SEARCH · PubMed Health

Results for “Surrogate variables analysis”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 379 records · Page 21Linked to original sources

PubMed2003

Gender differences in sleep apnea: the role of neck circumference.

STUDY OBJECTIVES: To determine whether differences in sleep apnea severity between men and women referred to a sleep clinic are related to the differences in neck circumference (NC). STUDY DESIGN: Case series. SETTING: University hospital sleep disorders clinic. PARTICIPANTS: A total of 3,942 patients (2,753 men and 1,189 women) referred to the sleep clinic. MEASUREMENTS AND RESULTS: All patients underwent nocturnal polysomnography. NC was used as a surrogate measure of upper airway obesity. We found that sleep apnea, defined an the apnea/hypopnea index (AHI) > 10/h, was significantly more frequent (60% vs 32%, chi(2) < 0.0001) and severe (mean +/- SE, 25 +/- 26/h vs 12 +/- 19/h, p < 0.0001) in men than in women. Men had significantly larger NC than women, but the difference became much less pronounced when we normalized NC to body height (0.24 +/- 0.02 vs 0.23 +/- 0.03, p < 0.0001). Men had significantly higher AHI than women even after controlling for age, body mass index (BMI), and neck/height ratio (NHR); analysis of covariance showed that mean AHI was 24.4 +/- 0.4 in men vs 14.8 +/- 0.7 in women (p < 0.0001). This difference persisted even when we matched men and women for NHR and BMI. Finally, multiple regression analysis revealed the following: (1) NHR was the most significant predictor of AHI, accounting for 19% of the variability; and (2) the slope of AHI vs NHR was significantly higher in men than in women. CONCLUSIONS: We conclude the following: (1) the frequency and severity of sleep apnea in the sleep clinic population is greater in men than women, and (2) factors other than NC, age, and BMI must contribute to these gender differences.

Anthropometry↗

PubMed2001

Concentration-controlled or effect-controlled trials: useful alternatives to conventional dose-controlled trials?

Historically, dose-finding trials have been confirmatory in nature despite the fact that these trials represent an important and essential 'learning' phase in the drug development process. About 10 years ago 2 alternatives to the randomised dose-controlled trial (RDCT) were proposed as being more informative trial types. Controlling systemic drug exposure in order to improve efficiency of a trial forms the basis for the suggestion of a randomised concentration-controlled trial (RCCT). For the common instance where pharmacodynamic variability is larger than pharmacokinetic variability, the randomised effect-controlled trial (RECT), where patients are randomised to the effect of interest was suggested as even more informative. A survey of the literature shows that the RCCT has been sparsely applied and RECT not at all. For RCCT, the practical complications of carrying out the study seldom makes it the study type of choice. For RECT, the limited number of suitable situations for its application and the fact that the same effect is used for randomisation and analysis may explain the lack of applications. As a somewhat more favourable trial type, we suggest the randomised biomarker-controlled trial (RBCT), where patients are randomised to a certain value or range of a biomarker whereas the analysis is performed on another, clinically more relevant, effect. Although the RBCT has some attractive features, for example contributing to validation of a biomarker as a surrogate for clinical outcome, it is unlikely to be extensively used. Instead, the main shift from confirming to learning in dose-finding trials is coming from the incorporation of well-known learning components into the RDCT (e.g. sparse concentration measurements combined with population pharmacokinetic-pharmacodynamic, biomarker measurements and analysis of effect measures throughout the entire trial period).

Dose-Response Relationship, Drug↗

PubMed2006

Optical vibrocardiography: a novel tool for the optical monitoring of cardiac activity.

We present an optical non-contact method for heart beat monitoring, based on the measurement of chest wall movements induced by the pumping action of the heart, which is eligible as a surrogate of electrocardiogram (ECG) in assessing both cardiac rate and heart rate variability (HRV). The method is based on the optical recording of the movements of the chest wall by means of laser Doppler interferometry. To this aim, the ECG signal and the velocity of vibration of the chest wall, named optical vibrocardiography (VCG), were simultaneously recorded on 10 subjects. The time series built from the sequences of consecutive R waves (on ECG) and vibrocardiographic (VV) intervals were compared in terms of heart rate (HR). To evaluate the ability of VCG signals as quantitative marker of the autonomic activity, HRV descriptors were also calculated on both ECG and VCG time series. HR and HRV indices obtained from the proposed method agreed with the rate derived from ECG recordings (mean percent difference <3.1%). Our comparison concludes that optical VCG provides a reliable assessment of HR and HRV analysis, with no statistical differences in term of gender are present. Optical VCG appears promising as non-contact method to monitor the cardiac activity under specific conditions, e.g., in magnetic resonance environment, or to reduce exposure risks to workers subjected to hazardous conditions. The technique may be used also to monitor subjects, e.g., severely burned, for which contact with the skin needs to be minimized.

Adult↗

PubMedDate not supplied

Advance directives: a policy-capturing approach.

Policy capturing was used to provide insight into those factors that people consider important in the decision of whether to accept life-sustaining medical treatment. First, open-ended interviews with community-dwelling elderly persons (n = 30) were conducted to determine the factors they would consider when drafting an advance directive. College students (n = 53) then made judgments as to whether they would accept life-sustaining treatment for each of 100 hypothetical vignettes comprising a similar set of factors. Results revealed that 1) students made consistent judgments, 2) there was considerable variability in their mean judgments, 3) the most influential factors were mental and physical functioning, 4) mental and physical functioning had an interactive effect on judgments, and 5) subjective estimates of importance were significantly related to policy-capturing weights. This approach for studying the relationship of individuals' values to their acceptance of life-sustaining therapy may be useful in future studies of patient and surrogate decision making.

Advance Directives↗

PubMed2002

Correlation between serotonin uptake in human blood platelets with the 44-bp polymorphism and the 17-bp variable number of tandem repeat of the serotonin transporter.

Dysfunctions of the central serotonin (5-hydroxytryptamine, 5-HT) system seem to be associated with psychiatric disorders such as schizophrenia or depression. Previous studies suggested that a 44-bp insertion/deletion polymorphism of the 5-HT transporter (5-HTT) promoter region might influence the transcriptional activity of the 5-HTT gene, and the insertion variant resulted in increased 5-HTT expression and 5-HT uptake. Moreover, a 17-bp variable number of tandem repeat (VNTR) polymorphism of the second intron may act as a transcriptional regulator with allele dependent differential enhancer-like properties. Since the 5-HTT of human platelets shares many properties with the transporter of neural tissue, platelets are widely used as a surrogate tissue source, possibly reflecting central 5-HT metabolism. Therefore, we investigated the impact of the 44-bp polymorphism and the 17-bp VNTR for 5-HT uptake in platelets of 50 male subjects. We found no significant effect of the 44-bp polymorphism and of the 17-bp VNTR on maximum rate (Vmax) of 5-HT uptake. However, individuals homozygous for the 5-HTT intron 2 allele with 12 repeats (STin2.12) of the 17-bp VNTR appeared to have lower affinity of 5-HT uptake than individuals heterozygous for the STin2.10/STin2.9 allele. This was also observed for the combined analysis of both polymorphisms. In conclusion, we found no association between the different genotypes of the 44-bp polymorphism and the 17-bp VNTR and maximum rate of 5-HT uptake into platelets.

Adult↗

PubMed2005

Age and FSH effects in fluorescence spectra from the cervix: an exploratory analysis.

INTRODUCTION: Real-time optical technologies that could diagnose cervical cancer could improve the detection of cervical cancer. Our group is studying the technology assessment of optical devices in the screening and diagnosis of cervical neoplasias. METHODS: We have conducted a diagnostic trial in 850 patients with referral Papanicolaou smears showing ASCUS or greater. Each colposcopically abnormal site and two normal sites were measured with fluorescence and reflectance spectroscopy and then biopsied. Each site generates a fluorescence excitation emission matrix that has a 3-dimensional map with peaks and valleys. RESULTS: The early exploration of these data is presented and shows an effect of age, Follicle Stimulating Hormone or FSH, and, curiously, of their interaction. We have examined other biographical variables like smoking, HPV positivity, grade of CIN, device used, probe used, race, ethnicity, gravidity, parity, previous treatments, and others. None are significant predictors of this finding of increased intensity, except age and FSH. CONCLUSIONS: The effect of age supports the work done on fresh tissue slices in trying to better understand the biology of fluorescence. The effect of FSH is not a surrogate for age, but an independently significant effect, for which we currently do not have an explanation. We are exploring if FSH is a surrogate for estrogenization by measuring estradiol levels and calculating the BMI.

Age Factors↗

PubMed2004

Health values of patients with chronic hepatitis C infection.

BACKGROUND: Patients with hepatitis C virus (HCV) infection report a reduction in health status, but it is not known how they value their state of health. We assessed health utilities directly from patients with HCV infection. METHODS: One hundred twenty-four patients with chronic HCV infection representing a cross section of disease severity were administered a disease-specific version of the Medical Outcomes Study 36-Item Short-Form Health Survey, the Beck Depression Inventory, and 3 direct health value measures, including the Rating Scale, Time Trade-off (TTO), and Standard Gamble (SG). Correlation among measures and factor analysis was performed. RESULTS: The mean modified Medical Outcomes Study 36-Item Short-Form Health Survey scores were lower than normative population values, particularly on the Physical Component Summary scale. This scale was poorly correlated with the Rating Scale, TTO, and SG scores among HCV-infected subjects. The mean +/- SE TTO score was 0.83 +/- 0.02, and the mean +/- SE SG score was 0.79 +/- 0.02. The TTO and SG scores failed to show significant variability in relation to disease activity as determined by serum alanine aminotransferase level, histologic stage, and presence of decompensated liver disease. The Beck Depression Inventory was significantly inversely correlated with the TTO and SG. CONCLUSIONS: Although quality of life is compromised in patients with chronic HCV infection, patient-derived health utilities are not strongly associated with health status or clinical measures. Utility measures obtained from patients with HCV differ significantly from previous surrogate measures of health values. Such differences in utilities could affect decision analyses and cost-effectiveness analyses of treatment interventions for individuals with HCV infection.

Adult↗

PubMed2003

The impact of clinical guidelines on surgical management in patients with thyroid cancer.

AIMS: Thyroid cancer is an uncommon but highly curable disease if treated optimally. The aim of this study was to determine whether clinical guidelines introduced locally at the beginning of 1999 were associated with better surgical outcome, using radioiodine uptake as a surrogate measure of completeness of thyroidectomy. MATERIALS AND METHODS: We reviewed the medical records of all patients with thyroid cancer referred to a cancer centre (n=176) 3 years before and 3 years after the introduction of guidelines. The uptake of radioiodine in the thyroid bed after thyroidectomy and before radioiodine ablation was used to assess the completeness of primary surgical treatment. RESULTS: The number of new cases referred to our centre increased from 80 in the 1996-1998 period to 94 during 1999-2001. This was largely because of an excess of papillary thyroid cancers. Documentation in the medical records of the pathological primary tumour size improved from 47.5% to 80.8% following the introduction of guidelines. A significant reduction in radioiodine uptake in the thyroid bed was observed following the introduction of guidelines (5.03% +/- 6.82 (SD) vs 2.75% +/- 5.10 (SD); P=0.005). Linear regression analysis of clinical variables indicated that the year of surgery was the only significant factor influencing radioiodine uptake in the thyroid bed (P=0.014). Twelve hospitals within the Northern Cancer Network carried out thyroid surgery for thyroid cancer in the pre-guideline era compared with seven hospitals in the post-guideline era. Surgeons who were members of the regional multidisciplinary thyroid cancer team operated on 35% of cases in the 1996-1998 period and 56.4% in the 1999-2001 period (P<0.01). CONCLUSIONS: The introduction of clinical guidelines in 1999 was associated with a reduction in the size of thyroid remnant after primary surgical treatment. This was accompanied by fewer hospitals undertaking thyroid surgery and more patients being operated on by surgeons who were members of the thyroid cancer multidisciplinary team.

Adenocarcinoma, Follicular↗

PubMed2003

Insulin gene VNTR genotype is associated with insulin sensitivity and secretion in infancy.

AIMS: We have previously demonstrated that insulin sensitivity and secretion at age 1 year was in part related to variation in weight and height gain during infancy. In order to determine whether genetic variation at the insulin gene could also influence these associations, we have studied the relationship between insulin gene variable number of tandem repeat (INS VNTR) genotypes, insulin secretion and early postnatal growth. METHODS: We assessed fasting and dynamic insulin secretion in 99 healthy infants at age 1 year, using a short intravenous glucose tolerance test (sIVGTT). Infants were genotyped at the -23 HphI locus, as a surrogate marker for INS VNTR allele classes I and III. Anthropometric data were recorded at birth and at 1 year. Data are shown as median (interquartile range). RESULTS: Fasting insulin levels were higher in III/III infants (n = 9) than in I/I infants [n = 55; 27.4 (17.6-75.6) pmol/l vs. 18.1 (10.3-25.2) pmol/l; P < 0.05]. Insulin secretion during the sIVGTT, as estimated by the serum insulin area under the curve, was also higher in III/III infants [2417 (891-4041) pmol min/l vs. 1208 (592-2284) pmol min/l; P < 0.05]. Fasting and postload plasma glucose levels were similar in both groups. Analysis of covariance showed that genotype differences in fasting insulin sensitivity and insulin secretion were independent of size at birth, postnatal growth velocity and current body mass index. CONCLUSIONS: Significant associations between INS VNTR genotype and both insulin sensitivity and secretion were apparent in infancy; these might interact with childhood appetite and nutrition to impact the development of childhood obesity and insulin resistance.

Analysis of Variance↗

PubMed1990

Assessing the gain in efficiency due to matching in a community intervention study.

COMMIT (Community Intervention Trial for Smoking Cessation) is a randomized study employing a matched pairs design. Pairs of communities were selected on the basis of their geographical proximity and were chosen to be matched on variables strongly expected to relate to the outcome variable, the smoking quit rate. However, quantitative information was not available to evaluate the efficiency gain from matching. We have used baseline smoking quit rates in the communities as a surrogate for the outcome measure to evaluate the gain in efficiency from the matching. Our method takes account of the possible imperfection of the surrogate as a representative of the true outcome. The method estimates an efficiency gain of at least 50 per cent using the matched design. We also evaluate the further gains in efficiency which would be made by using the baseline quit rate to balance the randomization.

Bias↗

PubMed2005

An assessment of dermal exposure to semi-synthetic metal working fluids by different methods to group workers for an epidemiological study on dermatitis.

BACKGROUND: Assessment of exposure assessment to metal working fluids (MWF) has almost exclusively focused on inhalation exposure. AIMS: To assess levels of, and factors affecting, dermal and inhalation exposure to semi-synthetic MWF, and to identify suitable dermal exposure grouping schemes among metal workers for an epidemiological survey on dermatitis of hands, forearms, and head. METHODS: A cross-sectional survey was conducted in four metal working machining departments of a truck manufacturing plant, estimating dermal and inhalation exposure levels to semi-synthetic metal working fluids (SMWF) in machine operators. Dermal exposure levels to SMWF were estimated by three different methods for dermal exposure assessment (VITAE, surrogate skin pad method, and a semi-quantitative dermal exposure assessment method (DREAM)). RESULTS: The identified factors affecting dermal exposure were similar for the three methods, although differences were found for estimated variability in dermal exposure levels between groups, within groups (among workers), and from day to day. With the VITAE method differences in exposure levels were detected between workers that were not detected with the surrogate skin pad method, and only partly with the DREAM method. CONCLUSIONS: Considering the additional effort and costs that use of the VITAE method entailed, the observational semi-quantitative DREAM method appeared to be more efficient for grouping of dermal exposure levels for the epidemiological study on dermatitis.

Cross-Sectional Studies↗

PubMed2001

Exercise capacity predicts health status in alpha(1)-antitrypsin deficiency.

Resting lung function is only weakly related to health status in chronic obstructive pulmonary disease, reflecting the multifactorial causes of impairment and the heterogeneous nature of the condition. The current study examined whether density mask analysis of high-resolution computed tomography (HRCT) or exercise capacity were better surrogates for health status in a well-defined, homogeneous group of patients with alpha(1)-antitrypsin deficiency (PiZ). Twenty-nine patients with predominantly lower zone emphysema on HRCT were studied. Exercise was assessed by incremental treadmill (V O(2) peak) and shuttle walking tests (ISWT) and health status by the St. George's Respiratory Questionnaire (SGRQ) and SF-36. Although lower zone expiratory HRCT was related to exercise capacity (rho = -0.64 and -0.63 for V O(2) peak and ISWT, respectively, p < 0.001), multiple regression analysis suggested that FEV(1) was a marginally better predictor (rho = -0.64 and -0.65, p < 0.001). HRCT also related significantly to health status (rho = -0.37 for SGRQ activity, p < 0.05), although again FEV(1) showed a stronger relationship (rho = -0.43, p = 0.01). However, exercise capacity was the best predictor of health status with the ISWT accounting for up to 55% of the variability seen in SGRQ total and up to 53% of the SF-36 domain scores (physical functioning). Although both HRCT and lung function relate to health status, exercise capacity is the best predictor of patients disability in these patients with predominantly lower zone emphysema.

Exercise Test↗

PubMed1999

Interpreting spirometric data: impact of substitution of arm span for standing height in adults from North India.

STUDY OBJECTIVE: To evaluate if direct substitution of arm span for height during interpretation of spirometry data leads to any significant statistical or clinical differences in Indian adults, and to compare this method with the use of height estimated indirectly from arm span. DESIGN: Cross-sectional. SETTING: Respiratory laboratory of a tertiary referral hospital in North India. PARTICIPANTS: Two hundred twenty-eight subjects referred for spirometry. MEASUREMENTS AND RESULTS: Standing height and arm span were measured for all subjects. Spirometry measurements included FVC, FEV1, FEV1/FVC, peak expiratory flow, and maximal midexpiratory flow. Predicted values for each parameter were calculated separately for height, arm span, and height estimated from fixed height:arm span ratio. Results were classified into normal, obstructive, and restrictive defects for each height, arm span, and estimated height measurement, and any abnormality was categorized as mild, moderate, or severe. Arm span exceeded height in 182 (79.82%) subjects. Thirty-seven (16.2%) and 32 (14.0%) results were classified or categorized incorrectly when arm span and estimated height were substituted respectively, for actual height, with a kappa estimate of agreement 0.779 and 0.808, respectively; 17.4% and 11.0% normal results were classified, respectively, as restrictive defects using arm span and estimated height. Limits of agreement, which were almost equally wide for both sets of data, were more than the permissible intraindividual variability for FVC and FEV1. CONCLUSIONS: The substitution of arm span for height introduces statistically significant changes in spirometry results. Use of height estimated from arm span using fixed ratio also leads to misclassification of data, though less than that caused by use of arm span alone. Height estimated from arm span can be substituted for actual height in patients in whom height cannot be measured reliably. Where racial/ethnic norms for height and arm span correlation are not available, arm span is a reasonable surrogate for standing height.

Adolescent↗

PubMed2002

Bedside quantification of atherosclerosis severity for cardiovascular risk stratification: a prospective cohort study.

OBJECTIVES: We sought to assess the ability of a new noninvasive method to quantify atherosclerosis severity and to examine its power to predict cardiovascular events. BACKGROUND: Drug prevention of cardiovascular events is effective but costly, leading to a debate about who should receive this treatment. Patient selection is often based on surrogate markers, but quantification of atherosclerosis severity is desirable. METHODS: Atherosclerosis severity was quantified by determination of specific aortic wall elastance in transthoracic echocardiography, applying the biomechanics of pulse wave propagation. After validating the method in 52 patients by measuring aortic plaque burden in transesophageal echo directly, another 336 patients were prospectively studied by monitoring atherosclerotic events at one year and comparing the results with conventional risk stratification. RESULTS: Specific aortic elastance was well correlated with plaque burden (p < 0.0001) and largely independent of confounding variables. Specific aortic elastance predicted the primary end point of "atherosclerotic death, myocardial infarction or stroke" at one year (p < 0.0002). Event rate at one year in the lowest specific elastance tertile was 1.8% (CI 0.0% to 4.3%), in the middle tertile 5.4% (CI 1.1% to 9.7%) and in the highest tertile 12.7% (CI 6.3% to 19%). Secondary end points supported these findings. Stepwise multivariate analysis identified specific aortic elastance, prior atherosclerotic events and left ventricular ejection fraction as independent risk predictors. Specific elastance was of incremental value to clinically identified variables. CONCLUSIONS: Bedside measurement of specific aortic elastance allows assessment of atherosclerosis severity. It predicts the risk for future atherosclerotic events beyond conventional risk factors, promising better targeting of pharmacologic prevention and improved cost effectiveness.

Adult↗

PubMed1995

Time-integrated blood lead concentration is a valid surrogate for estimating the cumulative lead dose assessed by tibial lead measurement.

The concentration of lead in tibia (Pb-T) was measured in vivo by a 109Cd K-shell X-ray fluorescence technique in 123 workers from a primary lead smelter (age: mean, 45 years; range, 30-61; duration of employment: mean, 20 years; range, 7-45). Their cumulative blood lead index (CBLI) was also calculated on the basis of the blood lead (Pb-B) records available from the company's medical files. Geometric mean for Pb-T was 49 micrograms Pb/g bone mineral (range, 15-167). The company's health surveillance programs, implemented since 1945, resulted in Pb-B values which rarely exceeded 70 micrograms Pb/dl whole blood. Pb-B at the time of Pb-T measurement averaged 31 micrograms Pb/dl (range, 6-62) and the geometric mean for CBLI amounted to 803 micrograms Pb/dl x year (range, 220-2130). Despite various assumptions and uncertainties inherent in the assessment of the cumulative lead dose through Pb-T measurement or CBLI calculation, the relation between both variables in the present lead smelter populations is very strong (rpearson = 0.80, P < 0.0001; age explained at the most 9.5% of the variance). The slope of the regression equation of log Pb-T vs log CBLI showed that a doubling of CBLI also corresponds to doubling of Pb-T. It may be concluded that a sound calculation of CBLI represents a valid surrogate for estimating the life time integrated dose of lead as assessed by the measurement of cortical bone lead (e.g., in tibia).

Adult↗

PubMed2006

Generalized linear models with ordinally-observed covariates.

An ordinally-observed variable is a variable that is only partially observed through an ordinal surrogate. Although statistical models for ordinally-observed response variables are well known, relatively little attention has been given to the problem of ordinally-observed regressors. In this paper I show that if surrogates to ordinally-observed covariates are used as regressors in a generalized linear model then the resulting measurement error in the covariates can compromise the consistency of point estimators and standard errors for the effects of fully-observed regressors. To properly account for this measurement error when making inferences concerning the fully-observed regressors, I propose a general modelling framework for generalized linear models with ordinally-observed covariates. I discuss issues of model specification, identification, and estimation, and illustrate these with examples.

Analysis of Variance↗

PubMed2006

Evaluation of ZAP-70 expression by flow cytometry in chronic lymphocytic leukemia: A multicentric international harmonization process.

The clinical course of patients with chronic lymphocytic leukemia (CLL) is heterogeneous with some patients requiring early therapy whereas others will not be treated for years. The evaluation of an individual CLL patient's prognosis remains a problematic issue. The presence or absence of somatic mutations in the IgVH genes is currently the gold-standard prognostic factor, but this technique is labor intensive and costly. Genomic studies uncovered that 70 kDa zeta-associated protein (ZAP-70) expression was associated with unmutated IgVH genes and ZAP-70 protein expression was proposed as a surrogate for somatic mutational status. Among the available techniques for ZAP-70 detection, flow cytometry is most preferable as it allows the simultaneous quantification of ZAP-70 protein expression levels in CLL cells and residual normal lymphocyte subsets. However, several factors introduce variability in the results reported from different laboratories; these factors include the anti-ZAP-70 antibody clone and conjugate, the staining procedure, the gating strategy, and the method of reporting the results. The need for standardization of the approach led to the organization of an international working group focused on harmonizing all aspects of the technique. During this workshop, a technical consensus was reached on the methods for cell permeabilization and immunophenotyping procedures. An assay was then designed that allowed comparison of two clones of anti-ZAP-70 antibody and the identification of the expression of this molecule in B, T, and NK cells identified in a four multicolor analysis. This procedure was applied to three stabilized blood samples, provided by the UK NEQAS group to all participating members of this study, in order to minimize variability caused by sample storage and shipment. Analysis was performed in 20 laboratories providing interpretable data from 14 centers. Various gating strategies were used and the ZAP-70 levels were expressed as percentage positive (POS) relative to isotype control or normal B-cells or normal T-cells; in addition the levels were reported as a ratio of expression in CLL cells relative to T-cells. The reported level of ZAP-70 expression varied greatly depending on the antibody and the method used to express the results. The CLL/T-cell ZAP-70 expression ratio showed a much lower interlaboratory variation than other reporting strategies and is recommended for multicenter studies. Stabilization results in decreased expression of CD19 making gating more difficult and therefore stabilized samples are not optimal for multicentric analysis of ZAP-70 expression. We assessed the variation of ZAP-70 expression levels in fresh cells according to storage time, which demonstrated that ZAP-70 is labile but sufficiently stable to allow comparison using fresh samples distributed between labs in Europe. These studies have demonstrated progress toward a consensus reporting procedure, and further work is underway to harmonize the preparation and analysis procedures.

Antibodies, Monoclonal↗

PubMed2002

Endemic hepatitis C virus infection in a Sicilian town: further evidence for iatrogenic transmission.

The prevalence of and risk factors for HCV and HBV infections in the general population and the predictive value of ALT screening in identifying anti-HCV positive subjects have been evaluated in a small Sicilian town. A random 1:4 sampling from the census of the general population was performed. Anti-HCV, HCV-RNA, HCV genotype, HBsAg, and anti-HBc were tested. The linkage between HCV infection and potential risk factors was evaluated by multiple logistic regression analysis. Among 721 subjects studied, 75 (10.4%) were anti-HCV positive. The HCV infection rate increased from 0.4% in subjects 10-29 years of age to 34% in those > 60 years of age. Among the 75 anti-HCV positive subjects, 66.7% were HCV-RNA positive and 36% had abnormal ALT, in contrast abnormal ALT levels were found in 4.3% of the 646 anti-HCV negative subjects (P < 0.01). HCV genotype 1b infected the majority (88.0%) of viremic subjects. Exposure to HBV infection (anti-HBc positivity) was found in 11.2% of subjects; HBsAg positivity was 0.7%. At multivariate analysis, two variables were associated with HCV infection: age > or = 45 years (OR 27.8; CI 95% = 11.0-70.2) and previous hospitalization (OR 2.5; CI 95% = 1.3-4.7). ALT testing had low positive predictive value (PPV = 49.1%) for HCV infection. The positive predictive value was good (88%) in people > or = 60 years of age, but minimal (16.7%) in those below 60. These findings indicate that HCV infection is common in the elderly, perhaps as a result of past iatrogenic transmission. The present low rate of HCV infection among the younger generations coupled with the low progression of the viral related liver damage does not support the projection of a future increasing incidence in the next decades of the burden of HCV-related chronic disease. HBV infection, formerly common in this area, is already in sharp decline. In an area of high HCV endemicity, screening of the general population by ALT cannot be used a surrogate marker to detect HCV infection in those susceptible to treatment.

Adolescent↗