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PubMed2000

Inferring infection processes of a parasitic nematode using population genetics.

The distribution of genetic differentiation in a population of the parasitic nematode Strongyloides ratti divided between rat hosts was determined. We applied population genetic theory to these data to determine the source of new infections. We estimate the rate at which a rat acquires a new infection from (a) the existing subpopulation of parasites within that rat ('self-reinfection') versus (b) the wider environment ('immigration'). We find that the observed levels of genetic diversity and differentiation in the study population are consistent with low to moderate rates of self-reinfection and inconsistent with high rates of self-reinfection.

Animals↗
PubMed1997

Incidence of Crohn's disease in Stockholm County 1955-1989.

AIM: To evaluate the incidence of Crohn's disease in Stockholm County between 1955 and 1989. METHODS: A cohort of 1936 patients with Crohn's disease was retrospectively assembled. Incidence rates and changes in disease distribution were assessed. RESULTS: The mean increase in incidence was 15% (95% confidence intervals 12% to 18%) per five year period with a mean annual incidence rate at 4.6/10(5) during the last two decades. The mean incidence for the entire study period was similar for men and women. The mean age at diagnosis increased from 25 years in 1960-64 to 32 years in 1985-89, partly because of an increasing proportion of patients aged at least 60 years at diagnosis. The proportion of patients with colonic Crohn's disease at the time of diagnosis increased from 15% to 32% (17% difference; 95% confidence intervals 12% to 23%) whereas the proportion of patients with ileocaecal disease decreased from 58% to 41% (17% difference; 95% confidence intervals 10% to 24%) during the study period. Elderly patients had a higher proportion of small bowel disease and a lower proportion of ileocolonic disease compared with the younger patients. CONCLUSION: The incidence rate of Crohn's disease in Stockholm has stabilised at 4.6/10(5) and the proportion of elderly patients has increased during a 35 year period. Colonic Crohn's disease has increased in frequency with a reciprocal decrease in ileocaecal disease.

Adolescent↗
PubMed2003

Crohn's disease, ulcerative colitis, and measles vaccine in an English population, 1979-1998.

STUDY OBJECTIVE: s: To study the hospitalised incidence of Crohn's disease (CD) and ulcerative colitis (UC) from 1979 to 1998; and to determine whether the introduction of the measles vaccination programme was associated with an increase in the young. DESIGN: Analysis of linked data on hospital admissions; a cohort analysis of the effect of the measles vaccination programme on the incidence of hospitalised CD and UC; and a comparison of these results with those from previous studies on the association between measles vaccine and CD or UC. SETTINGS: Southern England. SUBJECTS: People admitted to hospital with a main diagnosis of CD (1959 people) or UC (2018 people). MAIN RESULTS: Overall, the incidence of hospitalised CD showed no significant change over the 20 year period: the average change per year was 0.08% (95% confidence interval: -0.7% to 0.9%). The relative risk associated with the measles vaccination programme was not significant (0.91: 0.5 to 1.4). The estimate differed significantly from the relative risk of 3.0 obtained in the original study reporting an association, but agreed with the combined estimate from three subsequent studies (0.95: 0.6 to 1.5). The results for UC were similar. CONCLUSIONS: The incidence of hospitalised CD and UC remained stable over the 20 years, 1979 to 1998. Whatever caused the marked increases in CD and UC in the mid-20th century must itself have stabilised in this region. These results, together with those from other studies, provide strong evidence against measles vaccine causing CD or UC.

Adolescent↗
PubMed2003

Geographic excess of estrogen receptor-positive breast cancer.

Elevated and more rapidly increasing breast cancer incidence rates have been described for Marin County, California (CA), a homogeneous, high socioeconomic status population for which yearly surveillance is facilitated by its status as a county. The present study evaluates the histology and hormonal phenotype of the excess breast cancer cases occurring in white, non-Hispanic women living in Marin County between 1992 and 2000 and compares them with patterns occurring in the rest of the San Francisco Bay Area (SFBA) and other urban parts of CA. Incidence data for invasive breast cancer histological subtypes and estrogen receptor (ER) and progesterone receptor (PR) status were obtained from the 1992-2000 Surveillance, Epidemiology, and End Results program. Expected numbers for Marin County were computed based on age-specific rates for five other SFBA counties. Incidence rates were age-adjusted to the 2000 United States standard. Marin County breast cancer diagnoses during 1992-2000 compared with other SFBA and other urban CA Surveillance, Epidemiology, and End Results county rates for white, non-Hispanic women consisted of a disproportionate increase in ER+/PR+ tumors. The observed absolute excess (versus expected) numbers of Marin County ER+/PR+ lobular and nonlobular (predominantly ductal) cases were similar; however, the relative increase appeared greatest for lobular breast cancer. The progressive increase in breast cancer incidence rates observed in Marin County over the past decade is occurring in women with high prevalence of risk factors predisposing toward excess development of ER+/PR+ breast cancer.

Adult↗
PubMed1999

The influence of clinically induced variability on the bi-axial fracture strength of cemented aluminous core porcelain discs.

OBJECTIVES: Zinc phosphate cements are supplied in powder/liquid form so that a range of mixing ratios are naturally generated in clinical practice. However, these cements are known to have a deleterious effect on dental ceramics and the impact of variations in cement mixing on the strength of dental porcelain was investigated in the present study. METHODS: Vitadur-N core porcelain was fabricated into discs (15 mm diameter and 2 mm thickness), zinc phosphate cements of different mixing ratios were applied to the discs to produce a luting cement thickness and the samples were stored for 24 h prior to testing in a water-bath at 37 +/- 1 degrees C. The mean fracture strength, standard deviation and associated Weibull moduli (m) of the coated porcelain discs were determined as a function of mixing ratio using bi-axial flexure (ball-on-ring) by fracturing sets of 30 specimens coated with cements manipulated at different mixing ratios. RESULTS: The strength data for the coated porcelain discs showed little variation in magnitude and consistency ranging from 108 +/- 8.3 MPa (m = 14.0 +/- 2.6) at 1.7 g/ml to 112 +/- 8.5 MPa (m = 14.6 +/- 2.7) at 2.6 g/ml and 108 +/- 8.1 MPa (m = 14.4 +/- 2.6) at 3.2 g/ml. However, the plots of survival probability against strength for coated specimens prepared using mixing ratios below that recommended by the manufacturers' for luting purposes (2.6 g/ml), appeared to develop an asymmetry at the lower values of strength. SIGNIFICANCE: It was proposed that the increased corrosive acidic environment for cements prepared at mixing ratios below 2.6 g/ml may have extended pre-existing flaws in the porcelain discs thereby possibly producing the asymmetry in the survival distributions.

Aluminum Oxide↗
PubMedDate not supplied

A review of some extensions to generalized linear models.

Although generalized linear models are reasonably well known, they are not as widely used in medical statistics as might be appropriate, with the exception of logistic, log-linear, and some survival models. At the same time, the generalized linear modelling methodology is decidedly outdated in that more powerful methods, involving wider classes of distributions, non-linear regression, censoring and dependence among responses, are required. Limitations of the generalized linear modelling approach include the need for the iterated weighted least squares (IWLS) procedure for estimation and deviances for inferences; these restrict the class of models that can be used and do not allow direct comparisons among models from different distributions. Powerful non-linear optimization routines are now available and comparisons can more fruitfully be made using the complete likelihood function. The link function is an artefact, necessary for IWLS to function with linear models, but that disappears once the class is extended to truly non-linear models. Restricting comparisons of responses under different treatments to differences in means can be extremely misleading if the shape of the distribution is changing. This may involve changes in dispersion, or of other shape-related parameters such as the skewness in a stable distribution, with the treatments or covariates. Any exact likelihood function, defined as the probability of the observed data, takes into account the fact that all observable data are interval censored, thus directly encompassing the various types of censoring possible with duration-type data. In most situations this can now be as easily used as the traditional approximate likelihood based on densities. Finally, methods are required for incorporating dependencies among responses in models including conditioning on previous history and on random effects. One important procedure for constructing such likelihoods is based on Kalman filtering.

Animals↗
PubMed2000

Tests for homogeneity of the risk ratio in a series of 2x2 tables.

We often apply the risk ratio to measure the strength of a causal relationship between a suspected risk factor and a disease of interest. In this paper we consider testing the homogeneity of risk ratio over a series of 2x2 tables. In addition to the classical weighted least squares (CWLS) test procedure, we consider two test procedures using simple transformations of the CWLS statistic and develop three other asymptotically weighted test procedures. On the basis of Monte Carlo simulation, we conclude that the commonly-used CWLS test procedure is generally conservative, especially when the number of 2x2 tables is large and the mean group size per table is moderate or small. We further find that two of the test procedures discussed here can not only generally outperform the CWLS test procedure, but also perform well in a variety of situations considered in this paper. Finally, we illustrate the use of these testing procedures with an example of six randomized trials that assess the effects of aspirin on the prevention of death in post-myocardial infarction patients.

Aspirin↗
PubMed2005

A reconsideration of the Campylobacter dose-response relation.

As a major foodborne pathogen, Campylobacter jejuni receives much attention in quantitative risk assessment. To date, all dose-response assessments have been based on a single human feeding study which unfortunately provides incomplete and possibly biased information on the dose-response relation. An incident at a dairy farm, where several children from a school class became ill as a result of drinking raw milk contaminated with C. jejuni, appeared to show a very clear dose-response relation between the amount of milk consumed and the attack rate. This relation was very nearly exponentially shaped and, therefore, seemed to conflict with the rather slowly rising dose-response relation established in the feeding study. Here we show that both datasets can be reconciled when illness and infection are considered separately. This not only provides new information on the illness dose-response relation for Campylobacter, but also amends the infection dose-response relation because of their conditional dependence.

Adolescent↗
PubMed1998

Epidemiological study of myasthenia gravis in the province of Reggio Emilia, Italy.

We carried out a retrospective incidence, prevalence and mortality survey of myasthenia gravis in the province of Reggio Emilia in Northern Italy. Based on 49 patients, the mean incidence per year for the period 1980 through 1994 was 7.8 per 1,000,000. On 31 December 1994 the prevalence rate was 117.5 per 1,000,000 for all patients, either active or recovered (50 cases in a population of 427,493) and 103.4 per 1,000,000 for the active disease. In the 15-year period 1980-1994 the average mortality rate was 1.0 per 1,000,000 per year. The average age at onset was 44.6 +/- 21.0, and the average age at the time of prevalence determination was 51.1 +/- 19.6 for the active disease. At the time of diagnosis, 21 patients (36.8%) were classed in group I according to Osserman's criteria, 31 in group II (54.4%), (19 in group II-A and 12 in group II-B), and the other 5 (8.8%) in group III. Of all the prevalence cases, 6 (12%) were in remission without therapy and 6 with therapy, while most of the others 16 (32%) were classed in group I, 15 (30%) in group II, and 1 (2%) in group III. Thymectomy was performed in 20 patients (35.1%), 12 (21%) had thymoma (malignant in 4 cases), 6 had thymic hyperplasia while in two patients thymic histology was normal. The relation the grade of Osserman's scale at the time of incidence and the presence of thymoma were significant. Higher grades of Osserman's scale were associated were malignant thymoma. Furthermore the relationship between thymectomy and the grade of Osserman's scale at the date of prevalence was significant for the presence of lower grades of Osserman's scale in the patients submitted to thymectomy.

Adolescent↗
PubMed1998

Risk of colorectal cancer in relatives of patients with inflammatory bowel disease (Denmark)

OBJECTIVES: It has been suggested that inflammatory bowel disease (IBD) and colon cancer are associated because they have genetic susceptibility in common, rather than IBD causing cancer. We examined the risk of colorectal cancer in first-degree relatives of patients with IBD in order to evaluate if they share the same genetic susceptibility. METHODS: We identified patients with IBD in the Danish Hospital Discharge Registry. A cohort of all first-degree relatives to these patients were linked to the Danish Cancer Registry. Colorectal cancers observed were compared with expected values based on age, gender, and calendar-specific incidence rates in the general population. RESULTS: Among 4,496 patients with IBD, a total of 19,645 relatives were identified. For parents of patients with Crohn's disease, we observed 19 cases of colorectal cancer compared with 20 expected (standardized incidence ratio [SIR] = 1.0, 95 percent confidence interval [CI] = 0.6-1.5). For parents of patients with ulcerative colitis, 55 cases were observed compared with 51 expected (SIR = 1.1, CI = 0.8-1.4). CONCLUSIONS: The study did not corroborate the hypothesis that the same genetic factors play a significant role in the etiology of colorectal cancer and IBD, but more information is needed to disregard the possible link between IBD and colon cancer.

Adult↗
PubMed2002

A cohort study of dietary carotenoids and lung cancer risk in women (Canada).

OBJECTIVE: To investigate the association between dietary carotenoid intake and lung cancer risk in women. METHODS: A case-cohort study was undertaken in the Canadian National Breast Screening Study dietary cohort, which consists of 56,837 women who completed a self-administered dietary questionnaire. The cohort was recruited between 1980 and 1985, and during follow-up to the end of 1993 a total of 196 cohort members were diagnosed with incident lung cancer. For analysis, a subcohort consisting of a random sample of 5681 women was selected from the full dietary cohort. After exclusions for various reasons, the analyses were based on 155 cases and 5,361 non-cases. RESULTS: When compared to those in the lowest quartile level of intake, the adjusted incidence rate ratios (95% confidence intervals) for those in the highest quartile levels of alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, and lutein intake were 0.90 (0.51-1.58). 1.40 (0.76-2.59), 0.66 (0.33-1.32), 1.04 (0.61-1.76), and 1.26 (0.70-2.24), respectively; none of the associated tests for trend was statistically significant. CONCLUSION: These results suggest that there is no association between dietary carotenoid intake and lung cancer risk. at least for the range of intakes observed here.

Adult↗
PubMed1997

Stroke morbidity in professional drivers in Denmark 1981-1990.

BACKGROUND: Little has been published on the possible associations between professional driving and stroke although it is well documented from several countries that professional drivers have an increased risk of coronary heart disease. There are common aetiologic factors for coronary heart disease and stroke. The aim of the present study is to estimate the risk of stroke among professional drivers in 13 male and 4 female groups defined by employment status and industry. METHODS: Cohorts of all gainfully employed 20-59 year old Danes were formed to compare Standardized Hospitalization Ratios (SHR) for stroke between occupational groups. The follow-up period was 10 years. RESULTS: A consistent pattern of high risk was found for all groups of male drivers except removal men. The group 'All drivers' had an increased risk of stroke SHR = 130 for men (95% confidence interval [CI]: 123.6-137.5) and SHR = 148 for women (95% CI: 113.9-191.4). Standardization for employment status reduced the risks but they were still found to be statistically significantly increased: SHR = 114 for men (95% CI: 108.2-120.4) and SHR = 130 for women (95% CI: 100.0-168.0). CONCLUSIONS: Professional driving is associated with an increased risk of stroke morbidity.

Adult↗
PubMed2002

Incidence and short-term outcome of cerebral infarction in young adults in western Norway.

BACKGROUND AND PURPOSE: We sought to determine the incidence and short-term outcome of people aged 15 to 49 years with first-ever cerebral infarction in 1988-1997 in Hordaland County, Norway. METHODS: Cases were found from computer search of hospital registries and detailed review of patient records. Stroke subtype was classified according to the major intracranial artery affected. Short-term outcome was evaluated by the modified Rankin Scale (mRS). RESULTS: A total of 96 women and 136 men met the inclusion criteria. The average annual incidence was 11.4/100 000. Women outnumbered men among those aged <30 years (P=0.059); men predominated among those aged > or =30 years (P=0.004). A total of 148 patients had anterior circulation infarction (64%), and 84 had posterior circulation infarction (36%) (P<0.001). Patients with posterior circulation infarction had better mRS score at discharge (P=0.005). Eighty percent had favorable outcome (mRS score < or =2). The 30-day case fatality rate was 3.4%. The recurrence rate in hospital was 2.2%. CONCLUSIONS: The incidence was in the lower range compared with other reports from western Europe. Although men predominated, there was a strong trend toward more women among patients aged <30 years. Short-term outcome was generally good. Patients with posterior circulation infarction had significantly better short-term outcome.

Adolescent↗
PubMed2003

Improvements in treatment of coronary heart disease and cessation of stroke mortality rate decline.

BACKGROUND AND PURPOSE: Many countries observed rapidly declining stroke mortality rates during 1970-1990, followed by a slowing or a cessation of this decline. This slowing was seen for both sexes and all ages. Here we test the hypothesis that improvements in coronary heart disease (CHD) survival can explain this slowing through an increase in the number of CHD survivors at an increased risk for stroke. METHODS: We created multistate life-table models based on the survival experience of 46 years of follow-up of the Framingham Heart Study cohort. Improvements in survival after CHD were modeled by decreasing mortality rates for those with CHD. We analyzed whether improved CHD survival could result in a >3% increase in annual stroke mortality rates, which would be enough to eliminate the previously observed decline. RESULTS: CHD survival improvements led to an increase in the number of stroke deaths but also a concomitant increase in the total population size. Under no circumstances was there an annual increase in stroke mortality rates approaching 3% for both sexes and for younger and older age groups. CONCLUSIONS: The hypothesis that increases in the numbers of people with CHD, as a consequence of improvements in CHD survival, explain the observed slowing of the stroke mortality rate decline must be rejected. The true explanation is also likely to be a factor that changed markedly around 1990, but with more direct effects on stroke mortality.

Adult↗
PubMed2006

Adaptive evolution in a spatially structured asexual population.

We study the process of adaptation in a spatially structured asexual haploid population. The model assumes a local competition for replication, where each organism interacts only with its nearest neighbors. We observe that the substitution rate of beneficial mutations is smaller for a spatially structured population than that seen for populations without structure. The difference between structured and unstructured populations increases as the adaptive mutation rate increases. Furthermore, the substitution rate decreases as the number of neighbors for local competition is reduced. We have also studied the impact of structure on the distribution of adaptive mutations that fix during adaptation.

Adaptation, Biological↗
PubMed2005

A population-based description of glioblastoma multiforme in Los Angeles County, 1974-1999.

BACKGROUND: There have been reports that the incidence rates of brain tumors have increased over the past few decades, but most have considered all brain tumors together. The authors analyzed the pattern of glioblastoma multiforme (GBM) occurrence in Los Angeles County, California to shed light on the incidence and descriptive epidemiology of this type of brain tumor. METHODS: Data were obtained from the Los Angeles County Cancer Surveillance Program. Incidence rates were analyzed by gender, race, age at diagnosis, period of diagnosis (1974-1981, 1982-1988, or 1989-1999), and socioeconomic status (SES). In addition, data were stratified according to anatomic subsite. A multivariate model describing changes in rates by each of these variables was constructed. RESULTS: Age-specific incidence rates (ASIR) rose sharply after age 30 years. The peak ASIR was at age 70-74 years in males and at age 75-79 years in females. The age-adjusted incidence rate (AAIR) of GBM increased from 1974 to 1999 by an estimated 2.4% per year among males and 2.8% per year among females. Overall, males had a 60% increased risk of brain tumors compared with females. Males had a higher incidence of GBM compared with females at each anatomic subsite except the posterior fossa. The largest male:female ratio occurred in the occipital lobes. Non-Latino whites had the highest incidence rates (2.5 per 100,000) followed by Latino whites (1.8 per 100,000), and blacks (1.5 per 100,000). After 1989, compared with the period before magnetic resonance imaging (MRI) was available, there was an increase in GBM incidence rates among those with of higher SES that was most pronounced in females. The incidence of GBM was highest for frontal lobe tumors and for tumors that involved two or more lobes (overlapping tumors), followed by tumors in the temporal and parietal lobes. In the multivariate analysis, year of diagnosis, SES, gender, race (Latino but not black), site, and age at diagnosis all were important predictors of incidence rate. CONCLUSIONS: GBM incidence increased in Los Angeles County over the last 30 years and especially after 1989, suggesting that the introduction of MRI may have contributed to the increase. Individuals older than age 65 years experienced the greatest increase in incidence over time. Older age, male gender, higher SES, and non-Latino white race increased the risk of GBM. Previously unreported incidence rates for GBM among Latino whites were significantly lower than among non-Latino whites but were intermediate between non-Latino whites and blacks.

Adult↗
PubMed2002

Familial occurrence of autoimmune diseases and autoantibodies in a Caucasian population of patients with systemic lupus erythematosus.

To determine the prevalence of autoimmune diseases and autoantibodies in relatives of Caucasian patients with systemic lupus erythematosus (SLE) we questioned 118 patients for the prevalence of autoimmune diseases in their relatives. Multicase SLE families were selected for further investigation: assessment of the presence of antinuclear antibodies (ANA), thyroid antibodies and IgM rheumatoid factor (IgM-RF). Thirty-three patients reported the presence of 50 autoimmune diseases in 43 relatives. Twenty-two diagnoses could be either confirmed (n=14) or refuted (n=8). SLE clustered significantly within families of SLE patients. Multiple sclerosis and rheumatoid arthritis also seemed to cluster within families of lupus patients. The prevalence of ANA (24%) and thyroid antibodies (44%) in 29 relatives of multicase SLE families was raised (P<0.05). In conclusion, the prevalence of autoimmune diseases is raised in relatives of Caucasian SLE patients. Also, the prevalence of autoantibodies is raised in relatives of multicase SLE families, both suggesting genetic influences in the pathogenesis of the disease. These findings support the genome-wide screening of SLE patients to unravel factors responsible for genetic susceptibility to SLE.

Adult↗