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PubMed2001

Stratified case sampling and the use of family controls.

We compare the asymptotic relative efficiency (ARE) of different study designs for estimating gene and gene-environment interaction effects using matched case-control data. In the sampling schemes considered, cases are selected differentially based on their family history of disease. Controls are selected either from unrelated subjects or from among the case's unaffected siblings and cousins. Parameters are estimated using weighted conditional logistic regression, where the likelihood contributions for each subject are weighted by the fraction of cases sampled sharing the same family history. Results showed that compared to random sampling, over-sampling cases with a positive family history increased the efficiency for estimating the main effect of a gene for sib-control designs (103-254% ARE) and decreased efficiency for cousin-control and population-control designs (68-94% ARE and 67-84% ARE, respectively). Population controls and random sampling of cases were most efficient for a recessive gene or a dominant gene with an relative risk less than 9. For estimating gene-environment interactions, over-sampling positive-family-history cases again led to increased efficiency using sib controls (111-180% ARE) and decreased efficiency using population controls (68-87% ARE). Using case-cousin pairs, the results differed based on the genetic model and the size of the interaction effect; biased sampling was only slightly more efficient than random sampling for large interaction effects under a dominant gene model (relative risk ratio = 8, 106% ARE). Overall, the most efficient study design for studying gene-environment interaction was the case-sib-control design with over-sampling of positive-family-history-cases.

Bias↗
PubMed1989

Alcohol consumption among victims of violence and among comparable U.K. populations.

Controlled investigations of alcohol consumption in victims of assault are lacking. A prospective survey was performed to compare victims' drinking habits with age and sex matched U.K. populations. All 539 adult victims of assault who attended an inner-city Accident and Emergency (A and E) Department in 1986 were interviewed. Seventy-four per cent of male victims and 42% of female victims reported alcohol consumption in the 6 hours prior to assault: 30% of males and 4% of females had consumed greater than 10 units. Forty per cent males and 25% of females exceeded established safe-levels of consumption while 16% of males and 26% of females demonstrated abnormally high gamma-GT levels. Mean expenditure on alcohol by assault victims was 14% of net income, compared to 7.5% by the U.K. adult population overall. Results suggested that young male victims of assault may not be distinguishable from other young males on the basis of habitual or binge alcohol consumption. Assault victims over 25 years of age drank excessively compared to control populations and should be a priority group for alcohol education programmes.

Adolescent↗
PubMed1997

Occupational exposure to machining fluids and laryngeal cancer risk: contrasting results using two separate control groups.

This death certificate-based case-control study linked Connecticut Tumor Registry and Connecticut Division of Vital Statistics death data to determine whether machining fluid exposure is associated with laryngeal cancer risk. Laryngeal cancer cases were compared with oral cancer controls and general population controls. Level of exposure to machining fluids was imputed from the usual occupation and industry on the death certificate. Because exposure was infrequent among females, analysis was limited to males. When cases were compared to oral cancer controls, high exposure to machining fluids was associated with laryngeal cancer (odds ratio = 1.48; 95% confidence interval = 1.01-2.16), with a p-value for trend of 0.08. When cases were compared to population controls, no association between machining fluid exposure and laryngeal cancer was observed. A possible reason for the contrasting results, other than chance, is that exposure data quality for the cases and oral cancer controls may have differed from that of the population controls.

Case-Control Studies↗
PubMed1986

Nonoccupational risk indicators for astrocytomas in adults.

We performed a case-control study on astrocytomas to test previous hypotheses and to generate new ones. The study groups consisted of 78 cases, 197 clinical controls, and 92 population controls. Comparisons with both groups of controls showed an excess risk for persons who had lived in the vicinity of a farm. The risk for persons exposed to herbicides or insecticides was elevated, although less so compared with the population controls. Frequent intake of smoked food was associated with an excess risk compared with the population controls but not when compared with the clinical controls.

Adult↗
PubMed2004

The A-1087IL-10 allele is associated with cardiovascular disease in SLE.

The risk of cardiovascular disease (CVD) in SLE patients is very high. It is therefore surprising that IL-10 has been discussed both as pathogenic in SLE and as an atheroprotective cytokine. In contrast, TNF is believed to be atherogenic and we recently reported that raised activity in the TNF-system is implicated in SLE-related CVD. Twenty-six (aged 52 +/- 8 years) female patients with SLE and a history of CVD (myocardial infarction, angina, stroke or claudication) were compared with 26 age-matched SLE patients without CVD (SLE controls) or 26 age-matched population controls. The -1087IL-10 gene polymorphism was determined by PCR with restriction endonuclease mapping. Serum IL-10 and TNF-levels were determined by ELISA. The A allele frequency of -1087IL-10 gene in SLE/CVD was higher than in SLE controls (0.62 versus 0.42, p < 0.05). Ten (38%) of 26 SLE/CVD exhibited IL-10 AA genotype compared with five (19%) of 26 SLE controls. Serum IL-10 and TNF-levels were raised in SLE/CVD compared with SLE controls or population controls (p < 0.001). Furthermore, in SLE/CVD, a significantly reduced IL-10:TNF ratio was observed in patients with IL-10 AA genotype compared with AG or GG genotype (0.56 versus 0.77 versus 1.24, p < 0.05). In SLE controls and population controls, individuals with IL-10 GG genotype tended to have higher IL-10:TNF ratio. In conclusion, the A-1087IL-10 allele which has been reported to cause a lower capacity for IL-10 production could contribute to CVD in SLE. Furthermore, the IL-10 AA genotype is associated with reduced ratio of atheroprotective to atherogenic cytokines in SLE patients with CVD.

Alleles↗
PubMed1998

No evidence for allelic association of a human CTLA-4 promoter polymorphism with autoimmune thyroid disease in either population-based case-control or family-based studies.

OBJECTIVE: The cytotoxic T lymphocyte associated-4 (CTLA-4) gene is a candidate for T-cell mediated autoimmune disease and polymorphism has been reported to be associated with both type 1 diabetes and autoimmune thyroid disease. A previously unreported polymorphism of the promoter region of the human CTLA-4 gene has recently been described in a sample of a normal control population. We investigated the distribution of this polymorphism, situated at position -318 to the ATG start codon and resulting in a C-T change leading to an Mse I restriction site, in both population based case control studies and family studies in patients with Graves' disease (Caucasian and Hong Kong Chinese), autoimmune hypothyroidism and systemic lupus erythematosus (SLE). DESIGN: Target DNA was amplified using the polymerase chain reaction and the resulting product was digested using the Mse I restriction enzyme. PATIENTS: One hundred and ninety-one white UK Caucasian and 98 Hong Kong Chinese patients with Graves' disease, 78 white UK Caucasian patients with Graves' disease plus family members, 92 white UK Caucasian patients with autoimmune hypothyroidism, 13 white UK Caucasian patients with autoimmune hypothyroidism plus family members, 132 white UK Caucasian patients with systemic lupus erythematosus, 355 white UK Caucasian control subjects and 82 Hong Kong Chinese control subjects. MEASUREMENTS: Frequencies of the C and T alleles were compared between patients and control subjects using the chi 2-test and Fisher's exact test for small numbers. RESULTS: No association with the T allele was observed in any of the patient groups studied. CONCLUSION: These data suggest that the C-T change in exon 1 of the promoter region of the CTLA-4 gene does not play a role, nor is in linkage disequilibrium with a disease causing mutation, in the development of autoimmune disease.

Abatacept↗
PubMed1996

Assessing the quality and effects of hypertension control in populations.

The objectives of hypertension control include early detection, treatment and prevention of blood pressure (BP) elevations. In clinical situations, continuous evaluation of an Individual's treatment is an inherent part of normal follow-up. On the level of populations, however, evaluation of hypertension control calls for specially designed action. Evaluation is needed for several reasons; these are, inter alia, strategic (to improve the method); economic (to upgrade cost-effectiveness); and ethical reasons (to morally justify public action). Since hypertension control in populations is itself a complex process, its evaluation requires, multidimensional approaches. The methodologic experience from three WHO studies of this kind has been reported. These were done in different contexts: (1) evaluation of the effects of a special multicentre programme for hypertension control in populations; (2) long-term monitoring of cardiovascular disease incidence; and (3) a project for the assessment of levels and quality of hypertension control that is taking place spontaneously. In the first study, changes with time were compared in pairs of similar communities, of which one had been exposed to an organized programme for the control of hypertension ('intervention' vs 'reference' community). The second study uses an elaborate system of disease registers and surveys periodically a number of general populations. In the third study the actual level and quality of hypertension control was analysed in different, mostly European, populations; the findings related to the treatment of hypertension were compared with the standards suggested by WHO and ISH; other findings were assessed on the basis of common sense.

Community Medicine↗
PubMed2003

Insurance problems among inflammatory bowel disease patients: results of a Dutch population based study.

BACKGROUND AND AIMS: The majority of patients with inflammatory bowel disease (IBD) have a normal life expectancy and therefore should not be weighted when applying for life assurance. There is scant literature on this topic. In this study our aim was to document and compare the incidence of difficulties in application for life and medical insurance in a population based cohort of IBD patients and matched population controls. METHODS: A population based case control study of 1126 IBD patients and 1723 controls. Based on a detailed questionnaire, the frequency and type of difficulties encountered when applying for life and medical insurance in matched IBD and control populations were appraised. RESULTS: In comparison with controls, IBD patients had an 87-fold increased risk of encountering difficulties when applying for life assurance (odds ratio (OR) 87 (95% confidence interval (CI) 31-246)), with a heavily weighted premium being the most common problem. Patients of high educational status, with continuous disease activity, and who smoked had the highest odds of encountering such problems. Medical insurance difficulties were fivefold more common in IBD patients compared with controls (OR 5.4 (95% CI 2.3-13)) although no specific disease or patient characteristics were identified as associated with such difficulties. CONCLUSIONS: This is the first detailed case control study that has investigated insurance difficulties among IBD patients. Acquiring life and medical insurance constituted a major problem for IBD patients in this study. These results are likely to be more widely representative given that most insurance companies use international guidelines for risk assessment. In view of the recent advances in therapy and promising survival data on IBD patients, evidence based guidelines for risk assessment of IBD patients by insurance companies should be drawn up to prevent possible discriminatory practices.

Adolescent↗
PubMed2004

Occupational risk factors for mycosis fungoides: a European multicenter case-control study.

Mycosis fungoides (MF) is a rare disease with an unknown etiology. Its distribution suggests that occupational exposures may play a role. In the present study, we searched for occupational factors associated with MF. A European multicenter case-control study on seven rare cancers, including MF, was conducted from 1995 to 1997. Patients between 35 and 69 years of age diagnosed with MF (n = 134) were identified and their diagnoses were checked by a reference pathologist who classified 83 cases as definitive, 35 cases as possible, and 16 cases as not histologically verified. Of the 118 histologically verified cases, 104 were interviewed, of which 76 were definitive cases. As controls, we selected population controls and colon cancer controls to serve all seven case groups. Altogether, 833 colon cancer controls and 2071 population controls were interviewed. The response rate was 91.5% for cases (76 of the 83 definitive cases), and 66.6% for controls. A high risk of MF for men was observed in the industries of other non-metallic mineral products (Odds Ratio [OR] 5.3, 95% confidence interval [CI] = 1.7-16.2) and of wholesale trade (OR 3.6, 95% CI = 1.3-10.5). A high risk was found for female employees in the sector of pulp paper manufacture (OR 14.4, 95% CI = 2.2-95.1). The male occupations with the highest risks were glass formers, potters, and ceramics workers (OR 17.9, 95% CI = 5.4-59.4) and technical salesmen (OR 8.6, 95% CI = 2.4-30.8). For women, the occupations associated with the highest risks were government executives (OR 4.8, 95% CI = 1.0-22.6) and railway and road vehicles loaders (OR 3.9, 95% CI = 1.0-14.0). The results suggest that some occupational factors are associated with MF. Working as glass formers, pottery, and ceramics workers carried the highest risk, and these findings deserve further attention and replication. Females working in the paper and pulp industries may also be exposed to carcinogens of relevance to MF.

Adult↗
PubMed2005

An application of control region sequence as a matrilineage marker for Elliot's pheasant of a zoo population.

Control region sequence, an mtDNA marker, was usually used in phylogenesis analysis in species level or genetic structure study among populations. In this study, enlightened by its character of maternal heredity in vertebrates, we used control region sequence as a matrilineage marker for Elliot's pheasant (Syrmaticus ellioti) of Ningbo Zoo population. In Ningbo Zoo, 36 individuals of Elliot's pheasant were descendants from three female founders introduced in 1988. Three control region haplotypes (Ha, Hb, Hc) were identified by six variable nucleotide positions among the control region sequences over 36 individuals. The number of haplotypes was accorded with the number of female founders. Total 20 individuals (C04, C06, C08-11, C14, C20, C21, C23-29, C32, C34-36) shared haplotype a, while 12 individuals (C01, C05, C07, C12, C13, C16-19, C22, C30, C33) shared haplotype b and 4 individuals (C02, C03, C15, C31) shared haplotype c. Those individuals sharing the same haplotype were offspring from one female founder. In other words, there were three maternal lineages and the simple relationship among individuals was indicated. As a result, it seemed that the control region sequence was a useful marker for identification of matrilineage in this study. Meanwhile, the matrilineage information may be compensatory data if there were no any pedigree records in captive species for breeding management.

Animals↗
PubMed1999

Helicobacter pylori and the risk of colonic adenomas. Colorectal Adenoma Study Group.

AIMS: Previous studies have found a positive association between Helicobacter pylori infection and colorectal adenomas. The aim of the present study was to examine this association while taking possible confounding factors into account. METHODS: 98 serum samples were available from 182 patients with colorectal adenomas who entered a case-control study of colorectal adenomas and diet. The H. pylori status in patients was compared with a hospital control group and a population control group. RESULTS: H. pylori IgG antibodies were more common in colorectal polyp patients compared with either control group, the prevalence being 79% in cases compared with 62% in both control groups. The corresponding RR was 1.4 (0.76-2.6) compared with hospital controls and 2.1 (1.1-3.9) compared with population controls. After adjusting for possible confounding variables the association between H. pylori status and adenoma risk was even more marked. There was an RR of 1.6 (0.80-3.4) compared with hospital controls and an RR of 2.6 (1.3-5.4) compared with population controls, the latter association being statistically significant. CONCLUSION: These findings suggest a statistically significant association between H. pylori infection and colorectal polyps. A possible mechanism might be increased gastrin levels in H. pylori-infected subjects which exhibit a trophic effect on colonic mucosa.

Adenomatous Polyposis Coli↗
PubMed1989

[Design and implementation of a multicenter case-control study on bladder cancer in Spain].

The aim of a case-control design is to make a measurement of the highest possible accuracy, reducing to a minimum the possible selection, information and confusion biases. The design, methods and procedures of a multicentric study carried out in 14 hospitals from 4 autonomous communities in Spain are discussed. Overall 254 incident cases, 243 prevalent cases, 583 hospital controls and 530 population controls were included. The proportion of nonresponders was somewhat higher in population controls, particularly in large cities. Statistically significant differences between cases and controls were not found for socioeconomic levels, educational level, number of jobs, degree of response, duration of the interview, and errors of transcription and codification of information. Also, significant differences were not found between the population and hospital controls regarding diet habits and cigarette smoking. It is considered that a non-biased measurement of the association can be obtained from cases and hospital controls. The collected information was satisfactory. In spite of the lack of adequate facilities for research in hospitals, the development of multicentric etiologic studies is feasible.

Adenocarcinoma↗
PubMed2003

Markers of access to and quality of primary care for aboriginal people in Ontario, Canada.

OBJECTIVES: We evaluated primary care accessibility and quality for Ontario's aboriginal population. METHODS: We compared a defined aboriginal cohort with nonaboriginal populations with analogous geographic isolation and low socioeconomic status. We determined rates of hospitalization for the following indicators of adequacy of primary care: ambulatory care-sensitive (ACS) conditions and utilization of referral care-sensitive (RCS) procedures from administrative databases. RESULTS: ACS hospitalization rates, relative to the general population, were 2.54, 1.50, and 1.14 for the aboriginal population, the geographic control populations, and the socioeconomic control populations, respectively. The relative RCS procedure utilization rates were 0.64, 0.91, and 1.00, respectively. CONCLUSIONS: The increased ACS hospitalization rate and reduced RCS procedure utilization rate suggest that northern Ontario's aboriginal residents have insufficient or ineffective primary care.

Acute Disease↗
PubMed2006

Quality of care in China: scaling up a pilot project into a national reform program.

China's family planning program ranks as history's most intensive effort to control national population growth. Although advocates for global population control have lauded China's effort to limit births as afundamental part of its sustainable development goals, the country's population policy has also generated much international criticism. As China enters the new millennium, a long-overdue reform of its approach to implementing its family planning program has begun to refocus the program on clients' needs, informed choice of contraceptives, and better-quality services. Originally inspired by the 1994 International Conference on Population and Development held in Cairo, the reform program began as a pilot project among six counties and has now become a blueprint for reorienting the national family planning program. This article reviews the process by which a small, innovative pilot project was scaled up into a national reform effort and the key lessons learned about scaling up sensitive but necessary innovation in a difficult political environment.

China↗
PubMed1994

Lp(a) concentration and apo(a) isoform size. Relation to the presence of coronary artery disease in familial hypercholesterolemia.

We studied the relation between the concentration of lipoprotein(a) [Lp(a)] in plasma, apolipoprotein (a) [apo(a)] phenotype, and the clinical expression of coronary artery disease (CAD) in a previously described cohort of patients with familial hypercholesterolemia (FH) and an appropriate population of control subjects. The plasma concentration of Lp(a) was markedly skewed in both the FH and control populations; however, the distribution was less skewed in FH (50% greater than 300 mg/L) compared with control subjects (27% greater than 300 mg/L). Patients with FH had significantly higher median and mean log Lp(a) levels compared with control subjects. There was no difference in the level of Lp(a) between men and women in both the control and FH groups. Frequency distribution analysis of the major apo(a) isoform size for each subject showed that, in contrast to the near-normal distribution seen in control subjects, two major subpopulations were apparent in the FH cohort, based on apo(a) isoform size > 700 kD or < or = 700 kD. There was no correlation between Lp(a) plasma concentration and apo(a) isoform size in either population. FH subjects with smaller apo(a) isoforms were more likely to have a history of signs of, or symptoms of CAD than those with larger isoforms. These data illustrate that on the basis of Lp(a) plasma concentration alone, there is no significant difference between FH patients with and without signs or symptoms of CAD. In the control population the smaller apo(a) isoforms were associated with higher Lp(a) levels, whereas in the FH population both small and large apo(a) isoforms were associated with higher Lp(a) levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2003

Characteristics of women with cosmetic breast implants compared with women with other types of cosmetic surgery and population-based controls in Denmark.

Herein the authors describe characteristics of women with breast implants compared with women with other types of cosmetic surgery as well as population controls. All women who acquired breast implants from 1977 to 1997 were identified from the files of two private plastic surgery clinics in Denmark. Patient characteristics were obtained through a self-administered questionnaire. The magnitude of differences between patient and control groups was estimated using odds ratios and 95% confidence intervals. Women with breast implants had a significantly lower body mass index and reported a two-fold greater incidence of current smoking compared with women from the general population and compared with women with other cosmetic surgery. Women with implants reported a greater number of full-term pregnancies and were less likely than controls to have had their first birth at age 30 years or older. Women with implants were not more likely than women in either control group to report a history of diseases, including connective tissue diseases, cancer, or depression before their implant surgery. Women with cosmetic breast implants differ from women with other forms of cosmetic surgery and from general population controls with respect to characteristics that may importantly influence health outcomes and that need to be addressed in future breast implant studies.

Adult↗
PubMed2004

CARD15 gene polymorphisms in patients with spondyloarthropathies identify a specific phenotype previously related to Crohn's disease.

BACKGROUND: The association between spondyloarthropathy and Crohn's disease is well known. A risk for evolution to Crohn's disease has already been shown in the subgroup of patients with spondyloarthropathy associated with chronic gut inflammation. OBJECTIVE: To investigate whether the reported polymorphisms in the CARD15 gene, a susceptibility gene for Crohn's disease, are associated with the presence of preclinical intestinal inflammation observed in spondyloarthropathies. METHODS: 104 patients with spondyloarthropathies were studied. All underwent ileocolonoscopy with biopsies between 1983 and 2004. The prevalence of three single nucleotide polymorphisms in the CARD15 gene (R702W, G908R, and 1007fs) was assessed using restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR); the patients were compared with an ethnically matched Crohn's disease population and a control population. RESULTS: The carrier frequency of R702W, G908R, or 1007fs variants in the spondyloarthropathy populations (20%) was similar to the control population (17%), but increased to 38% in the spondyloarthropathy subgroup with chronic gut inflammation. This frequency was significantly higher than in the other spondyloarthropathy subgroups (p = 0.001) or the control group (p = 0.006), but not different from the Crohn's disease group (49%) (NS). This indicates that CARD15 polymorphisms are associated with a higher risk for development of chronic gut inflammation. CONCLUSIONS: CARD15 gene polymorphisms clearly identify a subgroup of patients with spondyloarthropathies associated with chronic intestinal inflammation.

Adolescent↗
PubMed1975

Male-linked translocations and the control of insect pest populations.

Published data on an experimental release of Culex pipiens carrying a male-linked translocation are re-examined and it is shown that the steady decline in translocation frequency after termination of releases agrees with theoretical expectations, because of the selective disadvantage of translocation heterozygote males. Systems based on negative heterosis or meiotic drive are considered whereby it might be possible to prolong the population control which would be achieved by a short term release.

Animals↗