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Control Data (control + data)
Selected AbstractsAnalysis of Matched Case,Control Data in Presence of Nonignorable Missing ExposureBIOMETRICS, Issue 1 2008Samiran Sinha Summary. The present article deals with informative missing (IM) exposure data in matched case,control studies. When the missingness mechanism depends on the unobserved exposure values, modeling the missing data mechanism is inevitable. Therefore, a full likelihood-based approach for handling IM data has been proposed by positing a model for selection probability, and a parametric model for the partially missing exposure variable among the control population along with a disease risk model. We develop an EM algorithm to estimate the model parameters. Three special cases: (a) binary exposure variable, (b) normally distributed exposure variable, and (c) lognormally distributed exposure variable are discussed in detail. The method is illustrated by analyzing a real matched case,control data with missing exposure variable. The performance of the proposed method is evaluated through simulation studies, and the robustness of the proposed method for violation of different types of model assumptions has been considered. [source] Conditional Likelihood Methods for Haplotype-Based Association Analysis Using Matched Case,Control DataBIOMETRICS, Issue 4 2007Jinbo Chen Summary Genetic epidemiologists routinely assess disease susceptibility in relation to haplotypes, that is, combinations of alleles on a single chromosome. We study statistical methods for inferring haplotype-related disease risk using single nucleotide polymorphism (SNP) genotype data from matched case,control studies, where controls are individually matched to cases on some selected factors. Assuming a logistic regression model for haplotype-disease association, we propose two conditional likelihood approaches that address the issue that haplotypes cannot be inferred with certainty from SNP genotype data (phase ambiguity). One approach is based on the likelihood of disease status conditioned on the total number of cases, genotypes, and other covariates within each matching stratum, and the other is based on the joint likelihood of disease status and genotypes conditioned only on the total number of cases and other covariates. The joint-likelihood approach is generally more efficient, particularly for assessing haplotype-environment interactions. Simulation studies demonstrated that the first approach was more robust to model assumptions on the diplotype distribution conditioned on environmental risk variables and matching factors in the control population. We applied the two methods to analyze a matched case,control study of prostate cancer. [source] The Mainz Severity Score Index: a new instrument for quantifying the Anderson,Fabry disease phenotype, and the response of patients to enzyme replacement therapyCLINICAL GENETICS, Issue 4 2004C Whybra Anderson,Fabry disease (AFD) is an X-linked disorder caused by deficient activity of the lysosomal enzyme ,-galactosidase A. The availability of enzyme replacement therapy (ERT) for this debilitating condition has led to the need for a convenient and sensitive instrument to monitor clinical effects in an individual patient. This study aimed to develop a scoring system , the Mainz Severity Score Index (MSSI) , to measure the severity of AFD and to monitor the clinical course of the disease in response to ERT. Thirty-nine patients (24 males and 15 females) with AFD were assessed using the MSSI immediately before and 1 year after commencing agalsidase alfa ERT. Control data were obtained from 23 patients in whom AFD was excluded. The MSSI of patients with AFD was significantly higher than that of patients with other severe debilitating diseases. The MSSI indicated that, although more men than women had symptoms classified as severe, overall, the median total severity scores were not significantly different between male and female patients. One year of ERT with agalsidase alfa led, in all patients, to a significant (p < 0.001) reduction in MSSI score (by a median of nine points). This study has shown that the MSSI score may be a useful, specific measure for objectively assessing the severity of AFD and for monitoring ERT-related treatment effects. [source] An adaptive clinical Type 1 diabetes control protocol to optimize conventional self-monitoring blood glucose and multiple daily-injection therapyINTERNATIONAL JOURNAL OF ADAPTIVE CONTROL AND SIGNAL PROCESSING, Issue 5 2009Xing-Wei Wong Abstract The objective of this study was to develop a safe, robust and effective protocol for the clinical control of Type 1 diabetes using conventional self-monitoring blood glucose (SMBG) measurements, and multiple daily injection (MDI) with insulin analogues. A virtual patient method is used to develop an in silico simulation tool for Type 1 diabetes using data from a Type 1 diabetes patient cohort (n=40) . The tool is used to test two prandial insulin protocols, an adaptive protocol (AC) and a conventional intensive insulin therapy (IIT) protocol (CC) against results from a representative control cohort as a function of SMBG frequency. With the prandial protocols, optimal and suboptimal basal insulin replacement using a clinically validated, forced-titration regimen is also evaluated. A Monte Carlo (MC) analysis using variability and error distributions derived from the clinical and physiological literature is used to test efficacy and robustness. MC analysis is performed for over 1 400 000 simulated patient hours. All results are compared with control data from which the virtual patients were derived. In conditions of suboptimal basal insulin replacement, the AC protocol significantly decreases HbA1c for SMBG frequencies ,6/day compared with controls and the CC protocol. With optimal basal insulin, mild and severe hypoglycaemia is reduced by 86,100% over controls for all SMBG frequencies. Control with the CC protocol and suboptimal basal insulin replacement saturates at an SMBG frequency of 6/day. The forced-titration regimen requires a minimum SMBG frequency of 6/day to prevent increased hypoglycaemia. Overaggressive basal dose titration with the CC protocol at lower SMBG frequencies is likely caused by uncorrected postprandial hyperglycaemia from the previous night. From the MC analysis, a defined peak in control is achieved at an SMBG frequency of 8/day. However, 90% of the cohort meets American Diabetes Association recommended HbA1c with just 2 measurements a day. A further 7.5% requires 4 measurements a day and only 2.5% (1 patient) required 6 measurements a day. In safety, the AC protocol is the most robust to applied MC error. Over all SMBG frequencies, the median for severe hypoglycaemia increases from 0 to 0.12% and for mild hypoglycaemia by 0,5.19% compared with the unrealistic no error simulation. While statistically significant, these figures are still very low and the distributions are well below those of the controls group. An adaptive control protocol for Type 1 diabetes is tested in silico under conditions of realistic variability and error. The adaptive (AC) protocol is effective and safe compared with conventional IIT (CC) and controls. As the fear of hypoglycaemia is a large psychological barrier to appropriate glycaemic control, adaptive model-based protocols may represent the next evolution of IIT to deliver increased glycaemic control with increased safety over conventional methods, while still utilizing the most commonly used forms of intervention (SMBG and MDI). The use of MC methods to evaluate them provides a relevant robustness test that is not considered in the no error analyses of most other studies. Copyright © 2008 John Wiley & Sons, Ltd. [source] Proton MR spectroscopic imaging of the medulla and cervical spinal cord,JOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 4 2007Richard A.E. Edden PhD Abstract Purpose To demonstrate the feasibility of quantitative, one-dimensional proton MR spectroscopic imaging (1D-MRSI) of the upper cervical spine and medulla at 3.0 Tesla. Materials and Methods A method was developed for 1D-point-resolved spectroscopy sequence (PRESS)-MRSI, exciting signal in five voxels extending from the pontomedullary junction to the level of the C3 vertebra, and performed in 10 healthy volunteers to generate control data. Results High-resolution 1D-MRSI data were obtained from all 10 subjects. Upper cervical spine concentrations of choline, creatine, and N-acetyl aspartate were estimated to be 2.8 ± 0.5, 8.8 ± 1.8, and 10.9 ± 2.7 mM, respectively, while in the medulla they were 2.6 ± 0.5, 9.1 ± 1.7, and 10.8 ± 0.9 mM. Conclusion Quantitative 1D-MRSI of the upper cervical spine has been shown to be feasible at 3.0 Tesla. J. Magn. Reson. Imaging 2007;26:1101,1105. © 2007 Wiley-Liss, Inc. [source] Curing dyslexia and attention-deficit hyperactivity disorder by training motor co-ordination: Miracle or myth?JOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 10 2007Dorothy VM Bishop Abstract: Dore Achievement Centres are springing up world-wide with a mission to cure cerebellar developmental delay, thought to be the cause of dyslexia, attention-deficit hyperactivity disorder, dyspraxia and Asperger's syndrome. Remarkable success is claimed for an exercise-based treatment that is designed to accelerate cerebellar development. Unfortunately, the published studies are seriously flawed. On measures where control data are available, there is no credible evidence of significant gains in literacy associated with this intervention. There are no published studies on efficacy with the clinical groups for whom the programme is advocated. It is important that family practitioners and paediatricians are aware that the claims made for this expensive treatment are misleading. [source] Skin permeability enhancement by low frequency sonophoresis: Lipid extraction and transport pathwaysJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 6 2003R. Alvarez-Román Abstract The objective of this study was to shed light on the mechanism(s) by which low-frequency ultrasound (20 KHz) enhances the permeability of the skin. The physical effects on the barrier and the transport pathway, in particular, were examined. The amount of lipid removed from the intercellular domains of the stratum corneum following sonophoresis was determined by infrared spectroscopy. Transport of the fluorescent probes nile red and calcein, under the influence of ultrasound, was evaluated by laser-scanning confocal microscopy. The results were compared with the appropriate passive control data and with data obtained from experiments in which the skin was exposed simply to the thermal effects induced by ultrasound treatment. A significant fraction (,30%) of the intercellular lipids of the stratum corneum, which are principally responsible for skin barrier function, were removed during the application of low-frequency sonophoresis. Although the confocal images from the nile red experiments were not particularly informative, ultrasound clearly and significantly (again, relative to the corresponding controls) facilitated transport of the hydrophilic calcein via discrete permeabilized regions, whereas other areas of the barrier were apparently unaffected. Lipid removal from the stratum corneum is implicated as a factor contributing the observed permeation enhancement effects of low-frequency ultrasound. However, microscopic observations imply that sonophoresis induces localized (aqueous?) permeation pathways at discrete sites. © 2003 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 92:1138,1146, 2003 [source] Bayesian incidence analysis of animal tumorigenicity dataJOURNAL OF THE ROYAL STATISTICAL SOCIETY: SERIES C (APPLIED STATISTICS), Issue 2 2001D. B. Dunson Statistical inference about tumorigenesis should focus on the tumour incidence rate. Unfortunately, in most animal carcinogenicity experiments, tumours are not observable in live animals and censoring of the tumour onset times is informative. In this paper, we propose a Bayesian method for analysing data from such studies. Our approach focuses on the incidence of tumours and accommodates occult tumours and censored onset times without restricting tumour lethality, relying on cause-of-death data, or requiring interim sacrifices. We represent the underlying state of nature by a multistate stochastic process and assume general probit models for the time-specific transition rates. These models allow the incorporation of covariates, historical control data and subjective prior information. The inherent flexibility of this approach facilitates the interpretation of results, particularly when the sample size is small or the data are sparse. We use a Gibbs sampler to estimate the relevant posterior distributions. The methods proposed are applied to data from a US National Toxicology Program carcinogenicity study. [source] Signal generation and clarification: use of case,control dataPHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 3 2001David W. Kaufman ScD Abstract Case-control surveillance systems are useful for ,signal' generation, i.e., signaling potential previously unidentified adverse effects of drugs. Two systems currently in operation, the Slone Epidemiology Unit's Case-Control Surveillance and the Birth Defects Study, have monitored drug effects since 1976. With extensive information on the diagnoses and covariates, the systems have the capacity to carry out in-depth analyses in which the outcome measure is more specifically defined and in which confounding is controlled, thus reducing the possibility of false alarms. Copyright © 2001 John Wiley & Sons, Ltd. [source] Procedural considerations for photographic-based joint angle measurementsPHYSIOTHERAPY RESEARCH INTERNATIONAL, Issue 4 2005Colin Dunlevy Abstract Background and Purpose Measuring static joint angles is important to clinicians involved in assessing, diagnosing and treating musculoskeletal disorders. Ne measurement techniques such as the Uillinn Method © (UM) employ the relatively new technology of digital photography and software to form a virtual goniometer. It is of central importance that the errors associated such new measurement techniques are known. Precision in joint angle measurement is a challenge and errors can arise from three separate categories: equipment error, examiner error or biological error. The aim of the present study was to discover the amount of equipment error associated with the UM and to present guidelines for the optimal use of a photographic based measurement technique Method This was a non-clinical agreement study design that attempted to describe the best possible agreement between a mathematical control dataset and the angles calculated from the virtual goniometer, which in this case was the UM. When this was established, the effect of rotation and placing the angle at the periphery of the camera's field of view were tested. Results The repeatability coefficient (RC) between the UM and the control data under optimal conditions was 0.81°; the typical error (TE) was 0.29° (n = 120). When the angle appeared at the edge of the photograph the RC increased to 2° and the TE to 0.73° (n = 48). When 5° rotation was introduced between the camera and the angle no increase in error was detected. However, increasing amounts of rotation above 5° was proportional to increases in the RC (RC at 10° = 2.3°; 20° = 3.86°; 30° = 14.8°; 40° = 27.27°) and the TE (TE at 10° = 0.83°; 20° = 2.7°; 30° = 5.3°; 40° = 9.8°) scores. Conclusion Photographic-based joint angle measurement techniques are subject to error if careful procedures are not observed. Best procedures include photography from a perpendicular viewpoint and centring the lens on the target angle. Copyright © 2005 John Wiley & Sons, Ltd. [source] Parents' safety beliefs and childhood agricultural injuryAMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 9 2009Muree Larson-Bright PhD Abstract Background This study examined potential associations between parental safety beliefs and children's chore assignments or risk of agricultural injury. Methods Analyses were based on nested case,control data collected by the 1999 and 2001 Regional Rural Injury Study-II (RRIS-II) surveillance efforts. Cases (n,=,425, reporting injuries) and controls (n,=,1,886, no injuries; selected using incidence density sampling) were persons younger than 20 years of age from Midwestern agricultural households. A causal model served as the basis for multivariate data analysis. Results Decreased risks of injury (odds ratio [OR] and 95% confidence intervals [CI]) were observed for working-aged children with "moderate," compared to "very strict" parental monitoring (0.60; 0.40,0.90), and with parents believing in the importance of physical (0.80; 0.60,0.95) and cognitive readiness (0.70, 0.50,0.90, all children; 0.30, 0.20,0.50, females) when assigning new tasks. Parents' safety beliefs were not associated with chore assignments. Conclusions Parents' safety beliefs were associated with reduced risk of childhood agricultural injury; the association was not mediated by chore assignments. Am. J. Ind. Med. Am. J. Ind. Med. 52:724,733, 2009. © 2009 Wiley-Liss, Inc. [source] Latest news and product developmentsPRESCRIBER, Issue 7 2007Article first published online: 11 JUL 200 Poor asthma control with off-licence prescribing Children who are prescribed off-licence medications are more likely to have poor asthma control, according to an analysis from Dundee (Br J Gen Practice 2007;57:220-2). The review of 17 163 consultations identified 1050 (6.1 per cent) who received a prescription for an unlicensed use (defined as not licensed for children or the particular age group, or dose not licensed). High doses (4.5 per cent) were more frequent than unlicensed indications (1.9 per cent). Children who received off-label prescriptions reported statistically significantly more symptoms in the day or night, symptoms during activity, and increased use of daily short-acting beta2-agonists. The authors note that off-label prescribing appears to be increasing. Atkins diet most effective over one year? The ultra low-carbohydrate, high-protein Atkins diet achieved greater weight loss than other popular diets in overweight women over one year, say US investigators (J Am Med Assoc 2007;297:969-77). The study compared the Atkins diet with three diets designed as low- or very high-carbohydrate, or based on USA nutritional guidance, in 311 women with body mass index 27-40. After one year, mean weight loss was 4.7kg with the Atkins diet , significantly greater than with the low- carbohydrate diet (1.6kg) but not compared with very high-carbohydrate (2.2kg) or the nutrition-based diet (2.6kg). Metabolic endpoints were comparable or more favourable in women using the Atkins diet. Androgen therapy linked to gum disease The majority of men treated with androgen deprivation therapy for prostate cancer are more likely to have periodontal disease (J Urol 2007;177:921-4). After controlling for risk factors, the prevalence of periodontal disease was 80.5 per cent among treated men compared with 3.7 per cent in matched controls not receiving treatment. There was no difference in bone mineral density between the groups but plaque scores were significantly higher among treated men. Food Commission rebuts MHRA on additives An independent watchdog has not accepted the MHRA's justification for including certain additives in medicines for children. The Food Commission (www.foodcomm.org.uk) found that most medicines for children contained additives, some of which , including azo dyes and benzoates , are not permitted in food. The Commission called on the pharmaceutical industry to stop using ,questionable additives'. The MHRA stated that the licensing process takes into account the likely exposure to excipients that are considered essential to make medicines palatable to children. Colouring helps children to identify the correct medicine, and preservatives ensure a reasonable shelf-life. A list of additives is included in the product's summary of product characteristics and patient information leaflet. In response, the Commission states: , , it is quite possible to flavour medicines with natural oils or extracts, and natural colourings such as beetroot and beta-carotene can be used instead of azo dyes. If parents were advised to give these medicinal products at mealtimes the manufacturers could also add a little sugar to sweeten their products, rather than relying on artificial sweeteners.' All triptans the same? There is no economic case for choosing one triptan over another and no evidence for preferring a particular triptan for adults, a systematic review has concluded. The Canadian Agency for Drugs and Technologies in Health (www.cadth.ca) found that published trials had compared most triptans with sumatriptan but not with one another, and most economic evaluations were flawed. New drug for HIV Janssen-Cilag has introduced darunavir (Prezista), a new protease inhibitor for the treatment of HIV infection. Licensed for highly pre- treated patients in whom more than one other pro- tease inhibitor regimen has failed, darunavir must be co-administered with ritonavir (Norvir). A month's treatment at the recommended dose of 600mg twice daily costs £446.70. Variation in liquid captopril for children The NHS uses a wide range of liquid formulations of captopril to treat children with heart failure , with no assurance of their bioequivalence (Arch Dis Child 2007; published online 15 March. doi: 10.1136/adc.2006.109389). Specialists in Leicester surveyed 13 tertiary paediatric cardiac centres and 13 hospitals that referred patients to them. Only three tertiary centres supplied the same liquid for-mulation of captopril as their referring hospitals. Four hospitals supplied tablets for crushing and dissolving in water; the other hospitals and centres used a total of nine different formulations. The authors say the formulations had widely varying shelf-lives, determined empirically in all but one case, and were used interchangeably despite a lack of quality control data to establish their bioequivalence. QOF CVD targets not good enough for GPs Two-thirds of GPs want Quality Outcome Framework (QOF) targets for cardiovascular disease brought into line with those of the Joint British Societies latest guidance (JBS2), according to a survey by doctor.net.uk. The survey of 1000 GPs showed that 88 per cent were aware of the JBS2 guidelines and most were already implementing the targets for lipids, blood pressure and blood glucose in some form; however, only 55 per cent were implementing the JBS2 obesity target and 14 per cent were implementing screening for the over-40s. The JBS2 target for lipids in at-risk patients is <4mmol per litre total cholesterol and <2 mmol per litre LDL-cholesterol, compared with <5 and <3mmol per litre respectively in QOF and the NSF. The survey was commissioned by Merck Sharp & Dohme and Schering- Plough. Fracture warning Following warnings in the US that rosiglitazone (Avandia) is associated with an increased risk of fractures in women, Takeda has advised prescribers that pioglitazone (Actos) carries a similar risk. An analysis of the company's clinical trials database has revealed an excess risk of fractures of bones below the elbow and knee. The incidence was similar to the excess risk associated with rosiglitazone and also confined to women. Scottish approvals The Scottish Medicines Consortium (www.scottish medicines.org.uk) has approved for use within NHS Scotland the sublingual tablet formulation buprenorphine/naloxone (Suboxone) for the treatment of opioid dependence. It has also approved the combined formulation of valsartan and amlodipine (Exforge) and the restricted use of the If inhibitor ivabradine (Procoralan). [source] Influence of sudden changes in management program on physiological and behavioral parameters in hensANIMAL SCIENCE JOURNAL, Issue 3 2004Ashraf M. KHALIL ABSTRACT The present study was designed to test the effects of sudden changes of food access and light duration on the physiological and behavioral parameters of hens. The physiological parameters investigated were heart rate (HR), body temperature (BT), and locomotor activity (LA) using a radiotelemetry system. After implantation of the telemetry transmitters, six hens were housed individually in cages under constant environmental conditions for 10 days with a photoperiod of 15 h light (04.00,19.00 hours), and food was available ad libitum at all times. After that, the same hens were subjected to a feed withdrawal trial, from 12.00 to 08.30 hours, followed by a lighting hour reduction trial by changing the time of lights-off from 19.00 to 14.00 hours. The physiological and behavioral data were recorded for 2 days before each trial, as control data. With the feed withdrawal trial, during the light and dark periods, HR and BT were significantly lower in the hens without food access than in the control. Whereas, LA was significantly lower only during the light period in the hens without food access than in the control. Further, the time spent resting increased significantly, but the time spent feeding decreased significantly in the hens without food access than in the control. Also, the number of times the cage was pecked and pecking of the feeder occured at a significantly higher level, while the number of times beaks were wiped occured at a significantly lower level in the hens without food access than in the control. With the lighting hour reduction trial, during the light period, HR and BT were significantly higher, whereas LA was significantly lower in the 'sudden light-off' treated hens than in the control. In addition, during the dark period, HR, BT and LA were significantly higher in the sudden light-off treated hens than in the control. Moreover, in the sudden light-off treated hens, the time spent preening and feeding decreased significantly, but the time spent resting increased significantly than in the control. It is concluded that sudden changes in a management program might result in many significant differences as were found in the physiological and behavioral parameters of hens in the present study. [source] Identification of a novel susceptibility locus for juvenile idiopathic arthritis by genome-wide association analysisARTHRITIS & RHEUMATISM, Issue 1 2009Anne Hinks Objective Juvenile idiopathic arthritis (JIA) is a chronic rheumatic disease of childhood. Two well-established genetic factors known to contribute to JIA susceptibility, HLA and PTPN22, account for less than half of the genetic susceptibility to disease; therefore, additional genetic factors have yet to be identified. The purpose of this study was to perform a systematic search of the genome to identify novel susceptibility loci for JIA. Methods A genome-wide association study using Affymetrix GeneChip 100K arrays was performed in a discovery cohort (279 cases and 184 controls). Single-nucleotide polymorphisms (SNPs) showing the most significant differences between cases and controls were then genotyped in a validation sample of cases (n = 321) and controls, combined with control data from the 1958 UK birth cohort (n = 2,024). In one region in which association was confirmed, fine-mapping was performed (654 cases and 1,847 controls). Results Of the 112 SNPs that were significantly associated with JIA in the discovery cohort, 6 SNPs were associated with JIA in the independent validation cohort. The most strongly associated SNP mapped to the HLA region, while the second strongest association was with a SNP within the VTCN1 gene. Fine-mapping of that gene was performed, and 10 SNPs were found to be associated with JIA. Conclusion This study is the first to successfully apply a SNP-based genome-wide association approach to the investigation of JIA. The replicated association with markers in the VTCN1 gene defined an additional susceptibility locus for JIA and implicates a novel pathway in the pathogenesis of this chronic disease of childhood. [source] Carcinogenicity study of GSM and DCS wireless communication signals in B6C3F1 miceBIOELECTROMAGNETICS, Issue 3 2007Thomas Tillmann Abstract The purpose of this study using a total of 1170 B6C3F1 mice was to detect and evaluate possible carcinogenic effects in mice exposed to radio-frequency-radiation (RFR) from Global System for Mobile Communication (GSM) and Digital Personal Communications System (DCS) handsets as emitted by handsets operating in the center of the communication band, that is, at 902 MHz (GSM) and 1747 MHz (DCS). Restrained mice were exposed for 2 h per day, 5 days per week over a period of 2 years to three different whole-body averaged specific absorption rate (SAR) levels of 0.4, 1.3, 4.0 mW/g bw (SAR), or were sham exposed. Regarding the organ-related tumor incidence, pairwise Fisher's test did not show any significant increase in the incidence of any particular tumor type in the RF exposed groups as compared to the sham exposed group. Interestingly, while the incidences of hepatocellular carcinomas were similar in EMF and sham exposed groups, in both studies the incidences of liver adenomas in males decreased with increasing dose levels; the incidences in the high dose groups were statistically significantly different from those in the sham exposed groups. Comparison to published tumor rates in untreated mice revealed that the observed tumor rates were within the range of historical control data. In conclusion, the present study produced no evidence that the exposure of male and female B6C3F1 mice to wireless GSM and DCS radio frequency signals at a whole body absorption rate of up to 4.0 W/kg resulted in any adverse health effect or had any cumulative influence on the incidence or severity of neoplastic and non-neoplastic background lesions, and thus the study did not provide any evidence of RF possessing a carcinogenic potential. Bioelectromagnetics 28:173,187, 2007. © 2006 Wiley-Liss, Inc. [source] Impact of Population Substructure on Trend Tests for Genetic Case,Control Association StudiesBIOMETRICS, Issue 1 2010Gang Zheng Summary Hidden population substructure in case,control data has the potential to distort the performance of Cochran,Armitage trend tests (CATTs) for genetic associations. Three possible scenarios that may arise are investigated here: (i) heterogeneity of genotype frequencies across unidentified subpopulations (PSI), (ii) heterogeneity of genotype frequencies and disease risk across unidentified subpopulations (PSII), and (iii) cryptic correlations within unidentified subpopulations. A unified approach is presented for deriving the bias and variance distortion under the three scenarios for any CATT in a general family. Using these analytical formulas, we evaluate the excess type I errors of the CATTs numerically in the presence of population substructure. Our results provide insight into the properties of some proposed corrections for bias and variance distortion and show why they may not fully correct for the effects of population substructure. [source] A Flexible Approach to Measurement Error Correction in Case,Control StudiesBIOMETRICS, Issue 4 2008A. Guolo Summary We investigate the use of prospective likelihood methods to analyze retrospective case,control data where some of the covariates are measured with error. We show that prospective methods can be applied and the case,control sampling scheme can be ignored if one adequately models the distribution of the error-prone covariates in the case,control sampling scheme. Indeed, subject to this, the prospective likelihood methods result in consistent estimates and information standard errors are asymptotically correct. However, the distribution of such covariates is not the same in the population and under case,control sampling, dictating the need to model the distribution flexibly. In this article, we illustrate the general principle by modeling the distribution of the continuous error-prone covariates using the skewnormal distribution. The performance of the method is evaluated through simulation studies, which show satisfactory results in terms of bias and coverage. Finally, the method is applied to the analysis of two data sets which refer, respectively, to a cholesterol study and a study on breast cancer. [source] Exploiting Gene-Environment Independence for Analysis of Case,Control Studies: An Empirical Bayes-Type Shrinkage Estimator to Trade-Off between Bias and EfficiencyBIOMETRICS, Issue 3 2008Bhramar Mukherjee Summary Standard prospective logistic regression analysis of case,control data often leads to very imprecise estimates of gene-environment interactions due to small numbers of cases or controls in cells of crossing genotype and exposure. In contrast, under the assumption of gene-environment independence, modern "retrospective" methods, including the "case-only" approach, can estimate the interaction parameters much more precisely, but they can be seriously biased when the underlying assumption of gene-environment independence is violated. In this article, we propose a novel empirical Bayes-type shrinkage estimator to analyze case,control data that can relax the gene-environment independence assumption in a data-adaptive fashion. In the special case, involving a binary gene and a binary exposure, the method leads to an estimator of the interaction log odds ratio parameter in a simple closed form that corresponds to an weighted average of the standard case-only and case,control estimators. We also describe a general approach for deriving the new shrinkage estimator and its variance within the retrospective maximum-likelihood framework developed by Chatterjee and Carroll (2005, Biometrika92, 399,418). Both simulated and real data examples suggest that the proposed estimator strikes a balance between bias and efficiency depending on the true nature of the gene-environment association and the sample size for a given study. [source] Analysis of Matched Case,Control Data in Presence of Nonignorable Missing ExposureBIOMETRICS, Issue 1 2008Samiran Sinha Summary. The present article deals with informative missing (IM) exposure data in matched case,control studies. When the missingness mechanism depends on the unobserved exposure values, modeling the missing data mechanism is inevitable. Therefore, a full likelihood-based approach for handling IM data has been proposed by positing a model for selection probability, and a parametric model for the partially missing exposure variable among the control population along with a disease risk model. We develop an EM algorithm to estimate the model parameters. Three special cases: (a) binary exposure variable, (b) normally distributed exposure variable, and (c) lognormally distributed exposure variable are discussed in detail. The method is illustrated by analyzing a real matched case,control data with missing exposure variable. The performance of the proposed method is evaluated through simulation studies, and the robustness of the proposed method for violation of different types of model assumptions has been considered. [source] An alternative design for small-scale school health experiments: does daily walking produce benefits in physical performance of school children?CHILD: CARE, HEALTH AND DEVELOPMENT, Issue 6 2009E. Mønness Abstract Background The mainstream randomized clinical trial is not always feasible in a school setting. There might be practical and ethical issues that make dividing school classes into an intervention and a control group impossible or undesirable, and there is a need to explore the validity of alternative designs and analyses. Methods An alternative to a randomized clinical trial in a physical performance experiment at a school is introduced and evaluated. The before-intervention data are utilized as control data for the intervention data in addition to adjust for pre-intervention differences. The strict class year structure of school data makes this possible. In a rural school in inland Norway, all school children joined the project of walking in a rugged terrain outside school for 20 min every school day during one school year. Measurements of low back static endurance, hamstrings flexibility, standing balance and cardiovascular fitness were made before and after the intervention. As intervention and ,aging' were confounded, the special use of the pre-intervention data, ,age-adjusted', is proposed to solve this issue. A comparison with having an independent control group is performed. Results The alternative analysing method is judged to yield valid results without having an independent control group. The age-adjusted analyses showed 11% increase in low back static endurance, 8% increase in hamstrings flexibility, 69% increase in balance and 6,13% increase in cardiovascular fitness. The effects were largest among those children who had the lowest performances before the intervention. Conclusion The introduced statistical methods display that, in a school population, evaluations from an experiment can be made without an independent control group. A 20-min walk during school time for 1 year seemed to improve physical performance. [source] | |||||||||||||||||||