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PubMed2004

Analytical approaches for transplant research.

It is highly desirable to base decisions designed to improve medical practice or organ allocation policies on the analyses of the most recent data available. Yet there is often a need to balance this desire with the added value of evaluating long-term outcomes (e.g. 5-year mortality rates), which requires the use of data from earlier years. This article explains the methods used by the Scientific Registry of Transplant Recipients in order to achieve these goals simultaneously. The analysis of waiting list and transplant outcomes depends strongly on statistical methods that can combine data from different cohorts of patients that have been followed for different lengths of time. A variety of statistical methods have been designed to address these goals, including the Kaplan-Meier estimator, Cox regression models, and Poisson regression. An in-depth description of the statistical methods used for calculating waiting times associated with the various types of organ transplants is provided. Risk of mortality and graft failure, adjusted analyses, cohort selection, and the many complicating factors surrounding the calculation of follow-up time for various outcomes analyses are also examined.

Cohort Studies↗
PubMed1991

Synchronization of hormonal time series: analytical approaches.

Comparison of the patterns of episodic secretion of two or more hormones measured simultaneously often suggests that peak levels tend to occur at around the same time. This visual impression can be misleading, however, as some peaks will occur simultaneously due to chance alone. Traditional cross-correlation methods are suitable for evaluating linkages among circadian and other smoothly varying rhythms, but are less well suited to correlating ultradian peaks. This paper proposes a method which entails identifying peaks of hormone secretion as discrete events in several different series, and counting the frequency of simultaneous and near-simultaneous peaks in temporal 'windows' of increasing width. The expected rates of random coincidences can be assessed by a variety of methods, including simulations and probability calculations. The method described utilizes simple techniques which make few assumptions about the character or stationarity of the series, comparing coincidence rates in the appropriately paired series with those in which a series in one subject is deliberately 'mismatched' with that of another subject. Using this approach, a significant excess of simultaneous peaks of luteinizing hormone (LH) and prolactin was found in normal subjects as compared with mismatched series (17% versus 6%; p less than 0.05). Hypogonadotrophic men treated with pulsatile gonadotrophin-releasing hormone (GnRH) have an even higher coincidence rate (26%). By contrast, the rate of coincidence between pulses of LH and cortisol is not significantly greater than that which would be expected due to chance.

Circadian Rhythm↗
PubMed1999

Estimates of the proportions of carcinogens and anticarcinogens in bioassays conducted by the U.S. National Toxicology Program. Application of a new meta-analytic approach.

A meta-analysis was performed in order to estimate the proportion of liver carcinogens, the proportion of chemicals carcinogenic at any site, and the corresponding proportion of anticarcinogens among chemicals tested in 397 long-term cancer bioassays conducted by the U.S. National Toxicology Program (NTP). Although the estimator used was negatively biased, the study provided persuasive evidence for a larger proportion of liver carcinogens (0.43, 90% CI: 0.35, 0.51) than was identified by the NTP (0.28). A larger proportion of chemicals carcinogenic at any site was also estimated (0.59, 90% CI: 0.49, 0.69) than was identified by the NTP (0.51), although this excess was not statistically significant. A larger proportion of anticarcinogens (0.66) was estimated than carcinogens (0.59). Despite the negative bias, it was estimated that 85% of the chemicals were either carcinogenic or anticarcinogenic at some site in some sex-species group. This suggests that most chemicals tested at high enough doses will cause some sort of perturbation in tumor rates.

Animals↗
PubMed2003

Characterization of the microbial community in indoor environments: a chemical-analytical approach.

An integrated procedure is presented whereby gas chromatography-ion trap mass spectrometry is used to determine chemical markers of gram-negative bacterial lipopolysaccharide (3-hydroxy fatty acids with 10 to 18 carbon atoms), gram-positive bacteria (branched-chain fatty acids with 15 and 17 carbon atoms), bacterial peptidoglycan (muramic acid), and fungal biomass (ergosterol) in samples of settled house dust. A hydrolysate of (13)C-labeled cyanobacterial cells is used as an internal standard for the first three markers. These analyses require two dust samples, one for 3-OH fatty acids, branched-chain fatty acids, and muramic acid and another for ergosterol. The method may be used to characterize microbial communities in environmental samples.

Air Pollution, Indoor↗
PubMed2004

Time dependent risk of gastrointestinal complications induced by non-steroidal anti-inflammatory drug use: a consensus statement using a meta-analytic approach.

OBJECTIVES: To provide an updated document assessing the global, NSAID-specific, and time dependent risk of gastrointestinal (GI) complications through meta-analyses of high quality studies. METHODS: An exhaustive systematic search was performed. Inclusion criteria were: RCT or controlled study, duration of 5 days at least, inactive control, assessment of minor or major NSAID adverse effects, publication range January 1985 to January 2003. The publications retrieved were assessed during a specifically dedicated WHO meeting including leading experts in all related fields. Statistics were performed conservatively. Meta-regression was performed by regressing NSAID adjusted estimates against study duration categories. RESULTS: Among RCT data, indolic derivates provided a significantly higher risk of GI complications related to NSAID use than for non-users: RR = 2.25 (1.00; 5.08) than did other compounds: naproxen: RR = 1.83 (1.25; 2.68); diclofenac: RR = 1.73 (1.21; 2.46); piroxicam: RR = 1.66 (1.14; 2.44); tenoxicam: RR = 1.43 (0.40; 5.14); meloxicam: RR = 1.24 (0.98; 1.56), and ibuprofen: RR = 1.19 (0.93; 1.54). Indometacin users had a maximum relative risk for complication at 14 days. The other compounds presented a better profile, with a maximum risk at 50 days. Significant additional risk factors included age, dose, and underlying disease. The controlled cohort studies provided higher estimates: RR = 2.22 (1.7; 2.9). Publication bias testing was significant, towards a selective publication of deleterious effects of NSAIDs from small sized studies. CONCLUSION: This meta-analysis characterised the "compound" and "time" aspects of the GI toxicity of non-selective NSAIDs. The risk/benefit ratio of such compounds should thus be carefully and individually evaluated at the start of long term treatment.

Aged↗
PubMed1986

Coconut matting bezoar identified by a combined analytical approach.

A rare type of bezoar composed of coconut matting was found in the stomach of a caucasian man. The exact identity of the fibres was established by scanning electron microscopy, x-ray energy spectroscopy, and microscopic infrared spectroscopy. This report illustrates the importance of these techniques for identifying the nature of foreign material.

Adult↗
PubMed2000

Inequalities in health. Analytic approaches based on life expectancy and suitable for small area comparisons.

STUDY OBJECTIVE: Simple measures of inequalities in health are proposed to facilitate the work of health policy makers and to build on the understanding of health differences between populations. In addition, it is aimed to make these measures applicable for comparisons of small populations and subgroups. METHODS: Inequalities in health or health deficiencies were quantified as the difference between the life expectancy of the subgroup of interest and that of the national population. Health deficiencies were divided into disease specific components by partial application of cause eliminated life table methods. To manage small numbers and to depict time trends, locally weighted regression smoothing was applied. Confidence intervals were constructed through Monte Carlo simulations. APPLICATIONS AND COMPARISONS: The proposed approaches were applied to the health situation in Cape Breton County, Nova Scotia, Canada, and disclosed the significance of different diseases and distinct patterns between communities. The proposed measures were also compared with the traditionally used standardised mortality rates and ratios. Here, the proposed measures appeared beneficial in that they are easier to comprehend and that they provide time trends and more robust estimates. CONCLUSIONS: The above advantages make the proposed approaches beneficial to health policy makers and epidemiologists. The approaches may also be incorporated in economic evaluations as well as in more sophisticated public health models.

Confidence Intervals↗
PubMed2002

The EUROSTROKE cohorts: a short description and data analytical approach.

This paper describes the design and methodology of the participating cohorts in the EUROSTROKE project. Information is given about the cohort sampling, its size, the follow up procedures and event classification. Information is also given about the measurement of the cardiovascular and cerebrovascular risk factors in each of the cohorts separately. The cohorts described are the Caerphilly study in Cardiff, United Kingdom; the Kuopio Ischaemic Heart disease study in Kuopio, Finland; the Portugal study in Coimbra, Portugal; the EPIC cohort in Athens, Greece; the Ilsa study from Firenze, Italy; the Rotterdam Study in Rotterdam, the Netherlands, and the Novosibirsk cohort in Novosibirsk, Russia.

Adult↗
PubMed2000

Causal effects in clinical and epidemiological studies via potential outcomes: concepts and analytical approaches.

A central problem in public health studies is how to make inferences about the causal effects of treatments or agents. In this article we review an approach to making such inferences via potential outcomes. In this approach, the causal effect is defined as a comparison of results from two or more alternative treatments, with only one of the results actually observed. We discuss the application of this approach to a number of data collection designs and associated problems commonly encountered in clinical research and epidemiology. Topics considered include the fundamental role of the assignment mechanism, in particular the importance of randomization as an unconfounded method of assignment; randomization-based and model-based methods of statistical inference for causal effects; methods for handling noncompliance and missing data; and methods for limiting bias in the analysis of observational data, including propensity score matching and sensitivity analysis.

Analysis of Variance↗
PubMed2005

Optimal peak systolic velocity threshold at duplex us for determining the need for carotid endarterectomy: a decision analytic approach.

PURPOSE: To determine the optimal peak systolic velocity (PSV) threshold at duplex ultrasonography (US) required to establish the need for carotid endarterectomy in symptomatic patients on the basis of the long-term cost-effectiveness outcomes of diagnostic testing and subsequent treatment. MATERIALS AND METHODS: From January 1997 through January 2000, a prospective medical ethics committee-approved multicenter study was conducted. After giving informed consent, patients with amaurosis fugax, transient ischemic attack, or minor stroke who underwent duplex US and digital subtraction angiography were included in the study. Selective ipsilateral carotid angiograms were obtained in at least three planes. Arteries that were nearly or totally occluded at duplex US were excluded because the PSV cannot be reliably measured in these vessels. Receiver operating characteristic (ROC) curves were constructed for the diagnoses of 70%-99% and 50%-99% stenoses. Optimal likelihood ratios were calculated on the basis of lifetime costs and quality-adjusted life-years derived at cost-effectiveness analysis and the prevalence of disease. The associated optimal sensitivities, specificities, and PSV thresholds were derived from the ROC curves. RESULTS: In this clinical study, 350 patients were included. The nonoccluded arteries in a total of 236 patients were assessable for ROC analysis. For the diagnosis of 70%-99% stenosis, the optimal likelihood ratio was 0.21, which was associated with a PSV threshold of 220 cm/sec, a sensitivity of 97% (127 of 131 patients; 95% confidence interval [CI]: 94%, 100%), and a specificity of 48% (50 of 105 patients; 95% CI: 38%, 57%). For the diagnosis of 50%-99% stenosis, the optimal likelihood ratio was 0.38, which was associated with a PSV threshold of 180 cm/sec, a sensitivity of 95% (182 of 191 patients; 95% CI: 92%, 98%), and a specificity of 69% (31 of 45 patients; 95% CI: 55%, 82%). CONCLUSION: On the basis of the lifetime outcomes of diagnostic testing and subsequent treatment, the optimal PSV thresholds for the diagnosis of 70%-99% and 50%-99% carotid artery stenoses in patients with amaurosis fugax, transient ischemic attack, or minor stroke were 220 cm/sec and 180 cm/sec, respectively.

Adult↗
PubMedDate not supplied

Reduction of regional cerebral blood flow and cognitive impairment in patients with Alzheimer's disease: evaluation of an observer-independent analytic approach.

The aim of the study was to evaluate an observer-independent semiquantitative analysis of brain imaging by single-photon emission computed tomography (SPECT) in patients with Alzheimer's disease (AD). Patients (n = 45, mean age 70 +/- 11 years) with a clinical diagnosis of AD according to NINCDS/ADRDA criteria were examined by 99mTc-ethylcysteine dimer SPECT. Following anatomic normalization and data extraction using three-dimensional stereotactic surface projection, a pixelwise comparison of ECD uptake was performed with the reference values of 10 cognitive intact controls of comparable age. The global relative decrease of cerebral blood flow in cortical association areas showed a significant inverse association with the overall level of cognitive functioning as assessed with the Mini Mental State Examination and with the cognitive section (CAMCOG) of the Cambridge Mental Disorders of the Elderly Examination. There were significant region-specific associations between left temporoparietal perfusion deficit and language performance and between right temporoparietal regional cerebral blood flow reduction and praxis. The results suggest that this observer-independent analysis of SPECT data provides a valid assessment of the pattern and severity of cortical perfusion abnormalities in patients with AD.

Adult↗
PubMed1981

Psychophysiology of the reaction time experiment: a factor analytic approach.

A principal component factor analysis with varimax rotation was applied to behavioral and physiological data from a group of 25 subjects comprising normals and depressives, in whom event-related slow brain potentials were recorded during performance of a fixed foreperiod, reaction time task. Five of the seven factors thus evinced were labelled 'activation', 'inhibition', 'resilience', 'depressivity-neuroticism' and 'extraversion', the remaining two factors being related to arousal in an unspecified manner. Although no clear-cut partitioning of variance into trait, state and task-related components was achieved, the contention is advanced that measurement of these factors and their patterning might contribute to psychophysiological diagnosis, provided they are substantiated by further research.

Adult↗