Abstract：
BACKGROUND:Identifying novel risk markers in cardiovascular patients remains a research priority. Longer follow-up generally is considered favorable in such studies, but associations of interest may become attenuated with increasing follow-up. This issue has not been adequately addressed in the context of patient cohorts. The current study analyzed the extent and mechanisms of attenuating associations in a cardiovascular patient cohort. METHODS:The associations of numerous biomarkers with all-cause mortality were estimated by multiple Cox regression in the Langzeiterfolge der KARdiOLogischen Anschlussheilbehandlung (KAROLA) prospective cohort study of 1204 patients who had participated in an inpatient rehabilitation program after an acute coronary syndrome (ACS) or coronary bypass operation. Hazard ratios were estimated based on the entire follow-up period (13 years), and after truncation at previous follow-up times (3, 4.5, 6, 8, 10 years). RESULTS:For the majority of markers, a clear and sometimes very pronounced attenuation of the hazard ratios could be observed with increasing follow-up duration. Differential attrition generally was not a sufficient explanation for this phenomenon, whereas further analyses suggested a role for reverse causality for some of the markers. Power analyses showed that the relationship of follow-up duration and statistical power can be counterintuitive in the presence of realistic amounts of attenuation. CONCLUSIONS:The attenuation of estimates of association in patient cohorts is a much more substantial and complex issue than currently appreciated. This has important implications for the design and interpretation of prognostic, as well as etiologic, studies which may be particularly relevant in the case of patient cohorts defined by an initial acute event.
journal_name
Clin Chemjournal_title
Clinical chemistryauthors
Breitling LP,Mons U,Hahmann H,Koenig W,Rothenbacher D,Brenner Hdoi
10.1373/clinchem.2016.263202subject
Has Abstractpub_date
2017-03-01 00:00:00pages
673-682issue
3eissn
0009-9147issn
1530-8561pii
clinchem.2016.263202journal_volume
63pub_type
杂志文章abstract：:Using Syva "EMIT" reagents and the Cobas Bio centrifugal analyzer, we have developed cost-effective assays for therapeutic drug monitoring of carbamazepine, phenobarbital, and phenytoin. With these optimized methods one can assay up to 2470 samples with a single 100-test EMIT kit with good precision and accuracy. Betw...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1989-08-01 00:00:00
abstract：:Two families with benign hyperphosphatasemia of intestinal origin were studied and compared with six other cases reported in the literature. No evidence of clinical abnormalities or explanations for the unusual enzyme concentrations were found. Agarose gel electrophoresis of alkaline phosphatase (ALP, EC 3.1.3.1) isoe...
journal_title：Clinical chemistry
pub_type： 杂志文章,评审
doi：
更新日期：1991-08-01 00:00:00
abstract：:We tested 231 urine samples by six immunoassay methods--EMIT d.a.u., EMIT II, Roche Abuscreen Online, Abbott TDx, Diagnostic Products Corp. (DPC) double-antibody radioimmunoassay (RIA), and Biosite Triage--and by negative chemical ionization gas chromatography/mass spectrometry to determine how the immunoassays perfor...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1994-03-01 00:00:00
abstract：:We describe a chromatographic procedure for sensitive (2.0 mumol/L), specific quantification of vanillylmandelic acid (VMA) in urine with iso-VMA as an internal standard. After rapid extraction from urine, the VMA is determined by isocratic reversed-phase ion-pair chromatography on a bonded C8 column and detection of ...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1986-04-01 00:00:00
abstract：:Several factors can limit the use of therapeutic drug monitoring (TDM) for cancer chemotherapeutic agents, including poorly defined concentration-effect relationships for many antineoplastic agents. This is further complicated by cancer being a highly heterogeneous group of diseases, each of which may have a unique co...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1998-02-01 00:00:00
abstract：BACKGROUND:The bleeding time (BT) test predicts a higher bleeding complication rate in populations at risk for inherited or acquired platelet dysfunction, but it is of limited assistance in evaluating individual patients. There are no reports of clinical outcomes after discontinuation of the BT test. METHODS:Interview...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：2001-01-01 00:00:00
abstract：:The advent of hybridoma technology has provided the immunotechnologist a finely tunable instrument that should permit a marked advance in the immunologic sciences. The ability to choose the precise antibody required and the virtually unlimited availability of easily purified antibodies have already resulted in the sim...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1981-09-01 00:00:00
abstract：:A continuous-monitoring method for measuring acid phosphatase activity with alpha-naphthyl phosphate as the substrate was critically evaluated and modified. Using partially purified prostatic acid phosphatase, we show that certain conditions for the assay must be satisfied to ensure linearity. These conditions include...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1976-12-01 00:00:00
abstract：:We compared the performance of an automated assay of creatine kinase MB isoenzyme (CK-MB) mass (Stratus) with that of a CK-MB enzymatic assay routinely used at our institutions. Both of these assays use the same CK-MB-specific monoclonal antibody to immunocapture CK-MB, thus providing a direct means of comparing a mas...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1989-10-01 00:00:00
abstract：BACKGROUND:Screening for heterozygous sequence changes in PCR products, also known as "mutation scanning", is an important tool for genetic research and clinical applications. Conventional methods require a separation step. METHODS:We evaluated the sensitivity and specificity of homogeneous scanning, using a saturatin...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：10.1373/clinchem.2003.029751
更新日期：2004-10-01 00:00:00
abstract：:We can detect the beta-globin gene sickle cell mutation by using an assay based on the ligase chain reaction. The simultaneous amplification of the human growth hormone gene in the same reaction serves as a control for the amount of template DNA or amplification efficiency. Ligation products, which are biotinylated at...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1997-01-01 00:00:00
abstract：:In iron deficiency, zinc protoporphyrin (ZPP) is produced instead of heme, and the ZPP concentration in erythrocytes is increased (normal < or = 40 mumol/mol heme). We investigated the relevance of ZPP for staging iron deficiency. ZPP was determined by hematofluorometry in samples from 103 patients. Nineteen patients ...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1994-05-01 00:00:00
abstract：:A liquid-chromatographic technique with a post-column enzymatic reaction and fluorescence detection was validated for analysis of individual bile acids in the serum of rats. Extraction recoveries averaged 91.1% (SD 6.9%) for all bile acids. The assay was sensitive (minimum detection of 16.8 pmol per 100-microL injecti...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1987-10-01 00:00:00
abstract：:I evaluated use of the fluorescence polarization technique to measure neocarzinostatin, a proteinaceous antitumor antibiotic, and its antibody, in serum. The antigen (neocarzinostatin), labeled with fluorescein isothiocyanate, was allowed to interact with its antibody in a cuvet, in the instrument, yielding an increas...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1978-12-01 00:00:00
abstract：:A modified fermentation procedure based on one described by Homer Smith in his textbook was used to eliminate glucose interference in the automated detrmination of inulin. The manifold of Fjeldbo and Stamey [J. Lab. Clin. Med. 72, 353 (1968)] was modified to enable us to insert the fermentation procedure without sacri...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1977-07-01 00:00:00
abstract：:We evaluated the EMIT (enzyme-multiplied immuno technique) and FPIA (fluorescence polarization immunoassay) urine screening systems for detection of benzodiazepine intake. Healthy male volunteers were given single oral therapeutic doses of alprazolam (2 mg), chlordiazepoxide (25 mg), flunitrazepam (1 mg), lorazepam (3...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1992-02-01 00:00:00
abstract：:Risk can lead to catastrophe. Risk-management systems are highly effective in preventing the catastrophes of fire, earthquakes, and work-site injuries. No such effective systems are present to prevent health and social problems. A practical, cost-effective system to manage risk in children is being developed by the no...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1992-08-01 00:00:00
abstract：:We developed a simple method for the analysis of bismuth (Bi) in biological tissue, using wet digestion for sample pretreatment. Bi was determined by electrothermal atomic absorption spectrometry with platinum as a matrix modifier to decrease the volatility of Bi. The furnace program included a gas stop for sensitivit...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1993-05-01 00:00:00
abstract：:The tricyclic antidepressants amitriptyline, nortriptyline, imipramine, and desipramine in serum of patients taking one of the drugs were quantified in two laboratories by high-performance liquid chromatography (HPLC) and enzyme-multiplied immunoassay (EMIT; Syva). Results for split samples were highly correlated, but...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1988-11-01 00:00:00
abstract：:Iron-depleted donors are at increased risk of developing anemia; if these donors could be identified by a screening test, iron supplementation or decreased donation frequency could be considered. Tests to determine serum ferritin, blood hemoglobin, and erythrocyte (Erc)-zinc protoporphyrin concentrations were examined...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1990-06-01 00:00:00
abstract：BACKGROUND:Vascular age is an emerging health indicator and predictor of end-organ damage to the heart, brain, and kidney. Although there have been many review publications concerning risk factors for vascular aging, most include cross-sectional epidemiological studies, limiting inferences about temporality. There is a...
journal_title：Clinical chemistry
pub_type： 杂志文章,评审
doi：10.1373/clinchem.2018.287623
更新日期：2019-01-01 00:00:00
abstract：:Urinary acidic and alcoholic catecholamine metabolites were isolated separately from 24-h urines by simple extraction procedures. After derivatization, extracts were analyzed by means of simultaneous gas chromatography on two different stationary phases. The quality of the assay was checked by running "normal" and enr...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1977-05-01 00:00:00
abstract：:3-Hydroxy-3-methylglutaric aciduria was detected in a newborn. The progress of the dietary therapy for the disorder was monitored by dual-column "high-performance" liquid chromatography with a computer-controlled photodiode array spectrophotometric detector. This procedure is a quick way to detect and monitor the prog...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1986-01-01 00:00:00
abstract：BACKGROUND:The multiple endocrine neoplasia 2 (MEN 2) syndromes [MEN 2A, MEN 2B, and familial medullary thyroid carcinoma (FMTC)] are caused by germline mutations of the RET protooncogene. Because 85% of MEN 2A patients and 30% of FMTC patients have mutations at codon 634, the recommended molecular analyses begin at ex...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：2001-11-01 00:00:00
abstract：:We evaluated a new multiple-channel chemistry analyzer, the Boehringer Mannheim "Diagnostic M." This instrument can perform 25 tests at the rate of 120 1.3-mL serum samples per hour. The instrument may be run in either a profile mode or single-test mode. In the single-test mode only the necessary reagent is pumped. th...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1982-01-01 00:00:00
abstract：:Zinc is determined in neutrophils and lymphocytes (isolated from whole blood on discontinuous gradients of Ficoll-Hypaque) and in microliter quantities of plasma and erythrocytes by flameless atomic absorption spectrophotometry with greater sensitivity than with conventional flame atomic absorption spectrophotometry. ...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1982-03-01 00:00:00
abstract：:We evaluated a new EMIT II monoclonal amphetamine/methamphetamine assay for screening human urine by comparing it with the EMIT d.a.u. monoclonal amphetamine/methamphetamine assay and a fluorescence polarization assay. The EMIT II assay has a cutoff of 1 mg/L d-methamphetamine. The EMIT II and EMIT d.a.u. assays were ...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1993-01-01 00:00:00
abstract：BACKGROUND:Quantification of integrated proviral HIV DNA by repetitive-sampling Alu-HIV PCR is a candidate virological tool to monitor the HIV reservoir in patients. However, the experimental procedures and data analysis of the assay are complex and hinder its widespread use. Here, we provide an improved and simplified...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：10.1373/clinchem.2013.219378
更新日期：2014-06-01 00:00:00
abstract：:Monoclonal antibodies were raised against neuron-specific enolase, gamma gamma-enolase, and used in an immunoradiometric assay (IRMA), with mono-disperse magnetizable particles as the solid phase. The assay's sensitivity was 0.4 microgram/L and the interassay coefficient of variation was less than 5% in the working ra...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1989-10-01 00:00:00
abstract：:To demonstrate oligoclonal IgG bands (I) in unconcentrated cerebrospinal fluid, we used isoelectric focusing in agarose followed by protein transfer to cellulose nitrate membrane, double-antibody peroxidase labeling, and avidin-biotin amplification. I can be reliably seen after isoelectric focusing of 5-microL specime...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1984-07-01 00:00:00
