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L Bernardinelli

Publications and source records attributed to L Bernardinelli.

At least 19 recordsLinked to original sources
PubMed2006

Bayesian mapping of multiple sclerosis prevalence in the province of Pavia, northern Italy.

The geographical analysis of a disease risk is particularly difficult when the disease is non-frequent and the area units are small. The practical use of the Bayesian modelling, instead of the classical frequentist one, is applied to study the geographical variation of multiple sclerosis (MS) across the province of Pavia, Northern Italy. 464 MS-affected individuals resident in the province of Pavia were identified on December 31st 2000. The overall prevalence was 94 per 100,000 inhabitants. This estimate indicates an increasing MS prevalence in the province, in accordance with the vast majority of the Italian areas where prevalence studies have been repeated. We mapped the geographical variation of MS prevalence across the 190 communes of the province both with a classical approach and a Bayesian approach. The frequentist approach produced an extremely dishomogeneous map, while the Bayesian map was much smoother and more interpretable. Our study underlines the usefulness of Bayesian methods to obtain reliable maps of disease prevalence and to identify possible clusters of disease where to carry out further epidemiological investigations.

Adolescent↗
PubMed2005

Tissue plasminogen activator antigen is strongly associated with myocardial infarction in young women.

Women who develop acute myocardial infarction (AMI) at a young age have fewer classical risk factors and less coronary stenosis than older women. In this rare population, it is plausible that a heightened hemostatic system may play an important mechanistic role in thrombus formation and in the development of AMI. We chose to investigate whether or not there is an association between premature AMI and the plasma concentrations of five hemostatic measurements that had been previously established as risk factors for AMI, and of the inflammation marker C-reactive protein (CRP). Women who had survived AMI at the age of 45 years or less (n = 141) were drawn from those admitted to 125 Italian coronary care units over a 3-year period. In them, and in an equal number of controls, plasma levels of immunoreactive tissue plasminogen activator (tPA), plasminogen activation inhibitor 1 (PAI-1), von Willebrand factor (VWF), fibrinogen, D-dimer and CRP were measured. Higher levels of VWF, fibrinogen, CRP and tPA were associated with AMI. After adjustment for both classical and hemostatic risk factors, only tPA maintained an independent association with AMI: the odds ratios (taken as an index of relative risk) for tPA values in the middle and higher tertiles were 2.86 (CI 1.63-5.02) and 8.18 (CI 2.66-25.20), respectively. In conclusion, there is a strong association between non-fatal AMI and increased plasma levels of tPA antigen. This finding is thought to be the expression of a reduced rather than enhanced fibrinolytic activity.

Adult↗
PubMed2004

Bayesian trio models for association in the presence of genotyping errors.

Errors in genotyping can greatly affect family-based association studies. If a mendelian inconsistency is detected, the family is usually removed from the analysis. This reduces power, and may introduce bias. In addition, a large proportion of genotyping errors remain undetected, and these also reduce power. We present a Bayesian framework for performing association studies with SNP data on samples of trios consisting of parents with an affected offspring, while allowing for the presence of both detectable and undetectable genotyping errors. This framework also allows for the inclusion of missing genotypes. Associations between the SNP and disease were modelled in terms of the genotypic relative risks. The performances of the analysis methods were investigated under a variety of models for disease association and genotype error, looking at both power to detect association and precision of genotypic relative risk estimates. As expected, power to detect association decreased as genotyping error probability increased. Importantly, however, analyses allowing for genotyping error had similar power to standard analyses when applied to data without genotyping error. Furthermore, allowing for genotyping error yielded relative risk estimates that were approximately unbiased, together with 95% credible intervals giving approximately correct coverage. The methods were also applied to a real dataset: a sample of schizophrenia cases and their parents genotyped at SNPs in the dysbindin gene. The analysis methods presented here require no prior information on the genotyping error probabilities, and may be fitted in WinBUGS.

Alleles↗
PubMed2002

An immunogenetic map of Lombardy (Northern Italy).

For this study we consulted the Bone Marrow Donors' Registry of Lombardy (Italy) and analyzed 43937 HLA-A,B phenotypes and 13922 HLA-A,B,DR phenotypes. We estimated the HLA-A,B and HLA-A,B,DR haplotype frequencies via the maximum-likelihood method. We analyzed the genetic structure of the 11 provinces of Lombardy by means of Principal Component Analysis and Correspondence Analysis, and estimated the variety of the different haplotypes at provincial level and the percentage of unique phenotypes at village level. We found 11189 different HLA-A,B phenotypes, 661 different HLA-A,B haplotypes and more than 4000 different HLA-A,B,DR haplotypes. We identified 20 villages, in Western Lombardy, very rich in unique/rare phenotypes. Here we report a formula which allows the identification of a putative donor matched for two haplotypes with a recipient. This result may be of great importance for the genetic study of the population of Lombardy and, even more, for bone marrow transplantation programs.

Alleles↗
PubMed2001

Association between the ancestral haplotype HLA A30B18DR3 and multiple sclerosis in central Sardinia.

Association and linkage studies have established the importance of the major histocompatibility complex (MHC) in the susceptibility for multiple sclerosis (MS). We carried out a case-control study to investigate the ancestral haplotype A30B18DR3 and MS in the Nuoro population of Sardinia, which is isolated and genetically distinct from other populations in the Mediterranean basin and characterized by genetic homogeneity, high level of inbreeding, low migration, high prevalence of MS, high frequency of the relevant haplotype, and high past malaria prevalence. Cases and controls were serologically typed for the currently recognized HLA-A, B, and DR antigens. We used a log-linear approach to fit a wide class of models. We tested our hypothesis comparing different models via a likelihood ratio test. We overcame the complication due to unknown gametic phase using expectation-maximization (EM) algorithm as the estimation method. We estimated confidence intervals for odds ratio by using a profile likelihood approach. We found that: (1) the ancestral haplotype A30B18DR3 was associated to MS after allowing for a possible stratification in cases and controls; (2) DR3 allele was conditional independent on disease status, given A30B18 haplotype; (3) there was a tendency for ORs for the high-risk haplotypes to be higher in the high malaria strata; however, this indication did not achieve statistical significance (P = 0.11).

Alleles↗
PubMed1998

The Sardinian IDDM study: 1. Epidemiology and geographical distribution of IDDM in Sardinia during 1989 to 1994.

Analysis of the geographical variation of risk for a disease is a key issue in descriptive epidemiology and may provide useful suggestions for planning further studies to identify the underlying causes. We adopted a Bayesian approach to investigate the geographical distribution of insulin-dependent diabetes mellitus (IDDM) incidence rate across Sardinia. Data on incidence of IDDM in children aged under 15 years (619 IDDM cases) in Sardinia was obtained by the Sardinian Eurodiab ACE register. The overall completeness of ascertainment was: 91.3%. The average yearly standardized incidence rate for the years 1989-1994 was 33.24 per 100000 (95% C.I. 30.60, 35.88), which is the second highest in Europe after Finland. Sex and age-specific risks were higher in males than in females. Considering the variation of IDDM risk according to the age at diagnosis, the risk profile increased up to the 13th year of age for both sexes, being steeper in males. The degree of geographical variation in IDDM risk was small with a slight difference between the highest and the lowest standardized rate across the map. Indeed, even the municipalities at lowest risk in Sardinia showed a risk higher than most European countries. The Sardinian population is genetically atypical, characterized by genetic homogeneity and marked susceptibility to autoimmune diseases. Our finding of a small geographical variation within the island coupled with a marked temporal trend previously observed in data on military conscripts could be interpreted as evidence of a relatively recent environmental aetiological factor that was uniformly distributed across the island and had its effect in a genetically predisposed population.

Age Factors↗
PubMed1998

An Italian epidemiological multicentre study of nocturnal enuresis.

OBJECTIVE: To estimate the prevalence of enuresis in schoolchildren in Italy. SUBJECTS AND METHODS: The Italian Club of Nocturnal Enuresis promoted a prevalence study of nocturnal enuresis using a self-administered questionnaire in seven cities in Northern, Central and Southern Italy. The association between enuresis and potential risk factors, e.g. a family history of enuresis, stress, socio-economic status and abnormal diurnal voiding habits, was investigated. The perceived impact on the child and on the family was also evaluated. A random-cluster sampling scheme was used to obtain a sample of primary and secondary schoolchildren from each city. One primary school and one secondary school for each socio-economic level was sampled in each city, giving a total of 42 schools surveyed; 9086 children were covered by the survey. In a cluster sampling method, the variance of prevalence is divided into two components, binomial and extra-binomial variability. Both the DSM III and DSM IV definitions of enuresis were used because at present, there is no consensus on the diagnostic criteria. RESULTS: Completed questionnaires were received from 7012 children, an overall response rate of 77.2%. Those aged 6-14 years were analysed, restricting the sample to 6892 children. There were 250 enuretic children using the DSM III definition of enuresis and 112 using the DSM IV definition. The overall prevalence was 3.88% and showed a decreasing trend with increasing age. Bedwetting was more frequent in boys than in girls. The prevalence of enuresis was higher when the child was from a family of low socio-economic status despite the child's age group. The logistic analysis showed that familiality, stress, birthweight, age of attaining diurnal continence, soiling and, for girls, menstruation, were statistically significant variables and thus contributed to predicting the probability of bedwetting, confirming the findings of previous studies. There was a large difference in prevalence using the two DSM definitions; a high percentage of DSM III enuretic children had more than two wet nights per week. CONCLUSION: It is important that a consensus about the 'working definitions' of enuresis is reached to avoid bias in the recruitment step, to carry out comparable epidemiological studies and to obtain adequate therapeutic responses.

Adolescent↗
PubMed1997

Disease mapping with errors in covariates.

We describe Bayesian hierarchical-spatial models for disease mapping with imprecisely observed ecological covariates. We posit smoothing priors for both the disease submodel and the covariate submodel. We apply the models to an analysis of insulin Dependent Diabetes Mellitus incidence in Sardinia, with malaria prevalence as a covariate.

Bayes Theorem↗
PubMed1995

Childhood Acute Lymphoblastic Leukemia: A Cluster in Southwestern Sardinia (Italy).

In response to public concern about an increase in the incidence of leukemia among children in southwestern Sardinia (Italy), incident cases of childhood cancer (ages 0-14) were ascertained among residents in the province of Cagliari, which comprises all of southern Sardinia, in 1974-89. Completeness of the ascertainment of leukemia cases was validated by comparison with estimates derived from official statistics of mortality and survival curves. A significant excess risk of childhood acute lymphoblastic leukemia (cALL) was found for children residing in the town of Carbonia. The risk was highest in 1983-85, when seven cases occurred versus 0.8 expected. No birth-cohort effect was observed. The cALL incidence rate was significantly higher among children born and residing in Carbonia than among children born in Carbonia but residing elsewhere. However, the cALL cases did not cluster within the town of Carbonia. The proximity of the largest industrial settlement in the region of Sardinia raised the suspicion that environmental pollution was responsible for the observed excess. Information about industrial emissions from this settlement prior to the appearance of the cALL cluster was not sufficient to reject or confirm the hypothesis.

Journal Article↗
PubMed1995

[Bayesian analysis of ecological studies].

Studying the space-time variation of risk for a given disease may give etiological clues and suggestions for planning further studies to investigate the underlying causes. When the observed events are rare, approaches based on maximum likelihood may lead to unstable and largely uninformative estimates of risk and of its time trend due to Poisson sampling variation. In this paper we propose a general Bayesian model for analyzing the variation of risk in space and time. We applied the Bayesian model to the analysis of the geographical variation of breast cancer mortality, to an ecological study on the correlation between lung cancer mortality and degree of urbanization and industrialization and to the analysis of the space-time variation of cumulative prevalence of Insulin Dependent Diabetes Mellitus (IDDM) as observed in military examinations between 1954 and 1989.

Bayes Theorem↗
PubMed1993

Childhood leukemia in south-west Sardinia (Italy).

AIM AND BACKGROUND: Public concern on an increased incidence of childhood leukemia in SW Sardinia prompted the authors to an epidemiological investigation. METHODS: Incident childhood neoplasms observed in the Cagliari province (Sardinia--Italy) in 1974-1989 were registered. Expected cases of the most frequent childhood cancers were calculated for each town, based on the sex-and age-specific incidence rates in the province. RESULTS: An excess risk of childhood acute lymphoblastic leukemia (ALL) was observed in Carbonia, a town located in the SW part of the province. The risk was highest in 1983-85, when 7 cases occurred versus 0.8 expected (RR = 8.7; 95% C.I. = 4.6, 16.3). No spatial clustering of ALL cases was observed within the town. CONCLUSIONS: A significantly higher than expected incidence of childhood ALL was observed in the town of Carbonia in 1983-85. In alternative to chance, possible exposure to environmental pollutants from a near industrial settlement is discussed as the cause of the observed excess, but it is far to be proven. Other hypotheses, including a viral infection in a population with increased susceptibility, as suggested for new urban settlements, cannot be discarded.

Adolescent↗
PubMed1993

Spatial correlation in ecological analysis.

This paper presents a statistical approach, originally developed for mapping disease risk, to ecological regression analysis in the presence of spatial autocorrelated extra-Poisson variation. An insight into the effect of allowing for spatial autocorrelation on the relationship between disease rates and explanatory variables is given. Examples based on cancer frequency in Scotland and Sardinia are used to illustrate the interpretation of regression coefficient and further methodological issues.

Analysis of Variance↗
PubMed1992

Empirical Bayes versus fully Bayesian analysis of geographical variation in disease risk.

This paper reviews methods for mapping geographical variation in disease incidence and mortality. Recent results in Bayesian hierarchical modelling of relative risk are discussed. Two approaches to relative risk estimation, along with the related computational procedures, are described and compared. The first is an empirical Bayes approach that uses a technique of penalized log-likelihood maximization; the second approach is fully Bayesian, and uses an innovative stochastic simulation technique called the Gibbs sampler. We chose to map geographical variation in breast cancer and Hodgkin's disease mortality as observed in all the health care districts of Sardinia, to illustrate relevant problems, methods and techniques.

Bayes Theorem↗
PubMed1987

Cancer mortality in an Italian rubber factory.

The purpose of the study was to describe the mortality experience of an Italian cohort of rubber workers and an attempt was made to identify any occupational cancer hazards that might currently be affecting men employed in this type of work. A total of 4917 male workers who first started working in a large rubber factory between 1962 and 1972 have been followed up until 31 January 1983. The number of deaths from all causes and from malignant neoplasms was determined and compared with the expected number of deaths calculated from mortality rates for the province in which the population of the plant lived. Mortality from all causes was 85% of that expected. A slight overall excess of deaths from cancer (SMR = 119) was found; this was entirely due to the excess mortality in the 35-44 age group. In order further to evaluate the possible existence of a cancer risk SMRs were analysed by duration of exposure, time since first exposure, and for specific sites of cancer. A trend in SMR with duration of exposure was found for employees with 10 years of follow up or more. A high risk for some tumour sites emerged.

Adolescent↗
PubMedDate not supplied

Statistical issues in the analysis of disease mapping data.

In this paper we discuss a number of issues that are pertinent to the analysis of disease mapping data. As an illustrative example we consider the mapping of larynx cancer across electoral wards in the North West Thames region of the U.K. Bayesian hierarchical models are now frequently employed to carry out such mapping. In a typical situation, a three-stage hierarchical model is specified in which the data are modelled as a function of area-specific relative risks at stage one; the collection of relative risks across the study region are modelled at stage two; and at stage three prior distributions are assigned to parameters of the stage two distribution. Such models allow area-specific disease relative risks to be 'smoothed' towards global and/or local mean levels across the study region. However, these models contain many structural and functional assumptions at different levels of the hierarchy; we aim to discuss some of these assumptions and illustrate their sensitivity. When relative risks are the endpoint of interest, it is common practice to assume that, for each of the age-sex strata of a particular area, there is a common multiplier (the relative risk) acting upon each of the stratum-specific risks in that area; we will examine this proportionality assumption. We also consider the choices of models and priors at stages two and three of the hierarchy, the effect of outlying areas, and an assessment of the level of smoothing that is being carried out. For inference, we concentrate on the description of the spatial variability in relative risks and on the association between the relative risks of larynx cancer and an area-level measure of socio-economic status.

Age Factors↗