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PubMed1989

Cholesterol and coronary heart disease prevention--a transatlantic consensus.

Recent research findings have enhanced interest in coronary heart disease prevention. Three expert panels, one in the United States and two in Europe, have addressed the subject and recommended appropriate action. The report of the United States Consensus Conference on Lowering Blood Cholesterol appeared in 1985, and the reports of the European Atherosclerosis Society and British Cardiac Society appeared in 1987. We discuss these reports and emphasize the proposals concerning cholesterol. We review the scientific background to the decisions of the expert panels, high-risk and population-based strategies, cholesterol screening and cholesterol reference levels for the initiation of treatment and therapeutic goals. Dietary recommendations are highlighted and the attention given to special groups such as women, the elderly and children is appraised. Finally, the recommendations of the reports regarding the other risk factors are discussed. We note the general consensus among them and outline the strategies and guidelines which advocate concerted effort to reduce the burden of coronary heart disease.

Adolescent↗
PubMed2005

Usefulness of HBME-1, cytokeratin 19 and galectin-3 immunostaining in the diagnosis of thyroid malignancy.

AIMS: To investigate the usefulness of immunohistochemical expression and immunolocalization of a panel of thyroid malignancy markers including HBME-1, cytokeratin (CK) 19 and galectin-3. METHODS AND RESULTS: We evaluated 170 thyroid lesions including 148 neoplastic lesions [84 papillary carcinomas (PC), 38 follicular carcinomas (FC), 18 follicular adenomas, one hyalinizing trabecular tumour, five medullary carcinomas, two anaplastic carcinomas] and 22 non-neoplastic lesions (12 adenomatous nodules and 10 Hashimoto's thyroiditis). HBME-1, galectin-3 and CK 19 were expressed in 94%, 72.6%, 72.6% of PCs and in 63%, 21%, 21% of FCs. The three markers were mostly negative in all normal tissues. Although the most helpful marker in terms of sensitivity and specificity for the follicular variant of PC and for FC diagnosis was HBME-1, when we consider the differentiation between cases of follicular variant of papillary carcinoma (FVPC) and FC or adenoma, in terms of percentage of positive cells, galectin-3 and CK 19 were more relevant. CONCLUSIONS: HBME-1 is the most sensitive marker for thyroid malignancy but the three markers may be useful in specific cases. This panel of markers is useful to differentiate the follicular patterned lesions, with special reference to the FVPC.

Biomarkers, Tumor↗
PubMed1983

Comparison of a new lancet and a hypodermic needle for skin prick testing.

Skin prick tests with a standard allergen panel were carried out in duplicate (one on each arm) on all patients referred to an allergy out-patient clinic. A new lancet with 1-mm point length and a disposable hypodermic needle were used. Patients were randomized to lancet-needle, lancet-lancet, or needle-needle, and the skin prick tests were done by experienced or inexperienced nurses. The mean of the biggest and smallest diameters was used as a measure of the size of the wheal. Skin reactions from a total of 142 patients were included. For both lancet and needle a significant difference was noted when comparing experienced versus inexperienced investigators' reproducibility expressed as coefficient of variation. There was no significant difference in reproducibility when comparing lancet and needle results, and no significant difference in wheal size when comparing with histamine references. Surprisingly, the reactions on left arms were generally larger than those on right arms.

Allergens↗
PubMed2005

Evaluation of the suitability of monoclonal antibodies for flow cytometric intracellular cytokine detection in porcine peripheral blood lymphocytes.

Panels of monoclonal antibodies (mAbs) specific for porcine interleukin (IL)-2, IL-4, IL-6, IL-12, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha were evaluated for their applicability in flow cytometric intracellular cytokine detection. Peripheral blood mononuclear cells were short-time stimulated in the presence of brefeldin-A, ionomycin and phorbol-12-myristate-13-acetate, fixed and incubated with the respective mAbs as well as phycoerythrin-conjugated second-step antibodies. Suitability of mAbs was judged by use of statistical data and by visual control of scattergrams, considering the capability of mAbs to discriminate between cytokine-positive and cytokine-negative cell populations. The number of suitable clones differed to a high degree between the investigated cytokines, but at least one mAb fitting for flow cytometric intracellular cytokine detection could be identified within each panel. Monoclonal Abs producing scattergrams with a clear demarcation between positive and negative cell populations were found within the anti-IL-2, IL-6 and IFN-gamma panels, whereas less well defined positive and negative cell populations could be generated by use of mAbs within the anti-IL-4 and TNF-alpha panels. Only one moderately fitting mAb was identified within the anti-IL-12 panel. After having evaluated the best fitting mAbs, these were used to obtain reference levels for the physiological range of porcine lymphocytic cytokine production in a second set of experiments. For that reason, 13 clinically healthy pigs aged between 6 weeks and 6 months were investigated. Data presented are given as mean +/- SD of the percentage of positive-staining lymphocytes: IL-2, 45.5 +/- 27.6; IL-4, 34.1 +/- 21.3; IL-6, 45.4 +/- 23.8; IL-12, 13.9 +/- 8.6; TNF-alpha, 43.4 +/- 11.3; IFN-gamma, 65.5 +/- 14.8.

Animals↗
PubMed2003

The potential role of flow cytometry in the diagnosis of small cell carcinoma.

CONTEXT: Virtually no information exists in the medical literature on the immunophenotyping of small cell carcinoma by flow cytometry. CD56, or neural cell adhesion molecule, is widely expressed by small cell carcinoma and easily measured by flow cytometry. OBJECTIVE: To determine the potential usefulness of flow cytometry in the diagnosis of small cell carcinoma. DESIGN AND SETTING: Retrospective data and archival material on 27 patients were obtained from community hospitals. Specimens (needle aspirations and tissue biopsies) from all patients demonstrated cytomorphologic and flow cytometric features consistent with small cell carcinoma. All measurements were performed at a large reference laboratory. Routine 3- and 4-color flow cytometry using a lymphoma antibody panel, including anti-CD56, was performed. Anti-cytokeratin antibody was also used in the last 12 cases. Immunohistochemical staining with a panel of conventional markers for neuroendocrine neoplasms was performed on available tissue for purposes of confirmation of small cell carcinoma. PATIENTS: Twenty-seven patients whose tissue specimens showed a clearly defined population of CD45-CD56+ cells by flow cytometry and cytomorphologic features consistent with small cell carcinoma. INTERVENTIONS: Needle aspiration (n = 3) and tissue biopsy (n = 24) from a variety of sites. RESULTS: CD56 positivity by flow cytometry was 100 to 1000 times that of the matched isotype control in 25 cases and 10 to 100 times that of the control in 2 cases. Cytokeratin positivity by flow cytometry was found in 12 of 12 cases. Immunohistochemical staining showed positivity for at least 1 cytokeratin and 1 or more neuroendocrine markers in 26 of 27 cases and confirmed the diagnosis of small cell carcinoma. CONCLUSIONS: Routine flow cytometry can identify a neuroendocrine phenotype that shows a strong correlation with confirmatory immunohistochemical markers in cases exhibiting cytomorphologic features of small cell carcinoma. Flow cytometry appears to complement and may possibly be a satisfactory alternative to immunohistochemical staining when small cell carcinoma is suspected.

Biomarkers, Tumor↗
PubMed2003

Quality assurance in human molecular genetics testing: status and recommendations.

OBJECTIVE: The role of genetic testing has expanded with rapidly developing technology and completion of the International Human Genome Project. Development of universally acceptable quality control methods and quality assurance standards trails technology. The principle that high-quality genetic testing is important for public health motivated the Centers for Disease Control and Prevention to formulate ways for improving quality assurance of human molecular genetics testing. PARTICIPANTS: Twenty-eight panelists were chosen based on expertise in molecular genetics testing and knowledge of quality assurance practices. Representatives of professional organizations, industries, and federal agencies participated in one or more of 3 panel meetings. Consensus recommendations were developed by the 15 panelists in the third meeting. EVIDENCE: Evidence was derived from experts' opinion during 3 panel meetings. Data compiled through laboratory visits and literature review were used as reference information. Need for this project was derived from the Final Report of the Task Force on Genetic Testing, produced by the National Institutes of Health and the Department of Energy in 1997, and the Summary Report of the Subcommittee Meeting on Genetics of the Clinical Laboratory Improvement Act Advisory Committee in 1997. CONSENSUS PROCESS: Research and development needs were identified using a participatory visioning approach. A modified nominal group process was used to reach consensus. CONCLUSIONS: Five core consensus recommendations were made: research for developing positive samples for quality assurance purposes, performance evaluation programs supplementing those in existence, establishment and support of laboratory-oriented consortia, establishment of a laboratory-focused database, and support of molecular genetics training programs.

Centers for Disease Control and Prevention, U.S.↗
PubMed1982

An analysis of alternative imputation strategies for individuals with partial data in the National Medical Care Expenditure Survey.

Data collection in the National Medical Care Expenditure Survey was applied to the same panel of sample households in six rounds of interviewing, with 1977 as the reference period. Approximately 11 percent of all survey participants provided data for only part of the time they were eligible to respond. To allow for national estimates of relevant health parameters, the data for the partial participants must be adjusted for the entire time frame for which they were eligible. Consequently, three alternative imputation strategies were considered for implementation: a weighted adjustment to the partial data, a substitution of data from complete participants who matched the partial respondents on relevant demographic characteristics, and use of only the data from participants with complete information to characterize the nation. To determine the optimal strategy, a controlled experiment was conducted by artificially creating partial data for participants with complete information, then adjusting the synthetically produced partial data by the three imputation strategies.

Analysis of Variance↗
PubMed1999

[Multicenter study of the variability and adequacy of antimicrobial therapy for community-acquired pneumonia in adults].

We performed a study to evaluate the variability and adequacy of prescribing antibiotics in community-acquired pneumonia (CAP) in 10 Spanish hospitals. We studied 452 patients with CAP. Initial empirical administration of antibiotics was prescribed in 90.7% of the cases, 82.5% as monotherapy. Macrolides and third and second generation cephalosporins were the most widely used groups of antibiotics. Penicillin and amoxicillin were only prescribed in 1. 7% of the patients. A significant variability between hospitals was observed. Reference patterns for the use of antibiotics in CAP were devised by a panel of experts. According to the recommendations of this panel, 29% of the total prescriptions were not adequate, with this percentage reaching 65% in outpatients older than 65 years or with comorbidity. This was mainly due to the fact that monotherapy with erythromycin, which was considered inadequate, was the most widely prescribed treatment.

Adult↗
PubMed1999

[Multicenter study of the variability and adequacy of antimicrobial therapy for community-acquired pneumonia in adults]

We performed a study to evaluate the variability and adequacy of prescribing antibiotics in community-acquired pneumonia (CAP) in 10 Spanish hospitals. We studied 452 patients with CAP. Initial empirical administration of antibiotics was prescribed in 90.7% of the cases, 82.5% as monotherapy. Macrolides and third and second generation cephalosporins were the most widely used groups of antibiotics. Penicillin and amoxicillin were only prescribed in 1.7% of the patients. A significant variability between hospitals was observed. Reference patterns for the use of antibiotics in CAP were devised by a panel of experts. According to the recommendations of this panel, 29% of the total prescriptions were not adequate, with this percentage reaching 65% in outpatients older than 65 years or with comorbidity. This was mainly due to the fact that monotherapy with erythromycin, which was considered inadequate, was the most widely prescribed treatment.

Journal Article↗
PubMed1989

Rheumatoid factors determined by fluorescence immunoassay: comparison with qualitative and quantitative methods.

Fluorescence immunoassay (FIA), a relatively new technique for measuring rheumatoid factors (RF), is automated, quantitative, and calibrated against the Centers for Disease Control reference material for RF. We studied the FIA method in relation to a panel of RF methods, both qualitative [latex (LA) and sheep cell agglutination (SSCA)], and quantitative [nephelometry and enzyme-linked immunoassay (ELISA)]. Regression analysis revealed a highly significant correlation between FIA and either LA (r = 0.90) or nephelometry (r = 0.87). The correlation between FIA and either SSCA (r = 0.62) or ELISA (r = 0.67) was less strong. FIA had the highest sensitivity (91%) of all these methods; the specificity was 86%. FIA provides an accurate, sensitive, and specific measure of RF, and is a good alternative for laboratories wanting to replace titer methods with automated laboratory analysis.

Enzyme-Linked Immunosorbent Assay↗
PubMedDate not supplied

Morbidity and mortality of dialysis.

The National Institutes of Health Consensus Development Conference on Morbidity and Mortality of Dialysis brought together experts in general medicine, nephrology, pediatrics, biostatistics, and nutrition as well as the public to address the following questions: (1) How does early medical intervention in predialysis patients influence morbidity and mortality? (2) What is the relationship between delivered dialysis dose and morbidity/mortality? (3) Can co-morbid conditions be altered by non-dialytic interventions to improve morbidity/mortality in dialysis patients? (4) How can dialysis-related complications be reduced? and (5) What are the future directions for research in dialysis? Following 1 1/2 days of presentations by experts and discussion by the audience, a consensus panel weighted the evidence and prepared their consensus statement. Among their findings, the consensus panel concluded that (1) patients in the predialysis phase, including children, should be referred to a renal team in an effort to reduce the morbidity and mortality incurred both during the predialysis period and when receiving subsequent dialysis therapy; (2) the social and psychological welfare and the quality of life of the dialysis patient are favorably influenced by the early predialytic and continued involvement of a multidisciplinary renal team; (3) attempts should be made to avoid a catastrophic onset of dialysis by instituting predialytic intervention and the appropriate initiation of dialysis access; (4) quantitative methods now available to objectively evaluate the relationship between delivered dose of dialysis and patient morbidity and mortality suggest that the dose of hemodialysis and peritoneal dialysis has been suboptimal for many patients in the United States; (5) factors contributing to underdialysis of some patients include problems with vascular and peritoneal access, nonadherence to dialysis prescription, and underprescription of the dialysis dose; (6) cardiovascular mortality accounts for approximately 50 percent of deaths in dialysis patients, and relative risk factors such as hypertension, smoking, and chronic anemia should be treated as soon as possible after diagnosis of chronic renal failure; (7) early detection and treatment of malnutrition contribute to improved survival of patients on dialysis; and (8) until prospective, randomized, controlled trials have been completed, a delivered hemodialysis dose at least equal to a measured fractional urea clearance of Kdrt/V of 1.2 (single pool) and a delivered peritoneal dialysis dose at least equal to a measured Kprt/V of 1.7 (weekly) are recommended.

Adult↗
PubMed2026

Quo vadis, BGA? A collaborative EDNAP exercise on the challenges and progress in forensic biogeographical ancestry inference.

There is a broad consensus that forensic tests for the prediction of externally visible characteristics (EVC) and analysis of biogeographic ancestry (BGA) of an individual are technically reliable. However, interpretation of the results and population-specific genotype distribution patterns remains challenging. EVC and BGA analyses provide valuable information for population genetics studies and as investigative leads for criminal cases, as well as for historical and contemporary identification tests. However, inaccurate or incorrect predictions, for example, from subjective bias in the interpretations made, have the potential to misdirect police investigations. The legal situation regarding EVC and BGA testing varies by country: ranging from countries where it is explicitly prohibited, to those without specific regulations on biogeographic ancestry prediction, and others that have already enacted laws governing its use. The reluctance to utilize these analyses is not only due to legal restrictions and data protection concerns, but also to initial limited sets of sufficiently comprehensive forensic DNA assays. Forensic BGA marker panels typically contain up to ∼300 SNPs. This relatively small number of genetic markers, along with limited reference population data, complicates the interpretation of results from donors of unknown origin. This paper presents the results of a collaborative EDNAP study, which, for the first time, evaluated the approach to reporting EVC and BGA data between international laboratories. For the study, DNA from nine individuals with self-reported ancestry was collected and analysed using various forensic panels differing in the number and composition of ancestry-informative markers genotyped, comprising: the Precision ID mtDNA Whole Genome Panel, the VISAGE Basic Tool and the VISAGE Enhanced Tool for Appearance and Ancestry Prediction, and the Ion AmpliSeq™ PhenoTrivium Panel. To ensure full data protection, all SNP genotypes and uniparental marker haplotypes obtained were not shared with third parties. Instead, the genetic data were analysed using a range of commonly used population analysis software packages. These analysis outcomes were then distributed to twelve European forensic laboratories (both academic and law enforcement institutions), who were asked to prepare reports based on their interpretation of the phenotypes and ancestry they inferred from the analysis data. A questionnaire sent alongside the genetic information, aimed to evaluate which difficulties were encountered by the participants in processing the BGA analysis data they were given.

Humans↗
PubMed2002

Role of physical activity and exercise training in neuromuscular diseases.

The objective of the State of the Science Roundtable conference was to provide a responsible assessment of the state of the science regarding exercise training and fatigue in humans and animals with neuromuscular diseases. The conference comprised a nonfederal, nonadvocate, 20-member panel that brought together exercise scientists, neuromuscular disease investigators, and clinicians during a 21/2 day workshop. The literature was searched using MEDLINE, and an extensive bibliography of references was created. Experts in each area presented reviews based on this literature. Scientific evidence was given precedence over clinical anecdotal experience. After the presentations, the panel answered predefined questions and developed conclusions based on the scientific evidence presented in open forum and the scientific literature. The panel presented a draft statement during the conference and produced this revised statement after the conference.

Animals↗
PubMed2026

Pedigree-assisted genotype imputation enables cost-effective genomic prediction in Penaeus vannamei.

Genomic selection in Penaeus vannamei has long been constrained by the high cost of dense genotyping. To address this limitation, we evaluated genotype imputation from a low-density 1 K panel to a medium-density 55 K panel of the "Yellow Sea Array No. 1" and examined its impact on genomic prediction for harvest body weight in P. vannamei. A four-generation pedigree including 30 great-grandparents, 39 grandparents, 100 parents, and 608 offspring was genotyped using the 55 K panel. A two-step experimental design was implemented to (i) assess the performance of different imputation algorithms under reference population scenarios with varying proportions of siblings, and (ii) compare six alternative reference population structures incorporating parents, ancestors, and siblings. Genotype imputation using the pedigree-based method FImpute v3.0 consistently achieved higher accuracy than the population-based method Beagle v5.5. Using this pedigree-assisted approach, imputation accuracy increased from 0.73 when only parental genotypes were used to 0.84 with the inclusion of 10% siblings, and subsequently plateaued at 0.87-0.90 when sibling representation reached 20%. Across the six reference population structures, imputation accuracy was primarily driven by the availability of parental genotypes, ranging from 0.50 to 0.56 in the absence of parents to 0.88-0.89 when both parents and ancestral generations were included. Accuracy remained high when both parents were available (0.84-0.87 with siblings; 0.73 without siblings) but declined substantially when only one parent was genotyped (0.65-0.68). Imputation accuracy was positively associated with both minor allele frequency (MAF) and linkage disequilibrium (max r2LD), with LD exerting the stronger influence. Heritability estimates derived from imputed 55 K genotypes were highly consistent with those obtained from the original 55 K data (0.39 ± 0.14 vs. 0.41 ± 0.14), indicating that genotype imputation did not compromise variance component estimation. In predictive ability analyses, pedigree-based BLUP (PBLUP) achieved higher predictive ability than genomic BLUP (GBLUP) based on the 1 K panel, with predictive abilities of 0.42-0.44 for PBLUP compared with 0.34-0.35 for GBLUP. Using imputed genotypes for genomic prediction further improved predictive ability relative to the true 1 K panel, yielding values ranging from 0.35 to 0.47. Notably, when parental genotypes were included in the reference population, GBLUP based on imputed genotypes surpassed the predictive ability of PBLUP and approached that achieved with the original 55 K genotypes (0.45-0.47). Collectively, these results provide the first empirical evidence that low- to medium-density genotype imputation, combined with pedigree information, can effectively support genomic prediction in P. vannamei. This study establishes a cost-efficient and scalable framework for implementing genomic selection in P. vannamei and provides a practical reference for the application of genomic selection in other aquaculture species with constrained breeding budgets.

Animals↗
PubMed1996

Recommendations of the Panel on Cost-effectiveness in Health and Medicine.

OBJECTIVE: To develop consensus-based recommendations for the conduct of cost-effectiveness analysis (CEA). This article, the second in a 3-part series, describes the basis for recommendations constituting the reference case analysis, the set of practices developed to guide CEAs that inform societal resource allocation decisions, and the content of these recommendations. PARTICIPANTS: The Panel on Cost-Effectiveness in Health and Medicine, a nonfederal panel with expertise in CEA, clinical medicine, ethics, and health outcomes measurement, was convened by the US Public Health Service (PHS). EVIDENCE: The panel reviewed the theoretical foundations of CEA, current practices, and alternative methods used in analyses. Recommendations were developed on the basis of theory where possible, but tempered by ethical and pragmatic considerations, as well as the needs of users. CONSENSUS PROCESS: The panel developed recommendations through 2 1/2 years of discussions. Comments on preliminary drafts prepared by panel working groups were solicited from federal government methodologists, health agency officials, and academic methodologists. CONCLUSIONS: The panel's methodological recommendations address (1) components belonging in the numerator and denominator of a cost-effectiveness (C/E) ratio; (2) measuring resource use in the numerator of a C/E ratio; (3) valuing health consequences in the denominator of a C/E ratio; (4) estimating effectiveness of interventions; (5) incorporating time preference and discounting; and (6) handling uncertainty. Recommendations are subject to the ¿rule of reason,¿ balancing the burden engendered by a practice with its importance to a study. If researchers follow a standard set of methods in CEA, the quality and comparability of studies, and their ultimate utility, can be much improved.

Cost-Benefit Analysis↗
PubMed2005

Case report: atypical presentation of anti-Rg(a).

The Rodgers (Rg(a)) antigen is a plasma protein that binds to the red blood cell (RBC) membrane. About 2 to 3% of the transfusion-recipient white population lacks the antigen and can produce anti-Rg(a) antibody. We report the case of a 70-yr-old man who presented with a medical history of hairy cell leukemia and profound pancytopenia that required RBC and platelet (PLT) transfusions. The patient had received 2 units of RBCs and 4 PLT concentrate pools. He was typed as O Rh(D) positive, with positive reactions in all 3-screen cells using the polyethylene glycol (PEG) indirect antiglobulin test/IAT (anti-IgG). Three antibody identification panels were performed, which all proved to be negative. A direct antiglobulin test and an auto-control were run, which were also negative. Since further investigations were needed, the patient's blood sample was sent to a reference laboratory where anti-Rg(a) was identified. Since the percentage of antigen-positive cells in the red cell panel was low, crossmatch compatible units of RBCs were transfused with no discernible immediate or delayed transfusion reaction. This report should alert hospital transfusion service personnel to recognize that, although the panel cells are usually reliable for antibody identification purposes, they may not have the antigens that are present on the screening cells.

ABO Blood-Group System↗