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PubMed1999

Photorefractive keratectomy for hyperopia: long-term nonlinear and vector analysis of refractive outcome.

PURPOSE: To characterize the refractive changes after excimer laser photorefractive keratectomy for the correction of hyperopia over a follow-up up to 3 years and to assess refractive stability and changes in astigmatism. DESIGN: Noncomparative, nonrandomized, retrospective, interventional case series. PARTICIPANTS: Thirty-eight hyperopic eyes of 28 patients (age range, 33-62 years) with refraction in the range +1.00 to +8.00 diopters (D). Mean attempted correction was +3.33+/-0.98 D (range, +1.00 to +4.00 D). Data were compared to those from 216 eyes treated for myopia in the range -1.00 to -12.70 D. INTERVENTION: The hyperopic correction was made using an erodible mask inserted in the laser optical pathway to produce a circular ablation measuring 6.5 mm in diameter. An axicon was then used to create a blend transition zone from 6.5 mm up to 9.4 mm in diameter. Eyes were evaluated 3 to 11 times (5.5+/-2.4) over a 3- to 34-month follow-up (16.8+/-8.4 months). MAIN OUTCOME MEASURES: Vector analysis of refractive error, applying a nonlinear statistical model fitting the spherical equivalent, and the sphere component data. The fit parameters were the long-term error at stabilization (epsilon(infinity)), the amount of regression (epsilon0), being the difference of refractive errors immediately after surgery and at stabilization, and the time constant (T1/2) giving the temporal scale length by which the overcorrection halves (regression half-life). Cylinder was analyzed by a linear regression. RESULTS: The initial overcorrection was much larger after hyperopic treatments than myopic ones (epsilon0 = -3.26+/-0.35 D vs. +1.43+/-0.35 D), and it takes typically four times longer to regress (T1/2 = 3.30+/-0.91 months). Refractive stabilization is reached after more than 1 year, with a satisfactory refractive result. The hyperopic treatment induces a mean astigmatism of 1.00 D, which remains constant throughout the follow-up, and tends to be aligned along the with-the-rule meridian. CONCLUSIONS: The advantages of a reasonably well-designed algorithm to correct hyperopia (epsilon(infinity) = +0.20+/-0.23 D) are counterbalanced by the long time to refractive stabilization and by the induced astigmatism.

Adult↗

PubMed2001

Use of interpolated climatic parameters to predict risk of blowfly-strike in Queensland sheep flocks.

The risk of blowfly-strike was investigated in 160 sheep flocks in Queensland, Australia. The association between blowfly-strike--measured by the use of pesticides in response to flystrike reported by flock managers during the period 1994-1997--and interpolated rainfall and temperature data was examined using survival analysis and stepwise regression. The statistical model explaining the most variation in risk of blowfly-strike included average maximum temperature and its second-order polynomial 4 months preceding flystrike. The model was validated using reports of blowfly-strike from 87 flocks during the period 1997-1999 (collected using the same method as for model construction) and interpolated maximum temperature data. Although there was overlap of 95% confidence intervals derived for model coefficients estimated using both construction and validation data sets, false-negative and false-positive misclassification percentages were 33.3 and 53.3%, respectively. False-negative misclassification was greater for flocks located in southern Queensland, and false-positive misclassification was greater for northern Queensland flocks.

Animals↗

PubMed2001

Time to first calving and calving interval in bovine virus diarrhoea virus (BVDV) sero-converted dairy herds in Norway.

Dairy herds in Møre and Romsdal County, Norway (regarded as initially free from the bovine virus diarrhoea virus (BVDV) infection) were studied retrospectively from 1992 to 1996. The herd reproductive performance (time to first calving, calving interval, and number of breeding services) was investigated for a potential effect of BVDV sero-conversion. The herd culling pattern--possibly affecting the above measurements--was included for investigation. Two different statistical models were used: the generalised estimating equation (GEE) method and multilevel modelling using Gibbs sampling. Though slightly different estimates resulted, both models agreed on an effect of BVDV in the second year after sero-conversion on the herd average time to first calving by--on an average-- 14-16 days. In subsets of case herds testing positive for BVDV antibodies among young stock, the impact on time to first calving tended to be more pronounced by an additional increase of 18 days. No effect on the number of breeding services for heifers or cows was observed (indicating a need to search for other determinants than reduced conception risk). There appeared to be no effect of BVDV on the herd average calving interval. There was a tendency for a higher risk for reporting animals lost/died in sero-converted herds, which we believe might be related to the occurrence of mucosal disease.

Abortion, Veterinary↗

PubMed2001

Development and validation of a combined temperature, water activity, pH model for bacterial growth rate of Lactobacillus curvatus.

A model was established to predict growth rate as a function of temperature, pH and water activity. The model is based on two, earlier developed models, one for growth rate as a function of temperature and water activity and the other for growth rate as a function of temperature and pH. Based on the assumption that combinatory effects between pH and water activity do not exist, the two models were multiplied to produce one overall model. The overall model was then fitted to data sets measured earlier, and the parameters of the model were determined. A new data set with values for controlling variables outside the range of the earlier developed model was then used to validate the overall model statistically. The model was well able to extrapolate outside the measured data range. Finally, the model was updated with all measured data. No significant changes in the parameters were found. The approach followed underpins the gamma concept, since in the gamma concept it is assumed that the effects of controlling variables can be multiplied, and cardinal parameters are not a function of other variables (temperature, pH, and water activity).

Biometry↗

PubMed2003

Using haplotype blocks to map human complex trait loci.

Understanding of linkage disequilibrium (LD) in human populations could facilitate the discovery of genes that influence complex human diseases. The "HapMap" project is now underway to characterize patterns of LD in the human genome. A pilot study showed "haplotype blocks" in 51 regions scattered throughout the genome. These intriguing results raise important questions about the nature of recombination, and highlight practical issues of marker collection, the influence of statistical modelling on apparent block structure, and the levels of genotyping necessary for studies of common diseases. Knowledge of local disequilibrium patterns may help identify common polymorphisms involved in complex disease, but completely new analytical methods and experimental designs will be required to identify important rare variants.

Chromosome Mapping↗

PubMed2002

Design and analysis of two-period studies of potentially disease-modifying treatments.

A number of two-period designs have been introduced in the neurological clinical trials literature to evaluate the effects of treatment on progressive diseases, using names such as withdrawal, active-extension, randomized withdrawal, randomized start, and staggered-start designs. After parallel groups complete the first period, treatment is either initiated or withdrawn in the second period in a subset of subjects. The purpose of the second period is to provide evidence of whether any effect of treatment observed during the first period is long-term ("disease-modifying") or short-term and transitory ("symptomatic"). A four-arm version, which we term a complete two-period design, has active/active, active/placebo, placebo/active and placebo/placebo respective treatment assignments in the two periods. We provide statistical models for these designs, describe some of the appropriate analyses, and investigate the relative efficiencies of various allocations and special cases. We describe extensions to full and partial factorial versions of such designs which permit efficient and simultaneous evaluation of disease-modifying and symptomatic effects of two or more treatments, along with possible interactions. Advantages and limitations of the various designs are discussed.

Alzheimer Disease↗

PubMedDate not supplied

[The problem of repeated measurements. Longitudinal analysis in epidemiology].

In longitudinal analyses subjects are repeatedly measured along time. They are mixed designs, characterised for their simultaneous consideration of two or more dimensions of analysis, in which time is one of the dimensions.Longitudinal analyses have important advantages with respect other designs. The most important is that they are more efficient, since they allow to distinguish between-individual and within-individual variation.Longitudinal analyses can be approached marginal and conditionally. Whereas the former allows to draw poblational, or average, inferences, the latter permits to draw individual inferences.The statistical models to use depend on the type of response variable. If the dependent variable is normally distributed one will use linear mixed models. When the response is a count one will use mixed Poisson regressions. Mixed binomial or multinomial logistic regressions should be used when the response would be categorical.

Epidemiologic Studies↗

PubMed2003

Fingers, hands or patients? The concept of independent observations.

In hand surgery trials, it is often possible to take several measurements from the same patient, because many disorders here affect bilateral or multiple structures, such as the hand itself, the finger joints or the tendons. Most conventional statistical analyses that take place on the level of hands, digit rays or joints rather than patients violate the assumption that observations should be independent. Furthermore, ignoring the multiplicity of data inflates sample size and thus may lead to spurious significance. This article describes three options to deal with such problems. First, the analysis can simply be restricted to only one measurement per patient. Second, a self-controlled design may be advantageous for conditions that usually have a bilateral pattern. Third, complex statistical modelling (involving generalized estimating equations) can be used to analyse all available measurements with adjustment for data dependency.

Controlled Clinical Trials as Topic↗

PubMed2002

Assessing vegetation exposure to ozone: is it possible to estimate AOT40 by passive sampling?

A statistical model for estimating AOT40 from time-integrated concentration data is presented and validated. AOT40 is a numerical index that describes the ozone exposure of ecosystems in terms of the hourly accumulated exposure over a threshold of 40 ppb. A rather simple model formulation was achieved by approximating the frequency distribution of hourly concentrations by the Gaussian probability distribution. The model represents a relationship between a time-averaged ozone concentration and the corresponding AOT40. Time-averaged concentration data are obtained when employing the passive sampling technique. For testing the method, passive sampling data with a 14-day sampling time were simulated by averaging continuous monitoring data. Data from eight background stations in Europe were used for calibration and testing. In spite of the simplifying assumption, the model performed well for the accumulated exposure when tested against independent data. The results show that it is possible to obtain a reasonable estimate of AOT40 even in the absence of continuous data, if the time-averaged concentration can be measured reliably.

Air Pollutants↗

PubMed1998

Prescribed versus delivered dialysis in acute renal failure patients.

The current study was designed first to determine separately the prescribed and delivered dose of dialysis and, second, to determine what factors lead to failure to deliver the prescribed dose of dialysis in patients with acute renal failure (ARF). Forty patients, who collectively underwent 136 dialysis treatments, were studied prospectively at two institutions. The results showed that almost half the prescriptions (49%) were for a Kt/V less than 1.2 and, more importantly, nearly 70% of the treatments delivered a Kt/V less than 1.2, the minimally acceptable dose defined in the Dialysis Outcomes Quality Initiative (DOQI) guidelines for chronic hemodialysis (CHD) patients. Patient predialysis weight was the most important variable associated with a low prescribed and delivered dose of dialysis, as well as lack of delivery of the prescribed dose of dialysis. From the statistical model, it is estimated that for every 10-kg increase in predialysis weight, the chance of prescribing or delivering a Kt/V less than 1.2 increased 4.6- and 1.95-fold, respectively. The lower than prescribed blood flow achieved by the temporary catheters and patients not receiving anticoagulation were variables also associated with not receiving the prescribed Kt/V. It is concluded that patients with ARF are prescribed and receive a dose of dialysis that would be considered inadequate for CHD patients. Until the association between dose of dialysis and outcome is better defined, it would be prudent that both the dialysis prescription and the delivery of dialysis to patients with ARF should be performed with the same care and goals as that currently received by patients with end-stage renal disease (ESRD).

Acute Kidney Injury↗

PubMed2003

Twenty-year follow-up study of long-term survival of limited-stage small-cell lung cancer and overview of prognostic and treatment factors.

PURPOSE: To predict the long-term survival results of clinical trials earlier than using actuarial methods and to assess the factors predictive of long-term cure in patients with limited-stage small-cell lung cancer. METHODS AND MATERIALS: Between 1981 and 1998, 1417 new cases of small-cell lung cancer were diagnosed in Saskatchewan, Canada, of which 244 were limited stage and treated with curative intent. They were followed to the end of February 2002. A parametric lognormal statistical model was retrospectively validated to determine whether long-term survival rates could be estimated several years earlier than is possible using the standard life-table actuarial method. RESULTS: The survival time of the uncured group followed a lognormal distribution. Four 2-year periods of diagnosis were combined, and patients were followed as a cohort for an additional 2 years. The estimated 10-year cause-specific survival rate was 13% by the lognormal model. The Kaplan-Meier calculation for 10-year cause-specific survival rate was 15% +/- 3%. The data also showed that the absence of mediastinal lymphadenopathy and higher chest radiotherapy dose were significant prognostic factors on multivariate analysis (p < 0.05). Among the 163 patients given prophylactic cranial irradiation, a higher biologically effective dose to the brain did not improve survival or decrease the incidence of brain metastases. CONCLUSION: The lognormal model has been validated for the estimation of survival in patients with limited-stage small-cell lung cancer. A higher biologically effective dose to the brain did not improve survival or decrease the incidence of brain metastases.

Algorithms↗

PubMed1999

Effect of number of motile sperms inseminated on reproductive performance of rabbit does.

The relationship between the number of motile sperms inseminated and fertility rate and litter size at birth in rabbits was investigated. A total of 651 artificial inseminations on multiparous rabbit does in different physiological states (lactating or not; sexually receptive or not) were inseminated with a number of motile cells/dose varying from about 1-20 x 10(6). The statistical model computed the following traits: maximum expected value (a), rate of approach to this value (b) and number of motile spermatozoa/dose needed to obtain threshold level (95% of the maximum). The physiological condition of the doe affected the reproductive performance. The sexual receptivity had significant effect during lactation: non-receptive does had the lowest fertility (a: 43.70%; P < 0.05) while no significant differences were found in non-lactating ones (73.80 vs. 89.11%). Also the rate of approach to this maximum was different: non-receptive does showed a higher dependence on spermatozoa number than receptive females (b: 0.69 and 0.58, respectively, in lactating and non-lactating does) and consequently more spermatozoa (13.1 and 11.1 x 10(6) motile/dose) were needed to reach the threshold value. The physiological state of the does did not affect litter size and only 4.1 x 10(6) of motile spermatozoa/dose are needed to reach the threshold value.

Animals↗

PubMed1991

Evaluation of antiarrhythmic drug effects with simultaneous analysis of single ventricular premature contractions, couplets and salvos.

To improve the clinical value of ambulatory Holter electrocardiographic (ECG) monitoring as a tool of antiarrhythmic therapy control, a new statistical model was developed. In a patient group at increased risk of sudden cardiac death, the spontaneous variability of ventricular arrhythmias was assessed, with simultaneous consideration of single ventricular premature complexes, couplets and salvos. The study included 100 patients who suffered from coronary heart disease or idiopathic dilated cardiomyopathy and for whom greater than 30 ventricular premature complexes/h and couplets had been demonstrated on the last Holter ECG before the study. Between 3 and 12 Holter recordings were made for each patient in a drug-free state; the mean follow-up period was 260 days (maximum 1,403). The mean hourly values of the ectopic events (EE) were assessed separately for ventricular premature complexes, couplets and salvos. The spontaneous variability (SV) was calculated for single ventricular premature complexes, couplets and salvos as SV = log (EEday 2 + 0.01/EEday 1 + 0.01) and linked in one, two and three dimensions. Compared with the consideration of only one type of arrhythmia (one-dimensional model), the simultaneous use of two or three types of arrhythmia (two- or three-dimensional model) resulted in considerably lower reduction and aggravation rates as sufficient proof of drug effects. With control intervals up to 1 week, the one-dimensional model yielded reduction rates for ventricular premature complexes, couplets and salvos of -63%, -90% and -95%, respectively. In contrast, with the three-dimensional model, the rates were -28%, -72% and -88%. The corresponding aggravation values were +370, +1,114% and +2,189% versus +38%, +256% and +747%.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Arrhythmia Agents↗

PubMed2000

Estimation of the amyotrophic lateral sclerosis incidence by capture-recapture method in the Limousin region of France.

Amyotrophic lateral sclerosis (ALS) is a rapidly fatal degenerative neurological disease categorized among motor neuron diseases. In the literature, the incidence of ALS varies between 0.7 and 2.4 per 100, 000 inhabitants. A study using the capture-recapture method (multiple records system analysis) was undertaken in Limousin (France) ascertaining all patients having onset of definite or probable ALS during the period 1994-1995. Three information sources able to identify these new ALS cases were selected: the first source was a computerized database of the Neurology Department of the University Hospital of Limoges; the second source consisted of the neurologists of the Limousin region and neighboring provinces (county-sized regions); the third source grouped the hospitals of the Limousin region and neighboring provinces (county-sized regions). During this period, 46 new cases of ALS were seen, corresponding to an observed mean annual incidence of 3.2 (+/-0.6) per 100,000 inhabitants. After standardization for age, the annual incidence was 2.5 per 100,000 inhabitants. The number of new cases estimated by the capture-recapture method was 70, corresponding to an estimated mean annual incidence of 4.9 (+/-1.0) for 100,000 inhabitants. Hence, statistical modeling utilizing partially overlapping information sources permitted a more exhaustive compendium of the new cases of ALS and may be a truer reflection of actual disease incidence than has been previously reported.

Amyotrophic Lateral Sclerosis↗

PubMed1998

Optimization of selectivity in high-performance liquid chromatography using desirability functions and mixture designs according to PRISMA.

A computer program for the mobile phase optimization of high-performance liquid chromatography (HPLC) is described. The desirability function technique combined to the prisma mixture design was employed to enhance the quality of HPLC separations. The use of statistical models to predict the behaviour of retention times (tR) and band broadening at the different eluent compositions obtained by prisma was examined for dansyl amides and coumarins. The study showed that the dependence between the eluent composition and tR values of dansyl amides and coumarins can be expressed using quadratic regression models with a high degree of accuracy. Band broadening given by means of the band width at half-height (wh) was described by a linear regression model. Both models were used in calculating and predicting the resolution (Rs) in various solvent combinations. The desirability function converted the calculated (Rs) value into the desirability value (D), and the overall optimum was then defined by means of the overall desirability. The optimal eluent mixtures for the separation of compounds were easily read from the contour plot inside the horizontal plane of the prisma model. A good separation was achieved using the optimized solvent combination. Depending on the aims of the optimal separation, the program allows either optimization of critical pairs or achieving the overall optimum giving a reasonable separation for as many compounds as possible.

Chromatography, High Pressure Liquid↗

PubMed1999

Relying solely on historical surgical times to estimate accurately future surgical times is unlikely to reduce the average length of time cases finish late.

STUDY OBJECTIVE: To determine whether using only previous cases' surgical times for predicting accurately surgical times of future cases is likely to reduce the average length of time cases finish late (after their scheduled finish times). DESIGN: Computer simulation. MEASUREMENTS AND MAIN RESULTS: Data from an operating room (OR) information system for two surgical suites were analyzed. For each case performed in fiscal year 1996, we searched backward for 1 year and counted the number of previous cases that were the same type of procedure performed by the same surgeon. Then, for each suite, surgical times were fitted to a statistical model estimating the effect of the type of procedure and who the surgeon was on surgical time. The estimated "variance components" were used in Monte-Carlo computer simulations to evaluate whether a hypothetical increase in the number of previous cases available to estimate the next case's surgical time would improve scheduling accuracy. Predictions of how long newly scheduled cases should take were impaired because 36.5% +/- 0.4% (mean +/- SE) of cases at a tertiary surgical suite and 28.6% +/- 0.7% of cases at an ambulatory surgery center did not have any cases in the previous year with the same procedure type and surgeon. Computer simulation was used to generate additional hypothetical cases. Using this data, even having many previous cases on which to base predictions of future surgical times would only decrease the average length of time that cases finish late by a few minutes. CONCLUSION: An OR manager considering using only historical surgical times to estimate future surgical times should first investigate, using data from their own surgical suite, what percentage of cases do not have historical data. Even if there are sufficient historical data to estimate future surgical times accurately, relying solely on historical times is probably an ineffective strategy to have future cases finish on time.

Ambulatory Surgical Procedures↗

PubMed2002

Estimation in medical imaging without a gold standard.

RATIONALE AND OBJECTIVES: In medical imaging, physicians often estimate a parameter of interest (eg, cardiac ejection fraction) for a patient to assist in establishing a diagnosis. Many different estimation methods may exist, but rarely can one be considered a gold standard. Therefore, evaluation and comparison of different estimation methods are difficult. The purpose of this study was to examine a method of evaluating different estimation methods without use of a gold standard. MATERIALS AND METHODS: This method is equivalent to fitting regression lines without the x axis. To use this method, multiple estimates of the clinical parameter of interest for each patient of a given population were needed. The authors assumed the statistical distribution for the true values of the clinical parameter of interest was a member of a given family of parameterized distributions. Furthermore, they assumed a statistical model relating the clinical parameter to the estimates of its value. Using these assumptions and observed data, they estimated the model parameters and the parameters characterizing the distribution of the clinical parameter. RESULTS: The authors applied the method to simulated cardiac ejection fraction data with varying numbers of patients, numbers of modalities, and levels of noise. They also tested the method on both linear and nonlinear models and characterized the performance of this method compared to that of conventional regression analysis by using x-axis information. Results indicate that the method follows trends similar to that of conventional regression analysis as patients and noise vary, although conventional regression analysis outperforms the method presented because it uses the gold standard which the authors assume is unavailable. CONCLUSION: The method accurately estimates model parameters. These estimates can be used to rank the systems for a given estimation task.

Diagnostic Imaging↗

PubMed1998

How to ensure data security of an epidemiological follow-up: quality assessment of an anonymous record linkage procedure.

A computerised record hash coding and linkage procedure is proposed to allow the chaining of medical information within the framework of epidemiological follow-up. Before their extraction, files are rendered anonymous using a one-way hash coding based on the standard hash algorithm (SHA) function, in order to respect the legislation on data privacy and security. To avoid dictionary attacks. two keys have been added to SHA coding. Once rendered anonymous, the linkage of patient information can be accomplished by means of a statistical model, taking into account several identification variables. Quality assessment of this anonymous record linkage procedure shows a specificity of 100% and a sensitivity of 95%.

Algorithms↗