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A generalized concordance correlation coefficient for continuous and categorical data.

This paper discusses a generalized version of the concordance correlation coefficient for agreement data. The concordance correlation coefficient evaluates the accuracy and precision between two measures, and is based on the expected value of the squared function of distance. We have generalized this coefficient by applying alternative functions of distance to produce more robust versions of the concordance correlation coefficient. In this paper we extend the application of this class of estimators to categorical data as well, and demonstrate similarities to the kappa and weighted kappa statistics. We also introduce a stratified concordance correlation coefficient which adjusts for explanatory factors, and an extended concordance correlation coefficient which measures agreement among more than two responses. With these extensions, the generalized concordance correlation coefficient provides a unifying approach to assessing agreement among two or more measures that are either continuous or categorical in scale.

Computer Simulation↗

Growth factor and cytogenetic abnormalities in cultured nevi and malignant melanomas.

It has been proposed that benign nevi that fail to differentiate normally may undergo stepwise growth and morphologic changes resulting in progression toward dysplastic nevi, which in some cases progress into malignant melanoma. In this study, we sought to determine the relationship between production of endogenous growth factors and the appearance of chromosomal abnormalities in cultured nevi and melanomas. Newly established cultures from 8 nevi with benign histology and 6 malignant melanomas, and 2 malignant melanoma cell lines were studied. Assays for mitogenic growth factors were based on stimulation of [3H]thymidine incorporation into DNA in Hs0294 malignant melanoma cells, produced by serum-free conditioned medium from nevus or melanoma cultures. Karyotypes were examined in cultures of an equivalent passage. Three of the 8 nevus cultures were mitogen-negative and displayed normal karyotypes; one nevus culture was mitogen-positive and had a normal karyotype, although the biopsied tissue demonstrated histologic evidence of benign melanocytic proliferation; one was mitogen-negative initially, but had an extra chromosome 8 in 2 of 50 cells; 3 were mitogen-positive and chromosomally abnormal. Each of the cultures in this latter group exhibited reciprocal translocation (rcpt) as the only identifiable abnormality [rcpt(6;15), rcpt(10;15), rcpt(15;20)], or a constitutional rcpt(4;5). Thus, there was direct correlation between growth factor production and chromosome abnormality in 6 of 8 benign nevus cultures. In the newly established melanoma cultures there was also concordance between growth factor and chromosomal status; conditioned media from 4 of 6 were mitogen-positive by at least one assay, and all 4 of the mitogen-positive cultures had chromosomally abnormal cell populations. Of the 2 melanoma cultures negative for growth factors, one was also negative for chromosome abnormality; the other had chromosomal change consisting of increased polyploidy. Both melanoma cell lines had abnormal karyotypes and were mitogen-positive. Though numerous chromosome changes were noted in the karyotypically abnormal melanoma cells, 6 of the 8 cultures exhibited abnormalities in chromosomes 1, 6, and/or 7. These data suggest that steps in the progression from benign nevi toward dysplastic nevi or malignant melanoma include: proliferation resulting from altered production of endogenous mitogenic growth factors; and development of specific chromosomal abnormalities.

Cells, Cultured↗

Factors influencing the stability of psychiatric diagnoses in the emergency setting: review of 934 consecutively inpatient admissions.

OBJECTIVE: This study aimed to examine the stability of psychiatric emergency diagnoses and factors influencing diagnostic concordance. METHODS: The concordance between psychiatric emergency and inpatient diagnoses was calculated using kappa coefficient. The groups with and without psychiatric diagnostic stability were compared to determine factors influencing diagnostic stability. RESULTS: Agreement between psychiatric emergency and inpatient diagnoses was fair (range of kappa=.48-.56) for bipolar, schizophrenia, schizoaffective and depressive disorders. Results indicated that patients with stable diagnoses between psychiatric emergency and inpatient settings are likely to arrive on legal holds and that patients without concurring diagnoses are likely to have a higher medical burden. CONCLUSION: Further studies exploring ways to improve diagnostic stability in psychiatric emergency setting are warranted.

Academic Medical Centers↗

[Coronary risk factors. The French paradox].

Concordant data suggest that the frequency of ischaemic heart diseases in France is relatively moderate and noticeably lower than in most industrial European or English-speaking countries. This fact is documented by mortality statistics and planned surveys (Parisian Prospective Study, Records, ENIM). This peculiarity does not seem to be ascribable to the level of the classical coronary risk factors in France. Thus, the incidence of ischaemic heart diseases observed in the Parisian Prospective Study is much lower than that of similar American studies, even after adjustment to risk factor levels. The dietary lipid intake of the French seems to be about the same as that of nationals of high coronary mortality countries. The French paradox lies in the contrast between a food rich in saturated fatty acids and a moderate coronary mortality rate, fairly similar to that observed in Mediterranean countries where the dietary fat intake is much smaller than in France. The high mean level of alcohol consumption in France might be one of the factors responsible for this French peculiarity.

Alcohol Drinking↗

Parent-youth concordance regarding violence exposure: relationship to youth psychosocial functioning.

PURPOSE: To examine the relationship between parent-youth concordance with regard to youth exposures to violence and youth psychosocial functioning, including perpetration of violence, distress symptomatology, and social skillfulness. METHODS: A battery of self-report questionnaires were completed by 333 parent-youth dyads residing in urban public housing developments. Concordance status (<50%, 50-80%, and >80%) was based on dyad agreement regarding youth's violence exposures. The relationship between concordance and psychosocial factors was assessed by a series of analyses of covariance tests. RESULTS: Parents underestimated the extent to which their children were victims of or witnesses to violence and suffered from distress symptoms. Low concordance status was associated with youth perpetration of violence and distress symptomatology, as well as lower self-esteem and problem-solving skillfulness. Youth in the low concordance group characterized their families as exhibiting less involvement, open communication, and parental monitoring. CONCLUSIONS: Concordance between parents and youth is associated with youth psychosocial competence and strong family functioning. Findings underscore the need to incorporate a parent component in primary and secondary violence-prevention programs. Further examination of the processes which contribute to concordance may enhance our ability to prevent youth engagement in violence and its untoward psychosocial sequelae.

Adolescent↗

Comparison between CoaguChek S- and Owren-type prothrombin time assay for monitoring anticoagulant therapy.

INTRODUCTION: Anticoagulation therapy with warfarin is monitored by the prothrombin time (PT) assay. The PT is standardized using international normalized ratios (INRs). By keeping the INR within specific values, it is possible to reduce potential complications from the treatment. To facilitate the PT monitoring, point-of-care devices suitable for capillary whole blood measurements have been developed. The aims of this study were to compare the INR values obtained by such a device, CoaguChek S, with those obtained from the Owren-type PT assay and to evaluate the differences seen. MATERIALS AND METHODS: In 351 consecutive warfarin-treated patients, INR was measured in capillary whole blood samples with CoaguChek S and was compared to venous plasma samples analyzed with the Owren PT method. Sixty-nine of these patients, including those deviating the most between the methods, were further evaluated according to levels of factor II (prothrombin), factor V, factor VII, factor X, fibrinogen, activated partial thromboplastin time (aPTT) and antiphospholipid antibodies. RESULTS: The results from CoaguChek S produced a correlation coefficient of 0.81 to the Owren-type PT assay and a concordance of 85.2%. Factor V and fibrinogen correlated significantly (p<0.05) to the degree of deviation between the methods. The presence of antiphospholipid antibodies did not influence the degree of deviation between the two methods. CONCLUSIONS: INR analysis of whole blood with CoaguChek S is comparable with INR measured in plasma with Owren chemistry. The activities of factor V and fibrinogen contribute to the deviation seen between the methods. Differences in sensitivity to antiphospholipid antibodies could not be demonstrated.

Anticoagulants↗

Spouse selection and environmental effects on spouse correlation in lung function measures.

PURPOSE: Concordance between spouses may be due to partner selection factors and/or the effects of marriage/environment. The extent to which partner selection factors contribute to spouse concordance has important implications for heritability studies. The aim of this study was to examine the magnitude of spouse correlation in lung function measures and its relationship to duration of marriage. METHODS: Cross-sectional and longitudinal data collected over the period 1969 to 1995 for 2615 couples from the Busselton Health Study have been analyzed using the program FISHER. RESULTS: Unadjusted correlations were around 0.45 for forced expiratory volume in 1 second (FEV1) and 0.25 for FEV1/FVC (forced vital capacity) and were reduced to 0.05 and 0.10, respectively, after adjustment for age, height, and smoking. No trend with marriage duration was apparent in both cross-sectional and longitudinal analyses but there was a significant downward trend in the correlations with age at marriage. CONCLUSIONS: The findings indicate that observed correlations in lung function measures are mostly due to partner selection factors and that partner selection factors have greater influence for couples that marry at younger ages. Family studies that aim to identify and separate genetic from other influences on lung function measures should not regard the mother-father correlation as due to common environment effects.

Adult↗

Environmental and familial risk factors in relation to the colorectal adenoma--carcinoma sequence: results of a case-control study in Burgundy (France).

A case-control study in the Cote-d'Or area (Burgundy, France) investigated the relationship between environmental and familial risk factors and the different steps of the adenoma-carcinoma sequence. Two adenoma groups (< 10 mm and > or = 10 mm), a polyp-free control group, a colorectal cancer group and a general population control group were recruited. Tobacco was associated with the risk of adenomas, and alcohol with the risk of large adenomas. They proved to be independently related to large adenoma formation when compared with controls. There was no association with cancer risk. Refined cereals, delicatessen, offal and fats appear to be risk factors along the adenoma-carcinoma sequence. This data does not support an increased risk with high consumption of fresh meat, or a protective effect of dairy products and calcium. A high consumption of vegetables was a protective factor for cancer, mainly in men. Excess weight and body mass index influenced the earlier step of the adenoma carcinoma sequence and excess calorie intake was risk factor for cancer. The decision to study precancerous lesions as well as cancer appears fruitful. Results suggest that the three stages of large bowel carcinogenesis are partly related to diet in different ways. They are concordant with risk factors recorded for colorectal cancer, but suggest some local specificities.

Adenoma↗

Design of the Genetics of Early Onset Cardiovascular Disease (GENECARD) study.

BACKGROUND: Coronary artery disease (CAD) is the leading cause of death and a leading cause of disability in the developed world. Early onset (premature) coronary artery disease (EOCAD) is known to have a particularly strong genetic component. However, the actual genes leading to this increased risk of CAD remain obscure. METHODS: The primary goal of the Genetics of Early Onset Cardiovascular Disease (GENECARD) study is to perform a genetic linkage study in 920 families with at least 1 sibling pair having EOCAD. The study sites include a US network of 15 cardiology practices and 5 additional sites located in Europe and the United States. We propose to identify chromosomal regions associated with increased susceptibility to EOCAD in this large sample of affected sibling pairs and nuclear families, where EOCAD is defined on the basis of having acute coronary syndrome (unstable angina or myocardial infarction), a revascularization procedure, or a positive functional imaging study at or before the age of 50 years in men or 55 years in women. To identify which genomic regions and genes are associated with increased susceptibility to EOCAD, we will use a comprehensive strategy comprising genomic screening, fine mapping, candidate gene analysis, and family-based association studies. RESULTS: Herein we describe the clinical characteristics, family history, and risk factor profiles of the 1168 members from 438 nuclear families included in the first, exploratory analysis. Analysis of the study population revealed a strong concordance of known cardiac risk factors among affected sibling pairs. There was significant concordance (P <. 01) among siblings with EOCAD for presence of diabetes (78% concordance), dyslipoproteinemia (67%), obesity (63%), and hypertension (56%). This level of concordance of risk factors among siblings might be expected, given the significant genetic components demonstrated for these metabolic susceptibility traits. However, there was also substantial sibling pair concordance (P <.01) for smoking history (74%), regular alcohol consumption (81%), and sedentary lifestyle (63%), environmental traits without known inherited predisposition. CONCLUSIONS: Analyses such as these will have implications for stratifying populations for the statistical analysis of the genome scan and on the choice of covariates for the follow-up studies of the initial genome screen analysis.

Adult↗

[Determinant factors of anemia in children].

OBJECTIVE: To present a review about the main determining factors of anemia in children under 5 years old. SOURCE OF DATA: Information was used from articles published in indexed national and international scientific journals, technical books and publications from international organizations. SUMMARY OF THE FINDINGS: Anemia constitutes the world's nutritional problem of the greater magnitude, and children under 5 years old represent one of the highest risk population groups. As with any public health problem, the origin of anemia is multi-causal and thus in this article the attempt is to interpret its direct or indirect relation with possible determinant factors and the main concordant or discordant findings in epidemiological studies. Among these factors are the social and economic conditions, the conditions of child health care, the child's nutritional state, the presence of morbidity, food consumption and biological factors. The role of the diet is emphasized with respect to the consumption and bioavailability of iron, and age of the child as the main determinants. CONCLUSIONS: Bearing in mind the magnitude of the problem and the breadth of its risk factors reviewed in this study, the implementation of urgent prevention and treatment measures for iron-deficiency anemia becomes necessary. It is important to stress that a single strategy may have little success if other measures are not taken simultaneously; the role of nutritional education being relevant, together with other implemented actions. Children under 2 years old and children who live in rural and deprived areas should be priorities in programs to combat anemia.

English Abstract↗

A case-control study of twin pairs discordant for Parkinson's disease: a search for environmental risk factors.

A previous study of twins with Parkinson's disease (PD) revealed low concordance, suggesting that genetic factors play a minor role in the etiology of PD. To identify possible environmental determinants of PD while maximally controlling for hereditary factors, 31 monozygotic twin pairs discordant for PD were interviewed by telephone. Information about possible risk factors was obtained from systematic and uniform interviews with cases and controls. The only statistically significant result was less cigarette smoking by PD patients (p less than 0.05). Thirteen dizygotic discordant twin pairs were evaluated with the same techniques, but there were no statistically significant differences between affected and unaffected twins.

Female↗

Association of a tumor necrosis factor promoter polymorphism with susceptibility to alcoholic steatohepatitis.

Twin concordance studies suggest that genetic factors play a role in determining why only a minority of heavy drinkers develop hepatitis and cirrhosis. Tumor necrosis factor alpha (TNF-alpha) has emerged as the "final common pathway" in the pathogenesis of alcohol-related hepatic necro-inflammation. We have examined the frequency of the two recently described polymorphisms of the TNF-alpha promoter in 150 patients with biopsy-proven alcoholic liver disease and 145 healthy volunteers. There was a significant excess of the rare allele (TNFA-A; G(-238) --> A) at position -238 in patients with steatohepatitis compared with controls or patients without this lesion. This is consistent with previous suggestions that the TNFA-A allele, which falls within a putative Y regulation box of the TNF-alpha promoter, is associated with increased TNF-alpha expression. No differences were observed for the polymorphism at position -308.

Age Factors↗

[Screening for abdominal aortic aneurysm during transthoracic echocardiography. A prospective study in 1202 consecutive patients at high risk: incidence, correlation with risk factors, feasibility, diagnostic accuracy, and increase in echocardiography time].

BACKGROUND: The rupture of abdominal aortic aneurysm is a pathology with a high mortality risk. Conversely, the study of the abdominal aorta is not routinely included in the echocardiography protocol, although it can be performed quickly and easily for screening of the aneurysm. The aim of this study was to evaluate screening of abdominal aortic aneurysm at the end of each echocardiographic exam performed at our laboratory. METHODS: From March 2002 to October 2003, 1202 patients aged > 40 years were studied at our echo-lab. After the first 4 months of screening, only patients at high risk were screened, namely men > 65 or < 65 years and women > 65 years with at least one risk factor for ischemic heart disease. We evaluated feasibility, diagnostic accuracy, incidence in the study population, interobserver variability, the correlation with risk factors for ischemic heart disease and the increase in total echocardiography time. RESULTS: The mean aortic diameter was 19.08 +/- 5.98 mm and feasibility was very high (95.6%). We found 62 unknown aneurysms and 20 localized aortic dilatations (incidence of 5.6 and 1.7%, respectively); the incidence of both of them was 9.1 in men and 1.6 in women. Multivariate analysis revealed male gender, older age and other arterial district pathologies as independent risk factors. The interobserver concordance was excellent as well as diagnostic accuracy. The mean time increase in routine echocardiography was 33.8 +/- 18.6 s. CONCLUSIONS: The abdominal aortic study at the end of a routine echocardiography, in patients at risk of aortic pathology because of age or other risk factors, is a simple and accurate method for screening of abdominal aortic aneurysm. It showed a very low cost, also due to the short-time increase in routine echocardiography.

Adult↗

Discomfort: not pain but still unpleasant feelings from the gut.

Most of the factors initiating food or fluid intake have already been studied, but much less is known about those terminating ingestion. We have hypothesised that discomfort originating from the gastrointestinal system may be one of those factors. Gut distension cause pain if the intestinal volume changes but merely discomfort if only the tension of the gut wall increases. It seems that mild unpleasantness (i.e. discomfort) arising from the gut as a result of moderate (quasi-isometric) distension, among and in concordance with other factors, may significantly reduce intake and hence contribute to physiological satiety. The arising discomfort can be detected by measuring the amount and rate of the ingestion, by recording and analysing ingestive behavior by taste-aversivity and taste-reactivity tests, etc. Conclusions of all experiments point to the same direction: tension increase in the gut wall causes discomfort and results in decrease of intake, i.e. satiety.

Animals↗

The borderline syndrome. I. Testing three diagnostic systems.

Diagnostic systems require testing on several factors: reliability, comprehensiveness, concordance with established use, specificity, and validity. Three sets of diagnostic criteria for the borderline have been proposed recently: the Gunderson et al criteria, the DSM-III criteria for borderline personality (BP) disorder, and the DSM-III criteria for schizotypal personality (SP) disorder. This article reviews work to date testing these systems on these factors. New data are presented from the retrospective application of these criteria to the clinical records of 400 diagnostically heterogeneous former inpatients at Chestnut Lodge, Rockville, Md; 330 of them also received systematic follow-up by interview an average of 15 years after discharge. Results strongly supported the validity of the DSM-III division of borderline into BP and SP. Although the BP and Gunderson et al criteria demonstrated high concordance, the latter appeared to offer some slight advantages for defining BP disorder.

Adolescent↗

Concordance of familial characteristics in Crohn's disease and ulcerative colitis.

The diagnosis of inflammatory bowel disease (IBD) in a proband increases the probability of a parallel IBD diagnosis in a family member. In this study, we were able to confirm the IBD diagnosis in 35 (9.9 percent) of the relatives of 352 registry probands. To confirm a proband's report of a positive family history of IBD, efforts were made to directly contact all first-degree relatives regardless of their IBD status (parents, siblings, and children). Consent to contact family members was obtained from the proband, who furnished the registry personnel with names, addresses, and phone numbers. We then attempted to contact each identified relative by phone. After verbal consent was obtained, family members were asked if they had been diagnosed with IBD. This diagnosis was confirmed by contacting the relative's physician. A McNemar (chi 2 Mc) matched-pair analysis was used to analyze concordance between the proband and the affected family member. Within the CD/CD (Crohn's disease) concordant pairs, sex was a significant risk factor. Sex was not a significant risk factor within the UC/UC (ulcerative colitis) concordant pairs. In the concordant surgery pairs, no surgical procedure was a significant risk factor for the prediction of a similar surgical procedure for the affected relative. In concordant extraintestinal complications, only the appearance of a skin rash was significantly related to the appearance of a skin rash in the affected relative.

Colitis, Ulcerative↗

Concurrent detection of minimal residual disease (MRD) in childhood acute lymphoblastic leukaemia by flow cytometry and real-time PCR.

Minimal (i.e. submicroscopic) residual disease (MRD) predicts outcome in childhood acute lymphoblastic leukaemia (ALL). To be used clinically, MRD assays must be reliable and accurate. Two well-established techniques, flow cytometry (FC) and polymerase chain reaction (PCR), can detect leukaemic cells with a sensitivity of 0.01% (10(-4)). We analysed diagnostic samples of 45 ALL-patients (37 B-lineage ALL, eight T-lineage ALL) by four-colour FC and real-time PCR. Leukaemia-associated immunophenotypes, at a sensitivity of MRD detection by FC at the 0.01% level, were identified in 41 cases (91%); antigen-receptor gene rearrangements suitable for MRD detection with a sensitivity of 0.01% or better by PCR were identified in 38 cases (84%). The combined use of FC and PCR allowed MRD monitoring in all 45 patients. In 105 follow-up samples, MRD estimates by both methods were highly concordant, with a deviation factor of <5 by Bland-Altman analysis. Importantly, the concordance between FC and PCR was also observed in regenerating bone marrow samples containing high proportions of CD19(+) cells, and in samples studied 24 h after collection. We conclude that both MRD assays yield generally concordant results. Their combined use should enable MRD monitoring in virtually all patients and prevent false-negative results due to clonal evolution or phenotypic shifts.

Adolescent↗

The effectiveness and cost-effectiveness of computed tomography screening for coronary artery disease: systematic review.

OBJECTIVES: To assess the clinical and cost-effectiveness of computed tomography (CT) screening for asymptomatic coronary artery disease; also to establish whether coronary artery calcification (CAC) predicts coronary events and adds anything to risk factor scores, and whether measuring CAC changes treatment. DATA SOURCES: Main electronic databases were searched up to 2005, with a MEDLINE update in February 2006. METHODS: A systematic review of screening studies and economic evaluations was carried out. Studies were included in the review if screening for coronary heart disease was the principal theme of the study, and if data were provided that allowed comparison of CT screening with current practice, which was taken to be risk factor scoring. Mismatches between CAC scores and risk factor scoring were of particular interest. A review of the case for screening against the criteria used by the National Screening Committee (NSC) for assessing screening programmes was also undertaken. RESULTS: No randomised control trials (RCTs) were found that assessed the value of CT screening in reducing cardiac events. Seven studies were identified that assessed the association between CAC scores on CT and cardiac outcomes in asymptomatic people and included 30,599 people. Six used electron-beam CT. The relative risk of a cardiac event was 4.4 if CAC was present, compared to there being no CAC. As CAC score increased, so did the risk of cardiac events. The correlation between CAC and cardiac risk was consistent across studies. There was evidence that CAC scores varied among people with the same Framingham risk factor scores, and that within the same Framingham bands, people with higher CAC scores had significantly higher cardiac event rates. This applied mainly when the CAC scores exceeded 300. There was little difference in event rates among the groups with no CAC, and scores of 1-100 and 101-300. In one study, CAC score was a better predictor of cardiac events than the Framingham risk scores. No studies were found that showed whether the addition of CAC scores to standard risk factor assessment would improve outcomes. There were reports from two observational studies that lowering of low-density lipoprotein cholesterol to about 3 mmol/l; or below with statin treatment modestly reduced CAC scores, but this was not confirmed in two RCTs. In three studies examining whether knowledge of CAC scores would affect compliance with lifestyle measures, perception of risk was affected, but it did not improve smoking cessation rates, although it did increase anxiety. There were a few economic studies of CT screening for heart disease, which provided useful data on costs of scans, other investigations and treatment, but relied on a number of assumptions, and were unable to provide definitive answers. One modelling study estimated that adding CT screening to risk factor scoring, and only giving statins to those with CAC score over 100, would save money, based on a cost per CT screen of US$400 and statin costs of US$1000 per annum per patient. However, the arrival of generic statins has reduced the price dramatically, and these savings no longer apply. CONCLUSIONS: CT examination of the coronary arteries can detect calcification indicative of arterial disease in asymptomatic people, many of whom would be at low risk when assessed by traditional risk factors. The higher the CAC score, the higher the risk. Treatment with statins can reduce that risk. However, CT screening would miss many of the most dangerous patches of arterial disease, because they are not yet calcified, and so there would be false-negative results: normal CT followed by a heart attack. There would also be false-positive results in that many calcified arteries will have normal blood flow and will not be affected by clinically apparent thrombosis: abnormal CT not followed by a heart attack. For CT screening to be cost-effective, it has to add value over risk factor scoring, by producing sufficient additional information to change treatment and hence cardiac outcomes, at an affordable cost per quality-adjusted life-year. There was insufficient evidence to support this. Most of the NSC criteria were either not met or only partially met. It would be useful to have more data on the distributions of risk scores and CAC scores in asymptomatic people, and the level of concordance between risk factor and CAC scores, the risk of cardiac events per annum according to CAC score and risk factor scores, information on the acceptability of CT screening, after information about the radiation dose, and an RCT of adding CT screening to current risk factor-based practice.

Coronary Artery Disease↗