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Biomedical subjects

Marie Reilly

Publications and source records attributed to Marie Reilly.

16 recordsLinked to original sources

Ethnic differences in the time trend of female breast cancer incidence: Singapore, 1968-2002.

BACKGROUND: From 1968 to 2002, Singapore experienced an almost three-fold increase in breast cancer incidence. This increase appeared to be different across the three main ethnic groups: Chinese, Malays and Indians. This paper used age-period-cohort (APC) modelling, to determine the effects of age at diagnosis, calendar period, and birth cohort on breast cancer incidence for each ethnic group. METHODS: This study included all breast cancer cases (n = 15,269) in the three ethnic groups, reported to the Singapore Cancer Registry from 1968 to 2002 between the ages 25 to 79. Age-specific fertility rates from the Department of Statistics were used to explore the role of fertility. RESULTS: In the 1970s, Indian women had the highest age-standardized breast cancer but by the mid-1980s the highest rates were seen among the Chinese. Remarkable differences were seen in the age-specific incidence rates by ethnic groups. After age 49, the incidence rates for the Chinese and Malays leveled off whereas it continued to rise in the Indians. While our analyses provided some evidence that an age-drift model described the trend seen in the Indians, age-period-cohort model and age-cohort model had the best fit for the Chinese and Malays aged 25 to 79 respectively. Overall, Chinese and Malay women born in later cohorts were at increased risk of developing breast cancer relative to their counterparts in the earlier cohorts. The three ethnic groups experienced similar changes in their fertility in the 1970s, which likely explained much of the increase in their breast cancer incidence but not the ethnic differences. There was a stronger inverse association between total fertility rate and pre-menopausal breast cancer incidence in the Chinese and Malays than the Indians. CONCLUSION: The observed dissimilarity among ethnic groups suggests ethnic differences in exposure or response to certain risk factors. It is likely that longer and subtler differences in childbearing trends and other risk factors may further explain these ethnic differences.

Adult↗

Familial aggregation of small-for-gestational-age births: the importance of fetal genetic effects.

OBJECTIVE: This study was undertaken to disentangle the maternal genetic, fetal genetic, and environmental effects for the risk of having small-for-gestational-age (SGA) offspring. STUDY DESIGN: By cross-linking the population-based Swedish Multi-Generation and Medical Birth Registers, we extracted 2,193,142 births between 1973 and 2001 with both parents identified. Odds ratios (OR) were calculated to estimate the relative risks, and generalized linear mixed models were used to estimate the contribution of genetic and environmental effects. RESULTS: Women whose full sisters had an offspring born SGA had a significantly increased risk of having a SGA offspring themselves (OR = 1.8, 95% CI 1.7-1.9), whereas the corresponding risk for brothers was lower (OR = 1.3, 95% CI 1.2-1.4). Thirty-seven percent of the liability was explained by fetal (including both maternal and paternal) genetic effects and 9% by maternal genetic effects. CONCLUSION: Genetic factors account for almost half of the liability to have SGA births. These effects are primarily caused by fetal genes.

Female↗

Accommodation of additional non-randomly sampled cases in a study of Helicobacter pylori infection in families.

Epidemiological studies with two-stage designs typically gather information about some covariates from all study subjects in the first sampling stage, while additional data from only a subset of the subjects are collected in the second sampling stage. Appropriate analysis of two-stage studies maintains validity and can also improve precision. We describe an application of a weighted likelihood method, mean-score logistic regression, to accommodate data from a cross-sectional study of Helicobacter pylori infection in children, where the study sample was enriched with additional non-randomly sampled cases. The present work exemplifies how careful analysis of epidemiological data from complex sampling schemes can adjust for potential selection bias, improve precision and enable a more complete investigation of factors of interest. Our results highlight the importance of H. pylori infected mothers and siblings as risk factors for the infection in children in Sweden.

Child↗

Re-use of case-control data for analysis of new outcome variables.

Case-control studies are usually defined to investigate risk factors for a single disease of interest. However, subsequent to data collection, investigators may wish to examine as an 'outcome' a variable that was an exposure in the original study. A naive analysis that disregards the sampling strategy that gave rise to the data is clearly prone to bias. We present here a simple approach to the analysis of such data using an appropriately weighted regression model. Viewing the problem as a two-stage design provides a unified framework for recognizing and defining the necessary weights when confronted with a variety of real data problems that at first seem unrelated. We provide illustrations that highlight the generality of the approach and demonstrate that the method gives essentially the same results as more specialized methods that require non-standard tools for analysis.

Adult↗

Modified vaccinia Ankara expressing HIVA antigen stimulates HIV-1-specific CD8 T cells in ELISpot assays of HIV-1 exposed infants.

Recombinant modified vaccinia virus Ankara expressing HIV-1 antigens (MVA.HIVA) was used in ELISpot assays to monitor HIV-1-specific T cell responses in infants. Responses to MVA.HIVA and HIV-1 peptides were examined in 13 infected and 81 exposed uninfected infants in Nairobi, Kenya. Responses to MVA.HIVA (38%) and peptide stimulation (38%) were similar in frequency (p=1.0) and magnitude (mean 176 versus 385 HIVSFU/10(6), p=0.96) in HIV-1 infected infants. In exposed uninfected infants, MVA.HIVA detected more positive responses and higher magnitude responses as compared to peptide. MVA.HIVA ELISpot is a sensitive method for quantification of HIV-1-specific CD8+ T cell responses in HIV-1 exposed infants. These results demonstrate the relevance of HIV-1 clade A consensus-derived immunogen HIVA for the viruses currently circulating in Nairobi.

CD8-Positive T-Lymphocytes↗

Profound changes in breast cancer incidence may reflect changes into a Westernized lifestyle: a comparative population-based study in Singapore and Sweden.

Breast cancer incidence in Sweden has always been approximately twice as high as in Singapore. In recent years, this difference is limited to postmenopausal women. The aim of this study was to explore the reasons behind these differences through the use of age-period-cohort modeling. This population-based study included all breast cancer cases reported to the Swedish and the Singapore cancer registries from 1968 to 1997, with a total of 135,581 Swedish and 10,716 Singaporean women. Poisson regression using age-period and age-cohort models was used to determine the effects of age at diagnosis, calendar period and birth cohort. Incidence rate ratios were used to summarize these effects. An age-cohort model provided the best fit to the data in both countries, indicating that changes over lifetime, rather than recent differences in medical surveillance, might account for the observed differences in these 2 populations. The changes over birth cohort were much greater among Singaporean women. The relative effect of age was very similar in the 2 countries. Analyses show that age and cohort effects may explain the differences in trends of female breast cancer incidence between Sweden and Singapore. The larger cohort effect seen in Singaporean women may be attributed to more rapid changes in reproduction and lifestyle patterns than that of Swedish women during the period studied. The incidence of breast cancer in postmenopausal women in Singapore will probably continue to rise in the coming decades to match the current Swedish rates.

Adult↗

Genetic implications of bilateral breast cancer: a population based cohort study.

BACKGROUND: Women with breast cancer are at high risk of bilateral breast cancer. We aimed to assess the incidence of bilateral breast cancer in relation to age and time since diagnosis of first cancer. METHODS: We analysed a population-based cohort of 123757 women with a first primary breast cancer diagnosed in Sweden from 1970 to 2000 for frequency of bilateral breast cancers and deaths by means of record linkage. Second primary breast cancers were categorised as synchronous bilateral breast cancers if diagnosed within 3 months of the first primary cancer or as metachronous if diagnosed more than 3 months after diagnosis of first primary cancer. FINDINGS: We identified 6550 women who had developed bilateral breast cancer. Age-incidence patterns of synchronous and unilateral breast cancer were similar, although the absolute rates of synchronous bilateral cancer were 50-100 times lower than those of unilateral cancer. A woman aged 80 years or older is at least twice as likely to be diagnosed with synchronous bilateral breast cancer than is a woman younger than 40 years. In the first 20 years after diagnosis of primary breast cancer, incidence of metachronous bilateral cancer decreased from about 800 per 10(5) person-years to 400 per 10(5) person-years in patients diagnosed with primary breast cancer before the age of 45 years, whereas incidence remained at 500-600 per 10(5) person-years in those age 45 years or older at diagnosis. After 30 years' follow-up, cumulative risk of metachronous bilateral breast cancer was about 15% irrespective of age at first primary breast cancer. INTERPRETATION: The higher than expected risk of synchronous bilateral breast cancer could be explained by non-genetic factors. By contrast, incidence of metachronous bilateral cancer fits neither a model of highly penetrant genes nor aggregation of environmental risk factors.

Adult↗

Trunk position in supine of infants born preterm and at term: an assessment using a computerized pressure mat.

PURPOSE: Trunk position may influence motor, cognitive, and social development during infancy and early childhood and has not been quantitatively assessed. The purpose of this study was to assess the trunk positions of infants born at term and preterm in supine using a computerized pressure mat. METHODS: Trunk position was represented as a ratio of head and pelvis to trunk pressure. Eighteen healthy infants born preterm with a mean gestational age of 31.9 weeks (25.0-34.6) and fifteen healthy infants born at term with a mean gestational age of 38.9 weeks (37.3-40.6) were assessed at 38 to 43 weeks gestational age. RESULTS: Infants born at term spent more than two-thirds of the time in either flexed or neutral trunk positions. No significant differences were found between infants born preterm and those born at term in total duration of flexion or extension or in flexion event duration. CONCLUSION: This study provides evidence that infants born preterm may not exhibit greater trunk extension tendencies in supine than infants born at term. Results should be interpreted with caution, however, because of the small sample size and large variability observed within the subject groups. Infants born at less than 30 weeks of gestation may demonstrate greater extension tendencies than those born at more than 30 weeks of gestation.

Case-Control Studies↗

Maternal and fetal genetic factors account for most of familial aggregation of preeclampsia: a population-based Swedish cohort study.

There is accumulated evidence for genetic influences on preeclampsia. However, no study has been able to separate the effects of maternal and fetal genetic factors from environmental factors, and there are still uncertainties about the origin and magnitude of the genetic effects. We used the population-based Swedish Birth and Multi-Generation Registries to identify a cohort of women who gave birth from 1987 through 1997. In order to separate the genetic and environmental contributions to preeclampsia, we analyzed pregnancy outcomes from families joined by full siblings. We included information from 244,564 sibling pairs (62,236 sister pairs, 63,288 brother pairs, and 119,040 sister-brother pairs), who had 701,488 pregnancies. We found that 35% of the variance in liability of preeclampsia was attributable to maternal genetic effects, 20% to fetal genetic effects (with similar contribution of maternal and paternal genetic effects), 13% to the couple effect, less than 1% to shared sibling environment, and 32% to unmeasured factors. Among women and men without a history of preeclampsia, partner change reduced the risk of preeclampsia (odds ratio, 0.6; 95 percent confidence interval, 0.4-0.9). Genetic factors account for more than half of the liability of preeclampsia, and maternal genes contribute more than fetal genes. We suggest that the couple effect is due to a genetic interaction between mother and father.

Adult↗

Modelling infectious disease transmission with complex exposure pattern and sparse outcome data.

We present a regression modelling framework to analyse infectious disease transmission during a time period where extensive exposure data are available, but where the outcome data are sparse. A latent variable model is used for each exposure time, allowing a straight-forward accumulation of risk for a collection of exposures for which outcome data are available. We describe an analysis of HIV infection from blood products among a cohort of haemophiliacs in Ireland between 1980 and 1985. The analysis provides estimates of the time pattern and batch effects; we show how analytical complexity such as smoothly varying coefficients or random coefficient models can be accommodated by the model. Finally, we discuss other problems where the model is applicable.

Cohort Studies↗

The effect of hormonal contraception on genital tract shedding of HIV-1.

OBJECTIVE: A previous cross-sectional study reported that hormonal contraception may be associated with increased infectivity in HIV-1 infected women. We conducted a prospective study to determine if cervical shedding of HIV-1 increased after initiating hormonal contraception. DESIGN: Shedding of HIV-1 DNA (a marker of HIV-1 infected cells) and HIV-1 RNA were measured before and after initiating hormonal contraception. METHODS: HIV-1 seropositive women were recruited from a Kenyan family planning clinic. At baseline, cervical secretions were collected for HIV-1 DNA and RNA assays in women initiating hormonal contraception; follow-up samples were collected a median of 64 days later. RESULTS: One-hundred and one women chose depot medroxyprogesterone (Depo), 53 chose low-dose oral contraceptives (OC), seven high-dose OC, and 52 progesterone-only OC. At follow-up, there was a significant increase in the prevalence of cervical HIV-1 DNA detection [from 42% to 52%, odds ratio (OR), 1.62; 95% confidence interval (CI), 1.03-2.63) for all hormonal contraception combined, and a trend for an increase for each individual type. Although the prevalence of cervical HIV-1 RNA increased slightly (from 82% to 86%; OR, 1.56; 95% CI, 0.83-3.03), the concentration of cervical HIV-1 RNA did not change significantly overall (from 2.81 to 2.84 log10 copies/swab; P = 0.77) or for individual contraception types. CONCLUSIONS: A modest but significant increase in shedding of HIV-1 DNA but not of HIV-1 RNA was detected after starting hormonal contraception. Our results may have important implications regarding the infectivity of women using hormonal contraception, and highlight the need for epidemiologic studies of transmission rates from women using and not using hormonal contraception.

Adolescent↗

QT dispersion, QT maximum and risk of cardiac death in the Caerphilly Heart Study.

BACKGROUND: It has been postulated that increased inter-lead differences in QT interval (QT dispersion) and the maximum QT interval (QTmax), in the standard 12-lead electrocardiogram (ECG), may be associated with an increased risk of cardiac death. The aims of this study were to assess the relationship between QT dispersion and QTmax, corrected and uncorrected for heart rate, and the risk of cardiac death. DESIGN: Nested case-control study within the Caerphilly prospective cohort study. METHODS: We studied 2512 men who participated in phase 1 of the Caerphilly study between 1979 and 1983. After a mean follow up of 7.1 years, 218 men had died from coronary heart disease and these men were compared with 218 age-matched controls. RESULTS: Data are presented on 422 patients with ECG suitable for analysis, 207 cases and 215 controls. Four trained observers measured the QT intervals and the reliability of each observer was estimated using repeat measurements on a randomly chosen sub-sample of ECGs. Median corrected QT dispersion and corrected QTmax were significantly higher in cases than in controls (51.9 versus 47.7 ms [P=0.01] and 430 versus 421 ms [P<0.001] respectively). In univariate analyses by quartiles of corrected QT dispersion and corrected QTmax, increased risk was largely confined to the upper quartile of the distribution with these subjects having twice the risk of those in the lower quartile [odds ratio (OR) 2.14, 95% confidence interval (CI) 1.2-3.7 and 2.56 (95% CI 1.5-4.5) respectively]. In logistic regression analysis, adjusted for age, smoking, body mass index, hypertension, history of myocardial infarction and ECG Minnesota code, we observed an increased risk in the upper quartile of the corrected QT dispersion relative to the other three quartiles combined [adjusted OR=1.74 (P=0.03)]. The magnitude of this association was increased in analyses based on the data from the most reliable observers. The association between corrected QTmax and cardiac death was attenuated in multivariate analysis. The findings in relation to both uncorrected QT dispersion and uncorrected QTmax were similar, i.e., consistent with a significant independent effect of QT dispersion but not QTmax for cardiac death in multivariate analysis. CONCLUSION: The data suggest that QT dispersion is an independent predictor of cardiac death provided it can be measured with sufficient reliability. The association is non-linear with increased risk largely confined to the upper quartile of the distribution. The QT maximum is not an independent predictor of cardiac death.

Body Mass Index↗

Temporal variation in Irish suicide rates.

Using Irish suicide data for the period 1990-1998, the independent effects of month and day adjusting for age, gender, and calendar year effects and distinguishing between holiday and working Mondays were assessed. The male suicide rate was significantly higher on working Mondays (+31%) and Saturdays (+14%), and during April, June, and August (+17%), after adjustment for the other variables. In contrast, female suicide rates were higher only in August (+35%) and exhibited no day effect. Teenage men had a greater elevation of risk on Saturdays, Sundays, and both working and holiday Mondays than any other group. The study findings should be taken into account in the planning of specialized health care services and helplines for suicidal people. Furthermore, the findings provide support for Gabennesch's (1988) broken promise theory and the relationship between dysfunctions of the serotonergic system and suicidal behavior.

Adolescent↗

Controlled withdrawal of selective serotonin reuptake inhibitor drugs in elderly patients in nursing homes with no indication of depression.

OBJECTIVE: The aim of the investigation was to study the effects of withdrawing selective serotonin reuptake inhibitor (SSRI) drugs in nursing home patients, who had no documented diagnosis or symptoms of depression. SETTING: The setting of the study was in 11 nursing homes in the county of Stockholm, Sweden. PARTICIPANTS: Participants were patients without dementia or history of depression who had received treatment with SSRI drugs for more than 6 months and who had no indications of anxiety disorder or major depression DESIGN: The included patients ( n=70) were randomized to either the intervention group (withdrawal of SSRI) or the control group (no change in treatment), 35 patients to each group. MAIN OUTCOME MEASURES: The patients were subjected to assessment using the following instruments: Montgomery-Asberg depression rating scale, global assessment for functioning, health index and a symptom assessment form. Assessment was made at the start of the study and at the 3-month and 6-month follow-ups. RESULTS: We found no significant difference between the intervention and control groups in any outcome measure. CONCLUSION: Treatment with SSRI drugs in patients without clinical major depression or anxiety disorder is often unjustified and should be discontinued.

Aged↗

Patterns of initial management of lung cancer in the Republic of Ireland: a population-based observational study.

OBJECTIVES: To examine geographic and temporal trends in the patterns of initial management of lung cancer in Ireland, and to describe differences in case management according to health board of residence. DESIGN: Population-based observational study using the database of the National Cancer Registry of Ireland. PATIENTS: 7286 patients with primary malignant lung tumours who were diagnosed in Ireland during the 5-year period from 1994 to 1998. METHODS: We compared health boards in terms of treatment patterns of small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) cases adjusting for differences in age, gender, and deprivation status. RESULT: Only half of the patients received any cancer-specific treatment. Radiotherapy was the most commonly employed single-treatment modality (21.7%) followed by surgery (12.3%) and chemotherapy (8.8%). Relative to the Eastern Health Board, the risk of being untreated was significantly higher for NSCLC patients living in the Western, Mid-Western, North, and South-Eastern Health Boards. For SCLC, only the Mid-Western and South-Eastern Heath Boards had significantly higher relative risks. For both groups, older patients were less likely to receive treatment, but we could not adjust for stage and comorbidity. CONCLUSION: We found wide regional variations in treatment rates of lung cancer in Ireland.

Adolescent↗

Randomized controlled intervention in cardiovascular drug treatment in nursing homes.

OBJECTIVE: To study drug treatment of patients with cardiovascular diseases (heart failure, post-myocardial infarction, angina pectoris, hypertonia or cardiac valvular disease) in nursing homes and assess effect of medication advice. INTERVENTION: The patients were randomized to an intervention or control group. Medication reviews were made by one specialist in clinical pharmacology and one in cardiology. Symptoms related to heart failure or adverse reactions to cardiovascular drugs were recorded using a questionnaire. Quality of life and activities of daily living (ADL) were assessed and follow-ups performed after 2 weeks and 3 months. Outcome measures were changes of drug therapy and the global scores computed from symptoms scales. RESULTS: Eighty patients were randomized. They had a mean age of 87 years and their average number of drugs was 9.6. Changed drug therapy was suggested in 40 patients and the advice was followed by the responsible physicians in 19 patients. The physicians mostly followed advice for changed furosemide therapy but not for introducing an ACE-inhibitor, probably due to uncertain diagnosis and need for follow-up after initiation of such therapy. No significant changes from baseline to later follow-up were found in the mean total scores of any questionnaire. CONCLUSION: Intervention did not affect cardiovascular symptoms. Drug revisions should involve more than one class of drugs in order to be cost-effective.

Activities of Daily Living↗