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Incidence in young adulthood-onset Type 1 diabetes mellitus in Lithuania during 1991-1997. Lithuanian Epidemiology Diabetes Study Group.

Our aim was to determine the incidence of Type 1 diabetes mellitus (T1DM) in the 15-39-yr-old Lithuanian population from 1991 to 1997. A specifically developed communications system with all endocrinologists/diabetologists and general practitioners involved in diabetes care covering 100% of the sample Lithuanian population was the initial data source. Annual reports from regional endocrinologists/diabetologists, death certificates and patients' lists from Diabetes Societies remained as secondary sources for case ascertainment. The annual incidence was calculated per 100,000 persons/yr. The trend in incidence was estimated by fitting the linear regression model with the annual incidence data. The total of 769 new cases (496 males and 273 females) of T1DM were recorded among the 15-39-yr-old population during the period 1 January 1991-31 December 1997. The average age-standardised incidence rate was 7.78 per 100,000 persons/yr [95% Poisson distribution confidence interval (CI) 7.25-8.35] and was slightly higher among males (9.68 per 100,000 persons/yr, 95% CI 8.87-10.57) than among females (5.71 per 100,000, 95% CI 5.07-6.43). Male/female ratio was 1.82 (95% CI 1.69-1.95). Results of the linear regression model showed that the incidence of T1DM in the 15-39-yr-old population had a tendency to increase. The incidence data of T1DM in Lithuania are appropriate to those in Poland and lower than in other countries of the Baltic Sea region.

Adolescent↗

Why are the majority of hereditary cases of early-onset breast cancer sporadic? A simulation study.

Population-based studies, including those of Ashkenazi Jews, have observed that at least 50% of women with early-onset breast cancer who carry a germ line mutation in BRCA1 or BRCA2 do not report a family history of the disease. That is, the majority of "hereditary" cases are "sporadic." Furthermore, the great majority of "familial breast cancers" are not hereditary. We conducted a simulation study to evaluate the probability that a woman with early-onset breast cancer is a mutation carrier, given the number of affected relatives, for a range of plausible values of allele frequency (0.001-0.01), and increased risk in mutation carriers (5-20, equivalent to cumulative risks to age 70 of 25-70%, respectively, for Australian women). Families consisted of a case proband and her mother, sisters, and maternal and paternal grandmothers, and aunts. The numbers of sisters and aunts were generated according to Poisson distributions, and ages were assigned according to a Weibull distribution. The simulated distributions of family history and of the prevalence of mutation carriers among case probands were in general similar to those observed in population-based studies, although there was a suggestion of heterogeneity of breast cancer risk in mutation carriers. As is being observed empirically in population-based samples, a family history of breast cancer was not a strong predictor of mutation status; each affected female relative increased the risk of being a mutation carrier by only 2- to 3-fold. The probability of being a mutation carrier was generally low, except in families with extreme histories of breast cancer.

Adult↗

Viral risks associated with wastewater reuse: modeling virus persistence on wastewater irrigated salad crops.

A model for virus decay on lettuce and carrot crops has been derived as part of a comprehensive wastewater irrigation microbial risk assessment model under development. Results from the decay modeling indicated the presence of a very persistent sub-population of viruses evidenced by an initial rapid phase of decay followed by a very slow phase. In addition, virus counts fitted a negative binomial rather than Poisson distribution indicating over-dispersion. Hence the data indicated that viruses were not uniformly distributed over the surfaces of both crops. The aim of this paper was to investigate the implications of over-dispersion and the presence of a very persistent sub-population of viruses for assessing viral illness from the consumption of lettuces and carrots irrigated with secondary treated effluent. When over-dispersion or clumping of viruses was accounted for, a significant increase in the heterogeneity in the risk estimates arose. In addition, predicted infection rates were significantly underestimated if the presence of a persistent sub-population of viruses was not considered in the decay kinetics of the risk model. Hence, both viral clumping and persistence sub-populations should be accounted for in future risk assessments of enteric viruses associated with wastewater reuse.

Agriculture↗

Second primary ovarian cancer among women diagnosed previously with cancer.

This study assessed the risk of second primary ovarian cancer among United States women diagnosed previously with invasive cancer. We analyzed data from cancer registries participating in the Surveillance, Epidemiology, and End Results program for women diagnosed with invasive cancer between 1973 and 1996. We calculated the risk [observed (O)/expected numbers (E)] of second primary ovarian cancer by cancer site and age at diagnosis of first primary cancer (<50 years and > or =50 years), race (all, white, and black), and years since first cancer (0-4, 5-9, 10-14, and 15-24 years). Statistical tests and 95% confidence intervals (CI) assumed a Poisson distribution. A significantly increased risk of ovarian cancer was found for women who were aged <50 years at diagnosis with melanoma (O/E = 3.5, 95% CI = 2.1-5.5) or cancer of the breast (O/E = 6.0, 95% CI = 4.9-7.2), cervix (O/E = 4.2, 95% CI = 2.6-6.3), corpus uteri (O/E = 11.9, 95% CI = 7.3-18.4), colon (O/E = 17.9, 95% CI = 11.1-27.3), or ovary (O/E = 4.9, 95% CI = 2.7-8.2). No increased risk was found for women aged > or =50 years. Ovarian cancer risk remained elevated after these first primary cancers 5-9 years after diagnosis; for breast and colon cancer, risk remained elevated 15-24 years after diagnosis. Women > or =50 years at diagnosis with melanoma or cancer of the cervix, corpus uteri, ovary, rectum, or lung and bronchus were at a decreased risk for second primary ovarian cancer. Ovarian cancer risk is higher than expected for women who were diagnosed with certain types of cancer at <50 years of age.

Age Factors↗

[Creutzfeldt-Jakob syndrome in the county of Storstrom during the period 1990-1999. Was there a significant accumulation of cases?].

INTRODUCTION: In the county of Storstrøm with about 250,000 inhabitants, ten cases of Creutzfeldt-Jacob disease (CJD) were diagnosed at the Department of Neurology, Naestved County Hospital during the decade 1990-1999. Only one case is to be expected every four years in the county. Therefore we decided to investigate if a significant accumulation had occurred. METHODS: Case records were examined to see whether the patients complied with the WHO criteria for possible, probable, or certain sporadic CJD. Poisson distribution with correction for age was used to compare the observed incidence with the expected incidence of 1 case/million/year. RESULTS: Eight cases complied with the diagnostic criteria: two certain, three probable, two possible, and one familial. The incidence of certain and probable cases was 1.9 per million per year during the period, which does not constitute a significant increase (p = 0.18). CONCLUSION: The result is consistent with the fact that all time or space clustering of CJD ever reported has proved ascribable to familial cases, and with the fact that case-control studies have never identified environmental risk factors for sporadic CJD.

Aged↗

[Sterility control: basic mathematical considerations (author's transl)].

The subject of control of sterility in homogenous lots by means of random sampling is discussed. The probability that non-sterile lots may be declared as accepted, was calculated by means of hypergeometric, binomial, and Poisson distribution. The following factors were considered: size of samples, size of lots, and degree of contamination of lots. The values obtained were reproduced in graphs (Figs. 1, 2, and 4). Reference is made to the conditions that have to be met in each case to enable a use of the various distribution functions for a calculation of the acceptance probability of non-sterile lots (Table 1). Furthermore, the necessary size of samples to contain at least one contaminated unit was calculated by means of binomial distribution for probabilities of 90, 95, and 99% (Fig. 3). For example, from a lot having a degree of contamination of 10%, 30 units would have to be assayed for sterility to recognize non-sterility of such a lot in 95% of cases. A degree of contamination of 1% would reguire already 300 units to be examined...

Mathematics↗

Quantitative real-time polymerase chain reaction for monitoring minimal residual disease in patients with advanced indolent lymphomas treated with rituximab, fludarabine, mitoxantrone, and dexamethasone.

Fludarabine and rituximab (Rituxan; Genentech, Inc, South San Francisco, CA, and IDEC Pharmaceuticals, San Diego, CA) are active against indolent lymphomas. We have previously shown the safety and efficacy of the combination of FND (fludarabine/mitoxantrone/dexamethasone) in relapsed and subsequently untreated patients with stage IV indolent lymphomas. Currently, we treat patients with stage IV indolent lymphomas who are previously untreated, younger than 60 years, human immunodeficiency virus-negative, and have adequate organ and marrow function with FND and random assignment to concurrent or delayed administration of rituximab. We have developed a quantitative real-time polymerase chain reaction assay for t(14;18). With 1 microg of DNA, this assay detects 0.6 copies in 55% of reactions, as expected for the Poisson distribution. When 1microg of DNA was analyzed in duplicate, cells with the t(14;18) were detected in peripheral blood of 22% of 152 volunteer blood donors. Quantitation showed that numbers of t(14;18) cells were higher than the statistical upper normal limit (mean of all volunteer values plus standard deviations) in 2% of volunteer blood donors. By contrast, 36% of blood or marrow specimens from follicular lymphoma patients were positive, and the number of cells with t(14;18) was higher than the normal upper limit in 26%. The presence of cells with t(14;18) and their numbers are prospectively quantitated in blood and marrow of patients treated with FND plus rituximab to determine their clinical significance both at presentation and during therapy.

Actins↗

[Studies on the spatial and familial aggregation of double Y nuclear family in gastric cancer pedigree].

OBJECTIVE: To explore whether there existed spatial and familial aggregation in gastric cancer in Yangzhong City of Jiangsu Province. METHODS: Using the data collected from cancer incidence registry and report system in Yangzhong City and newly designed investigation for double Y nuclear family, a genetic epidemiological study was conducted in 448 nuclear pedigrees with gastric cancer and 437 control pedigrees, involving 5 242 family members. RESULTS: Chi square test of goodness-of-fit for Poisson distribution showed there was difference between real incidence rate of gastric cancer in all townships and towns in Yangzhong and expected distribution, with chi(2) = 191.07, P < 0.001. The highest rate was in Sanyao, Changhong and Youfang townships, which was 2.2 times higher as that in the areas with low-incidence rate. Prevalence rate of gastric cancer was significantly higher in the siblings (5.42%) and parents (8.65%) of the probands, than that in siblings and parents of their spouses (4.94% and 3.20%, respectively). Prevalence rate of gastric cancer in the offspring with both parents suffered from gastric cancer was the highest, 22.58%. Test for goodness-of-fit of binominal distribution showed that there was significant difference between observed number and expected number of pedigrees with gastric cancer, with P < 0.0001. CONCLUSION: There was not only significantly spatial aggregation of gastric cancer in Yangzhong City, but also familial aggregation, which coincided with a mode of multi-genetic inheritance based on preliminary results and laid a foundation for exploring the difference in gentic susceptibilities and environmental factors for gastric cancer in Yangzhong City.

China↗

[Risk of drug-induced agranulocytosis: an approximation to risk analysis arising from spontaneous notification of agranulocytosis cases among patients treated with calcium dobesilate].

BACKGROUND: Frequently, decisions about the safety of drugs are based on isolated cases of patients that develop a disease, while they have been taken a drug. A new method to detect, using spontaneous reporting, increases in agranulocytosis risk among patients treated with calcium dobesilate is shown. METHOD: Using data of dobesilate sales, the maximum number of patients treated in a year was calculated. Spontaneous reports of agranulocytosis associated to dobesilate notified along the period 1985-2000 were identified. The number and the maximum number of cases explained by the agranulocytosis risk in a general population were calculated using the distribution of Poisson, assuming several reporting rates. Similarly, the influence of number of patients older than 60 and the duration of exposure to the drug were analysed. RESULTS: The number of spontaneously reporting cases of agranulocytosis associated to dobesilate, in the period 1985-2000 was not greater than the maximum number of cases predicted by the agranulocytosis risk in a general population. Probably, a high number of dobesilate-treated patients had an advanced age and/or took the drug during several months. In these conditions, it is more difficult to identify an increase of risk associated to drug. CONCLUSIONS: To calculate the risk of agranulocytosis associated to a drug is required to consider the basal risk of agranulocytosis in a general population as well as its possible modifications in the population of patients treated with the drug.

Adverse Drug Reaction Reporting Systems↗

What is natural fertility? The remodeling of a concept.

This paper applies three log-linear models to Louis Henry's original 1961 natural fertility data in order to test various assumptions leading to ways of obtaining a standard natural fertility schedule through explicit modeling. "The models specify that births follow an independent Poisson distribution for each age interval of each population. All parameters are estimated through an iterative maximum-likelihood procedure." The author suggests that the model selected provides better estimates of the standard natural fertility function than previous models.

Demography↗

Migration models incorporating interdependence of movers.

"In this paper we describe a development of the Poisson model in which households are assumed to migrate independently, but the expected number of migrants is given by a Poisson distribution generalized by an empirically given household-size distribution.... The model is fitted to data on short-distance migration within the English county of Hereford and Worcester.... The data set used comes from the Special Migration Statistics (series II) produced as part of the 1981 British Census." The sparse nature of the data raises problems in assessing goodness of fit, because the deviance value is unusually low. This is tackled using simulation methodology.

Demography↗

[Study of the incidence of invasive pneumococcal disease in neonates and childre aged less than 5 years in the Basque country and Navarre (Spain)].

BACKGROUND: Streptococcus pneumoniae is the most commonly reported bacterial cause of bacteremia and bacteremic pneumonia and the second most frequent cause of meningitis. OBJECTIVE: To establish the incidence, characteristics and serotypes causing invasive pneumococcal disease in children aged less than 5 years in two Autonomous Communities in Spain, the Basque country and Navarre, between 31 May 1988 and 1 June 2001. PATIENTS AND METHODS: We performed a descriptive, observational and retrospective study. The study population was composed of children diagnosed with invasive pneumococcal disease in the public and private hospitals with a pediatrics departments. Invasive pneumococcal disease was defined as isolation of S. pneumoniae in blood, cerebrospinal fluid or any other sterile biological fluid. Medical records were reviewed and demographic and diagnostic variables were analyzed. Age-adjusted frequency rates were established for both regions using direct standardization. Confidence intervals were obtained by Poisson distribution. SPSS for Windows 10.0 and Epidat 2.1 were used for the analysis. Data were obtained from the 1999 municipal population census. RESULTS: One hundred seventy-one children aged 0-5 years were included. A total of 40.9 % (70 patients) were aged less than 12 months and 68.4 % were aged 0-2 years; 16.4 % had received drug therapy before diagnosis. The most common forms of presentation were occult bacteremia (45.6 %), bacteremic pneumonia (27.5 %) and meningitis (14.6 %). The most frequent complications involved the respiratory tract, with pleural effusion in 23 % of cases of pneumonia. The standardized annual incidence rate of invasive pneumococcal disease (cases per 100,000) in children aged 0-59 months was 58.82 (95 % CI: 27.99-89.65) in Navarre and 55.35 (95 % CI: 38.81-71.88) in the Basque Country. In children aged 0-23 months, the overall incidence was 93.49 cases per 100,000 children (95 % CI: 77.32-112.04) and in infants aged 0-11 months, it was 110,21 cases per 100,000 children (95 % CI: 85.91-139.24). The incidence rates for meningitis and bacteremia in children aged 0-23 months was 15.98 (95 % CI: 9.76-24.68) and 51.14 (95 % IC: 39.38-65.30) cases per 100.000 children. Fifty-nine strains were serotyped. The most frequent serotypes/groups were 1, 4, 6B, 14, 18C, 19 and 23F. A total of 52.15 % of the serotypes were penicillin-susceptible and 93 % were cefotaxime-susceptible. The serotypes/groups with the highest rates of resistance were 6B, 14,19, 23F and 35. CONCLUSION: Our incidence rates are similar to those observed in other countries such as the United States and are higher than those reported for the rest of Europe. Vaccine coverage is similar to that described in other articles.

Child, Preschool↗

The use of negative binomial modelling in a longitudinal study of gastrointestinal parasite burdens in Canadian dairy cows.

The epidemiology of bovine gastrointestinal nematodes was investigated through a 1-year (October 1999 to September 2000) longitudinal study in 38 Canadian dairy herds from 4 different provinces (Prince Edward Island, Quebec, Ontario, Saskatchewan). For each herd, fecal egg counts from 8 randomly selected animals were performed on a monthly or quarterly basis. Larval cultures were performed once, to determine the species breakdown of the parasites. All producers were interviewed regarding herd management practices. The observed fecal egg counts were low in this study, with a range from 0 to 419 nematode eggs per 5 g of feces. The mean count was 9.8 and the median was 1. Standard transformations failed to normalize the data, which followed an over-dispersed Poisson distribution. A zero inflated negative binomial model was applied to assess factors that would influence the fecal egg counts. Identified associations were: egg counts were lowest in the winter and highest in the late spring; first-lactation cattle had higher counts than older cows; if manure was spread mechanically on pastures used by lactating cattle the egg counts were higher; and if manure was spread on heifer-pastures, the adult cows had lower counts. In herds where pasture use was more extensive, the cattle had higher fecal egg counts. The difference in pasture exposure was found to be a main contributor to an observed difference in fecal egg counts among herds in the 4 provinces.

Animal Husbandry↗

The Use of Spectral Analysis of Limiting Dilution for Investigating the Immune Response.

In this study we present a method for characterizing a spectrum of cells engaged in the humoral response by two parameters: the frequency and potential activity of antigen specific precursor cells. Spleen cells from mice immunized with ovalbumin were placed in microcultures in a limiting dilution assay. The values derived from positive cultures in an activity/cell number plot were compatible with Poisson distributions for distinct families of precursor cells displaying either positive or negative (suppressor-like) activities. Proposed limiting dilution spectral analysis combines the potentialities of the standard limiting dilution analysis with those provided by histograms of distribution according to the activity of positive cultures. This method opens new opportunities in detecting and characterizing distinct groups of limiting precursor cells.

Journal Article↗

Quantitative studies on the precursors of cytotoxic lymphocytes. I. Characterization of a clonal assay and determination of the size of clones derived from single precursors.

A microculture system for estimating the frequency of cytotoxic lymphocyte precursors (CLP) to alloantigens is described. Cytotoxic T lymphocytes (CL) were generated by culturing limiting numbers of RNC (H-2k)-nu/+lymph node (LN) cells with irradiated C3D2F1 (H-2k/d) spleen cells in the presence of RNC-nu/nu spleen cells for 7 days in microtiter trays. At the end of the culture period, individual wells were assayed for cytotoxic effector cells directed against 51CrP815 (H-2d) target cells. The effector cells generated under these conditions are sensitive to killing by rabbit anti-mouse brain serum and guinea pig complement. The process of differentiation from precursors to CL is radiation sensitive (Do approximately 180 rads). The frequency of precursors for H-2d was calculated by fitting the proportion of nonresponding cultures to the zero order term of the Poisson distribution, Po = e-vn, where Po = per cent nonresponders, v = precursor frequency, and N = number of LN cells cultured per well. The frequency of precursors in the RNC-nu/+LN population responding to the H-2d haplotype was found to be 1 in 776. Under conditions where no backstimulation is possible, the frequency of precursors responding to the H-2d haplotype is 1 in 885 for B6-nu/+LN and 1 in 2550 for B6-nu/+ spleen, respectively. In combination with a visual assay for individual CL, it was found that the average clone size per precursor after 7 days in culture is about 1040. Our assay could detect clones with as few as 40 CL/well. Since the average clone size in 26 times the detection limit, we conclude that the assay for CLP is highly sensitive and does not represent a minimum estimate.

Animals↗

[Visual acuity and driver's licence among young people. Are routine vision tests necessary?].

The minimum visual acuity for obtaining a driver's licence for smaller vehicles in Norway is 0.5 (5/10). However, visual acuity is not routinely tested on application for the licence. Among 720 conscripts examined by a draft board, five (0.694%) had a visual acuity of less than 0.5, and did not have spectacles or lenses. The estimated standard deviation is 0.31%. The upper 95% one sided confidence limit was estimated to be 1.46% (Poisson-distribution). It is concluded that checking the vision of all applicants for a driver's licence would have only a marginal effect on safety.

Adult↗

Using mandatory data collection on multiresistant bacteria for internal surveillance in a hospital.

OBJECTIVES: Multiresistant pathogens cause major clinical problems and considerably increase treatment costs. Since 2001 the Protection Against Infection Act (PIA) obligates hospitals in Germany to the documentation of multiresistant bacteria. We analyzed the use of these data for routine internal surveillance. METHODS: We used standard data collected for the mandatory documentation and studied consecutive diagnoses of Methicillin-resistant Staphylococcus aureus (MRSA) in a 893-bed tertiary level hospital in North Rhine-Westphalia in Germany. Based on the Poisson distribution for the cumulative yearly incidence of MRSA, we defined a threshold level for an outbreak. RESULTS: During a 12-month time period 80 patients were diagnosed with MRSA. The time structure and spatial distribution of different MRSA phenotypes (defined through specific antibiotic resistance patterns) were consistent with the within-hospital transmission. In the two preceding time periods of 12 months each, 15 respectively 8 patients with MRSA were found. The defined alert threshold level for cumulative yearly incidence was crossed in the beginnings of the outbreak. CONCLUSION: Monitoring the mandatory data collected on multiresistant bacteria allows the early detection of accumulations suspect for the within-hospital transmission. This knowledge can be used for a fast reaction and breaking off the transmission chains.

Data Collection↗

Incidence of pancreatitis in HIV-1-infected individuals enrolled in 20 adult AIDS clinical trials group studies: lessons learned.

OBJECTIVE: To report on the incidence of clinical- and laboratory-defined pancreatitis in HIV-1-infected individuals treated with antiretrovirals (ARVs). METHODS: Pancreatitis incidence rates were calculated based on a Poisson distribution for subjects enrolled in 1 or more of 20 Adult AIDS Clinical Trials Group studies from October 1989 through July 1999. RESULTS: A total of 8451 subjects were enrolled. The overall pancreatitis rates were 0.61 per 100 person-years (PYs) clinical and 2.23 per 100 PYs clinical/laboratory. Pancreatitis rates for single, dual, and triple nucleoside reverse transcriptase inhibitors (NRTIs) were similar. Rates of pancreatitis in didanosine (ddI) arms seemed to be dose dependent. Pancreatitis rates in ddI/hydroxyurea (HU) arms were not significantly different from the rates for ddI alone. Overall pancreatitis rates for ddI/stavudine (d4T) trials were high at 4.16 per 100 PYs clinical and 6.25 per 100 PYs clinical/laboratory. The highest rates were seen with the combination of indinavir (IDV)/ddI/d4T with or without HU. CONCLUSIONS: The combination of NRTIs and definition has an impact on the incidence of pancreatitis. Standardization of definition and more comprehensive evaluations are needed to determine how much of this pancreatitis is directly caused by ARVs and how much is attributable to preexisting comorbidities and other known risk factors.

Acquired Immunodeficiency Syndrome↗