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Tuberculin skin test: estimation of positive and negative predictive values from routine data.

OBJECTIVE: To estimate, using routinely available data, the predictive values of tuberculin testing with 2TU RT23 for detection of latent tuberculosis infection (LTBI) in the Dutch population as a basis for recommendations on cut-off values at various levels of infection prevalence. DESIGN: Smoothed distributions of TST reactions among 312 tuberculosis patients and 2848 healthy non-BCG-vaccinated persons were used to estimate the sensitivity and specificity at various cut-off values. RESULTS: Sensitivity was 98.9% at 5 mm, 95.4% at 10 mm and 79.8% at 15 mm cut-off. Specificity with the corresponding cut-offs was 95.3%, 96.3% and 97.1% before and 98.0%, 98.8% and 99.6% after adjustment for presumed LTBI. At 10 mm, the positive predictive value (PPV) was > 75% if the infection prevalence in the tested population was at least 10%, but strongly declined with lower prevalences. For lower prevalences a cut-off of 15 mm was proposed, as this results in a higher PPV without greatly affecting the negative predictive value. CONCLUSION: Estimation of the predictive values of the TST from routine data can be useful for establishing cut-off values for detection of LTBI in different populations with different tuberculin preparations.

Adult↗

Individualized drug utilization statistics. Analysing a population's drug use from the perspective of individual users.

The Danish retail pharmacies' drug subsidy system is completely computerized. The data are person-identifiable, making it possible to chart the population's drug use from the perspective of individual users. We decided to explore the potential of this data source and to analyse heavy drug users specifically. The analysis encompassed all 890,352 prescriptions presented by citizens of Odense in 1991. There was a total sales volume of 32 million defined daily doses consumed by 113,468 adult drug users, corresponding to 65.1% of the adult population. We found 2388 heavy drug users, defined by an annual purchase of more than 2000 defined daily doses. Heavy drug users accounted for 1.4% of the adult population and 22.9% of drug sales. They were remarkably well characterized by their main therapeutic class, which constituted a median of 47% of their drug use. A median of 97% of each heavy user's drugs were issued by one main prescriber. We conclude that heavy drug use can generally be ascribed to severe disease rather than to irresponsible prescribing. For the most important drug classes, we present various epidemiological measures of drug use, including 1-year prevalence, incidence, duration of therapy and some measures of skewness in utilization. If analysed regularly these measures can disclose subtle trends in clinical drug use that would not be evident from the wholesale figures.

Age Distribution↗

Statistical analyses of counts and distributions of restriction sites in DNA sequences.

Counts and spacings of all 4- and 6-bp palindromes in DNA sequences from a broad range of organisms were investigated. Both 4- and 6-bp average palindrome counts were significantly low in all bacteriophages except one, probably as a means of avoiding restriction enzyme cleavage. The exception, T4 of normal 4- and 6-palindrome counts, putatively derives protection from modification of cytosine to hydroxymethylcytosine plus glycosylation. The counts and distributions of 4-bp and of 6-bp restriction sites in bacterial species are variable. Bacterial cells with multiple restriction systems for 4-bp or 6-bp target specificities are low in aggregate 4- or 6-bp palindrome counts/kb, respectively, but bacterial cells lacking exact 4-cutter enzymes generally show normal or high counts of 4-bp palindromes when compared with random control sequences of comparable nucleotide frequencies. For example, E. coli, apparently without an exact 4-bp target restriction endonuclease (see text), contains normal aggregate 4-palindrome counts/kb, while B. subtilis, which abounds with 4-bp restriction systems, shows a significant under-representation of 4-palindrome counts. Both E. coli and B. subtilis have many 6-bp restriction enzymes and concomitantly diminished aggregate 6-palindrome counts/kb. Eukaryote, viral, and organelle sequences generally have aggregate 4- and 6-palindromic counts/kb in the normal range. Interpretations of these results are given in terms of restriction/methylation regimes, recombination and transcription processes, and possible structural and regulatory roles of 4- and 6-bp palindromes.

Animals↗

Intravascular ultrasound image segmentation: a three-dimensional fast-marching method based on gray level distributions.

Intravascular ultrasound (IVUS) is a catheter based medical imaging technique particularly useful for studying atherosclerotic disease. It produces cross-sectional images of blood vessels that provide quantitative assessment of the vascular wall, information about the nature of atherosclerotic lesions as well as plaque shape and size. Automatic processing of large IVUS data sets represents an important challenge due to ultrasound speckle, catheter artifacts or calcification shadows. A new three-dimensional (3-D) IVUS segmentation model, that is based on the fast-marching method and uses gray level probability density functions (PDFs) of the vessel wall structures, was developed. The gray level distribution of the whole IVUS pullback was modeled with a mixture of Rayleigh PDFs. With multiple interface fast-marching segmentation, the lumen, intima plus plaque structure, and media layers of the vessel wall were computed simultaneously. The PDF-based fast-marching was applied to 9 in vivo IVUS pullbacks of superficial femoral arteries and to a simulated IVUS pullback. Accurate results were obtained on simulated data with average point to point distances between detected vessel wall borders and ground truth <0.072 mm. On in vivo IVUS, a good overall performance was obtained with average distance between segmentation results and manually traced contours <0.16 mm. Moreover, the worst point to point variation between detected and manually traced contours stayed low with Hausdorff distances <0.40 mm, indicating a good performance in regions lacking information or containing artifacts. In conclusion, segmentation results demonstrated the potential of gray level PDF and fast-marching methods in 3-D IVUS image processing.

Algorithms↗

Aging and recognition memory: changes in regional cerebral blood flow associated with components of reaction time distributions.

We used H(2)15O positron emission tomography (PET) to measure age-related changes in regional cerebral blood flow (rCBF) during a verbal recognition memory task. Twelve young adults (20 to 29 years) and 12 older adults (62 to 79 years) participated. Separate PET scans were conducted during Encoding, Baseline, and Retrieval conditions. Each of the conditions involved viewing a series of 64 words and making a two-choice response manually. The complete reaction time (RT) distributions in each task condition were characterized in terms of an ex-Gaussian model (convolution of exponential and Gaussian functions). Parameter estimates were obtained for the mean of the exponential component (tau), representing a task-specific decision process and the mean of the Gaussian component (mu) representing residual sensory coding and response processes. Independently of age group, both tau and mu were higher in the Encoding and Retrieval conditions than in the Baseline condition, and tau was higher during Retrieval than during Encoding. Age-related slowing in task performance was evident primarily in mu. For young adults, rCBF activation in the right prefrontal cortex, in the Retrieval condition, was correlated positively with mu but not with tau. For older adults, rCBF changes (both increases and decreases) in several cortical regions were correlated with both mu and tau. The data suggest that the attentional demands of this task are relatively greater for older adults and consequently lead to the recruitment of additional neural systems during task performance.

Adult↗

Reference thresholds for 24-h, diurnal, and nocturnal ambulatory blood pressure mean values in pregnancy.

OBJECTIVES: Several studies have indicated that the use of the 24-h mean of blood pressure, mainly using reference thresholds derived from the general non-pregnancy practice, does not provide a proper test for diagnosis of hypertension in pregnancy. This prospective study examines previously derived reference thresholds for the 24-h, diurnal, and nocturnal mean of blood pressure as potential screening tests for the diagnosis of hypertension in pregnancy. METHODS: We studied 235 normotensive and 168 hypertensive pregnant women, who provided 2430 blood pressure series sampled every 20 min during the day and every 30 min at night for 48 consecutive hours once every 4 weeks from the first obstetric visit until delivery. Sensitivity and specificity for each parameter are based on the comparison of the distributions of mean blood pressure values with reference thresholds previously established from an independent population of 113 pregnant women also evaluated monthly by 48-h ambulatory monitoring throughout gestation. RESULTS: Sensitivity of mean blood pressure values, above 70% at all stages of pregnancy, was higher than that obtained from clinic blood pressure measurements, which were always below 14%. The poorest results were consistently obtained for the nocturnal mean. Sensitivity was similar for the 24-h and the diurnal mean, with values ranging from 71% for diastolic blood pressure in the first trimester of pregnancy to 93% for systolic blood pressure in the third trimester. Systolic blood pressure consistently provided better sensitivity than diastolic blood pressure at all gestational ages. CONCLUSIONS: This prospective study on women systematically studied by 48-h ambulatory monitoring throughout gestation indicates that mean ambulatory blood pressure values provide higher sensitivity and specificity than conventional measurements. Moreover, results indicate that diagnosis of hypertension in pregnancy based on ambulatory blood pressure should be established from thresholds much lower than those currently used in clinical practice.

Adult↗

The first-generation whole-genome radiation hybrid map in the horse identifies conserved segments in human and mouse genomes.

A first-generation radiation hybrid (RH) map of the equine (Equus caballus) genome was assembled using 92 horse x hamster hybrid cell lines and 730 equine markers. The map is the first comprehensive framework map of the horse that (1) incorporates type I as well as type II markers, (2) integrates synteny, cytogenetic, and meiotic maps into a consensus map, and (3) provides the most detailed genome-wide information to date on the organization and comparative status of the equine genome. The 730 loci (258 type I and 472 type II) included in the final map are clustered in 101 RH groups distributed over all equine autosomes and the X chromosome. The overall marker retention frequency in the panel is approximately 21%, and the possibility of adding any new marker to the map is approximately 90%. On average, the mapped markers are distributed every 19 cR (4 Mb) of the equine genome--a significant improvement in resolution over previous maps. With 69 new FISH assignments, a total of 253 cytogenetically mapped loci physically anchor the RH map to various chromosomal segments. Synteny assignments of 39 gene loci complemented the RH mapping of 27 genes. The results added 12 new loci to the horse gene map. Lastly, comparison of the assembly of 447 equine genes (256 linearly ordered RH-mapped and additional 191 FISH-mapped) with the location of draft sequences of their human and mouse orthologs provides the most extensive horse-human and horse-mouse comparative map to date. We expect that the foundation established through this map will significantly facilitate rapid targeted expansion of the horse gene map and consequently, mapping and positional cloning of genes governing traits significant to the equine industry.

Animals↗

Attempted suicide and major public holidays in Europe: findings from the WHO/EURO Multicentre Study on Parasuicide.

OBJECTIVE: The aim of the study was to examine the relationship between suicide attempts and major public holidays in Europe. METHOD: The analysis was based on data on 24 388 suicide attempts by persons aged 15 years or older in the period 1989-1996. Data from 13 centres (representing 11 countries) participating in the WHO/EURO Multicentre Study on Parasuicide were analysed. The analysis of the fluctuation of suicide attempts around public holidays was based on the daily number of suicide attempts for each centre. For each day in the period under examination a mean number of suicide attempts (mu) was calculated. The analysis was based on the assumption that the data followed a Poisson distribution. The observed number of daily suicide attempts was compared with the expected number of attempts. A multiplicative model for the expected number in each centre was developed. RESULTS: Before Christmas there were fewer suicide attempts than expected, and after Christmas there were approximately 40% more attempts than expected. In addition, more attempts than expected were registered on New Year's Day. In countries where people have the day off work on Whit Monday there were significantly fewer attempts during the 3 days before, but where Whit Monday is a normal working day significantly fewer attempts occurred on the Monday to Wednesday after Whit Sunday. CONCLUSION: There appears to be a transposition of a significant number of suicide attempts from before (and during) a major public holiday until after it. The division of holidays into non-working and working days showed that a 'holiday effect' could only be found around major public holidays, particularly Christmas, Easter and Whitsun. These findings support the theory of the 'broken-promise effect' for major public holidays.

Adolescent↗

A preliminary study of serum ferritin reference range in the adult Ghanaian.

Serum ferritin levels were determined in 85 Healthy Ghanaian adults (45 men and 39 women) with a Ciba Corning 125I-Ferritin procedure. Concentrations showed a non-guassian distribution. Values for males ranged from 5.6-273 ng/ml and from 0.74-135 ng/ml for females. The non-guassian nature of the distribution necessitated a logarithmic transformation of the data in order to calculate the serum ferritin reference range (Mean +/- 2SD) for the subjects. The reference range for the males (antilogarithm) was 8.5-306.5 ng/ml (mean = 51.0 ng/ml). The reference range for the Ghanaian women was 3-112 ng/ml (mean = 18.0 ng/ml). The reported reference range for the Caucasian male is 7-350 ng/ml (mean -51.0 ng/ml) and for the Caucasian female, 5-135 ng/ml (mean = 22.0 ng/ml). These Ghanaian reference ranges agree closely with the caucasian values. Data from this preliminary study suggest serum ferritin values of < 8.5 ng/ml and < 3 ng/ml could serve as cut-off points below which iron deficiency may be said to be present in the adult Ghanaian male and female respectively when the same method of analysis is used. A further study of ferritin levels in the Ghanaian is recommended. Pending further work, continued use of the conventional cut-off points of 20 ng/ml for males and 10 ng/ml for females to identify iron-deficient individuals is in order. These conventional cut-off points enhance chances for identifying iron-deficient individuals.

Adult↗

Locally linear discriminant analysis for multimodally distributed classes for face recognition with a single model image.

We present a novel method of nonlinear discriminant analysis involving a set of locally linear transformations called "Locally Linear Discriminant Analysis (LLDA)." The underlying idea is that global nonlinear data structures are locally linear and local structures can be linearly aligned. Input vectors are projected into each local feature space by linear transformations found to yield locally linearly transformed classes that maximize the between-class covariance while minimizing the within-class covariance. In face recognition, linear discriminant analysis (LDA) has been widely adopted owing to its efficiency, but it does not capture nonlinear manifolds of faces which exhibit pose variations. Conventional nonlinear classification methods based on kernels such as generalized discriminant analysis (GDA) and support vector machine (SVM) have been developed to overcome the shortcomings of the linear method, but they have the drawback of high computational cost of classification and overfitting. Our method is for multiclass nonlinear discrimination and it is computationally highly efficient as compared to GDA. The method does not suffer from overfitting by virtue of the linear base structure of the solution. A novel gradient-based learning algorithm is proposed for finding the optimal set of local linear bases. The optimization does not exhibit a local-maxima problem. The transformation functions facilitate robust face recognition in a low-dimensional subspace, under pose variations, using a single model image. The classification results are given for both synthetic and real face data.

Algorithms↗

Novel point mutations in the mitochondrial DNA detected in patients with dilated cardiomyopathy by screening the whole mitochondrial genome.

Dilated cardiomyopathy (DCM) is widely accepted as a pluricausal or multifactorial disease. Because of the linkage between energy metabolism in the mitochondria and cardiac muscle contraction, it is reasonable to assume that mitochondrial abnormalities may be responsible for some forms of DCM. We analysed the whole mitochondrial genome in a series of 45 patients with DCM for alterations and compared the findings with those of 62 control subjects. A total of 458 sequence changes could be identified. These sequence changes were distributed among the whole mitochondrial DNA (mtDNA). An increased number of novel missense mutations could be detected nearly in all genes encoding for protein subunits in DCM patients. In genes coding for NADH dehydrogenase subunits the number of mtDNA mutations detected in patients with DCM was significantly increased (p < 0.05) compared with control subjects. Eight mutations were found to occur in conserved amino acids in the above species. The c.5973G > A (Ala-Trp) and the c.7042T > G (Val-Asp) mutations were located in highly conserved domains of the gene coding for cytochrome c oxidase subunit. Two tRNA mutations could be detected in the mtDNA of DCM patients alone. The T-C transition at nt 15,924 is connected with respiratory enzyme deficiency, mitochondrial myopathy, and cardiomyopathy. The c.16189T > C mutation in the D-loop region that is associated with susceptibility to DCM could be detected in 15.6% of patients as well as in 9.7% of controls. Thus, mutations altering the function of the enzyme subunits of the respiratory chain can be relevant for the pathogenesis of dilated cardiomyopathy.

Adult↗

A genomic screen of autism: evidence for a multilocus etiology.

We have conducted a genome screen of autism, by linkage analysis in an initial set of 90 multiplex sibships, with parents, containing 97 independent affected sib pairs (ASPs), with follow-up in 49 additional multiplex sibships, containing 50 ASPs. In total, 519 markers were genotyped, including 362 for the initial screen, and an additional 157 were genotyped in the follow-up. As a control, we also included in the analysis unaffected sibs, which provided 51 discordant sib pairs (DSPs) for the initial screen and 29 for the follow-up. In the initial phase of the work, we observed increased identity by descent (IBD) in the ASPs (sharing of 51.6%) compared with the DSPs (sharing of 50.8%). The excess sharing in the ASPs could not be attributed to the effect of a small number of loci but, rather, was due to the modest increase in the entire distribution of IBD. These results are most compatible with a model specifying a large number of loci (perhaps >/=15) and are less compatible with models specifying </=10 loci. The largest LOD score obtained in the initial scan was for a marker on chromosome 1p; this region also showed positive sharing in the replication family set, giving a maximum multipoint LOD score of 2.15 for both sets combined. Thus, there may exist a gene of moderate effect in this region. We had only modestly positive or negative linkage evidence in candidate regions identified in other studies. Our results suggest that positional cloning of susceptibility loci by linkage analysis may be a formidable task and that other approaches may be necessary.

Adolescent↗

Fos expression is induced by increased nitric oxide release in rat spinal cord dorsal horn.

The relationship between exogenous or endogenous nitric oxide and c-fos, an immediate-early gene which can further activate the production of other substances in the central nervous system, was investigated in this study. We found that Fos expression is increased after intradermal capsaicin injection, which also leads to endogenous nitric oxide release in the spinal cord. The increased Fos expression is distributed in neurons of the superficial layers and lamina V of the dorsal horn on the side ipsilateral to the injection. The increased Fos expression is blocked by N(G)-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor, but not by its inactive isomer N(G)-nitro-D-arginine methyl ester. Fos expression was also increased following the perfusion of 3-morpholino-sydnonimine, a nitric oxide donor, into the dorsal horn through a microdialysis fiber. The increased Fos was distributed within 400 microm from the edge of the microdialysis fiber. Although Fos expression was increased with 3-morpholino-sydnonimine perfusion compared to that seen with artificial cerebrospinal fluid perfusion, there was still some Fos immunostaining in the control sections. Following perfusion of artificial cerebrospinal fluid in the spinal cord of rats pretreated with N(G)-nitro-L-arginine methyl ester, it was found that Fos staining was reduced significantly compared to the control sections from animals without N(G)-nitro-L-arginine methyl ester pretreatment. These results suggest that nitric oxide helps mediate Fos expression induced by an intradermal capsaicin injection. We conclude that both endogenous and exogenous nitric oxide induce Fos expression. Involvement of nitric oxide in the development of central sensitization may affect nociceptive processing by increasing Fos expression. Since many other substances which are related to pain mechanisms can be induced by Fos, it is suggested that nitric oxide may regulate production of these substances through activation of Fos. Nitric oxide is not only involved in the development of central sensitization, but is also involved in the activation of control mechanisms affecting nociception.

Animals↗

Distribution of coronary artery calcium by race, gender, and age: results from the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: Coronary artery calcium (CAC) has been demonstrated to be associated with the risk of coronary heart disease. The Multi-Ethnic Study of Atherosclerosis (MESA) provides a unique opportunity to examine the distribution of CAC on the basis of age, gender, and race/ethnicity in a cohort free of clinical cardiovascular disease and treated diabetes. METHODS AND RESULTS: MESA is a prospective cohort study designed to investigate subclinical cardiovascular disease in a multiethnic cohort free of clinical cardiovascular disease. The percentiles of the CAC distribution were estimated with nonparametric techniques. Treated diabetics were excluded from analysis. There were 6110 included in the analysis, with 53% female and an average age of 62 years. Men had greater calcium levels than women, and calcium amount and prevalence were steadily higher with increasing age. There were significant differences in calcium by race, and these associations differed across age and gender. For women, whites had the highest percentiles and Hispanics generally had the lowest; in the oldest age group, however, Chinese women had the lowest values. Overall, Chinese and black women were intermediate, with their order dependent on age. For men, whites consistently had the highest percentiles, and Hispanics had the second highest. Blacks were lowest at the younger ages, and Chinese were lowest at the older ages. At the MESA public website (http://www.mesa-nhlbi.org), an interactive form allows one to enter an age, gender, race/ethnicity, and CAC score to obtain a corresponding estimated percentile. CONCLUSIONS: The information provided here can be used to examine whether a patient has a high CAC score relative to others with the same age, gender, and race/ethnicity who do not have clinical cardiovascular disease or treated diabetes.

Age Factors↗

Minimization method for balancing continuous prognostic variables between treatment and control groups using Kullback-Leibler divergence.

This paper proposes a method for balancing prognostic variables between treatment and control groups in design of clinical trials. It assumes that some of prognostic variables are continuous and others are categorical and that they are independently distributed. The proposed method uses the Kullback-Leibler divergence (KLD) as the index of difference in distribution between two groups. It sequentially allocates each subject to a group using a biased coin method so as to reduce the estimate of KLD. That is, when first i subjects have been allocated to two groups and the (i+1)th subject is enrolled, the KLD is estimated if the (i+1)th subject was to be allocated to either of the groups, and the subject is then allocated with a certain probability, e.g. 0.80, so as to make the KLD small. Simulation studies based on the hypothetical prognostic variables and on the actual data of hyperlipidemia patients were carried out in order to compare the proposed method with the Pocock-Simon method, which transforms the continuous prognostic variables into categorical variables by dividing the whole scale into several categories. The p values of homogeneity test of means and variances were used to evaluate the achieved balance. The observed p values in the proposed method were better than those in the Pocock-Simon method. In addition to the balance, the precision of parameter estimates assuming analysis of covariance model was examined. The results showed the precision of estimators tended to be more stable in the proposed method than the Pocock-Simon method.

Clinical Trials as Topic↗

Aquatic ecotoxicological indicators in life-cycle assessment.

This paper compares available options for the aquatic ecotoxicological effect factor component in life-cycle assessment (LCA). The effect factor is expressed here as the change in risk per unit change in cumulative exposure, delta effect/delta exposure. The comparison is restricted to approaches linked, implicitly as well as explicitly, to species-sensitivity distributions (SSDs). This draws on recent insights for chemical mixtures and identifies the implications of different model choices. In spite of the many options, assumptions, and areas for further research, it is concluded that a single effect factor basis represents the best available practice for use in LCA at this time, deltaPAF(ms)/deltaC = 0.5/HC50, where deltaPAF(ms) is the change in the (potentially affected) fraction (PAF) of species that experiences an increase in exposure above a specified effect level, accounting for the presence of complex background mixtures (ms), deltaC is the change in cumulative exposure concentration of the chemical of interest, and HC50 is the median, chronic hazardous concentration for regional, multiple-species systems. The resultant aquatic effect factors are risk-based and can be estimated readily for many chemicals using available methods, without the need to describe the entire SSDs and without the need for additional data. For example, the octanol-water partitioning coefficient provides a sufficient estimation basis for about 50% of existing chemicals that have a narcosis mode of action. This also is relevant in LCA for chemicals that are at low concentrations in the environment, concentrations below the biological thresholds at which more specific modes of action would be of relevance.

Animals↗

Comparative study of bone mineral density, calcium, and vitamin D status in the Gujarati and white populations of Leicester.

OBJECTIVES: To evaluate differences in bone mineral density (BMD), calcium, and vitamin D status between the Gujarati (South Asian) and white populations resident in Leicester and to determine whether this was linked to lifestyle factors. DESIGN: An observational cross sectional study of randomly selected Gujarati and white volunteers aged from 20-40 years. SETTING: City of Leicester. PARTICIPANTS: Subjects were randomly selected by age (20-40 years) and ethnicity. A total of 262 individuals volunteered to participate, of which 201 (51 white females, 71 Gujarati females, 37 white males, 42 Gujarati males) were eligible for the study. MAIN OUTCOME MEASURES: Results of questionnaire, BMD at the hip and lumbar spine, and measurement of serum calcium, albumin, alkaline phosphatase, and 25-hydroxyvitamin D. RESULTS: Male and female white subjects were significantly taller and heavier than their Gujarati counterparts. There was a statistically significant difference in BMD both at the spine (p<0.001) and hip (p<0.001) between the white and Gujarati females with the Gujaratis having a lower BMD. There was a trend for Gujarati males to have a lower BMD at the hip and spine than their white counterparts but these figures did not reach statistical significance. The intensity of cigarette smoking and the amount of alcohol consumption were both higher in the white male and female subjects. Sunlight exposure (>4 hours per day) was significantly higher in white subjects compared with Gujaratis. There were no significant differences in the mean level of serum calcium or alkaline phosphatase between the Gujaratis and whites. A significantly higher proportion (p<0.001) of the Gujarati men and women had a vitamin D level that was not measurable (that is, below the lower limit of the laboratory range of normal). Of those who had a measurable level (that is, in the normal range) mean levels of vitamin D were lower (p<0.05) in the Gujarati men and women. CONCLUSION: The present study is the first of its kind to note a low BMD in Gujarati subjects of South Asian origin compared with their white counterparts, living in Leicester. This study also confirms the presence of low serum vitamin D levels in Gujaratis. There is a need for more research in South Asians with regard to the collection of normal BMD values. This could provide a more meaningful reference range for identifying South Asians at risk of osteoporotic fractures and may have public health implications of relevance to this ethnic group.

Adult↗

A mixed approach and a distribution-free multiple imputation technique for the estimation of a multivariate probit model with missing values.

In the present paper a mixed generalized estimating/pseudo-score equations (GEPSE) approach together with a distribution-free multiple imputation technique is proposed for the estimation of regression and correlation structure parameters of multivariate probit models with missing values for an ordered categorical time-invariant variable. Furthermore, a generalization of the squared trace correlation (RT2) for multivariate probit models, denoted by pseudo-RT2, is proposed. A simulation study was conducted, simulating a probit model with an equicorrelation structure in the errors of an underlying regression model and using two different missing mechanisms. For a low 'true' correlation the difference between the GEPSE, a generalized estimating equations (GEE) and a maximum likelihood (ML) estimator were negligible. For a high 'true' correlation the GEPSE estimator turned out to be more efficient than the GEE and very efficient relative to the ML estimator. Furthermore, the pseudo-RT2 was close to RT2 of the underlying linear model. The mixed approach is illustrated using a psychiatric data set of depressive in-patients. The results of this analysis suggest that the depression score at discharge from a psychiatric hospital and the occurrence of stressful life events seem to increase the probability of having an episode of major depression within a one-year interval after discharge. Furthermore, the correlation structure points to short-time effects on having or not having a depressive episode, not accounted for in the systematic part of the regression model.

Depressive Disorder↗