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Analysis of heart rate variability during head-up tilt testing in a patient with idiopathic postural orthostatic tachycardia syndrome (POTS).

A 16-year-old boy was diagnosed with idiopathic postural orthostatic tachycardia syndrome (POTS) during head-up tilt testing. During a passive tilt, the patient's heart rate (HR) increased by 30 beats/min within 5 min. After 25 min of tilting, his HR further increased to 133 beats/min and he began to complain of lightheadedness and weakness without hypotension. Power spectral analysis of HR variability during the tilt test revealed that the ratio of low and high frequency powers increased with the onset of orthostatic intolerance. Propranolol (10mg every morning) dramatically alleviated his clinical symptoms, and he has been asymptomatic with gaining weight after discontinuing his crowded train commuting.

Adolescent↗

A model for harmonization of routine clinical chemistry results between clinical laboratories.

Clinical chemistry laboratory results from different laboratories often show large between-laboratory variation due to factors such as differences in method principles, method applications, calibration procedures or the application of different instrument factor settings within the same calibration procedure. We have examined the possible use of common calibrators to reduce this variation. Three different calibrators were compared: A, freeze-dried preparations of pooled patients' serum samples, spiked to give three concentration levels; B, freeze-dried preparations of pooled patients' serum samples selected on the basis of elevated enzyme activities at three levels; C, a single calibrator consisting of frozen pooled serum samples. These calibrators were sent to 11 participating laboratories together with 14 fresh patients' serum samples. We report the variation of the results of 21 general clinical chemistry analytes obtained in the patients' serum samples before and after recalculation on the basis of the results of the calibrators. For most analytes the use of a multiple point linear regression calibration function is able to reduce the between-laboratory variation considerably from more than 30% (enzymes) to values well within the bias limits set by European quality specifications, when the necessary conditions are met. These conditions include the commutability of the calibrator(s) with fresh patients' material. For the enzymes, calibrator material originating from selectively pooled patients' samples appeared to be necessary, whereas for the substrates selectively pooled serum calibrators spiked with exogenous supplements may be used. For harmonization to be effective in practice, calibrators need to be stable over time and to carry assigned values set by certified reference laboratories, and the quality performance of participating laboratories should be appropriately monitored.

Calibration↗

Measurement of urinary porphyrins and porphyrin precursors in Dutch hospital laboratories: a review of quality control over 5 years.

BACKGROUND: We evaluated a quality control scheme for the measurement of urinary uroporphyrin, coproporphyrin, total urinary porphyrins and precursors of urinary porphyrins, delta-aminolevulinic acid and porphobilinogen that was performed in The Netherlands during a period of 5 years. METHODS: Six quality control samples were distributed each year to the participating laboratories. Mean concentrations and the corresponding coefficients of variation were calculated. RESULTS: Coefficients of variation varied widely and were very high in the concentration ranges that can be found in patients with low-grade porphyria. CONCLUSION: Commutable calibrators are needed to improve the laboratory diagnosis of porphyria.

Aminolevulinic Acid↗

Controlled human exposure to methyl tertiary butyl ether in gasoline: symptoms, psychophysiologic and neurobehavioral responses of self-reported sensitive persons.

The 1990 Clean Air Act mandated oxygenation of gasoline in regions where carbon monoxide standards were not met. To achieve this standard, methyl tertiary butyl ether (MTBE) was increased to 15% by volume during winter months in many locations. Subsequent to the increase of MTBE in gasoline, commuters reported increases in symptoms such as headache, nausea, and eye, nose, and throat irritation. The present study compared 12 individuals selected based on self-report of symptoms (self-reported sensitives; SRSs) associated with MTBE to 19 controls without self-reported sensitivities. In a double-blind, repeated measures, controlled exposure, subjects were exposed for 15 min to clean air, gasoline, gasoline with 11% MTBE, and gasoline with 15% MTBE. Symptoms, odor ratings, neurobehavioral performance on a task of driving simulation, and psychophysiologic responses (heart and respiration rate, end-tidal CO(2), finger pulse volume, electromyograph, finger temperature) were measured before, during, and immediately after exposure. Relative to controls, SRSs reported significantly more total symptoms when exposed to gasoline with 15% MTBE than when exposed to gasoline with 11% MTBE or to clean air. However, these differences in symptoms were not accompanied by significant differences in neurobehavioral performance or psychophysiologic responses. No significant differences in symptoms or neurobehavioral or psychophysiologic responses were observed when exposure to gasoline with 11% MTBE was compared to clean air or to gasoline. Thus, the present study, although showing increased total symptoms among SRSs when exposed to gasoline with 15% MTBE, did not support a dose-response relationship for MTBE exposure nor the symptom specificity associated with MTBE in epidemiologic studies.

Adult↗

Evaluation of take-home organophosphorus pesticide exposure among agricultural workers and their children.

We analyzed organophosphorus pesticide exposure in 218 farm worker households in agricultural communities in Washington State to investigate the take-home pathway of pesticide exposure and to establish baseline exposure levels for a community intervention project. House dust samples (n = 156) were collected from within the homes, and vehicle dust samples (n = 190) were collected from the vehicles used by the farm workers to commute to and from work. Urine samples were obtained from a farm worker (n = 213) and a young child (n = 211) in each household. Dust samples were analyzed for six pesticides, and urine samples were analyzed for five dialkylphosphate (DAP) metabolites. Azinphosmethyl was detected in higher concentrations (p < 0.0001) than the other pesticides: geometric mean concentrations of azinphosmethyl were 0.53 micro g/g in house dust and 0.75 micro g/g in vehicle dust. Dimethyl DAP metabolite concentrations were higher than diethyl DAP metabolite concentrations in both child and adult urine (p < 0.0001). Geometric mean dimethyl DAP concentrations were 0.13 micro mol/L in adult urine and 0.09 micro mol/L in child urine. Creatinine-adjusted geometric mean dimethyl DAP concentrations were 0.09 micro mol/g in adult urine and 0.14 micro mol/g in child urine. Azinphosmethyl concentrations in house dust and vehicle dust from the same household were significantly associated (r2 = 0.41, p < 0.0001). Dimethyl DAP levels in child and adult urine from the same household were also significantly associated (r2 = 0.18, p < 0.0001), and this association remained when the values were creatinine adjusted. The results of this work support the hypothesis that the take-home exposure pathway contributes to residential pesticide contamination in agricultural homes where young children are present.

Adult↗

Differences in tumor-associated protein levels among middle-age Flemish women in association with area of residence and exposure to pollutants.

We measured tumor-associated proteins (TAPs) and pollutants in blood, serum, and urine of 200 nonsmoking women 50-65 years of age, residing in the rural municipality of Peer or in Hoboken or Wilrijk, industrial suburbs of Antwerp, Belgium. Persons with occupational exposures or commuting to other towns were excluded. Residents from Hoboken had significantly higher levels of blood lead and serum zinc and polychlorinated biphenyls. Surprisingly, residents of Peer had significantly higher levels of serum cadmium, dioxin-like activity in blood fat, and urinary 1-hydroxypyrene. For 5 of the 12 TAPs assessed in this study, we observed significant differences in serum levels among residents of the three municipalities after adjusting for personal or lifestyle parameters. Although we found levels of internal exposure to pollutants to be quite homogeneous in Flanders, we found significantly higher levels of TAPs only in the industrial suburbs. In multiple regression with all 29 available personal, lifestyle, and internal exposure parameters, blood lead levels showed a positive association with serum levels of anti-p53, carcino-embryonic antigen (CEA), and tissue polypeptide-specific antigen (TPS) and with an index for mean TAP level (I(tap)); dioxin-like activity in serum and serum copper showed a positive association with serum CA 125 (cancer antigen 125); and serum zinc showed a positive association with serum levels of c-erbB-2 ectodomain and TPS. An index of internal exposure showed a positive association with serum levels of both CEA and anti-p53 and with I(tap). This study provides some evidence that levels of internal exposure such as those present in Flanders, in particular concerning lead, are indeed associated with biologic effects.

Aged↗

Exposure of the general population to gasoline.

This paper summarizes the currently available information on gasoline exposure to the general population. In general, the largest contribution to the time weighted exposures results from exposures while indoors, which are influenced by the outside air, indoor sources, and attached garages. Personal activities, including refueling and commuting, contribute significantly higher exposures but last for only a small portion of the 24-hr time weighted average. The highest exposed group includes those individuals living near large service stations and those with contaminated water supplies.

Air Pollutants↗

The effect of ambient carbon monoxide on low birth weight among children born in southern California between 1989 and 1993.

We evaluated the effect of carbon monoxide (CO) exposures during the last trimester of pregnancy on the frequency of low birth weight among neonates born 1989-1993 to women living in the Los Angeles, California, area. Using birth certificate data for that period, we assembled a retrospective cohort of infants whose mothers resided within 2 miles of 1 of 18 CO monitoring stations. Based on the gestational age and birth date of each child, we estimated last-trimester exposure by averaging the corresponding 3 months of daily CO concentrations registered at the monitoring station closest to the mother's residence (determined from the birth certificate). Where data were available (at 6 stations), we also averaged measurements taken daily for nitrogen dioxide and ozone and those taken at 6-day intervals for particulate matter [less than/equal to]10 microm (PM10) to approximate last-trimester exposures to other pollutants. Overall, the study cohort consisted of 125,573 singleton children, excluding infants born before 37 or after 44 weeks of gestation, those weighing below 1,000 or above 5,500 g at birth, those for whom fewer than 10 days of CO measurements were available during the last trimester, and those whose mothers suffered from hypertension, diabetes, or uterine bleeding during pregnancy. Within the cohort, 2,813 (2.2%) were low in birth weight (between 1,000 and 2,499 g). Exposure to higher levels of ambient CO (>5.5 ppm 3-month average) during the last trimester was associated with a significantly increased risk for low birth weight [odds ratio (OR) = 1.22; 95% confidence interval (CI), 1.03-1.44] after adjustment for potential confounders, including commuting habits in the monitoring area, sex of the child, level of prenatal care, and age, ethnicity, and education of the mother.

Adolescent↗

Paediatric inter-facility transport: the parents' perspective.

A telephone survey was conducted to evaluate the impact on families of inter-facility paediatric transport to a tertiary care centre. The 54 families who responded were almost unanimous in their appreciation of the transport service and the expertise of the attendants. However, many experienced problems, including finances, child care, travel arrangements and accommodation. Most problems were encountered by those who did not accompany the child in the transport vehicle, lived at a distance so that they could not commute and did not use hospital accommodation. Further research is suggested to assess the extent of the problems families face and to determine appropriate solutions.

Adolescent↗

Retrospective detection of potential medication errors involving drugs with similar names.

OBJECTIVE: To estimate frequencies of potential errors involving similarly named drugs using a retrospective claims database and measure the association between frequencies of potential errors and two measures of drug name similarity, edit distance (minimum number of insertions, substitutions, or deletions of characters required to change a given word into another target word) and normalized edit distance (proportion of letters that must be changed to commute one word to another, and ranges from 0 to 1, with 0 indicating identical words, and 1 indicating a pair of words with no common letters). DESIGN: Retrospective database analysis. SETTING: Idaho Medicaid claims data from 1993 to 2000. PATIENTS: Not applicable. INTERVENTION: Potential errors were detected using adjacent claims generated by dispensing of one drug followed by dispensing of the other drug with a similar name. In all, four potential error criteria were developed: two for detecting potential refill errors and two for detecting potential initial errors. A total of 10 drug pairs were randomly selected from the Idaho Medicaid claims database for each value of edit distance, which ranged from 1 to 30 (n = 300). MAIN OUTCOME MEASURES: Frequencies of potential medication errors in claims sequences for initial and refill claims, edit distance, and normalized edit distance. RESULTS: Of 300 drug pairs studied, 106 (35.33%) were involved in at least one potential error. A total of 1,138 dispensing episodes satisfied the criteria for potential errors. Frequencies of potential errors per drug pair were negatively associated with edit distance (r = -0.133, P < .05) and normalized edit distance (r = -0.226, P < .01). Frequencies of potential initial errors also were negatively associated with edit distance (r = -0.126, P < .05) and normalized edit distance (r = -0.222, P < .01). Potential refill errors also had negative association with edit distance (r = -0.134, P < .05) and normalized edit distance (r = -0.226, P < .01). CONCLUSION: Error criteria were successfully applied to a retrospective claims database to detect potential initial and refill errors that involved similarly named drugs.

Databases, Factual↗

Pharmacist and physician collaboration in the patient's home.

OBJECTIVE: To review the historical perspective and current incidence of home visits by physicians and pharmacists, discuss the concept of pharmacists providing care "incident-to" the physician, and introduce a new endeavor of collaborative, incident-to home visits by a pharmacist and physician. DATA SOURCES: A literature search was performed using MEDLINE (1966-May 2003). The search terms used were home visit, house call, incident-to, collaborative care, physician, and pharmacist. STUDY SELECTION AND DATA EXTRACTION: All pertinent articles were evaluated. DATA SYNTHESIS: Home visits were once considered a hallmark of patient care, but have decreased to an average of 0.4 home visits per week for primary care physicians. Home visits are essential for patients unable to commute to the office due to a disability or illness. However, home visits also allow the physician to determine how conditions affect a patient's everyday life, in addition to assessing the living environment. Minimal documented evidence exists of pharmacists making home visits and no documented evidence exists of pharmacists and physicians collaboratively making home visits. The pharmacist complements the value of the visit by assessing medication appropriateness as well as medication administration, storage, accessibility, and adherence. CONCLUSIONS: Current practice styles often compromise services that were once paramount to patient care, as evidenced by a decline in home visits. Recent trends in health care attempt to compensate for high-volume practices and managed care restrictions. A collaborative relationship between a pharmacist and physician with visits into the patient's home is a movement toward improved continuity of care.

House Calls↗

The influence of poster prompts on stair use: The effects of setting, poster size and content.

OBJECTIVES: There is evidence that poster prompts increase stair use. The present study was concerned with the effects of poster size, poster message, and setting on stair use. DESIGN: Using a quasi-experimental design, four observational studies were undertaken in which stair and escalator use were logged during 2-week baseline periods and 2-week intervention periods. METHODS: In the first two studies, observations were undertaken in two shopping centres (total N = 30,018) with the size of poster varying. In the other two studies (total N = 37,907), one in a shopping centre and one in a train station, two poster messages were tested in both sites. RESULTS: Pedestrian traffic volume was controlled for statistically. There were significant increases in stair use with A1- and A2-, but not A3-size posters. Overall, the two different poster messages were both effective in encouraging stair use. Interactions between gender and message setting, however, reflected the fact that the 'stay healthy, save time' poster had little impact on female shoppers but was highly effective for female commuters. CONCLUSION: These results suggest that developers of health-promotion posters pay attention to poster size. They also indicate that it is insufficient to segment audiences by gender without considering the setting and motivational context.

Journal Article↗

Influence of the order of diattenuator, retarder, and polarizer in polar decomposition of Mueller matrices.

Polar decomposition consists of representing an arbitrary Mueller matrix with a product of three simpler matrices, but, since these matrices do not commute, the result depends on the order in which they are multiplied. We show that the six possible decompositions can be classified into two families and that one of these families always leads to physical elementary matrices, whereas the other does not.

Journal Article↗

Characterization of a new certified reference material for human cardiac troponin I.

BACKGROUND: To address the continuing need for the standardization of clinical human cardiac troponin I (cTnI) assays, NIST, with the assistance of the AACC/IFCC Cardiac Troponin I Standardization Committee, has developed a new certified reference material, Standard Reference Material (SRM) 2921: Human Cardiac Troponin Complex. METHODS: The concentration of cTnI in SRM 2921 was determined through a combination of reversed-phase liquid chromatography (LC) with ultraviolet detection and amino acid analysis. Characterization of the intact troponin subunits was accomplished through reversed-phase LC coupled with mass spectrometry. Posttranslational modifications to the cTnI in SRM 2921 were investigated by combining proteolytic digestion with matrix-assisted laser desorption/ionization mass spectrometry. Additionally, reference concentration values for cTnT and cTnC were also determined. RESULTS: The concentration of human cTnI in SRM 2921 is 31.2 (1.4) mg/L (where 1.4 mg/L is the uncertainty at a 95% level of confidence), as certified through a method that provides traceability to the International System of Units (SI). Reference concentration values of the cTnT and cTnC subunits were determined to be 36.9 (3.8) mg/L and 24.2 (1.3) mg/L, respectively. CONCLUSIONS: This first cTnI reference material should provide SI traceability to clinical cTnI assays once commutability has been validated, and could assist in the international harmonization of cTnI assays as a tool for understanding the underlying causes of interassay variability.

Chromatography, Liquid↗

Plasma pancreatic lipase activity: from analytical specificity to clinical efficiency for the diagnosis of acute pancreatitis.

Using five procedures (turbidimetry with the Boehringer Mannheim kit and with a home made reagent, reflectometry with the Eastman Kodak kit, colorimetry with the Sigma kit, and UV spectrophotometry with the Wako kit), lipase activity was assayed in the same group of 60 healthy adults and in 30 patients suffering from acute pancreatitis (n = 197 samples) as well as in a purified and stabilized preparation of human pancreatic lipase. Results indicated considerable inter-assay discrepancies for the mean values of the patients' results: catalytic activity concentrations differed by a factor of up to 16 according to the measurement procedures. For each method, mean patients' results were also expressed as multiples of the upper limit of normal values. This method of presentation did not significantly improve the intra-assay agreement, with maximal relative differences as high as 13-fold. When each method was calibrated with the same material (human pancreatic lipase), the inter-assay agreement was considerably improved. The causes of inter-assay disagreement are discussed in detail, and the necessity for a validated lipase calibrator is stressed, in order to improve the efficiency of the information transmitted by clinical laboratories to clinicians. A strategy is proposed, which includes development of a reference method and reference material, and a study of inter-assay commutability of secondary calibrators for a set of methods.

Acute Disease↗

Characterisation and evaluation of external quality assessment scheme serum. Discussion paper from the European External Quality Assessment (EQA) Organisers Working Group C.

This work reviews the procurement, specification and manufacture of serum for external quality assessment (EQA) and provides a checklist for scheme organisers. Guidance on the assessment of commutability and notes on the use of EQA materials to assess assay problems are provided. The importance of the appropriateness of materials in respect of scheme design and objectives, and the essential nature of a detailed specification prior to manufacture are emphasised.

Blood↗

International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Standardization Project for the Measurement of Lipoprotein(a). Phase 2: selection and properties of a proposed secondary reference material for lipoprotein(a).

The International Federation of Clinical Chemistry and Laboratory Medicine Working Group for the Standardization of Lipoprotein(a) Assays has initiated a project to select a secondary reference material for lipoprotein(a) that can standardize the measurement of this lipoprotein. Most of the analytical problems with lipoprotein(a) assays are due to apolipoprotein(a) kringle 4 type 2 reactive antibodies and values being expressed in mg/l mass units rather than as nmol/l of apolipoprotein(a) particles. In Phase 2, four manufactured materials were compared for analytical performance, commutability properties and method harmonization in 27 lipoprotein(a) test systems. Results of precision and linearity testing were comparable for all materials whereas testing for the harmonization effect resulted in an among-assay coefficient of variation for corrected lipoprotein(a) values of between 11% and 22%. The material that gave maximum harmonization achieved a variation of < 8% for 18 immunonephelometric and immunoturbidimetric assay systems. It can be hypothesized that this residual variation in part takes into account the inaccuracy of lipoprotein(a) measurement due to apolipoprotein(a) size polymorphism. On the basis of acceptable analytical performance, maximal harmonization effect and documented stability, a lyophilized material has been selected as the common calibrator for lipoprotein(a) to be used in a value transfer procedure by diagnostic companies.

Evaluation Studies as Topic↗

IFCC primary reference procedures for the measurement of catalytic activity concentrations of enzymes at 37 degrees C. International Federation of Clinical Chemistry and Laboratory Medicine. Part 7. Certification of four reference materials for the determination of enzymatic activity of gamma-glutamyltransferase, lactate dehydrogenase, alanine aminotransferase and creatine kinase accord.

This paper is the seventh in a series dealing with reference procedures for the measurement of catalytic activity concentrations of enzymes at 37 degrees C and the certification of reference preparations. Other parts deal with: Part 1. The Concept of Reference Procedures for the Measurement of Catalytic Activity Concentrations of Enzymes; Part 2. Reference Procedure for the Measurement of Catalytic Concentration of Creatine Kinase; Part 3. Reference Procedure for the Measurement of Catalytic Concentration of Lactate Dehydrogenase; Part 4. Reference Procedure for the Measurement of Catalytic Concentration of Alanine Aminotransferase; Part 5. Reference Procedure for the Measurement of Catalytic Concentration of Aspartate Aminotransferase; Part 6. Reference Procedure for the Measurement of Catalytic Concentration of Gamma-Glutamyltransferase. A document describing the determination of preliminary reference values is also in preparation. The certification of the catalytic activity concentrations as determined by the recently elaborated IFCC primary reference methods at 37 degrees C of four enzyme preparations, namely IRMM/IFCC 452 (gamma-glutamyltransferase), IRMM/IFCC 453 (lactate dehydrogenase 1), IRMM/IFCC 454 (alanine aminotransferase) and IRMM/IFCC 455 (creatine kinase) is described. Homogeneity data were derived from previous results. Stability was assessed using recently obtained data as well as data from previous stability studies. The collaborative study for value assignment was performed under a strict quality control scheme to ensure traceability to the primary reference method. Uncertainty of the materials was assessed in compliance with the Guide to the Expression of Uncertainty in Measurement. The certified values obtained at 37 degrees C are 1.90 microkat/l +/- 0.04 microkat/l (114.1 U/l +/- 2.4 U/l), for gamma-glutamyltransferase, 8.37 microkat/l +/- 0.12 microkat/l (502 U/l +/- 7 U/l), for lactate dehydrogenase 1, 3.09 microkat/l +/- 0.07 microkat/l (186 U/l +/- 4 U/l), for alanine aminotransferase and 1.68 microkat/l +/- 0.07 microkat/l (101 U/l +/- 4 U/l), for creatine kinase. The materials are intended for internal quality control as well as for the evaluation of test systems as required by recent European Union legislation. Furthermore, the materials can be used to transfer accuracy from a reference method to a routine procedure provided the procedures exhibit the same analytical specificity and the certified materials are commutable.

Alanine Transaminase↗