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PubMed1998

An exploration of GPs' use of MRI: a critical incident study.

BACKGROUND: Direct access to Magnetic Resonance Imaging (MRI) is becoming available to GPs in the UK, offering major benefits for the improved diagnosis and management of certain clinical conditions. Variations in usage of this service may be large, and effective locally produced guidelines are not currently available. The Department of General Practice is conducting a research programme to develop and evaluate methods to optimize MRI use by GPs. OBJECTIVES: We aimed to describe the current use of MRI by GPs in South Glamorgan; to summarize their reasons for requesting MRI; and to produce criteria to assess the appropriateness of magnetic resonance (MR) scan requests. METHODS: Using the critical incident technique, 25 GPs were interviewed about recent scans requested for patients with knee and lumbar spine complaints. A local panel of primary and secondary care doctors was convened to develop criteria for assessing MR scan requests. RESULTS: Sixty-two scan requests were discussed. Doctors' reasons for requesting MR scans were identified and classified. Reasons for requests included personal, contextual and biomedical variables. Fifteen patients (24%) were managed in primary care following MRI when otherwise they would have been referred. When referrals were made, GPs felt able to reinforce the request and occasionally to direct the patient somewhere more appropriate. The panel reviewed the interview data to produce objective criteria to assess scan requests. The criteria reflect the relative importance of non-biomedical variables in the decision to request MRI. CONCLUSION: The study identified those reasons which are important to GPs when requesting MR scans and the impact of this new technology upon patient management. Interview data have been used to inform locally developed consensus criteria, which will be made available as practice guidelines as the research programme progresses.

Aged↗
PubMed1999

Comparative characteristics of the Israeli Newcastle disease virus field strains by means of a wide panel of monoclonal antibodies against hemagglutinin-neuraminidase glycoprotein.

Fourteen mouse monoclonal antibodies (MAB) were tested for their ability to react with 15 reference and 52 local Newcastle disease virus (NDV) strains isolated in Israel during the last decade from feral birds. All the field isolates had no antigenic difference when examined by classic serological tests. However, MAB-mediated analysis revealed wide antigenic heterogeneity amongst the studied viruses. By the pattern of the MAB reactivity, all the isolates could be distributed into 13 groups.

Animals↗
PubMed1982

Deficiency of the second complement component association with the HLA haplotype A10, B18 in a normal population.

Serum C2 activity was measured in 135 individuals drawn from a panel of 418 tissue-typed blood donors. The study group included all donors with HLA antigens A10 and B18. Heterozygote C2 deficiency (C2Dhet) was defined by reference to the range of C2 activity in previously studied obligate heterozygotes. Five donors were C2Dhet. Family studies confirmed that C2Dhet was associated in all instance with an A10, B18 haplotype. The minimum frequency for C2Dhet was 1.2% in the panel of 418 donors and 62.5% in those donors with an A10, B18 haplotype.

Complement C2↗
PubMed2002

Developing and testing methods for improving patient-oriented mental health care.

There is a trend in nursing policy and practice towards allowing patients to participate actively in their treatment and the services they use. The author concludes, based on an earlier qualitative study, that psychiatric patients in a hospital environment want a more active role in their treatment and that psychiatric nurses also aim at more active patient participation. In mental health care, professionals often define the needs of patients in terms of their own expertise and tend to overlook the variety of the service users' needs. The need to improve and empower psychiatric patients is a considerable challenge to present-day nursing. The purpose of this paper is to describe the theoretical background of tools used to assess patients' involvement in mental health care and the process by which credibility can be determined in rating the panel phase of instrument construction. The instruments, based on a qualitative study using grounded theory, produced a model of patient initiatives in psychiatric nursing. Content validity refers to the determination of the substantive representativeness or relevance of the items of an instrument. Face validity has been defined as validity conferred by a lay persons' acceptance that a procedure, statement or instrument appears to be sound or relevant. In the panel rating, the raters were experts. They evaluated the readability, consistency and content validity of the instruments' items. In the instrument for nurses, the content validity was 0.84 and consistency 0.91; this corresponds to 0.91 and 0.95, respectively, in the instrument for patients.

Humans↗
PubMed2001

Flow cytometric analysis of childhood leukemias.

OBJECTIVE: To collect demographic data for childhood (less than 15 years) leukemias in Karachi, describe the accuracy of the cell surface markers routinely used in the flow cytometric analysis of leukemic cells and arrive at an ideal panel of antibodies for analyzing leukemic samples. MATERIALS AND METHODS: Data from 62 consecutive cases of childhood leukemias referred to the Department of Pathology, Aga Khan University Hospital, (AKUH) between January 1995 and December 1998 was analyzed using Epi Info Version 6. Flow cytometry on all samples was performed using standard protocols. RESULTS: The mean age of patients was 8.2 years and 49 (79%) were males. Fifty (81%) had acute lymphoblastic leukemias of which 50% were CD10 positive and 24% CD10 negative Pre-B cell leukemias. Among all Pre B cell All 98% were positive for CD19, 96% for CD22, 89% for HLA-DR and 67% for CD10. Of the 10 AML cases, 100% were positive for CD33, 90% for CD13, 80% for CD19 and 70% for HLA-DR. CONCLUSION: The mean age in this study population was significantly higher and percentage of CD10 positive Pre-B All is lower than that in the West. Both these factors might be responsible for the poorer prognosis of these patients. It is not possible to specify a minimum or maximum panel of antibodies that should be used for phenotyping all cases of childhood leukemias. A certain degree or redundancy is essential in any panel of antibodies used for flow cytometry of leukemias.

Acute Disease↗
PubMed2002

Radiation dose reduction in chest radiography using a flat-panel amorphous silicon detector.

AIM: The aim of this study was to evaluate the image quality and the potential for radiation dose reduction with a digital flat-panel amorphous silicon detector radiography system. MATERIAL AND METHODS: Using flat-panel technology, radiographs of an anthropomorphic thorax phantom were taken with a range of technical parameters (125kV, 200mA and 5, 4, 3.2, 2, 1, 0.5, and 0.25mAs) which were equivalent to a radiation dose of 332, 263, 209, 127, 58.7, 29, and 14 microGy, respectively. These images were compared to radiographs obtained by a conventional film-screen radiography system at 125kV, 200mA and 5mAs (equivalent to 252 microGy) which served as reference. Three observers evaluated independently the visibility of simulated rounded lesions and anatomical structures, comparing printed films from the flat-panel amorphous silicon detector and conventional x-ray system films. RESULTS: With flat-panel technology, the visibility of rounded lesions and normal anatomical structures at 5, 4, and 3.2mAs was superior compared to the conventional film-screen radiography system. (P< or =0.0001). At 2mAs, improvement was only marginal (P=0.19). At 1.0, 0.5 and 0.25mAs, the visibility of simulated rounded lesions was worse (P< or =0.004). Comparing fine lung parenchymal structures, the flat-panel amorphous silicon detector showed improvement for all exposure levels down to 2mAs and equality at 1mAs. CONCLUSION: Compared to a conventional x-ray film system, the flat-panel amorphous silicon detector demonstrated improved image quality and the possibility for a reduction of the radiation dose by 50% without loss in image quality.

Humans↗
PubMed2006

Collaborative study to evaluate a new ELISA test to monitor the effectiveness of rabies vaccination in domestic carnivores.

To prevent any introduction of rabies, many rabies-free countries have adopted a scheme requiring the rabies vaccination of pets associated with a serological test. FAVN test and RFFIT are the current OIE prescribed techniques to perform this assay. A qualitative indirect ELISA (Serelisa) test has been recently described as a screening test to monitor the effectiveness of rabies vaccination of pets. A lack of sensitivity requires ELISA negative samples to be retested using an OIE confirmatory test. This raised the question whether this new test could be reasonably proposed as an alternative tool in the context of international trades of pets. The Community Reference Institute of Nancy organized a short trial to answer this question. In this study, 16 laboratories tested a panel of their own samples with FAVN test/RFFIT and the Serelisa. The comparison of results revealed that the performance of the Serelisa is highly heterogeneous. A lack of sensitivity was detected in 50% of participants, when 25% of laboratories obtained a significant rate of false positive results. This last point questions the pertinence of using the Serelisa in the context of international trades by preventing any movements of insufficiently or non-protected animals.

Animals↗
PubMed2000

Immunophenotyping of peripheral blood, ranges of serum chemistries and clinical hematology values of healthy chimpanzees (Pan troglodytes).

This paper presents clinical chemistry, hematology and immunophenotyping data from 102 chimpanzees over a 2-year period. The groupings were: 3 years or less, 4-7 years, and 8 + years. These data are intended to augment formerly published information on these parameters and to serve as a concise reference guide for primate veterinarians and researchers for whom these data may be useful. This study has larger samplings than previously published data and more panel constituents by immunophenotyping.

Animals↗
PubMed1997

Mouse/human chimeric IgG1 and IgG4 antibodies directed to the house dust mite allergen Der p 2: use in quantification of allergen specific IgG.

BACKGROUND AND OBJECTIVE: Chimeric mouse/human monoclonal IgG1 and IgG4 antibodies were developed against the house dust mite allergen Der p 2. These chimeric IgG antibodies, hIgG1-Dp2 A and hIgG4-Dp2 A, have the same binding characteristics as the previously reported chimeric hIgE-Dp2 A and are composed of the heavy chain variable domains and light chains of the original murine monoclonal antibody 2B12, whereas the heavy chain constant domains have been replaced by the human IgG1 or IgG4 heavy chain. The expression level of hIgG1-Dp2 A and hIgG4-Dp2 A was 1 and 3.5 microg/mL, respectively. METHODS AND RESULTS: Since all IgG in these culture supernatants is allergen-specific, they are useful reference reagents and enable the calculation of the amount of allergen specific IgG1 and IgG4 antibodies in absolute IgG amounts. The results obtained with two panels of sera from patients in immunotherapeutic treatment were evaluated and compared in Der p 2 IgE, IgG1 and IgG4 RAST and with reversed IgG4 RAST using labelled purified Der p 2. Close agreement between the results for the two IgG4 assays was found. CONCLUSION: With these chimeric reference reagents the quantities of isotype specific antiallergen antibodies can be calculated and compared.

Animals↗
PubMed2006

Standard setting: comparison of two methods.

BACKGROUND: The outcome of assessments is determined by the standard-setting method used. There is a wide range of standard-setting methods and the two used most extensively in undergraduate medical education in the UK are the norm-reference and the criterion-reference methods. The aims of the study were to compare these two standard-setting methods for a multiple-choice question examination and to estimate the test-retest and inter-rater reliability of the modified Angoff method. METHODS: The norm-reference method of standard-setting (mean minus 1 SD) was applied to the 'raw' scores of 78 4th-year medical students on a multiple-choice examination (MCQ). Two panels of raters also set the standard using the modified Angoff method for the same multiple-choice question paper on two occasions (6 months apart). We compared the pass/fail rates derived from the norm reference and the Angoff methods and also assessed the test-retest and inter-rater reliability of the modified Angoff method. RESULTS: The pass rate with the norm-reference method was 85% (66/78) and that by the Angoff method was 100% (78 out of 78). The percentage agreement between Angoff method and norm-reference was 78% (95% CI 69% - 87%). The modified Angoff method had an inter-rater reliability of 0.81-0.82 and a test-retest reliability of 0.59-0.74. CONCLUSION: There were significant differences in the outcomes of these two standard-setting methods, as shown by the difference in the proportion of candidates that passed and failed the assessment. The modified Angoff method was found to have good inter-rater reliability and moderate test-retest reliability.

Clinical Competence↗
PubMed1993

Epidemiology of chronic fatigue syndrome: the Centers for Disease Control Study.

The US Centers for Disease Control initiated physician-based chronic fatigue syndrome (CFS) surveillance systems in four cities in September 1989 to determine the prevalence, incidence, course and impact of the illness. The participating physicians have referred to our surveillance system 590 patients who were ill during the first two years of surveillance with severe, debilitating, unexplained fatigue for at least the preceding six months. Referred patients were screened for psychiatric disorders preceding, concurrent with, and subsequent to the onset of their fatigue by specially trained nurses using a modified Diagnostic Interview Schedule. Complete health histories were obtained by interview and review of medical records and a basic panel of standard laboratory diagnostic tests were conducted. Four physicians have independently reviewed the health information of 337 of the patients for classification. Approximately 26% of patients referred to the surveillance system met the CFS case definition in all regards, 14% lacked one or more of the required eight symptom criteria, 15% were judged to have another possible or known medical illness which could account for the severe fatigue, and the remaining 45% did not meet the case definition because of histories of psychiatric disorders preceding the onset of fatigue. Minimum prevalence rates for the period 1 September 1989 to 1 September 1991 ranged from 2.0 to 7.3 per 100,000 of the general population across the four study sites and rates based on prorated data ranged from 4.6 to 11.3 per 100,000. More than 80% of the CFS cases were female, most were white, and their average age at onset was approximately 30 years.

Adult↗
PubMed2005

Evaluation of a commercial assay for the detection of mumps specific IgM antibodies in oral fluid and serum specimens.

BACKGROUND: An IgM antibody capture radioimmunoassay (MACRIA) has been used in the UK Reference Laboratory for the detection of mumps specific IgM antibodies in oral fluid and serum samples. The method has proved both sensitive and specific and has been used for the surveillance of mumps since 1994. The use of radioactive labels has restricted the use of MACRIA to specialised laboratories and alternative, non-isotopic, sensitive assays capable of detecting the low levels of specific antibodies in oral fluid have not been available. Recently, a novel mumps specific IgM capture enzyme immunoassay (MACEIA) utilising recombinant mumps nucleoprotein (rMuVN) and monoclonal antibodies to the nucleoprotein, produced by Microimmune Limited, has been developed for use with both serum and oral fluid samples. OBJECTIVES: In this study, we have evaluated the performance of the Microimmune MACEIA for both serum and oral fluid against specimens tested by MACRIA. STUDY DESIGN: The panel consisted of matched serum and oral fluid specimens from 137 cases of suspected mumps received in the Virus Reference Department for routine investigation from March 2003 to October 2004. RESULTS: The sensitivity, specificity, positive and negative predictive value of the Microimmune MACEIA on serum samples compared to MACRIA were 98.8%, 100.0%, 100.0% and 98.5%, respectively. The sensitivity, specificity, positive and negative predictive value of the Microimmune MACEIA on oral fluid samples compared to Microimmune MACEIA and MACRIA consensus results on the paired serum samples were 90.3%, 97.6%, 98.3% and 87.1%, respectively. CONCLUSIONS: The Microimmune MACEIA was found to be a rapid, sensitive and specific alternative to MACRIA for the detection of mumps specific IgM in sera and oral fluids.

Biological Assay↗
PubMed1989

Mononuclear cell types in cerebrospinal fluid and blood of patients with multiple sclerosis. Quantitation by immunoenzyme microassay with panel of monoclonal antibodies.

Phenotypic distribution of mononuclear cells in cerebrospinal fluid (CSF) and peripheral blood from patients with multiple sclerosis (MS) and, for reference, patients with acute aseptic meningoencephalitis (AM), and in blood only from healthy controls, was studied with an immunoenzymatic microassay enabling analysis even in the presence of a normal CSF cell count. In MS, increased CD5+ (pan-T) cell proportion in CSF compared with blood was not reflected by changes of CD4+ or CD8+ cells, while in AM, an increase of CD4+ cells was registered. Therefore, a population of CD5+, CD4-, and CD8- cells may be anticipated to exist in CSF of patients with MS. Numbers of OKB7+, OKM1+, or HLA-DR+ cells did not distinguish between MS and AM. Proliferating cells expressing transferrin receptors (OKT9+ cells) were generally few or absent in CSF and not useful as a marker of disease activity in either MS or AM.

Acute Disease↗
PubMed1998

Reliability of panel-based guidelines for colonoscopy: an international comparison.

BACKGROUND: This study examined the reliability of explicit guidelines developed using the RAND-UCLA appropriateness method. METHODS: The appropriateness of over 400 indications for colonoscopy was rated by two multispecialty expert panels (United States and Switzerland). A nine-point scale was used, which was consolidated into three categories of appropriateness: appropriate, uncertain, inappropriate. The distribution of appropriateness ratings between the two panels and the intrapanel and interpanel agreement for categories of appropriateness were calculated for all possible indications. Similar statistics were calculated for a series of 577 primary care patients referred for colonoscopy in Switzerland. RESULTS: Over 80% of all indications (348) could be directly compared. The proportions of indications classified as appropriate, uncertain, or inappropriate were 28.4%, 24.7%, 46.6% and 33.0%, 23.0%, 44.0% for the U.S. and the Swiss panels, respectively. Interpanel agreement was excellent for all the possible indications (kappa value: 0.75) and lower for actual cases (kappa value: 0.51) because of lower agreement for the most frequently encountered indications. CONCLUSIONS: Good agreement between the two sets of criteria was found, pointing to the reliability of the method. Partial disagreement occurred essentially for a few, albeit frequently encountered, indications for use of colonoscopy in cases of uncomplicated lower abdominal pain or constipation.

Colonoscopy↗
PubMed2026

Pangenomes aid accurate detection of large insertions and deletions from targeted sequencing: the case of cardiomyopathies.

BACKGROUND: Gene panels represent a widely used strategy for genetic testing in a vast range of Mendelian disorders. While this approach aids reliable bioinformatic detection of short coding variants, it often fails to detect many larger variants. Recent studies have recommended the adoption of pangenome references (as opposed to linear reference genomes like GRCh38) to augment detection of large variants from targeted sequencing, potentially providing diagnostic laboratories with the possibility to streamline diagnostic work-ups and reduce costs. METHODS: Here, we analyze 1969 cardiomyopathy cases and 1805 controls sequenced with the Illumina Trusight Cardio panel using a pangenome-based workflow (GRAF) and five conventional orthogonal methodologies (GATK HaplotypeCaller, GATK-gCNV, ExomeDepth, Manta and Lumpy-SV) to detect variants &#x2265;&#x2009;20&#xa0;bp in size. RESULTS: Following lab-based variant validation by means of PCR and Sanger sequencing, we show that GRAF conjugates higher precision and recall (F1 score 0.86) compared with other methods (F1 0-0.57) in detecting potentially pathogenic variants &#x2265;&#x2009;20&#xa0;bp from short-read panel data. Results were complemented by a comparison of the tools' performance in detecting ground truth variants on reference sample HG002 from Genome In A Bottle, which confirmed GRAF to outperform other tools also on exome sequencing (F1 0.97 vs. 0-0.94). Notably, in the HG002 benchmark dataset, GRAF also showed slightly improved performance compared to GATK HaplotypeCaller in the identification of small variants (1-19&#xa0;bp; F1 0.975 vs. 0.968). CONCLUSIONS: Our results indicate that pangenome-based workflows aid improved detection of large variants from targeted sequencing data in the clinical context and suggest that they may contribute to more unified variant detection frameworks for all-size genetic variants in the future.

Humans↗
PubMed2006

Evaluation of multiplex flow cytometric opsonophagocytic assays for determination of functional anticapsular antibodies to Streptococcus pneumoniae.

The determination of functional antipneumococcal capsular polysaccharide antibodies by sequential testing of pre- and postvaccination serum samples one serotype at a time is sample-intensive and time-consuming and has a relatively low throughput. We tested several opsonophagocytic assay (OPA) formats, including the reference killing method, a monovalent bacterium-based flow method, a trivalent bacterium-based flow method, and a tetravalent bead-based flow method using a panel of sera (4 prevaccination and 16 postvaccination, from healthy adults immunized with the 23-valent pneumococcal polysaccharide vaccine). The trivalent and tetravalent methods allow simultaneous measurements of opsonic antibodies to multiple pneumococcal serotypes. The trivalent bacterial-flow OPA had significant correlation to the reference OPA method and to a previously published flow cytometric OPA (r values ranged from 0.61 to 0.91, P < 0.05) for serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F. The tetravalent OPA had significant correlation to all OPA method formats tested (r values from 0.68 to 0.92, P < 0.05) for all seven serotypes tested. This tetravalent OPA is an alternative to other OPA methods for use during vaccine evaluation and clinical trials. Further, the flow cytometric multiplex OPA format has the potential for expansion beyond the current four serotypes to eight or more serotypes, which would further increase relative sample throughput while reducing reagent and sample volumes used.

Adult↗