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C G Fraser

Publications and source records attributed to C G Fraser.

At least 55 records · Page 3Linked to original sources

A comparison of analytical goals for haemoglobin A1c assays derived using different strategies.

Analytical goals for the performance characteristics of assays of haemoglobin A1c (HbA1c) have been investigated using different assumptions for generation of estimates, these being based on strategies using data on biological variation and on the clinical use of results. The derived goals are highly dependent on the assumptions made. In general, in monitoring of patients (using results from the same laboratory), the analytical imprecision is the most demanding, whereas bias (inaccuracy) is the most important characteristic when strategies for several centres (laboratories) to achieve similar results are invoked. Goals for analytical quality should be given in a form in which both analytical imprecision and bias (or systematic error) are specified. When several goals are to be considered (for different relevant assumptions), the most demanding should be used.

Diabetes Mellitus, Type 1↗

Analytical goals for interference.

Objective analytical goals for interference in clinical biochemical methods have not yet been advocated. We propose that, since total analytical error is ideally less than half the within-subject biological coefficient of variation (CVI), the maximum allowable systematic error produced by an interferent (I) is: I less than CVI-(1.96 CVA + SE), where CVA is the relevant experimental analytical imprecision and SE is the systematic error. Such a goal may be applicable also to non-specificity, matrix effects and carryover.

Chemistry Techniques, Analytical↗

Generation and application of analytical goals in laboratory medicine.

Desirable standards of performance of laboratory tests, termed analytical goals, are required for use in quality assurance, evaluation of methods, reagent kit sets and instruments, discussions with clinicians and gaining additional laboratory resources. Traditionally, goals have been derived from fractions of the reference interval, opinions of clinicians, the state of the art, views of individuals and groups and data on biological variation. All have disadvantages, but the last is currently favoured by many as the best strategy to delineate general goals. Recent more novel approaches have been concerned with the definition of goals for particular clinical situations, but these have not been widely accepted as yet. Further work is required on the setting of goals for performance characteristics other than imprecision and inaccuracy and on the use of goals in the design of effective quality control procedures.

Blood Chemical Analysis↗

The necessity of achieving good laboratory performance.

The results of clinical biochemistry tests are used in the diagnosis of diabetes mellitus by comparing them with reference values or agreed international criteria. Low analytical imprecision is required so that reference values are not unduly widened by analytical variability. Most laboratory test results are used in monitoring. Low analytical imprecision is required so that changes seen in sequential results reflect stability, amelioration or deterioration, not simply analytical variability. Analytical bias should be absent so that results are (1) comparable in individuals over time as methods evolve and instrumentation changes, (2) equivalent over locale since tests may be done in practitioners' surgeries, outpatient clinics, and laboratories, and (3) able to be interpreted against the fixed criteria. A plethora of strategies have been proposed to set numerical desirable standards of performance, these being termed analytical goals, including use of reference values, opinions of clinicians, state of the art, the views of experts, and data on biological variation. Use of data on within-subject biological variation is currently considered the best approach. A generally applicable goal is that the total error should be less than one-half of the within-subject biological variation. Achievement of this adds about 10% through analytical variability to the true test variability. Analytical goals (CV, %) for glucose, fructosamine, urinary albumin, and haemoglobin A1 assays are 2.2, 2.1, 18, and 3.3%, respectively. These goals are targets worthy of attainment, not inflexible criteria of acceptance or rejection of methods.

Albuminuria↗

Analytical goals for haematology tests.

All analytical methods can be defined in terms of their practicability and reliability performance characteristics. Desirable standards of performance, or analytical goals, are required for these, particularly for imprecision and inaccuracy. Goals for imprecision have been set using a variety of methods including reference values, opinions of clinicians, views of individuals, and data on biological variation. The last approach is currently favoured; desirable imprecision is equal to or less than one-half of the biological within-subject variation. If this goal is met, total variability of test results is increased by less than about 10% due to analytical variability. Valid estimates of within-subject variability are available for the complete blood count. The goal for inaccuracy is that methods should have no bias so that results are comparable over time and geography; goals based on biological variation should be viewed and used, therefore, as goals for total error. In current practice, some of the goals cannot be met; they should be considered as targets worthy of achievement, not as inflexible criteria of acceptance or rejection of methods.

Blood Chemical Analysis↗

Setting analytical goals for random analytical error in specific clinical monitoring situations.

Strategies abound for the setting of analytical goals in clinical chemistry. Many, especially those more recently proposed for particular clinical situations, are concerned with tests used in diagnosis. We suggest a general theory for the setting of goals in situations that specifically involve the monitoring of individuals. Goals are calculated from the formula CVA less than [(delta c 2/2Z2)-CVB2]1/2, where CVA is the analytical imprecision (as coefficient of variation, CV); delta c is the percentage change in serial results that is considered clinically significant; Z is the Z-statistic, which depends only on the probability selected for statistical significance; and CVB is the average inherent within-subject biological variation (as CV). Examples given show applications in hematology and in monitoring diabetes mellitus, chronic renal failure, and hepatitis. The derived goals are for total random analytical error (imprecision and intermittent systematic variation), and provide objective criteria that should be achieved in practice. The effect of analytical variability on both variability in test results and the probability that a stated change can be considered significant should be calculated whether or not the goals are attained.

Chemistry, Clinical↗

Guidelines (1988) for training in clinical laboratory management. International Federation of Clinical Chemistry (IFCC) Education Division and International Union of Pure and Applied Chemistry (IUPAC) Clinical Chemistry Division Commission on Teaching of Clinical Chemistry.

Trainees in laboratory medicine must develop skills in laboratory management. Guidelines are detailed for laboratory staff in training, directors responsible for staff development and professional bodies wishing to generate material appropriate to their needs. The syllabus delineates the knowledge base required and includes laboratory planning and organisation, control of operations, methodology and instrumentation, data management and statistics, financial management, clinical use of tests, communication, personnel management and training, and research and development. Methods for achievement of the skills required are suggested. A bibliography of IFCC publications and other material is provided to assist in training in laboratory management.

Administrative Personnel↗

The biochemical effects of high-dose inhaled salbutamol in patients with asthma.

We have studied the biochemical effects of high doses of inhaled salbutamol in 14 asthmatic patients age 38 years, FEV1 62%. Cumulative doubling doses of inhaled salbutamol were given every 20 min as follows: 100 micrograms, 200 micrograms, 500 micrograms, 1000 micrograms, 2000 micrograms, 4000 micrograms. Plasma glucose, potassium, and magnesium were measured at each step of the dose-response curve. Salbutamol produced significant hypokalaemic and hyperglycaemic effects, but no significant change in magnesium. There were linear log-dose responses for both glucose (r = 0.58) and potassium (r = -0.46). There were wide individual variations in maximum responses to salbutamol 4000 micrograms (as means and 95% confidence intervals): delta glucose 1.46 (0.83 to 2.09) mmol/l, delta potassium -0.38 (-0.64 to -0.12) mmol/l. Thus, hypokalaemic and hyperglycaemic effects may occur with doses of salbutamol similar to those currently used for nebulizer therapy (2.5-5 mg). We postulate that during acute exacerbations of airflow obstruction these changes may be accentuated and become clinically relevant.

Administration, Inhalation↗

Biologic variation of urinary albumin: consequences for analysis, specimen collection, interpretation of results, and screening programs.

Studies on the analytic and biologic variability of albumin concentration, albumin/creatinine ratio, and albumin excretion rate in first morning, random, and 24-hour urine specimens from healthy subjects suggest that (1) first morning specimens are preferred, (2) results should be expressed as albumin concentration, (3) assay of creatinine confers little advantage, (4) an analytical precision of coefficient of variation (CV) less than 18% is satisfactory, and (5) semiquantitative or qualitative analyses are suitable for screening programs. The intraindividual variation of albumin concentration in first morning specimens from diabetics is such that no threshold value gives the desired 100% nosological sensitivity. However, a threshold value of 30 mg/L confers 100% specificity, and a single abnormal result therefore requires initiation of therapy. Patients with negative results should continue to be monitored regularly.

Adolescent↗