Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Imputation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 397 records · Page 22Linked to original sources
PubMed2002

[Acute generalized exanthematous pustulosis due to fluconazole].

INTRODUCTION: Fluconazole (Triflucan(R)), a systemic triazole antifungal agent is largely prescribed and some cutaneous side effects have already been described. We report the first case of acute generalized exanthematous pustulosis due to this molecule in a patient with cutaneous candidosis. CASE REPORT: A 65 year-old-woman was treated with fluconazole (200 mg/day) for a persistent cutaneous candidosis infection on the buttocks. After the third dose, the patient presented with a pustular eruption with erythema located on her trunk and in her large skin folds. The eruption was associated with fever at 39 degrees C, asthenia and neutrophilia (9,000/mm(3)). The histologic examination and the negativity of microbiological cultures were consistent with the diagnosis of acute generalized exanthematous pustulosis. The eruption cleared with local steroids in about ten days. Nineteen days later, the same pustular eruption occurred but without fever nor neutrophilia. DISCUSSION: Clinical, biological and histological manifestations were consistent with the diagnosis of acute generalized exanthematous pustulosis due to fluconazole. According to the imputability criteria of Begaud et al., intrinsic imputability of fluconazole was possible (I2). According to the classification of the EuroSCAR study, it was certain. No similar case of recurrence had already been described after the withdrawal of the molecule. We believe this is the first case of acute generalized exanthematous pustulosis due to fluconazole (extrinsic imputability: B0).

Acute Disease↗
PubMedDate not supplied

[Adverse drug effect notifications by nurses and comparison with cases reported by physicians].

The aim of the present study was to investigate the characteristics of adverse drug reactions reported by hospital doctors and nurses from Toulouse University Hospital between 1992 and 1993. During these two years, doctors and nurses reported 1498 and 164 adverse drug reactions respectively. Nurses reported significantly more cutaneous side effects than doctors (50 vs 24 per cent). Doctors reported significantly more neuropsychiatric, haematologic, hepatic or renal side effects than nurses. Imputability (causal relation) score of adverse drug reactions given by nurses was higher than that of doctors: nurses reported more observations with imputability equal to I3 (likely: 55 vs 46 per cent) and less with imputability equal to I1 (doubtful: 3 vs 23 per cent). Serious side effects (as defined by WHO) were more often seen by doctors (19 per cent) than by nurses (10 per cent). The more frequently suspected drugs were antiinfectious agents (35 per cent) and analgesics (7 per cent) for nurses, and neurotropic drugs (23 per cent) for doctors. Side effects reported by nurses were mainly observed after parenteral administration (48 per cent) whereas doctors reported mostly side effects seen after oral route (66 per cent). This study underlines the characteristics of adverse drug reactions which can be reported by nurses.

Adverse Drug Reaction Reporting Systems↗
PubMed1996

[How to prove the role of renal artery stenosis as a cause of arterial hypertension].

A renal artery stenosis is definitely responsible for hypertension when the correction of stenosis has resulted in the cure of hypertension. Imputability strategy consists in prior collection of indirect data allowing to predict the efficiency of surgical or angioplasty repair, leading to treatment indications. This strategy is based upon the pathophysiological link between hemodynamic abnormalities, increased renin secretion downstream the stenosis, and hypertension. Imputability methods are designed to examine the renine-dependency of hypertension, and both asymmetric renin secretion and renal hemodynamics if stenosis is unilateral. This asymmetry could be enhanced by acute converting enzyme inhibition. Imputability and screening strategies could be fruitfully associated in high risk patients.

Humans↗
PubMed2025

Genetic architecture and analysis practices of circulating metabolites in the NHLBI Trans-Omics for Precision Medicine Program.

Circulating metabolite levels partly reflect the state of human health and diseases and can be impacted by genetic determinants. Hundreds of loci associated with circulating metabolites have been identified; however, most findings focus on predominantly European ancestry or single-study analyses. Leveraging the rich metabolomics resources generated by the National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) Program, we harmonized and accessibly cataloged 1,729 circulating metabolites among 25,058 ancestrally diverse samples. From our comparison of multiple methods, we provided a set of reasonable strategies for outlier and imputation handling to process metabolite data and show that inverse normalization by study and half-minimum imputation provide mostly similar results for pooled or meta-analysis. Following the practical analysis framework, we further performed a genome-wide association analysis on 1,135 selected metabolites using whole-genome sequencing data from 16,359 individuals passing the quality-control filters and discovered 1,775 independent loci associated with 667 metabolites. Among 160 unreported locus-metabolite pairs, we identified associations with loci locating within previously implicated metabolite-associated genes, as well as associations with loci locating in genes such as GAB3 and VSIG4 (located on the X chromosome) that may play a role in metabolic regulation. In the sex-stratified analysis, we revealed 85 independent locus-metabolite pairs with evidence of sexual dimorphism, which were located in well-known metabolic genes such as FADS2, D2HGDH, SUGP1, and UGT2B17, strongly supporting the importance of exploring sex difference in the human metabolome. Taken together, our study depicted the genetic contribution to circulating metabolite levels, providing additional insight into the understanding of human health.

Humans↗
PubMed1996

The analysis of incomplete data in the three-period two-treatment cross-over design for clinical trials.

The additional time to complete a three-period two-treatment (3P2T) cross-over trial may cause a greater number of patient dropouts than with a two-period trial. This paper develops maximum likelihood (ML), single imputation and multiple imputation missing data analysis methods for the 3P2T cross-over designs. We use a simulation study to compare and contrast these methods with one another and with the benchmark method of missing data analysis for cross-over trials, the complete case (CC) method. Data patterns examined include those where the missingness differs between the drug types and depends on the unobserved data. Depending on the missing data mechanism and the rate of missingness of the data, one can realize substantial improvements in information recovery by using data from the partially completed patients. We recommend these approaches for the 3P2T cross-over designs.

Analysis of Variance↗
PubMed1998

A comparison of smoothing techniques for CD4 data measured with error in a time-dependent Cox proportional hazards model.

The use of CD4+ T-lymphocyte counts as a covariate presents some unique challenges in survivorship analyses due to the variability of this marker. If one does not account for the measurement error component of this variability in some manner, the estimate of the relative risk parameter in a time-dependent Cox model is biased towards zero, and coverage levels of confidence intervals may be seriously incorrect. We use a two-stage approach to reduce the variability in the observed CD4 counts in order to obtain a more accurate estimate of the relative risk parameter and more valid summary statistics. In the first stage, population based smoothing methods derived from a random-effects model plus a stochastic process or individual based smoothing methods are used to replace the observed longitudinal CD4 counts with less variable imputes at each failure time. In the second stage, we use the imputes in a time-dependent Cox model to estimate the risk parameter and its associated summary statistics. We compare the smoothing methods in simulation studies and find that the use of these smoothing methods results in a substantial reduction in bias for the true risk parameter estimate, better efficiency, and more accurate coverage rates in confidence intervals. We apply our two-stage smoothing methods to the marker CD4 in the ACTG-019 clinical trial part B.

AIDS-Related Complex↗
PubMed2000

Analysis and design issues for studies using censored biomarker measurements with an example of viral load measurements in HIV clinical trials.

For many biomarkers, the range (L,R) over which they can be quantified is restricted by technical limitations, leading to some measurements that are left or right censored. However, despite the widespread availability of statistical methods for the analysis of censored data, many studies use an imputed value for censored measurements (for example, replacing a value <L by L, or by L/2). Commonly, an analysis that ignores such imputation is then used. In clinical trials, this leads to bias and a loss of power in evaluating treatment effects. In this paper, a review of appropriate statistical methods for parametric and non-parametric analysis of such measurements is presented. This includes methods for situations in which baseline measurements are available. New results concerning design issues such as sample size determination are also presented. The paper is illustrated using two examples of studies that included censored measurements of viral load in HIV-infected subjects.

Biomarkers↗
PubMed1999

Measuring and modelling pollution for risk analysis.

The great scale and complexity of environmental risk analysis offers major methodological challenges to those engaged in policymaking. In this paper we describe some of those challenges from the perspective gained through our work at the University of British Columbia (UBC). We describe some of our experiences with respect to the difficult problems of formulating environmental standards and developing abatement strategies. A failed but instructive attempt to find support for experiments on a promising method of reducing acid rain will be described. Then we describe an approach to scenario analysis under hypothetical new standards. Even with measurements of ambient environmental conditions in hand the problem of inferring actual human exposures remains. For example, in very hot weather people will tend to stay inside and population levels of exposure to e.g. ozone could be well below those predicted by the ambient measurements. Setting air quality criteria should ideally recognize the discrepancies likely to arise. Computer models that incorporate spatial random pollution fields and predict actual exposures from ambient levels will be described. From there we turn to the statistical issues of measurement and modelling and some of the contributions in these areas by the UBC group and its partners elsewhere. In particular we discuss the problem of measurement error when non-linear regression models are used. We sketch our approach to imputing unmeasured predictors needed in such models, deferring details to references cited below. We describe in general terms how those imputed measurements and their errors can be accommodated within the framework of health impact analysis.

Air Pollution↗
PubMed2004

Assessing intrasample variation: analysis of Rapa Nui (Easter Island) museum cranial collections example.

Osteological studies both old and new have utilized various Polynesian cranial samples, individually or in combination, to assess the racial composition of prehistoric Polynesians as a group, with regards to other Pacific populations, or to represent the Polynesian peoples as a whole in various multivariate analyses of worldwide populations. However, few of these studies have assessed the degree of intrasample variation produced when data derived from skeletal samples from different Polynesian islands (populations) are pooled to represent "Polynesians" as a whole. A similar argument can be made when data derived from various museum skeletal samples of the same Polynesian population are pooled to produce a larger sample representing that particular Polynesian population (Murrill [1968] Cranial and postcranial skeletal remains from Easter Island; Minneapolis: University of Minnesota Press; Stefan [2002] Am. J. Phys. Anthropol. [Suppl.] 34:147). This study examined Easter Island crania curated at various museums in North America, South America, and Europe to assess whether significant differences exist among the museum collections of Rapa Nui (Easter Island) skeletal material. A NORM statistical program (Schafer and Olsen [1997] NORM, version 1.01; University Park: Pennsylvania State University) for multiple imputation of incomplete multivariate datasets was utilized to estimate missing data. A variance comparison method, which utilizes variance/covariance matrices derived from "hypothesis" and "baseline/reference" samples (Key and Jantz [1990] Hum. Evol. 5:457-469; Key and Jantz [1990] Am. J. Phys. Anthropol. 82:53-59) was used to compare the Rapa Nui museum samples. This method is designed to test whether variability in a "hypothesis" museum sample exceeds "normal within-group variability" represented by the "baseline/reference" sample. The method was applied to six Rapa Nui museum samples (AANMW, MNHN-KB, MNHN-NAE, NHM, MH, and AMNH). The results indicate that the museum "hypothesis," male and female samples, exhibited little intrasample variability from the "baseline/reference" sample (MAPSE), though the samples were collected at different times and by different individuals. These results show the ability of multiple imputation and variance comparison methodologies to predict missing variables while maintaining the inherent variance/covariance structure and to discriminate sample variation in artificially assembled samples.

Anthropology, Physical↗
PubMed2005

Presentation and analysis of data on radiographic outcome in clinical trials: experience from the TEMPO study.

OBJECTIVE: To evaluate different methods of presentation and analysis of radiographic data in a rheumatoid arthritis (RA) randomized controlled trial. METHODS: A double-blind randomized controlled trial including 682 patients with active RA who were treated with methotrexate, etanercept, or a combination of the 2 drugs was used for this study. Probability plots of the change from baseline to year 1 were produced to visualize progression, and were compared with usual descriptive statistics. The primary analysis of the trial (based on annualized actual mean change from baseline in total Sharp score at 1 year, using linear imputation) was challenged using various ways of handling missing information with alternative imputation methods, and by various statistical analyses including analysis of covariance (ANCOVA) and mixed model analysis on both raw and log-transformed data. RESULTS: Probability plots provided detailed insight into the differentiated treatment effects between the 3 arms of this study. As adjuncts to formal hypothesis testing, these plots were more useful for presenting data than were summary descriptive statistics or use of preset cutoff points to define lack of progression. Additional analyses presented here support the results obtained with the per-protocol analysis that showed an advantage of the combination treatment compared with the monotherapy arms and for etanercept versus methotrexate alone. Various ways of handling missing information confirmed the robustness of the results. In addition, both ANCOVA and mixed model analyses on raw and on log-transformed data produced similar results. CONCLUSION: We suggest a panel of alternative analysis methods and alternative ways of handling missing information to verify that the radiographic results reported in an randomized controlled trial are not influenced by technical factors, such as interpolation, handling of missing data, and choice of statistical tests.

Adult↗
PubMed2025

Genetic Architecture of Idiopathic Inflammatory Myopathies From Meta-Analyses.

OBJECTIVE: Idiopathic inflammatory myopathies (IIMs, myositis) are rare systemic autoimmune disorders that lead to muscle inflammation, weakness, and extramuscular manifestations, with a strong genetic component influencing disease development and progression. Previous genome-wide association studies identified loci associated with IIMs. In this study, we imputed data from two prior genome-wide myositis studies and analyzed the largest myositis data set to date to identify novel risk loci and susceptibility genes associated with IIMs and its clinical subtypes. METHODS: We performed association analyses on 14,903 individuals (3,206 patients and 11,697 controls) with genotypes and imputed data from the Trans-Omics for Precision Medicine reference panel. Fine-mapping and expression quantitative trait locus colocalization analyses in myositis-relevant tissues indicated potential causal variants. Functional annotation and network analyses using the random walk with restart (RWR) algorithm explored underlying genetic networks and drug repurposing opportunities. RESULTS: Our analyses identified novel risk loci and susceptibility genes, such as FCRLA, NFKB1, IRF4, DCAKD, and ATXN2 in overall IIMs; NEMP2 in polymyositis; ACBC11 in dermatomyositis; and PSD3 in myositis with anti-histidyl-transfer RNA synthetase autoantibodies (anti-Jo-1). We also characterized effects of HLA region variants and the role of C4. Colocalization analyses suggested putative causal variants in DCAKD in skin and muscle, HCP5 in lung, and IRF4 in Epstein-Barr virus (EBV)-transformed lymphocytes, lung, and whole blood. RWR further prioritized additional candidate genes, including APP, CD74, CIITA, NR1H4, and TXNIP, for future investigation. CONCLUSION: Our study uncovers novel genetic regions contributing to IIMs, advancing our understanding of myositis pathogenesis and offering new insights for future research.

Humans↗
PubMed2002

The economic burden of prostate cancer, California, 1998.

BACKGROUND: Prostate cancer is the most common malignancy diagnosed among men in the United States. This article reviews previous studies of the annual cost of all cancers and of prostate cancer in the United States and California and estimates the direct and indirect costs of prostate cancer in California in 1998. METHODS: Hospitalization costs, including costs of primary and secondary diagnoses of prostate cancer, were derived from the California Hospital Discharge data set (CHDS). Charges were converted to costs using hospital specific cost-to-charge ratios and an imputed cost for Health Maintenance Organization hospitalizations. Other direct medical costs were derived from the 1997 Medical Expenditure Panel Survey. Indirect mortality costs are the product of the number of deaths and the expected value of a male's future earnings taking into account age at death, earning patterns at successive ages, labor force participation, imputed value of housekeeping services, and a 3% discount rate. RESULTS: Prostate cancer direct health care costs in California were estimated at 180 million dollars, and lost productivity from premature death was estimated at 180 million dollars, for a total cost of 360 million dollars in 1998. The disease is largely one of older men; hospitalization costs account for three-fifths of total direct costs, and Medicare and private health insurance share almost equally in paying for hospital care. CONCLUSIONS: It is critical to identify cost-effective screening efforts that permit early detection of prostate cancer to reduce illness, premature deaths, and the high costs of prostate cancer.

Adolescent↗
PubMed1976

Afferents to the cerebellar lateral nucleus. Evidence from retrograde transport of horseradish peroxidase after pressure injections through micropipettes.

HRP was injected by pressure from glass capillary micropipettes unilaterally into the lateral nucleus of rat so as to encompass the entire nucleus, but without spread into the interpositus nuclei. The cells of origin of the afferents to the lateral nucleus were studied after retrograde transport of the HRP. The reticulotegmental nucleus of the pons was labelled bilaterally and is the major source of crossed and uncrossed reticular imputs. The pontine nuclei also provide extensive crossed and uncrossed afferents. The inferior olive gives a large crossed olivo-lateral nucleus projection and a minor uncrossed input. The trigeminal nuclear complex--the nucleus of the spinal tract and the mesencephalic, principal sensory, and motor nuclei--all provide uncrossed afferents. The rostral portion of the lateral reticular nucleus gives a small crossed and uncrossed projection while the perihypoglossal nuclei and the dorsal parabrachial body give crossed afferents to the lateral nucleus. The norepinephrine afferent system from the locus coeruleus is represented by one or two heavily labelled cells and the serotonin raphe systems come from at least five raphe subgroups, the dorsal, superior centralis, pontis, obscurus and magnus nuclei. No evidence was found for commissural fibers between ipsilateral or contralateral cerebellar nuclei, or afferent axons from the spinocerebellar nuclei and the paramedian retricular nucleus. The significance of these sources of afferent imputs to the lateral cerebellar nucleus is discussed. The question is raised of the direct relationship between size of terminal axonal arborization and the quantity of HRP granules present in a cell retrograde transport. The limitations of the HRP method for detecting subtle local differences in the distribution of afferents within the heterogeneous groups of neurons in the lateral nucleus are discussed.

Animals↗
PubMed2004

Conditional multipoint linkage analysis using affected sib pairs: an alternative approach.

Recently, Liang et al. ([2001b] Genet. Epidemiol. 21:105-122) proposed a conditional approach to assess linkage evidence on the target region by incorporating linkage information from an unlinked (reference) region using allele shared IBD (identity-by-decent) from affected sib pairs. This is carried out by conditioning on the IBD sharing value at the estimated trait locus of the reference region. Since markers considered are typically non-fully informative, the IBD sharing at each marker needs to be estimated (or imputed). In this report, we propose an alternative approach to deal with the IBD sharing in the reference region. This new approach makes full use of the observed data without having to categorize the imputed IBD sharing as needed in Liang et al. ([2001b] Genet. Epidemiol. 21:105-122). We compare these two approaches by simulating data from a variety of two-locus models including heterogeneity, additive and multiplicative with either fully informative markers or non-fully informative markers. The performance of both approaches is quite comparable showing consistent estimates of the trait locus and key genetic parameters.

Alleles↗
PubMed2006

A mixed logit model of health care provider choice: analysis of NSS data for rural India.

In order to address the persistent problems of access to and delivery of health care in rural India, a better understanding of the individual provider choice decision is required. This paper is an attempt in this direction as it investigates the determinants of outpatient health care provider choice in rural India in the mixed multinomial logit (MMNL) framework. This is the first application of the mixed logit to the modeling of health care utilization. We also use the multiple imputation technique to impute the missing prices of providers that an individual did not visit when she was ill. Using data from National Sample Survey Organization of India, we find the following: price and distance to a health facility play significant roles in health care provider choice decision; when health status is poor, distance plays a less significant role in an adult's provider choice decision; price elasticity of demand for outpatient care varies with income, with low-income groups being more price-sensitive than high-income ones. Furthermore, outpatient care for children is more price-elastic than that for adults, which reflects the socio-economic structure of a typical household in rural India where an adult's health is more important than that of a child for the household's economic sustenance.

Choice Behavior↗
PubMed2003

Design and analysis of unit cost estimation studies: How many hospital diagnoses? How many countries?

We evaluated three questions that commonly arise when unit costing exercises for multinational trials are conducted: (1). In countries where investigators plan to collect hospital unit cost estimates for a selected set of diagnoses, how should one estimate unit costs for the remaining diagnoses observed in the trial for which cost data were not collected? (2). For how many hospital diagnoses should estimates be obtained? (3). For how many countries should they be obtained? We addressed these questions using unit cost data collected in four western European countries and three relative value measures from the US Medicare diagnosis-related group (DRG) payment system. We found that the arithmetic mean length of stay from the US DRG payment system was a good predictor of unit costs in four countries in Europe. We also found that the imputation error decreased as the number of hospital diagnoses and countries sampled increased, but that the rate of reduction in error shrank. Finally, we found that - given the existence of a reliable method for cost imputation - from a pure information standpoint, it is better to obtain estimates for fewer hospital diagnoses from more countries than the reverse.

Costs and Cost Analysis↗
PubMed2005

The analysis of incomplete cost data due to dropout.

Incomplete data due to premature withdrawal (dropout) constitute a serious problem in prospective economic evaluations that has received only little attention to date. The aim of this simulation study was to investigate how standard methods for dealing with incomplete data perform when applied to cost data with various distributions and various types of dropout. Selected methods included the product-limit estimator of Lin et al. the expectation maximisation (EM-) algorithm, several types of multiple imputation (MI) and various simple methods like complete case analysis and mean imputation. Almost all methods were unbiased in the case of dropout completely at random (DCAR), but only the product-limit estimator, the EM-algorithm and the MI approaches provided adequate estimates of the standard error (SE). The best estimates of the mean and SE for dropout at random (DAR) were provided by the bootstrap EM-algorithm, MI regression and MI Monte Carlo Markov chain. These methods were able to deal with skewed cost data in combination with DAR and only became biased when costs also included the costs of expensive events. None of the methods were able to deal adequately with informative dropout. In conclusion, the EM-algorithm with bootstrap, MI regression and MI MCMC are robust to the multivariate normal assumption and are the preferred methods for the analysis of incomplete cost data when the assumption of DCAR is not justified.

Algorithms↗
PubMed1989

Reversibility and prevention of intraspinal peptidergic loss caused by sciatic nerve lesions.

We have investigated the reversibility and prevention of peptidergic losses in the lumbar spinal cord caused by permanent resection of sciatic nerve. The lesion triggers a series of degenerative events involving the substance P sensory imput as well as met-enkephalin interneurons of the substantia gelatinosa. The degenerative processes are evident 10 days after sciatic nerve lesion and are gradually reversible as shown by radioimmunoassay and quantitative immunocytochemistry. Recovery begins 30 days postlesioning and full restoration is observed at 90 days. Serotonin (5-HT) turnover is markedly affected by sciatic nerve lesion as soon as 24 hr postlesioning, when 5-HT metabolism is enhanced, returning to control levels just preceding the peptide alterations; 5-HT metabolism then undergoes a transient period of hypoactivity which correlates with the beginning of the peptidergic restorative processes. Altogether these results, with previous observations showing that 5-HT depletion prevents metenkephalin interneurons degeneration triggered by the lesion (Di Giulio et al.: J Neurosci Res 18:443-448, 1987), suggest a role for 5-HT in the synaptic plasticity of the substantia gelatinosa of the spinal cord. The administration of gangliosides (10 or 50 mg/kg) to sciatic-nerve-lesioned animals fully prevented the metenkephalinergic degeneration without affecting the degenerative atrophy of the lesioned substance P sensory imput.

Animals↗