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Standards for the electronic transfer of clinical data: progress and promises.

Data exchange standards have two components: the message format or syntax and the dictionary of codes (semantics). For many applications, message standards already have been developed. For a few kinds of clinical entities, such as drugs, these code systems (e.g., the National Drug Code) are virtually complete, but a few gaps must be filled and an agreement must be reached about the level of granularity needed. The available codes for clinical descriptors are inadequate but the National Library of Medicine's Universal Medical Language (UML) project will do much to redress this deficiency. Codes for clinical variables such as blood pressure and blood glucose which have methods, units, normal ranges, and physiologic correlates are very inadequate. CPT4 provides some of the needed codes but has huge gaps. An early effort to extend CPT4 is included in ASTM 1238. Work being done by ASTM E31.12 and the Euclides project will offer robust codes for clinical laboratory measurements. If we want to pool data from different institutions for clinical and policy research, universal codes for observations are prerequisite. And agreement of an international coding system for observation-bearing variables should be a major agenda item for standards groups in the next year. Our goal has been to standardize the communication of clinical data between clinical systems, not the systems themselves or their internal operation. In fact, standardizing the internals of clinical application could be counterproductive at the present. It would deflect energy from, and delay the spread of, CDI standards. Moreover, it gives undue attention to computer systems, rather than the data they contain. The data are the most expensive part of any data system. They are the raison d'être for such systems. Computer systems come and go. The data last forever. Yet we have been mesmerized by the computer system while ignoring its contents. As a result, most computer-stored clinical data must live like the tragic boy in the bubble. They cannot "live" outside of the computer system in which they were born. So, we find at every hospital the bizarre rituals of humans reading computer-generated reports so they can type this information in another computer. Electronic (e.g., stored clinical) data should not depend upon the internals of a particular program, language, or machine for its interpretation. The clinical data entered into one computer system should be directly available to any other computer system that now receives them through manual transcription. Data interchange standards give life to our data--independent of the source system.

Abstracting and Indexing↗

The standards movement builds momentum.

The success of efforts to build health information networks and to implement computerized patient records will hinge on the development of standards for the electronic format and content of financial and clinical transactions. Without standards, sharing data among disparate systems will be extremely cumbersome, and drawing conclusions based on research will prove difficult. For years, several volunteer groups have been toiling to develop these standards. These efforts are beginning to pay off. This special report summarizes the latest trends in standards development. This series of stories includes an update on efforts to develop standard data sets for financial and administrative transactions; a guide to the jargon of health care electronic data interchange, an overview of efforts to speed the development of standards for computerized records; and a case study of a hospital implementing one set of clinical standards.

Clinical Medicine↗

Development of a draft British standard: the assessment of heat strain for workers wearing personal protective equipment.

Existing methods for estimating heat stress, enshrined in British/International Standards (the Wet Bulb Globe Temperature (WBGT) index [BS EN 27243] and the Required Sweat Rate equation [BS EN 12515; ISO 7933 modified]), assume that the clothing worn by the individual is water vapour permeable; the WBGT index also assumes that the clothing is relatively light. Because most forms of personal protective equipment (PPE) either have a higher insulative value than that assumed or are water vapour impermeable, the Standards cannot be accurately applied to workers wearing PPE. There was, therefore, a need to develop a British Standard which would allow interpretation of these existing Standards for workers wearing PPE. Relevant information was obtained through reviewing the literature and consulting experts. Two questionnaire surveys of potential users of the Standards were conducted, and physiological data collected both experimentally and in work situations were considered. The information collected was used to develop the draft British Standard. It provides information and data on: The general effect of PPE on heat balance of the body (the ability of the body to maintain its 'core' temperature within an acceptable range). The effect of specific forms of PPE on metabolic heat production rate. The thermal insulation and evaporative resistance of types of PPE. The effect of the closure of the garments to the body on heat transfer. The effect of the PPE on the proportion of the body covered. The effect of an air supply (for example, Breathing Apparatus [BA]) to the wearer. Guidance is given on conducting an analysis of the work situation, taking account of the impact of PPE. Detailed methods of interpreting both BS EN 27243 and BS EN 12515 for workers wearing PPE are given, taking account of the factors listed above. Three worked examples using BS EN 27243 and BS EN 12515 are given in the Annex of the draft Standard.

Body Temperature Regulation↗

H.H. Dale and the London Centre for WHO standards--some milestones of the early years.

Henry Dale, a Nobel laureate and statesman of science, helped to organize the meetings in 1923 and 1925 to set up international standards for insulin and other biologicals. He made the National Institute for Medical Research one of the two world centres for standards. Some milestones in the work of the London centre are described: (i) the first standards; (ii) vitamins and hormones; (iii) WHO standards for many antibiotics; (iv) the provision of an international working standard for ACTH; (v) the old and new methods of ampouling; (vi) the impact of research and immunoassay on the need for standards; and (vii) the special ECBS sessions for endocrinology and haematology. Dale tells how he had to preserve the first batch of insulin for use as the standard instead of for treatment.

Adrenocorticotropic Hormone↗

New concepts and methods of standardizing predictive value, accuracy and incorrect diagnostic rate.

OBJECTIVE: To express the value of a diagnostic test under standardized and comparable conditions. STUDY DESIGN: Four new concepts of standardizing positive predictive value (SPPV), standardizing negative predictive value (SNPV), standardizing accuracy (SAc) and standardizing an incorrect diagnostic test were developed. The theoretical positive predictive value (SPPV), theoretical negative predictive value (SNPV), theoretical accuracy (SAc) and theoretical incorrect diagnosis rate (SIDR), which are not affected by a different constituent ratio of disease and nondisease groups and are obtained under the theoretical standard condition that the sample size in the disease group equals that in the nondisease group, were defined. Based on these concepts and the principles and methods of statistics and evaluation of diagnostic tests, corresponding formulas were deduced. RESULTS: The formulas are: SPPV = a(b + d)/[a(b + d) + b(a + c)] = Se/(1 + Se - Sp), SNPV = d(a + c)/[c(b + d) + d(a + c)] = Sp/(1 - Se + Sp), SAc = [a(b + d) + d(a + c)]/[2(a + c)(b + d)] = (Se + Sp)/2, and SIDR = [b(a + c) + c(b + d)]/[2(a + c)(b + d)] = (2 - Se - Sp)/2. Here, a, b, c and d refer to the case numbers of true positives, false positives, false negatives and true negatives; Se and Sp refer, respectively, to sensitivity and specificity. CONCLUSION: SPPV, SNPV, SAc and SIDR are very useful for expressing and evaluating the value of a diagnostic test under standardized and comparable conditions.

Breast Neoplasms↗

[Pediatric parenteral nutrition: are standard solutions better than individualized ones?].

OBJECTIVE: Pediatric parenteral nutrition (PN) in Spain has traditionally been prescribed and made up on an individual basis. This practice entails daily indication of the quantity of each of the components of the PN bag as well as precise calculations for its formulation and preparation. The main advantages of individualized prescriptions are their flexibility and precise biochemical control. The aim of this study was to determine whether pediatric PN can be standardized in a tertiary care hospital. PATIENTS AND METHODS: We reviewed the composition of all the pediatric PN bags prepared in our hospital from 1.1.1996 to 31.12.1998. Each individual prescription was compared with a standard PN fulfilling the following criteria: a) Holiday-Segar equation for volume; b) 1 kcal/ml (10 %), and c) macronutrient distribution: 8-15 % amino acids, 55-65 % dextrose; 30-35 % lipids. The results of this comparison were used to estimate the number of bags fulfilling all three criteria and those that fulfilled only the third. We also reviewed the distribution of PN bags prepared according to the protocol used in our center which allows three options: standard PN, individualized prescription, and individualized prescription except electrolytes, supplied in fixed concentrations per liter of PN. RESULTS: Five hundred fifty-four patients received 7,921 PN bags. The mean duration of PN was 14.3 days and the mean number of PN per day was 7.2. Only 4.5 % fulfilled all three criteria but 16.2 % satisfied at least the last criterion. If the three criteria for standardization were applied, only one PN bag/day could be prepared. Analysis of the application of our protocol revealed that of all the PN bags prepared only 27.9 % were partially or totally standardized. However, exclusion of neonates increased this figure to 53.2 %. CONCLUSIONS: If rigid standardization criteria are applied, only a small number of PN bags can be prepared in a tertiary hospital. Combining both standard and tailored PN could reduce pharmacy workload and costs while maintaining flexibility.

Follow-Up Studies↗

[The use of ELISA systems for control of epizootics: safety of test standards using batch assays].

One of the advantages of ELISA techniques is to achieve a higher degree of safety by standardization. Bases of these standardizations should be, if available, international or national standards in combination with cutoff definitions. The cutoff definitions should be expressed, separate for the main kinds of samples, defined as a dilution of the standard. Those definitions can replace the mostly awkward and involved test descriptions as usual in official regulations. To guarantee a high grade of reliability it is a matter of urgent necessary to test (if possible by the producer) each serial (lot) of ELISA and to describe their capacities with regard of sensitivity and specificity. Separate pretests may be done with the main kinds of samples with well known reactions (negative and weak positive). The results are to compare to those of the cutoff-related dilutions of the standard in the same matrix. These descriptions of the capacities of each serial (lot) are safe bases for use of the serial. Key concepts are the quotients of the minimum positive value divided by the maximum negative or alternatively the mean value of the positive minus the threefold standard deviation divided by the mean value of the negative plus the threefold standard deviation.

Animals↗

The international standard for dihydrostreptomycin.

In 1950, the Department of Biological Standards, National Institute for Medical Research, London, was authorized by the WHO Expert Committee on Biological Standardization to proceed with the establishment of an International Standard for Dihydrostreptomycin. A 50-g batch of dihydrostreptomycin was obtained and was compared with the Standard Preparation of Dihydrostreptomycin of the Food and Drug Administration (FDA), United States Department of Health, Education and Welfare, in a collaborative assay in which seven laboratories in five countries participated.In all, 76 assays were carried out; 62 of these were done by biological methods, using Staphylococcus aureus, Bacillus subtilis, or Klebsiella pneumoniae, and the remaining 14 by physicochemical methods. The results were subjected to standard methods of analysis, and the overall weighted mean potency (calculated from the results of biological assays only) was 0.958, with limits of error of 99.6% to 100.4%.Since the FDA Standard Preparation is considered to be substantially pure dihydrostreptomycin sulfate, the content of dihydrostreptomycin base (after allowing for known moisture content) is assumed to be 79.2%. The potency of the International Standard has been established as 760 International Units per mg, so that, on the foregoing assumption, one International Unit may be regarded as equivalent to the activity of one microgram of dihydrostreptomycin base.

Biological Assay↗

The international standard for anti-Brucella-abortus serum.

In field trials on the eradication of brucellosis from dairy herds in Great Britain, which began in 1933, a serum standard of reference was used for the examination of agglutinating suspensions prepared in different laboratories. In 1937, the Office International des Epizooties (OIE) adopted this standard and made recommendations for its use internationally. These recommendations were revised by OIE in 1948, by the Third Inter-American Congress on Brucellosis and by the Joint FAO/WHO Expert Panel on Brucellosis in 1950, and again by the latter body in 1952. A new batch equivalent in potency to the original standard was established by the WHO Expert Committee on Biological Standardization in 1952 as the International Standard for Anti-Brucella abortus Serum.The International Standard, or a national standard of equivalent potency, ensures comparability of the titres obtained in different countries by different methods, and the results of such comparisons can be expressed in a simple manner by describing the titres in terms of International Units of Brucella antibody.

Brucella abortus↗

Standardization of two immunological HbA1c routine assays according to the new IFCC reference method.

The measurement of HbA1c is meanwhile well established as the most important parameter in clinical chemistry for monitoring the long term metabolic control of diabetic patients. However, the comparability of HbA1c values obtained by different methods in different laboratories and different countries is limited since there was no internationally agreed reference method available. Additionally the % HbA1c values, based on the most common DCCT values are too high due to well known non specificity of the DCCT standardization protocol. Recently a new reference method for the determination of HbA1c was developed and has been approved by the IFCC as the future basis for the worldwide standardization of HbA1c routine assays. The two routine methods from Roche Diagnostics (both based on the immunoturbidimetric determination of the stable glucose adduct to the N-terminal group of the hemoglobin beta chain, Roche-Hitachi/Tina-quant [a] and COBAS INTEGRA) are directly standardized against this new reference method. Both routine methods are based on a two step approach: in a first step the total Hb is quantified by a colorimetric method and in a second step the stable glucose adduct to the N-terminal group of the hemoglobin beta chain is quantified by immunoturbidity (HbA1c mass). Consequently, first the standardization of the total Hb assay was reconfirmed by method comparisons against the cyanomethemoglobin reference method. Second, the standardization of the HbA1c mass was done by running method comparisons against the new IFCC reference method. The resulting new calibrator values for HbA1c [mass] and total Hb [mass] allow a direct estimation of % HbA1c according to IFCC just by calculating the HbA1c [mass]/total Hb [mass] ratio. Good linear correlations were obtained when comparing the routine methods against the new IFCC reference, indicating the high specificity of these immunological approaches. The following correlations are obtained: Hitachi / Tina-quant [a] (Y) versus IFCC reference method (X): Y = -0.031 + 1.009 x X; r = 0.995. COBAS INTEGRA (Y) versus IFCC reference method (X): Y = -0.156 + 1.006 x X; r = 0.997. Hitachi / Tina-quant [a] (Y) versus Integra (X); (both standardized according to IFCC): Y = 0.057 + 1.003 x X; r = 0.997. The HbA1c values obtained with this new IFCC standardization are significantly lower than the well known DCCT values. Due to the specificity of the immunological approach which is very close to the analyte as defined by the IFCC reference method, no further corrections of the obtained % HbA1c values are necessary. A slope/intercept correction formula is derived which allows the transformation of IFCC values into the DCCT numbers if requested.

Blood Chemical Analysis↗

Assessing competency competently: toward a rational standard for competency-to-stand-trial assessments.

This article reports on a survey of forensic psychiatrists and psychologists who read two case study vignettes and assessed whether each criminal defendant was competent to stand trial, using three differently worded standards of competency: one that focused on whether the defendant's thinking was rational, a second that focused on whether the defendant's behavior was rational, and a third that did not use the word "rational." The objective was to discover whether forensic examiners would distinguish among the standards (i.e., find the defendant competent under one standard but not under another) or whether they would find the defendant competent under all standards or incompetent under all standards. In responding to both vignettes, more than three-fourths of all respondents either found the defendant competent under all three standards or incompetent under all three standards. In addition, in answering one vignette, the respondents were divided almost equally in deciding whether the defendant was competent to stand trial. These results are analyzed and respondents' comments are discussed. The article concludes with specific proposals to improve competency-to-stand-trial assessments.

Adult↗

Alkaline phosphatase activity from human osteosarcoma cell line SaOS-2: an isoenzyme standard for quantifying skeletal alkaline phosphatase activity in serum.

Earlier we described a kinetic assay for quantifying skeletal alkaline phosphatase (ALP) isoenzyme activity in serum. The precision of the assay depends on including ALP standards for the skeletal, hepatic, intestinal, and placental isoenzymes. We wondered whether human osteosarcoma cells could provide an efficient alternative to human bone or Pagetic serum as a source of the skeletal ALP standard. ALP activities prepared from five human osteosarcoma cell lines were compared with a bone-derived ALP standard with respect to heat stability and sensitivity to chemical effectors. Two of the cell lines (SaOS-2 and TE-85) contained ALP activities that resembled the bone-derived standard. We selected SaOS-2 cells for additional evaluation (as a potential source of isoenzyme standard), because they contained 40-50 times more ALP activity than did the TE-85 cells. To include the SaOS-2 cell-derived ALP activity in the quantitative isoenzyme assay, we diluted the enzyme in a solution containing heat-inactivated (i.e., ALP-negative) human serum. Surprisingly, this dilution caused a 60-125% increase in maximum enzyme activity. In the quantitative assay of ALP isoenzyme in serum, the SaOS-2 derived ALP was indistinguishable from the serum skeletal ALP standard, with respect to the above criteria and assay variations. Evidently ALP from SaOS-2 cells is suited as a standard for measuring skeletal ALP activity in this assay.

Alkaline Phosphatase↗

[The use of an internal standard for the correction of deviations in densitometry of thin-layer chromatograms (author's transl)].

In order to obtain a better reproducibility in quantitative determination of amino acids in amounts of picomoles an internal standard was used. A mixture of ten amino acids was diluted and dansylated. 0.1 microliter of each solution was separated by two-dimensional thin-layer chromatography on polyamide sheets (3 x 3 cm). Each chromatogram was photographed with four different exposure times under ultraviolet light. The dark spots in the photographic negatives were measured by television densitometry. A number of factors influence the reproducibility of this method: loading volume, photographic exposure time and processing, and quenching of fluorescence. As an internal standard, which is influenced by all these factors, DANS-hydroxyproline was added to each solution. By using this standard, the variations in exposure time and fluorescence quenching can be corrected satisfactorily. The relative standard deviation of the mean value of four photographs of one chromatogram is 2%. The results on correction of the volume deviation were not so satisfying. The relative standard deviation of the mean of twelve different chromatograms can be reduced from 34% for the initially measured data, to 8% for the values corrected by the internal standard. It seems necessary to carry out three or more determinations of one solution. In this case the relative standard error of the mean is 2%.

Amino Acids↗

Interlaboratory standardization of glycated hemoglobin determinations.

As the clinical utility of glycated hemoglobin (gHb) measurement increases, so does the need for standardization of values between different methods and different laboratories. Using three different methods, we examined the feasibility of interlaboratory standardization of gHb measurement. A liquid-chromatographic (HPLC) system from our research laboratory was designated the reference method. For gHb standards we used erythrocyte hemolysates prepared from blood samples from nondiabetic and diabetic subjects. Values assigned to each standard were based on the mean of multiple gHb determinations by the HPLC method. A clinical laboratory routinely prepared hemolysates and assayed gHb by commercially available ion-exchange ("mini column") and affinity chromatographic methods. For each assay a standard curve was constructed and gHb values were derived from these curves. Samples analyzed in the clinical laboratory were also analyzed in the research laboratory and the curve-derived values were compared with the HPLC-measured values, to determine the accuracy of our interlaboratory standardization procedure. Correlations were excellent (r = 0.99). The lack of significant differences between calculated and HPLC-measured values indicates that interlaboratory standardization is feasible.

Chromatography, Affinity↗

A calibration protocol for serum-based secondary standards.

In this procedure, tentative calibration values are assigned to secondary standards by analysis of that material with the routinely used instrument calibrated by use of the former lot of material. Aliquots of serum from patients are then analyzed by the routine method and an appropriate calibration method in which primary standards are used. If the patient-sera results by both methods are the same, the assigned calibration value is assumed to be correct; if not, the calibration value of the secondary-standard material is adjusted to produce agreement in patient-sera results between the two methods. Thus, calibration of the routine method is linked via the calibration method to primary standards as the criterion of accuracy. This approach corrects for matrix interference of serum-based secondary standards. All that is expected for the secondary standard to obtain an accurate result for patient sera is to produce an analytical signal (irrespective of the origin of the signal) that is equivalent to the calibration value. Differences were significant between the secondary-standard calibration value we determined by this procedure and that assigned by the manufacturer for bilirubin, calcium, phosphorus, chloride, CO2, creatinine, glucose, sodium, uric acid, and commonly measured enzymes.

Autoanalysis↗

Poor comparability of prothrombin fragment 1 + 2 values measured by two commercial ELISA methods: influence of different anticoagulants and standards.

We compared F 1 + 2 results obtained with two commercial ELISA methods (Behring and Baxter) assaying the same plasma samples. There was little correlation between the results of the two methods, as shown by the low correlation coefficient (r = 0.50) and by low percentage of concordant classification (normal or abnormal) of the samples (24%). Such poor correlation is probably due to the different anticoagulants suggested, because correlation improved when both methods were carried out in plasmas collected with the same anticoagulant. However, the Baxter method still gave significantly lower F 1 + 2 values than the Behring method. Assuming that this difference is due to the use of standards with different F 1 + 2 concentrations, the standards from Behring and Baxter were evaluated by both methods. Parallel dose-response curves were obtained when the standards were run by the Behring method but not by the Baxter method, indicating that the two standards are qualitatively different. This study demonstrates that the two F 1 + 2 methods give different values for the same samples and that these values are poorly correlated. Standardization of the F 1 + 2 assays cannot be achieved easily simply by using a common standard and the use of different anticoagulants appears to be the main reason for poor standardization.

Adolescent↗

[Improvements from the reference material CRM 470 in the standardization of the determination of serum proteins].

The introduction of the CRM 470 in 1993 (certified reference material for 14 serum proteins) and its utilization by industrial companies for cross-calibrating their commercial standards has been an important break-through in protein standardization. This improvement has been clearly illustrated by the last national quality control survey performed in France in may 1995. At this time, about 60% of the 1,870 participants have already adopted the new standardization. The between-run precision (interlaboratory and intertechnique) has been considerably improved by the use of the new international standard (5.8 to 12.2% versus 10 to 24.1% before standardization); the same is true for accuracy. These results should convince the last reluctant laboratories to adopt the new standardization. Thus, it seems now possible to define reference ranges for serum proteins: this is the new task assigned to the Committee for Plasma Protein Standardization of the IFCC.

Blood Proteins↗

Short-wavelength automated perimetry and standard perimetry in the detection of progressive optic disc cupping.

OBJECTIVE: To compare progression in short-wavelength automated perimetry (SWAP) and white-on-white (standard) perimetry in eyes with progressive glaucomatous changes of the optic disc detected by serial stereophotographs. METHODS: Forty-seven glaucoma patients with at least 2 disc stereophotographs more than 2 years apart, along with standard perimetry and SWAP examinations within 6 months of each disc photo of the same eye, were included in the study. The mean follow-up time was 4.1 years (range, 2.0-8.9 years). Baseline and follow-up stereophotographs were then graded and compared for the presence of progression. Progression in standard perimetry and SWAP, using the Advanced Glaucoma Intervention Study scoring system and a clinical scoring system, was compared between eyes with progressive change on stereophotographs and those without. RESULTS: Twenty-two of 47 eyes showed progressive change by stereophotographs. There was a statistically significant difference in the mean change in Advanced Glaucoma Intervention Study scores for both standard perimetry (P<.004) and SWAP (P<.001) between the progressed and nonprogressed groups. The sensitivity, specificity, and area under the receiver operator characteristic curve were higher using SWAP than standard perimetry when evaluated by either algorithm. This was statistically significant only in the area under the receiver operator characteristic curve for the Advanced Glaucoma Intervention Study scoring system (P =.04). CONCLUSIONS: Short-wavelength automated perimetry identified more patients than standard perimetry as having progressive glaucomatous changes of the optic disc. Compared with standard perimetry, SWAP may improve the detection of progressive glaucoma. Arch Ophthalmol. 2000;118:1231-1236

Aged↗