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PubMed2002

[Nosocomial epidemic outbreak of acute gastroenteritis by Norwalk-like virus].

BACKGROUND: From the notification of an acute gastroenteritis outbreak in a nursing home, an epidemiological study was started to determine the characteristics of the outbreak and its spreading pattern and to identify determining factors. PATIENTS AND METHOD: A study of historic cohorts was performed and the case was defined by the presence of diarrhea and vomiting. Spatial aggregation in double rooms was analyzed by a binomial distribution and temporal aggregation was analyzed by a relative risks model. The variables in the study allowed us to calculate the adjusted relative risk; the odds ratio was calculated in relation to the meal on day January 30. RESULTS: We studied 95.9% residents. The total attack rate was 28.7% (31.8% employees, 30.1% permanent residents and 15.2% day residents). The attack rate in rotation health personnel was 45.2%. Spatial and temporal spread in double rooms was negative. There was a significant association with the disease in rotator employees (RR = 3.22; CI 95%, 1.30-7.99; p = 0.02). No association was found between eating and disease (OR = 1.5; CI 95%, 0.4-6.1; p = 0.46). Norwalk-like virus was isolated in four faecal samples. CONCLUSIONS: This epidemic outbreak had the characteristic of a nosocomial infection with a likely person-to-person transmission mechanism. The main factor contributing to the spread of the infection was the existence of employees in permanent contact with residents with an important physical and mental impairment, hence highly dependent on the care provided by these health workers.

Acute Disease↗
PubMed2000

Thrombocytopenia in term infants: a population-based study.

OBJECTIVE: To assess the prevalence and causes of thrombocytopenia among full-term infants. METHODS: We conducted a 1-year, population-based surveillance study involving all full-term infants (at least 37 weeks' gestation) born to native Finnish women in Helsinki. In cases of thrombocytopenia (cord platelet count less than 150 x 10(9)/L) clinical risk factors were evaluated and immunologic studies were performed on both parents and on the infant; 95% confidence intervals (CIs) were calculated on the basis of binomial distribution. RESULTS: Platelet counts were done in cord blood from 4,489 infants, 84.9% of the study population. Eighty-nine infants had platelet counts below 150 x 10(9)/L (2.0%; 95% CI 1.5, 2.3) in cord blood and 11 were less than 50 x 10(9)/L (0.24%; 95% CI 0.10, 0.38). All causes of clinically important thrombocytopenia, those presenting with bleeding and requiring treatment, were related to fetomaternal alloimmune thrombocytopenia. The incidence of severe alloimmune thrombocytopenia was one in 1500 live births and one in 900 of all thrombocytopenia. An immunologic mechanism was involved in ten of 65 (15.4%; 95% CI 6.6, 24.2) infants studied and in four of 15 (26.7%; 95% CI 4.3, 49.1) cases of severe thrombocytopenia. CONCLUSION: Immunologic studies should be considered in all cases of severe neonatal thrombocytopenia for careful monitoring and prevention of potentially severe complications in subsequent pregnancies.

Female↗
PubMed2000

Rapid enzymatic urine screening test to detect bacteriuria in pregnancy.

OBJECTIVE: To determine the sensitivity, specificity, and positive and negative predictive values of an enzymatic urine screening test for diagnosing bacteriuria in pregnancy. METHODS: Clean-catch midstream urine samples were collected from 383 women who had routine prenatal screening for bacteriuria. Sensitivity, specificity, and positive and negative predictive values for each screening test (enzyme activity, nitrites or leukocytes on dipstick, and bacteria or pyuria on microscopic examination) were estimated using urine culture as the criterion standard. Urine cultures were considered positive if they grew 10(4) colony-forming units of a single uropathogen. Standard deviations used to calculate 95% confidence intervals were based on binomial distribution. A sample of 30 urine specimens was selected to evaluate interrater agreement using Cohen's kappa statistic. RESULTS: Five of 383 samples were contaminated, leaving 378 samples for evaluation. Thirty of 43 specimens with positive urine culture had positive enzyme activity. Of 335 samples with no growth, 150 had negative enzyme activity. Sensitivity, specificity, and positive and negative predictive values for the Uriscreen enzymatic screening test (Bard Patient Care Division, Murray Hill, NJ) were 70%, 45%, 14%, and 92%, respectively. Sensitivity of the Uriscreen was lower than that of bacteria alone. Interrater agreement for Uriscreen testing was high among the three testers (kappa =.86). CONCLUSION: The Uriscreen enzymatic screening test had inadequate sensitivity for rapid screening for bacteriuria in pregnancy.

Bacteriuria↗
PubMed1998

Statistical models predicting embryo survival to term in cattle after embryo transfer.

Embryo survival to term in recipient cattle is highly variable. We examined calving data in the published literature to determine whether a model of binomial independence or a model which includes an embryo (e) and recipient term (r), adequately explain observed embryo survival rates following attempts to induce twin calving using transfer of two embryos. To achieve this we examined 32 published papers which provided us with 47 sets of data concerning 4560 recipients with either 0, 1 or 2 calves born. In each set of data, the observed embryo survival rate to term (p) (number of calves born/number of embryos) was calculated and the expected number of recipients with either 0, 1 or 2 calves born was determined, assuming a binomial distribution. Parameters for the second model were estimated using maximum-likelihood procedures. The model of embryo independence was rejected in 85% of the sets of data, suggesting that factors other than the embryo are important sources of variation in embryo survival or loss. The proposed e and r model of embryo survival adequately describes the published data in recipients receiving either single or twin embryos. In general, only 50-70% of embryos and recipients are sufficiently competent to result in a calving. Variation among laboratories producing either in vitro or in vivo derived embryos was due to variation in recipient and not embryo competence. It is argued that e rather than observed embryo survival rate, and r rather than observed pregnancy rate, should be used to compare differences among embryo treatments and groups of recipients, respectively. Acceptance of this proposition should permit faster progress in identifying the biology of superior embryos and recipients, which is a prerequisite to improving embryo survival rate in cattle. Collectively, the published data are not consistent with a model of embryo independence, and that a model of embryo survival to term which recognises recipient as well as embryo contributions to embryo survival may be more appropriate in cattle.

Animals↗
PubMed1980

Time of fertilisation and sex of infants.

The sex of a human zygote may depend on the time during the mother's menstrual cycle that it is formed. Direct data to support this hypothesis suggest that male zygotes tend to be formed both early and late in the fertile period, and female zygotes in the middle. Criticisms of the direct data seem to be only that measurements of the timing of events around conception are inexact. There are several kinds of indirect data: (1) the variation of sex ratio with war and with duration of marriage, and (2) the non-binomial distribution of the combination of the sexes in human dizygotic twins and other mammalian polyzygotic litters. The sex of a zygote may be determined by maternal gonadotrophin levels when it is formed. This elaboration of the hypothesis could explain the low sex ratio in Negroes.

Abortion, Spontaneous↗
PubMed1986

Cryotherapy for active retinopathy of prematurity.

Twenty-eight patients with bilateral symmetrical Stage 3 retinopathy of prematurity (ROP) and plus disease had one eye assigned to cryotherapy and the other to control. The majority of patients weighed under 1000 grams at birth and females outnumbered males by nearly a two-to-one ratio.+ Cryotherapy was generally performed at a gestational age of less than 40 weeks and a mean chronologic age of 10 weeks. Eleven patients showed improvement in both the treated and untreated eyes possibly due to variables among prematures not identified in the study. Eleven other patients experienced improvement in the treated eye and progression in the untreated eye. Using the binomial distribution on the latter group the P value was 0.0005 with a one-tailed hypothesis test and 0.001 with a two-tailed test, suggesting that in the sampled population cryotherapy appears to be preferred over no treatment.

Cryosurgery↗
PubMed1998

Application and evaluation of a mailed questionnaire for an epidemiologic study of Corynebacterium pseudotuberculosis infection in horses.

The objective of this study is to describe the design, application and validity of a self-administered (mailed) questionnaire to collect data on potential risk factors for Corynebacterium pseudotuberculosis infection in California horses. Horses admitted to the UC Davis Veterinary Medical Teaching Hospital (VMTH) between 1 July 1992 and 30 June 1994 served as the study base for case identification and simple random sampling of 800 control horses. A questionnaire was mailed to owners of the study horses, followed by a reminder postcard and a second copy of a questionnaire. Data were collected on owner and horse identity and demographics, horse management and use, geographic location, and general health-related issues. Return pattern over time as well as differential return proportions were described. The overall return proportion was 66% (587/890), and the completion proportion 55% (491/890). The number of returns over time followed a negative binomial distribution, with over 90% of all returns being in by the end of the fifth week after mailing, and over 99% at the end of the tenth week. Some categories within the variables age (between 2 and 3 years), breed (Thoroughbred and Standardbred horses) and gender (stallions) had significantly lower return proportions than expected (differential return; p < 0.05). The profile of these horses fits a section of the racehorse population that is served by the VMTH. Age, breed and disease status information was available from the VMTH medical records and from the questionnaire, and was used to determine the validity of the survey data. There was good agreement between the data from the two sources, and we therefore concluded that the quality of the survey information was sufficient to perform a risk-factor analysis. The mailed survey provided a rapid and cost-effective method of collecting additional information to supplement existing medical records.

Animals↗
PubMed2002

Some examples of, and some problems with, the use of nonlinear logistic regression in predictive food microbiology.

A new technique, nonlinear logistic regression, is described for modelling binomially distributed data, i.e., presence/absence data where growth is either observed or not observed, for applications in predictive food microbiology. Some examples of the successful use of this technique are presented, where the controlling factors are temperature, water activity, pH and the concentration of lactic acid, a weakly dissociating organic acid. Generally speaking, good-fitting models were obtained, as evidenced using various performance measures and goodness-of-fit statistics. As may be expected with a new statistical technique, some problems were encountered with the implementation of the modelling approach and these are discussed.

Escherichia coli↗
PubMed1997

Safety evaluation and confidence intervals when the number of observed events is small or zero.

A common objective in many clinical studies is to determine the safety of a diagnostic test or therapeutic intervention. In these evaluations, serious adverse effects are either rare or not encountered. In this setting, the estimation of the confidence interval (CI) for the unknown proportion of adverse events has special importance. When no adverse events are encountered, commonly used approximate methods for calculating CIs cannot be applied, and such information is not commonly reported. Furthermore, when only a few adverse events are encountered, the approximate methods for calculation of CIs can be applied, but are neither appropriate nor accurate. In both situations, CIs should be computed with the use of the exact binomial distribution. We discuss the need for such estimation and provide correct methods and rules of thumb for quick computations of accurate approximations of the 95% and 99.9% CIs when the observed number of adverse events is zero.

Confidence Intervals↗
PubMed1997

Photodynamic therapy for premalignant lesions in DMBA-treated hamsters: a preliminary study.

PURPOSE: Photodynamic therapy (PDT) involves the selective destruction of neoplastic cells through the activation of a photosensitizer by light. We have previously shown that the photosensitizer Photofrin (porfimer sodium) is selectively accumulated in transformed lesions destined to become malignant, but not yet definable histologically as precancers. The aim of this investigation was to determine if this premalignant tissue could be selectively destroyed by systemically administered Photofrin activated by 630 nm red light via an argon dye laser. MATERIALS AND METHODS: The carcinogenic model used was the DMBA (9, 10 dimethyl 1,2 benzanthracene)-treated hamster cheek pouch. The animals were treated with 0.5% DMBA in acetone thrice weekly for 6 weeks (experiment I, premalignant lesions), or 12 weeks (experiment II, malignant lesions). Ten animals were in experiment I; nine animals were in experiment II. These were divided into experimental and control subgroups. The 6-week experimental group received PDT and CO2 laser incision into the DMBA-treated area. The CO2 laser was used as a promoter of neoplasia in a field that had already undergone initiation from the DMBA treatment. The control groups received either CO2 laser incision alone into the DMBA-treated field or CO2 laser incision and argon pumped dye laser treatment (without Photofrin). The 12-week experimental group received PDT after CO2 laser excision of tumors. The controls received CO2 excision alone, or CO2 excision combined with postoperative hyperthermia. RESULTS: One hundred percent (three of three) of cheeks in experiment I receiving PDT developed necrosis of the treated area within 24 to 48 hours, but 0% (0 of three) subsequently developed tumors. No necrosis was seen in control cheeks receiving Photofrin without irradiation (0 of four) or irradiation without Photofrin (0 of six), and 56% (five of nine) of cheeks exposed to identical carcinogenic stimulus, without PDT, developed tumors (n = 9). In experiment II, 0% (0 of six) of cheeks receiving postoperative PDT developed tumor recurrence. In experiment II controls, 50% (three of six) of cheeks that underwent excision and hyperthermia developed tumor recurrence. In cheeks treated only with CO2 laser excision of tumors, a recurrence rate of 67% (four of six) was noted. These results were found to be statistically significant by the Student t-test on the binomial distribution (P < .01). One animal was treated with DMBA for 6 weeks, administered Photofrin, and the right cheek was irradiated and the animal was left for 30 weeks. The irradiated cheek epithelium necrosed but no cancer developed, whereas the positive control cheek developed a large cancer. CONCLUSION: These results suggest that photodynamic therapy possesses significant potential in elimination of premalignant tissue. This could be beneficial in treating potentially premalignant lesions such as oral leukoplakia, and useful as adjunctive therapy in removal of areas of field cancerization adjacent to surgical sites.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2001

Consensus evidence evaluation in resuscitation research: analysis of Type I and Type II errors.

OBJECTIVE: This paper addresses the following statistical question: 'if genuine improvements in cardiopulmonary resuscitation (CPR) were discovered that doubled the probability of resuscitation success in a series of randomized clinical trials, would they be recognized and incorporated into consensus guidelines?'. METHODS: Statistical powers for hypothetical individual clinical trials comparing experimental and control CPR were computed as a function of the study N when the true probabilities for immediate survival, 24 h survival, and discharge survival in the experimental group were twice those in the control group. Next, the binomial distributions describing the numbers of statistically significant studies in a series of equally powered trials of the same intervention were determined. These were compared with varying criteria for consensus among expert reviewers, expressed in terms of the number of 'positive' studies showing a statistically significant difference that reviewers would require before approving the experimental method. RESULTS: False-negative evaluations (i.e. failures to approve a technique that actually doubled survival) were extremely common under a wide range of realistic assumptions and consensus criteria, especially when simulated long-term survival data were considered. Similar methods showed that false-positive evaluations would be extremely rare, provided that at least two of the clinical trials in a series showed a statistically significant benefit of the experimental method. CONCLUSIONS: Optimization of evidence evaluation can and should be carried out to make better use of available data in creating resuscitation guidelines. One simple approach is the 'two and one quarter test': if at least two well-conducted studies in a series are significantly positive (P<0.05) comprising at least one-quarter of all studies in the series, a positive effect can be inferred with small Type I and Type II errors. In addition, greater reliance on modern, unbiased methods such as cumulative meta-analysis is needed to increase the sensitivity of evidence evaluation for detecting useful innovations in resuscitation.

Clinical Protocols↗
PubMed1997

A genetic basis for the sudden infant death syndrome sex ratio.

Sudden infant death syndrome, in 36 global data sets comprising 67378 postneonatal autopsied cases, has a male fraction of 0.612 which is significantly greater than the male birth fraction of 0.5122. Each of the sex ratios in the 36 data sets cannot be rejected as a random sample from a P = 0.612 binomial distribution. We hypothesize that an X-linked two-allele (a,A) single gene may be responsible for this consistent behavior. The Hardy-Weinberg principle predicts, given a 5% excess male birth rate, that a recessive allele (a) associated with sudden infant death syndrome, having a frequency of q = 2/3, could be responsible for the male fraction of 0.612. The absence of the A allele would be a necessary precondition for sudden infant death syndrome. We hypothesize that the syndrome occurs only with additional rare environmental conditions and rare physiological factors leading to extreme hypoxic stress, which reduces the sudden infant death syndrome rate to the order of 1 per 1000 live births.

Cohort Studies↗
PubMed1997

Reduced intraocular pressure after phacoemulsification and posterior chamber intraocular lens implantation.

PURPOSE: To ascertain whether phacoemulsification with posterior chamber intraocular lens (IOL) implantation causes long-term reduction in intraocular pressure (IOP). SETTING: Private practice, Kempten, Germany. METHODS: Intraocular pressure was measured in both eyes of 120 consecutive patients who were unilaterally phakic after phacoemulsification a mean of 17 months +/- 17 (SD) previously. Mean age of the 36 men and 84 women was 76 +/- 10 years. Data were analyzed using binomial distribution and the Wilcoxon signed-rank test. RESULTS: The median ratio of IOP in the pseudophakic eye to IOP in the phakic eye was 0.83. The IOP was lower in the pseudophakic eye in 96 patients (80%). The median IOP was 12 mm Hg in the pseudophakic eyes and 14 mm Hg in the phakic eyes (P < .001). As measured by the interquartile range, IOP distribution was more centered in the pseudophakic than in the phakic eyes (3 versus 4). The IOP in the pseudophakic eyes remained lower to the last measurement, 5 years postoperatively, and appeared to be independent of patient age. Lower IOP in the pseudophakic eye was consistently present in patients with higher IOP in the phakic eye (16 to 22 mm Hg). CONCLUSION: Phacoemulsification with posterior chamber IOL implantation reduced IOP in most but not all patients with a preoperative IOP of 22 mm Hg or less. This reduction was maintained over several years, with the cause yet to be established. Lower IOP may decrease the risk of subsequent glaucomatous nerve damage in these patients.

Aged↗
PubMed2002

Computational selection of distinct class- and subclass-specific gene expression signatures.

In this investigation we used statistical methods to select genes with expression profiles that partition classes and subclasses of biological samples. Gene expression data corresponding to liver samples from rats treated for 24 h with an enzyme inducer (phenobarbital) or a peroxisome proliferator (clofibrate, gemfibrozil or Wyeth 14,643) were subjected to a modified Z-score test to identify gene outliers and a binomial distribution to reduce the probability of detecting genes as differentially expressed by chance. Hierarchical clustering of 238 statistically valid differentially expressed genes partitioned class-specific gene expression signatures into groups that clustered samples exposed to the enzyme inducer or to peroxisome proliferators. Using analysis of variance (ANOVA) and linear discriminant analysis methods we identified single genes as well as coupled gene expression profiles that separated the phenobarbital from the peroxisome proliferator treated samples and discerned the fibrate (gemfibrozil and clofibrate) subclass of peroxisome proliferators. A comparison of genes ranked by ANOVA with genes assessed as significant by mixedlinear models analysis [J. Comput. Biol. 8 (2001) 625] or ranked by information gain revealed good congruence with the top 10 genes from each statistical method in the contrast between phenobarbital and peroxisome proliferators expression profiles. We propose building upon a classification regimen comprised of analysis of replicate data, outlier diagnostics and gene selection procedures to utilize cDNA microarray data to categorize subclasses of samples exposed to pharmacologic agents.

Algorithms↗
PubMed1991

Recovery of adult stages and microfilaraemia after low dose inoculation of third stage larvae of Litomosoides carinii in Sigmodon hispidus.

Because of the negative binomial distribution of filarial third stage larvae (L3) in their vectors, under natural conditions only a few are usually transferred per bite. After an inoculation of 5 L3 per animal into eight host animals at least one developed a long lasting patency based on one reproductive female only. After an inoculation of 15 L3, three of eight animals developed long lasting patency, harbouring between two and five fertile females. The rates of adult stages recovered were 0.43 and 0.30 respectively. The parasitaemias of the six patent animals in both experimental groups increased with the number of reproductive females present (r = 0.89, p = less than 0.005). All non-patent animals which were mf-negative in the pleural fluid and lung blood as well had a single sex or no worm load. In only one animal was there an apparently normal but non-reproductive pair of worms without any pathological alterations of the host animal. Encapsulated adult worms were found rarely, but independent of the final worm load or inoculation dose and always beside normal adults. In three of the 16 animals inoculated with 5 or 15 L3 patency passed after 10-12 weeks p.i., in two others it seemed to pass soon. After inoculation of 30, 40 or 60 L3 per animal patency passed early in about one half of 105 animals, when they were observed up to 24-36 weeks p.i. In conclusion all types of host defensive reactions are already visible after inoculation with such small doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1980

A rapid technique for the recovery of strongyloid infective larvae from pasture and soil samples.

A technique is described for the recovery of infective larvae of strongyloid nematodes from sediment resulting from the washing of pasture and soil samples. The process of recovery and counting of larvae is described by a model based on the binomial distribution. Tests of the technique have shown that it will recover approximately 50% of the larvae present in samples of pasture sediment of either 7.5 or 12.5 ml in volume after centrifugation. The efficiency of the technique was independent of the number of larvae present in samples of pasture sediment. The technique was shown to be less efficient and more variable in recovery of larvae from samples of soil sediment. Estimations in efficiency of recovery from soil sediment ranged from 64 to 110.2% and a significant effect of volume of sediment on recovery was detected.

Animals↗
PubMed2003

Modelling the transmission dynamics of Echinococcus granulosus in dogs in rural Kazakhstan.

Cystic echinococcosis, caused by Echinococcus granulosus, is an emerging disease in many parts of the world and, in particular, in eastern Europe and the former Soviet Union. This paper examines the abundance of infection of E. granulosus in the definitive host in southern Kazakhstan. Observed data are fitted to a mathematical model in order to decide if the parasite population is partly regulated by definitive host immunity and to define parameters in the model. Such data would be useful to develop simulation models for the control of this disease. Maximum likelihood techniques were used to define the parameters and their confidence limits in the model and the negative binomial distribution was used to define the error variance in the observed data. The results indicated that there were 2 distinct populations of dogs in rural Kazakhstan which had significantly different exposures to E. granulosus. Farm dogs, which are closely associated with livestock husbandry, particularly sheep rearing, had a relatively high mean abundance of 631 parasites per dog and a prevalence rate of approximately 23%. The best fit to the model indicated that there was significant herd immunity in the dog at this infection pressure. In contrast, village dogs which were more likely to be kept as pets had a much lower mean abundance of parasites of only 27 parasites per dog and a lower prevalence of 5-8%. With this village population of dogs, the best fit indicated negligible herd immunity.

Aging↗
PubMed1997

Experimental Ascaris suum infection in the pig: worm population kinetics following single inoculations with three doses of infective eggs.

To study population kinetics during primary Ascaris suum infections, 3 groups of 52 pigs each were inoculated with 100, 1000, or 10,000 infective eggs. In all groups, the majority of larvae was found in the liver on day 3 post inoculation (p.i.) and in the lungs on day 7 p.i. Liver white spots, caused by migrating larvae, were most numerous at day 7 p.i., whereafter they gradually healed, and only low numbers of granulation-tissue type white spots and lymphonodular white spots persisted at days 21-56 p.i. Independent of dose level, 47-58% of the inoculated eggs were recovered as larvae in the small intestine on day 10 p.i., but most larvae were eliminated at days 17-21 p.i. This elimination started earlier and removed a higher percentage of the worms with increasing inoculation dose, resulting in small strongly aggregated worm populations by day 28 p.i. (k of the negative binomial distribution was low: 0.2-0.4) without significant differences between groups. Thus, overdispersion, which is a characteristic of both porcine and human ascarosis, is found here under experimental conditions where aggregation factors like host behaviour, transmission rate, host status etc have been partly or totally controlled.

Animals↗