International Journal of Epidemiology

Published by Oxford University Press

Online ISSN: 1464-3685


Print ISSN: 0300-5771


What is a case-control study?
  • Article

July 2004


59 Reads

T Marshall

Figure 1 Locations of the 10 survey sites and number recruited. Open circles indicate rural areas and solid circles indicate urban areas. Number recruited at baseline in each area is shown in brackets  
Table 1 Selected characteristics of study participants at baseline survey, 2004-08
Figure 2 Proportion of participants born in each calendar year. Open bars indicate people born during these years were eligible for only part of the 4-year recruitment period at baseline survey due to age restriction. The effects of the 1959–61 famine vary by site. The small numbers of participants born before 1930 or after 1973 are shown as 1930 or 1973, respectively  
Table 2 Anthropometric characteristics, physical activities and prevalence of prior disease at baseline survey, 2004-08
Table 3 Spearman correlation coefficients for selected physical measurements between baseline survey and re-survey among 19 788 participants
China Kadoorie Biobank of 0.5 million people: Survey methods, baseline characteristics and long-term follow-up
  • Article
  • Full-text available

December 2011


440 Reads






Large blood-based prospective studies can provide reliable assessment of the complex interplay of lifestyle, environmental and genetic factors as determinants of chronic disease. The baseline survey of the China Kadoorie Biobank took place during 2004-08 in 10 geographically defined regions, with collection of questionnaire data, physical measurements and blood samples. Subsequently, a re-survey of 25,000 randomly selected participants was done (80% responded) using the same methods as in the baseline. All participants are being followed for cause-specific mortality and morbidity, and for any hospital admission through linkages with registries and health insurance (HI) databases. Overall, 512,891 adults aged 30-79 years were recruited, including 41% men, 56% from rural areas and mean age was 52 years. The prevalence of ever-regular smoking was 74% in men and 3% in women. The mean blood pressure was 132/79 mmHg in men and 130/77 mmHg in women. The mean body mass index (BMI) was 23.4 kg/m(2) in men and 23.8 kg/m(2) in women, with only 4% being obese (>30 kg/m(2)), and 3.2% being diabetic. Blood collection was successful in 99.98% and the mean delay from sample collection to processing was 10.6 h. For each of the main baseline variables, there is good reproducibility but large heterogeneity by age, sex and study area. By 1 January 2011, over 10,000 deaths had been recorded, with 91% of surviving participants already linked to HI databases. This established large biobank will be a rich and powerful resource for investigating genetic and non-genetic causes of many common chronic diseases in the Chinese population.

Size at birth as a predictor of mortality in adulthood: A follow-up of 350 000 person-years

June 2005


140 Reads

Small body size at birth, as a marker of an adverse intrauterine environment, has recently emerged as an important risk factor for death from cardiovascular disease. Our aim was to study the relationship between small size at birth and all-cause and non-cardiovascular mortality, which has been poorly documented. We studied 13 830 individuals born between 1924 and 1944 in Helsinki, Finland, at term as singletons. Dates and primary causes of death between 1971 and 1998 were obtained from the Finnish National Death Register. 1668 men and 671 women died during the follow-up at the mean age of 56.0 (range 26.7-74.9) years. Lower birthweight was associated with increased all-cause mortality in females (Odds ratio (OR) for 1 kg decrease in birthweight 1.25, 95% CI 1.05-1.49; P = 0.01) but not in males (OR 1.08; 0.96-1.19; P = 0.2; P for sex-birthweight interaction = 0.09). Similarly, short length at birth was a predictor of all-cause mortality in females (OR for 1 cm decrease 1.10; 1.05-1.15; P < 0.0001) but not in males (OR 1.01; 0.98-1.02; P = 0.4; P for sex-length at birth interaction = 0.002). Low birthweight and short length at birth predicted premature death in adulthood (<55 years) in both sexes. In males, death from cardiovascular disease (n = 654) was associated with lower birthweight (OR for 1 kg decrease 1.33; 1.12-1.59; P = 0.001), and length (OR 1.05; 1.00-1.10; P = 0.03), and in females death from cardiovascular disease (n = 179) was associated with short length at birth (OR 1.11; 1.02-1.20; P = 0.02). In females death from non-cardiovascular diseases was predicted by low birthweight (OR 1.25; 1.01-1.54; P = 0.04) and short length at birth (OR 1.09; 1.03-1.15; P = 0.003) (n = 475), but not in males (n = 975; P for interaction = 0.02 and 0.004, respectively). Cancer-related death was associated with higher birthweight (OR for 1 kg decrease 0.76; 0.61-0.95; P = 0.02) and ponderal index (OR for 1 kg/m(3) increase 0.95; 0.91-0.99; P = 0.01) in males (n = 361) but not in females (n = 269). Small size at birth is associated with increased all-cause mortality at all ages among adult women but only with premature death in adult men. Among women death from both cardiovascular and non-cardiovascular causes is associated with small body size at birth. Among men an association between small birthsize and later cardiovascular disease is counterbalanced by an association between large body size at birth and later cancer.

Body mass index and cardiovascular disease in the Asia-Pacific Region: an overview of 33 cohorts involving 310 000 participants

September 2004


92 Reads

Few prospective data from the Asia-Pacific region are available relating body mass index (BMI) to the risks of stroke and ischaemic heart disease (IHD). Our objective was to assess the age-, sex-, and region-specific associations of BMI with cardiovascular disease using individual participant data from prospective studies in the Asia-Pacific region. Studies were identified from literature searches, proceedings of meetings, and personal communication. All studies had at least 5000 person-years of follow-up. Hazard ratios were calculated from Cox models, stratified by sex and cohort, and adjusted for age at risk and smoking. The first 3 years of follow-up were excluded in order to reduce confounding due to disease at baseline. A total of 33 cohort studies, including 310 283 participants, contributed 2 148 354 person-years of follow-up, during which 3332 stroke and 2073 IHD events were observed. There were continuous positive associations between baseline BMI and the risks of ischaemic stroke, haemorrhagic stroke, and IHD, with each 2 kg/m(2) lower BMI associated a 12% (95% CI: 9, 15%) lower risk of ischaemic stroke, 8% (95% CI: 4, 12%) lower risk in haemorrhagic stroke, and 11% (95% CI: 9, 13%) lower risk of IHD. The strengths of all associations were strongly age dependent, and there was no significant difference between Asian and Australasian cohorts. This overview provides the most reliable estimates to date of the associations between BMI and cardiovascular disease in the Asia-Pacific region, and the first direct comparisons within the region. Continuous relationships of approximately equal strength are evident in both Asian and Australasian populations. These results indicate considerable potential for cardiovascular disease reduction with population-wide lowering of BMI.

Cohort Profile: The Chennai prospective study of mortality among 500 000 adults in Tamil Nadu, South India

January 2008


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A prospective study of half a million adults living in the city of Chennai (formerly Madras) arose out of discussions at the 1994 International Cancer Congress in Delhi about how to assess the effects of tobacco on health in different parts of India. Chennai is the capital of the South Indian state of Tamil Nadu, and it is India's fourth most populous city. Two large-scale epidemiological studies of tobacco and other factors were established: a case-control study1 that could provide reasonably reliable results quickly, and a prospective cohort study that could provide more robust results over a longer period. (A parallel prospective study of 100000 adults, not included in this profile, is in progress in the nearby rural area of Villupuram; Figure 1.) The case-control analyses,1 which involved 43000 adult deaths during 1995-97 and 35000 controls who had been living with a case, indicated that smoking is a cause of, among other things, about half of all tuberculosis (TB) deaths among men. The prospective cohort study, which recruited half a million participants between 1998 and 2001, is described here.

Figure 3 Male stroke and CHD mortality at 30 kg/m 2 compared with 25 kg/m 2 in China and the USA, estimated using year 2000 mortality rates at age 50-69 years. Number at top of the bar is mortality rate (annual deaths per 1000 men). (A) For China, the mortality rate at 25 kg/m 2 was taken as the average rate (mean of rates at age 50-54, 55-59, 60-64 and 65-69 years) for the whole Chinese population (calculated as a 30:70 weighted average of the rates for selected urban areas and selected rural areas provided by China to the WHO), and the mortality rate at 30 was calculated as that at 25 kg/ m 2 multiplied by the relevant HR from this study. (B) For USA, the average WHO mortality rate (same age categories as for China) was assumed to be that at 28.5 kg/m 2 , and the mortality rates at 30 and 25 kg/m 2 were calculated by multiplying this rate by male HRs derived from the Prospective Studies Collaboration 7 
Body mass index and mortality in China: A 15-year prospective study of 220 000 men

January 2012


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In China, there have been few large prospective studies of the associations of body mass index (BMI) with overall and cause-specific mortality that have simultaneously controlled for biases that can be caused by pre-existing disease and smoking. Prospective cohort study of 224 064 men, of whom 40 700 died during follow-up between 1990-91 and 2006. Analyses restricted to 142 214 men aged 40-79 years at baseline with no disease history and, to further reduce bias from pre-existing disease, at least 5 years of subsequent follow-up, leaving 17 800 deaths [including 4165 stroke, 1297 coronary heart disease (CHD), 3121 chronic obstructive pulmonary disease (COPD)]. Adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) per 5 kg/m(2) calculated within either a lower (15 to <23.5 kg/m(2)) or higher (23.5 to <35 kg/m(2)) range. The association between BMI and all-cause mortality was U-shaped with the lowest mortality at ∼22.5-25 kg/m(2). In the lower range, 5 kg/m(2) higher BMI was associated with 14% lower mortality (HR 0.86, 95% CI 0.82-0.91); in the upper range, it was associated with 27% higher mortality (HR 1.27, 95% CI 1.15-1.40). The absolute excess mortality in the lower range was largely accounted for by excess mortality from specific smoking-related diseases: 54% by that for COPD, 12% other respiratory disease, 13% lung cancer, 11% stomach cancer. The excess mortality in the upper BMI range was largely accounted for by excess mortality from specific vascular diseases: 55% by that for stroke, 16% CHD. In this range, 5 kg/m(2) higher BMI was associated with ∼50% higher mortality from stroke (HR 1.61, 95% CI 1.36-1.92) and CHD (HR 1.48, 95% CI 1.12-1.95). For China, previous evidence may have overestimated the excess mortality at low BMI but underestimated that at high BMI. The main way obesity kills in China appears to be stroke.

Figure 1 Incidence a of disability pension by sex and age in the county Nord-Trøndelag compared to the total country (Norway)—1974–1998 a Age-adjusted by direct standardization—standard population—Norway—1 January 1995, 16–66 years.  
Social determinants of disability pension: A 10-year follow-up of 62 000 people in a Norwegian county population

January 2003


123 Reads

Non-medical factors may be important determinants for granting disability pension (DP) even though disability is medically defined, as in Norway. The aim of this analysis was to identify determinants of DP in a total county population in a 10-year follow-up study. Participants were people without DP, 20- to 66-years-old in 1984-1986. The baseline data were obtained in the Nord-Trøndelag Health Study (HUNT): 90 000 people were invited to answer questionnaires on health, disease, social, psychological, occupational, and lifestyle factors. Information on those who later received DP was obtained from the National Insurance Administration database in 1995. Data analyses were performed using Cox regression analyses. The incidence of DP showed great variation with regards to age and gender, accounting for an overall increase in the follow-up period. Low level of education, low self-perceived health, occupation-related factors and any long-standing health problem were found to be the strongest independent determinants of DP. Low level of education and socioeconomic factors contributed more to younger people's risk compared to those over 50 years. For people under 50 years of age with a low level of education compared to those with a high level of education, the age-adjusted relative risk for DP was 6.35 for men and 6.95 for women. The multivariate-adjusted relative risk was 2.91 and 4.77, respectively. Even for a medically based DP, low socioeconomic status, low level of education and occupational factors might be strong determinants when compared to medical factors alone. These non-medical determinants are usually not addressed by individual based health or rehabilitation programmes.

Cancer Incidence among 78 000 Asthmatic Patients

January 1994


53 Reads

Vesterinen E (Department of Allergic Diseases, Helsinki University Central Hospital, Meilahdentie Helsinki, Finland), Pukkala E, Timonen T and Aromaa A. Cancer incidence among 78 000 asthmatic patients. International Journal of Epidemiology 1993; 22: 976-982. The risk of cancer was evaluated among 77 952 asthma patients with bronchial asthma. The series was obtained through linkage of two registers: the Finnish Social Insurance Institution's file of asthma patients and the Finnish Cancer Registry. There was a significant excess risk of lung cancer in both sexes, the standardized incidence ratio (SIR) being 1.32 among men and 1.66 among women. In women, the risk of cancer of the rectum was significantly increased (SIR 1.42), whereas the risks of cancer of the corpus uteri and multiple myeloma were lower than expected (SIR 0.76 and 0.53, respectively). In men, the incidence of cancer of the larynx was significantly reduced (SIR 0.63) and that of the bladder increased (SIR 1.25). When both sexes were combined, cancers of the colon (SIR 1.17) and rectum (SIR 1.28) also showed a significantly elevated risk. A reduction in risk was seen in stomach cancer (SIR 0.88) and lymphatic leukaemia (SIR 0.55). The increased lung cancer risk may be due to local inflammatory changes. It is possible that differences in the immune system, e.g. natural killer cell activity, explain some of the reduced cancer risks

Table 1 . Continued 
Table 1 Demographic and reproductive characteristics 
Temporal trends of main reproductive characteristics in ten urban and rural regions of China: the China Kadoorie Biobank study of 300 000 women

March 2014


82 Reads

Chinese women's reproductive patterns have changed significantly over the past several decades. However, relatively little is known about the pace and characteristics of these changes either overall or by region and socioeconomic status. We examined the cross-sectional data from the China Kadoorie Biobank cohort study that recruited 300 000 women born between 1930 and 1974 (mean age: 51 years) from 10 socially diverse urban and rural regions of China. Temporal trends in several self-reported reproductive characteristics, and effect modification of these trends by area and education (as a surrogate for socioeconomic status), were examined. The overall mean age at menarche was 15.4 (standard deviation 1.9) years, but decreased steadily over the 45 birth cohorts from 16.1 to 14.3 years, except for an anomalous increase of ∼1 year for women exposed to the 1958-61 famine in early adolescence. Similarly large changes were seen for other characteristics: mean parity fell (urban: 4.9 to 1.1; rural: 5.9 to 1.4); mean age at first birth increased (urban: 19.0 to 25.9 years; rural: 18.3 to 23.8 years); and birth spacing increased after 1980 to over 5 years. Breastfeeding declined after 1950 in urban and, after 1980, in rural women; and 68% of urban and 48% of rural women experienced a terminated pregnancy. Mean age at menopause increased from 47.9 to 49.3 years. There have been striking changes in reproductive factors over time and between areas among these Chinese women. Their effects on major chronic diseases should be investigated.

Subgroups at high risk for ischaemic heart disease: Identification and validation in 67 000 individuals from the general population

October 2014


34 Reads

Background: The aetiology of ischaemic heart disease (IHD) is complex and is influenced by a spectrum of environmental factors and susceptibility genes. Traditional statistical modelling considers such factors to act independently in an additive manner. The Patient Rule-Induction Method (PRIM) is a multi-model building strategy for evaluating risk attributable to context-dependent gene and environmental effects. Methods: PRIM was applied to 9073 participants from the prospective Copenhagen City Heart Study (CCHS). Gender-specific cumulative incidences were estimated for subgroups defined by categories of age, smoking, hypertension, diabetes, body mass index, total cholesterol, high-density lipoprotein cholesterol and triglycerides and by 94 single nucleotide variants (SNVs).Cumulative incidences for subgroups were validated using an independently ascertained sample of 58 240 participants from the Copenhagen General Population Study (CGPS). Results: In the CCHS the overall cumulative incidences were 0.17 in women and 0.21 in men. PRIM identified six and four mutually exclusive subgroups in women and men, respectively, with cumulative incidences of IHD ranging from 0.02 to 0.34. Cumulative incidences of IHD generated by PRIM in the CCHS were validated in four of the six subgroups of women and two of the four subgroups of men in the CGPS. Conclusions: PRIM identified high-risk subgroups characterized by specific contexts of selected values of traditional risk factors and genetic variants. These subgroups were validated in an independently ascertained cohort study. Thus, a multi-model strategy may identify groups of individuals with substantially higher risk of IHD than the overall risk for the general population.

Table 1 Characteristics of the population at baseline by category of height-adjusted peak flow and age at baseline 
Figure 3 Cause-specific hazard ratios (HR) for a 100 L/min decrease in height-adjusted peak expiratory flow (h-PEF) (L/min) by 5-year follow up period (FUP). HRs are adjusted for 5-year baseline age group, area, smoking, and education. Area of square is inversely proportional to floated variance of log HR. Error bars indicate 95% confidence intervals (CI) 
Peak flow as a predictor of cause-specific mortality in china: Results from a 15-year prospective study of 170 000 men

June 2013


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Forced expiratory volume in one second (FEV1) is inversely associated with mortality in Western populations, but few studies have assessed the associations of peak expiratory flow (PEF) with subsequent cause-specific mortality, or have used populations in developing countries, including China, for such assessments. A prospective cohort study followed ∼170 000 Chinese men ranging in age from 40-69 years at baseline (1990-1991) for 15 years. In the study, height-adjusted PEF (h-PEF), which was uncorrelated with height, was calculated by dividing PEF by height. Hazard ratios (HR) for cause-specific mortality and h-PEF, adjusted for age, area of residence, smoking, and education, were calculated through Cox regression analyses. Of the original study population, 7068 men died from respiratory causes (non-neoplastic) and 22 490 died from other causes (including 1591 from lung cancer, 5469 from other cancers, and 10 460 from cardiovascular disease) before reaching the age of 85 years. Respiratory mortality was strongly and inversely associated with h-PEF. For h-PEF ≥ 250 L/min, the association was log-linear, with a hazard ratio (HR) of 1.29 (95% CI: 1.25-1.34) per 100 L/min reduction in h-PEF. The association was stronger but not log-linear for lower values of h-PEF. Mortality from combined other causes was also inversely associated with h-PEF, and the association was log-linear for all values of h-PEF, declining with follow-up, with HRs per 100 L/min reduction in h-PEF of 1.13 (1.10-1.15), 1.08 (1.06-1.11), and 1.06 (1.03-1.08) in three consecutive 5-year follow-up periods. Specifically, lower values of h-PEF were associated with higher mortality from cardiovascular disease and lung cancer, but not from other cancers. A lower value of h-PEF was associated with increased mortality from respiratory and other causes, including lung cancer and cardiovascular disease, but its associations with the other causes of death declined across the follow-up period.

Infant and disease characteristics of the study populations
Infant birthweight and risk of childhood cancer: International population-based case control studies of 40 000 cases

February 2015


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Background: High birthweight is an established risk factor for childhood leukaemia. Its association with other childhood cancers is less clear, with studies hampered by low case numbers. Methods: We used two large independent datasets to explore risk associations between birthweight and all subtypes of childhood cancer. Data for 16 554 cases and 53 716 controls were obtained by linkage of birth to cancer registration records across five US states, and 23 772 cases and 33 206 controls were obtained from the UK National Registry of Childhood Tumours. US, but not UK, data were adjusted for gestational age, birth order, plurality, and maternal age and race/ethnicity. Results: Risk associations were found between birthweight and several childhood cancers, with strikingly similar results between datasets. Total cancer risk increased linearly with each 0.5 kg increase in birthweight in both the US [odds ratio 1.06 (95% confidence interval 1.04, 1.08)] and UK [1.06 (1.05, 1.08)] datasets. Risk was strongest for leukaemia [USA: 1.10 (1.06, 1.13), UK: 1.07 (1.04, 1.10)], tumours of the central nervous system [USA: 1.05 (1.01, 1.08), UK: 1.07 (1.04, 1.10)], renal tumours [USA: 1.17 (1.10, 1.24), UK: 1.12 (1.06, 1.19)] and soft tissue sarcomas [USA: 1.12 (1.05, 1.20), UK: 1.07 (1.00, 1.13)]. In contrast, increasing birthweight decreased the risk of hepatic tumours [USA: 0.77 (0.69, 0.85), UK: 0.79 (0.71, 0.89) per 0.5 kg increase]. Associations were also observed between high birthweight and risk of neuroblastoma, lymphomas, germ cell tumours and malignant melanomas. For some cancer subtypes, risk associations with birthweight were non-linear. We observed no association between birthweight and risk of retinoblastoma or bone tumours. Conclusions: Approximately half of all childhood cancers exhibit associations with birthweight. The apparent independence from other factors indicates the importance of intrauterine growth regulation in the aetiology of these diseases.

Body Height and Hip Fracture: A Cohort Study of 90 000 Women

September 1995


30 Reads

Hip fractures are a major public health problem. Recent studies have noted a connection between body height and hip fracture. We investigated the relationship between body height and hip fracture using a prospective cohort of over 92,000 American, predominantly white, female nurses who were followed for 10 years, from June 1980 to June 1990. The women, participants in the Nurses Health Study, were aged 35-59 in 1980. Women 5'8" or taller were more than twice as likely as women under 5'2" to sustain a hip fracture, after accounting for age, body mass index, cigarette smoking and alcohol consumption (multivariate relative risk 2.40, 95% confidence interval: 1.43-4.02; P for trend < 0.0001). Height appears to be an important independent risk factor for hip fracture among American women. Height should be included as a confounder in studies of hip fracture, and taller, elderly women should be advised to consider preventive measures.

Use of period analysis for providing more up-to-date estimates of long-term survival rates: Empirical evaluation among 370 000 cancer patients in Finland

May 2002


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Providing up-to-date estimates of cancer patient survival rates is an important task of cancer registries. A few years ago, a new method of survival analysis, denoted period analysis, was proposed to enhance the recency of long-term survival estimates. The aim of this paper is to provide a comprehensive empirical evaluation of the use of this method. Using data from the nationwide Finnish Cancer Registry, we compare 5-year and 10-year relative survival rates of 371 849 patients diagnosed with one of the 16 most common forms of cancer in Finland at various time intervals between 1953 and 1992 with the most up-to-date estimates of 5-year or 10-year relative survival that might have been obtained in those time intervals by traditional methods of survival analysis and by period analysis of survival. Survival rates strongly increased over time for most forms of cancer. For these cancers, traditional estimates of 5- and 10-year survival rates would have severely lagged behind the survival rates later observed for newly diagnosed patients, and period analysis would consistently have provided much more up-to-date estimates of survival rates. We conclude that period analysis should be implemented as a standard tool for providing up-to-date estimates of long-term survival rates by cancer registries.

Suicide rates in rural Tamil Nadu, South India: Verbal autopsy of 39 000 deaths in 1997–98

March 2007


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In India, death registration is not complete, especially in rural areas. Chiefly for other purposes special efforts were made to identify all deaths that occurred during 1997-98 in rural areas of one of the districts in Tamil Nadu, South India, and the verbal autopsy was done. Trained non-medical field interviewers interviewed surviving spouses, close associates or neighbours, and wrote the verbal autopsy reports in the local language (Tamil). The reports were reviewed independently by two physicians to arrive at the probable underlying cause of death. About 5% of the data were randomly selected for re-interview. The verbal autopsy was done for 38 836 deaths. Injuries accounted for 18.5% of the total deaths. About half of these were suicides. The average annual suicide rate for men and women were 71 and 53/100 000, respectively. Three-fourths of all suicides were in the socially and economically productive age-group of 15-44 years. At ages 15-24 years the female suicide rate of 109/100 000 exceeded the male rate of 78/100 000; suicide was responsible for 49% of all deaths in women and 38% of all deaths in men at these ages. This is the second largest study to date that has used verbal autopsy to estimate mortality rates in India. Suicides accounted for 9% of total deaths, and the ratio of male to female suicide was 1: 0.72. The overall (male + female) annual suicide rate was 62/100 000 population. The female suicide rate at ages 15-24 years was higher than the male rate in that age-group and other female age-groups. About 50% of suicides were by self-poisoning, one-third by hanging and one-eighth by self-immolation.

Table 1 Baseline characteristics of participants by alcohol drinking, among men aged 40-79 years at baseline in 1990-91 
Table 2 Numbers of deaths and standardized hazard ratios for cause-specific deaths by alcohol drinking, among men aged 40-79 years without prior diseases at 
hazard ratios for total mortality by alcohol drinking and smoking status, among men aged 40-79 years without prior diseases at baseline excluding the first 3 years of follow-up 
Alcohol drinking and overall and cause-specific mortality in China: Nationally representative prospective study of 220 000 men with 15 years of follow-up

May 2012


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Regular alcohol drinking contributes both favourably and adversely to health in the Western populations, but its effects on overall and cause-specific mortality in China are still poorly understood. A nationally representative prospective cohort study included 220,000 men aged 40-79 years from 45 areas in China in 1990-91, and >40,000 deaths occurred during 15 years of follow-up. Cox regression was used to relate alcohol drinking to overall and cause-specific mortality, adjusting for age, area, smoking and education. Overall, 33% of the participants reported drinking alcohol regularly at baseline, consuming mainly distilled spirits, with an estimated mean amount consumed of 372 g/week (46.5 units per week). After excluding all men with prior disease at baseline and the first 3 years of follow-up, there was a 5% [95% confidence interval (CI) 2-8] excess risk of overall mortality among regular drinkers. Compared with non-drinkers, the adjusted hazard ratios among men who drank <140, 140-279, 280-419, 420-699 and ≥ 700 g/week were 0.97, 1.00, 1.02, 1.12 and 1.27, respectively (P < 0.0001 for trend). The strength of the relationship appeared to be greater in smokers than in non-smokers. There was a strong positive association of alcohol drinking with mortality from stroke, oesophageal cancer, liver cirrhosis or accidental causes, a weak J-shaped association with mortality from ischaemic heart disease, stomach cancer and lung cancer and no apparent relationship with respiratory disease mortality. Among Chinese men aged 40-79 years, regular alcohol drinking was associated with a small but definite excess risk of overall mortality, especially among smokers.

Figure 1 Flow chart of the KPSC Children’s Health Study 
Table 1 Demographic characteristics of KPSC members 2-19 years of age who are currently included or excluded from the KPSC Children's Health Study
Figure 2 Source of race and ethnicity information in the KPSC Children’s Health Study 
Table 2 Percentage of active KPSC members on 15 January 2005, 0-24 years of age and the percentage retained in the KP plan between 2005 and 2010 Retention of active members (%) in years
Cohort Profile: The KPSC Children's Health Study, a population-based study of 920 000 children and adolescents in southern California

July 2011


224 Reads

Increasing concerns focus on the effects ofobesity on morbidity and health-related quality of lifeissues, particularly in cases of paediatric onset ofobesity. However, the economic burden and long-termhealth consequences of extreme childhood obesity arelargely unknown and ill-defined because there havebeen no large prospective epidemiological studies thatincluded enough extremely obese children to deliverstable estimates of the health consequences.To address current gaps in the knowledge aboutthe health consequences of extreme childhood obes-ity, we created a contemporary cohort study of chil-dren and adolescents 2–19 years of age in southernCalifornia who are actively enrolled in a large, pre-paid, integrated managed healthcare system. TheKaiser Permanente Southern California (KPSC)Children’s Health Study is an ongoing cohort studythat currently includes 4920000 children and adoles-cents and continues to enrol new patients joiningthe health plan. The study is currently supported bya grant from the National Institute of Diabetes andDigestive and Kidney Disorders (R21DK085395;Principal Investigator: Koebnick) and by KaiserPermanente Direct Community Benefit Funds.Since 2007, new screening guidelines for paediatricweight management have been implemented at KPSCoffering a unique opportunity to fill current know-ledge gaps regarding the disease burden associatedwith childhood obesity. These guidelines include regu-lar screening of blood lipids, liver enzymes and mark-ers of glucose metabolism recommended for childrenat or above the 95th percentile of BMI-for-age accord-ing to the 2000 sex-specific Centers for DiseaseControl and Prevention (CDC) growth charts

Figure 1 Association of APOE genotypes in studies of European ancestry individuals with (a) LDL-cholesterol (b) carotid intima-media thickness, (c) ischaemic stroke and (d) ischaemic stroke (trend analysis). Black boxes indicate summary estimates with their size proportional to weight. For (c) and (d), the x-axis is plotted in the log-scale with distance between APOE genotypes equal to mean difference of LDL-C in mmol/l. For (d), the effect estimate of trend analysis indicates an OR of 1.33 (95% CrI: 1.17, 1.52) per 1 mmol/l increase in LDL-C 
Table 1 Continued
Figure 2 APOE genotypes and lipid and apolipoprotein traits. The graphs are displayed in standardized scale to allow comparability and show standardized mean
Figure 3 APOE genotypes and mean differences for inflammatory traits. The graphs are displayed in standardized scale to allow comparability and show standardised mean differences of biomarker levels with APOE genotypes with " 3/ " 3 as reference. The values (on the right) correspond to absolute weighted mean difference. Black boxes indicate estimates proportional to counts and horizontal lines represent 95% CI. Ln, natural log transformed 
Figure 4 Association of APOE genotypes with ischaemic stroke in all ethnicities with (a) ischaemic stroke, (b) ischaemic stroke (trend analysis). Black boxes indicate summary estimates with their size proportional to weight. The x-axis is plotted in the log-scale with distance between APOE genotypes equal to mean difference of LDL-C in mmol/l. For (b), the effect estimate of trend analysis indicates an OR of 1.39 (95% CrI: 1.25, 1.54) per 1 mmol/l increase in LDL-C 
Apolipoprotein E genotype, cardiovascular biomarkers and risk of stroke: Systematic review and meta-analysis of 14 015 stroke cases and pooled analysis of primary biomarker data from up to 60 883 individuals
Background: At the APOE gene, encoding apolipoprotein E, genotypes of the ε2/ε3/ε4 alleles associated with higher LDL-cholesterol (LDL-C) levels are also associated with higher coronary risk. However, the association of APOE genotype with other cardiovascular biomarkers and risk of ischaemic stroke is less clear. We evaluated the association of APOE genotype with risk of ischaemic stroke and assessed whether the observed effect was consistent with the effects of APOE genotype on LDL-C or other lipids and biomarkers of cardiovascular risk. Methods: We conducted a systematic review of published and unpublished studies reporting on APOE genotype and ischaemic stroke. We pooled 41 studies (with a total of 9027 cases and 61,730 controls) using a Bayesian meta-analysis to calculate the odds ratios (ORs) for ischaemic stroke with APOE genotype. To better evaluate potential mechanisms for any observed effect, we also conducted a pooled analysis of primary data using 16 studies (up to 60,883 individuals) of European ancestry. We evaluated the association of APOE genotype with lipids, other circulating biomarkers of cardiovascular risk and carotid intima-media thickness (C-IMT). Results: The ORs for association of APOE genotypes with ischaemic stroke were: 1.09 (95% credible intervals (CrI): 0.84-1.43) for ε2/ε2; 0.85 (95% CrI: 0.78-0.92) for ε2/ε3; 1.05 (95% CrI: 0.89-1.24) for ε2/ε4; 1.05 (95% CrI: 0.99-1.12) for ε3/ε4; and 1.12 (95% CrI: 0.94-1.33) for ε4/ε4 using the ε3/ε3 genotype as the reference group. A regression analysis that investigated the effect of LDL-C (using APOE as the instrument) on ischaemic stroke showed a positive dose-response association with an OR of 1.33 (95% CrI: 1.17, 1.52) per 1 mmol/l increase in LDL-C. In the separate pooled analysis, APOE genotype was linearly and positively associated with levels of LDL-C (P-trend: 2 × 10(-152)), apolipoprotein B (P-trend: 8.7 × 10(-06)) and C-IMT (P-trend: 0.001), and negatively and linearly associated with apolipoprotein E (P-trend: 6 × 10(-26)) and HDL-C (P-trend: 1.6 × 10(-12)). Associations with lipoprotein(a), C-reactive protein and triglycerides were non-linear. Conclusions: In people of European ancestry, APOE genotype showed a positive dose-response association with LDL-C, C-IMT and ischaemic stroke. However, the association of APOE ε2/ε2 genotype with ischaemic stroke requires further investigation. This cross-domain concordance supports a causal role of LDL-C on ischaemic stroke.

HIV incidence in 3 years of follow-up of a Zimbabwe cohort - 1998-2000 to 2001-03: Contributions of proximate and underlying determinants to transmission

March 2008


89 Reads

In recent years, HIV prevalence has begun to decline in Zimbabwe, which has been associated with reductions in sexual risk behaviour. Here, we analyse the determinants of HIV incidence in this period of decline and estimate the population-level impact of identified risk factors. A population-based cohort of 1672 HIV-negative adult males and 2465 HIV-negative adult females was recruited between 1998 and 2000. Each individual was then followed-up 3 years later. The influence and inter-relationship of social, behavioural and demographic variables were examined using a proximate determinants framework. To explore the population-level influence of a variable, methods were developed for estimating a risk factor's contribution to the reproductive number (CRN). HIV incidence was 19.9 [95% confidence interval (CI) 16.3-24.2] per 1000 person years in men and 15.7 (95% CI 13.0-18.9) in women. Multiple sexual partners, having an unwell partner, and reporting another sexually transmitted disease were risk factors that captured the main aspects of the proximate determinants framework: individual behaviour, partnership characteristics and the probability of transmission, respectively. If the proximate determinants fully captured risk of HIV infection, underlying factors would not influence a fully parameterized model. However, a number of underlying social and demographic determinants remained important in regression models after including the proximate determinants. For both sexes, having multiple sexual partners made a substantial CRN, but, for women, no behaviour explained more than 10% of new infections. The proximate determinants did not explain the majority of new infections at the population level. This may be because we have been unable to measure some risks, but identifying risk factors assumes that those acquiring infections are somehow different from others who do not acquire infections. That they are not suggests that in this generalized epidemic there is little difference in readily identifiable characteristics of the individual between those who acquire infection and those who do not.

Table 2 Association between parental history of diabetes and birthweight 
Figure 4 Path analysis of associations between participant birthweight, parental history of diabetes and participant diabetes. **P < 0.001. The regression coefficients presented in brackets represent the coefficients achieved when single pairwise associations are investigated 
Parental diabetes and birthweight in 236 030 individuals in the UK Biobank Study

December 2013


62 Reads

The UK Biobank study provides a unique opportunity to study the causes and consequences of disease. We aimed to use the UK Biobank data to study the well-established, but poorly understood, association between low birthweight and type 2 diabetes. We used logistic regression to calculate the odds ratio for participants' risk of type 2 diabetes given a one standard deviation increase in birthweight. To test for an association between parental diabetes and birthweight, we performed linear regression of self-reported parental diabetes status against birthweight. We performed path and mediation analyses to test the hypothesis that birthweight partly mediates the association between parental diabetes and participant type 2 diabetes status. Of the UK Biobank participants, 277 261 reported their birthweight. Of 257 715 individuals of White ethnicity and singleton pregnancies, 6576 had type 2 diabetes, 19 478 reported maternal diabetes (but not paternal), 20 057 reported paternal diabetes (but not maternal) and 2754 participants reported both parents as having diabetes. Lower birthweight was associated with type 2 diabetes in the UK Biobank participants. A one kilogram increase in birthweight was associated with a lower risk of type 2 diabetes (odds ratio: 0.74; 95% CI: 0.71, 0.76; P = 2 × 10(-57)). Paternal diabetes was associated with lower birthweight (45 g lower; 95% CI: 36, 54; P = 2 × 10(-23)) relative to individuals with no parental diabetes. Maternal diabetes was associated with higher birthweight (59 g increase; 95% CI: 50, 68; P = 3 × 10(-37)). Participants' lower birthweight was a mediator of the association between reported paternal diabetes and participants' type 2 diabetes status, explaining 1.1% of the association, and participants' higher birthweight was a mediator of the association between reported maternal diabetes and participants' type 2 diabetes status, explaining 1.2% of the association. Data from the UK Biobank provides the strongest evidence by far that paternal diabetes is associated with lower birthweight, whereas maternal diabetes is associated with increased birthweight. Our findings with paternal diabetes are consistent with a role for the same genetic factors influencing foetal growth and type 2 diabetes.

Figure 1 Measles and rubella incidence rates, Georgia, 1958-2007 
Table 2 Measles vaccination coverage rates, 1980-2005, Georgia 
Table 3 Laboratory testing for measles and rubella IgM antibodies, national measles and rubella laboratory, Georgia, 2004-05 
Ongoing measles and rubella transmission in Georgia, 2004-05: Implications for the national and regional elimination efforts

December 2008


648 Reads

In 2004-05, Georgia experienced large-scale concurrent measles and rubella outbreaks. We analysed measles and rubella epidemiology in Georgia to describe disease trends, determine the cause of the outbreaks, identify challenges to achieving disease elimination goals and propose interventions to overcome them. We reviewed national measles and rubella surveillance and vaccination coverage data, focusing on the 2004-05 outbreaks, and conducted a measles vaccine effectiveness (VE) study using data from a 2004 school-based outbreak. Before 2004, the last large measles outbreak after measles vaccination was introduced (in 1966) in Georgia, was in 1988 (incidence rate, 36/100 000); the highest year for rubella was 1985 (110/100 000). During 2004-05, 8391 measles cases and 5151 rubella cases were reported (most of them diagnosed clinically). Of 358 suspected measles cases tested, 181 (51%) were positive for measles-IgM antibody; of 240 suspected rubella cases tested, 50 (21%) were positive for rubella-IgM antibody. Over 90% of measles cases were in persons born after 1979; 90% of rubella cases were in persons born after 1987. Approximately 41% of measles cases and 88% of rubella cases were unvaccinated. Estimated measles VE (>/=1 vs 0 doses) was 86% (95% CI, 58-96%). The outbreak likely resulted from failure to vaccinate rather than vaccine failure. Susceptible persons likely accumulated due to the long absence of large outbreaks and decreased coverage after the collapse of Soviet Union. To interrupt measles and rubella transmission in Georgia and achieve disease elimination goals by 2010, supplementary immunization activities should target children and young adults.

Figure 2 Summary of the financial support provided by central and local government and other sources for China CARES, 2004–07. ‘Other source’ includes: financial support from international institutions and bilateral organizations, foundations and NGOs 
Table 2 China CARES programme satisfaction indicators among key informants and beneficiaries at the end of 5 years of implementation, 2008-09
Design and implementation of a China comprehensive AIDS response programme (China CARES), 2003-08

December 2010


97 Reads

Prior to 2003, there was limited capacity for an HIV/AIDS response in China. In early 2003, China launched a 5-year China Comprehensive AIDS Response Programme (China CARES) to contain the spread of HIV infection and reduce its impact. This article describes the China CARES' practices and experiences. China CARES covered 83.3 million people in 127 programme sites chosen from 28 provinces based on HIV prevalence. Each China CARES site was required to carry out surveillance and surveys to understand the local HIV/AIDS epidemic, to deliver primary interventions to reduce new HIV infections among and from high-risk groups, to prevent mother-to-child transmission, to treat AIDS patients with antiretroviral medicines and to provide support services to families affected by HIV/AIDS. Data were collected to monitor and evaluate implementation. HIV/AIDS prevention knowledge and awareness improved significantly in China CARES sites from <30% in 2004 to 86% in 2008. The number of persons tested for HIV increased by 67% between 2005 and 2007 from 1.5 to 2.5 million. China CARES enrolled 23 000 patients in anti-retroviral treatment and supported 6007 AIDS orphans. Among pregnant women, 81.8% received counselling and 75.8% received HIV testing during antenatal care, while 92.9% of HIV-infected pregnant women and 85.5% of their newborns received anti-retroviral prophylaxis. During the project period, no known HIV transmissions occurred through blood transfusions. China CARES has facilitated AIDS prevention, treatment and care in resource-poor, rural and ethnic minority areas of China.

Figure 1 Map of location of clinical sites (Perinatal protocol and LILAC protocol) 
Table 1 Continued
Table 2 Characteristics of the paediatric population (n ¼ 1481)
The NICHD International Site Development Initiative perinatal cohorts (2002-09)

February 2011


76 Reads

70provided by the protocol, and initiation and manage-ment of ARV treatment or prophylaxis were decidedby individual site investigators as per ARV availability,Published by Oxford University Press on behalf of the International Epidemiological Association 2011 International Journal of Epidemiology 2011;1–8doi:10.1093/ije/dyr024

Figure 1 Data quality evaluation for data being used in estimation of HIV/AIDS in China in 2007 and 2009. (A) Population size data and (B) HIV prevalence data. FPD: Former plasma donors 
Table 2 China's national HIV/AIDS estimates, 2003-09
Table 3 Estimated number of PLWHA in China, by transmission mode: 2003-09
Estimating the number of people living with HIV/AIDS in China: 2003-09

December 2010


147 Reads

Before 2003, little was known about the scale of China's HIV/AIDS epidemic. In 2003, the Chinese government produced national estimates with support from the Joint United Nations Programme on HIV/AIDS, the World Health Organization and the United States Centers for Disease Control and Prevention. Subsequent national estimation exercises were carried out in 2005, 2007 and 2009. We describe these estimation processes and present the results of China's HIV/AIDS estimation exercises from 2003 to 2009. The Workbook Method was used to generate national HIV/AIDS estimates. Data from the provincial level were used in 2003, data from the prefecture level were used in 2005 and data from the county level were used in 2007 and 2009. Data at the lowest level of aggregation were used to estimate risk group population size and HIV prevalence. Data from lower levels were combined into national estimates. At the end of 2003, 2005, 2007 and 2009, there were an estimated 0.84, 0.65, 0.70 and 0.74 million people living with HIV/AIDS in China, respectively, with an overall HIV prevalence of 0.05-0.06%. The number of new HIV infections decreased from 70 000 in 2005, to 50 000 in 2007, to 48 000 in 2009. Data quality improvements have increased the precision of China's HIV estimates. Repeated estimates have improved understanding of the HIV/AIDS epidemic in China. HIV estimates are a valuable tool for guiding national AIDS policies evaluating HIV prevention and control programmes.

The relationship between high blood glucose and socio-economic position in childhood and adulthood in Korea: findings from the Korean National Health and Nutrition Examination, 2007-09

March 2012


40 Reads

Unlike the older birth cohort (1943-65), the younger birth cohort (1966-79) has enjoyed much improved standards with dramatic developments in Korea. This article investigated the relationship between socio-economic position (SEP) and risk of high blood glucose, including impaired fasting glucose (IFG) and type 2 diabetes mellitus (T2D) by birth cohort. Of the 11 830 persons, 9792 persons aged 30-64 years participated in National Health and Nutrition Examination Surveys. We categorized four SEP groups based on education level in childhood and adulthood within two birth cohorts. High blood glucose included IFG (n = 2594) and T2D (n = 738). Odds ratio (OR) and 95% confidence interval (CI) were estimated by logistic regression. There was a significantly higher risk of high blood glucose in the younger cohort than in the older cohort. In the younger cohort, the ORs for males of declining SEP and of stable low SEP were OR: 1.50 (95% CI 1.12-2.00) and OR: 1.45 (95% CI 1.08-1.93), respectively. After adjustments, corresponding ORs were 1.47 (95% CI 1.09-1.98) and 1.54 (95% CI 1.14-2.08), respectively. In younger women, the corresponding ORs were 1.68 (95% CI 1.17-2.41) and 1.87 (95% CI 1.30-2.69), respectively; however, obesity attenuated the former relationship. For women in the older cohort, this inverse relationship was found only among those with a stable low SEP (OR 1.31, 95% CI 1.04-1.66); no significance was found after adjustments. There was no significant inverse relationship in the older cohort for men. The relationship between lower SEP and elevated risk of high blood glucose was stronger in the younger birth cohort, and obesity attenuated this inverse relationship in women only.

Table 1 Conditions that confound or simulate the ECG diagnosis of MI 
World Health Organization definition of myocardial infarction: 2008-09 revision

October 2010


1,949 Reads

WHO has played a leading role in the formulation and promulgation of standard criteria for the diagnosis of coronary heart disease and myocardial infarction since early 1970s. The revised definition takes into consideration the following: well-resourced settings can use the ESC/ACC/AHA/WHF definition, which has new biomarkers as a compulsory feature; in resource-constrained settings, a typical biomarker pattern cannot be made a compulsory feature as the necessary assays may not be available; the definition must also have provision for diagnosing non-fatal events with incomplete information on cardiac biomarkers and the ECG; to facilitate epidemiologic monitoring definition must recognize fatal events with incomplete or no information on cardiac biomarkers and/or ECG and/or autopsy and/or coronary angiography. Category A definition is the same as ESC/ACC/AHA/WHF definition of MI, and can be applied to settings with no resource constraints. Category B definition of MI is to be applied whenever there is incomplete information on cardiac bio-markers together with symptoms of ischaemia and the development of unequivocal pathological Q waves. Category C definition (probable MI) is to be applied when individuals with MI may not satisfy Category A or B definitions because of delayed access to medical services and/or unavailability of electrocardiography and/or laboratory assay of cardiac biomarkers. In these situations, the term probable MI should be used when there is either ECG changes suggestive of MI or incomplete information on cardiac biomarkers in a person with symptoms of ischaemia with no evidence of a non-coronary reason. This article presents the 2008-09 revision of the World Health Organization (WHO) definition of myocardial infarction (MI) developed at a WHO expert consultation.

Figure 1 Among 62 919 patients included in this analysis, the 54 338 (86.4%) of patients located in the 327 counties/districts with at least 20 patients each were plotted on this map, with each county/district stratified by predominant mode of HIV transmission 
Figure 2 Baseline characteristics among all 62 919 patients included in this analysis, stratified over time by the number of new patients initiating highly active antiretroviral therapy (HAART), route of transmission, baseline CD4 cell count and treatment regimen. The number of new patients included by year is shown in the top graph. Note: 2009 data are only to June 1 2009. P < 0.0001 for the change in each comparison (number of new patients, route of infection, baseline CD4 cell count and initial HAART regimen) over time 
Changing baseline characteristics among patients in the China National Free Antiretroviral Treatment Program, 2002-09

December 2010


44 Reads

To improve HIV treatment in China by determining changes over time of patient characteristics (geographic, clinical and route of HIV infection) among patients enrolled in the China National Free Antiretroviral Treatment Program. Patients in the national treatment database from 1 June 2002 to 1 June 2009 were eligible. Patients were excluded if <18 years old, not previously treatment-naïve, missing initial treatment date or not initiated on triple drug therapy. About 62 919 patients were included, located across 54.8% of counties/districts throughout mainland China; 86.4% were concentrated in 11.1% of counties/districts. Median age was 38 years, 41% female, 45.4% former plasma donors (FPDs), 33.9% sexually infected and 15.5% injection drug users (IDUs). Median baseline CD4 cell count was 129/µl. In 2002, 100% of treated were FPDs with no CD4 cell counts. By 2009, 59% of the treated were sexually infected and 96% had baseline CD4 cell counts. Injection drug users remained a minority of those treated. Limited treatment resources can be focused on areas with more patients. Greater emphasis needs to be placed on earlier HIV diagnosis and treatment. New strategies must be identified to bring HIV-infected IDUs into treatment. Routine HIV testing would identify those at risk earlier.

Figure 1 Adjusted regression results [b (SE)] for height in centimetres according to DDE category by age. (Relative height is the ratio of adjusted mean height among those in a given exposure group to those in the referent exposure group. Reference group: ,15 mg/l. The reference category is firstborn white females from the Boston centre whose mothers were 24.3 years-old, non-smokers, had a low SEI, a prepregnancy BMI of 22.8 kg/m 2 , a height of 1.61 m, 
Prenatal exposure to 1,1-dichloro-2,2-bis (p-chlorophenyl)ethylene (p,p '-DDE) in relation to child growth

August 2006


60 Reads

To examine the relation between prenatal 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE) exposure (a metabolite of the insecticide DDT) and child growth during the first 7 years of life. Design Prospective cohort study. Participants 1,712 children born between 1959 and 1966 with measured p,p'-DDE concentrations in their mother's serum samples from pregnancy. Setting Multicenter US Collaborative Perinatal Project (CPP). The highest prenatal concentrations of p,p'-DDE (>or=60 microg/l), as compared with the lowest (<15 microg/l), were associated with decreased height at age 1 year [adjusted coefficient (SE) = -0.72 cm (0.37), n = 1,540], 4 years [-1.14 cm (0.56), n = 1,289], and 7 years [-2.19 (0.46), n = 1,371]. Among subjects in lower categories of exposure no association was observed. The findings suggest that high prenatal exposure to p,p'-DDE decreases height in children. Impaired growth may be a general indicator of toxicity and suggests that specific organ systems (e.g. endocrine) could be affected.

Seasonal Influences on the Risk of Cardiac Malformation: Nature of the Problem and Some Results from a Study of 10,077 Cases

February 1972


8 Reads

Rose, V. (Dept. of Cardiology and Research Institute of the Hospital for Sick Children, University of Toronto, Toronto 5, Canada), Hewitt, D., and Mimer, J. Seasonal influences on the risk of cardiac malformation. Int. J. Epid.1972, 1 : 235–244. Birth date and diagnostic data on 10,077 cases of congenital heart disease studied at the Hospital for Sick Children, Toronto, were used in Part I to illustrate some problems of epidemiological method that require further attention in the search for seasonal influences on malformation. Among the birth-rate patterns noted in the Toronto data are: (a) A slight but significant excess of congenital heart disease as a whole in the fall and winter, rates for October-March averaging 6–7 per cent higher than those for April-September. (b) A much more strongly marked excess of cases with transposition of the great arteries during August-January. (c) Distinct seasonal peaks in the fall (for males) and spring (for females) of cases with pulmonary valve stenosis. (d) A stronger correlation for males than females between rubella exposure and patent ductus arteriosus. (e) Significant changes from year to year in the percentage of males among newborn cases of congenital heart disease as a whole. The seasonal pattern recently reported from New England for coarctation of the aorta cannot be detected in Ontario.

Physical Activity and 10.5 Year Mortality in the Multiple Risk Factor Intervention Trial (MRFIT)

October 1991


25 Reads

The effect of habitual leisure time physical activity (LTPA) on the 10.5-year total and cause-specific mortality rates was studied in 12,138 middle-aged men at high risk for coronary heart disease (CHD) who participated in the MRFIT. The level of LTPA as determined by the Minnesota questionnaire was inversely related to rate of death from cardiovascular (CVD), coronary heart disease (CHD), and all-causes, but was unrelated to the cancer death rate. The least active men (LTPA tertile 1) had excess mortality rates of 22%, 27%, and 15% for CVD, CHD, all-causes, respectively, as compared to more active men in the middle third (tertile 2). Additional LTPA (tertile 3) was not associated with further attenuation of mortality rates. Proportional hazards regression analysis only slightly weakened risk differentials. This study supports previous observations that regular LTPA is associated with a reduced rate of CVD mortality, independent of other risk factor levels.

Epidemiology 101: II. An Undergraduate Prospectus

July 1979


8 Reads

Lilienfeld D E [Department of Mathematical Sciences, The Johns Hopkins University, Faculty of Engineering, 34th and Charles Streets, Baltimore, Maryland, 21218 USA], Epidemiology 101: II. An undergraduate prospectus. International Journal of Epidemiology 1979 8: 181–183.

A cost-benefit analysis of programmatic use of CVD 103-HgR live oral cholera vaccine in a high-risk population

March 1997


66 Reads

Cholera spread to Latin America in 1991; subsequently, cholera vaccination was considered as an interim intervention until long-term solutions involving improved water supplies and sanitation could be introduced. Three successive summer cholera outbreaks in northern Argentina and the licensing of the new single-dose oral cholera vaccine, CVD 103-HgR, raised questions of the cost and benefit of using this new vaccine. This study explored the potential benefits to the Argentine Ministry of Health of treatment costs averted, versus the costs of vaccination with CVD 103-HgR in the relatively confined population of northern Argentina affected by the cholera outbreaks. Water supplies and sanitation in this area are poor but a credible infrastructure for vaccine delivery exists. In our cost-benefit model of a 3-year period (1992-1994) with an annual incidence of 2.5 case-patients per 1000 population and assumptions of vaccine efficacy of 75% and coverage of 75%, vaccination of targeted high risk groups would prevent 1265 cases. Assuming a cost of US$602 per treated case and of US$1.50 per dose of vaccine, the total discounted savings from use of vaccine in the targeted groups would be US$132,100. The projected savings would be altered less by vaccine coverage (range 75-90%) or efficacy (60-85%) changes than by disease incidence changes. Our analysis underestimated the true costs of cholera in Argentina because we included only medical expenditures; Indirect losses to trade and tourism had the greatest economic impact. However, vaccination with CVD 103-HgR was still cost-beneficial in the base case.

Chang JS, Tsai CR, Tsai YW, Wiemels JLMedically diagnosed infections and risk of childhood leukaemia: a population-based case-control study. Int J Epidemiol 41(4): 1050-1059

July 2012


34 Reads

Previous studies on the association between childhood infections and childhood leukaemia have produced inconsistent results, likely due to the recall error/bias of infection data reported by the parents. The current study used a population-based and record-based case-control design to evaluate the association between childhood leukaemia and infections using the National Health Insurance Research Database of Taiwan. In all, 846 childhood acute lymphoblastic leukaemia (ALL) and 193 acute myeloid leukaemia (AML) patients newly diagnosed between 2000 and 2008, aged >1 and <10 years, were included. Up to four controls (3374 for ALL and 766 for AML) individually matched to each case on sex, birth date and time of diagnosis (reference date for the controls) were identified. Conditional logistic regression was performed to assess the association between childhood leukaemia and infections. Having any infection before 1 year of age was associated with an increased risk for both childhood ALL (odds ratio = 3.2, 95% confidence interval 2.2-4.7) and AML (odds ratio = 6.0, 95% confidence interval 2.0-17.8), with a stronger risk associated with more episodes of infections. Similar results were observed for infections occurring >1 year before the cases' diagnosis of childhood leukaemia. Children with leukaemia may have a dysregulated immune function present at an early age, resulting in more episodes of symptomatic infections compared with healthy controls. However, confounding by other infectious measures such as birth order and day care attendance could not be ruled out. Finally, the results are only relevant to the medically diagnosed infections.

Table 2 Sample characteristics at baseline by average daily total alcohol consumption in women (n ¼ 5690) 
Heavy drinking occasions in relation to ischaemic heart disease mortality- An 11-22 year follow-up of the 1984 and 1995 US National Alcohol Surveys

October 2011


51 Reads

The relationship between alcohol consumption and ischaemic heart disease (IHD) risk is complex and several issues remain unresolved because many studies used rather crude exposure measures often based on one or two questions. The objective of this study was to investigate the association between heavy drinking occasions and IHD mortality while controlling for average daily alcohol intake and separating former drinkers from lifetime abstainers. Cox regression analyses were used with IHD mortality as the outcome in a sample of 9934 participants of the US National Alcohol Surveys conducted in 1984 and 1995. To the end of 2006, 326 deaths from IHD were recorded in the 11- to 22-year follow-up period. Any past heavy drinking occasions in former drinkers [hazard ratio (HR) = 2.06; 95% confidence interval (95% CI): 1.10-3.85] compared with former drinkers without such drinking occasions, and any heavy drinking occasion in current drinkers at baseline (HR = 2.05; 95% CI: 1.03-3.98) compared with current drinkers with average daily intake of one to two drinks, were associated with higher IHD mortality in men and any heavy drinking occasions among drinkers of up to 1 drink average consumption in women with similar effect size. Confounding effects from age, race, education, employment, income, marital status, geographical region, depression score, survey period or other drug use were small. Among former and current drinkers, heavy drinking occasions should be taken into account when examining the complex association of alcohol consumption on IHD mortality risk.

Low birthweight and Type 2 diabetes: A study on 11 162 Swedish twins

October 2004


33 Reads

To investigate the association between low birthweight and diabetes in a population-based Swedish twin sample. Method A cohort of 11 162 same-sexed Swedish twins born between 1906 and 1958 was used in order to investigate the risk of developing Type 2 diabetes between and within twin pairs by utilizing random effects linear models. Between pairs there was a significant increase in risk of developing Type 2 diabetes for a 1-kg increase in their mean birthweight (odds ratio [OR] = 2.13; P < 0.01), adjusted for age, sex, body mass index (BMI), and smoking status. The corresponding risk within pair was 2.03 (P = 0.07) for monozygotic twins and 1.15 (P = 0.71) for dizygotic twins. The test of the heterogeneity of the within and between effects showed no significant difference between the estimates. The study suggests that reduced fetal growth increase the risk of Type 2 diabetes due to an in utero programming effect possibly caused by intrauterine malnutrition. However, it does not exclude the possibility of a common genetic mechanism.

Pearce MS, Deary IJ, Young AH, Parker L. Growth in early life and childhood IQ at age 11 years: the Newcastle Thousand Families Study. Int J Epidemiol 34, 673-677

July 2005


34 Reads

It has been suggested that in addition to genetic factors, fetal and post-natal growth influence childhood cognition, although it is unclear whether such an effect continues throughout childhood. This study aimed at investigating the potential relationships between childhood IQ at age 11 years and birth weight and height at the ages of 9 and 13 years, after adjusting for the confounding factors available to this investigation. The Newcastle Thousand Families study, a prospectively followed cohort, originally consisted of all 1142 births in the city of Newcastle in May and June 1947. Using data on 733 members of this cohort, we investigated the associations between IQ at age 11, and birth weight and height at ages 9 and 13 years. Birth weight showed no association with childhood IQ. However, height at age 9 years was a significant predictor of childhood IQ after adjusting for socioeconomic status (standardized regression coefficient b = 2.6, 95% CI 1.6-3.6, P < 0.0001). Height at age 13 was also a significant predictor of IQ after adjusting for socioeconomic status (b = 3.4, 95% CI 2.3-4.4, P = 0.001), and explained an additional 2.5% of the variation in IQ scores to that already explained by socioeconomic status and height at age nine. These results suggest a continuing effect of post-natal growth on childhood cognition beyond the age of 9 years. Post-natal growth, which may be influenced by genetic factors and nutrition and socioeconomic circumstances in childhood, may be more important than fetal growth in terms of childhood cognition.

One for every 113 inhabitants: Cigarette vending machines in Germany [6]

September 2006


87 Reads

14-17 (n 5 104) 38 (36.54%) 37 (35.58%) 61 (58.65%) 54 (51.92%) 13 (12.50%) 10 (9.62%) 4 (3.85%) 18-25 (n 5 529) 248 (46.88%) 208 (39.32%) 363 (68.62%) 201 (38.00%) 33 (6.24%) 80 (15.12%) 24 (4.54%) 26-91 (n 5 2969) 1102 (37.12%) 976 (32.87%) 2145 (72.25%) 833 (28.06%) 97 (3.27%) 360 (12.13%) 220 (7.41%) S 1388 (38.53%) 1221 (33.90%) 2569 (71.32%) 1088 (30.21%) 143 (3.97%) 450 (12.49%) 248 (6.89%) c 2 (2)

Lefkowitz ES, Garland CF. Sunlight, vitamin D, and ovarian cancer mortality rates in US women. Int J Epidemiol 23, 1133-1136

January 1995


51 Reads

In general, ovarian cancer incidence and mortality is higher in northern than southern latitudes. This ecologic study tests the hypothesis that vitamin D produced in the skin from sunlight exposure may be associated with a protective action in ovarian cancer mortality. The association between average annual sunlight energy and age-specific ovarian cancer mortality rates in counties containing the 100 largest US cities was evaluated for 1979-1988. Simple linear regression was performed by decade using sunlight and ozone as independent variables and ovarian cancer rates as the dependent variable. Multiple regression was used to adjust for ozone and sulphur dioxide, since these atmospheric components may absorb ultraviolet light. Fatal ovarian cancer in these areas was inversely proportional to mean annual intensity of local sunlight in a univariate analysis (P = 0.0001), and in a regression adjusted for air pollution (P = 0.04). The association was also seen when restricted to 27 major urban areas of the US; however, probably due to a small sample size, this statistic did not reach significance. This ecologic study supports the hypothesis that sunlight may be a protective factor for ovarian cancer mortality.

Figure 1 Cumulative frequency chart to show the gestational age at delivery by ethnic group 
Table 2 Proportion of preterm deliveries by ethnic group and maternal age 
Table 3 The estimated odds (OR) ratios for the association between Black ethnicity and preterm delivery 
Table 4 The estimated odds ratios (OR) for the association between Asian ethnic group and preterm delivery 
Table 5 The estimated odds ratios of meconium stained amniotic fluid at birth by ethnic group and time of delivery 
Does gestation vary by ethnic group? A London-based study of over 122,000 pregnancies with spontaneous onset of labour

March 2004


2,898 Reads

Evidence exists that normal gestational length varies with ethnicity. This UK-based study compares gestational length amongst a cohort of white European, Black and Asian women. The cohort comprised 122 415 nulliparous women with singleton live fetuses at the time of spontaneous labour, giving birth in the former North West Thames Health Region, London, UK. The median gestational age at delivery was 39 weeks in Blacks and Asians and 40 weeks in white Europeans. Black women with normal body mass index (BMI) (18.5-24.9 kg/m(2)) had increased odds of preterm delivery (odds ratio [OR] = 1.33, 95% CI: 1.15, 1.56, adjusted for deprivation and BMI) compared with white Europeans. The OR of preterm delivery was also increased in Asians compared with white Europeans (OR = 1.45, 95% CI: 1.33, 1.56, adjusted for single unsupported status and smoking). Meconium stained amniotic fluid, which is a sign of fetal maturity, was statistically significantly more frequent in preterm Black and Asian infants and term Black infants compared with white European infants. This research suggests that normal gestational length is shorter in Black and Asian women compared with white European women and that fetal maturation may occur earlier.

What is a Case of Tuberculosis? The Tuberculosis Case Spectrum in Eight Countries Evaluated from 1235 Case Histories and Roentgenograms

February 1973


4 Reads

Case histories and chest roentgenograms of patients who comprised representative samples of all cases diagnosed in eight different areas in Europe, Asia and America were submitted for central review and analysis. The case spectrum differed considerably among the centers. The average extent of disease varied between 0.9 and 2.1 quarters of a lung field; the frequency of cavitation between 27 and 50 per cent; and the average diameter of the cavities between 1 and 3 cm. In some centers, the cases were predominantly of a fibrotic-productive nature, while they were mostly exudative in others. Finally, the frequency of bacillary cases varied between 49 per cent and 85 per cent. Even within patients of the same category, for example in respect to nature or extent of disease, great variability was observed. Patients with similar bacteriologic status were not homogeneous with respect to radiologic characteristics as judged by either average extent of disease of frequency of cavitation. The case spectrum of tuberculosis differs greatly in various places. This finding is significant for international comparisons of tuberculosis statistics. The use of an appropriate radiologic classification in addition to the widely recommended bacteriologic definition of a case may be useful for estimation of long-range prognsis and may provide important leads for epidemiologic studies.

Socioeconomic position and twins' health: A life-course analysis of 1266 pairs of middle-aged Danish twins

March 2007


30 Reads

The association between socioeconomic circumstances and health in adulthood could come about through processes that may be divided into factors experienced early in life and those experienced in later adulthood. In order to disentangle the influences on health of the early genetic, prenatal and rearing environmental factors from environmental factor later in life, we compared the health status among male and female twin pairs who lived together during childhood and were discordant or concordant on adult socioeconomic position. A cross-sectional survey among a random sample of middle-aged Danish twins was conducted in 1998-99. The study population included 1266 like-sex twin pairs [52.5% monozygotic (MZ) and 47.6% dizygotic (DZ)]. Data were obtained on childhood and adult social class and on height, BMI, grip strength, depression symptoms, self-rated health, cognitive function, physical activity, smoking, alcohol and food intake. The expected associations between the individual twins' adult social class and health measures were observed. Among DZ male twins discordant on adult social class, the higher social class twin was on average significantly taller and had higher cognitive test scores. Among DZ female twins discordant on adult social class, the higher social class female twin was more physically active and had a higher cognitive test score. There were no significant health disparities or behavioural differences between the members of MZ twin pairs discordant on adult social class. For most health outcomes, the variability within twin pairs was related to zygosity (higher for DZ than for MZ) but not to social class. This study suggests that the relationship between adult social class and health outcomes in Denmark is due mainly to selection effects rather than a causal effect of social class exposures on health and behaviour.

Blood Pressure by Age in Childhood and Adolescence: A Review of 129 Surveys Worldwide

January 1990


12 Reads

Brotons C (Epidemiology Research Centre, School of Public Health, The University of Texas Health Science Center at Houston, Houston, Texas, USA), Singh P, Nishio T and Labarthe D R. Blood pressure by age in childhood and adolescence: a review of 129 surveys worldwide. International Journal of Epidemiology 1989, 18: 824–829. The pre-adult patterns of change in blood pressure with age have been investigated by review and pooled analysis of the relevant worldwide literature. The results indicate, foremost, the almost universal overall upward progression of blood pressure levels between ages 6 and 18 years, separately for systolic, fourth-phase and fifth-phase diastolic pressures (SBP, DBP4, DBP5). This report summarizes results of an extensive literature search based on 129 qualifying publications, in many languages, of which 79 yielded data adequate for a pooled age-sex-specific analysis for boys and girls aged 6–18 years. More than 200 000 observations were available for SBP and nearly 100 000 each for DBP4 and DBP5, respectively. In this overall pool, SBP increased uniformly for boys from age 6–12 and for girls from 6–9, at 1.4 mm Hg/yr; for boys the slope increased abruptly to 3.2 mm Hg/yr from 12–15 and fell to 0 at age 18; for girls the maximum increase was only 2.1 mm Hg/yr, from 9–13, and it reversed at age 16, reaching –3.4 mm Hg/yr from 17–18. Thus for SBP the absolute values for boys and girls were identical up to age nine and nearly so to age 14 and then separated, with values for girls increasing only slightly to age 16 and actually decreasing to age 18. A similar separation of age-specific values by sex occurred with DBP4, but not until age 16, after which DBP4 decreased for girls. For DBP5, values were more nearly equal for boys and girls at all ages but did separate at age 12, with girls having the higher values. DBP4 and DBP5 had much lesser slopes of change than did SBP across the whole age range, and DBP5 was consistently about 5 mm Hg lower than DBP4.

Smoking Cessation and Changes in Respiratory Symptoms in Two Populations Followed for 13 Years

September 1993


11 Reads

To investigate the relationship between persistence and incidence rates of respiratory symptoms, and the cession of cigarette smoking, the data from longitudinal studies conducted in Cracow, Poland and Tucson, USA were analysed jointly. Among 1722 subjects smoking at the beginning of the study, 468 had given up smoking at the 13-year followup. The persistence and incidence rat- of chronic cough, chronic phlegm, wheeze and attacks of breathleasnesa were reduced by 60% in ex-smokers compared to the subjects continuing to smoke. The beneficial effects of smoking cessation were decreased in subjects smoking more cigarettes per day in the past and starting to smoke at a younger age. The symptoms were leas likely if smoking ceased before the onset of any respiratory disease. These reaults were similar in the Cracow and Tucson populations, confirming the universal nature of the observations.

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