The Advisory Committee on Immunization Practices recommends annual influenza vaccination for all health care personnel (HCP) to reduce influenza-related morbidity and mortality among both HCP and their patients and to decrease absenteeism among HCP (1-5).To estimate influenza vaccination coverage among U.S. HCP for the 2014-15 influenza season, CDC conducted an opt-in Internet panel survey of 1,914 HCP during March 31-April 15, 2015.Overall, 77.3% of HCP survey participants reported receiving an influenza vaccination during the 2014-15 season, similar to the 75.2% coverage among HCP reported for the 2013-14 season (6).Vaccination coverage was highest among HCP working in hospitals (90.4%) and lowest among HCP working in longterm care (LTC) settings (63.9%).By occupation, coverage was highest among pharmacists (95.3%) and lowest among assistants and aides (64.4%).Influenza vaccination coverage was highest among HCP who were required by their employer to be vaccinated (96.0%).Among HCP without an employer requirement for vaccination, coverage was higher for HCP working in settings where vaccination was offered on-site at no cost for 1 day (73.6%) or multiple days (83.9%) and lowest among HCP working in settings where vaccine was neither required, promoted, nor offered on-site (44.0%).Comprehensive vaccination strategies that include making vaccine available at no cost at the workplace along with active promotion of vaccination might help increase vaccination coverage among HCP and reduce the risk for influenza to HCP and their patients (1,6,7).The opt-in Internet panel survey was conducted for CDC by Abt Associates, Inc. (Cambridge, Massachusetts) during March 31-April 15, 2015, to provide estimates of influenza vaccination coverage among HCP during the 2014-15 influenza season.Two preexisting national opt-in Internet sources were used to recruit HCP for the survey.Professional clinical HCP (physicians, nurse practitioners, physician assistants, nurses, dentists, pharmacists, allied health professionals, technicians, and technologists) were recruited from the current membership roster of Medscape, a medical website managed by WebMD Health Professional Network.*Medscape's terms of service explicitly permit WebMD Professional Network to contact members about programming, including survey research; members receive an honorarium for completing surveys.HCP in other occupations (e.g., assistants,

During May 24–September 5, 2015, the United States experienced typical low levels of seasonal influenza activity. Influenza A (H1N1)pdm09 (pH1N1), influenza A (H3N2), and influenza B viruses were detected worldwide and were identified sporadically in the United States. All of the influenza viruses collected from U.S. states and other countries during that time have been characterized antigenically and/or genetically as being similar to the influenza vaccine viruses recommended for inclusion in the 2015–16 Northern Hemisphere vaccine. During May 24–September 5, 2015, three influenza variant† virus infections were reported; one influenza A (H3N2) variant virus (H3N2v) from Minnesota in July, one influenza A (H1N1) variant (H1N1v) from Iowa in August, and one H3N2v from Michigan in August.

BACKGROUND:Accurate and precise measurement of blood cholesterol plays a central role in the National Cholesterol Education Program's strategy to reduce the morbidity and mortality attributable to coronary heart disease. Matrix effects hamper the ability of manufacturers to adequately calibrate and validate traceability to the National Reference System for Cholesterol (NRS/CHOL). CDC created the Cholesterol Reference Method Laboratory Network (CRMLN) to improve cholesterol measurement by assisting manufacturers of in vitro diagnostic products with validation of the traceability of their assays to the NRS/CHOL.METHODS:CRMLN laboratories established the CDC cholesterol reference method (modification of the Abell-Levy-Brodie-Kendall chemical method) and are standardized using CDC frozen serum reference materials. CRMLN laboratories use common quality-control materials and participate in monthly external performance evaluations conducted by CDC. The CRMLN performance criteria require member laboratories to agree with CDC within +/-1.0% and maintain a CV < or =2.0%.RESULTS:From 1995 to 200 the CRMLN laboratories met the accuracy criterion 97% of the time and the precision criterion 99% of the time. During this time period, the CRMLN maintained an average bias to CDC of 0.01% and an average collective CV of 0.33%.CONCLUSIONS:CDC established the CRMLN as the first international reference method laboratory network. The CRMLN assists manufacturers in the validation of the calibration of their diagnostic products so that clinical laboratories can measure blood cholesterol more reliably. The CRMLN can serve as a model for other clinical analytes where traceability to a hierarchy of methods is needed and matrix effects of the field methods with processed calibrators or reference materials are present.

Background: Detection of cobalamin deficiency is increasingly important, and methylmalonic acid (MMA) appears to be a useful marker. Information on interlaboratory variation and on methodological differences for MMA in serum and plasma is limited.Methods: Using gas chromatography/mass spectrometry, 13 laboratories participated in a 2-day analysis of 8 serum and 11 EDTA-plasma specimens. Results were analyzed for imprecision, recovery, and differences among laboratories and methods.Results: The mean among-laboratory imprecision (CV) was 19% and 21% for serum and plasma samples, respectively, and 9.3% and 7.8% for serum and plasma samples with added MMA, respectively. The mean within-laboratory (among-run) CV was 13% for both serum and plasma samples and 5.2% and 4.9% for serum and plasma samples with added MMA. Within-method imprecision was the same or higher than among-method imprecision. The mean among-laboratory recovery of MMA was 105% and 95% in serum and plasma, respectively. Most laboratories showed a proportional bias relative to the consensus mean of up to 15%. Two laboratories reported results that on average were almost 30% higher than the consensus mean.Conclusions: No method differences were found, but significant among-laboratory imprecision was found in the present study. Improvements are needed to reduce the analytical imprecision of most laboratories, and attention must be focused on calibration issues. Differences among laboratories can be improved by introducing high-quality reference materials and by instituting external quality assessment programs. (C) 1999 American Association for Clinical Chemistry.

BACKGROUNDInformation on interlaboratory variation and especially on methodological differences for plasma total homocysteine is lacking.METHODSWe studied 14 laboratories that used eight different method types: HPLC with electrochemical detection (HPLC-ED); HPLC with fluorescence detection (HPLC-FD) further subdivided by type of reducing/derivatizing agent; gas chromatography/mass spectrometry (GC/MS); enzyme immunoassay (EIA); and fluorescence polarization immunoassay (FPIA). Three of these laboratories used two methods. The laboratories participated in a 2-day analysis of 46 plasma samples, 4 additional plasma samples with added homocystine, and 3 plasma quality-control (QC) pools. Results were analyzed for imprecision, recovery, and methodological differences.RESULTSThe mean among-laboratory and among-run within-laboratory imprecision (CV) was 9.3% and 5.6% for plasma samples, 8.8% and 4.9% for samples with added homocystine, and 7.6% and 4.2% for the QC pools, respectively. Difference plots showed values systematically higher than GC/MS for HPLC-ED, HPLC-FD using sodium borohydride/monobromobimane (however, for only one laboratory), and EIA, and lower values for HPLC-FD using trialkylphosphine/4-(aminosulfonyl)-7-fluoro-2,1,3-benzoxadiazole. The two HPLC-FD methods using tris(2-carboxyethyl) phosphine/ammonium 7-fluoro-2,1,3-benzoxadiazole-4-sulfonate (SBD-F) or tributyl phosphine/SBD-F, and the FPIA method showed no detectable systematic difference from GC/MS.CONCLUSIONSAmong-laboratory variations within one method can exceed among-method variations. Some of the methods tested could be used interchangeably, but there is an urgent need to improve analytical imprecision and to decrease differences among methods.

We examine the effect of systematic bias and random error, quality control, and intraperson biological variation on the National Cholesterol Education Program (NCEP) clinical classifications for reported lipid measurements. We consider misclassification to occur if a true lipid homeostatic set point is within a desirable range but the reported lipid value is in a high-risk range, or if a true lipid homeostatic set point is in a high-risk range but the reported lipid value is in a desirable range. To evaluate the overall adequacy of the NCEP guidelines to ensure correct patient classification, we construct operating characteristic curves for total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. We demonstrate that if laboratories are meeting the NCEP guidelines for inherent bias and analytic precision and are using standard quality-control (QC) procedures incorporating at least two QC samples per analytical run from each of two QC pools (for a total of 4 QC samples), the current NCEP guidelines are adequate to ensure (probability >0.90) correct patient classifications regardless of the size of the systematic bias of the laboratory or increased random analytic error. Thus we suggest that at least two concentrations of QC material be included in the QC scheme to ensure that the measurement system is operating within desired specifications across the entire range of desirable and high-risk lipid concentrations and to ensure with high probability that patients are correctly classified.

We read with concern the recent paper by Fallest-Strobl, Olafsdottir, Wiebe, and Westgard (1) in which the authors state, “… the NCEP recommendations fail to adequately consider the quality control requirements necessary to detect medically important systematic errors.” We also note that Westgard, Petersen, and Wiebe (2) published a similar paper in 1991 questioning the adequacy of the NCEP recommendations for total cholesterol. We appreciate the importance of the issues addressed in these two papers and find no fault in the majority of the derivations. We do notice, however, that the authors did not address the conditional nature of their calculations. That is, the OPSpecs charts do not take into account the fact that a patient result will only be reported when the quality control (QC) run associated with the patient specimen is considered to be in control. Thus, the OPSpecs charts relate to the conditional probability that a measured patient result will exceed a specified limit, not to the joint probability of patient misclassification. For misclassification to occur, the measured patient result must not only exceed the specified limit, but the QC procedure must also fail to indicate an out-of-control condition. Without taking into account the probability that the QC procedure will fail to detect an out-of-control condition, the authors do not accomplish their stated intention to evaluate the NCEP recommendations with regard to “quality control procedures that are necessary to detect unstable operation” (2). Incorporating QC performance into the OPSpecs charts requires inclusion of the probability that a patient result will be reported on the basis of the QC outcome of the analytic run in which the patient specimen was measured. To illustrate our point, consider the intended 0.95 probability of correct classification chosen by the authors. This conditional probability does not reflect the overall likelihood of correct … bAuthor for correspondence.

To determine the relative merits of two quantitative methods used to estimate the summary effects of observational studies, the authors compared two methods of meta-analysis. Each quantified the relation between oral contraceptive use and the risk for ovarian cancer. One analysis consisted of a meta-analysis using summary data from 11 published studies from the literature (MAL) in which the study was the unit of analysis, and the second consisted of a meta-analysis using individual patient data (MAP) in which the patient was the unit of analysis. The authors found excellent quantitative agreement between the summary effect estimates from the MAL and the MAP. The MAP permits analysis 1) among outcomes, exposures, and confounders not investigated in the original studies, 2) when the original effect measures differ among studies and cannot be converted to a common measure (e.g., slopes vs. correlation coefficients), and 3) when there is a paucity of studies. The MAL permits analysis 1) when resources are limited, 2) when time is limited, and 3) when original study data are not available or are available only from a biased sample of studies. In public health epidemiology, data from original studies are often accessible only to limited numbers of research groups and for only a few types of studies that have high public health priority. Consequently, few opportunities for pooled analysis exist. However, from a policy view, MAL will provide answers to many questions and will help in identifying questions for future investigation.

We have developed and evaluated a new procedure for detecting trends in quality-control measurements and applied it to laboratory data. The method requires the use of sequential or "moving" slope estimates to identify trends. Formulae are derived to estimate the regression error for the moving slope directly from the standard deviation of the analytical measurements obtained during characterization runs. Control limits for the moving slope depend only on this regression error, the span of the slope, and the desired statistical level of control. The moving slope can be plotted with control limits to determine out-of-control points. The statistical power of the moving slope is found to be much greater than that of an often-used test for trends. An example of the use of the moving slope is shown for quality-control measurements for total cholesterol obtained over several years. We conclude that the moving slope procedure has considerably more statistical power than trend rules and that it yields more useful information to the analyst.

In 1987 a collaborative study was initiated with 140 laboratories worldwide to evaluate the effects of analytical method and lyophilization on the measurement of different concentrations of apolipoproteins (apo) A-I and B in four lyophilized serum pool samples. This survey confirmed that the lyophilized apo Reference Material of the International Union of Immunological Societies (IUIS) is useful for apo A-I assays as an international serum-based reference material, because among-method variation is negligible. The apo A-I concentration value of 1.24 g/L is now assigned to the IUIS Reference Material (CDC 1883) by a Centers for Disease Control RIA in-house reference method. Use of lyophilized serum preparation as a reference material for some modes of apo B measurement is questionable because of lyophilization and matrix effects. Both radial immunodiffusion and liquid immunoprecipitin methods demonstrated bias in measured apo B concentrations, compared with overall method-weighted means values on the IUIS Reference Material. Because of the uncertainty associated with LDL primary standard, protein analysis, and concentration differences among analytical methods, assigning a single apo B concentration value to the IUIS Reference Material appears inadvisable at present.

In 1989 the Committee on Apolipoproteins of the International Federation of Clinical Chemistry and the Centers for Disease Control conducted an international survey of total-protein measurements of isolated low-density lipoproteins (LDL) and delipidated high-density lipoproteins (HDL), and of their relationships to the National Institute of Standards and Technology (NIST) bovine serum albumin (BSA) Standard Reference Material (SRM). Most of the 93 apolipoprotein laboratories surveyed use the Lowry total-protein method. Results reported with the LDL preparations demonstrated a large bias and variation among methods; those with delipidated HDL were not as great, but were similar to those for BSA. Performance improved appreciably with use of the Lowry-sodium dodecyl sulfate method and the NIST BSA SRM for protein measurement. The total CVs, including among-laboratory and within-laboratory errors, averaged approximately 50% and 23% for LDL, 17% and 11% for HDL, and 18% and 11% for BSA solutions by all methods and by the Lowry methods, respectively. Regardless of the methods used, greater variability of the protein measurements was seen with the normally occurring LDL than with the nonlipoprotein BSA or delipidated HDL. The mean CV values for all samples among laboratories averaged between 10% and 15% with the modified Lowry methods; the biuret method gave the highest among-laboratory CV, 34%; the Kjeldahl had the lowest, 7.7%. Use of the same methodology and primary nonapolipoprotein standard is essential for comparability of protein results for apolipoprotein primary standard solutions. This is especially true for apolipoprotein B, because its inherent properties and lability make protein analysis difficult. This study supports the use of a standardized selected Lowry-sodium dodecyl sulfate method traceable to quantitative amino acid analysis as a point of reference for determining the protein concentration of primary calibration reference materials for apolipoproteins.

Isolates of rabies virus from terrestrial animals in six geographically separate rabies enzootic areas of the United States were examined with a panel of monoclonal antibodies to the viral N protein. Characteristic differences in immunofluorescence reactions permitted the formation of five antigenically distinct reaction groups from the 328 isolates tested. Distinctive reaction patterns were also identified for isolates from four species of bats. These observations were used to determine the role of infected bats in 19 cases of rabies that had occurred in terrestrial animals living in areas free of enzootic rabies in terrestrial wildlife and to estimate the contribution of infected bats to rabies in cats and foxes in the United States. The findings suggest that monoclonal antibodies can be used to study the prevalence, distribution, and transmission of rabies among wildlife species.