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PubMed2000

Statistical models for analysis of cytogenetic biomarkers.

BACKGROUND: Bleomycin-induced chromosomal breaks (CB) and sister chromatid exchange (SCE) in peripheral blood lymphocytes have been shown to be sensitive cytological markers for susceptibility to DNA damage in patients with various types of cancer and in healthy controls. Factors such as age, sex, smoking, and alcohol consumption could affect the values of some of these biomarkers and should be considered as covariates when analyzing cytogenetic biomarkers because these factors can affect the frequency of CB and SCE. METHODS: We propose a statistical method using negative binomial (NB) distribution to evaluate the numbers of CB and SCE. In order to determine the best model to represent the frequency of CB and SCE, we compared the NB model with the widely used Poisson model and log-transformed normal model by using generalized linear models. To demonstrate the better fit of the NB model, we analyzed three different data sets from studies conducted at The University of Texas M.D. Anderson Cancer Center. The first set was a case-control study of lung cancer in a population of African Americans and Mexican Americans (286 cases and 156 controls), the second set consisted of 311 head and neck cancer patients, and the third set consisted of 105 Hodgkin's disease patients. RESULTS: For CB; the estimates of the variability for Hodgkin's disease, head and neck, and lung cancers were 487.24, 502.82, and 520.15, respectively. For SCE, the estimates of the variability for Hodgkin's disease was 9777.01. For CB, the dispersion estimates under the three models (Poisson, NB, and Normal) for Hodgkin's disease, head and neck, and lung cancers were: 12.30, 1.20, 0.85; 8.94, 1.05, 0.22; and 10.10, 1.05, 0.25, respectively. For SCE (Hodgkin's disease only), the dispersion estimates under the three models (Poisson, NB, and Normal) were 30.91, 1.11, 0.10, respectively. CONCLUSIONS: Our results demonstrate that the NB model provides a better interpretation and fit for the frequency of CB and SCE in different cancer types. Therefore, we recommend it as a model for the analysis of cytogenetic biomarkers.

Biomarkers↗
PubMed2001

[When will mammography screening reduce breast cancer mortality?].

BACKGROUND: Norwegian authorities have decided to start a mass mammography screening programme. One third of the population has been included in a pilot study from 1996. The Cancer Registry of Norway maintains that there will be at least a 30% reduction in mortality, but that an effect may not be detected until the ten-year follow-up. METHODS: We assume that the effect of mammography screening is constantly increasing over a ten-year period before maximum effect is reached. We also assume that the effect of screening in the age group 50-74 years is 80% of maximum effect. We simulate Norwegian breast cancer mortality rates under the assumption that mammography screening reduces breast cancer mortality in the age group 50-69 years with 15% and 30% effects, respectively. We also simulate 30% and 50% effect in the pilot study. RESULTS: If the effect in the Norwegian population is 30%, one may expect to see a significant decline after five years; however, if the effect is only 15%, one has to wait for a longer time. If the effect is 50%, as the Cancer Registry of Norway has argued, one should see a significant effect in the pilot study after six years. CONCLUSIONS: We think it a contradiction to argue that mammography screening reduces breast cancer mortality by 30%, but that one has to wait ten years to observe an effect on national mortality rates. We suggest that the breast cancer mortality rate in the pilot study is estimated. We also argue that observed reductions of less than 10% in Sweden, Finland and England are strong evidence that the effect of mammography today is far less than 30%.

Aged↗
PubMed2000

Rasch models overview.

This overview of Rasch measurement models begins with a conceptualization of our continuous experiences that are often captured as discrete observations. It goes on to discuss the properties that are require of measures if they are to transcend the occasion in which they were collected, and concludes with a discussion the spiral of inferential development. This is followed by a discussion of the mathematical properties of the Rasch family of models that allow the transformation of discrete deterministic counts into continuous probabilistic abstractions on which science is based. The overview concludes with a discussion of six of the family of Rasch models, Binomial Trials, Poisson Counts, Rating Scale, Partial Credit, and Ranks and the types of data for which these models are appropriate.

Binomial Distribution↗
PubMed1992

AIDS prevalence by income group in Philadelphia.

We sought to track recent changes in AIDS incidence and prevalence in the city of Philadelphia (PA, U.S.A.) using morbidity and mortality data reported to the health department. We stratified the data by the mean per capita income in census tracts where people with AIDS resided. Estimates made without adjustment for the time lag between events and their entry into the database undercount both recent AIDS diagnoses and recent AIDS deaths. Therefore, we used a previously published method to adjust for the lag in reporting diagnoses and developed a method to adjust for the lag in reporting deaths. We calculated prevalent cases as the difference between cumulative cases and cumulative deaths. Between 1988 and 1990, annual AIDS incidence per 100,000 Philadelphia residents increased by 21% (from 25.9 to 31.4) and AIDS prevalence per 100,000 population increased by 62% (from 30.2 to 48.8). AIDS prevalence increased 113% (from 29.8 to 63.6) in low-income tracts, 88% (from 27.8 to 52.3) in middle-income tracts, and 14% (from 32.5 to 37.2) in high-income tracts. The 62% increase in AIDS prevalence and the shift toward people in poorer neighborhoods imply a need for public funding for AIDS care that is far larger than would be suggested by the general 21% increase in AIDS incidence over the same period.

Acquired Immunodeficiency Syndrome↗
PubMed1992

The prevalence of risk factors for venous thromboembolism among hospital patients.

BACKGROUND: This study provides an estimate of the prevalence of risk factors for venous thromboembolism among hospital patients. METHODS: The presence of risk factors for venous thromboembolism was determined from a retrospective review of the medical records of 1,000 randomly selected patients in 16 acute care hospitals in central Massachusetts. RESULTS: The most common risk factors for venous thromboembolism were age 40 years (59%) or more, obesity (28%), and major surgery (23%). The average number of risk factors increased with increasing age. One or more risk factors for venous thromboembolism were present in 78% of hospital patients, two or more in 48%, three or more in 19%, four or more in 6%, and five or more in 1%. CONCLUSION: Risk factors for venous thromboembolism are common among hospital patients, suggesting that prophylaxis should be widely employed. The cost-effectiveness and risk benefit of prophylaxis is well established in patients undergoing major surgery. Further studies are needed to confirm the benefit of prophylaxis in patients with nonsurgical risk factors for venous thromboembolism.

Age Factors↗
PubMed2003

Statistical model of amino acid code of protein secondary structure.

In the previous paper (Shestopalov, 2003) we presented the amino acid code of protein secondary structure as a partial solution of the fundamental problem of the protein three-dimensional structure calculation from the amino acid sequence. Here a statistical model of the code is described. The model is based on the structural data from 2258 protein chains (417,112 amino acid residues used). 60 and 61% of the secondary structure, calculated using the model, coincide, respectively, with the observed secondary structure in the training subset and test subset (104 protein chains and 21,166 residues used). This is equal to the threshold value for all the secondary structure calculations, based on the models, where, similarly as here, only the nearest and middle-range interactions are considered. Therefore the constructed model can be applied for the protein structure prediction from the amino acid sequence, especially when additional information is used along with expert analysis, as in the most successful prediction methods. The model can be used for analysis of the secondary structure changes during protein folding by comparison of the calculated and observed secondary structures. The information about the conformationally invariant segments can serve for the simulation of the supersecondary structure formation. One can try to obtain and examine the protein subset, in which the calculated and observed secondary structures are very similar.

Amino Acid Sequence↗
PubMed2004

Accounting for historical information in designing experiments: the Bayesian approach.

Two of the most important statistical problems in human and animal experimentation are the selection of an appropriate number of units to include in a given study and the allocation of these units to the various treatments. Properly addressing these issues allows the units to be used as efficiently as possible, which can contribute to addressing the overall issue of reducing the number of subjects in experimentation. To do so, reliable historical information is of particular importance. In the present paper, we describe the Bayesian approach to determining sample size and allocating units, with particular regard to how the use of historical data can be optimised. The paper focuses on two specific problems: the comparison of normal means and of binomial proportions.

Bayes Theorem↗
PubMedDate not supplied

Oral health-related quality of life in patients treated with fixed, removable, and complete dentures 1 month and 6 to 12 months after treatment.

PURPOSE: This study described oral health-related quality of life (OHRQoL) before and after treatment in patients with fixed, removable, and complete dentures. MATERIALS AND METHODS: OHRQoL was measured using the German version of the Oral Health Impact Profile (OHIP-G) in a convenience sample of 107 prosthodontic patients at baseline and 1 and 6 to 12 months after treatment. The sum of OHIP-G item responses (OHIP-G49, range 0 to 196) characterized OHRQoL impairment in 42 patients treated with fixed prosthodontics, 31 patients treated with removable dentures, and 34 patients treated with complete dentures. OHIP-G49 medians were compared with the OHRQoL level in a general population sample (n = 2,026). A multivariable binomial regression analysis, controlling for the effects of baseline OHRQoL and follow-up wave, was used to compare the level of impaired OHRQoL in different prosthodontic treatment groups at follow-ups. RESULTS: OHRQoL improved in 96% of the subjects. OHIP-G49 medians reached the level of OHRQoL in the general population 1 month after treatment (fixed prosthodontics patients 6 OHIP-G units; general population subjects 5 units; removable denture patients 23 units, 15 units in general population subjects; complete denture patients 13 units, 23 units in general population subjects). OHIP-G49 medians were below population norms 6 to 12 months after treatment. In patients treated with removable/complete dentures, the expected posttreatment OHIP-G49 problem rate was 1.9 times the problem rate in patients treated with fixed prosthodontics, holding baseline OHIP-G49 and follow-up wave constant. CONCLUSION: OHRQoL changed substantially comparing pretreatment scores with 1 and 6 to 12 months of follow-up in patients treated with fixed, removable, and complete dentures.

Adult↗
PubMed2004

An in vivo evaluation of the diagnostic quality ultra-speed versus insight intraoral dental film.

Twelve sets of FMS (full mouth survey) radiographs were taken by California licensed radiology technicians. Ten of the sets of FMS radiographs were taken using Ultra-Speed "D" film on the left side of the patient and Insight "F" speed film on the right side of the patient. The remaining two sets of films were taken using Insight Film on both sides of the patient to act as a control. Ten faculty members of the Diagnostic Department were asked to evaluate the twelve sets of FMS radiographs and report whether they had a preference for the right side, left side, or no preference. Criteria for preference were diagnostic ability and clarity of the films. The results of the study showed a preference for the right side (65.7%), which was imaged with Insight Film, compared to the left side (34.3%), which was imaged with Ultra-Speed Film.

Absorptiometry, Photon↗
PubMed1992

The vectorial efficiency of Simulium yahense populations in south-eastern Ghana.

Adult female Simulium yahense were identified amongst catches of S. damnosum s. 1. caught at Tsatsadu Falls and Wegbe in south-eastern Ghana. Dissections of stained flies to assess the species' role as a vector of onchocerciasis in the region revealed as many as 357 L3 per 1000 biting flies in a sample from Wegbe. When the data from the two sites were combined 154 L3 per 1000 biting flies and 315 L3 per 1000 parous flies were recorded. The values for wet season samples were about 12% higher than those for the dry season. The results are discussed in relation to other studies of S. yahense populations and regarding the species' recent spread in Ghana and Togo.

Animals↗
PubMed1992

Observations on the bionomy of Allocreadium isoporum (Looss, 1894) (Trematoda: Allocreadiidae).

From October 1985 until July 1987, the bionomy of the trematode Allocreadium isoporum (Looss, 1894) was studied in the Rokytná River (the Danube basin), Czechoslovakia. While clams of the genera Sphaerium Scopoli and Pisidium Pfeiffer apparently serve as its first intermediate hosts, mayfly larvae Ephemera danica Müll. were found (prevalence 8%, intensity 1-5 metacercariae per mayfly) to be the only second intermediate host of A. isoporum in the locality. The most important definitive host is chub, Leuciscus cephalus (L.), in which the seasonal dynamics of A. isoporum occurrence and maturation was followed. The parasite exhibits here a distinct seasonal cycle of maturation which is shown mainly by quantitative changes in the ratio of young to mature worms containing eggs. The trematodes containing eggs occur almost throughout the year, but mainly in the spring and early summer (maximum in May), and after the oviposition they leave the host. New infections are acquired by chub all the year round. This seasonal periodicity is determined by ecological factors, mainly the temperature regime in the locality. A isoporum infections in chub in this locality are dependent on the body size of host fishes; the highest degree of A. isoporum infection occurs in fishes 20-25 cm long, the prevalence decreasing somewhat in larger fishes; infection is associated with changes in the food composition of chub of different size groups.

Animals↗
PubMed1991

Alternating chemotherapy with cyclophosphamide/adriamycin/vincristine (CAV) and cisplatin/etoposide (PVP) against small cell lung cancer. Eastern Shikoku Lung Cancer Chemotherapy Group.

Seventy-four confirmed small cell lung cancer (SCLC) patients received alternating combination chemotherapy with CAV and PVP. The CAV comprised of cyclophosphamide 800 mg/m2 on day 1, adriamycin 50 mg/m2 on day 1 and vincristine 1.4 mg/m2 on day 1, administered every 3-4 weeks. The PVP comprised cisplatin 80 mg/m2 on day 1 and etoposide 75 mg/m2 on day 1-5 administered every 3-4 weeks. Of these 74 patients, 63 (85.1%) achieved complete or partial responses with 16 (21.6%) obtaining a complete response. The median survival time was 13.2 months: 10.4 months in patients with extensive disease (ED), 16.3 months in those with limited disease (LD). A three-year disease-free period was achieved in eight patients (11.2%: 4.8% with ED, 16.8% with LD). The median duration of response was 28.3 weeks: 20.1 weeks with ED and 44.0 weeks with LD. The most commonly encountered side effects were nausea, vomiting, alopecia and myelosuppression but all were tolerable. We consider CAV-PVP to be an effective combination regimen for treating SCLC.

Adult↗
PubMed2006

Are KISS data representative of German intensive care units? Statistical issues.

OBJECTIVES: Data collected within the German nosocomial infection surveillance system KISS are recommended as reference data for judging nosocomial infection rates in German intensive care units (ICUs). It is unknown whether the KISS data tend to under- or overestimate the true infection incidence rates. In this article, methodological aspects of the SIR1 study on the incidence of nosocomial infections are discussed, with the aim of estimating unbiased incidence rates of nosocomial infections in interdisciplinary German ICUs and examining whether the KISS data are representative. METHODS: We discuss the following methodological issues: 1) Sample size estimation. 2) Stratified random sampling of German ICUs. 3) Investigation of seasonal effects. 4) Statistical modeling of incidence rates using a negative binomial regression model. 5) Comparison of weighted incidence rates with the standardized rate ratio (SRR). RESULTS: Random sampling proved difficult to realize in practice since many ICUs refused to participate, particularly those in small hospitals. Analysis was adjusted for hospital size. No seasonal trends were found in the KISS data. Due to marked differences between ICUs, the number of infections is over-dispersed compared to a Poisson model, so negative binomial regression was used. Fifty ICUs were observed for two consecutive months each, corresponding to 21,832 patient days, during which 262 infections occurred. Infections were more frequent in large hospitals. The incidence rates provided by the SIR study are on average (SRR) 1.89 (1.63-2.20) times as large as those estimated by the KISS system. CONCLUSION: For estimating nosocomial infection incidence rates, random sampling and statistical modeling of over-dispersion were successfully performed. The study provides evidence that the KISS surveillance system tends to underestimate the true incidence rates of nosocomial infections in German ICUs.

Binomial Distribution↗
PubMed2006

Independence estimating equations for controlled clinical trials with small sample sizes--interval estimation.

OBJECTIVES: The application of independence estimating equations (IEE) for controlled clinical trials (CCTs) has recently been discussed, and recommendations for its use have been derived for testing hypotheses. The robust estimator of variance has been shown to be liberal for small sample sizes. Therefore a series of modifications has been proposed. In this paper we systematically compare confidence intervals (CIs) proposed in the literature for situations that are common in CCTs. METHODS: Using Monte-Carlo simulation studies, we compared the coverage probabilities of CIs and non-convergence probabilities for the parameters of the mean structure for small samples using modifications of the variance estimator proposed by Mancl and de Rouen [7], Morel et al. [8] and Pan [3]. RESULTS: None of the proposed modifications behave well in each investigated situation. For parallel group designs with repeated measurements and binary response the method proposed by Pan maintains the nominal level. We observed non-convergence of the IEE algorithm in up to 10% of the replicates depending on response probabilities in the treatment groups. For comparing slopes with continuous responses, the approach of Morel et al. can be recommended. CONCLUSIONS: Results of non-convergence probabilities show that IEE should not be used in parallel group designs with binary endpoints and response probabilities close to 0 or 1. Modifications of the robust variance estimator should be used for sample sizes up to 100 clusters for CI estimation.

Algorithms↗
PubMed2006

A note on testing for intervention effects on binary responses.

OBJECTIVES: In some circumstances controlled trials are not feasible and treatments can only be evaluated using clinical databases. Here we consider the situation where treatment is introduced at a particular calendar time and can only be evaluated by comparison with historical controls. In these circumstances Heuer and Abel recommended using change-point methods to search for change in characteristics over the whole study period rather than simply comparing treated and untreated patients. Their recommendation is to only conclude that the intervention had an effect if a change-point could be demonstrated close in time to the introduction of the new treatment. This reduces the risk of false positives caused by confounding changes in population characteristics or changes in patient management. For binary data we develop a method that follows their philosophy and apply it to an observational study in the treatment of pin sites after orthopaedic surgery. METHODS: Tests for change in binomial probabilities based on Brownian bridge and Hansen's approximation for maximally selected chi(2) statistics are compared to an exact test by Worsley. The approximate method is generalized to logistic regression models allowing for covariates. RESULTS: The agreement of the exact and approximate method is good for sample sizes of 100 or more. The actual test size of the Hansen approximate test allowing for covariates is close to the nominal level, whereas the Brownian bridge approximation is slightly conservative. The change in pin site treatment significantly reduces the risk of infection for both adults and children. CONCLUSIONS: We consider the Hansen approximation to provide a very good and very simple method for obtaining the p-value when testing for a change in binary data event probabilities, with or without covariates.

Adult↗
PubMed2006

Caries prevalence of 11.5 year-olds between 1989 and 2001 in a province of North-Eastern Greece.

OBJECTIVE & DESIGN: To compare cross-sectional caries prevalence data of 11.5 year old children over a 13 year period (1989-2001) and to evaluate the maximum effect of the applied preventive programme (sealants to 1st molars and 6-year health education) on DMFT values during the last five years. PARTICIPANTS: Using the records of a Public Health Centre (PHC) in NE Greece, a number (153-250) of children aged 11.5-years were selected from each calendar year, constituting 11 study groups (totalling 2,217 children), stratified by area of residency. METHOD: Annual oral health education sessions provided in 1990, a year after the PHC was established. Light-cured fissure sealants were systematically mass introduced in 1996. The same dentist completed all DMFT records in the dental clinic during the children's routine visits. DMFT was analysed using two Poisson and two Binomial models for both data from all years, and for the last five years. The models had as factors: "Time" (year of examination of the study group), "Residency" (semi urban, rural lowland, rural highland), number of "Sealed 1st molars" and "Sealed posterior teeth". RESULTS: All the factors were highly statistically significant (p<0.001). Dental health was found to be good (DMFT=0), improving progressively year by year (range 12-50%). The mean DMFT decreased steadily from 4.5 (in 1989) to 1.81 (in 2001). The Significant Caries index was almost halved (from 8.08 to 4.23). CONCLUSION: An important improvement in the caries status of 11.5 year-olds since 1989 has been demonstrated, irrespective of the residency. The systematic application of fissure sealants to all 1st molars, parallel to the cumulative effect of the 6-year health education programme per child, played a significant role in reducing disparities in disease prevalence, despite the difficulty of improving rates of decline when the caries levels are relatively low.

Binomial Distribution↗
PubMed2006

[How to draw a conclusion in motherless parentage testing using short tandem repeats as genetic makers].

OBJECTIVE: To calculate the exclusion power of STR loci in motherless parentage testing and to discuss how to draw a conclusion if there are inconsistent loci. METHODS: Based on the law of inheritance and allele frequency, the powers of exclusion of STR loci in motherless parentage testing (PE(M)) were calculated. Based on the mean PE(M) and mutation rate of 13 CODIS loci. The probabilities of inconsistence under paternity and non-paternity were calculated respectively according to binomial theorem. RESULTS: The PE(M) of locus having co-dominate alleles could be calculated as: PE(M) = (i = 1)sigma (n) p i 2(1-p (i))2+ (i < j)sigma (n) 2p (i)p (j)(1-p (i)-p (j))2. According to the formula, the average PE(M) of 13 CODIS was 0.411. Based on the mean PE(M) and mutation rate, the likelihood ratio of true father to random man (paternity index) was got using binomial theorem. CONCLUSION: The conclusion in motherless parentage testing could be drawn based on the likelihood ratio (paternity index) derived from mean PE(M) and mutation ratio.

Algorithms↗
PubMed1991

Gnathostomiasis in Thailand: a survey on intermediate hosts of Gnathostoma spp. with special reference to a new type of larvae found in Fluta alba.

To clarify current status of gnathostomiasis in Thailand, a survey on intermediate hosts has been carried out at various localities since 1987. It was found that Fluta alba (Fresh water eel) as well as Channa striata (snake-headed fish) might be important in playing a role of transmitting the infection either among humans or reservoir animals. During the three years from 1987 to 1989, larvae of Gnathostoma spinigerum were found in 80-100% of F. alba obtained from markets in Nakhon Nayok, with a maximum recovery of 2,582 larvae per eel. Among larvae found in these eels, five were peculiar in possessing four rows of hooklets with complicated branches at the base. Epithelial cells of the intestine of these larvae contained 1-2 nuclei. These observations indicate that the larvae are different from those of reported species of Gnathostoma from Thailand including G. spinigerum, suggesting a possibility of the advanced third-stage larvae of G. malaysiae.

Animals↗