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Alfredo Morabia

Publications and source records attributed to Alfredo Morabia.

At least 37 records · Page 2Linked to original sources
PubMed2005

The pioneering use of a questionnaire to investigate a food borne disease outbreak in early 20th century Britain.

This paper describes the investigation by a British local government board inspector in 1902, H Timbrell Bulstrode, into the cause of an outbreak of enteric fever after a mayoral banquet given at Winchester. This investigation helped to confirm the role of oysters as an agent of transmission of typhoid fever. The data are also reanalysed using a modern approach, which confirmed the role of oysters (odds ratio = 11.2, 95% CI 2.5 to 50.1). This episode is illustrative of the role of British public health inspectors at the turn of the 20th century as well as of the conditions in which the technique of investigating outbreaks of food borne diseases using a standardised menu was developed. Current methods of outbreak investigations that differ from Bulstrode's pioneering work are also discussed.

Animals↗
PubMed2005

The obesity epidemic as harbinger of a metabolic disorder epidemic: trends in overweight, hypercholesterolemia, and diabetes treatment in Geneva, Switzerland, 1993-2003.

Increases in obesity, hypercholesterolemia, and diabetes may be under way in Europe. We have reported the only data available from the 1990s for continuous monitoring of chronic disease risk factors in random samples of a general European population. In random surveys (1993-2003) of 6164 men and 6107 women in Geneva, overweight and obesity combined increased in both men and women; hypercholesterolemia prevalence also rose; diabetes treatment increased in men. Only population-based interventions can prevent the impending epidemic of obesity-related disorders.

Adult↗
PubMed2005

Epidemiological causality.

Epidemiological methods, which combine population thinking and group comparisons, can primarily identify causes of disease in populations. There is therefore a tension between our intuitive notion of a cause, which we want to be deterministic and invariant at the individual level, and the epidemiological notion of causes, which are invariant only at the population level. Epidemiologists have given heretofore a pragmatic solution to this tension. Causal inference in epidemiology consists in checking the logical coherence of a causality statement and determining whether what has been found grossly contradicts what we think we already know: how strong is the association? Is there a dose-response relationship? Does the cause precede the effect? Is the effect biologically plausible? Etc. This approach to causal inference can be traced back to the English philosophers David Hume and John Stuart Mill. On the other hand, the mode of establishing causality, devised by Jakob Henle and Robert Koch, which has been fruitful in bacteriology, requires that in every instance the effect invariably follows the cause (e.g., inoculation of Koch bacillus and tuberculosis). This is incompatible with epidemiological causality which has to deal with probabilistic effects (e.g., smoking and lung cancer), and is therefore invariant only for the population.

Biology↗
PubMed2004

Spectrum bias: a quantitative and graphical analysis of the variability of medical diagnostic test performance.

The performance of a medical diagnostic test may vary in a subgroup of patients according to the severity and clinical presentation of the disease. This phenomenon is often referred to as the spectrum effect. There is currently no technique to determine in which situations this spectrum effect may lead to a spectrum bias, that is, a distortion of the posterior probability which can potentially affect the clinical decision. We show that spectrum bias, on either a positive or a negative test result, can be expressed as the subgroup-specific likelihood ratio (LR) divided by the LR in the overall population of patients. This assessment of spectrum bias is independent of the pretest probability. We present here the test statistic and its variance and also propose a mode of graphically visualizing the presence of spectrum bias. We applied it to 15 examples from the literature, of which three are discussed in detail. In two examples, there was spectrum bias: (1) diagnosis of urinary tract infection in subgroups of low or high risk patients when using the dipstick test, and (2) diagnosis of left ventricular hypertrophy using electrocardiography in subjects with different body mass index. In a third example, there was no spectrum bias for the diagnosis of coronary heart disease in subgroups of patients defined by age, sex or comorbidities when using exercise electrocardiography. As sensitivity and specificity usually vary in opposite directions from one subgroup to the other, the ratio of LRs tends to remain constant, resulting in no or little spectrum bias. We conclude that spectrum effect is more common than spectrum bias and that clinical decisions are affected only under certain conditions.

Adult↗
PubMed2004

Evolution of epidemiologic methods and concepts in selected textbooks of the 20th century.

Textbooks are an expression of the state of development of a discipline at a given moment in time. By reviewing eight epidemiology textbooks published over the course of a century, we have attempted to trace the evolution of five epidemiologic concepts and methods: study design (cohort studies and case-control studies), confounding, bias, interaction and causal inference. Overall, these eight textbooks can be grouped into three generations. Greenwood (1935) and Hill (first edition 1937; version reviewed 1961)'s textbooks belong to the first generation, "early epidemiology", which comprise early definitions of bias and confounding. The second generation, "classic epidemiology", represented by the textbooks of Morris (first edition 1957; version reviewed 1964), MacMahon & Pugh (first edition 1960; version reviewed 1970), Susser (1973), and Lilienfeld & Lilienfeld (first edition 1976; version reviewed 1980), clarifies the properties of cohort and case-control study designs and the theory of disease causation. Miettinen (1985) and Rothman (1986)'s textbooks belong to a third generation, "modern epidemiology", presenting an integrated perspective on study designs and their measures of outcome, as well as distinguishing and formalizing the concepts of confounding and interaction. Our review demonstrates that epidemiology, as a scientific discipline, is in constant evolution and transformation. It is likely that new methodological tools, able to assess the complexity of the causes of human health, will be proposed in future generations of textbooks.

Epidemiologic Methods↗
PubMed2004

Population-based study of SR-BI genetic variation and lipid profile.

The variability of the Class B Type I Scavenger Receptor (SR-BI) gene in human populations and the relation of its variants to blood lipids was investigated in a random sample of 1756 untreated adult residents of Geneva, Switzerland, during 1999-2000. A three-step study approach yielded the following results: (1) resequencing the gene's exons and flanking regions in 95 subjects identified four common single nucleotide polymorphisms (SNPs with rare allele frequency >3%); (2) association study of the four common SNPs in subjects with extreme HDL-cholesterol (HDL-C) and LDL-C phenotypes (186 "atherogenic cases" and 185 "non-atherogenic controls") showed that the synonymous exon 8 C-T (allelic frequency 48%) polymorphism, A350A, was associated with atheroprotection in men (odds ratios (OR) = 0.36, 95% confidence intervals (CI) = 0.15-0.90, P < 0.03), but not in women (2.09, 0.79-5.49, P = 0.14); and (3) population clinical effects of A350A genotypes assessed in all 1756 subjects, showed that the case-control study findings reflected a protective HDL-C effect in men (CC: 1.17 mmol/L, CT: 1.22 mmol/L, and TT: 1.24 mmol/L, trend P = 0.0062) and a deleterious LDL-C effect in women (CC: 3.58 mmol/L, CT: 3.72 mmol/L, and TT: 3.79 mmol/L, trend P = 0.014). The allelic frequencies of the common SR-BI variants appear to be very similar in European and North American populations. The HDL-C effect increased with age. SR-BI A350A appears to have gender-specific and age-related effects on cholesterol transport lipoproteins.

Adult↗
PubMed2004

Sedentarism affects body fat mass index and fat-free mass index in adults aged 18 to 98 years.

OBJECTIVE: Body mass index does not discriminate body fat from fat-free mass or determine changes in these parameters with physical activity and aging. Body fat mass index (BFMI) and fat-free mass index (FFMI) permit comparisons of subjects with different heights. This study evaluated differences in body mass index, BFMI, and FFMI in physically active and sedentary subjects younger and older than 60 y and determined the association between physical activity, age, and body composition parameters in a healthy white population between ages 18 and 98 y. METHODS: Body fat and fat-free mass were determined in healthy white men (n = 3549) and women (n = 3184), between ages 18 and 98 y, by bioelectrical impedance analysis. BFMI and FFMI (kg/m2) were calculated. Physical activity was defined as at least 3 h/wk of endurance-type activity for at least 2 mo. RESULTS: Physically active as opposed to sedentary subjects were more likely to have a low BFMI (men: odds ratio [OR], 1.4; confidence interval [CI], 0.7-2.5; women: OR 1.9, CI 1.6-2.2) and less likely to have very high BFMI (men: OR, 0.2; CI, 0.1-0.2; women: OR, 0.1; CI, 0.02-0.2), low FFMI (men: OR, 0.5; CI, 0.3-0.9; women: OR, 0.7; CI, 0.6-0.9), or very high FFMI (men: OR, 0.6; CI, 0.4-0.8; women: OR, 0.7; CI, 0.5-1.0). Compared with subjects younger than 60 y, those older than 60 y were more like to have very high BFMI (men: OR, 6.5; CI, 4.5-9.3; women: OR, 14.0; CI, 9.6-20.5), and women 60 y and older were less likely to have a low BFMI (OR, 0.4; CI, 0.2-0.5). CONCLUSIONS: A clear association was found between low physical activity or age and height-normalized body composition parameters (BFMI and FFMI) derived from bioelectrical impedance analysis. Physically active subjects were more likely to have high or very high or low FFMI. Older subjects had higher body weights and BFMI.

Adipose Tissue↗
PubMed2004

Association of physical activity intensity levels with overweight and obesity in a population-based sample of adults.

BACKGROUND: Clarify the association between physical activity intensity and overweight/obesity. METHODS: Population-based 1997-2001 survey in Geneva, Switzerland (n=5,757, ages 35 to 74). Intensity of physical activity energy expenditure (EE) defined as percentage of total EE in moderate activities [3-3.9 x basal metabolism rate (BMR), e.g., normal walking, household chores] and high-intensity activities (> or =4 x BMR, e.g., brisk walking, sports). Overweight or obesity based on measured body mass index (BMI). RESULTS: Comparing participants in the lowest vs. the highest tertile of the percentage of high-intensity EE, the odds ratios (ORs) were, for obesity vs. normal weight, 2.8 (95% confidence interval: 2.0-3.8, P<0.0001) in men and 2.4 (1.7-3.4, P<0.0001) in women. For obese vs. overweight, the men/women ORs were 1.9 (1.4-2.6, P<0.0001)/1.5 (1.0-2.2, P<0.05). For overweight vs. normal weight, the men/women ORs were 1.4 (1.1-1.7, P<0.002)/1.7 (1.3-2.1, P<0.0001). Less or no relationship was found for the percentage of moderate-intensity EE. CONCLUSIONS: This cross-sectional study cannot determine whether exercise is an effective strategy for weight control or whether overweight or obese people exercise less. However, clear dose-response associations in both genders between obesity or overweight and energy expenditure in high (but not in moderate)-intensity activities are findings with potentially major public health implications meriting validation in an experimental intervention study.

Adult↗
PubMed2004

Nutritional assessment: lean body mass depletion at hospital admission is associated with an increased length of stay.

BACKGROUND: Low fat-free mass may be an independent risk factor for malnutrition that results in an increased length of hospital stay (LOS). OBJECTIVES: The objectives were to compare differences in fat-free mass and fat mass at hospital admission between patients and healthy control subjects and to determine the association between these differences and the LOS. DESIGN: Patients (525 men, 470 women) were prospectively recruited at hospital admission. Height-corrected fat-free mass and fat mass (fat-free-mass index or fat-mass index; in kg/m2) were determined in patients at admission by bioelectrical impedance analysis and were compared with values for sex-, age-, and height-matched control subjects. Patients were classified as well-nourished, moderately depleted, or severely depleted on the basis of a Subjective Global Assessment questionnaire and a body mass index (in kg/m2) < or > 20. RESULTS: Low fat-free mass was noted in 37% and 55.6% of patients hospitalized 1-2 d and > 12 d, respectively. The odds ratios were significant for fat-free-mass index and were higher in patients with a LOS of > 12 d [men (odds ratio: 5.6; 95% CI: 3.1, 10.4), women (4.4; 2.3, 8.7)] than in those with a LOS of 1-2 d [men (3.3; 2.2, 5.0), women (2.2; 1.6, 3.1)]. Severe nutritional depletion was significantly associated only with a LOS > 12 d. CONCLUSION: Fat-free mass and fat-free-mass index were significantly lower in patients than in control subjects. Because the fat-free-mass index is significantly associated with an increased LOS, provides nutritional assessment information that complements that from a Subjective Global Assessment questionnaire, and is a more sensitive determinant of the association of fat-free mass with LOS than is a weight loss > 10% or a body mass index < 20, it should be used to evaluate nutritional status.

Adipose Tissue↗
PubMed2004

Incidence and risk factors of perioperative respiratory adverse events in children undergoing elective surgery.

BACKGROUND: Adverse respiratory events remain one of the major causes of morbidity during anaesthesia, especially in children. The purpose of this prospective study was to determine the incidence of perioperative respiratory adverse events (PRAE) during elective paediatric surgery and to identify the risk factors for these events. METHODS: Potential risk factors (atopy, eczema, rhinitis, food allergy, previous allergic tests, pollens or animal allergy, passive smoking, obstructive sleep disorders) were assessed using the International Society on Allergy and Asthma (ISAAC) questionnaire, which was submitted to the parents during preoperative anaesthetic assessment. Anaesthetic and surgical conditions were systematically recorded. A multivariate logistic regression explaining PRAE was developed in 800 children. RESULTS: The intraoperative incidence of respiratory adverse events was 21% and the incidence in the postanesthetic care unit was 13%. According to the multivariate analysis, children not anaesthetized by a specialist paediatric anaesthesiologist have 1.7 increased risk to present PRAE (95% CI = 1.13-2.57). Children anaesthetized for ear, nose, throat (ENT) surgery had a 1.57-fold higher risk of PRAE compared with other procedures (95% CI = 1.01-2.44). Furthermore, there was a synergistic interaction when two risk factors: residents and ENT surgery, were concomitant: the odds ratio (OR) of PRAE during non-ENT surgical procedures was 1.43 (95% CI = 0.91-2.24), but increased to 2.74-fold (95% CI = 1.15-4.32) for ENT surgery. The risk of PRAE was significantly lower when the anaesthetic technique included tracheal intubation with relaxants (OR = 0.6, 95% CI = 0.45-0.95) and decreased by 8% with each increasing year of age. CONCLUSIONS: This study demonstrates a high incidence of PRAE in paediatric surgical patients without respiratory tract infections, which appears to be primarily determined by the age of the child and the anaesthetic care rather than by the child's medical history.

Airway Obstruction↗
PubMed2004

Does walking 15 minutes per day keep the obesity epidemic away? Simulation of the efficacy of a populationwide campaign.

Small physical activity increases may prevent weight gain in most populations. Geneva residents completed validated quantitative physical activity frequency questionnaires from 1997 to 2001. Fifteen minutes per day of moderate or brisk walking, or 30 minutes per day of slow walking, could increase physical activity at the population level; however, if the specific goal is to approach expending 420 kJ/d (100 kcal/d) through walking, the duration should be closer to 60 minutes for slow walking and 30 minutes for moderate or brisk walking.

Adult↗
PubMed2003

Association of extreme blood lipid profile phenotypic variation with 11 reverse cholesterol transport genes and 10 non-genetic cardiovascular disease risk factors.

This study explored the genetic basis of the combination of extreme blood levels of HDL-C and LDL-C, a well-studied endophenotype for CVD, which has several attractive features as a target for genetic analysis: (1) the trait is moderately heritable; (2) non-genetic risk factors account for a significant but still limited portion of the phenotypic variance; (3) it is known to be moderated by a number of gene products. We exhaustively surveyed 11 candidate genes for allelic variation in a random population-based sample characterized for known CVD risk factors and blood lipid profiles. With the goal of generating specific etiological hypotheses, we compared two groups of subjects with extreme lipid phenotypes, from the same source population, using a case-control design. Cases (n=186) were subjects, within the total sample of 1708 people, who scored in the upper tertile of LDL-C and the lowest tertile of HDL-C, while controls (n=185) scored in the lowest tertile of LDL-C and the upper tertile of HDL-C. We used logistic regression and a four-tiered, systematic model building strategy with internal cross-validation and bootstrapping to investigate the relationships between the trait and 275 genetic variants in the presence of 10 non-genetic risk factors. Our results implicate a subset of nine genetic variants, spanning seven candidate genes, together with five environmental risk factors, in the etiology of extreme lipoprotein phenotypes. We propose a model involving these 14 genetic and non-genetic risk factors for evaluation in future independent studies.

Adult↗
PubMed2003

Important increase of invasive lobular breast cancer incidence in Geneva, Switzerland.

A recent paper from the United States reported a sharp and unexplained increase in invasive lobular breast cancer incidence since 1977 (Li et al., Cancer 2000;88:2561-9). We investigated if this trend was also present in Geneva, Switzerland, where breast cancer incidence is one of the highest in Europe. We analyzed trends in breast cancer incidence according to histologic subtype, age and stage, to clarify the pattern. Our population-based study includes all histologically confirmed invasive breast carcinomas (n = 6,247) recorded between 1976 and 1999 at the Geneva Cancer Registry. Breast histology was classified as ductal carcinoma, lobular carcinoma and other. Incidence trends were studied by log-linear regression analyses. Models including effects of age, period and birth cohorts were used to describe rising incidence trends. The incidence of ductal carcinoma increased 1.2% per year (p(trend) < 0.001) from 85.2 to 110.1/100,000. This increase concerned women aged 50-69 years and early-stage tumors. Lobular cancer incidence increased disproportionately (14.4% per year, p(trend) < 0.01) and rose from 2.9 to 20.5/100,000. This increase affected all age categories and both localized and advanced stages. In addition, a strong age-cohort effect was present (p < 0.05), and women aged 50-59 years born after 1944 experienced the most marked increase. Our study shows a disproportionate increase of lobular breast cancer incidence compared to ductal cancer incidence. Contrary to ductal cancer, trends for lobular cancer are unlikely to be explained by increased use of screening mammography. Other explanations must be researched, in particular the role played by hormone replacement therapy.

Aged↗
PubMed2003

Optimal step length EM algorithm (OSLEM) for the estimation of haplotype frequency and its application in lipoprotein lipase genotyping.

BACKGROUND: Haplotype based linkage disequilibrium (LD) mapping has become a powerful and cost-effective method for performing genetic association studies, particularly in the search for genetic markers in linkage disequilibrium with complex disease loci. Various methods (e.g. Monte-Carlo (Gibbs sampling); EM (expectation maximization); and Clark's method) have been used to estimate haplotype frequencies from routine genotyping data. RESULTS: These algorithms can be very slow for large number of SNPs. In order to speed them up, we have developed a new algorithm using numerical analysis technology, a so-called optimal step length EM (OSLEM) that accelerates the calculation. By optimizing approximately the step length of the EM algorithm, OSLEM can run at about twice the speed of EM. This algorithm has been used for lipoprotein lipase (LPL) genotyping analysis. CONCLUSIONS: This new optimal step length EM (OSLEM) algorithm can accelerate the calculation for haplotype frequency estimation for genotyping data without pedigree information. An OSLEM on-line server is available, as well as a free downloadable version.

Algorithms↗
PubMed2003

Association between lipoprotein lipase (LPL) gene and blood lipids: a common variant for a common trait?

S447X, a serine substitution by a stop codon on base 99 of exon 9 of the lipoprotein lipase (LPL) gene, has beneficial effects on blood lipids. Other LPL alleles are associated with lipid levels, but whether one of these variants predominates remains elusive. We performed a systematic survey to identify single-nucleotide polymorphisms (SNPs) in all 10 LPL exons and flanking regions by resequencing the gene in 95 subjects. Of 24 variants, 14 were common (> or = 3%). We assayed the common SNPs in 186 cases with atherogenic lipid profiles (low HDL, high LDL) and 185 nonatherogenic controls (high HDL, low LDL). Only S447X and exons 6 (base +73) and 10 (base -11) were individually associated with case-control status (P<0.05, adjusted for major nongenetic covariates with known lipid effects). There were no significant SNP x gender interactions. In adjusted multi-SNP and haplotypic analyses, S447X was interpretable as the sole predictor, with a 2-3-fold reduction in the odds of being atherogenic vs. nonatherogenic (adjusted OR, 0.39; 95% CI, 0.21-0.73). S447X and base -11 of exon 10 were statistically interchangeable because they are strongly associated (r=0.92, P<0.0001), but we posit that the LPL association with lipid profile is more likely attributable to the functional S447X rather than the nonfunctional exon 10 SNP. It appears that the S447X variant of LPL may be another rare example (like APOE4, factor V-Leiden, and PPAR gamma Pro12Ala) of a common variant predisposing to a common disorder.

Case-Control Studies↗