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Does race predict stroke readmission? An analysis using the truncated negative binomial model.

BACKGROUND: Although it is known that the risk of first-ever stroke is higher for blacks than for whites, it is unclear what their relative risk is for stroke recurrence. METHODS: Using statewide inpatient data from California, 4,784 blacks and 33,684 whites having one or more stroke admissions during the year 2000 were identified. For blacks and whites, age- and sex-adjusted incidence rates were calculated for the index stroke admission using direct standardization (to the U.S. resident population for the year 2000). Various statistical models for count data were applied, with the best one being used in subsequent age-specific multivariate analyses for the number of stroke admissions. RESULTS: For the index stroke admission, the age- and sex-adjusted incidence rate per 100,000 was 366 (95% CI 355-377) for blacks and 204 (95% CI 202-207) for whites. Those having two or more stroke admissions accounted for less than 20% of the total number of patients. The truncated negative binomial (TNB) model gave the best fit not only to the California data but also to the data reanalyzed from several prior studies done in various countries [i.e., the United Kingdom (Oxfordshire and South London), Switzerland (Lausanne). Australia (Western Australia) and the United States (Nueces County, TX)]. In this study, predictors of stroke readmission changed according to age. For those aged 65-74 years old, blacks showed a higher risk of readmission than whites by 40% after adjustment for patient and hospital factors (RR 1.40, 95% CI 1.19-1.64). This excess risk was lower in other age groups. CONCLUSIONS: These findings suggest that blacks remain a high-risk group after an initial stroke and warrant appropriate intervention. Future studies on recurrent stroke should consider age-specific TNB models.

Adolescent↗

Inferring steady state single-cell gene expression distributions from analysis of mesoscopic samples.

BACKGROUND: A great deal of interest has been generated by systems biology approaches that attempt to develop quantitative, predictive models of cellular processes. However, the starting point for all cellular gene expression, the transcription of RNA, has not been described and measured in a population of living cells. RESULTS: Here we present a simple model for transcript levels based on Poisson statistics and provide supporting experimental evidence for genes known to be expressed at high, moderate, and low levels. CONCLUSION: Although the model describes a microscopic process occurring at the level of an individual cell, the supporting data we provide uses a small number of cells where the echoes of the underlying stochastic processes can be seen. Not only do these data confirm our model, but this general strategy opens up a potential new approach, Mesoscopic Biology, that can be used to assess the natural variability of processes occurring at the cellular level in biological systems.

Base Sequence↗

A model for AIDS pathogenesis.

The idea is put forward and analysed numerically, that within an infected person HIV evolves to increase its reproductivity within the population of CD4+ cells. A mathematical model predicts initial viremia and CD4+ cell drop after HIV infection and thereafter a slow progressive decline in the number of CD4+ cells, although for an extended period HIV is kept at a relatively low level by an active immune response. The time span T until the number of CD4+ cells falls below 20 per cent of its normal value depends on several model parameters. Assuming Gaussian distributions for these parameters, the model predicts a distribution function for T which resembles the observed distribution function for the incubation period to AIDS.

Acquired Immunodeficiency Syndrome↗

Additional risk factors influence excess mortality in heterozygous familial hypercholesterolaemia.

Life expectancy of patients with familial hypercholesterolaemia is decreased. Some untreated patients reach a normal life span and, therefore, additional risk factors and the type of mutation in the low-density lipoprotein (LDL) receptor gene are likely to influence the clinical outcome. We determined all cause mortality in kindreds with the disorder, who were untreated, in order to study (a) additional risk factors for coronary artery disease (CAD) and (b) the types of LDL receptor gene mutations that may contribute to a poor prognosis. The mortality in all 855 first-degree relatives of 113 unrelated patients was compared to the Dutch population after standardisation for age, gender, and calendar period. Analyses restricted to affected relatives could have underestimated the mortality risk due to lack of information about severe cases, who died prematurely. Therefore, all first-degree relatives were analysed and as a result the standardised mortality ratios (SMRs) exhibit only 50% of the excess mortality from familial hypercholesterolaemia. We observed 190 deaths in 32048 person-years leading to an overall SMR of 1.34 (95% confidence interval (CI) 1. 16-1.55, P=0.001). High excess mortality occurred in males between age 40 and 54 (SMR 2.34, 95% CI 1.60-3.31, P<0.001). The excess mortality decreased during the last decades. This change of mortality over calendar time shows that additional risk factors modulate the mortality from the disorder. The SMR of 62 families referred with premature CAD was 1.62 (95% CI 1.32-1.93, P<0.001) and the SMR was 1.10 (95% CI 0.86-1.34, P=0.4) in 51 families without premature CAD. The mortality risk of kindreds with null alleles was similar to that of kindreds with other mutations. In conclusion, the burden of the untreated disorder occurred mainly among middle-aged males and was not influenced by the type of mutation. Additional risk factors increased excess mortality significantly and are highlighted by the presence of premature CAD among first-degree relatives. This underscores the need for active identification of all hypercholesterolaemic relatives of such patients.

Adolescent↗

Marijuana use and medically attended injury events.

STUDY OBJECTIVE: This study evaluated the relation between self-reported marijuana use and 3-year incidence of injury. METHODS: We conducted a retrospective cohort study of adult Kaiser Permanente Medical Care Program members who underwent multiphasic health examinations between 1979 and 1986 (n=4,462). Injury-related outpatient visits, hospitalizations, and fatalities within 3 years of examination were determined. RESULTS: Outpatient injury events totaled 2,524; 1,611 participants (36%) had at least 1 injury-related outpatient visit. Injury-related hospitalizations (n=22) and fatalities (n=3) were rare. Among men, there was no consistent relation between marijuana use and injury incidence for either former users (rate ratio, 1.15; 95% confidence interval [CI], .97 to 1.36) or current users (rate ratio, 0.97; 95% CI, .81 to 1.17), compared with those who had never used marijuana. Among women, former and current users showed little difference in their rate of later injury compared with never users; the rate ratios were 1.05 (95% CI, .87 to 1.26) and 1.20 (95% CI, 1.00 to 1.44), respectively. No statistically significant associations were noted between marijuana use and cause-specific injury incidence in men or women. CONCLUSION: Among members of a health maintenance organization, self-reported marijuana use in adult men or women was not associated with outpatient injury within 3 years of marijuana use ascertainment.

Adolescent↗

The Swedish coeliac disease epidemic with a prevailing twofold higher risk in girls compared to boys may reflect gender specific risk factors.

In the mid 1980s the incidence of coeliac disease in Swedish children below 2 years of age increased threefold within a few years, and after a 10-year high incidence period returned equally rapidly to the previous level. Analysing the epidemic with respect to any change in female to male ratio over time, or shift in age at diagnosis, may increase the understanding of coeliac disease aetiology. In a population-based incidence study of childhood coeliac disease, 2151 cases (811 boys/1340 girls) were diagnosed from 1973 to 1997. Incidence rates and relative risks (RRs) were calculated by gender, age at diagnosis and calendar time. Cumulative incidences by age and gender were calculated for different birth cohorts. A twofold higher risk (RR: 1.9, 95% confidence interval (CI) 1.7-2.1) for coeliac disease in girls as compared to boys prevailed throughout the epidemic. Further, during the post-epidemic period there was an upward shift in age at diagnosis. So far, however, a majority of the cases diagnosed at older ages belong to birth cohorts of the epidemic period, i.e. cohorts that already had a high coeliac disease risk before 2 years of age. Our results suggest that girls as compared to boys may be genetically more vulnerable to environmental exposures influencing the immunological processes towards coeliac disease. Further, an increased risk for coeliac disease during the first years of life due to, for example, unfavourable infant dietary habits, may result in an increased total childhood risk for coeliac disease. A longer follow-up, even into adulthood, is needed to determine whether or not the lifetime risk has changed.

Adolescent↗

Incidence of gastric B-cell lymphomas: a population-based study in Germany.

BACKGROUND: While the clinical and experimental knowledge concerning gastric lymphomas is increasing, there is a scarcity of epidemiological data. PATIENTS AND METHODS: A population-based sample of patients in Franconia and Saarland in Germany was collected from a clinical trial, hospital archives and a cancer registry. RESULTS: Over a period of 3 years, 94 patients with primary gastric lymphoma were recorded out of a total population of 3.5 million. The standardised incidence rates in Saarland and Franconia were 0.7 and 0.8 cases per 100 000, respectively. Patients were predominantly from higher age groups (mean age 62.1 years) and the incidence in men was slightly more than in women (P <0.03). The distribution of histological subtypes in Franconia was as follows: marginal zone B-cell lymphomas (MZBL), 58%; diffuse large-cell B-cell lymphoma (DLBL), 33%; and mixed forms, 9%. Helicobacter pylori could be detected histologically in 84% of all cases, 95% of MZBL cases and 68% of DLBL cases. CONCLUSIONS: Incidence rates of gastric lymphoma in Germany were similar to that in other European countries, except England, where rates are lower. The subtype-specific differences of H. pylori infection rates could be due to differences in carcinogenesis or to secondary changes during malignant transformation.

Adult↗

Incidence and spectrum of non-Hodgkin lymphoma in Chinese migrants to British Columbia.

The incidence and spectrum of non-Hodgkin lymphoma (NHL) differ between the Chinese and Caucasian populations. Using population-based registries, we studied the pattern of NHL in Chinese migrants to British Columbia (BC). The records of all NHL cases of Chinese descent diagnosed between 1980 and 1997 were retrieved. Age-standardized incidences were calculated by 5-year intervals in terms of age and calendar years and the relative rates were compared between the migrant, Hong Kong and BC populations. The histological distribution of NHL was compared with 4500 consecutive NHL cases diagnosed in the two populations. A total of 211 cases of migrant NHL were identified, with an age-standardized incidence rate of 7.11 per 100 000 per year, compared with the Hong Kong and BC rates of 7.91 [standardized incidence ratio (SIR) = 0.86, P = 0.01] and 11.88 (SIR = 0.56, P < 0.01). The standardized rates of follicular lymphoma remained low, but the incidence of gastric and nasal natural killer/T lymphomas in migrants were lower than expected. Genetic factors appeared to be stronger than environmental factors in governing the overall incidence of NHL in Chinese. However, certain subtypes of lymphoma may show decreased rates in migrants because of environmental factors.

Adolescent↗

Migraine in the United States: epidemiology and patterns of health care use.

OBJECTIVE: To determine the prevalence and distribution of migraine in the United States as well as current patterns of health care use. METHODS: A random-digit-dial, computer-assisted telephone interview (CATI) survey was conducted in Philadelphia County, PA, in 1998. The CATI identifies individuals with migraine (categories 1.1 and 1.2) as defined by the diagnostic criteria of the International Headache Society with high sensitivity (85%) and specificity (96%). Interviews were completed in 4,376 subjects to identify 568 with migraine. Those with 6 or more attacks per year (n = 410) were invited to participate in a follow-up interview about health care utilization and family impact of migraine; 246 (60.0%) participated. RESULTS: The 1-year prevalence of migraine was 17.2% in females and 6.0% in males. Prevalence was highest between the ages of 30 and 49. Whereas 48% of migraine sufferers had seen a doctor for headache within the last year (current consulters), 31% had never done so in their lifetimes and 21% had not seen a doctor for headache for at least 1 year (lapsed consulters). Of current or lapsed consulters, 73% reported a physician-made diagnosis of migraine; treatments varied. Of all migraine sufferers, 49% were treated with over-the-counter medications only, 23% with prescription medication only, 23% with both, and 5% with no medications at all. CONCLUSION: Relative to prior cross-sectional surveys, epidemiologic profiles for migraine have remained stable in the United States over the last decade. Self-reported rates of current medical consultation have more than doubled. Moderate increases were seen in the percentage of migraine sufferers who use prescription medications and in the likelihood of receiving a physician diagnosis of migraine.

Adolescent↗

Ten-year update on mortality among mild-steel welders.

OBJECTIVES: This study is an update on the lung cancer risk of mild-steel welders with no asbestos exposure using a cohort of nonwelders for comparison. METHODS: The subjects came from three United States (US) plants that manufactured heavy equipment. The follow-up was extended from 1988 to 1998. The welders were not exposed to asbestos (typical of shipyard welders) or to chromium or nickel (present in stainless steel). RESULTS: There were 108 lung cancer deaths among the welders and 128 such deaths among the nonwelders (double the previous number of lung cancer deaths). The standardized mortality ratio (SMR) for lung cancer was 1.46 [95% confidence interval (95% CI 1.20-1.76] for the welders and 1.18 (95% CI 0.98-1.40) for the nonwelders, both in comparison with the US general population. Direct comparison between the welders and nonwelders yielded a rate ratio of 1.22 (95% CI 0.93-1.59). Analyses using a 15-year lag time did not differ greatly from those of an unlagged analysis. There were no marked trends for lung cancer risk by duration of exposure or latency. Evidence from cross-sectional data from a sample of the cohort indicated that the welders smoked somewhat more than the US population and more than the nonwelders. An approximate adjustment of the rate ratios for possible confounding by smoking suggested that smoking may have accounted for about half of the excess lung cancer observed among the welders versus that of either reference population. CONCLUSIONS These data provide suggestive but not conclusive evidence of a modest lung cancer risk from mild-steel welding.

Adult↗

Association of different intravenous iron preparations with risk of bacteremia in maintenance hemodialysis patients.

AIM: In vitro evidence suggests that different intravenous iron (i.v. Fe) preparations may be associated with different infection rates. This observational study was to determine if different bacteremia rates are associated with different types or amounts of i.v. Fe preparations. MATERIALS AND METHODS: This retrospective, single-center study was carried out from April 2001 November 2002, a period in which a global switch from ferric gluconate (FG) to iron sucrose (IS) occurred. During Period I (April 2001 - January 2002) FG was the only i.v. Fe administered in our hemodialysis unit. During Period II (February 2002 - November 2002) IS was the only i.v. Fe administered in our unit. Group A (n = 63) received hemodialysis during both Period I and Period II. Group B (n = 41) received hemodialysis either during Period I or Period II. RESULTS: More bacteremic episodes occurred while IS than while FG was being administered. The adjusted bacteremia incidence rate ratios (IRRs) associated with use of IS vs. FG were 2.92 (95% CI, 1.01 - 8.5) and 2.84 (95% CI 1.32 - 6.09) in Groups A and B, respectively. The adjusted bacteremia IRRs associated with receiving > 2,000 mg of i.v. Fe were 2.42 (95% CI 1.03 - 5.6) and 1.54 (95% CI 0.43 - 5.69) in Groups A and B, respectively. Use of catheters as hemodialysis access increased bacteremia risk in both groups. CONCLUSIONS: Use of iron sucrose is associated with higher bacteremia rates than ferric gluconate. The potential association between the cumulative amount of i.v. Fe administered and bacteremia risk is unclear. Randomized clinical trials are needed to verify our findings.

Aged↗

Learning input correlations through nonlinear temporally asymmetric Hebbian plasticity.

Triggered by recent experimental results, temporally asymmetric Hebbian (TAH) plasticity is considered as a candidate model for the biological implementation of competitive synaptic learning, a key concept for the experience-based development of cortical circuitry. However, because of the well known positive feedback instability of correlation-based plasticity, the stability of the resulting learning process has remained a central problem. Plagued by either a runaway of the synaptic efficacies or a greatly reduced sensitivity to input correlations, the learning performance of current models is limited. Here we introduce a novel generalized nonlinear TAH learning rule that allows a balance between stability and sensitivity of learning. Using this rule, we study the capacity of the system to learn patterns of correlations between afferent spike trains. Specifically, we address the question of under which conditions learning induces spontaneous symmetry breaking and leads to inhomogeneous synaptic distributions that capture the structure of the input correlations. To study the efficiency of learning temporal relationships between afferent spike trains through TAH plasticity, we introduce a novel sensitivity measure that quantifies the amount of information about the correlation structure in the input, a learning rule capable of storing in the synaptic weights. We demonstrate that by adjusting the weight dependence of the synaptic changes in TAH plasticity, it is possible to enhance the synaptic representation of temporal input correlations while maintaining the system in a stable learning regime. Indeed, for a given distribution of inputs, the learning efficiency can be optimized.

Action Potentials↗

The "Kriging" model of spatial genetic structure in human population genetics.

This paper presents the application of Kriging technique in the field of human population genetics for quantifying the spatial genetic heterogeneity of HLA-A locus in the area of China,and for mapping its spatial genetic structure using the measurement of synthetic genetic structure (SPC) and the principal components (PC). Both principles of the method and the basic equations are given. The Kriging model has several advantages over other interpolation and smoothing methods. Firstly, it relies on the structure of the spatial genetic semivariogram model, which can be used to quantify the spatial genetic heterogeneity of the locus (loci) before mapping its spatial genetic structure. Secondly, it is virtually unbiased in the interpolation situation,where the location to be estimated is surrounded by data on all sides and is influenced within the range of these data. Thirdly, it allows of estimative error of interpolation, which can be used to appraise the predicting effect for the spatial estimation,and the error maps can be used to decide where to introduce new sampling population genetic data. However, the "Kriging" model also has some disadvantages. Firstly,when the theoretical spatial genetic semivariogram can not be fitted by any models, the "Kriging" model can not be set up. Secondly, if the Kriging model was built by a poor spatial genetic semivariogram,the Kriging estimation standard deviation is remarkably high in the whole area, hence the Kriging model can not be suitable to estimating the distribution of spatial genetic structure. In these situations,the interpolation algorithm, whose assumption is spatial random rather than spatial autocorrelation,such as the Cavalli-Sforza method in Genography, inverse distance-weighted methods, splines, should be used to estimate or map the distribution of spatial genetic structure.

Genetics, Population↗

Age-related accident risks: longitudinal study of Swedish iron ore miners.

The study investigated whether occupational accident risks were equally distributed across age categories over time in the context of production reorganization and work rationalization in a Swedish iron ore mine between 1980 and 1993. Three phases of reorganization, defined by productivity levels, and four age categories were related to age-related accident risk ratios using the Poisson-regression method. Accident risk ratios (ARRs) were found systematically to be higher during the two first phases and also for younger workers, in the cases of both nonspecific and specific accident risks. The steady reduction in accident rates observed did not favor all age groups of workers to the same extent. For two accident patterns out of five, workers in their thirties and forties recorded higher ARRs than those in their fifties.

Accidents, Occupational↗

Geographical epidemiology of prostate cancer in Great Britain.

Prostate cancer incidence has increased during recent years, possibly linked to environmental exposures. Exposure to environmental carcinogens is unlikely to be evenly distributed geographically, which may give rise to variations in disease occurrence that is detectable in a spatial analysis. The aim of our study was to examine the spatial variation of prostate cancer in Great Britain at ages 45-64 years. Spatial variation was examined across electoral wards from 1975-1991. Poisson regression was used to examine regional, urbanisation and socioeconomic effects, while Bayesian mapping techniques were used to assess spatial variability. There was an indication of geographical differences in prostate cancer risk at a regional level, ranging from 0.83 (95% CI: 0.78-0.87) to 1.2 (95% CI: 1.1-1.3) across regions. There was significant heterogeneity in the risk across wards, although the range of relative risks was narrow. More detailed spatial analyses within 4 regions did not indicate any clear evidence of localised geographical clustering for prostate cancer. The absence of any marked geographical variability at a small-area scale argues against a geographically varying environmental factor operating strongly in the aetiology of prostate cancer.

Bayes Theorem↗

Epidemiology of hepatitis C virus antibodies in blood donors from the province of Latina, Italy.

In order to calculate the incidence of hepatitis C virus (HCV) antibodies in blood donors and to verify the efficacy of the pre-donation method (testing blood samples of potential donors at least 3 months in advance of their first donation), we performed a retrospective cohort study in 1995 and in the period 1996-2000 at the blood transfusion unit in Latina (Italy). Third generation ELISA method as well as RIBA-3 were used. 5,978 donors in 1995 and 20,741 in the 1996-2000 period were analysed. The age of donors (prevalently male, 78.5%) was between 18 and 65 (median 38). A total of 110 borderline and 62 positives were found with ELISA, of which 75 borderlines and 42 positives in 1995, and the remaining in the 1996-2000 period (p > 0.5). Percentage of HCV antibodies dropped from 8.5% in 1995 to 5.45% in the 1996-2000 period. The non reactivity and undetermined status were found in 82.1 and 9.4% respectively in 1995, and 69.1 and 25.45% respectively in the 1996-2000 period. The incidence of HCV antibodies was 167.28 cases per 100,000 person-years in 1995 and 4.13 per 100,000 person-years in the 1996-2000 period, 2.5 times lower than the national one. There was a statistically significant association between dental care and RIBA positivity (RR: 2.63; p = 0.045). This study, moreover, evidences how pre-donation practices, if extended to a national basis, may be able to nullify the dangers associated with post-transfusional hepatitis and to reduce the number of false positives and of blood packs donated but either unused or destroyed.

Adolescent↗

An update of cancer mortality among the French cohort of uranium miners: extended follow-up and new source of data for causes of death.

The follow-up of the French cohort of uranium miners has been extended to 1994, and a new source of information for causes of death has been used. The paper presents the new results regarding the risk of death among the cohort, and analyses the impact of the methodological changes on these results. The extension of the follow-up results in a substantial increase in statistical power compared with previous analysis (+25% for person-years and +74% for the number of deaths). The use of the National Mortality Database as the principal source for causes of death allows to reduce the potential bias in the calculation of standardized mortality ratios (SMR). As a consequence, an excess risk of deaths from laryngeal cancer, suggested in the first analysis, is not confirmed. The analysis shows the existence of an excess risk of deaths from lung cancer among French uranium miners (85 observed deaths, SMR = 1.9, 95% confidence interval CI: 1.5-2.3), and an increase of this risk with cumulative exposure to radon (excess relative risk per 100 working level month = 0.6, 95% CI: 0.1-1.2). These results confirm the existence of a risk of death from lung cancer in a population chronically exposed to relatively low levels of radon.

Adult↗

Prevalence of glaucoma in Thailand: a population based survey in Rom Klao District, Bangkok.

AIM: To determine prevalence, demography, mechanism, and visual morbidity of glaucoma in urban Thai people. METHODS: 790 subjects aged 50 years or older from Rom Klao district, Bangkok, Thailand, were enumerated in a population based cross sectional study. Each subject underwent the following investigations: visual acuity, visual field testing, slit lamp examination, applanation tonometry, gonioscopy, and an optic disc examination after mydriasis. Main outcome measures included visual acuity (logMAR), visual fields, intraocular pressure (IOP), gonioscopic characteristics, vertical cup/disc ratio (VCDR), prevalence of types of glaucoma. Glaucoma was diagnosed on the basis of optic disc appearance and visual field defects. In eyes in which the optic disc could not be examined, glaucoma was diagnosed when visual acuity was <3/60 and either IOP >99.5th percentile or there was evidence of previous glaucoma surgery. RESULTS: 701 subjects were examined (response rate 88.7%). In eyes with "normal" suprathreshold visual fields, the mean IOP was 13.3 mm Hg (97.5th percentile = 20 mm Hg). The 97.5th and 99.5th percentiles of VCDR were 0.72 and 0.86 respectively. Of the 701 subjects examined in the clinic, 27 had glaucoma (3.8%, 95% CI: 2.5 to 5.6), 16 had primary open angle glaucoma (POAG, prevalence 2.3%, 95% CI: 1.3 to 3.7), six were primary angle closure glaucoma (PACG, prevalence 0.9%, 95% CI: 0.3 to 1.9), and five were secondary glaucoma (SecG, prevalence 0.7%, 95% CI: 0.2 to 1.7). Among the 43 unilaterally blind subjects, glaucoma was the cause in five subjects (12%). One subject was bilaterally blind due to glaucoma (prevalence 11%, 95% CI: 0.3 to 61.9). 28 people (4%) were glaucoma suspects on the basis of optic disc appearance and six on the basis of visual fields only. 98 subjects (14%) had "occludable angles" in either eye, 22 of whom had primary angle closure (PAC, prevalence 3.1%, 95% CI: 1.9 to 4.7); 14 had peripheral anterior synechiae in either eye and eight had ocular hypertension (OHT). CONCLUSIONS: POAG accounted for 67% of all glaucoma, PACG 21%, and secondary glaucomas 12%. Glaucoma was the second most common cause of severe unilateral visual loss.

Age Distribution↗