Longitudinal study of associations between perceived health status and self reported diseases in the French Gazel cohort.

STUDY OBJECTIVE: Although perceived health status is an indicator widely used in epidemiological studies, its relation to various diseases is not well known. The objective of this study is to examine these relations in detail. DESIGN: Marginal models used for a longitudinal study of the association between three health scales and 47 diseases among 12 164 men and 44 diseases among 4415 women. SETTING: French Gazel cohort during the period from 1991 to 1996. MAIN RESULTS: The general health status scale was significantly associated with 43 diseases among men, and 31 among women. Some of these significantly associated diseases were physical (for example, cancer and cerebrovascular accident) and others, psychological (for example, depression). The mental fatigue scale was more specifically associated with psychological disorders, including sleep problems, depression, and nervous diseases. Moreover, modifications in subjects' assessment of their health from one year to the next were generally associated with modifications in reported diseases. CONCLUSION: Although the mechanism that relates the presence of a disease to perceived health status remains in question, these results show clearly that there is a close association between these two domains that justifies the use of perceived health as a proxy for self reported diseases.

Biological and pathological factors affecting plasma gamma-glutamyl transpeptidase and alkaline phosphatase activity in the elderly.

A high percentage of abnormally elevated plasma alkaline phosphatase (AP) and gamma-glutamyltranspeptidase (GGT) was found in a homogeneous population of 741 elderly subjects. The respective role of pathological and biological factors (age, sex, weight) upon the two plasma enzymatic activities has been analyzed. In disagreement with previous reports, it was observed that abnormal AP and GGT values could be readily explained by their association with specific diseases. The apparent relationship between abnormal levels of plasma AP and GGT activities and age, sex or weight reflected merely a different distribution of the pathology according to these biological parameters. In the absence of non-specific elevations of plasma AP and GGT activities with age, the usual reference values for these tests, although established on younger populations, still apply to the aged.

Plasma ferritin in old age. Influence of biological and pathological factors in a large elderly population.

The effects of biological (age, sex, weight) and pathological factors on plasma ferritin concentrations were documented in 776 unselected elderly patients aged 80.9 +/- 9.7 yr. A marked shift towards high values (159 +/- 142 micrograms/l) was observed in this elderly population together with the persistence of the well-known sex-related difference in ferritin levels (higher levels in men). Twenty-five percent of the population had high levels of ferritin (greater than or equal to 220 micrograms/l) but 75% of these high values (i.e. 18.5% of the population) could be readily explained by their known association with a particular pathology (inflammatory syndrome, renal failure, cardiovascular diseases, alcoholism). Only 6% of the population had unexplained high ferritin concentrations. Therefore, our data strongly suggest that the repeatedly reported increase of ferritin in the aged population is merely related to an age-associated pathology and may not be a normal physiological event occurring during the process of aging.

Evaluation of screening methods for Down's syndrome using bootstrap comparison of ROC curves.

This paper concerns the prediction of fetal Down's syndrome in pregnant women. Down's syndrome is the most common congenital cause of severe mental retardation. We elaborate two predictive functions of trisomy 21, combining maternal age and a maternal serum marker. We evaluated them by means of receiver operating characteristic (ROC) curves which give a representation of sensitivity and specificity of a prediction model when varying the cutoff of the predictor on the whole spectrum. Since normal statistical methods for comparison of ROC curves rely on distributional assumptions which were not verified, we used bootstrapping of ROC curves as a check for the statistical significance of differences between the areas under the curves.

[Measurement of arterial pressure in children. Influence of the resting time, inflatable surface and type of arm-band]. / Mesure de la pression artérielle de l'enfant. Influence du temps de repos, de la surface gonflable et du type de brassard.

Measurements of arterial pressure in children should be standardized as much as possible. The influence on readings of three factors--pre-measurement resting time, area of the inflatable surface and type of cuff--was investigated in 151 children divided into several homogeneous groups. The study showed that reliable values can only be surface area, it would appear that no modern apparatus provides accurate readings for all age groups. The cuff itself is of little importance, but diastolic pressure values are slightly increased when cuffs with an unprotected bladder are used.

[Mortality of dilated myocardiopathies as a function of continuation of alcohol drinking. Multivariate analysis concerning 236 patients]. / Mortalité des myocardiopathies dilatées en fonction de la poursuite de l'alcoolisation. Analyse multivariée sur 236 malades.

A retrospective study was conducted in 236 consecutive patients with dilated cardiomyopathy to determine the characteristics of the disease in heavy alcohol drinkers (n = 110) and to study its outcome, using a Cox model, according to whether the patients were abstainers (n = 49) or continued to indulge drinking (n = 61). At the time of diagnosis, pulmonary pressures were higher in heavy drinkers than in abstainers. During a mean follow-up period of 39 +/- 27 months, 80 patients died of heart disease, viz.: 46 out of 127 non-alcoholic patients (36.2 per cent), 31 out of 61 heavy drinkers (50.8 per cent) and 3 out of 49 patients who had given up alcohol (6.12 per cent). Thus, independently of other parameters, abstinence is a highly significant (P less than 0.001) factor of favourable prognosis in dilated cardiomyopathy.

Discriminant analysis: methods and program.

Because of the disparity in the results obtained using different methods of discriminant analysis, we have written and used a unique program to test them. These methods can be divided into two groups corresponding to a classical probabilistic approach (i.e., Bayesian methods) or a topological approach (i.e., Sebestyen method).

DISBAR: a program for two-group discriminant analysis on mixed variables after binary coding.

The program DISBAR is particularly adapted to medical data which often concern several measurements of different types (mixed variables) collected on patients divided into 2 groups according to a binary response variable such as survival or non-survival. DISBAR leads to a simple geometrical representation of the observations providing an easy allocation rule for a new case. The computer time required to run the program DISBAR is negligible in comparison with the one necessary to perform any other discriminant analysis of binary variables. DISBAR combines in practice computational facility with good results and easy interpretation.

Use of longitudinal data analysis in the determination of a global score for total hip replacement indication in osteoarthritis patients.

BACKGROUND: A composite index would help in medical practice for considering total hip replacement (THR) in hip osteoarthritis. In association with other parameters, such as age or general status, this index could serve to objectively determine the time to THR surgery, and might be used as an outcome measure in therapeutic trials. The objective of this study was to propose such an index, taking into account symptomatic, structural and therapeutic variables, and impact on lifestyle. METHODS: A curve-fitting procedure and a marginal model were used to highlight the average change in the variables over time. A discrete Cox model, with time-dependent covariates. was then performed to study the association between the variables and hip surgery, leading to the construction of a composite index. RESULTS: The smoothing and fitting analysis suggested takes into account not only the variables, but also the changes in their values during the preceding year, when studying the association between variables and hip surgery. Five covariates were retained in the Cox model, among them only one concerns the changes during the preceding year, showing that the values of the covariates are more important that their changes during the preceding year for THR indication. The coefficients of the model were transformed into new coefficients, so that their sum provided a severity score with individual values 0-100. DISCUSSION: Based on the values of reliable variables recorded during the four last visits, this score can be regarded as a valid index able to objectively help with THR indications. This score might also be used as an outcome measure in therapeutic trials.

Criteria for generalized and focal osteoarthritis.

STUDY OBJECTIVE: to identify homogeneous, distinct subgroups of osteoarthritis patients based on distribution of osteoarthritis lesions. STUDY DESIGN: cross-sectional, prospective, multicenter. Patients with osteoarthritis of the hip, knee, fingers, or spine. DATA COLLECTED: clinical and radiologic features at 41 joint sites. METHODS: multivariate statistical analysis including a) k-mean clustering analysis followed by ascending hierarchical classification b) and a tree-structured discriminant method to confirm and to characterize the subgroups obtained using the clustering method. RESULTS: The 1021 patients were first classified into five categories with an error rate (obtained by cross-validation) of 7.6%. The tree obtained by segmentation took into account manifestations of osteoarthritis at the hands, knees and spine. Irrespective of the reason for seeking medical advice, patients with bilateral involvement of the fingers or with involvement of the spine and both femorotibial joints were classified as having generalized osteoarthritis; in contrast, focal osteoarthritis was defined as the absence of involvement of the fingers and of either the spine or the knees. CONCLUSION: The statistical analysis provided a classification system that would be easy to use in everyday clinical practice. Prospective studies are needed to evaluate the potential clinical relevance of this system.

Evaluation of a functional index and an articular index in ankylosing spondylitis.

We describe an index of functional impairment and a system of scoring joint tenderness for use in the assessment of ankylosing spondylitis. The functional index consists of 20 questions and the articular index is based on the scoring of a total of 10 joint responses after movement or firm digital pressure. These indices are simple to establish and not time consuming. They have a high degree of intra- and interobserver reproducibility. The indices showed changes in short term clinical trials of antiinflammatory drugs; these changes were highly correlated with the patient's overall assessment of his own clinical condition.

Cumulative effects of age and pathology on plasma carcinoembryonic antigen in an unselected elderly population.

Plasma CEA was measured in 776 institutionalized elderly patients, 593 women and 183 men, whose mean age was 80.8 +/- 9.7 yr. Of these subjects 39 were found to be free of any pathology and were considered as a control group. All the other subjects had a variety of diseases, malignant or not, known or not known to be associated with elevated CEA. This study showed that elderly people in their 80s, in apparent good health, had higher levels of CEA (3.0 +/- 1.4 ng/ml) than younger people. These levels were shown to be significantly increased in a large number of non-malignant diseases. No correlation could be found between elevated CEA values and autopsy finding or drug administration. Using the chi square test, the number of patients with CEA levels greater than 5 ng/ml was found to be significantly higher in chronic renal failure and cancer. Mortality was also found to be higher in patients with CEA levels greater than 5 ng/ml during a 25-month follow-up. Higher levels of CEA in elderly subjects in apparent good health, as well as increase of these levels in a large set of non-malignant pathology, must thus be kept in mind when interpreting data arising from old people because of both the false-positive (healthy elderly subjects) and the cumulative effects of polypathology on plasma CEA.

[Local tolerance of subcutaneous heparin. Double-blind comparison of calcium and sodium heparins (author's transl)]. / Tolérance locale de l'héparine sous-cutanée. Comparaison en double insu de deux sels de calcium et de sodium.

One hundred and twelve subcutaneous injections of concentrated heparin (25,000 IU/ml), half in sodium heparin and half in calciparine, both with an identical heparin cation, were given in doses varying from 0.2 ml to 0.5 ml by a single operator in a double-blind study to assess the comparative local tolerance of the two heparin salts. The occurrence of bruising at the point of injection, more frequent with sodium heparin than with Calciparine, proved to be the distinguishing factor. Overall after 48 hours, 31 hematomas were observed with the sodium salt versus 20 with calciparine. McNemar's test of comparing matched proportions confirms this result (p = 0.03) and, with the order of the two treatments taken into consideration, J.J. Gart's exact test gives p = 0.0101.

Two methods of discrimination on qualitative variables.

The methods of discrimination on qualitative variables are generally based on the estimation of density distribution in each group yk (k = 1, 2, ..., K). Two kinds of estimation are proposed and the correspondent computer program is presented. The results of a medical example are compared with those obtained by using a logistic model used by different authors when dealing with discrimination problems.

[Criteria for the evaluation of the antirheumatic (antiinflammatory) drugs in man]. / Etudes d'un système de critéres pour l'évaluation, chez l'Homme, de l'effet des médicaments anti-rhumatismaux (anti-inflammatoires).

Comparison of 5 antiinflammatory drugs and placebo in a double blind, short term, cross-over trial conducted in patients suffering from rheumatoid arthritis. 15 measurements were used and studied. With classical unidimensional statistical tests it was not possible to discriminate active drugs between them. Multidimensional analysis (correspondance analysis and discriminant analysis) are more sensitive and allow us to distinguish active drugs with only 11 criterion.

Age- and sex-associated modification of plasma melatonin concentrations in man. Relationship to pathology, malignant or not, and autopsy findings.

Plasma melatonin concentrations were determined in 757 unselected elderly patients aged 80.9 +/- 9.7 years. The daytime (8-9.30 h) plasma levels of melatonin were in the so-called normal range in only one third of the population whereas 65% of the subjects had abnormal levels of the hormone, most often decreased i.e. less than 0.17 nmol/l (53%) and sometimes increased i.e. 0.43 nmol/l or higher (12%). A control group of healthy elderly subjects showed the same distribution as the entire population. A sex-difference with significantly higher levels of plasma melatonin in elderly women was observed. With respect to pathology and autopsy findings high levels of the hormone correlated with cancer, chronic renal failure, cardiovascular disease, biological inflammatory syndrome and diabetes. Low levels correlated with neurologic disease, tobacco or alcohol addiction. However, some of these relations were found to be sex-related as they were observed in women but not in men. Our data indicate that pineal function seems to be often altered in elderly human subjects and suggest potential diagnostic applications of melatonin determination.

Defining disease activity in ankylosing spondylitis: is a combination of variables (Bath Ankylosing Spondylitis Disease Activity Index) an appropriate instrument?

OBJECTIVE: Disease activity has been defined using a self-administered instrument, focusing on fatigue, axial pain, peripheral pain, enthesopathy and morning stiffness [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)]. This validated instrument is simple and takes 40 s to complete, but whether the index is an accurate expression of the component parts, or whether additional weighting would enhance its efficacy, is unclear. METHODS: Four hundred and seventy-three patients with ankylosing spondylitis received placebo or active non-steroidal anti-inflammatory drug (NSAID) for 6 weeks, and changes between entry and completion were captured by BASDAI and the individual components. Principle component analysis (PCA) was used to explore the best combinations of variables in decreasing order of explained total dispersion and to assess whether a single sum (or algebraic expression) best defined disease activity status. RESULTS: At entry, the correlation between BASDAI and the first axis was 0.99, 0.11 with the second, and zero thereafter. Data at study end and relating to change revealed a 100% correlation (R = 1) between the first axis and the sum, with zero for the remainder. CONCLUSIONS: The data support BASDAI as being a valid and appropriate composite to define disease activity in ankylosing spondylitis. Developed as a simple sum of its components, BASDAI has excellent content validity.

Outcome variables in ankylosing spondylitis: evaluation of their relevance and discriminant capacity.

The clinical status of ankylosing spondylitis (AS) can be defined by several domains (e.g., pain, function, metrology, laboratory) and subcomponents within each domain (e.g., pain using visual analog scale, Schober's within metrology). Our aim was (1) To define groups of highly correlated variables in order to determine the most relevant; and (2) to evaluate the capacity of different clinical and biological variables that best discriminate between placebo and active nonsteroidal drugs in AS. Patients with active AS (n=423) were followed prospectively over 6 weeks while receiving placebo (n=121) or active nonsteroidal antiinflammatory drugs (n=352). Eighteen variables were studied, including global assessment, pain, stiffness, functional indices, metrology, disease activity index, and laboratory markers. Statistics included (1) Evaluation of the relevance of the different domains by multivariate analysis (CART tree-structure classification; variable clustering); and (2) evaluation of the discriminant capacity by univariate analysis [i.e., differences in the standardized response mean (SRM) (mean change/SD) between placebo and active drug. A value > or =0.60 was considered relevant]. Four clusters were identified (patient's subjective perception, inflammatory symptoms, metrology, laboratory data) with multiple correlation R2 revealing the most relevant variables to be the Bath Ankylosing Spondylitis Functional Index (BASFI; 0.75), night pain (0.62), Schober's test (0.58), and platelet count (0.55), respectively, within each cluster. In terms of discriminant power (SRM) the patient perceived global status (0.84), lumbar pain (0.73), night pain (0.71), physician global assessment (0.66), and BASFI (0.65) were most relevant in the univariate analysis. Among the 4 most relevant domains are subjective perception, inflammatory symptoms, metrology, and laboratory. Multivariate analysis of the data reveals that the spinal pain and the patient global assessment are the variables that best discriminate between placebo and active nonsteroidal drug in short term studies.