Ventilatory management casebook. Error in blood gas sampling resulting in a spurious interpretation of compensated metabolic acidosis.
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Acidosis↗
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Particle penetration through sampling prefilters illustrates the analysis error in NIOSH-type procedures for nickel carbonyl.
Sampling and analysis of aerosols generated by plasma are cutting of stainless steel have qualitatively demonstrated particle penetration of sampler prefilters utilized in the National Institute for Occupational Safety and Health (NIOSH)-type and impinger sampler analytical procedures for measuring the presence of nickel carbonyl. These results illustrate that only a small mass of nickel-containing particles need penetrate the prefilters to exaggerate greatly the inferred concentration of nickel carbonyl. Strong evidence was obtained via the chemiluminescence method that nickel carbonyl concentrations in fact were very low (less than 1 ppb).
Aerosols↗
[Quantitation of regional cerebral blood flow using 123I-IMP from a single SPECT scan and a single blood sampling--analysis on statistical error source and optimal scan time].
Recently, a method has been proposed to measure quantitative regional cerebral blood flow (rCBF) in man using N-isopropyl-p-[123I]-iodoamphetamine (IMP) and single photon emission tomography (SPECT). In this method (IMP-ARG method), a functional map of rCBF was calculated from a single SPECT scan data set, in which effects of the clearance of IMP from the brain was taken into account by employing the 2 compartment model. To avoid the procedures of frequent and/or continuous sampling of the arterial blood that was required in determination of the input function, use of a standard input function and calibrating it by one blood sampling were validated. The present study was intended to investigate the sensitivity to various sources of errors in the IMP-ARG method such as (1) effects of individual difference of the arterial input function, (2) effects of ambiguity of the regional distribution volume (Vd) of IMP, and (3) effects of inaccuracy of the SPECT measurement. It was shown in the present simulation study that errors in the calculated rCBF values were dependent on the SPECT mid-scan time (MST), and that the minimum error corresponded to the MST of approximately 30 min after the IMP infusion. With this optimal MST, errors in rCBF due to the individual difference of the input function was approximately 10%, and the errors due to the ambiguity of the Vd were approximately 8%. The total accuracy of the calculated rCBF in the IMP-ARG method was, therefore, estimated as approximately 13%. Although a relatively large error was expected at a high rCBF area, this study strongly suggested the IMP-ARG method being useful and accurate for providing the quantitative rCBF map for a clinical use.
Amphetamines↗
Reliability and sensitivity of frozen-section pancreatic biopsy.
A collaborative Veterans Administration and University of California, Davis Medical Center group of 586 patients with histologically proved pancreatic carcinoma was reviewed. During laparotomy, 159 patients underwent 251 frozen-section pancreatic biopsies with subsequent permanent section examination of the same tissue block. All 112 positive frozen-section diagnoses were corroborated on permanent sectioning. The 47 patients with false-negative biopsy specimens were equally divided between sampling and interpretation error. We conclude that in this group of 159 pancreatic cancer patients, 30% failed to be correctly diagnosed by intraoperative frozen-section biopsy. This failure was due to patient sampling and interpretation error in equal proportion. Interpretation error rates were not influenced by the type or number of biopsies. Patient sampling error is apparently reduced by repeated biopsy, and specimen sampling error occurred less frequently with wedge biopsy.
Biopsy↗
Design and operation of the 1995 National Survey of Family Growth.
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Adolescent↗
Increasing power for tests of genetic association in the presence of phenotype and/or genotype error by use of double-sampling.
Phenotype and/or genotype misclassification can: significantly increase type II error probabilities for genetic case/control association, causing decrease in statistical power; and produce inaccurate estimates of population frequency parameters. We present a method, the likelihood ratio test allowing for errors (LRTae) that incorporates double-sample information for phenotypes and/or genotypes on a sub-sample of cases/controls. Population frequency parameters and misclassification probabilities are determined using a double-sample procedure as implemented in the Expectation-Maximization (EM) method. We perform null simulations assuming a SNP marker or a 4-allele (multi-allele) marker locus. To compare our method with the standard method that makes no adjustment for errors (LRTstd), we perform power simulations using a 2/k factorial design with high and low settings of: case/control samples, phenotype/genotype costs, double-sampled phenotypes/genotypes costs, phenotype/genotype error, and proportions of double-sampled individuals. All power simulations are performed fixing equal costs for the LRTstd and LRTae methods. We also consider case/control ApoE genotype data for an actual Alzheimer's study. The LRTae method maintains correct type I error proportions for all null simulations and all significance level thresholds (10%, 5%, 1%). LRTae average estimates of population frequencies and misclassification probabilities are equal to the true values, with variances of 10e-7 to 10e-8. For power simulations, the median power difference LRTae-LRTstd at the 5% significance level is 0.06 for multi-allele data and 0.01 for SNP data. For the ApoE data example, the LRTae and LRTstd p-values are 5.8 x 10e-5 and 1.6 x 10e-3, respectively. The increase in significance is due to adjustment in the LRTae for misclassification of the most commonly reported risk allele. We have developed freely available software that performs our LRTae statistic.
Journal Article↗
Fixed-interval matching-to-sample: intermatching time and intermatching error runs.
Four pigeons were trained on a matching-to-sample task in which reinforcers followed either the first matching response (fixed interval) or the fifth matching response (tandem fixed-interval fixed-ratio) that occurred 80 seconds or longer after the last reinforcement. Relative frequency distributions of the matching-to-sample responses that concluded intermatching times and runs of mismatches (intermatching error runs) were computed for the final matching responses directly followed by grain access and also for the three matching responses immediately preceding the final match. Comparison of these two distributions showed that the fixed-interval schedule arranged for the preferential reinforcement of matches concluding relatively extended intermatching times and runs of mismatches. Differences in matching accuracy and rate during the fixed interval, compared to the tandem fixed-interval fixed-ratio, suggested that reinforcers following matches concluding various intermatching times and runs of mismatches influenced the rate and accuracy of the last few matches before grain access, but did not control rate and accuracy throughout the entire fixed-interval period.
Journal Article↗
Psychological impact of abortion: methodological and outcomes summary of empirical research between 1966 and 1988.
A systematic "roadmap" through the medical literature that empirically examines the incidence of psychological sequelae of induced abortion is presented. Because outcome incidence rates and methodological profiles vary substantially across studies, selective use of articles from this literature without an accompanying rationale for that selectivity could foster erroneous conclusions. Information compiled here can facilitate a rapid methodological critique of citations in abortion-related materials. Investigations published in English between January 1966 and April 1988 that quantitatively examined psychological sequelae using prospective, retrospective, or comparative methodologies are summarized in tables to produce a synopsis of the demographics, methodological limitations, and gross statistical features of each article. This quantitative guide is designed to facilitate appropriate use of the current literature, provide needed background to assess positions arising from the currently available data, and provide methodological focus for planning better studies in the future.
Abortion, Induced↗
The effect of phenotype variation on detection of linkage in the COGA data.
Error in phenotypic measurement can significantly compromise ability to detect linkage. We assessed the impact of introducing phenotypic measurement error on our ability to detect a quantitative trait locus in the Collaborative Study on the Genetics of Alcoholism (COGA) data. The impact of introducing three different types of errors was evaluated: 1) errors generated by sampling from a normal distribution; 2) errors generated by permuting phenotype values between subjects; and 3) errors generated by sampling from a uniform error distribution.
Alcoholism↗
Reference sample method reduces the error caused by variable cryosection thickness in Fourier transform infrared imaging.
Fourier transform infrared imaging (FT-IRI) is a novel technique for characterization of the biochemical composition of biological tissues, e.g., articular cartilage. The use of cryosections is preferred in FT-IRI. Unfortunately, significant variation in section thickness often impairs the suitability of cryosections for quantitative FT-IRI analysis. The present study introduces an inexpensive reference sample method for quantitative analysis. In this technique, specimen absorption is normalized with that of nitrocellulose membrane embedded and cryosectioned with the sample. Mean variation of the infrared absorption in cartilage specimens was 11.5%, 12.1%, and 20.6% for 5 microm, 10 microm, and 14 microm thick sections, respectively, without normalization. Normalization reduced the variation to 5.2%, 4.0%, and 4.6% for the same sections, respectively. The normalization method enables usage of cryosections for quantitative work and significantly reduces the cost and time needed for FT-IRI analysis.
Animals↗
Further development of a robust workup process for solution-phase high-throughput library synthesis to address environmental and sample tracking issues.
During further improvement of a high-throughput, solution-phase synthesis system, new workup tools and apparatus for parallel liquid-liquid extraction and evaporation have been developed. A combination of in-house design and collaboration with external manufacturers has been used to address (1) environmental issues concerning solvent emissions and (2) sample tracking errors arising from manual intervention. A parallel liquid-liquid extraction unit, containing miniature high-speed magnetic stirrers for efficient mixing of organic and aqueous phases, has been developed for use on a multichannel liquid handler. Separation of the phases is achieved by dispensing them into a newly patented filter tube containing a vertical hydrophobic porous membrane, which allows only the organic phase to pass into collection vials positioned below. The vertical positioning of the membrane overcomes the hitherto dependence on the use of heavier-than-water, bottom-phase, organic solvents such as dichloromethane, which are restricted due to environmental concerns. Both small (6-mL) and large (60-mL) filter tubes were developed for parallel phase separation in library and template synthesis, respectively. In addition, an apparatus for parallel solvent evaporation was developed to (1) remove solvent from the above samples with highly efficient recovery and (2) avoid the movement of individual samples between their collection on a liquid handler and registration to prevent sample identification errors. The apparatus uses a diaphragm pump to achieve a dynamic circulating closed system with a heating block for the rack of 96 sample vials and an efficient condenser to trap the solvents. Solvent recovery is typically >98%, and convenient operation and monitoring has made the apparatus the first choice for removal of volatile solvents.
Amides↗
False-negative Papanicolaou smears from women with cancerous and precancerous lesions of the uterine cervix.
The occurrence from 1980 to 1989 of false-negative Papanicolaou smears in women with cancerous and precancerous lesions of the uterine cervix was studied. The 4,781 cases of cancer (2,814 invasive carcinomas and 593 carcinomas in situ) and precancerous lesions (418 severe dysplasias, 748 moderate dysplasias and 208 mild dysplasias) included 70 cases (1.5%) with false-negative smears. These 70 cases included 43 invasive carcinomas (61.4%), 17 carcinomas in situ and adenocarcinomas in situ (24.2%), and 10 dysplasias (14.4%); all were diagnosed histologically. The mean age of women with false-negative smears was 44.1 +/- 13.7 years. Review of the original cytologic samples showed a screening error in 41 cases (58.5%), an interpretation error in 2 cases (2.9%) and a sampling error in 27 cases (38.6%). Methods for eliminating false-negative smears are discussed.
Adult↗
The calculation of errors and the choice of sampling times in the determination of irreversible disposal rates in vivo by isotope experiments.
In well-known methods of estimating rates of irreversible disposal (utilization) in vivo the rates are calculated from the areas to infinity under specific radioactivity-time (S-t) or quantity-of-label-time (q-t) curves obtained by measurements on samples of plasma after intravenous injection of labelled substrate. The errors in the calculated rates are mostly those of the estimates of the areas. These errors are of two kinds: random, caused by the variances of the values of S or q, and systematic, caused by differences between the curves used to interpolate between these values and the true curves. A rigorous method is given for calculating the random errors from the variances of the values of S or q, and is applied to choosing the best times to sample the plasma from small animals from which few plasma samples can be taken. A procedure for estimating systematic errors is also given. Programs in BASIC language to carry out the calculations are deposited as Supplementary Publication SUP 50058 (5 pages) at the British Library (Lending Division), Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms given in Biochem. J. (1975) 145, 5.
Isotopes↗
Getting the right blood to the right patient: the contribution of near-miss event reporting and barrier analysis.
Safety and reliability in blood transfusion are not static, but are dynamic non-events. Since performance deviations continually occur in complex systems, their detection and correction must be accomplished over and over again. Non-conformance must be detected early enough to allow for recovery or mitigation. Near-miss events afford early detection of possible system weaknesses and provide an early chance at correction. National event reporting systems, both voluntary and involuntary, have begun to include near-miss reporting in their classification schemes, raising awareness for their detection. MERS-TM is a voluntary safety reporting initiative in transfusion. Currently 22 hospitals submit reports anonymously to a central database which supports analysis of a hospital's own data and that of an aggregate database. The system encourages reporting of near-miss events, where the patient is protected from receiving an unsuitable or incorrect blood component due to a planned or unplanned recovery step. MERS-TM data suggest approximately 90% of events are near-misses, with 10% caught after issue but before transfusion. Near-miss reporting may increase total reports ten-fold. The ratio of near-misses to events with harm is 339:1, consistent with other industries' ratio of 300:1, which has been proposed as a measure of reporting in event reporting systems. Use of a risk matrix and an event's relation to protective barriers allow prioritization of these events. Near-misses recovered by planned barriers occur ten times more frequently then unplanned recoveries. A bedside check of the patient's identity with that on the blood component is an essential, final barrier. How the typical two person check is performed, is critical. Even properly done, this check is ineffective against sampling and testing errors. Blood testing at bedside just prior to transfusion minimizes the risk of such upstream events. However, even with simple and well designed devices, training may be a critical issue. Sample errors account for more than half of reported events. The most dangerous miscollection is a blood sample passing acceptance with no previous patient results for comparison. Bar code labels or collection of a second sample may counter this upstream vulnerability. Further upstream barriers have been proposed to counter the precariousness of urgent blood sample collection in a changing unstable situation. One, a linking device, allows safer labeling of tubes away from the bedside, the second, a forcing function, prevents omission of critical patient identification steps. Errors in the blood bank itself account for 15% of errors with a high potential severity. In one such event, a component incorrectly issued, but safely detected prior to transfusion, focused attention on multitasking's contribution to laboratory error. In sum, use of near-miss information, by enhancing barriers supporting error prevention and mitigation, increases our capacity to get the right blood to the right patient.
ABO Blood-Group System↗
Use of control sample for estimation of prediction error in multivariate determination of lidocaine solutions with non-column chromatographic diode array UV spectroscopy.
The aim of this study was to investigate the ability of a control sample, of known content and identity, to diagnose and correct errors in the predictions when the same multivariate calibration model was used for analysis of new samples over time. A calibration set consisting of 16 samples with a known content of lidocaine was analysed and two external test sets, A and B, were used for the validation. Test set A contained 15 samples with different concentrations of lidocaine and test set B contained three samples with different lidocaine content, which were analysed six times in order to obtain a measure of repeatability. The multivariate calibration was done with PLS regression on UV spectra collected between 245 and 290 nm. A representative UV spectrum was exported from the collected DAD files by two methods, average spectrum over the whole file and average spectrum over the sample plug. Test set A was analysed further on another three occasions together with a control sample. The results showed that the control sample could be used to give a diagnosis and estimate of the prediction error. Moreover, the measured prediction error of the control sample could also be used to correct the predictions, thereby reducing the prediction error. Finally, some practical considerations regarding use of the proposed DAD method with a control sample are presented. The procedure suggested could lead to an efficient analytical approach where the same calibration model could be used over time without recalibration, which may be attractive in industrial quality control or screening analysis in pharmaceutical research.
Chromatography, High Pressure Liquid↗
Sensitivity of HER-2/neu antibodies in archival tissue samples: potential source of error in immunohistochemical studies of oncogene expression.
HER-2/neu oncogene amplification and overexpression of breast cancer tissue has been correlated with poor prognosis in women with both node-positive and node-negative disease. However, several studies have not confirmed this association. Review of these studies reveals the presence of considerable methodological variability including differences in study size, follow-up time, techniques and reagents. The majority of papers with clinical follow-up information are immunohistochemical studies using archival, paraffin-embedded breast cancers, and a variety of HER-2/neu antibodies have been used in these studies. Very little information, however, is available about the ability of the antibodies to detect overexpression following tissue processing for paraffin-embedding. Therefore, a series of antibodies, reported in the literature or commercially available, were evaluated to assess their sensitivity and specificity as immunohistochemical reagents. Paraffin-embedded samples of 187 breast cancers, previously characterized as frozen specimens for HER-2/neu amplification by Southern blot and for overexpression by Northern blot, Western blot, and immunohistochemistry, were used. Two multitumor paraffin-embedded tissue blocks were prepared from the previously analyzed breast cancers as a panel of cases to test a series of previously studied and/or commercially available anti-HER-2/neu antibodies. Immunohistochemical staining results obtained with 7 polyclonal and 21 monoclonal antibodies in sections from paraffin-embedded blocks of these breast cancers were compared. The ability of these antibodies to detect overexpression was extremely variable, providing an important explantation for the variable overexpression rate reported in the literature.
Antibodies↗
Adenocarcinoma in situ of the cervix.
BACKGROUND: The current study examines 1) the sensitivity of detection and 2) sampling and screening/diagnostic error in the cytologic diagnosis of adenocarcinoma in situ (AIS) of the cervix. The data were taken from public and private sector screening laboratories reporting 25,000 and 80,000 smears, respectively, each year. METHODS: The study group was comprised of women with a biopsy diagnosis of AIS or AIS combined with a high-grade squamous intraepithelial lesion (HSIL) who were accessioned by the Western Australian Cervical Cytology Registry (WACCR) between 1993-1998. Cervical smears reported by the Western Australia Centre for Pathology and Medical Research (PathCentre) or Western Diagnostic Pathology (WDP) in the 36 months before the index biopsy was obtained were retrieved. A true measure of the sensitivity of detection could not be determined because to the authors' knowledge the exact prevalence of disease is unknown at present. For the current study, sensitivity was defined as the percentage of smears reported as demonstrating a possible or definite high-grade epithelial abnormality (HGEA), either glandular or squamous. Sampling error was defined as the percentage of smears found to have no HGEA on review. Screening/diagnostic error was defined as the percentage of smears in which HGEA was not diagnosed initially but review demonstrated possible or definite HGEA. Sensitivity also was calculated for a randomly selected control group of biopsy proven cases of Grade 3 cervical intraepithelial neoplasia (CIN 3) accessioned at the WACCR in 1999. RESULTS: For biopsy findings of AIS alone, the diagnostic "sensitivity" of a single smear was 47.6% for the PathCentre and 54.3% for WDP. Nearly all the abnormalities were reported as glandular. The sampling and screening/diagnostic errors were 47.6% and 4.8%, respectively, for the PathCentre and 33.3% and 12.3%, respectively, for WDP. The results from the PathCentre were better for AIS plus HSIL than for AIS alone, but the results from WDP were similar for both groups. For the CIN 3 control cases, the "sensitivity" of a single smear was 42.5%. CONCLUSIONS: To the authors' knowledge epidemiologic studies published to date have not demonstrated a benefit from screening for precursors of cervical adenocarcinoma. However, in the study laboratories as in many others, reasonable expertise in diagnosing AIS has been acquired only within the last 10-15 years, which may be too short a period in which to demonstrate a significant effect. The results of the current study provide some encouraging baseline data regarding the sensitivity of the Papanicolaou smear in detecting AIS. Further improvements in sampling and cytodiagnosis may be possible.
Adenocarcinoma↗
Outpatient order accuracy. A College of American Pathologists Q-Probes study of requisition order entry accuracy in 660 institutions.
CONTEXT: Laboratory test order entry errors potentially delay diagnosis, consume resources, and cause patient inconvenience. OBJECTIVE: To evaluate the frequency and causes of computer order entry errors in outpatients. DESIGN: Cross-sectional survey and prospective sample of errors. Participants answered questions about their test order entry policies and practices. They then examined a sample of outpatient requisitions and compared information on the requisition with information entered into the laboratory computer system. Order entry errors were divided into 4 types: tests ordered on the requisition, but not in the computer; tests performed but not ordered on the requisition; physician name discrepancies; and test priority errors. PARTICIPANTS: Six hundred sixty laboratories enrolled in the College of American Pathologists Q-Probes program. MAIN OUTCOME MEASURE: Overall order entry error rate. RESULTS: A total of 5514 (4.8%) of 114 934 outpatient requisitions were associated with at least 1 order entry error. The median participant reported 1 or more order errors on 6.0% of requisitions; 10% of institutions reported errors with at least 18% of requisitions. Of the 4 specific error types, physician name discrepancies had the highest error rate, and test priority errors the lowest error rate. Four institutional factors were significantly associated with higher overall error rates: orders verbally communicated to the laboratory; no policy requiring laboratory staff to compare a printout or display of ordered tests with the laboratory requisitions to confirm that orders had been entered correctly; failure to monitor the accuracy of outpatient order entry on a regular basis; and a higher percentage of occupied beds (ie, a busier hospital). CONCLUSIONS: Computer order entry errors are common, involving 5% of outpatient requisitions. Laboratories may be able to decrease error rates by regularly monitoring the accuracy of order entry, substituting written and facsimile orders for verbal orders, and instituting a policy in which orders entered into computer systems are routinely rechecked against orders on requisitions.
Ambulatory Care↗