinoma tissue sampling directly affects the cancer marker-capacity of VEGF family members

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Pringels, Sarah; Van Damme, Nancy; De Craene, Bram; Pattyn, Piet; Ceelen, Wim; Peeters, Marc; Grooten, Johan

2012-01-01

mRNA levels of members of the Vascular Endothelial Growth Factor family (VEGF-A, -B, -C, -D, Placental Growth Factor/PlGF) have been investigated as tissue-based markers of colon cancer. These studies, which used specimens obtained by surgical resection or colonoscopic biopsy, yielded contradictory results. We studied the effect of the sampling method on the marker accuracy of VEGF family members. Comparative RT-qPCR analysis was performed on healthy colon and colon carcinoma samples obtained by biopsy (n = 38) or resection (n = 39) to measure mRNA expression levels of individual VEGF family members. mRNA levels of genes encoding the eicosanoid enzymes cyclooxygenase 2 (COX2) and 5-lipoxygenase (5-LOX) and of genes encoding the hypoxia markers glucose transporter 1 (GLUT-1) and carbonic anhydrase IX (CAIX) were included as markers for cellular stress and hypoxia. Expression levels of COX2, 5-LOX, GLUT-1 and CAIX revealed the occurrence in healthy colon resection samples of hypoxic cellular stress and a concurrent increment of basal expression levels of VEGF family members. This increment abolished differential expression of VEGF-B and VEGF-C in matched carcinoma resection samples and created a surgery-induced underexpression of VEGF-D. VEGF-A and PlGF showed strong overexpression in carcinoma samples regardless of the sampling method. Sampling-induced hypoxia in resection samples but not in biopsy samples affects the marker-reliability of VEGF family members. Therefore, biopsy samples provide a more accurate report on VEGF family mRNA levels. Furthermore, this limited expression analysis proposes VEGF-A and PlGF as reliable, sampling procedure insensitive mRNA-markers for molecular diagnosis of colon cancer